Comparative efficacy of non-pharmacological adjuvant therapies for quality of life in the patients with breast cancer receiving chemo- or radio-therapy: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer in women worldwide. When treated by chemotherapy and/or radiotherapy, there are various non-pharmacological adjuvant therapies (NPATs) recommended for helping the patients with breast cancer alleviate multiple side effects induced by chemotherapy and/or radiotherapy and improve quality of life (QoL). However, the existing evidence does not suggest the therapy with the best effectiveness among a variety of NPATs. This study is to compare the effectiveness of different NPATs on QoL in the patients with breast cancer using Bayesian network meta-analysis (NMA). METHODS AND ANALYSIS: We will conduct a comprehensive search strategy in the relevant databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/Default.aspx), Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wan Fang Data). The random or quasi-random controlled trails that compare different NPATs in patient with breast cancer who received the chemotherapy and/or radiotherapy will be included. We only focus on the outcome of QoL which can be assessed by a series of tools. The risk of bias for included studies will be appraised using the Cochrane Collaboration's tool for assessing risk of bias. The standard pairwise meta-analysis and a Bayesian NMA will be conducted. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required since this is an NMA based on published studies. We will submit our NMA to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42017078143.

Chromium picolinate supplementation for overweight or obese adults.

BACKGROUND: Obesity is a global public health threat. Chromium picolinate (CrP) is advocated in the medical literature for the reduction of bodyweight, and preparations are sold as slimming aids in the USA and Europe, and on the Internet. OBJECTIVES: To assess the effects of CrP supplementation in overweight or obese people. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, ISI Web of Knowledge, the Chinese Biomedical Literature Database, the China Journal Full text Database and the Chinese Scientific Journals Full text Database (all databases to December 2012), as well as other sources (including databases of ongoing trials, clinical trials registers and reference lists). SELECTION CRITERIA: We included trials if they were randomised controlled trials (RCT) of CrP supplementation in people who were overweight or obese.We excluded studies including children, pregnant women or individuals with serious medical conditions. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts for relevance. Screening for inclusion, data extraction and 'Risk of bias'assessment were carried out by one author and checked by a second. We assessed the risk of bias by evaluating the domains selection,performance, attrition, detection and reporting bias. We performed a meta-analysis of included trials using Review Manager 5. MAIN RESULTS: We evaluated nine RCTs involving a total of 622 participants. The RCTs were conducted in the community setting, with interventions mainly delivered by health professionals, and had a short- to medium-term follow up (up to 24 weeks). Three RCTs compared CrPplus resistance or weight training with placebo plus resistance or weight training, the other RCTs compared CrP alone versus placebo.We focused this review on investigating which dose of CrP would prove most effective versus placebo and therefore assessed the results according to CrP dose. However, in order to find out if CrP works in general, we also analysed the effect of all pooled CrP doses versus placebo on body weight only.Across all CrP doses investigated (200 µg, 400 µg, 500 µg, 1000 µg) we noted an effect on body weight in favour of CrP of debatable clinical relevance after 12 to 16 weeks of treatment: mean difference (MD) -1.1 kg (95% CI -1.7 to -0.4); P = 0.001; 392 participants;6 trials; low-quality evidence (GRADE)). No firm evidence and no dose gradient could be established when comparing different doses of CrP with placebo for various weight loss measures (body weight, body mass index, percentage body fat composition, change in waist circumference).Only three studies provided information on adverse events (low-quality evidence (GRADE)). There were two serious adverse events and study dropouts in participants taking 1000 µg CrP, and one serious adverse event in an individual taking 400 µg CrP. Two participants receiving placebo discontinued due to adverse events; one event was reported as serious. No study reported on all-cause mortality,morbidity, health-related quality of life or socioeconomic effects. AUTHORS' CONCLUSIONS: We found no current, reliable evidence to inform firm decisions about the efficacy and safety of CrP supplements in overweight or obese adults.

Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells.

Cancer stem cells are implicated in resistance to ionizing radiation (IR) and chemotherapy. Honokiol, a biphenolic compound has been used in traditional Chinese medicine for treating various ailments. In this study, we determined the ability of honokiol to enhance the sensitivity of colon cancer stem cells to IR. The combination of honokiol and IR suppressed proliferation and colony formation while inducing apoptosis of colon cancer cells in culture. There were also reduced numbers and size of spheroids, which was coupled with reduced expression of cancer stem cell marker protein DCLK1. Flow cytometry studies confirmed that the honokiol-IR combination reduced the number of DCLK1+ cells. In addition, there were reduced levels of activated Notch-1, its ligand Jagged-1, and the downstream target gene Hes-1. Furthermore, expression of components of the Notch-1 activating γ-secretase complex, presenilin 1, nicastrin, Pen2, and APH-1 was also suppressed. On the other hand, the honokiol effects were mitigated when the Notch intracellular domain was expressed. To determine the effect of honokiol-IR combination on tumor growth in vivo, nude mice tumor xenografts were administered honokiol intraperitoneally and exposed to IR. The honokiol-IR combination significantly inhibited tumor xenograft growth. In addition, there were reduced levels of DCLK1 and the Notch signaling-related proteins in the xenograft tissues. Together, these data suggest that honokiol is a potent inhibitor of colon cancer growth that targets the stem cells by inhibiting the γ-secretase complex and the Notch signaling pathway. These studies warrant further clinical evaluation for the combination of honokiol and IR for treating colon cancers.

Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects.

DNA mismatch repair is required for correcting any mismatches that are created during replication and recombination, and a defective mismatch repair system contributes to DNA damage-induced growth arrest. The colorectal cancer cell line HCT116 is known to have a mutation in the hMLH1 mismatch repair gene resulting in microsatellite instability and defective mismatch repair. Honokiol is a biphenolic compound that has been used in traditional Chinese medicine for treating various ailments including cancer. This study was designed to test the hypothesis that honokiol enhances the radiosensitivity of cancer cells with mismatch repair defect (HCT116) compared with those that are mismatch repair proficient (HCT116-CH3). We first determined that the combination of honokiol and γ-irradiation treatment resulted in dose-dependent inhibition of proliferation and colony formation in both cell lines. However, the effects were more pronounced in HCT116 cells. Similarly, the combination induced higher levels of apoptosis (caspase 3 activation, Bax to Bcl2 ratio) in the HCT116 cells compared with HCT116-CH3 cells. Cell cycle analyses revealed higher levels of dead cells in HCT116 cells. The combination treatment reduced expression of cyclin A1 and D1 and increased phosphorylated p53 in both cell lines, although there were significantly lower amounts of phosphorylated p53 in the HCT116-CH3 cells, suggesting that high levels of hMLH1 reduce radiosensitivity. These data demonstrate that honokiol is highly effective in radiosensitizing colorectal cancer cells, especially those with a mismatch repair defect.