Background: β-Lapachone is a quinone-containing compound found in red lapacho (Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. Methods: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription–polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. Results: We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Conclusions: Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.
A reduced number and/or reduced activity of natural killer (NK) cells, which are important for defense against a variety of cancers and viral infections, occur under various stress conditions and in patients with various diseases. In this article, we report that the 30% to 50% ethanol precipitate of oyster extract (EPOE50) dose-dependently enhanced the activity of mouse spleen NK cells in vitro and in vivo. The activity of EPOE50 was eluted with a molecular weight of about 2000 by gel filtration and was inactivated by periodate but not by proteinase K. The activity of highly purified NK cells was also augmented by EPOE50 but not by oligodeoxyribonucleotide 1585, which mimics bacterial DNA. Administration of EPOE50 to mice stimulated splenic NK cell activity without a change in splenic NK cell populations. Although the proliferation of B16 tumor cells in vitro was slightly stimulated by EPOE50, the growth of B16 melanoma in vivo was dose-dependently suppressed by administration of EPOE50. Taken together, our results indicate that EPOE50 augmented NK cell activity and that its administration to mice inhibited tumor growth presumably through the activation of NK cells and also suggest that the active substance is a sugar-containing oligomer or polymer and is not of bacterial origin.
Background: Although epidemiological research demonstrates that there is an association between lifestyle factors and risk of breast cancer recurrence, progression of disease, and mortality, no comprehensive lifestyle change clinical trials have been conducted to determine if changing multiple risk factors leads to changes in biobehavioral processes and clinical outcomes in women with breast cancer. This article describes the design, feasibility, adherence to the intervention and data collection, and patient experience of a comprehensive lifestyle change clinical trial (CompLife). Methods: CompLife is a randomized, controlled trial of a multiple-behavior intervention focusing on diet, exercise, and mind-body practice along with behavioral counseling to support change. The initial exposure to the intervention takes place during the 4 to 6 weeks of radiotherapy (XRT) for women with stage III breast cancer and then across the subsequent 12 months. The intervention group will have 42 hours of in-person lifestyle counseling during XRT (7-10 hours a week) followed by up to 30 hours of counseling via video connection for the subsequent 12 months (weekly sessions for 6 months and then monthly for 6 months). The primary outcome is disease-free survival. Multiple secondary outcomes are being evaluated, including: (1) biological pathways; (2) overall survival; (3) patient-reported outcomes; (4) dietary patterns/fitness levels, anthropometrics, and body composition; and (5) economic outcomes. Qualitative data of the patient experience in the trial is collected from exit interviews, concluding remarks, direct email correspondences, and web postings from patients. Results: Fifty-five patients have been recruited and randomized to the trial to date. Accrual of eligible patients is high (72%) and dropout rates extremely low (5%). Attendance to the in-person sessions is high (95% attending greater than 80% of sessions) as well as to the 30 hours of video counseling (88% attending more than 70% of sessions). Adherence to components of the behavior change intervention is high and compliance with the intensive amount of data collection is exceptional. Qualitative data collected from the participants reveals testimonials supporting the importance of the comprehensive nature of intervention, especially the mind-body/mindfulness component and social support, and meaningful lifestyle transformations. Conclusion: Conducting a comprehensive, multicomponent, lifestyle change clinical trial for women with breast was feasible and collection of biobehavioral outcomes successful. Adherence to behavior change was high and patient experience was overwhelmingly positive.
Introduction: After allogeneic hematopoietic stem cell transplantation (HSCT), NK cell reconstitution, which is crucial for positive outcomes, is dominated by the CD56bright subset with low NK cell cytotoxicity (NKCC) activity. Moderate exercise has been described as a potent NK cell stimulus in adults with cancer. Purpose: To determine the effects of a moderate-intensity exercise program on NK cell recovery early after HSCT and the feasibility of this intervention. Methods: Six children undergoing allogeneic HSCT were randomized to an exercise program (EP) or control (CT) group. The EP group performed a 10-week training combining in-hospital and home-based EP. Results: We observed a significant increase in the posttraining/pretraining ratio of the CD56dim subset (EP = 1.27 ± 0.07; CT = 0.99 ± 0.08; P < .005) of the EP group. The ratio of NKCC was 8 times greater in the EP group. Conclusion: Data suggest that a moderate-intensity EP program performed early after HSCT is feasible and might redistribute the CD56dim/CD56brigh NK cell subset, improving NKCC. The results are still preliminary and must be interpreted with caution.
Chronic inflammation may be a causative factor in breast cancer. One possible underlying mechanism is the generation of oxidative stress, which may favor tumorigenic processes. Antioxidant consumption may, therefore, help reduce tissue inflammation levels. However, few studies have explored this relation in breast tissue. We aimed to evaluate correlations between antioxidant (vitamin A/retinol, vitamin C, vitamin E, β-carotene, α-carotene, lycopene, lutein/zeaxanthin, β-cryptoxanthin, selenium, and zinc) intakes and protein expression levels of interleukin (IL)-6, tumor necrosis factor-α, C-reactive protein, cyclooxygenase-2, leptin, serum amyloid A1, signal transducer and activator of transcription 3, IL-8, IL-10, lactoferrin, and transforming growth factor-β measured in the normal breast tissue of 160 women diagnosed with breast cancer. Antioxidant intakes were collected using a self-administered food frequency questionnaire. Inflammation marker expression was assessed by immunohistochemistry. Correlations between antioxidant intakes and inflammatory marker expression were evaluated using Spearman’s partial correlation coefficients (r) for all women and for premenopausal and postmenopausal women separately. After Bonferroni correction, negative correlations were observed between dietary β-tocopherol and IL-10 expression in all women combined (r = –0.26, P = .003) and among postmenopausal women (r = –0.39, P = .003). For all women, a negative correlation was found between total zinc intakes and IL-10 (r = –0.26, P = .002). Among postmenopausal women, dietary selenium intake was negatively correlated with the expression of lactoferrin (r = –0.39, P = .003). No associations were observed in premenopausal women. Our findings suggest that consumption of specific antioxidants, including β-tocopherol, zinc, and selenium, may act on the breast tissue through mechanisms affecting the expression of some inflammation markers, particularly among postmenopausal women.
Artificial light at night (ALAN) for elongating photophase is a new source of pollution. We examined the association between measured ALAN levels and breast cancer (BC) standard morbidity ratio (SMR) at a statistical area (SA) level in an urban environment. Sample size consisted of 266 new BC cases ages 35-74. Light measurements (lux) were performed in 11 SAs. A new calculated variable of morbidity per SA size (SMR35-74/km2) was correlated with the light variables per road length, using Pearson correlations (P < .05, 1-tailed). Looking for a light threshold, we correlated percentage of light points above SA light intensity median with SMR35-74/km2. SMR35-74/km2 was significantly and positively strongly correlated with mean, median, and standard-deviation (SD) light intensity per road length (r = .79, P < .01, R2 = .63; r = .77, P < .01, R2 = .59; and r = .79, P < .01, R2 = .63). Light threshold results demonstrate a marginally significant positive moderate correlation between percentage of points above 16.3 lux and SMR35-74/km2 (r = .48, P < .07; R2 = .23). In situ results support the hypothesis that outdoor ALAN illumination is associated with a higher BC-SMR in a specific area and age group. Moreover, we suggest an outdoor light threshold of approximately 16 lux as the minimal intensity to affect melatonin levels and BC morbidity. To the best of our knowledge, our attempt is the first to use this method and show such association between streetlight intensity and BC morbidity and therefore should be further developed.
Most of the present anticancer drugs are highly cytotoxic and focus mainly on killing tumor cells rather than slowing the progress of cancer metastasis. Evidence has been reported that bridges the mechanisms of inflammation and tumor invasion. Therefore, we evaluated the potency in cancer metastasis chemoprevention of compounds and a coumarin extracted from Murraya exotica, which is known for its anti-inflammation bioactivity. By carrying out experiments in vitro, we found the root extracts more efficient than the leaf extracts in restraining cell migration of MDA-MB-231 cells, while leaf extracts presented slightly stronger inhibition of tumor cell adhesion at low concentrations. In addition, compared to root extracts, a novel coumarin identified previously from root extracts showed equal inhibition on cancer cell adhesion and less inhibition on cell migration. All extracts used in this study presented low cytotoxicity in vitro. Through comparison of the contents of leaf and root extracts from M exotica, several compounds are considered promising against cancer metastasis. This study evaluates the worth of further development of M exotica to find its effect on cancer metastasis chemoprevention.
Background. Murraya koenigii (L.) Spreng, is a significant herb of traditional Ayurvedic system of medicine. Koenimbine, a carbazole alkaloid isolated from this plant holds antiproliferative and apoptotic effects. The aim of this study was to assess koenimbine-induced DNA damage and to clarify the role of free radicals in cell death mechanisms, using HepG2 cells. Methods. The level of cytotoxicity was assayed by MTT assay. To elucidate the role of glutathione (GSH), the intracellular GSH level was analyzed. The effect of koenimbine in the cell mitochondria was evaluated using mitochondrial membrane potential (MMP) changes. Single cell gel electrophoresis assay was used to examine the level of DNA damage. Heat shock proteins, Hsp 70 and Hsp 90 expressions were checked at mRNA and protein level. Ascorbic acid and catalase were used as control antioxidants. Results. It was observed that koenimbine considerably increased DNA damage in HepG2 cells at subcytotoxic concentrations. Koenimbine induced the increased levels of reactive oxygen species (ROS) and reduction of GSH level in HepG2 cells, together with time-dependent loss of MMP. In addition, results clearly showed that koenimbine encouraged cells to express Hsp 70 and Hsp 90 in a concentration-dependent manner up to a concentration of 100 µM and a time-dependent manner at 24-hour incubation both at transcriptional and translational levels. The antioxidant capacity of ascorbic acid was found to be not as prominent as to catalase throughout the study. Conclusion. Based on these data it can be concluded that koenimbine causes DNA strand breaks in HepG2 cells, probably through oxidative stress. Moreover, the oxidative stress induced was closely associated with MMP reduction and GSH depletion associated with HSP modulation at subcytotoxic concentration.
Background: Osteosarcoma is a malignant bone tumor prevalent in adolescents with poor prognosis. Toona sinensis showed potent antiproliferation effect on lung, melatonin, ovary, colon, and liver cancers. However, the effects of the species on osteosarcoma cells are rarely investigated. Results: In this study, we found fraction 1 of Toona sinensis leaf (TSL-1) resulted in inhibition of cell viability in MG-63, Saos-2, and U2OS osteosarcoma cell lines, while it only caused a moderate suppressive effect on normal osteoblasts. In addition, TSL-1 significantly elevated lactate dehydrogenase leakage and induced apoptosis and necrosis in Saos-2 cells. TSL-1 increased mRNA expression of pro-apoptotic factor Bad. Most important, TSL-1 significantly suppressed Saos-2 xenograft tumor growth in nude mice by increasing caspase-3. The IC-50 of TSL-1 for the 3 tested osteosarcoma cells is around 1/9 of that for lung cancer cells. Conclusion: We demonstrated that TSL-1, a fractionated extract from TSL, caused significant cytotoxicity to osteosarcoma cells due to apoptosis. In vivo xenograft study showed that TSL-1 suppressed the growth of osteosarcoma cells at least in part by inducing apoptosis. Our results indicate that TSL-1 has potential to be a promising anti-osteosarcoma adjuvant functional plant extract.
Cancers involving the oral cavity, head, and neck regions are often treated with cisplatin. In cancer therapy, the main target is to eliminate unwanted cancerous cells. However, reports on the nonselective nature of this drug have raised few concerns. Incorrect nutritional habits and lifestyle practices have been directly linked to cancer incidence. Nutrients with antioxidant activity inhibit cancer cells development, destroying them through oxidative stress and apoptosis. α-tocopherol, the potent antioxidant form of vitamin E is a known scavenger of free radicals. In vitro study exhibited effective antitumor activity of α-tocopherol on ORL-48 at 2.5 ± 0.42 µg/mL. Cisplatin exhibited stronger activity at 1.0 ± 0.15 µg/mL, but unlike α-tocopherol it exhibited cytotoxicity on normal human epidermal keratinocytes at very low concentration (<0.1 µg/mL). Despite the lower potency of α-tocopherol, signs of apoptosis such as the shrinkage of cells and appearance of apoptotic bodies were observed much earlier than cisplatin in time lapse microscopy. No apoptotic vesicles were formed with cisplatin, instead an increased population of cells in the holoclone form which may suggest different induction mechanisms between both agents. High accumulation of cells in the G0/G1 phase were observed through TUNEL and annexin V-biotin assays, while the exhibition of ultrastructural changes of the cellular structures verified the apoptotic mode of cell death by both agents. Both cisplatin and α-tocopherol displayed cell cycle arrest at the Sub G0 phase. α-tocopherol thus, showed potential as an antitumour agent for the treatment of oral cancer and merits further research.
Danggui Buxue Decoction (DBD), a classical formula of traditional Chinese medicine (TCM), has an impact on promoting hematopoiesis. The aim of our study was to determine whether DBD can prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. We conducted a phase II randomized prospective controlled clinical study. From December 2013 to February 2015, 106 patients were enrolled and randomly assigned (1:1) to the TCM group and control group. The primary end point was incidence of grade 3-4 neutropenia. The secondary end points included incidence of grade 3-4 neutropenia in each cycle, incidence of anemia, and incidence of thrombopenia during 4 cycles. Seventeen patients withdrew from this study, and 89 patients were included in the final analysis. Incidences of grade 3-4 neutropenia during 4 cycles were 57.1% in the TCM group and 59.6% in the control group, and there was no significant difference (P = .816). Similarly, no significant differences were observed between the 2 groups for incidence of grade 3-4 neutropenia in each cycle. While incidences of anemia were 54.8% and 66.6% for the TCM group and control group, respectively (P = .280), incidences of thrombopenia were 11.9% for the TCM group and 4.3% for the control group (P = .248). No significant differences were observed for the incidence of other nonhematological toxicities between the 2 groups. DBD failed to prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. Further studies are warranted to validate the efficacy of DBD in selected patients.
Coenzyme Q0 (CoQ0; 2,3-dimethoxy-5-methyl-1,4-benzoquinone), a major active constituent of Antrodia camphorata, has been shown to inhibit human triple-negative breast cancer (MDA-MB-231) cells through induction of apoptosis and cell-cycle arrest. Ecological studies have suggested a possible association between ultraviolet B (UVB) radiation and reduction in the risk of breast cancer. However, the underlying mechanism of the combination of CoQ0 and UVB in human estrogen receptor–positive breast cancer (MCF-7) remains unclear. In this study, the possible effect of CoQ0 on inducing apoptosis in MCF-7 cells under exposure to low-dose UVB (0.05 J/cm2) has been investigated. CoQ0 treatment (0-35 µM, for 24-72 hours) inhibits moderately the growth of breast cancer MCF-7 cells, and the cell viability was significantly decreased when the cells were pretreated with UVB irradiation. It was noted that there was a remarkable accumulation of subploid cells, the so-called sub-G1 peak, in CoQ0-treated cells by using flow cytometric analysis, which suggests that the viability reduction observed after treatment may result from apoptosis induction in MCF-7 cells. CoQ0 caused an elevation of reactive oxygen species, as indicated by dichlorofluorescein fluorescence, and UVB pretreatment significantly increased CoQ0-induced reactive oxygen species generation in MCF-7 cells. In addition, cells were exposed to CoQ0, and the induction of DNA damage was evaluated by single-cell gel electrophoresis (comet assay). CoQ0-induced DNA damage was remarkably enhanced by UVB pretreatment. Furthermore, CoQ0 induced apoptosis in MCF-7 cells, which was associated with PARP degradation, Bcl-2/Bax dysregulation, and p53 expression as shown by western blot. Collectively, these findings suggest that CoQ0 might be an important supplemental agent for treating patients with breast cancer.
Introduction: Surgical resection in patients with non–small cell lung cancer (NSCLC) may be associated with significant morbidity, functional limitations, and decreased quality of life. Objectives: The objective is to present health-related quality of life (HRQoL) changes over time before and 1 year after surgery in patients with NSCLC participating in a rehabilitation program. Methods: Forty patients with NSCLC in disease stage I to IIIa, referred for surgical resection at the Department of Cardiothoracic Surgery RT, Rigshospitalet, were included in the study. The rehabilitation program comprised supervised group exercise program, 2 hours weekly for 12 weeks, combined with individual counseling. The study endpoints were self-reported HRQoL (Functional Assessment of Cancer Therapy–Lung, European Organization for Research and Treatment in Cancer–Quality of Life Questionnaire-QLQ-C30, Short-Form-36) and self-reported distress, anxiety, depression, and social support (National Comprehensive Cancer Network Distress Thermometer, Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support), measured presurgery, postintervention, 6 months, and 1 year after surgery. Results: Forty patients were included, 73% of whom completed rehabilitation. Results on emotional well-being (P < .0001), global quality of life (P = .0032), and mental health component score (P = .0004) showed an overall statistically significant improvement during the study. Conclusion: This feasibility study demonstrated that global quality of life, mental health, and emotional well-being improved significantly during the study, from time of diagnosis until 1 year after resection, in patients with NSCLC participating in rehabilitation.
Previously, we have shown that boehmenan, a natural product isolated from the dried stem of Caulis clematidis armandii, exhibits various biological activities. The current study investigated the effects of boehmenan on the growth of human epidermoid carcinoma A431 cells. Cell viability and 50% inhibiting concentration (IC50) were assessed by CellTiter-Glo luminescent cell viability assay. Cell cycle arrest was measured by flow cytometry. Intracellular reactive oxygen species production and mitochondrial membrane potential (m) collapse were analyzed by a fluorescence spectrophotometer. The activation of epidermal growth factor receptor signaling pathway was evaluated by Western blot. The results showed that boehmenan significantly inhibited the growth of A431 cells (IC50 = 1.6 µM) in a concentration- and time-dependent manner. This compound also blocked cell cycle progression at G2/M phase and modulated mitochondrial apoptosis-related proteins, as evidenced by upregulating p21, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase protein levels and by downregulating Bcl-2, pro-caspase-9 levels. In addition, boehmenan also markedly induced intracellular reactive oxygen species production and m depolarization in a concentration-dependent manner. Furthermore, boehmenan-attenuated epidermal growth factor mediated the phosphorylation of signal transducer and activator of transcription 3 (STAT3), p70 ribosomal protein S6 kinase (p70S6)/S6 in a concentration-dependent manner. Taken together, our results suggest that boehmenan-mediated antiproliferative property in A431 cells was mediated partially by modulation of mitochondrial function and inhibition of STAT3 and p70S6 signal pathways.
Houttuynia cordata Thunb (H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata–induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata–mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata–mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A–FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.
The BCR-ABL kinase inhibitor, imatinib mesylate, is the front-line treatment for chronic myeloid leukemia, but the emergence of imatinib resistance has led to the search for alternative drug treatments. There is a pressing need, therefore, to develop and test novel drugs. Natural products including plants, microorganisms, and halobios provide rich resources for discovery of anticancer drugs. In this article, we demonstrate that emodin inhibited the growth of K562 cells harboring BCR-ABL in vitro and in vivo, and induced abundant apoptosis, which was correlated with the inhibition of PETN/PI3K/Akt level and deletion of BCR-ABL. These findings suggest that emodin is a promising agent to kill K562 cells harboring BCR-ABL.
JC-001 is a Chinese medicine that has been used to treat liver disease; however, its significance in cancer treatment has not been characterized. In this study, we used an immunocompetent tumor model to characterize the antitumor activity of JC-001. A total of 48 Hepa 1-6 tumor-bearing C57BL/6 mice were randomly grouped into 4 groups and treated with H2O or JC-001 via oral administration. After hepatoma cell lines, including HepG2, Hep3B, SK-Hep-1, and Hepa 1-6, underwent 96 hours of JC-001 treatment, a low cytotoxic effect was observed. In contrast, no direct cytotoxic effect of JC-001 on a normal human liver cell line, THLE-3, was observed under the same incubation conditions. Using a murine tumor model, we found that tumor growth could be inhibited by JC-001 in C57BL/6 mice but not in immunodeficient mice. Histopathological analysis of tumors from C57BL/6 mice revealed immune cell infiltration in tumors from the JC-001–treated group, as observed by hematoxylin and eosin staining; in addition, Ki67, hypoxia-inducible factor-1-α, and high mobility group box 1 expression levels were suppressed in the tumors. Both the coculture assay and murine spleen mRNA quantitative PCR analyses demonstrated that JC-001 could suppress Th17 immunity. Our data suggest that JC-001 is a Chinese medicine with low cytotoxicity that can significantly suppress tumor growth by immune regulation. This herbal remedy has great potential for future clinical application in hepatoma therapy.
Background. Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. Methods. The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor–positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. Results. Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly (P < .001) with age (<50 years, 74.1%; 50-60 years, 54.1%; >65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. Conclusions. This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.
Background: Mindfulness-based interventions (MBIs) to address self-regulation and lifestyle behaviors (diet, physical activity) may benefit endometrial cancer survivors (ECS), who are at increased risk for morbidity and mortality associated with obesity. However, the acceptability of mindfulness training and whether it can augment behavior change in ECS is unknown. We aimed to examine; 1) the feasibility of the Mindfulness in Motion + Diet (MIM+D) intervention and 2) the preliminary efficacy of MIM+D for improving mindfulness, diet, PA and health-related quality of life (HRQL). Methods: ECS (Mage=62.4, ±5yrs from diagnosis) completed assessments at baseline, 8 and 14 weeks. Feasibility was determined by intervention completion surveys, attendance and adherence data. We used repeated measures ANOVA’s (SPSS 22.0) and effect size estimates (Cohen’s d) to examine changes in mindfulness, diet, PA, and HRQL over time. Results: Thirteen ECS (76%) completed the MIM+D program and attendance (≥6/8 sessions) was 90%. Women reported favorably on the overall quality (mean of 4.75/5) and benefits of the MIM+D program; however, would have preferred receiving MIM+D closer to diagnosis. Intention to treat analyses found MIM+D did not significantly improve any outcomes. However, an intervention completers analysis showed significant change in mindfulness (p=.0039) and small to moderate estimates for change in fruits and vegetable intake (d=.23), MVPA (d=.45), RAND SF-36: MCS (d=.46), and sleep quality (d=.68). Conclusions: Integrating mindfulness training into behavioral interventions is feasible and ECS that adhere to these lifestyle programs may benefit. However, to future research should examine the-long term effects of mindfulness-based behavioral lifestyle interventions.
Background: Prostatectomy is associated with short- and long-term morbidity, which includes attenuation of muscle function and deterioration of lean body mass. Physical function is a known predictor of morbidity and mortality, with initial evidence indicating that presurgical exercise is associated with fewer postsurgical complications and shorter hospitalization. The aim was to determine the feasibility of a supervised presurgical exercise program for prostate cancer (PCa) patients scheduled for prostatectomy. Methods: Ten men (68+6.4 years old) with localized PCa undertook a 6-week resistance and aerobic exercise program prior surgery. Training was undertaken twice weekly and patients were assessed at baseline, presurgery, and 6 weeks postsurgery. Outcome measures included muscle and physical performance, body composition, urinary incontinence and questionnaire. Results: Muscle strength increased by 7.5% to 24.3% (P < .05) from baseline to presurgery but decreased to pretraining levels postsurgery, except for knee extensor strength (P = .247). There were significant improvements (P < .05) in the 6-m fast walk (9.3%), 400-m walk (7.4%), and chair rise (12.3%) at presurgery. Following surgery, improvements in physical performance were maintained. There was no change in lean or fat mass prior to surgery, but lean mass declined by 2.7 kg (P = .014) following surgery. There were no adverse effects from the exercise program. Conclusions: Exercise undertaken prior to prostatectomy improved muscle and physical performance, with functional benefits maintained 6 weeks postsurgery. Presurgical exercise for PCa patients has the potential to facilitate recovery by improving physical reserve capacity, especially in men with poor muscle nd physical performance.
Background: Among cancer care providers (CCPs), lack of knowledge constitutes an important barrier to the discussion of complementary and alternative medicine (CAM) use with patients. This study assessed CCPs’ needs and preferences regarding CAM information and training (I&T). Methods: An online survey was completed by 209 general practitioners, 437 medical specialists, 159 oncology nurses and medical assistants, and 244 psychologists and social workers engaged in cancer care. Latent class analysis (LCA) was used to identify subgroups of individuals with distinct preference patterns regarding I&T content. Results: CCPs prefer CAM I&T to be provided as lectures, information platforms on the internet, workshops, and e-mail newsletters. Concerning subject matters, many CCPs considered CAM therapy options for the treatment of a variety of cancer disease- and therapy-related symptoms to be very important (75%-72% of the sample); the same applies to an "overview of different CAM therapies" (74%). LCA identified 5 latent classes (LCs) of CCPs. All of them attached considerable importance to "medical indication," "potential side effects," and "tips for usage." LCs differed, however, in terms of overall importance ratings, the perceived importance of "patients’ reasons" for using specific CAM therapies, "case examples," and "scientific evidence." Notably, the 5 LCs were clearly present in all 4 occupational groups. Conclusions: CAM I&T should provide CCPs with an overview of different CAM therapies and show how CAM might help in treating symptoms cancer patients frequently demonstrate (eg, fatigue). Moreover, I&T programs should be flexible and take into account that individual information needs vary even within the same occupational group.
Background. Phyllanthus emblica L (PEL), a well-known medical plant, has been used in Asian countries for a long time. Increasing evidence suggests that it can prevent the tumorigenesis of cancer associated with nonresolving inflammation. However, the possible anti-inflammatory mechanism responsible for preventing tumorigenesis of precancerous lung lesions is not well elucidated. Materials and methods. Male A/J mice were randomly divided into 5 groups with 10 mice in each group: (1) blank group (saline), (2) benzo(a)pyrene [B(a)P] group, (3) and (4) B(a)P + PEL (5 g/kg/d, 10 g/kg/d, administered by gavage), (5) B(a)P + celecoxib (30 mg/kg/d, administered by gavage). Nodes on the lung surface were observed and calculated. The levels of macrophage inflammatory protein (MIP-2), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA) kits. Cyclo-oxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-α), IL-1β, miR-101, and Lin28B protein levels were evaluated by immunohistochemistry and Western blotting. Results. PEL extract treatment significantly reduced the number of nodes on the lung surface and attenuated B(a)P-induced levels of proinflammatory cytokines MIP-2, TNF-α, IL-6, and IL-1β in lung tissue. The protein expressions of COX-2 and HIF-α were significantly decreased by the treatment of PEL. In addition, both PEL extract and celecoxib markedly upregulate the expression of miR-101 while downregulating IL-1β and Lin28B levels. Conclusion. Our study indicated that treatment with PEL extract can not only protect the lung from inflammatory injury but effectively prevent precancerous lung lesions through regulating the IL-1β/miR-i101/Lin28B signaling pathway.
Background. Insomnia is a prominent complaint of cancer patients that can significantly affect their quality of life and symptoms related to sleep quality. Conventional drug approaches have a low rate of success in alleviating those suffering insomnia. The aim of this systematic review was to assess the efficacy of acupuncture in the management of cancer-related insomnia. Methods. A total of 12 databases were searched from their inception through January 2016 without language restriction. Randomized controlled trials (RCTs) and quasi-RCTs were included if acupuncture was used as the sole intervention or as an adjunct to another standard treatment for any cancer-related insomnia. The data extraction and the risk of bias assessments were performed by 2 independent reviewers. Results. Of the 90 studies screened, 6 RCTs were included. The risk of bias was generally unclear or low. Three RCTs showed equivalent effects on the Pittsburgh Sleep Quality Index and 2 RCTs showed the similar effects on response rate to those of conventional drugs at the end of treatment. The other RCT showed acupuncture was better than hormone therapy in the numbers of hours slept each night and number of times woken up each night. The 3 weeks of follow-up in 2 RCTs showed superior effects of acupuncture compared with conventional drugs, and a meta-analysis showed significant effects of acupuncture. Two RCTs tested the effects of acupuncture on cancer-related insomnia compared with sham acupuncture. One RCT showed favourable effects, while the other trial failed to do so. Conclusion. There is a low level of evidence that acupuncture may be superior to sham acupuncture, drugs or hormones therapy. However, the number of studies and effect size are small for clinical significance. Further clinical trials are warranted.
Purpose. Acute myeloid leukemia (AML) is the most deadly subtype of leukemia, and many patients with this disease seek other complementary therapies, one of which is Chinese medicine. We set out to provide reliable data regarding the benefit of Chinese herbal medicine (CHM) for AML patients, using mortality as the main outcome measure. We also characterized the herbal prescriptions of patients. Methods. Using the Taiwanese National Health Insurance Research Database, we performed a nationwide population-based cohort study among AML patients from 1997 to 2010. The Cox regression model was used to adjust for comorbidities and other variables, and the hazard ratios (HRs) of CHM users and non–CHM users were compared. Results. After 1:1 matching, 498 patients were included into the study. The HR of the CHM group was 0.41 (95% CI = 0.26-0.65; P = .0001) compared with the non-CHM group. This decrease in HR was also shown to be dose dependent (P < .001). The 3 single-herbs most commonly prescribed were Salvia miltiorrhiza (Dan Shen), Astragalus membranaceus (Huang Qi), and Spatholobus suberectus (Ji Xue Teng). The 3 mutli-herb products most commonly prescribed were Jia Wei Xiao Yao San, Gui Pi Tang, and Qi Ju Di Huang Wan. Conclusion. Prospective controlled clinical data is still needed, however, this study provides real-world data regarding the benefit AML patients may have from CHM. This study suggests that all AML patients, regardless of age or other prognostic factors, may achieve longer survival times when receiving CHM in addition to standard therapy.
Purpose: Essential thrombocythemia, polycythemia vera, and myelofibrosis are rare chronic hematological malignancies known as myeloproliferative neoplasms (MPNs) and are characterized by deregulated myeloid lineage cell production, splenomegaly, and heterogeneous symptom profiles. MPN patients suffer from a significant symptom burden (eg, fatigue, depressive symptoms, early satiety) and an impaired overall quality of life (QoL). Current treatments typically include pharmacological approaches, which may come with additional side effects and may be limited by treatment-associated toxicities (ie, cytopenias). Nonpharmacological approaches such as physical activity may be beneficial for reducing symptom burden and improving QoL. To date, no studies have examined physical activity as a nonpharmacological approach in MPN patients despite preliminary evidence supporting its benefit in other hematological cancers. The purpose of this article is to (1) review the literature related to physical activity and specific hematological cancer subtypes and to (2) make suggestions for future research involving physical activity in MPN patients as a symptom management strategy. Methods: A brief review of studies examining physical activity in leukemias, lymphomas, and myelomas (excluding stem-cell transplant patients) was conducted. Results: There is preliminary evidence to suggest that physical activity may be an effective approach to improve patient-reported outcomes (fatigue, depression, anxiety, sleep), physical fitness (cardiovascular fitness, balance, body composition), and overall QoL in other hematological cancers. Conclusions: Based on encouraging findings in other hematological cancers, future research should examine the feasibility and effectiveness of physical activity in MPN patients.
Flavokawain B (FKB) is known to possess promising anticancer abilities. This is demonstrated in various cancer cell lines including HeLa cells. Cervical cancer is among the most widely diagnosed cancer among women today. Though FKB has been shown to be effective in treating cancer cells, the exact molecular mechanism is still unknown. This study is aimed at understanding the effects of FKB on HeLa cells using a microarray-based mRNA expression profiling and proteome profiling of stress-related proteins. The results of this study suggest that FKB induced cell death through p21-mediated cell cycle arrest and activation of p38. However, concurrent activation of antioxidant-related pathways and iron sequestration pathway followed by activation of ER-resident stress proteins clearly indicate that FKB failed to induce apoptosis in HeLa cells via oxidative stress. This effect implies that the protection of HeLa cells by FKB from H2O2–induced cell death is via neutralization of reactive oxygen species.
Purpose: To define the use of complementary and alternative medicine (CAM) in individuals presenting for care at a comprehensive cancer center. Patients and Methods: A total of 17 639 individuals presenting to an NCI-designated Comprehensive Cancer Center (and consortium sites) completed a questionnaire regarding CAM use. Data were analyzed using the univariate 2 test to assess CAM use associated with a number of variables, including cancer status, age, gender, marital status, ethnicity, race, employment, and education level. Results: Eighty-seven percent of individuals who completed the CAM survey acknowledged CAM therapy use within the previous 12 months. Of the 5 broad categories of CAM, the most commonly used were biologically based approaches (14 759/17 639 [83.67%]), mind-body interventions (4624/17 485 [26.45%]), manipulative and body-based therapies (3957/17 537 [22.56%]), alternative medical systems (429/15 952 [2.69%]), and energy therapies (270/15 872 [1.7%]). CAM use was more prevalent among women, non-Hispanics, Caucasians, patients 60 to 69 years of age, and those who are married, have a higher level of education, and are employed (P < .005). Conclusions: This is the largest report of CAM use in individuals presenting for care at a comprehensive cancer center. Our analysis revealed that a very high percentage of patients utilize CAM. Because many of these CAM interventions are not studied in oncology patients, additional research on safety, efficacy, and mechanisms of action are essential. Furthermore, it is important that oncologists understand CAM modalities and counsel their patients about their use.
Women are exposed to indoor and outdoor artificial light at night (ALAN) in urban and rural environments. Excessive exposure to hazardous ALAN containing short wavelength light may suppress pineal melatonin production and lead to an increased breast cancer (BC) risk. Our objective was to address the differences in BC risks related to light exposure in urban and rural communities. We examined indoor and outdoor light habits of BC patients and controls that had lived in urban and rural areas in a 5-year period, 10 to 15 years before the time of the study. Individual data, night time sleeping habits and individual exposure to ALAN habits were collected using a questionnaire. A total of 252 women (110 BC patients and 142 controls) participated in this study. The sample was divided to subgroups according to dwelling area and disease status. Age matching was completed between all subgroups. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for urban and rural women separately, using binary logistic regression. OR results of urban population (92 BC patients and 72 control) revealed that BC risk increases with daily use of cellphone (OR = 2.13, 95% CI = 1.01-4.49, P < .05) and residence near strong ALAN sources (OR = 1.51, 95% CI = 0.99-2.30, P < .06). Nevertheless, BC risk decreases if a woman was born in Israel (OR = 0.44, 95% CI = 0.21-0.93, P < .03), longer sleep duration (OR = 0.75, 95% CI = 0.53-1.05, P < .1), and reading with bed light illumination before retiring to sleep (OR = 0.77, 95% CI = 0.61-0.96, P < .02). Furthermore, in the rural population (18 BC patients and 66 control) BC risk increases with the number of years past since the last menstruation (OR = 1.12, 95% CI = 1.03-1.22, P < .01). However, BC risk decreases with longer sleep duration (OR = 0.53, 95% CI = 0.24-1.14, P < .1), reading with room light illumination before retiring to sleep (OR = 0.55, 95% CI = 0.29-1.06, P < .07), and sleeping with closed shutters during the night (OR = 0.66, 95% CI = 0.41-1.04, P < .08). These data support the idea that indoor and outdoor nighttime light exposures differ between urban and rural women. Therefore, we suggest that women can influence BC risk and incidence by applying protective personal lighting habits. Further studies with larger sample sizes are needed to strengthen the results.
Background. Malignant pleural effusion (MPE) is a common complication in most malignancies. Despite its frequent occurrence, current knowledge of MPE remains limited and the effect of the management is still unsatisfying. Traditional Chinese medicine (TCM) external treatment has unique advantages, such as quicker efficacy and fewer side effects. Objective. To observe the effects and safety of Kang’ai Xiaoshui ointment (TCM herbal ointment) in MPE. Design. This was a placebo-controlled double-blinded randomized study. A total of 80 patients were enrolled, of which 72 were randomized to receive Kang’ai Xiaoshui ointment or placebo at an allocation ratio of 1:1. Kang’ai Xiaoshui ointment or placebo was applied on the thorax wall for 8 hours daily. The intervention lasted 2 weeks. Kang’ai Xiaoshui ointment consisted of Astragalus membranaces (黄), Semen pharbitidis (牛子), Cassia twig (桂枝), Pericarpium arecae (大腹皮), Curcuma zedoary (术), Borneol (冰片), and other substances. In both groups, diuresis and drainages were used as needed. Outcomes covered the quantity of pleural effusion evaluation, TCM Symptom Scale, Karnofsky Performance Scale, and safety indicators such as routine blood test, blood biochemistry test, and response table of skin irritation. Results. Of 72 patients randomized to receive Kang’ai Xiaoshui ointment or placebo along with symptomatic treatment, the response rate was documented as 42.4% for the treatment group and 25.0% for the placebo group (P = .138). As for the TCM symptom scale, the treatment group showed improvement in chest distress (P = .003), fullness and distention (P = .042), shortness of breath (P < .001), no statistical significance in palpitation (P = .237), and pain (P = .063), whereas the placebo group did not show statistical significance in any of the 5 symptoms. Major adverse events related to the treatment, mainly skin irritation, were distributed equally. Conclusions. Kang’ai Xiaoshui ointment showed a potential of reducing MPE, and it could alleviate symptoms of dyspnea. Thus, it may be appropriate as a supplementary intervention for MPE. There were some flaws in the study design. A larger scale and better designed trial is advocated.
Background. Large-scale surveys of complementary traditional Chinese medicine (TCM) use in pediatric cancer patients are lacking. The aim of our study was to investigate the use of TCM in pediatric cancer patients. Methods. We analyzed cancer patients younger than 18 years (n = 12 965) who were registered in the National Health Insurance Research Database in Taiwan between 2001 and 2011. Patients were categorized into TCM or non–TCM users based on their use of TCM. Results. In Taiwan, 8086 (62.4%) children with cancer sought TCM treatment at some point. Children in older age groups, including school-aged children and adolescents, were more likely to use TCM. There was no significant difference in the distributions of gender and urbanization. The 3 most common diseases for which TCM users visited the clinic were neoplasm (33.2%), respiratory system disease (32.9%), and infectious disease (8.86%). The most commonly utilized TCM therapy was Chinese herbal remedies. Patients who had comorbid conditions such as allergic rhinitis, dyspepsia, disorders of menstruation, and disease of the musculoskeletal system and connective tissue tended to visit TCM clinics. Conclusions. Adjunctive TCM use is not low in Taiwanese children with cancer. Further studies to investigate the efficacy and safety of TCM in children with cancer are warranted.
Purpose. So-called spontaneous remissions in cancer often seem to occur after febrile events. Mistletoe preparations (MPs) are used off-label intravenously to induce fever within concepts of integrative oncology. We wanted to investigate the frequency of febrile reactions and safety related to intravenously applied MPs (IAMPs). Methods. This was a retrospective analysis of data from consecutive cancer patients who were treated in 2 anthroposophic hospitals with IAMPs. The main outcome parameter was the rate of core temperature increase to ≥38.5°C within 24 hours after IAMPs. Secondary outcome parameters were Common Toxicity Criteria for Adverse Events (CTCAE; version 4.0). Results. 59 patients, with in total 567 IAMPs, were analyzed; 45 patients (76%, 95% CI = 65%-87%) had an increase of core temperature to ≥38.5°C after at least 1 treatment. Mean increase in temperature was 1.5°C ± 0.8°C. Adverse events were mostly fever-related symptoms (headache, joint pain, shivering). Grade 1 allergic reactions were documented in 0.6% of treatments. CTCAEs grade 3 to 5 did not occur; 38/59 patients had advanced and/or metastatic disease. Conclusion. IAMPs resulted in febrile reactions to >38.5°C in the majority of patients and can be considered as safe. Adverse events were mostly related to fever and were not severe.
Background. The use of natural health products in prostate cancer (PrCa) is high despite a lack of evidence with respect to safety and efficacy. Fish-derived omega-3 fatty acids possess anti-inflammatory effects and preclinical data suggest a protective effect on PrCa incidence and progression; however, human studies have yielded conflicting results. Methods. A search of OVID MEDLINE, Pre-MEDLINE, Embase, and the Allied and Complementary Medicine Database (AMED) was completed for human interventional or observational data assessing the safety and efficacy of fish-derived omega-3 fatty acids in the incidence and progression of PrCa. Results. Of 1776 citations screened, 54 publications reporting on 44 studies were included for review and analysis: 4 reports of 3 randomized controlled trials, 1 nonrandomized clinical trial, 20 reports of 14 cohort studies, 26 reports of 23 case-control studies, and 3 case-cohort studies. The interventional studies using fish oil supplements in patients with PrCa showed no impact on prostate-specific antigen levels; however, 2 studies showed a decrease in inflammatory or other cancer markers. A small number of mild adverse events were reported and interactions with other interventions were not assessed. Cohort and case-control studies assessing the relationship between dietary fish intake and the risk of PrCa were equivocal. Cohort studies assessing the risk of PrCa mortality suggested an association between higher intake of fish and decreased risk of prostate cancer–related death. Conclusions. Current evidence is insufficient to suggest a relationship between fish-derived omega-3 fatty acid and risk of PrCa. An association between higher omega-3 intake and decreased PrCa mortality may be present but more research is needed. More intervention trials or observational studies with precisely measured exposure are needed to assess the impact of fish oil supplements and dietary fish-derived omega-3 fatty acid intake on safety, PrCa incidence, treatment, and progression.
Purpose. Doxorubicin has been found to be associated with insulin resistance in animal models. Onion, a so-called functional food, is noted to affect the insulin signaling pathway of diabetes in vitro. To our knowledge, this is the first study to investigate the effects of consuming fresh yellow onions on insulin-related indices compared with a low–onion-containing diet among breast cancer (BC) patients treated with doxorubicin. Methods. This parallel-design, randomized, triple-blind, controlled clinical trial was conducted on 56 eligible BC patients (aged 30-63 years), diagnosed with invasive ductal carcinoma. Following their second cycle of chemotherapy, subjects were assigned in a stratified-random allocation to receive body mass index–dependent 100 to 160 g/d of onion as high onion group (HO; n = 28) or 30 to 40 g/d small onions in low onion group (LO; n = 28) for 8 weeks intervention. Participants, care givers, and those who assessed laboratory analyses were blinded to the assignments (IRCT Registry No.: IRCT2012103111335N1). Results. The compliance level of participants in the analysis was as high as 87.85%. A total of 23 available cases was analyzed in each group. The daily use of HO resulted in a significant decrease in serum fasting blood glucose and insulin levels in comparison with LO, over the period of study (P < .001). Posttreatment with HO showed a significant decrease in homeostasis model of assessment-insulin resistance relative to changes in the LO group (P < .05). A comparison of the changes that occurred throughout pre- and postdose treatments indicated improved quantitative insulin sensitivity check index (P < .05) and controls on C-peptide in the HO group (P < .05). Conclusions. The present study demonstrated the effectiveness of onion to ameliorate hyperglycemia and insulin resistance in BC during doxorubicin-based chemotherapy.
Although it may sound unpleasant, camel urine has been consumed extensively for years in the Middle East as it is believed to be able to treat a wide range of diseases such as fever, cold, or even cancer. People usually take it by mixing small drops with camel milk or take it directly. The project aims to study the effects of camel urine in inhibiting the growth potential and metastatic ability of 4T1 cancer cell line in vitro and in vivo. Based on the MTT result, the cytotoxicity of camel urine against 4T1 cell was established, and it was dose-dependent. Additionally, the antimetastatic potential of camel urine was tested by running several assays such as scratch assay, migration and invasion assay, and mouse aortic ring assay with promising results in the ability of camel urine to inhibit metastatic process of the 4T1 cells. In order to fully establish camel urine’s potential, an in vivo study was carried out by treating mice inoculated with 4T1 cells with 2 different doses of camel urine. By the end of the treatment period, the tumor in both treated groups had reduced in size as compared to the control group. Additional assays such as the TUNEL assay, immunophenotyping, cytokine level detection assay, clonogenic assay, and proteome profiler demonstrated the capability of camel urine to reduce and inhibit the metastatic potential of 4T1 cells in vivo. To sum up, further study of anticancer properties of camel urine is justified, as evidenced through the in vitro and in vivo studies carried out. Better results were obtained at higher concentration of camel urine used in vivo. Apart from that, this project has laid out the mechanisms employed by the substance to inhibit the growth and the metastatic process of the 4T1 cell.
Objective. The aim of this study was to determine the feasibility, acceptability, and safety of using moxibustion for treating anorexia and improving quality of life in patients with metastatic cancer. Methods. We conducted a randomized sham-controlled trial of moxibustion. Sixteen patients with metastatic cancer were recruited from Daejeon, South Korea. The patients were randomly placed into a true or a sham moxibustion group and received 10 true or sham moxibustion treatments administered to the abdomen (CV12, CV8, CV4) and legs (ST36) over a 2-week period. Outcome measures included interest in participating in the trial, identification of successful recruitment strategies, the appropriateness of eligibility criteria, and compliance with the treatment plan (ie, attendance at treatment sessions). Clinical outcomes included results of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), answers on the European Organization for Research and Treatment of Cancer 30-item core quality of life (EORTC QLQ-C30) questionnaires, scores on the visual analogue scale (VAS), and the results from blood tests and a safety evaluation. Results. Moxibustion was an acceptable intervention in patients with metastatic cancer. Compliance with the treatment protocol was high, with 11 patients completing all 10 treatments. No serious adverse events related to moxibustion occurred, but 4 patients in the true moxibustion group reported mild rubefaction, which disappeared in a few hours. Conclusion. This study suggests that moxibustion may be safely used to treat anorexia and improve quality of life in patients with metastatic cancer. However, further research is needed to confirm this result.
Fuzheng Qingjie (FZQJ) granules, a compound Chinese medicine, have been used as an adjuvant therapy for alimentary tract cancers. However, the underlying anticancer mechanisms are still not well understood. In the present study, HepG2 cells were treated with FZQJ-containing serum. Cell proliferation was evaluated using MTT assay. Apoptosis was analyzed using a flow cytometer. Cell ultrastructure was observed under a transmission electron microscope. The mitochondrial membrane potential () was examined with JC-1 dye. In H22 tumor–bearing mice, CD4+ T cells, CD8+ T cells, CD3+ T cells, and natural killer (NK) cells in peripheral blood were evaluated cytometrically. Interleukin (IL)-2 and tumor necrosis factor (TNF)-α levels were measured using radioimmunoassay.The mRNA levels of Bax and Bcl-2 were examined by reverse transcription–polymerase chain reaction. The protein levels of Bax, Bcl-2, cytochrome C, caspase 3 and 9, PARP, and CD69 were examined by Western blotting. The apoptotic cells in tissues were observed using TUNEL method. Alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine (CRE) were detected by an automatic biochemical analyzer. The results showed that FZQJ-containing serum remarkably inhibited proliferation of HepG2 cells in dose- and time-dependent manners, induced HepG2 cell apoptosis and caused a decrease of . Analysis of tumor tissue showed that FZQJ-induced apoptosis was accompanied by downregulation of Bcl-2 and upregulation of Bax, release of cytochrome c, activation of caspase 3 and 9, and cleavage of PARP. In addition, FZQJ increased the percentages of CD4+ T and NK cells, the ratio of CD4+/CD8+ T cells as well as the levels of serum TNF-α. FZQJ also increased CD69 expression in tumor tissue. No hepatorenal toxicity was observed in H22 tumor–bearing mice. These results indicated that FZQJ could inhibit the growth of hepatoma cells via regulating immune function and inducing mitochondria mediated apoptosis.
The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 mRNA; TXL potently reversed most multidrug resistance via downregulation of MDR-1 protein. In conclusion, the comprehensive and holistic effects of TXL were demonstrated with (a) mutual accentuation and mutual enhancement, (b) mutual counteraction and mutual suppression, and (c) mutual antagonism among the 3 constituent fractions. Moreover, the design of the present study may lead to further development of more tissue-specific effective drugs with minimal side effects for clinical use in combating carcinoma.
Purpose. Advanced cancer patients with disease progression develop cachexia. Nevertheless, cancer patients at nutritional risk have shown improved body weight and quality of life with oral nutritional supplements. Method. This was a randomized controlled trial in adult female cancer patients (n = 63) attending palliative clinics, with symptoms of cachexia. Eligible patients were randomly distributed into control (n = 33) and intervention (n = 30) groups. Both groups were provided with nutritional and physical activity counseling, but the intervention group received an additional 100 g of Improved Atta (IAtta) for 6 months daily consumption. This study was designed to assess the efficacy of IAtta (with counseling) in enhancing the health status of cachexic patients. Anthropometric measurements, dietary intake, physical activity level and quality of life parameters were assessed at baseline, after 3 months, and at the end of 6 months. Results. Patients in the control group (n = 15) had significantly decreased body weight (P = .003), mid–upper-arm circumference (P = .002), and body fat (P = .002) by the end of intervention. A trend of body weight gain in the intervention group (n = 17; P = .08) and significant increase of body fat (P = .002) was observed; moreover, patients reported a significant improvement in fatigue (P = .002) and appetite scores (P = .006) under quality-of-life domains at the end of intervention. Conclusions. Embedding a nutrition-sensitive intervention ( IAtta ) within Indian palliative care therapy may improve quality of life and stabilize body weight in cancer cachexia patients.
Hypotheses. Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. Study design. We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. Methods. 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. Results. The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. Conclusion. Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.
Background. The Chinese herbal mixture, Tien-Hsien liquid (THL), has been used as an anticancer dietary supplement for more than 20 years. Our previous studies have shown that THL can modulate immune responseand inhibit tumor growth. In this study, we further evaluated the effect of THL on anticancer immune response in mice vaccinated with -ray-irradiated tumor cells. Methods. The antitumor effect of THL was determined in mice vaccinated with low-tumorigenic CT-26-low colon cancer cells or -ray-irradiated high-tumorigenic CT-26-high colon cancer cells. The number of natural killer (NK) cells and T lymphocytes in the spleen was analyzed by flow cytometry. The tumor-killing activities of NK cells and cytotoxic T lymphocytes (CTLs) were analyzed by flow cytometry using YAC-1 and CT-26-high cells, respectively, as target cells. The levels of IFN-, IL-2, and TNF-α were determined by ELISA. Results. THL suppressed the growth of CT-26-high tumor in mice previously vaccinated with low-tumorigenic CT-26-low cells or -irradiated CT-26-high cells. THL increased the populations of NK cells and CD4+ T lymphocytes in the spleen and enhanced the tumor-killing activities of NK cells and CTL in mice vaccinated with -irradiated CT-26-high cells. THL increased the production of IFN-, IL-2, and TNF-α in mice vaccinated with -irradiated CT-26-high cells. Conclusion. THL can enhance the antitumor immune responses in mice vaccinated with killed tumor cells. These results suggest that THL may be used as a complementary medicine for cancer patients previously treated with killed tumor cell vaccines, radiotherapy, or chemotherapy.
Background. Very few studies have been conducted to examine the prevalence, frequency, perceived effectiveness, and possible influencing factors of use of meditation in patients with cancer. Objectives. To examine use of mindfulness sitting medication (MSM) in Chinese American women in treatment of cancer, its relationship to specific symptom distress, and possible influencing factors of MSM. Methods. Volunteer participants were recruited through the American Cancer Society support groups. The participants completed a demographic data form, a researcher-developed criteria and checklist for MSM, and the Memorial Symptom Assessment Scale–Short Form. Results. Eighty-nine Chinese American women with a mean age of 58 years completed the questionnaires. Twenty-one patients (24%) reported the use of MSM during active treatment of cancer. Patients who had higher education, better income, better English proficiency, and health insurance were more likely to use MSM. Patients who had more symptom distress also reported to use more MSM. Most patients (20/21) who used meditation considered it effective. After controlling other variables, better English proficiency, breast cancer, and higher symptom distress predicted the use of MSM in Chinese American women in treatment of cancer. Conclusions. About 24% of Chinese American women used MSM in the treatment of cancer and most of them considered it effective. Symptom distress and English proficiency levels predicted the use of MSM. Implications for Practice. Given the effectiveness of MSM, oncology nurses could recommend using MSM in Chinese American women in treatment of cancer, especially for patients who had higher symptom distress.
Background. Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. Methods. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Results. Kefir water was cytotoxic toward 4T1 cells at IC50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water–treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water–treated group. Conclusions. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment.
Background. Naturopathic oncology in conjunction with conventional treatment is commonly referred to as integrative oncology (IO). Clinics directed by oncology board certified NDs (Fellows of the American Board of Naturopathic Oncology or FABNOs) provide high-quality data for describing IO therapies, their costs and measuring clinical outcomes. Purpose. To describe the types of IO therapies prescribed to breast cancer patients by ND FABNO physicians. Study participants (n = 324). Women who sought care at 1 of 6 naturopathic oncology clinics in Washington State were asked to enroll in a prospective 5 year observational outcomes study. Methods. Medical records were abstracted to collect treatment recommendations and cost data. Results. More than 72 oral or topical, nutritional, botanical, fungal and bacterial-based medicines were prescribed to the cohort during their first year of IO care. Trametes versicolor was prescribed to 63% of the women. Mind-body therapy was recommended to 45% of patients, and 49% received acupuncture. Also, 26% were prescribed injectable therapy, including mistletoe, vitamin B complex (12%), IV ascorbate (12%), IV artesunate (7%), and IV nutrition and hydration (4%). Costs ranged from $1594/year for early-stage breast cancer to $6200/year for stage 4 breast cancer patients. Of the total amount billed for IO care for 1 year for breast cancer patients, 21% was out-of-pocket. Conclusions. IO care for women with breast cancer consists of botanical and mushroom oral therapies, parenteral botanical and nutrient therapy, mind-body medicine and acupuncture. IO clinic visits and acupuncture are partially paid for by medical insurance companies.
Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan (Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells.
Cysteine X cysteine (CXC) chemokine receptor 4 (CXCR4) and C-X-C motif chemokine 12 (CXCL12) were originally identified as chemoattractants between immune cells and sites of inflammation. Since studies have validated an increased level of CXCL12 and its receptor in patients with colorectal cancers, CXCL12/CXCR4 axis has been considered as a valuable marker of cancer metastasis. Therefore, identification of CXCR4 inhibitors has great potential to abrogate tumor metastasis. Onbaekwon (OBW) is a complex herbal formula that is derived from the literature of traditional Korean medicine Dongeuibogam. In this study, we demonstrated that OBW suppressed CXCR4 expression in various cancer cell types in a concentration- and time-dependent manner. Both proteasomal and lysosomal inhibitors had no effect to prevent the OBW-induced suppression of CXCR4, suggesting that the inhibitory effect of OBW was not due to proteolytic degradation but occurred at the transcriptional level. Electrophoretic mobility shift assay further confirmed that OBW could block endogenous activation of nuclear factor kappa B, a key transcription factor that regulates the expression of CXCR4 in colon cancer cells. Consistent with the aforementioned molecular basis, OBW abolished cell invasion induced by CXCL12 in colon cancer cells. Together, our results suggest that OBW, as a novel inhibitor of CXCR4, could be a promising therapeutic agent contributing to cancer treatment.
Objective. The study aimed to explore latent profiles of coping in Chinese women newly diagnosed with breast cancer and examine the differences of psychological distress, demographic, and medical characteristics across profiles. Methods. Latent profile analysis was used to identify 3 classes of copers based on data from 618 Chinese women newly diagnosed with breast cancer who completed questionnaires assessing their coping strategies and psychological distress. Results. "Adaptive coper," reporting most use of adaptive cognitive coping strategies, behaviors of acceptance and shifting attention, and least use of maladaptive cognitive coping strategies, had the best psychological adjustment. "Negative coper," characterized by most use of maladaptive cognitive coping strategies, least use of adaptive cognitive coping strategies except "putting in perspective," and median levels of medical coping behaviors, had the worst psychological adjustment. "Inconsistent coper," with great use of all cognitive coping strategies, and most behaviors of fighting against the disease, and fewest behaviors of attention shift, had relatively high levels of psychological distress. Younger age, less education, shorter time since diagnosis, widowed, living in rural areas, and undergoing chemotherapy are possible markers for patients with less adaptive coping patterns. Conclusions. Interventions should be developed according to the different coping profiles of patients, and the key group to target is "negative copers," who may benefit from cognitive behavioral approaches that combine emotion, cognition and behavior, which could help them more effectively appraise and cope with stressful events.
The aim of this study was to investigate the anticancer effect of a combination of D-fraction polysaccharide from Grifola frondosa (DFP) and vitamin C (VC) on hepatocellular carcinoma in vitro. DFP is a bioactive extract from the maitake mushroom. Anticancer activity was demonstrated using various concentrations of DFP alone or in combination with VC against the human hepatocarcinoma SMMC-7721 cell line. To investigate the anticancer mechanism, studies designed to detect cell apoptosis were conducted. Results from the MTT assay indicated that a combination of DFP (0.2 mg/mL) and VC (0.3 mmol/L) led to a 70% reduction in cell viability. Flow cytometry results indicated that DFP/VC treatment induced apoptosis in approximately 65% SMMC-7721 cells. Cell cycle analysis identified cell cycle arrest at the G2/M phase following DFP/VC treatment for 48 hours. In addition, cellular morphological changes were observed using transmission electron microscopy. Western blot analysis revealed that the upregulation of BAX, downregulation of Bcl-2, activation of poly-(ADP-ribose)-polymerase (PARP), and the release of cytochrome c were observed in cells treated with the combination of DFP/VC, which showed that the mechanism of anticancer activity in the SMMC-7721 hepatocarcinoma cells involved induction of apoptosis.
Purpose. Availability without prescription restriction, low cost, and simple oral administration allow cancer patients to use probiotics without knowledge of potential risks. We present a survey of probiotic use and the association with patient tumor characteristics in cancer patients treated at the outpatient department of the National Cancer Institute in Slovakia. Patients and Methods. Between March and December 2014, 499 patients were asked to evaluate their overall experience with probiotics by questionnaire form, including the length and method of use relative to anticancer therapy, expectations, side-effect experiences, understanding of the possible risks, dietary supplement use, and others. The relevant data were statistically evaluated. Results. The cohort consisted of 323 women (64.7%) and 176 men (35.3%); 91.6% were undergoing chemotherapy (2.6% together with radiotherapy) and 8.4% had no anticancer therapy. The prevalence of probiotic use was 28.5% and only 12 patients using probiotics (8.5%) described negative side effects. Most patients declared consideration of probiotic use based on recommendation from a physician (37.3%) or a pharmacist (14.8%). Nevertheless, up to 86.6% of patients declared no knowledge of possible risks. Statistically significant correlation was found between probiotic use and age of patients (P < .008), gender (P < .023), and taking other dietary supplements (P < .000002). Conclusions. In this prospective study, we present for the first time the prevalence, side-effect experience, and aspects that most likely influence probiotic use in cancer patients. Minimal knowledge of risks underlines the importance of an active approach by oncologists to inform patients about probiotic safety.
Background. Chinese herbal medicine (CHM) has been used for thousands of year in Eastern countries. First-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment is the standard treatment in stage IV pulmonary adenocarcinoma patients who had tumor EGFR mutations. This study was to find the efficacy of CHM on lung cancer treatment. Materials and Methods. We retrospectively reviewed chart records of our stage IV EGFR-mutated pulmonary adenocarcinoma patients who received first-line EGFR-TKI treatment from January 2010 to September 2014. Results. Total, 527 patients were studied. Among them, 34 patients received CHM treatment, including 24 patients who received CHM treatment from the beginning of first-line EGFR-TKI treatment and 10 patients who started to receive CHM treatment after their disease had progressed to EGFR-TKI treatment. Median progression-free survival (PFS) of first-line EGFR-TKI treatment was numerically better in patients who also received CHM than those who did not (12.1 months vs 10.5 months, P = .7668). Overall survival of those 24 patient who received CHM treatment together with EGFR-TKI was 30.63 months (95% CI = 11.7 to not reached), compared to 23.67 months in the remaining patients (95% CI = 21.37-26; hazard ratio = 0.75; P = .399). No increase of CHM-related toxicities was found during CHM treatment, compared with EGFR-TKI treatment alone (P > .05). Conclusion. Alternative CHM treatment during first-line EGFR-TKI treatment did no harm to the patients and PFS and overall survival was numerically better, although not significant, than those patients who did not receive CHM treatment.
Background. This meta-analysis examined the effects of exercise training on length of hospital stay, postoperative complications, exercise capacity, 6-minute walking distance (6MWD), and health-related quality of life (HRQoL) in patients following resection of non–small cell lung cancer (NSCLC). Methods. This review searched PubMed, EMBASE, and the Cochrane Collaboration data base up to August 16, 2015. It includes 15 studies comparing exercise endurance and quality of life before versus after exercise training in patients undergoing lung resection for NSCLC. Results. This review identified 15 studies, 8 of which are randomized controlled trials including 350 patients. Preoperative exercise training shortened length of hospital stay; mean difference (MD): –4.98 days (95% CI = –6.22 to –3.74, P < .00001) and also decreased postoperative complications for which the odds ratio was 0.33 (95% CI = 0.15 to 0.74, P = .007). Four weeks of preoperative exercise training improved exercise capacity; 6MWD was increased to 39.95 m (95% CI = 5.31 to 74.6, P = .02) .While postoperative exercise training can also effectively improve exercise capacity, it required a longer training period; 6MWD was increased to 62.83 m (95% CI = 57.94 to 67.72) after 12 weeks of training (P < .00001). For HRQoL, on the EORTC-QLQ-30, there were no differences in patients’ global health after exercise, but dyspnea score was decreased –14.31 points (95% CI = –20.03 to –8.58, P < .00001). On the SF-36 score, physical health was better after exercise training (MD = 3 points, 95% CI = 0.81 to 5.2, P = .007) while there was no difference with regard to mental health. The I2 statistics of all statistically pooled data were lower than 30%. There was a low amount of heterogeneity among these studies. Conclusions. Evidence from this review suggests that preoperative exercise training may shorten length of hospital stay, decrease postoperative complications and increase 6MWD. Postoperative exercise training can also effectively improve both the 6MWD and quality of life in surgical patients with NSCLC, but requiring a longer training period.
Docetaxel (DTX) is an effective commercial anticancer agent for chemotherapy in non–small cell lung cancer (NSCLC), breast cancer, gastric cancer, and prostate cancer, but its adverse effects including edema, neurotoxicity, and hair loss limit its application. To improve the chemotherapeutic efficacy of DTX and reduce adverse effects, combination therapy is one of the alternative methods. So chrysin, which has various biological activities including anticancer effects, was considered. In vitro, the combination of chrysin and DTX was investigated in A549 cells. Increased cytotoxicity, suppressed cellular proliferation, and induced apoptosis were observed with posttreatment of chrysin following DTX treatment. In vivo, chrysin enhanced the tumor growth delay of DTX and increased DTX-induced apoptosis in the A549-derived xenograft model. Furthermore, chrysin prevented DTX-induced edema in ICR mouse. These results indicated that chrysin strengthened the therapeutic efficacy of DTX and diminished the adverse effect of DTX, suggesting chrysin could be exploited as an adjuvant therapy for NSCLC.
Lavandula angustifolia is the most widely cultivated Lavandula species. The extraction of its flower and leaves has been used as herbal medicine. In this study, the in vitro antitumor activities were tested on human prostate cancer PC-3 and DU145 cell lines. Flow cytometry technology was applied to study apoptosis induction and cell cycle arrest. The PC-3 cell line was used to establish subcutaneous xenograft tumors in nude mice. Paraffin sections from xenograft tumor specimens were used in the TUNEL (terminal deocynucleotide transferase dUTP nick end labeling) assay and an immunohistochemistry assay to detect cell proliferation markers Ki67 and PCNA. Lavender essential oil, linalool, and linalyl acetate showed stronger inhibitory effect on PC-3 cells than on DU145 cells. The apoptotic cell populations observed in PC-3 cells treated with lavender essential oil, linalool, and linalyl acetate were 74.76%, 67.11%, and 56.14%, respectively. The PC-3 cells were mainly arrested in the G2/M phase. In the xenograft model with PC-3 cell transplantation, essential oil and linalool significantly suppressed tumor growth. The immunosignals of Ki67 and PCNA in the essential oil, linalool, and linalyl acetate treatment groups were significantly lower than that of the control group in xenograft tumor sections. The TUNEL assay indicated that each of the 3 phytochemicals significantly induced apoptosis compared to the control group. This study provides novel insight and evidence on the antiproliferative effect of L angustifolia essential oil and its major constituents on human prostate cancer. The antitumor effect was associated with cell proliferation inhibition and apoptosis induction in xenograft tumors.
Background. Cancer patients widely seek integrative oncology which embraces a wide variety of treatments and system approaches. Objective. To investigate the concepts, therapeutic goals, procedures, and working conditions of integrative oncology doctors in the field of anthroposophic medicine. Methods. This qualitative study was based on in-depth interviews with 35 highly experienced doctors working in hospitals and office-based practices in Germany and other countries. Structured qualitative content analysis was applied to examine the data. Results. The doctors integrated conventional and holistic cancer concepts. Their treatments aimed at both tumor and symptom control and at strengthening the patient on different levels: living with the disease, overcoming the disease, enabling emotional and cognitive development, and addressing spiritual or transcendental issues according to the patient’s wishes and initiatives. Therapeutic procedures were conventional anticancer and symptom-relieving treatments, herbal and mineral remedies, mistletoe therapy, art therapies, massages and other external applications, nutrition and lifestyle advice, psychological support, and multiple forms of empowerment. The approach emphasised good patient-doctor relationships and sufficient time for patient encounters and decision-making. Individualization appeared in several dimensions and was interwoven with standards and mindlines. The doctors often worked in teams and cooperated with other cancer care–related specialists. Conclusion. Integrative cancer care pursues an individualized and patient-centered approach, encompassing conventional and multimodal complementary interventions, and addressing, along with physical and functional needs, the emotional and spiritual needs of patients. This seems to be important for tumor and symptom control, and addresses major challenges and important goals of modern cancer care.
Hypothesis. Anthocyanins possess well-known biological effects and suppress DNA damage induced by therapeutic topoisomerase poisons. Our study focusses on the modulatory effects of anthocyanidins—malvidin (MAL) and pelargonidin (PEL)—on topoisomerase II poison mitoxantrone (MXT)-induced cytotoxicity and genotoxicity in in vitro and in vivo conditions. Study design. HepG2 cells were treated with MXT (1-10 µM), MAL (10-100 µM,) and PEL (5-640 µM) to determine cell viability. Further, experiments on cytotoxicity and apoptosis induction by single agents or combinations were performed. In vitro and in vivo antigenotoxic effect of MAL/PEL against MXT was evaluated in human lymphocytes and mouse bone marrow cells. Methods. Cytotoxicity of test agents and apoptosis induction in HepG2 cells was assessed by MTT assay, trypan blue dye exclusion assay and Hoechst 33258 staining. Antigenotoxic effects of MAL/PEL against MXT were assessed in co-treated human lymphocytes and bone marrow from mice that received MXT intraperitoneally 30 minutes post MAL/PEL oral administration Results. Dose-dependent cytotoxicity was observed with all 3 test agents in HepG2 cells. Highest test concentration of 100 µM MAL, 640 µM PEL, and 10 µM MXT decreased HepG2 cell viability by 80%, 30%, and 90%, respectively. The combination of 1 µM MXT + 80 µM MAL reduced cell viability better than single agents. MAL/PEL treatment significantly reduced MXT-induced genotoxicity in human lymphocytes and micronuclei formation in mice. Conclusion. Combination of MAL/PEL with lower doses of MXT, especially MAL+MXT increases the cytotoxicity in cancer cells. In addition, MXT treatment with MAL/PEL reduced MXT-induced genotoxicity and protected normal cells during chemotherapy.
Formation of new blood vessels from preexisting vasculature is an indispensable process in tumor initiation, invasion, and metastasis. Novel therapeutic approaches target endothelial cells involved in the process of angiogenesis, due to their genetic stability relative to the rapidly mutating drug-resistant cancer cells. In the present study, we investigated the effect of an active fraction from Emilia sonchifolia, belonging to the family Asteraceae, a plant well known for its anti-inflammatory and antitumor effects, on the inhibition of tumor-specific angiogenesis. Administration of the active fraction from E sonchifolia (AFES; 5 mg/kg, body weight, intraperitoneally) containing the major compound -humulene significantly inhibited B16F10 melanoma-induced capillary formation in C57BL/6 mice. The level of serum vascular endothelial growth factor and serum proinflammatory cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and granulocyte-macrophage colony-stimulating factor were also reduced significantly. At the same time, administration of AFES significantly enhanced the production of antiangiogenic factors such as tissue inhibitor of matrix metalloproteinase-1. Dose-dependent reduction can be seen in the budding and expansion of microvessels from rat thoracic aorta by AFES treatment. Inhibition of the activation of proenzyme to active enzyme of matrix metalloproteinase along with a successful reduction of proliferation, invasion, and migration of human umbilical vein endothelial cells demonstrated the antiangiogenic effect of AFES in vitro. To date, no study has examined the antiangiogenic activity of this plant with already well-known anti-inflammatory and antitumor effects. Results obtained in the present study by using both in vivo and in vitro angiogenic models altogether proved the inhibitory effect of AFES on tumor-specific neovessel formation.
Purpose. Fatigue is an important problem in children receiving intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Exercise may be an effective intervention for fatigue. Individualized yoga represents an ideal intervention because it can be tailored according to an individual child’s needs. Little is known about how to structure a standardized yoga program for intensivelytreated children. Therefore, this study describes the development of a yoga program and an approach to monitoring sessions suitable for hospitalized children receiving intensive chemotherapy or HSCT. Methods. The yoga program was designed to increase mobility in hospitalized children and to provide children with relaxation techniques that could be used independently in a variety of environments. The program was founded on 4 key tenets: safety, adaptability, environmental flexibility, and appeal to children. We also developed quality and consistency assurance procedures. Results. A menu format with a fixed structure was selected for the yoga program. Each yoga session contained up to 6 sections: breathing exercises, warmup exercises, yoga poses, balancing poses, cool-down poses, and final relaxation. Yoga instructors selected specific yoga poses for each session from a predetermined list organized by intensity level (low, moderate, or high). Monitoring procedures were developed using videotaping and multirater adjudication. Conclusion. We created a standardized yoga program and an approach to monitoring that are now ready for incorporation in clinical trials. Future work should include the adaptation of the program to different pediatric populations and clinical settings.
Background. Cell-free DNA circulates in cancer patients and induces in vivo cell transformation and cancer progression in susceptible cells. Based on this, we hypothesized that depletion of circulating DNA with DNAse I and a protease mix could have antitumor effects. Study design. The study aimed to demonstrate that DNAse I and a protease mix can degrade in vitro DNA and proteins from the serum of healthy individuals and cancer patients, and in vivo in serum of Wistar rats. Moreover, the antitumor effect of the systemically administered enzyme mix treatmentwas evaluated in nude mice subcutaneously grafted with the human colon cancer cell line SW480. Results. The serum DNA of cancer patients or healthy individuals was almost completely degraded in vitro by the enzymatic treatment, but no degradation was found with the enzymes given separately. The intravenous administration of the enzymes led to significant decreases in DNA and proteins from rat serum. No antitumor effect was observed in immunodeficient mice treated with the enzymes given separately. In contrast, the animals that received both enzymes exhibited a marked growth inhibition of tumors, 40% of them having pathological complete response. Conclusion. This study demonstrated that systemic treatment with DNAse I and a protease mix in rats decreases DNA and proteins from serum and that this treatment has antitumor effects. Our results support the hypothesis that circulating DNA could have a role in tumor progression, which can be offset by depleting it. Further studies are needed to prove this concept.
Introduction. Surgical resection in patients with non–small cell lung cancer (NSCLC) may be associated with significant morbidity, functional limitations, and decreased quality of life. Objectives. The safety and feasibility of a preoperative and early postoperative rehabilitation program in patients operated for NSCLC was determined in a nonhospital setting, with focus on high-intensity interval exercise. Methods. Forty patients with biopsy-proven NSCLC stages I to IIIa referred for surgical resection at the Department of Cardiothoracic Surgery RT, Rigshospitalet, University of Copenhagen, were randomly assigned to 1 of 4 groups (3 intervention groups and 1 control group). The preoperative intervention consisted of a home-based exercise program, while the postoperative exercise program comprised a supervised group exercise program involving resistance and high-intensity interval cardiorespiratory exercise 2 hours weekly for 12 weeks combined with individual counseling. The study endpoints were inclusion rate, adherence, and number of adverse events. Results. Forty patients (of 124 screened; 32%) were included and randomized into the 4 groups. The postoperative exercise was completed by 73% of the patients randomized to this intervention. No adverse events were observed, indicating that the early postoperative exercise program is safe. The preoperative home-based exercise program was not feasible due to interfering diagnostic procedures and fast-track surgery that left only 1 to 2 weeks between diagnosis and surgery. Conclusion. The early postoperative exercise program for patients with NSCLC was safe and feasible, but in a fast-track set up, a preoperative home-based exercise program was not feasible for this population.
Objective. This is a review of spiritually based interventions (eg, mindfulness-based stress reduction) that utilized psychoneuroimmunological (PNI) outcome measures in breast cancer survivors. Specifically, this review sought to examine the evidence regarding relationships between spiritually based interventions, psychosocial-spiritual outcomes, and biomarker outcomes in breast cancer survivors. Methods. A systematic search of 9 online databases was conducted for articles of original research, peer-reviewed, randomized and nonrandomized control trials from 2005-2015. Data were extracted in order to answer selected questions regarding relationships between psychosocial-spiritual and physiological measures utilized in spiritually based interventions. Implications for future spiritually based interventions in breast cancer survivorship are discussed. Results. Twenty-two articles were reviewed. Cortisol was the most common PNI biomarker outcome studied. Compared with control groups, intervention groups demonstrated positive mental health outcomes and improved or stable neuroendocrine-immune profiles, although limitations exist. Design methods have improved with regard to increased use of comparison groups compared with previous reviews. There are few spiritually based interventions that specifically measure religious or spiritual constructs. Similarly, there are few existing studies that utilize standardized religious or spiritual measures with PNI outcome measures. Findings suggest that a body of knowledge now exists in support of interventions with mindfulness-breathing-stretching components; furthermore, these interventions appear to offer potential improvement or stabilization of neuroendocrine-immune activity in breast cancer survivors compared to control groups. Conclusion. From a PNI perspective, future spiritually based interventions should include standardized measures of religiousness and spirituality in order to understand relationships between and among religiousness, spirituality, and neuroendocrine-immune outcomes. Future research should now focus on determining the minimum dose and duration needed to improve or stabilize neuroendocrine-immune function, as well as diverse setting needs, including home-based practice for survivors who are too ill to travel to group sessions or lack economic resources.
Although current chemotherapeutic agents are active at the beginning of therapy, the most common risk is the development of resistance during later stages in almost all cancer types including breast cancer. Hence, investigation of novel drugs is still a priority goal for cancer treatment. The objective of the present study is to investigate the anticancer effect of a derivative of stilbene, deoxyrhapontigenin (DR) isolated from Rheum undulatum L. root extracts against the chemoresistant MCF-7/adr and its parental MCF-7 human breast cancer cells. The morphological images indicate that DR induces an extensive cytoplasmic vacuolation in breast cancer cells. Mechanistic investigations revealed that DR treatment causes endoplasmic reticulum (ER) dilation and upregulated the expression of ER stress markers GRP78, IRE1α, eIF2α, CHOP, JNK, and p38. Subsequently, we also identified that DR increases the levels of apoptotic fragment of PARP (89 kDa) in breast cancer cells. Blocking the expression of one of the components of the ER stress–mediated apoptosis pathway, CHOP using siRNA significantly decreased DR-induced apoptotic cleavage of PARP. In summary, the present study suggests that the induction of ER stress–mediated apoptosis by DR may account for its cytotoxic effects in human breast cancer cells.
Background. Chinese herbal medicines reportedly increase efficacy and minimize toxicity of chemotherapy; however, little attention has been paid to how poor study quality can bias outcomes. Methods. We systematically searched MEDLINE, TCMLARS, EMBASE, and Cochrane Library for randomized controlled trials of Chinese herbal medicines combined with fluorouracil-based chemotherapy compared with the same chemotherapy alone. We screened for eligibility, extracted data, and pooled data with random-effects meta-analysis. Outcome measures were survival, toxicity, tumor response, performance status, quality of life, and Cochrane Risk of Bias (ROB) criteria to critically evaluate the quality of reporting in the randomized trials included in the meta-analysis. Results. We found 36 potentially eligible studies, with only 3 (those with low ROB) qualifying for meta-analysis. Two reported chemotherapy-related diarrhea reduced by 57% (relative risk [RR] = 0.43; 95% CI = 0.19-1.01; I2 test for variation in RR due to heterogeneity = 0.0%), with nonsignificant results. Two reported white blood cell toxicity reduced by 66% (RR = 0.34; 95% CI = 0.16-0.72; I2 test for variation in RR due to heterogeneity = 0.0%), with statistically significant results. Stratifying analysis by studies with high versus low ROB, we found substantial overestimation of benefit: Studies with high ROB overestimated by nearly 2-fold reduction of platelet toxicity by Chinese herbal medicines (RR = 0.35, 95% CI = 0.15-0.84 vs RR = 0.65, 95% CI = 0.11-3.92). Studies with high ROB overestimated by nearly 2-fold reduction of vomiting toxicity (RR = 0.45, 95% CI = 0.33-0.61 vs RR = 0.87, 95% CI = 0.48-1.58). And, studies with high ROB overestimated by 21% the reduction in diarrhea toxicity (RR = 0.34, 95% CI = 0.20-0.58 vs RR = 0.43, 95% CI = 0.19-1.01). Studies with high ROB also overestimated by 16% improvement in tumor response (RR = 1.39, 95% CI = 1.18-1.63 vs RR = 1.20; 95% CI = 0.81-1.79). Not accounting for ROB would have exaggerated evidence of benefit and failed to detect nonsignificance of results. Conclusions. In the present analysis, involving 36 studies, 2593 patients, 20 outcomes, 36 medical institutions, and 271 named research authors, 92% of the data points were from studies at high ROB. Given the poor quality of the data in studies identified, it cannot be concluded whether combining Chinese herbs with chemotherapy reduces toxicity of chemotherapy.
Background. Cognitive impairment is a common complaint among cancer survivors, significantly impacting working memory, attention, executive function, and information processing speed. This meta-analysis aims to evaluate the effect of neuropsychological interventions on the cognitive function of non–central nervous system (non-CNS) cancer survivors. Methods. Three databases (PubMed, PsycInfo, and CAJ Full-text Database) were searched from January 2010 to September 2015. Controlled clinical trials of neuropsychological interventions for the treatment of cognitive impairment in cancer survivors were considered for inclusion. Results. A total of 10 eligible trials were included in this meta-analysis. Three trials assessed the effects of cognitive rehabilitation (CR) interventions, and the weighted mean difference (WMD) for the overall intervention effect was –0.19 (95% confidence interval [CI] = –2.98 to 2.61). Two trials examined the effects of cognitive training (CT) interventions on the cognitive function of cancer survivors; the standardized mean difference (SMD) for the overall effect was 0.52 (95% CI = 0.06 to 0.98). The overall effect of CR interventions on neuropsychological status at postintervention was 5.66 (95% CI = 2.97 to 8.35). The SMD of CR and CT intervention for objective function by verbal learning tests was 0.50 (95% CI = 0.19 to 0.81) at postintervention, and 0.58 (95% CI = 0.19-0.98) at follow-up assessment within 6 months. Conclusion. Findings from this meta-analysis indicate that neuropsychological interventions can improve cognitive function in non-CNS cancer survivors, and support the need for future research. However, the conclusion from this meta-analysis was based on trials with small sample sizes. Future research should be conducted using a larger sample size. Relevant clinical implications were discussed accordingly.
Purpose. Breast cancer and oncological treatment can result in significant acute and late localized and systemic negative effects on health-related physical fitness and physical function. The aim of this single-arm study was to examine the effects of a 12-week community-based multimodal exercise program on health-related physical fitness and physical function in breast cancer survivors. Methods. A total of 52 female breast cancer survivors (mean age = 59.7 ± 10.4 years) completed supervised exercise training consisting of (1) aerobic conditioning, (2) resistance training, and (3) balance and flexibility training, for 30 minutes each, totaling 90 minutes twice weekly for 12 weeks. Pretreatment and posttreatment outcome measures—mobility: (1) Timed Up and Go (TUG) and (2) 6-minute walk test (6MWT); muscular strength: (3) leg press strength and (4) chest press strength; upper-extremity flexibility: (5) back scratch test; and balance: (6) functional reach (FR) and (7) single-leg stance time—were assessed and compared. Results. Postintervention assessment measures given as percentage improvement and effect size (ES) for mobility, TUG (18%, 0.59), and 6MWT (14%, 0.74) were significantly (P < .001) improved. Outcome measures of muscular strength, leg press strength (32%, 0.58) and chest press strength (40%, 0.61), both significantly (P < .001) improved. Postintervention assessment measure of upper-extremity flexibility (42%, 0.41) showed significant (P < .001) improvements. Outcome measures for balance, FR (18%, 0.75) and single leg stance time (24%, 0.30), showed significant (P < .001) improvements. Conclusions. Outcome measures showed moderate to large ES improvements after participants completed the 12-week multimodal exercise program for breast cancer survivors.
Objective. To investigate the clinical effect and the overall survival (OS) rate of patients with advanced non–small cell lung cancer (NSCLC) who have undergone Wheel Balance Cancer Therapy (WBCT). Methods. The cases of 33 patients with advanced NSCLC who were treated with WBCT at the East West Cancer Center (EWCC) between October 4, 2004, and October 3, 2013, without undergoing concurrent conventional treatment were analyzed. The Kaplan-Meier method was used to estimate the OS of the cases, and the median OS was calculated according to age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), conventional-treatment history, WBCT treatment duration, and histological tumor type. Results. The median OS of all patients was 31.1 (95% confidence interval [CI] = 3.5-58.7) months; the OS rates were 63.6% and 24.2% at years 1 and 2, respectively. The median OS rates of patients under and over 65 years were 45.2 (95% CI = 13.5-76.9) and 19.5 (95% CI = 7.1-31.8) months, respectively (P = .189). The median OS rates of patients who received WBCT for >14 days but <28 days and those who received WBCT for ≥28 days were 16.2 (95% CI = 13.3-19.2) and 45.2 (95% CI = 14.4-76.0) months, respectively (P = .437). The median OS rates of patients who had undergone prior conventional treatment and those who had not were 45.2 (95% CI = 9.1-81.3) and 3.9 (95% CI = unable to calculate) months, respectively (P = .000). The median OS rates of patients with squamous cell carcinoma (SCC) and non-SCC lung cancer were 5.6 (95% CI = unable to calculate) and 45.2 (95% CI = 9.1-81.3) months, respectively (P = .262). The median OS rate of patients with ECOG PS ≥3 was 14.3 (95% CI = 8.8-19.8) months; that of patients ECOG PS <3 could not be calculated. However, the mean OS rates of patients with ECOG PS <3 and with ECOG PS ≥3 were 85.7 (95% CI = 58.4-113.0) and 12.7 (95% CI = 8.5-16.9) months, respectively (P = .000). No severe adverse events were encountered. Conclusions. Our study indicates that WBCT might be effective to prolong the length of survival for patients with advanced NSCLC who have previously undergone conventional treatment and have an ECOG PS <3.
In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer.
Toona sinensis (TS) is one of the most popular vegetarian dishes in Taiwan. It has been shown to exhibit antioxidant, antiangiogenic, antiatherosclerotic, and anticancer properties. In this study, we demonstrated the ability of aqueous leaf extracts from TS to promote immune responses in BALB/c mice and to exhibit anti-leukemia activity in murine WEHI-3 cells. BALB/c mice were injected intravenously with WEHI-3 cells and then treated orally with TS (50 mg/kg). In vivo study showed that TS treatment reduced liver and spleen enlargement in WEHI-3 bearing mice compared with the untreated group. Furthermore, TS also decreased white blood cells (WBC), indicating inhibition of differentiation of the precursor of macrophages in WEHI-3 bearing mice. Treatment of WEHI-3 cells with TS (0-75 μg/mL for 24 hours) significantly reduced cell viability. Furthermore, TS treatment–induced late apoptosis was confirmed by Annexin-V/PI staining. Western blot analyses revealed that treatment of WEHI-3 cells with TS statistically increased the protein expression level of cytochrome c in the cytoplasm and activates caspase-3. Notably, TS treatment caused a dramatic reduction in Bcl-2 and increase in Bax protein levels. TS may disturb the Bcl-2 and Bax protein ratio and induce apoptosis. This reports confirms the antitumor activity of this nutritious vegetable potentially against leukemia.
Background. Complementary and alternative medicine (CAM) use is common among cancer patients, but the majority of CAM studies do not specify the time periods in relation to cancer diagnoses. We sought to define CAM use by cancer patients and investigate factors that might influence changes in CAM use in relation to cancer diagnoses. Methods. We conducted a cross-sectional survey of adults diagnosed with breast, prostate, lung, or colorectal cancer between 2010 and 2012 at the Lineberger Comprehensive Cancer Center. Questionnaires were sent to 1794 patients. Phone calls were made to nonrespondents. Log binomial/Poisson regressions were used to investigate the association between cancer-related changes in CAM use and conversations about CAM use with oncology providers. Results. We received 603 (33.6 %) completed questionnaires. The mean age (SD) was 64 (11) years; 62% were female; 79% were white; and 98% were non-Hispanic. Respondents reported the following cancer types: breast (47%), prostate (27%), colorectal (14%), lung (11%). Eighty-nine percent reported lifetime CAM use. Eighty-five percent reported CAM use during or after initial cancer treatment, with category-specific use as follows: mind-body medicine 39%, dietary supplements 73%, body-based therapies 30%, and energy medicine 49%. During treatment CAM use decreased for all categories except energy medicine. After treatment CAM use returned to pretreatment levels for most CAMs except chiropractic. Initiation of CAM use after cancer diagnosis was positively associated with a patient having a conversation about CAM use with their oncology provider, mainly driven by patient-initiated conversations. Conclusions. Consistent with previous studies, CAM use was common among our study population. Conversations about CAM use with oncology providers appeared to influence cessation of mind-body medicine use after cancer diagnosis.
Five different crude polysaccharides from guava seed (GSPS), bitter buckwheat (BBPS), common buckwheat (CBPS), red Formosa lambsquarters (RFLPS), and yellow Formosa lambsquarters (YFLPS) were isolated to treat human prostate cancer PC-3 cells via direct action or tumor immunotherapy. The splenocyte- and macrophage-conditioned media (SCM and MCM) were prepared using individual selected polysaccharides, and then SCM or MCM was further collected to treat PC-3 cells. The relationship between PC-3 cell growth and Th1/Th2 cytokines in SCM as well as proinflammatory/anti-inflammatory cytokine secretion profiles in MCM were delineated. The results showed that all 5 selected polysaccharides did not significantly inhibit PC-3 cell growth via direct action. However, SCM or MCM cultured in the absence or presence of 5 selected polysaccharides significantly (P < .05) inhibited PC-3 cell growth. MCM cultured with 5 polysaccharides dose dependently enhanced their inhibitory effects on the viabilities of PC-3 cells than those cultured without polysaccharides. There was a significant (P < .05) negative correlation between PC-3 cell viabilities and (interleukin [IL]-6 + tumor necrosis factor [TNF]-α)/IL-10 level ratios in the corresponding MCM, implying that macrophages suppress PC-3 cell growth through decreasing secretion ratios of proinflammatory/anti-inflammatory cytokines in a tumor microenvironment.
Background. Ursolic acid (UA) is a triterpene found in different plant species, possessing antitumor activity, which may be a result of its antiangiogenic effect. However, UA has low water solubility, which limits its use because the bioavailability is impaired. To overcome this inconvenience, we developed long-circulating and pH-sensitive liposomes containing ursolic acid (SpHL-UA). We investigated the antiangiogenic effect of free UA and SpHL-UA in murine brain cancer and human breast tumor models by means of determination of the relative tumor volume, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and histopathological analysis. Methods. The animals were treated with dimethyl sulfoxide in 0.9% (w/v) NaCl, free UA, long-circulating and pH-sensitive liposomes without drug (SpHL), or SpHL-UA. The animals were submitted to each treatment by intraperitoneal injection for 5 days. The dose of free UA or SpHL-UA was equal to 23 mg/kg. Results. Tumor growth inhibition was not observed in human breast tumor–bearing animals. For murine gliosarcoma-bearing animals, a slight tumor growth inhibition was observed in the groups treated with free UA or SpHL-UA (9% and 15%, respectively). No significant change in any of the parameters evaluated by DCE-MRI for both experimental models could be observed. Nevertheless, the evaluation of the mean values of magnetic resonance parameters of human breast tumor–bearing animals showed evidence of a possible antiangiogenic effect induced by SpHL-UA. Histopathological analysis did not present significant change for any treatment. Conclusion. SpHL-UA did not show antiangiogenic activity in a gliosarcoma model and seemed to induce an antiangiogenic effect in the human breast tumor model.
Rotundic acid (RA) is a pentacyclic triterpenic acid. Apoptotic effects of RA at 4, 8, or 16 µM in OE33 and A549 cell lines, an esophageal squamous cancer cell line and a non–small-cell lung cancer cell line, were examined. RA at 4 to 16 µM inhibited the survival of both cell lines. RA at 8 and 16 µM decreased Bcl-2 expression and at 4 to 16 µM upregulated Bax and cleaved caspase-3 expression. RA treatments decreased the ratio of Bcl-2/Bax in those cells. RA at 4 to 16 µM lowered Na+-K+-ATPase activity and reduced mitochondrial membrane potential in OE33 and A549 cells. RA at 8 and 16 µM enhanced DNA fragmentation and caspase-3 and caspase-9 expression in OE33 cells. In A549 cells, RA increased caspase-3 expression in a concentration-dependent manner; but only at 8 and 16 µM, it upregulated caspase-9 expression. RA treatments at 4 to 16 µM decreased protein kinase c activity, suppressed the expression of cytochrome c and apoptosis-inducing factor, and lowered the production of reactive oxygen species, vascular endothelial growth factor, transforming growth factor-β1, and tumor necrosis factor-α in both cell lines. RA at 8 and 16 µM downregulated hypoxia-inducible factor-1α expression. These findings suggest that RA could penetrate into OE33 and A549 cells and execute cytotoxic activities.
Purpose. Dyspnea is a common and distressing symptom for patients with lung cancer (LC) because of disease burden, therapy toxicity, and comorbid illnesses. Acupuncture is a centuries-old therapy with biological plausibility for relief of dyspnea in this setting. This pilot study aimed to evaluate the feasibility and preliminary effectiveness of acupuncture for dyspnea among patients with LC. Methods. Eligible patients had a diagnosis of LC and clinically significant dyspnea without a clear organic cause. The treatment consisted of 10 weekly acupuncture sessions, with a follow-up visit 4 weeks after therapy. The primary outcome was dyspnea severity as measured using a validated Numerical Rating Scale (NRS) of 0 to 10 (10 being "most severe shortness of breath imaginable"). Results. We enrolled 12 patients in the study. The median age was 64.5 years; 66.7% of the patients were female, and 66.7% were Caucasians. Among those enrolled, 10 (83.3%) were able to complete all 10 acupuncture sessions. Acupuncture was well tolerated; adverse events were mild and self-limited. Mean (SD) dyspnea scores on the NRS improved from 6.3 (1.7) at baseline to 3.6 (1.9; P = .003) at the end of treatment and 3.2 (2.3; P = .008) at follow-up. Fatigue and quality of life also improved significantly with acupuncture (P < .05). Conclusion. Among patients with LC, acupuncture was well tolerated and exhibited promising preliminary beneficial effects in the treatment of dyspnea, fatigue, and quality of life. Performing a trial in this population appears feasible.
Hypothesis. This study examines moderators and mediators of a yoga intervention targeting quality-of-life (QOL) outcomes in women with breast cancer receiving radiotherapy.Methods. Women undergoing 6 weeks of radiotherapy were randomized to a yoga (YG; n = 53) or stretching (ST; n = 56) intervention or a waitlist control group (WL; n = 54). Depressive symptoms and sleep disturbances were measured at baseline. Mediator (posttraumatic stress symptoms, benefit finding, and cortisol slope) and outcome (36-item Short Form [SF]-36 mental and physical component scales [MCS and PCS]) variables were assessed at baseline, end-of-treatment, and 1-, 3-, and 6-months posttreatment. Results. Baseline depressive symptoms (P = .03) and sleep disturbances (P < .01) moderated the Group x Time effect on MCS, but not PCS. Women with high baseline depressive symptoms in YG reported marginally higher 3-month MCS than their counterparts in WL (P = .11). Women with high baseline sleep disturbances in YG reported higher 3-months MCS than their counterparts in WL (P < .01) and higher 6-month MCS than their counterparts in ST (P = .01). YG led to greater benefit finding than ST and WL across the follow-up (P = .01). Three-month benefit finding partially mediated the effect of YG on 6-month PCS. Posttraumatic stress symptoms and cortisol slope did not mediate treatment effect on QOL. Conclusion. Yoga may provide the greatest mental-health–related QOL benefits for those experiencing pre-radiotherapy sleep disturbance and depressive symptoms. Yoga may improve physical-health–related QOL by increasing ability to find benefit in the cancer experience.
Introduction. Improved models of care are needed to meet all the support needs of people with cancer, which encompass psychological, emotional, physical, spiritual, sexual, occupational, social and existential needs. The aim of this article is to (a) evaluate short- and long-term impacts of using a whole person approach to support people with cancer on the Living Well with the Impact of Cancer Course (LWC) and (b) use these data to inform strategic decisions about future service provision at Penny Brohn UK. Methods. Longitudinal mixed-methods service evaluation (n = 135). Data collected included health-related quality of life (HRQoL) (FACIT-SpEx); Concerns (types and severity–MYCaW); lifestyle behavior (bespoke questionnaire), and participants’ experiences over 12 months postcourse. Results. Statistically and clinically significant improvements from baseline to 12 months in severity of MYCaW Concerns (n = 64; P < .000) and mean total HRQoL (n = 66; P < .000). The majority of MYCaW concerns were "psychological and emotional" and about participants’ well-being. Spiritual, emotional, and functional well-being contributed most to HRQoL improvements at 12 months. Barriers to maintaining healthy lifestyle changes included lack of support from family and friends, time constraints, and returning to work. Three to 6 months postcourse was identified as the time when more support was most likely to be needed. Conclusions. Using a whole person approach for the LWC enabled the needs of participants to be met, and statistically and clinically significant improvements in HRQoL and MYCaW Concerns were reported. Qualitative data analysis explored how experiencing whole person support enabled participants to make and sustain healthy lifestyle changes associated with improved survivorship. Barriers experienced to making health behavior change were also identified. These data then informed wider and more person-centered clinical provision to increase the maintenance of positive long-term behavior changes. Comparison of whole person approaches to cancer treatment and support and standard care are now urgently needed.
Objective. Both the Chinese herbal compound Songyou Yin (SYY) and swimming exercise have been shown to have protective effects against liver cancer in animal models. In this study, we investigated whether SYY and moderate swimming (MS) have enhanced effect on suppressing progression of liver cancer by immunomodulation. Methods. C57BL/6 mice were transplanted with Hepa1-6 murine liver cancer cell lines and received treatment with SYY alone or SYY combined with MS. The green fluorescent protein (GFP)-positive metastatic foci in lungs were imaged with a stereoscopic fluorescence microscope. Flow cytometry was used to test the proportion of CD4 +, CD8 + T cells in peripheral blood and the proportions of CD4 + CD25 + Foxp3 + Treg cells in peripheral blood, spleen, and tumor tissues. Cytokine transforming growth factor (TGF)-β1 level in serum was detected by ELISA. Results. SYY plus MS significantly suppressed the growth and lung metastasis of liver cancer and prolonged survival in tumor-burdened mice. SYY plus MS markedly raised the CD4 to CD8 ratio in peripheral blood and lowered the serum TGF-β1 level and the proportions of Treg cells in peripheral blood, spleen, and tumor tissue. The effects of the combined intervention were significantly superior to SYY or MS alone. Conclusion. The combined application of SYY and MS exerted an enhanced effect on suppressing growth and metastasis of liver cancer by strengthening immunity.
Background. The role of whole grains, refined cereals, and legumes in preventing or initiating colorectal cancer (CRC) is still uncertain. The aim of this study is to examine the possible association between the consumption of whole grains, refined cereals, and legumes and the risk of developing CRC among Jordanian population. Methods. A validated food frequency questionnaire was used to collect dietary data with regard to intake of whole grains, refined cereals, and legumes. A total of 220 diagnosed CRC participants and 281 CRC-free control participants matched by age, gender, occupation, and marital status were recruited. Logistic regression was used to estimate the odds of developing CRC in relation to the consumption of different types of whole grains, refined cereals, and legumes. Results. The odds ratio (OR) for developing CRC among cases consumed refined wheat bread at all meals was 3.1 compared with controls (95% CI: 1.2-7.9, P-Trend = 0.001); whereas the OR associated with whole wheat bread was 0.44 (95% CI: 0.22-0.92, P-Trend = 0.001). The statistical evaluation for daily consumption of rice suggested a direct association with the risk of developing CRC, OR = 3.0 (95% CI: 0.27-33.4, P-Trend = 0.020). Weekly consumption of macaroni was associated with CRC with OR of 2.4 (95% CI: 1.1-5.3, P-Trend = 0.001). The consumption of corn, bulgur, lentils, and peas suggested a protective trend, although the trend was not statistically significant. Conclusion. This study provides additional indicators of the protective role of whole grains and suggests a direct association between consumption of refined grains and higher possibility for developing CRC.
Background. Interventions are needed to alleviate memory difficulty in cancer survivors. We previously showed in a phase III randomized clinical trial that YOCAS©® yoga—a program that consists of breathing exercises, postures, and meditation—significantly improved sleep quality in cancer survivors. This study assessed the effects of YOCAS©® on memory and identified relationships between memory and sleep. Study design and methods. Survivors were randomized to standard care (SC) or SC with YOCAS©® . 328 participants who provided data on the memory difficulty item of the MD Anderson Symptom Inventory are included. Sleep quality was measured using the Pittsburgh Sleep Quality Index. General linear modeling (GLM) determined the group effect of YOCAS©® on memory difficulty compared with SC. GLM also determined moderation of baseline memory difficulty on postintervention sleep and vice versa. Path modeling assessed the mediating effects of changes in memory difficulty on YOCAS©® changes in sleep and vice versa. Results. YOCAS©® significantly reduced memory difficulty at postintervention compared with SC (mean change: yoga=–0.60; SC=–0.16; P<.05). Baseline memory difficulty did not moderate the effects of postintervention sleep quality in YOCAS©® compared with SC. Baseline sleep quality did moderate the effects of postintervention memory difficulty in YOCAS©® compared with SC (P<.05). Changes in sleep quality was a significant mediator of reduced memory difficulty in YOCAS©® compared with SC (P<.05); however, changes in memory difficulty did not significantly mediate improved sleep quality in YOCAS©® compared with SC. Conclusions. In this large nationwide trial, YOCAS©® yoga significantly reduced patient-reported memory difficulty in cancer survivors.
Purpose. Studies have demonstrated beneficial health effects from yoga interventions in cancer patients, but predominantly in breast cancer. Research on its role in alleviating prostate cancer (PC) patients’ side effects has been lacking. Our primary goal was to determine the feasibility of recruiting PC patients on a clinical trial of yoga while they underwent external beam radiation therapy (RT). Methods. Twice-weekly yoga interventions were offered throughout the RT course (6-9 weeks). Baseline demographic information was collected. Feasibility was declared if 15 of the first 75 eligible PC patients approached (20%) were successfully accrued and completed the intervention. Additional end points included standardized assessments of fatigue, erectile dysfunction (ED), urinary incontinence (UI), and quality of life (QOL) at time points before, during, and after RT. Results. Between May 2013 and June 2014, 68 eligible PC patients were identified. 23 patients (34%) declined, and 45 (56%) consented to the study. 18 (40%) were voluntarily withdrawn due to treatment conflicts. Of the remaining 27, 12 (30%) participated in ≥50% of classes, and 15 (59%) were evaluable. Severity of fatigue scores demonstrated significant variability, with fatigue increasing by week 4, but then improving over the course of treatment (P = .008). ED, UI, and general QOL scores demonstrated reassuringly stable, albeit not significant trends. Conclusions. A structured yoga intervention of twice-weekly classes is feasible for PC patients during a 6- to 9-week course of outpatient radiotherapy. Preliminary results are promising, showing stable measurements in fatigue, sexual health, UI, and general QOL.
Objective. To evaluate the effectiveness of Jian Pi Li Qi (JPLQ) decoction in improving quality of life of patients with hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE). Methods. A randomized, double-blind, placebo-controlled trial was conducted. A total of 150 patients with HCC were randomly assigned into 3 groups. Groups were designed as follows: neither herbal medicine nor placebo administration (group A), placebo treatment (group B), and JPLQ decoction treatment (group C). The measurement methods of the observed outcomes include MD Anderson Symptom Inventory–Gastrointestinal module, armpit temperature, and laboratory tests. Results. Among the 140 patients studied, the 12 symptoms rated as most severe, which characterize postembolization syndrome (PES), were fever, pain, fatigue, nausea, disturbed sleep, distress, lack of appetite, drowsiness, dry mouth, vomiting, constipation, and feeling bloated. All these increased significantly (all P < .05) after TACE; 7 symptoms, including fever, pain, fatigue, lack of appetite, drowsiness, dry mouth, and constipation (all P < .05), were found to be relieved significantly by JPLQ. JPLQ also improved the liver function damage caused by TACE. Conclusion. JPLQ decoction may be an effective modality to relieve PES and protect liver function in patients with HCC after TACE.
The use of prior exercise training has shown promise in minimizing doxorubicin (DOX)-induced physical impairments. The purpose of this study was to compare changes in thymus mass, thymocyte (T-cell) number, and tissue peroxidation following chronic endurance exercise and DOX treatment in the rat. The thymus mass, number of viable T-cells, and levels of malondialdehyde and 4-hydroxyalkenals (MDA+4-HAE) were compared 3 days post-injection between rats assigned to the following treatment conditions: (a) 10 weeks of endurance training, followed by a saline injection 24 hours after the last training session (TM+SAL); (b) treadmill training as above, followed by a single, bolus 10-mg/kg injection of DOX (TM+10); (c) treadmill training with 12.5 mg/kg of DOX (TM+12.5); (d) sedentary (without exercise) and a saline injection (SED+SAL); (e) sedentary with 10 mg/kg of DOX (SED+10); and (f) sedentary with 12.5 mg/kg (SED+12.5). Thymic mass and T-cell numbers significantly decreased following DOX injections. TM rats exhibited significantly less lipid peroxidation compared with paired-dose SED groups. TM+10 did not significantly differ from SED+SAL in thymic levels of lipid peroxidation. We conclude that chronic endurance exercise decreases levels of lipid peroxidation in the thymus seen with acute DOX treatment.
Background. Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer–related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose. To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low, moderate, and high loads. The impact on lymphedema status and associated symptoms was also compared. Methods. A total of 21 women, 62 ± 10 years old, with BCRL participated in the study. Participants completed low-load (15-20 repetition maximum [RM]), moderate-load (10-12 RM), and high-load (6-8 RM) exercise sessions consisting of 3 sets of 6 upper-body resistance exercises. Sessions were completed in a randomized order separated by a 7- to 10-day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation. Lymphedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using Visual Analogue Scales for pain, heaviness, and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results. No significant changes in creatine kinase, C-reactive protein, interleukin-6, and tumor necrosis factor-α were observed following the 3 resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the 3 resistance exercise conditions. Conclusions. The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads.
Background. Fatigue is a major problem in children with cancer. The objective was to examine the feasibility of performing a clinical trial of homeopathic treatment for fatigue in children receiving chemotherapy. Materials. This was a single-institution, open-label, pilot study. Children 2 to 18 years old, diagnosed with cancer, and receiving chemotherapy were eligible. Participants were given individualized homeopathic treatment for a maximum of 14 days. In-home or clinic assessments were conducted up to 3 times weekly. Feasibility was defined as the ability to recruit and administer homeopathy to 10 participants within 1 year. Fatigue was measured using the Symptom Distress Scale daily and the PedsQL Multidimensional Fatigue Module weekly. Results. Between April 2012 and April 2014, 155 potential participants were identified. There were 45 eligible and contacted patients; 36 declined participation, 30 because they were not interested; 9 agreed to participate, but 1 participant withdrew prior to treatment initiation. Median length of homeopathic treatment was 10.5 (range = 6 to 14) days. All parents found homeopathic treatment to be easy or very easy to follow. Conclusions. Trials of individualized homeopathy for fatigue reduction in pediatric cancer are not feasible in this context; lack of interest was a primary reason. Alternative approaches to evaluating homeopathy efficacy are needed.
Objective. Acquired chemoresistance is a major obstacle in the clinical management of ovarian cancer. Therefore, searching for alternative therapeutic modalities is urgently needed. Bitter melon (Momordica charantia) is a traditional dietary fruit, but its extract also shows potential medicinal values in human diabetes and cancers. Here, we sought to investigate the extract of bitter melon (BME) in antitumorigenic and cisplatin-induced cytotoxicity in ovarian cancer cells. Methods. Three varieties of bitter melon were used to prepare the BME. Ovarian cancer cell lines, human immortalized epithelial ovarian cells (HOSEs), and nude mice were used to evaluate the cell cytotoxicity, cisplatin resistance, and tumor inhibitory effect of BME. The molecular mechanism of BME was examined by Western blotting. Results. Cotreatment with BME and cisplatin markedly attenuated tumor growth in vitro and in vivo in a mouse xenograft model, whereas there was no observable toxicity in HOSEs or in nude mice in vivo. Interestingly, the antitumorigenic effects of BME varied with different varieties of bitter melon, suggesting that the amount of antitumorigenic substances may vary. Studies of the molecular mechanism demonstrated that BME activates AMP-activated protein kinase (AMPK) in an AMP-independent but CaMKK (Ca2+/calmodulin-dependent protein kinase)-dependent manner, exerting anticancer effects through activation of AMPK and suppression of the mTOR/p70S6K and/or the AKT/ERK/FOXM1 (Forkhead Box M1) signaling cascade. Conclusion. BME functions as a natural AMPK activator in the inhibition of ovarian cancer cell growth and might be useful as a supplement to improve the efficacy of cisplatin-based chemotherapy in ovarian cancer.
Background. Breast cancer patients may experience various symptoms that affect the quality of life significantly and they seek complementary and alternative medicine (CAM). To meet the needs of patients, we developed an integrative outpatient care program. Methods. This program provided CAM consultation and acupuncture for breast cancer patients at Taipei Veterans General Hospital. The outcome measures included Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) and patient satisfaction questionnaires on the first visit (baseline) and at 6 months. Results. Forty-five breast cancer patients were enrolled. All patients completed the study. The median age was 53.3 (±8.3). The symptoms most often experienced during previous cancer treatments were fatigue (35.6%), arthralgia (20%), nausea (6.7%), and insomnia (6.7%). The symptoms most wished to be diminished by the patients were arthralgia (22.2%), insomnia (17.8%), and fatigue (15.6%). Thirty-four patients (75.6%) had sought CAM therapy to reduce these symptoms. Fifteen patients (33.3%) received CAM consultation only and 30 (66.7%) received acupuncture in addition. Sixteen patients completed at least 6 sessions of acupuncture. No serious adverse effect was reported. In the SF-12 Questionnaire on all the patients, physical component summary (PCS) was 49.6 (±5.6) at baseline and 44.9 (±7.6) at 6 months (P = .001); the mental component summary (MCS) was 44.7 (±6.1) at baseline and 52.3 (±9.3) at 6 months (P < .001). For patients who had completed acupuncture, PCS was 49.2 (±4.9) at baseline and 41.4 (±7.6) at 6 months (P = .148); the MCS was 45.6 (±6.2) at baseline and 49.7 (±11) at 6 months (P = .07). Thirty-eight (84.4%) patients were satisfied with this program. Conclusions. Our results demonstrated that an integrative outpatient care program of conventional and Chinese medicine is feasible. Most patients were satisfied with this program and the quality of life was improved. It is important to conduct more research to build a model that integrates CAM with conventional medicine in Taiwan.
The present study was conducted to evaluate the potential of flaxseed oil to prevent chemically induced skin cancer in mice. Cancer was induced on 2-stage skin carcinogenesis model by single topical application of 7,12 dimethylbenz [a]anthracene (DMBA), as, initiator, and two weeks later it was promoted by croton oil treatment thrice a week on the dorsal surface of mice for 16 weeks. Flaxseed oil (FSO; 100µL/animal/d) was orally administered 1 week before and 1 week after DMBA application (Peri-initiation stage). The animals of the FSO-administered group showed a significant reduction in tumor incidence (76.67%), cumulative number of tumors (37), tumor yield (3.7), and tumor burden (4.81) when compared with the carcinogen-treated control animals. Biochemical parameters in skin and liver tissue such as LPO and phase I enzymes were significantly (P < .01) reduced in the FSO-treated experimental group, whereas the phase II enzymes (GST, DT-diaphorase) and antioxidant parameters (GSH, GPx, SOD, catalase, and vitamin C) exhibited a significant (P < .01) elevation when compared with the animals of the carcinogen-treated control group. Histopathological alterations in the carcinogen-treated control animals were also observed in the form of epidermal hyperplasia, keratinized pearl formation, and acanthosis in skin and tumors, whereas these were found to be reduced after FSO administration. The results of the present study demonstrate that the oral administration of FSO has the potential to modulate the levels of LPO, antioxidants, and detoxification enzymes in the DMBA-croton oil–induced skin carcinogenesis in mice.
Introduction. This qualitative study seeks to explore the role within the context of Australian breast cancer oncology treatments that traditional Chinese medicine (TCM) practitioners play in the treatment of breast cancer. Methods. Semistructured interviews were used on 2 groups: the first group was TCM practitioners who were recognized experts in breast cancer, and the second group consisted of TCM practitioners who treated breast cancer as part of their practice but were not recognized experts. Data analysis was achieved through grounded theory with open coding. Results. The main themes reported on here are the following: the role of TCM in the biomedical management of breast cancer, TCM strategies for the management of breast cancer, and the perceived holistic approach of the TCM practitioner and the importance of a TCM diagnosis in the role of breast cancer care. Discussion. The role of TCM in biomedical breast cancer management is a supportive one; however, this role is difficult as there is a lack of understanding of TCM by biomedical practitioners. The viewpoints of practitioners differed on key strategies of TCM: diagnosis, and treatment protocols. Patients sought the holistic approach of TCM practitioners as they felt it addressed all aspects of their health and not just the symptoms relating to breast cancer. Conclusion. The lack of an integrated medicine approach in relation to TCM makes it difficult to demonstrate the value of the contribution TCM can make to biomedicine in the field of breast care oncology. Effectiveness studies are needed that can accurately represent TCM in this field.
The biggest challenge for the treatment of multidrug resistant cancer is to deliver a high concentration of anticancer drugs to cancer cells. Icariside II is a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties, but poor solubility and significant efflux from cancer cells limited its clinical use. In our previous study, a self-assembled mixture of micelles (TPGS–Icariside II–phospholipid complex) was successfully constructed, which could substantially increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells. In this study, we evaluate the anticancer effect of the mixed micelles encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast cancer cell line. The cellular uptake of the micelles was confirmed by fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2-fold less than the free drug. The in vitro study showed Icar-MC induced more apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor efficacy compared with the administration of free drug, without causing significant body weight changes in mice. The antitumor effect was further verified by magnetic resonance imaging and immunohistochemical assays for Ki-67, a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2 ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This study suggests that phospholipid/TPGS mixed micelles might be a suitable drug delivery system for Icariside II to treat multidrug resistant breast cancer.
Background. Peripheral neuropathy is the dose limiting toxicity of bortezomib in patients with multiple myeloma (MM). Objectives. To examine the safety, feasibility and efficacy of acupuncture in reducing bortezomib-induced peripheral neuropathy (BIPN) symptoms. Methods. Patients with MM experiencing persistent BIPN ≥grade 2 despite adequate medical intervention and discontinuation of bortezomib received 10 acupuncture treatments for 10 weeks (2x/week for 2 weeks, 1x/week for 4 weeks, and then biweekly for 4 weeks). Responses were assessed by the Clinical Total Neuropathy Score (TNSc), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire, and the Neuropathy Pain Scale (NPS). Repeated-measures analysis of variance was used to test for monotonic decline in scores on each of the measures. Serial serum levels of proinflammatory and neurotrophic cytokines were obtained at baseline and weeks 1, 2, 4, 8, and 14. Results. Twenty-seven patients with MM were enrolled in the trial. There were no adverse events associated with the acupuncture treatments. TNSc data were deemed invalid and therefore were not reported. At weeks 10 and 14, FACT/GOG-Ntx and NPS showed significant reduction suggesting decreased pain, and improved function (P values were <.0001 for both FACT/GOG-Ntx and NPS at weeks 10 and 14). However, nerve conduction studies did not significantly change between baseline assessment and end of study. There was no correlation in serum cytokines for responders versus none responders. Conclusions. Acupuncture is safe, feasible and produces subjective improvements in patients’ symptoms. A follow-up randomized controlled trial is warranted.
Background. Intravenous vitamin C (IVC) is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings. We conducted a systematic review of human interventional and observational studies assessing IVC for use in cancer patients. Methods. We searched MEDLINE, EMBASE, The Cochrane Library, CINAHL, and AMED from inception to April 2013 for human studies examining the safety, effectiveness, or pharmacokinetics of IVC use in cancer patients. Results. Of 897 records, a total of 39 reports of 37 studies were included: 2 randomized controlled trials (RCTs), 15 uncontrolled trials, 6 observational studies, and 14 case reports. IVC dosing ranged from 1 g to more than 200 g ascorbic acid per infusion, typically administered 2 to 3 times weekly. IVC does not appear to increase toxicity or interfere with antitumor effects of gemcitabine/erlotinib therapy or paclitaxel and carboplatin. Based on 1 RCT and data from uncontrolled human trials, IVC may improve time to relapse and possibly enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC may improve quality of life, physical function, and toxicities associated with chemotherapy, including fatigue, nausea, insomnia, constipation, and depression. Case reports document several instances of tumor regression and long-term disease-free survival associated with use of IVC. Conclusion. There is limited high-quality clinical evidence on the safety and effectiveness of IVC. The existing evidence is preliminary and cannot be considered conclusive but is suggestive of a good safety profile and potentially important antitumor activity; however, more rigorous evidence is needed to conclusively demonstrate these effects. IVC may improve the quality of life and symptom severity of patients with cancer, and several cases of cancer remission have been reported. Well-designed, controlled studies of IVC therapy are needed.
Lung cancer is the leading cause of cancer death worldwide, and most chemotherapeutic drugs have limited success in treating this disease. Furthermore, some drugs show undesirable side effects due to the enrichment of cancer stem cells (CSCs) that are present, leading to resistance to conventional chemotherapy and tumor relapse. CSCs possess self-renewal characteristics, aggressive tumor initiating activity, and ability to facilitate tumor metastasis. Therefore, development of nontoxic agents that can potentiate chemotherapy and eliminate CSCs would be highly desirable. In the present study, we investigated whether Sasa quelpaertensis leaf extracts (SQE) and cisplatin (CIS), individually or in combination, would exert anti-CSC and antimetastatic effect in H1299 and A549 human lung cancer cells. Following these treatments, cell growth, phosphorylation of phosphoinositide-3 kinase, and activation of the mammalian target of rapamycin were inhibited. Decreased serial sphere formation, clonogenicity, and expression of major stem cell markers, such as CD44 and SOX-2, in CD44+ cancer stem cells were also observed. In addition, inhibition of cell migration and invasion in both cell lines as well as inhibition of matrix metalloproteinase-2 activity and expression were detected. Importantly, the anticancer stemness and antimetastasis effects in each of these assays were greater for the combined treatment with SQE and CIS than with each treatment individually. In conclusion, the data suggest that SQE alone, or in combination with CIS, represents a promising therapeutic strategy for eliminating cancer stemness and cell invasion potential of CSCs, thereby treating and preventing metastatic lung cancer cells.
Purpose. While fatigue is the most commonly reported symptom of chemotherapy, there are currently no effective treatments for chemotherapy-induced fatigue (CIF). We used a mouse model to examine the benefits of quercetin on CIF as measured by voluntary wheel running activity and sought to determine whether quercetin may be associated with a decrease in inflammation and/or anemia. Methods. Mice were assigned to 1 of 4 groups: placebo-vehicle (Plac-PBS), placebo-5-fluorouracil (Plac-5FU), quercetin-vehicle (Quer-PBS), or quercetin-5-fluorouracil (Quer-5FU). All mice were given a daily injection of either 60 mg/kg of 5-FU or phosphate buffered saline (PBS) for 5 days. Quercetin (0.02%) treatment was administered in the food 3 days prior to 5-FU administration and for the duration of the experiment (ie, days –2 to 14). A second group of mice was sacrificed at 5 and 14 days post initial injection for assessment of monocyte chemoattractant protein-1 (MCP-1) and anemia. Results. Voluntary wheel running was reduced in both the Plac-5FU and Quer-5FU groups following 5-FU injection (P < .05). However, the Quer-5FU group recovered to baseline levels by approximately day 7, whereas the Plac-5FU group remained suppressed. MCP-1 was significantly elevated at 14 days in Plac-5FU (P < .001), but no changes were seen with Quer-5FU. Treatment with 5-FU resulted in anemia at both 5 days and 14 days; however, quercetin blocked this effect at 14 days (P < .001). Conclusion. These results demonstrate the beneficial effect of quercetin on improving recovery of voluntary physical activity following 5-FU treatment, which may be linked to a decrease in inflammation and anemia.
Hypotheses. Although there is evidence that psychosocial and behavioral interventions (PBIs) increase well-being, improve coping and adjustment, and reduce distress among cancer patients, findings regarding PBIs as a means for prolonging survival were not convincing. Conflicting findings resulted in tremendous controversies over the efficacy of PBIs. This study aims at estimating the pooled effects of PBIs on survival of cancer patients. Study Design and Methods. Randomized controlled trials (RCTs) testing the effects of any kind of PBIs on the survival of cancer patients included in MEDLINE, EMBASE, Cancer Lit, CINAHL, Cochrane Library, and reference lists of relevant articles were retrieved and reviewed by 2 independent researchers. Data items derived from the articles included time and duration of study, intervention types and doses, and numbers of patients dying and surviving 1, 2, 4, and 6 years after intervention. Estimation of the collective effects of the interventions used meta-analysis via Review Manager (version 5). Results. A total of 15 RCTs met inclusion criteria, involving 2041 subjects (1118 in intervention and 923 in control groups). Inclusive total mean Mantel-Haenszel risk ratios (RRs) ranged from 0.83 to 0.99, and 3 of these effect sizes were statistically nonsignificant. Yet when the RCTs with less than 30 hours of PBIs were excluded, all the RRs decreased to some extent, with the RR for the first 2 years being decreased to 0.69 (95% CI, 0.55-0.87) and 0.82 (95% CI, 0.71-0.95), respectively. Conclusion. PBIs with adequate intervention doses prolong survival at least for some cancer patients in the first 2 years after intervention, although longer term effects need to be determined via more studies.
Acupuncture is being adopted by cancer patients for a wide range of cancer-related symptoms including highly prevalent psychological symptoms like depression, anxiety, insomnia, and impairment in quality of life. Pharmacological treatment of prevalent symptoms like anxiety, depression, and sleep disturbance can contribute to the high chemical burden already carried by cancer patients, creating additional side effects. As a result, patients and providers alike are interested in evidence-based nonpharmacologic alternatives like acupuncture for these symptoms. This article reviews the current literature (January 2000 through April 2013) for acupuncture in cancer-related psychological symptoms with attention to both efficacy and acupuncture-specific methodology. All published studies that met our review criteria demonstrate a positive signal for acupuncture for the treatment of depression, anxiety, sleep disturbance, and for improving quality of life with most results showing statistical significance. However, there are only a handful of acupuncture studies that were specifically designed to evaluate depression, sleep disturbance, and quality of life as primary outcomes, and no studies were found that looked at anxiety as a primary outcome in this population. Published studies in cancer patients and survivors show that acupuncture treatment is not only safe but also more acceptable with fewer side effects than standard of care pharmacological treatments like antidepressants. Finally, there is wide variability in both the implementation and reporting of acupuncture methods in the literature, with only 2 of 12 studies reporting full details of acupuncture methods as outlined in the revised Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines, published in 2010 and providing an essential framework for the reporting of acupuncture methodology. This lack of methodological detail affects outcomes, generalizability, and validity of research involving acupuncture. Reasons for ongoing challenges in the development of high-quality acupuncture trials are discussed. In conclusion, results are encouraging for the development of randomized trials to directly evaluate the therapeutic impact of acupuncture in cancer-related psychological symptoms, including depression, anxiety, sleep disturbance, and quality of life, but attention to acupuncture methodological specific challenges in the development of high-quality research is necessary.
Objective. Chemotherapy-induced oral mucositis (COM) is characterized by painful inflammation with prolonged damage that involves the pathological pain-evoking prostaglandin E2 (PGE2). We previously found that gargling with hangeshashinto (HST), a traditional Japanese medicine, was effective for the treatment of COM. However, little is known regarding the mechanisms. Our aim was to identify the active ingredients and clarify the characteristic effects of HST on the PGE2 system. Methods. Prostanoids produced by human oral keratinocytes (HOK) stimulated with IL-1β were measured by enzyme immunoassay. Active ingredients that regulate PGE2 production were identified and quantified by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and a culture system of HOK cells. Results. Inducible PGE2, PGD2, and PGF2α, metabolites of cyclooxygenase (COX) pathways, were reduced by HST (10-300 µg/mL) without inducing cytotoxicity. The active ingredients of HST were quantified by LC-MS/MS, and [6]-shogaol, [6]-gingerol, wogonin, baicalein, baicalin, and berberine were shown to reduce PGE2 production. A mixture of these 6 ingredients at concentrations equal to 300 µg/mL of HST strongly suppressed PGE2 production to the same level as HST. [6]-Shogaol and [6]-gingerol did not decrease COX-2 mRNA expression and mostly inhibited PGE2 metabolic activity in an assay using intact HOK cells, suggesting that they regulate PGE2 synthesis at the posttranscriptional level. Wogonin, baicalin, and berberine inhibited expression of COX-2 mRNA without affecting PGE2 metabolic activity. Moreover, wogonin, but not [6]-shogaol, suppressed phosphorylation of mitogen-activated protein kinases (p38s and JNKs). Conclusions. These lines show that HST includes several PGE2-regulating ingredients that have different mechanisms and can function as a multicomponent and multitarget agent for treatment of COM, indicating that HST may be beneficial in a new medical strategy for COM treatment.
Aim of study: To investigate the inhibitory effect of Coptidis rhizome aqueous extract (CRAE) on vascular endothelial growth factor (VEGF) expression and tumor angiogenesis in hepatocellular carcinoma (HCC). Methods: Quality control of CRAE was determined. Secretion of VEGF protein and expression of its mRNA in MHCC97L and Hep G2 cells were measured with enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. Synthesis of nascent protein was determined by AHA-protein-labeling technologies. The in vivo antiangiogenic effect of CRAE was evaluated with a xenograft model. Results: Absence of organochlorine pesticides in CRAE was found, and phytochemical analysis showed that its components were in proportion of magnoflorine 2.2%, jatrorrhizine 1.68%, palmatine 4.4%, and berberine 13.8%. CRAE exhibited significant inhibition on VEGF secretion from MHCC97L and HepG2 cells at nontoxic doses. The mRNA transcripts of VEGF could not be inhibited by CRAE; however, synthesis of VEGF nascent protein was potently blocked by CRAE. CRAE intervention increased the phosphorylation of eukaryotic elongation factor 2 (eEF2) in HCC cells, which blocked eEF2 activity for proceeding nascent protein synthesis. The activity of eEF2 was restored in CRAE-treated HCC cells in the presence of A484594, leading to the recovery of VEGF expression. Berberine was found to be the major active component in CRAE; however, CRAE is more effective in inhibiting eEF2 activity compared to berberine treatment alone, suggesting the additive effect of other components present. Reduction of tumor size and neovascularization were observed in mice xenograft model. Conclusion: Our study postulates the antiangiogenic effect of CRAE on hepatocellular carcinoma via an eEF2-driven pathway.
Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NFB, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice.
Pancreatic carcinoma remains one of the main causes for cancer-related death. Intratumoral application of anticancer agents is discussed as a promising method for solid tumors such as pancreatic cancer. Endoscopic ultrasound provides a good tool to examine and treat the pancreas. European mistletoe (Viscum album L) is a phytotherapeutic commonly used in integrative oncology in Central Europe. Its complementary use seeks to induce immunostimulation and antitumoral effects as well as alleviate chemotherapeutic side effects. Intratumoral mistletoe application has induced local tumor response in various cancer entities. This off-label use needs to be validated carefully in terms of safety and benefits. Here we report on 39 patients with advanced, inoperable pancreatic cancer, who received in total 223 intratumoral applications of mistletoe, endoscopic ultrasound guided or under transabdominal ultrasound control. No severe procedure-related events were reported. Adverse drug reactions were mainly increased body temperature or fever in 11% and 14% of the applications, respectively. Other adverse drug reactions, such as pain or nausea, occurred in less than 7% of the procedures. No severe adverse drug reaction was recorded. Patients received standard first- and second-line chemotherapy and underwent adequate palliative surgical interventions as well as additive subcutaneous and partly intravenous mistletoe application. A median survival of 11 months was observed for all patients, or 11.8 and 8.3 months for stages III and IV, respectively. Due to the multimodal therapeutic setting and the lack of a control group, the effect of intratumoral mistletoe administration alone remains unclear. This retrospective analysis suggests that intratumoral-applicated mistletoe might contribute to improve survival of patients with pancreatic cancer. In conclusion, the application is feasible and safe, and its efficacy should be evaluated in a randomized controlled trial.
In spite of billions of dollars spent on cancer research each year, overall cancer incidence and cancer survival has not changed significantly in the last half century. Instead, the recent projection from the World Health Organization suggests that global cancer incidence and death is expected to double within the next decade. This requires an "out of the box" thinking approach. While traditional medicine used for thousands of years is safe and affordable, its efficacy and mechanism of action are not fully reported. Demonstrating that traditional medicine is efficacious and how it works can provide a "bed to bench" and "bench to bed" back approach toward prevention and treatment of cancer. This current review is an attempt to describe the contributions of traditional Korean medicine (TKM) to modern medicine and, in particular, cancer treatment. TKM suggests that cancer is an outcome of an imbalance of body, mind, and spirit; thus, it requires a multimodal treatment approach that involves lifestyle modification, herbal prescription, acupuncture, moxibustion, traditional exercise, and meditation to restore the balance. Old wisdoms in combination with modern science can find a new way to deal with the "emperor of all maladies."
Purpose. To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design. Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results. Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion. Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.
Hypothesis. Qigong exercise is a popular method for relieving the side effects of conventional cancer treatments in survivors of breast cancer, yet its effects are not empirically assessed. This study aimed to investigate the effects of qigong exercise on upper limb lymphedema, arterial resistance, and blood flow velocity in survivors with breast cancer and mastectomy. Study Design. This study was conducted as a prospective clinical trial. Methods. Eleven survivors of breast cancer with qigong experience (mean age = 58.3 ± 10.1 years) were assigned to the experimental group and 12 survivors of breast cancer without qigong experience (mean age = 53.8 ± 4.2 years) were assigned to the control group. They all had breast cancer–related lymphedema. All procedures were completed within one session. After baseline measurements were taken, the experimental group performed 18 Forms Tai Chi Internal Qigong for approximately 6 minutes while the control group rested for similar duration in a sitting position. Both groups were then reassessed. All participants were measured on their affected upper limb circumference (by using tape measures), peripheral arterial resistance, and blood flow velocities (using a Doppler ultrasound machine). Results. The between-group differences were not significant for all outcome measures at baseline (P > .05). The circumferences of the affected upper arm, elbow, forearm and wrist decreased after qigong exercise (P < .05). However, no significant difference was found in the circumference measures between the 2 groups posttest (P > .0125). In terms of vascular outcomes, the resistance index decreased and the maximum systolic arterial blood flow velocity (SV) and minimum diastolic arterial blood flow velocity (DV) increased significantly after qigong exercise (P < .05). The between-group difference was close to significant for SV (P = .018) and was significant for DV (P < .001) posttest. Conclusion. Qigong exercise could reduce conventional cancer therapy side effects such as upper limb lymphedema and poor circulatory status in survivors of breast cancer. However, such effects may be temporary, and further studies must be conducted to explore longer term effects.
Emerging trends for cancer chemotherapy show promising developments with the better understanding of molecules delivering more potent and powerful capabilities. But these are severely limited because of increased side effects and higher probability of tumor recurrence. In this scenario, putative exploration of the indigenous and untapped resources modulating immune system to deliver adequate but potent chemopreventive effects appeals considerable interest. However, these require rigorous scientific validation with regard to potency compared with the existing drugs. Aegle marmelos (Linnaeus) Correa (family Rutaceae), a plant component of polyherbal formulation, Indukantha Ghritha, is known for its widespread medicinal values. But the chemopreventive potential has not been explored in comparison to existing anticancer agents. Our attempt contributes the scientific evidence for beneficial immunoprophylactic and antitumor functions in mice challenged with ascites tumors, Dalton’s lymphoma ascites, and Ehrlich’s ascites carcinoma either alone or in combination with cyclophosphamide and 5-fluorouracil. Specifically, the petroleum ether extracts of this plant (AMPE) prophylactically activated a cascade of host defense mechanisms by stimulating or restoring total white blood cell count, macrophage phagocytosis, hematopoiesis, lymphocyte proliferation and functions (CD4+ and CD8+) either naturally or under conditions of impaired immunity like in ascites tumor or during standard agent chemotherapy. Overall, AMPE also elicited strong antitumor effects by increasing median survival time and life span, while reducing murine ascites tumor volume and viable tumor counts on par with cyclophosphamide and 5-fluorouracil especially when administered prophylactically. This study also identified 2 putative components, xanthorrhizol and marmelosin, which could be imparting the immunoprophylactic and antitumor effects in transplantable tumor models. Thus, our attempts provide sufficient proof to warrant further to test this drug in higher animal models or in patients with high risk for tumor recurrence and/or immunocompromised diseases.
The use of ionizing radiation, which is the cornerstone of cancer treatment, is compromised by the radiosensitivity of normal tissues. A chemical that can give selective benefit to the normal cells against the deleterious effects of ionizing radiation has been a long-sought goal. However, most of the compounds studied have shown inadequate clinical application owing to their inherent toxicity, undesirable side effects, and high cost. Studies carried out in the past 2 decades have shown that some of the classical Indian Ayurvedic drugs (Amritaprasham, Ashwagandha Rasayana, Brahma Rasayana, Chyavanprasha, Narasimha Rasayana, and Triphala Churna) possess radioprotective effects. In the current review, an attempt is made to summarize the radioprotective observations of these Ayurvedic drugs and the mechanisms responsible for the radioprotective effects.
Radiation-induced skin damage is one of the most common complications of radiotherapy. In order to combat these side effects, patients often turn to alternative therapies, which often include antioxidants. Antioxidants such as those in the polyphenol chemical class, xanthine derivatives, tocepherol, sucralfate, and ascorbate have been studied for their use in either preventing or treating radiotherapy-induced skin damage. Apart from their known role as free radical scavengers, some of these antioxidants appear to alter cytokine release affecting cutaneous and systemic changes. We review the role of antioxidants in treating and preventing radiation-induced skin damage as well as the possible complications of using such therapy.
Objectives. The aims of this study were to determine the effect of conjugated linoleic acid (CLA) supplementation on inflammatory factors and matrix metalloproteinase (MMP) enzymes in rectal cancer patients undergoing chemoradiothetrapy. Method and Material. In this randomized, double-blind, placebo-controlled pilot study, 34 volunteer patients with rectal cancer undergoing chemoradiotherapy assigned into the CLA group (n = 16), receiving 3 g CLA/d, and placebo group (n = 18) receiving placebo capsules (sunflower oil) for 6 weeks. The supplementation began 1 week before starting RT (loading period) and continued every day during treatment. Before and after intervention, serum tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, MMP-2, MMP-9, and high-sensitivity C-reactive protein (hsCRP) were measured by enzyme-linked immunosorbent assay (ELISA) kits and immunoturbidimetric method, respectively. Independent t tests and paired t tests were used to compare parameters between and within groups, respectively. Results. In the CLA group, the mean serum TNF-α, IL-1β, hsCRP, MMP-9, and MMP-2 levels reduced insignificantly. However, significant changes in TNF-α (P = 0.04), hsCRP (P = 0.03), and MMP-9 (P = 0.04) concentrations were observed in the CLA group when compared with the placebo group. The mean serum IL-6 level remained unchanged in the CLA group but increased remarkably in the placebo group. Conclusion. According to our results, CLA supplementation improved inflammatory factors, MMP-2, and MMP-9 as biomarkers of angiogenesis and tumor invasion. It seems that CLA may provide new complementary treatment by reducing tumor invasion and resistance to cancer treatment in patients with rectal cancer.
Introduction. Listening to music can positively benefit neurophysiological and emotional responses as well as promote relaxation, which may be especially beneficial for cancer patients undergoing painful and anxiety inducing treatments. The purpose of the present study was to conduct an evidenced-based systematic review and meta-analysis of randomized controlled trials of music interventions to reduce anxiety for adult cancer patients undergoing medical treatment. Methods. A systematic literature search was conducted and data were abstracted from all eligible studies. Studies were included if they tested a music therapy randomized controlled trial in adult cancer patients (in active treatment), assessed anxiety postintervention using a validated measure, were published in English (or were translatable), and accessible in full text. Studies were qualitatively reviewed by the first author and 2 raters independently assessed each study using the PEDro scale. Standardized mean differences between experimental and control groups were calculated for studies meeting a specified methodological rigor score with accessible means and standard deviations postintervention. Heterogeneity and publication bias were explored. Results. Thirteen randomized controlled trials were included with 4 eligible for meta-analysis. Studies varied in intervention methodology and utilization of anxiety measures. Almost all studies reported either a significant difference in anxiety between groups postintervention or a significant decrease in anxiety over time in the music intervention group. Meta-analytic results of 4 studies (4/13) demonstrated that differences in anxiety between experimental and control groups were not significant in the main analysis or subgroup analysis. Studies demonstrated heterogeneity in anxiety results. Publication bias was not evident. Conclusion. The meta-analytic results failed to demonstrate a positive effect on anxiety among adult cancer patients in treatment but may in part be attributed to the small sample size. These findings are in contrast to a prior meta-analysis that analyzed all studies regardless of methodological rigor. More research is needed to ascertain the most optimal intervention methodology and which cancer populations or treatment modalities are appropriate for such an intervention.
Purpose. Complementary and traditional medicine (CTM) plays an important role in culture-centered care for cancer patients in the Middle East. In this article, we have studied the attitudes of Arab CTM therapists concerning integration of complementary medicine within the conventional supportive cancer care of Arab patients in northern Israel. Methods. Semistructured interviews were held with 27 Arab therapists who use medicinal herbs, the Quran, and various CTM modalities, with the aim of characterizing their treatment practices and learning about their perspectives regarding conventional cancer care. Results. We first summarized the different characteristics of the various CTM therapists, including training, typical practice, and so on. Thematic analysis revealed that folk healers and complementary medicine therapists describe their role as supportive and secondary to that of physicians. Their goal was not to cure patients with cancer but rather to enhance their quality of life by reducing the severity of both the disease symptoms and the side effects of cancer treatment. Religious healers, by contrast, purport to cure the disease. While folk healers opt for parallel alternative care and complementary therapists support integrative care, religious healers claimed that they offer an alternative to conventional medicine in terms of both etiology and practice. Conclusions. The majority of Arab CTM therapists support integration of their treatments with the conventional system, but in practice, they are not sure how to bring about this change or create a parallel model in which 2 different systems are active, but not integrated. Our findings emphasized the need to promote doctor–CTM practitioner communication based on structured referral and bidirectional consultation. Moreover, we recommend intensifying research on the efficacy and safety of CTM in the Middle East and the potential role in promoting culture-based supportive care.
Introduction. Many women with ovarian cancer are choosing to include complementary and alternative medicine (CAM) substances in conjunction with their conventional treatment for ovarian cancer. Many oncologists express concern that the adjunct use of CAM substances may be detrimental to the achievement of therapeutic levels of chemotherapy leading to increases in drug toxicity, under-treatment of disease or other adverse events. In an effort to ascertain the extent of the potential problem with simultaneous use of CAM with conventional treatment we undertook comprehensive systematic review of published case reports describing CAM-related adverse events among ovarian cancer patients. Study design. This article describes a systematic literature review. Methods. The Natural Medicines Comprehensive Database (NMCD). PubMed, EMBASE® and the Cochrane Central Register of Controlled Trials (CCTR) were systematically reviewed for research articles pertaining to case reports describing adverse events in patients, and clinical trials which examined the effects of herbs and supplements used during cancer treatment. Results. Only one case report and one clinical trial were identified which met our inclusion criteria and were relevant to the current investigation. Conclusion. Although there are concerns about the potential for adverse events related to concurrent use of CAM substances during conventional treatment we found few case reports and clinical trials in the literature which support this.
Objective. The purpose of this randomized controlled trial (RCT) was to examine the feasibility and acceptability of a Tai Chi Chih (TCC) intervention in senior female cancer survivors with physical functioning limitations, and its effects on health-related quality of life (QOL). Design. This was a two-armed, parallel group, RCT with 12-weeks of Tai Chi Chih or Health Education Control. Methods. Sixty-three senior (M age = 67 years, SD = 7.15) female cancer survivors (83% breast cancer, stages I-III) with physical functioning limitations (SF-12 Health Survey role-physical & physical functioning subscales) were randomized to 12-weeks of TCC or Health Education control (HEC). Primary outcomes were feasibility and acceptability. Secondary outcomes included health-related QOL (SF-36 Health Survey), and participants’ qualitative feedback on the intervention. Results. Retention (TCC = 91%; HEC = 81%) and class attendance (TCC = 79%; HEC = 83%) rates, and satisfaction levels for both study arms were high, but did not significantly differ from one another. At one-week post-intervention, none of the SF-36 scores differed between the TCC and HEC groups. Within-group analyses revealed significant improvements in the mental component summary score in TCC (p = 0.01), but not in HEC. Qualitative analyses indicated that the TCC group felt they received mental and physical benefits, whereas HEC group reported on social support benefits and information received. Conclusion. The TCC intervention was found to be a feasible and acceptable modality for senior female cancer survivors. Future, larger definitive trials are needed to clarify TCC dosage effects on QOL in this vulnerable population.
Objective. Ethanolic extract of Gymnema sylvestre (GS) leaves is used as a potent antidiabetic drug in various systems of alternative medicine, including homeopathy. The present study was aimed at examining if GS also had anticancer potentials, and if it had, to elucidate its possible mechanism of action. Methods. We initially tested possible anticancer potential of GS on A375 cells (human skin melanoma) through MTT assay and determined cytotoxicity levels in A375 and normal liver cells; we then thoroughly studied its apoptotic effects on A375 cells through protocols such as Hoechst 33258, H2DCFDA, and rhodamine 123 staining and conducted ELISA for cytochrome c, caspase 3, and PARP activity levels; we determined the mRNA level expression of cytochrome c, caspase 3, Bcl2, Bax, PARP, ICAD, and EGFR signaling genes through semiquantitative reverse transcriptase polymerase chain reaction and conducted Western blot analysis of caspase 3 and PARP. We also analyzed cell cycle events, determined reactive oxygen species accumulation, measured annexin V-FITC/PI and rhodamine 123 intensity by flow cytometry. Results. Compared with both normal liver cells and drug-untreated A375, the mortality of GS-treated A375 cells increased in a dose-dependent manner. Additionally, GS induced nuclear DNA fragmentation and showed an increased level of mRNA expression of apoptotic signal related genes cytochrome c, caspase 3, PARP, Bax, and reduced expression level of ICAD, EGFR, and the anti-apoptotic gene Bcl2. Conclusion. Overall results indicate GS to have significant anticancer effect on A375 cells apart from its reported antidiabetic effect, indicating possibility of its palliative use in patients with symptoms of both the diseases.
Background and hypotheses. Postcancer cognitive impairment (PCCI) is observed in a substantial number of breast cancer survivors, persisting for as long as 20 years in some subgroups. Although compensatory strategies are frequently suggested, no restorative interventions have yet been identified. This study examined the feasibility of EEG biofeedback ("neurofeedback") and its potential effectiveness in reducing PCCI as well as the fatigue, sleep disturbance, and psychological symptoms that frequently accompany PCCI. Study design. This was a 6-month prospective study with a waitlist control period followed by an active intervention. Participants were female breast cancer survivors (n = 23), 6 to 60 months postchemotherapy, with self-reported cognitive impairment. Methods. Four self-report outcome measures (Functional Assessment of Cancer Therapy–Cognitive Function [FACT-Cog], Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT-Fatigue], Pittsburgh Sleep Quality Index [PSQI], and Brief Symptom Inventory [BSI]-18) were administered 3 times during a 10-week waitlist control period, 3 times during a 10-week (20-session) neurofeedback training regimen, and once at 4 weeks postneurofeedback. Results. All 23 participants completed the study, demonstrating the feasibility of EEG biofeedback in this population. Initially, the sample demonstrated significant dysfunction on all measures compared with general population norms. Repeated-measures ANOVAs revealed strongly significant improvements (P < .001) on all 4 cognitive measures (perceived cognitive impairment, comments from others, perceived cognitive abilities, and impact on quality of life [QOL]), the fatigue scale, and the 4 psychological scales (somatization, depression, anxiety and global severity index) as well as on 3 of 8 sleep scales (quality, daytime dysfunction, and global). Two of the other sleep scales (latency and disturbance) were significant at P < .01, and 1 (use of medication) at P < .05; 2 were not significant. Improvements were generally linear across the course of training, and were maintained at the follow-up testing. At the follow-up testing, the sample no longer differed significantly from normative populations on 3 of the 4 FACT-Cog measures (impairment, impact on QOL, and comments), FACIT-Fatigue, PSQI sleep quality and habitual efficiency, or any of the BSI-18 measures of psychological disturbance. Conclusions. Data from this limited study suggest that EEG biofeedback has potential for reducing the negative cognitive and emotional sequelae of cancer treatment as well as improving fatigue and sleep patterns.
Background. Many women use black cohosh as a natural treatment for menopausal symptoms. However, controversy exists around safety in breast cancer, because of its purported estrogenic activity. We conducted a systematic review of black cohosh use in women with or at risk of breast cancer. Methods. We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to July 2012 and October 2012 for human interventional or observational data pertaining to the safety and efficacy of black cohosh in patients with or at risk of breast cancer, including an assessment of the effect of black cohosh on estrogen responsive tissues. Results. Of 450 records, we included 26 articles: 14 randomized controlled trials, 7 uncontrolled trials, and 5 observational studies.The evidence on efficacy for hot flashes is divided, with some benefits seen when compared with baseline, but not when compared with placebo. Two observational studies found no association between black cohosh and risk of breast cancer, whereas 2 studies reported significant reductions in risk of primary breast cancer among postmenopausal women (adjusted odds ratio = 0.47, 95% confidence interval = 0.27-0.82), and risk of recurrence (adjusted hazard ratio = 0.75, 95% confidence interval = 0.63-0.89). Seventeen trials showed no significant impact on circulating hormone levels or proliferation in estrogen responsive tissues. Conclusions. Current evidence does not support an association between black cohosh and increased risk of breast cancer. There is a lack of evidence supporting the efficacy of black cohosh for reduction of hot flashes in breast cancer patients. Given conflicting but promising results, and apparent safety, further research is warranted.
Managing cancer-related chronic pain is challenging to health care professionals as well as cancer patients and survivors. The management of cancer-related pain has largely consisted of pharmacological treatments, which has caused researchers to focus on neurotransmitter activity as a mediator of patients’ perception of pain rather than the electrical activity during neurobiological processes of cancer-related pain. Consequently, brain-based pain treatment has focused mainly on neurotransmitters and not electrical neuromodulation. Neuroimaging research has revealed that brain activity is associated with patients’ perceptions of symptoms across various diagnoses. The brain modulates internally generated neural activity and adjusts perceptions according to sensory input from the peripheral nervous system. Cancer-related pain may result not only from changes in the peripheral nervous system but also from changes in cortical activity over time. Thus, cortical reorganization by way of the brain’s natural, plastic ability (neuroplasticity) may be used to manage pain symptoms. Physical and psychological distress could be modulated by giving patients tools to regulate neural activity in symptom-specific regions of interest. Initial research in nononcology populations suggests that encouraging neuroplasticity through a learning paradigm can be a useful technique to help treat chronic pain. Here we review evidence that indicates a measurable link between brain activity and patient-reported psychological and physical distress. We also summarize findings regarding both the neuroelectrical and neuroanatomical experience of symptoms, review research examining the mechanisms of the brain’s ability to modify its own activity, and propose a brain-computer interface as a learning paradigm to augment neuroplasticity for pain management.
Resistance exercise has great potential to aid in the management of breast cancer–related lymphedema (BCRL), but little is known regarding the acute response of performing resistance exercises with the affected limb. Purpose. To examine the acute impact of upper body resistance exercise on the amount of swelling and severity of symptoms in women with BCRL and to compare these effects between resistance exercise involving high and low loads (heavier vs lighter weights). Methods. Seventeen women aged 61 ± 9 years with mild to severe BCRL participated in this study. Participants completed a high load (6-8 repetition maximum) and low load (15-20 repetition maximum) exercise session consisting of 2 sets of 5 upper body resistance exercises in a randomized order separated by a 10- to 12-day wash-out period. The extent of swelling was assessed using bioimpedance spectroscopy, dual-energy x-ray absorptiometry, and arm circumference measurements. The severity symptoms were assessed using the visual analogue scale (pain, heaviness, and tightness) and a modified Brief Pain Inventory. Measurements were taken pre-exercise, immediately post-exercise, 24 hours post-exercise, and 72 hours post-exercise. Results. No changes in the extent of swelling or the severity of symptoms were observed between pre-exercise and immediately post-exercise, 24 hours post-exercise, or 72 hours post-exercise. No differences in the response to the high or low load exercise were observed. Conclusions. Upper body resistance exercise does not acutely increase swelling or feelings of discomfort/pain, heaviness tightness in the affected limb of BCRL patients when performed at either high or low loads.
Many studies confirm that a majority of patients undergoing cancer therapy use self-selected forms of complementary therapies, mainly dietary supplements. Unfortunately, patients often do not report their use of supplements to their providers. The failure of physicians to communicate effectively with patients on this use may result in a loss of trust within the therapeutic relationship and in the selection by patients of harmful, useless, or ineffective and costly nonconventional therapies when effective integrative interventions may exist. Poor communication may also lead to diminishment of patient autonomy and self-efficacy and thereby interfere with the healing response. To be open to the patient’s perspective, and sensitive to his or her need for autonomy and empowerment, physicians may need a shift in their own perspectives. Perhaps the optimal approach is to discuss both the facts and the uncertainty with the patient, in order to reach a mutually informed decision. Today’s informed patients truly value physicians who appreciate them as equal participants in making their own health care choices. To reach a mutually informed decision about the use of these supplements, the Clinical Practice Committee of The Society of Integrative Oncology undertook the challenge of providing basic information to physicians who wish to discuss these issues with their patients. A list of leading supplements that have the best suggestions of benefit was constructed by leading researchers and clinicians who have experience in using these supplements. This list includes curcumin, glutamine, vitamin D, Maitake mushrooms, fish oil, green tea, milk thistle, Astragalus, melatonin, and probiotics. The list includes basic information on each supplement, such as evidence on effectiveness and clinical trials, adverse effects, and interactions with medications. The information was constructed to provide an up-to-date base of knowledge, so that physicians and other health care providers would be aware of the supplements and be able to discuss realistic expectations and potential benefits and risks.
Purpose. To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA)undergoing radiotherapy. Methods. Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables. Results. A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control. Conclusions. MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.
Objectives. The National Cancer Institute (NCI) Best Case Series (BCS) Program provides an independent review of medical records, imaging, and pathology of cancer patients treated with unconventional therapies. The goal of the NCI BCS Program is to identify preliminary evidence of tumor regression and assess whether there is sufficient evidence to move forward with NCI-initiated research. The objective was to review case reports submitted by 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. Design. Retrospective review of case reports of 4 practitioners from India who used ayurvedic and homeopathic therapies to treat cancer. Results. A total of 68 cases were submitted to the NCI BCS Program. Fifty-one percent of the cases represented homeopathy and 49% ayurveda. Of the 68 cases, 32 (47%) of the cases were collectively designated as "persuasive" (P) or "supportive"(S), and 36 (53%) as "not evaluable." Forty-one (60%) patients did not have any prior conventional treatment. Conclusion. The challenge for submitters rests in their ability to supply sufficient documentation for the NCI BCS Program. The NCI BCS Program represents a unique avenue for the rigorous evaluation of "best cases" to identify complementary and alternative medicine modalities that are promising for prospective preclinical evaluation or prospective research.
Hypothesis. Although several conventional therapeutic options for advanced renal cell carcinoma (RCC) are currently available, the unsatisfactory outcomes demand establishing more effective interventions. D-fraction (PDF), a bioactive proteoglucan of Maitake mushroom, demonstrates anticancer and immunomodulatory activities, which are also shown to be potentiated by vitamin C (VC). We thus hypothesized that a combination of PDF and VC (PDF + VC) could be an alternative approach to more effectively inhibit the growth of RCC. Study design. We examined the dose-dependent effects of PDF + VC on RCC cell viability and also performed biochemical assays to explore the growth regulatory mechanism. Methods. Human RCC, ACHN cell line, was employed and exposed to varying concentrations of PDF or VC and their combinations. Cell viability at specified times was determined by MTT assay. Lipid peroxidation assay, cell cycle analysis, and Western blot analysis were also performed. Results. PDF or VC alone led to the significant reduction in cell viability at 72 hours with PDF >500 µg/mL and VC ≥300 µM. When various combinations of PDF and VC were tested, the combination of the ineffective concentrations of PDF (300 µg/mL) and VC (200 µM) resulted in ~90% cell death in 24 hours. Lipid peroxidation assay then indicated significantly (~2.5 fold) elevated oxidative stress with this PDF + VC. Cell cycle analysis also indicated a G1 cell cycle arrest following a 6-hour PDF + VC treatment. Western blots further revealed a downregulation of Bcl2, an upregulation of Bax, and proteolytic activation of PARP (poly[ADP-ribose] polymerase) in PDF + VC-treated cells, indicating induction of apoptosis. Conclusion. The present study demonstrates that the combination of PDF and VC can become highly cytotoxic, inducing severe cell death in ACHN cells. This cytotoxic mechanism appears to be primarily attributed to oxidative stress, accompanied by a G1 cell cycle arrest. Such cell death induced by PDF + VC could be more likely linked to apoptosis, as indicated by the modulation of apoptosis regulators (Bcl2, Bax, and PARP). Therefore, as PDF and VC may work synergistically to induce apoptotic cell death, they may have clinical implications in an alternative, improved therapeutic modality for advanced RCC.
Introduction. Cancer diagnosis and treatment are often associated with physical and psychosocial impairments. Many cancer patients request complementary and alternative therapies such as mind-body medicine. Concept. The department of internal and integrative medicine at the Essen-Mitte Clinics offer a mind-body medicine day care clinic for cancer patients that is based on the Mindfulness-Based Stress Reduction Program and the mind-body medicine cancer program of the Harvard Mind/Body Medical Institute. The program encompasses mindfulness training, yoga, mindful exercise, nutrition, naturopathic self-help strategies, and cognitive restructuring. Cases. Two patients who had participated in the day care clinic program are presented here. One patient presented with anxiety and depression after recently diagnosed breast cancer and the other with psychological impairments as a result of multiple nevi excision after malignant melanoma surgery. Both patients improved in terms of anxiety and further psychological symptoms. Conclusions. The Essen-Mitte Clinics mind-body medicine day care clinic appears to alleviate psychological consequences of cancer and its treatment. Further studies and randomized controlled trials are necessary to confirm these results.
The development of nontoxic agents that can selectively enhance the cytotoxicity of chemotherapy is an important aim in oncology. This study evaluates the ability of infrasound exposure to sensitize glioblastoma cells to cisplatin-induced apoptosis. The infrasound was delivered using a device designed to replicate the unique infrasound emissions measured during external Qigong treatments. Human glioblastoma cell lines harboring wild-type p53 (U87) or mutant p53 (U251, SF210, and SF188) were treated in culture with cisplatin, infrasound emissions, or the combination of the 2 agents. Induction of apoptosis was quantified after 24 hours by flow cytometry following annexin V/propidium iodide staining. Infrasound emissions alone, delivered at moderate levels (~10 mPa) with dynamic frequency content (7-13 Hz), did not induce apoptosis, yet combining infrasound with cisplatin augmented the induction of apoptosis by cisplatin in all the 4 cell lines (P < .05). Increased cellular uptake of the fluorophore calcein associated with infrasound exposure was quantified by fluorescence microscopy as well as flow cytometry, demonstrating increased cell membrane permeability. The 4 cell lines differed in the degree to which infrasound exposure increased calcein uptake, and these differences were predictive of the extent to which infrasound enhanced cisplatin-induced apoptosis. When exposed to specific frequencies, membrane permeabilization also appeared to be differentially responsive for each cell line, suggesting the potential for selective targeting of tissue types using isolated infrasonic frequencies. Additionally, the pressure amplitudes used in this study were several orders of magnitude less than those used in similar studies involving ultrasound and shock waves. The results of this study provide support for using infrasound to enhance the chemotherapeutic effects of cisplatin in a clinical setting.
Background. Traditional Chinese herbal medicine (TCHM) is widely used for advanced gastric cancer (AGC) in China. In this study, the authors analyzed the prognostic factors of selected patients with AGC, and further studied the efficacy of TCHM (a herbal formula for invigorating spleen, formerly named Wei Chang’ An) on AGC. Methods. Patients with uncured AGC were prospectively enrolled. All patients were enrolled to either the TCHM group or non-TCHM group. TCHM was administered orally to the patients in the TCHM group for 3 months or more. Cox regression analysis was performed to determine survival trends adjusted for clinical and demographic factors. Kaplan–Meier curves were used to assess the differences in survival time. Results. There were a total of 399 eligible patients with histologically confirmed adenocarcinoma of the stomach from 2001 to 2009. In the overall group, Cox regression analysis suggested that histological type (P = .016), radiotherapy (P = .000), cycle of chemotherapy (P = .000), and TCHM (P = .000) were independent prognostic factors. In a stratification analysis of stage for 213 patients who received 3 or more cycles of chemotherapy, there was a significant increase in median overall survival from 14.0 (non-TCHM group) to 20.0 (TCHM group) months (hazard ratio [HR] = 0.538, 95% confidence interval [CI] 0.385-0.750, P = .000). Among 186 patients who did not receive chemotherapy, but best supportive care, there was a significant increase in median overall survival from 7.0 (non-TCHM group) to 14.8 (TCHM group) months (HR = 0.443, 95% CI = 0.299-0.657, P = .000). Conclusions. TCHM has an important potential value for improving the prognosis of patients with AGC.
Background. The anomalous fruits of Gleditsia sinensis Lam. (Leguminosae), a crude drug in China, have long been used in traditional Chinese medicine for the treatment of various diseases. The saponin fraction isolated from the fruits (SFGS) is considered as the active component for the antitumor activity of this crude drug. Objectives. The present study was performed to investigate the anti-angiogenesis activities and active constituents of SFGS. Methods. Human umbilical vein endothelial cells (HUVECs) were treated with SFGS in the presence or absence of basic fibroblast growth factor (bFGF) in vitro. The proliferation, migration, and tube formation were studied by MTT, Transwell, and 2D Matrigel assays, respectively. The cell cycle and apoptosis were analyzed by flow cytometry. Enzyme-linked immunosorbent assay for protein expression of vascular endothelial growth factor (VEGF) and western blot analysis for caspase-3, caspase-8, and caspase-9 as well as Fas were performed. In addition, the effects of 13 saponin compounds isolated from SFGS on the tube formation of HUVECs were screened, and the structure–activity relationships were discussed. Results. SFGS, at concentrations (1, 3, and 10 µg/mL) without significant cytotoxicity on endothelial cells, significantly inhibited the proliferation, migration, and tube formation of HUVECs induced by bFGF (10 ng/mL). It moderately arrested the cell cycle to G1 phase but greatly induced cell apoptosis and increased the expressions of caspases-3, caspase-8, and Fas but not caspase-9 in HUVECs. Moreover, SFGS did not affect the bFGF-induced autosecretion of VEGF from endothelial cells. Among the 13 saponin compounds tested, gleditsiosides B, I, J, O, and Q showed inhibition of the tube formation at a concentration of 3 µM, and only gleditsioside B exerted significant inhibition at 1 µM. Conclusion. SFGS is substantially able to prevent angiogenesis by interfering with multiple steps. The findings provide a new explanation for the antitumor effects of G sinensis fruits. Gleditsiosides B, I, J, O, and Q are probably the main active constituents of SFGS.
Furano-1,2-naphthoquinone (FNQ), a biologically active component of Avicennia marina, has been demonstrated to display anticancer activity. FNQ exerted cytotoxicity with the G2/M cell cycle arrest and apoptosis in Ca9-22 cells. FNQ-induced G2/M arrest was correlated with a marked decrease in the expression levels of cyclin A and cyclin B, and their activating partner cyclin-dependent kinases (CDK) 1 and 2 with concomitant induction of p27. FNQ-induced apoptosis was accompanied by Bax and Bad upregulation, and the downregulation of Bcl-2, Bcl-XL, Mcl-1, and X-linked inhibitor of apoptosis (XIAP), resulting in cytochrome C release and sequential activation of caspase-9 and caspase-3. Mechanistic studies showed that FNQ suppressed Src phosphorylation, PI3K, and Akt activation in Ca9-22 cells. Moreover, the Src inhibitor PP2 reduced the phosphorylation of Src and activation of PI3K/Akt, which was comparable with FNQ treatment. The combined treatment of FNQ with PP2 enhanced the cell cycle arrest and apoptosis and also led to the downregulation of Bcl-XL, Mcl-1, XIAP, cyclin A, cyclin B, CDK1, and CDK2 and upregulation of p27, Bax, and Bad. These findings suggest that FNQ-mediated cytotoxicity of Ca9-22 cells is related with the G2/M cell cycle arrest and apoptosis via inactivation of Src and PI3K/Akt–mediated signaling pathways.
Ginkgolide B (GB), the primary active component of Ginkgo biloba extracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine cell viability. The apoptosis rates of cells were measured by flow cytometric analysis. The expression of apoptosis-associated and proliferation-associated proteins was detected by Western blot. The cytotoxicity of GB was analyzed using a lactate dehydrogenase assay. Treatment with 100 µM GB for 3 days significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells, respectively, as determined by MTT assay. Similarly, the apoptotic cell population was increased when treated with GB in a dose-dependent manner both in SKOV3 and CAOV3 cells. These effects were characterized by the upregulation of p21, p27, cleaved capase-3, and cleaved caspase-8 and downregulation of cyclin D1. In addition, a combined treatment of low concentrations of GB and CDDP showed an additive effect on the inhibition of SKOV3 cell proliferation. Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.
Previous cytotoxic (anticancer) evaluations of Elephantopus mollis were mainly focused on its elephantopin derivatives neglecting the combined effect of the phytochemicals in its traditionally used extracts. In this study, the cytotoxic mechanism of its extracts was investigated using methylene blue assay. The cytotoxic screening results revealed the ethyl acetate extract as the most potent extract by displaying prominent dose-dependent and time-dependent growth inhibitions in human liver carcinoma HepG2 cells with the lowest EC50 value of 9.38 ± 0.43 µg/mL after 72 hours of treatment. Acute exposure of the HepG2 cells to the ethyl acetate extract produced a significant regulation of caspase-3 with the peak expression at 8 hours of treatment (P < .05). DNA fragmentation indicated by DeadEnd Apoptosis Detection System–labeled nuclei cells confirmed that the extract induced apoptotic cell death through caspase-3-dependent pathway in HepG2 cells.