Resveratrol is a phytoalexin produced by many plants, and the skin of red grapes is particularly rich in resveratrol which accounts for the "French Paradox". Besides its protection of the cardiovascular system, it can affect the processes underlying all three stages of carcinogenesis, involving tumor initiation, promotion and progression. It has also been shown to suppress angiogenesis and metastasis. The anti-carcinogenic effects of resveratrol appear to be closely associated with its capacity to interact with multiple molecular targets involved in cancer development, while minimizing toxicity in normal tissues as tested. By reviewing many in vitro and in vivo studies, also considering both the supporting and challenging evidences, we are provided with a theory in support of the use of resveratrol in human cancer chemoprevention, in combination with either chemotherapeutic drugs or cytotoxic factors for the highly efficient treatment of drug refractory tumor cells. Anti-carcinogenic potential for cancer chemoprevention and anticancer therapy, which is one of the pleiotropic effects of resveratrol, is so called a new enlightenment of French Paradox.

Omeprazole significantly reduced the morbidity of stress-related UGI bleeding in patients with ICH due to its effective prophylactic effect without increasing the risk of nosocomial pneumonia, but it did not reduce the 1-month mortality or ICU stay. Further evaluation of high-dose omeprazole as the drug of choice for patients presenting with UGI bleeding is warranted. Clinical trial registration no.: ChiCTR-TRC-12001871, registered at the Chinese clinical trial registry (http://www.chictr.org/en/proj/show.aspx?proj=2384).

Background: An altered pattern of epigenetic modifications is central to the development and progression of various tumors. We studied epigenetic changes involving multiple modifications of histones to better predict prognosis of glioma patients.Methods: Immunohistochemistry was done to investigate global histone modification expression of histone 3 lysine 4 dimethylation (H3K4diMe), histone 4 arginine 3 monomethylation (H4R3monoMe), histone 4 lysine 20 trimethylation (H4K20triMe), and acetylation of histone 3 lysine 9 (H3K9Ac), histone 3 lysine 18 (H3K18Ac), histone 4 lysine 12 (H4K12Ac), and histone 4 lysine 16 (H4K16Ac) in resected tumor samples of 230 glioma patients. Data were analyzed using a recursive partitioning analysis (RPA).Results: RPA classified the patients into 10 distinct prognostic groups based on WHO grade, histology, and histone modifications: H3K9Ac (<88% or ≥88% tumor cells), H3K4diMe (<64% or ≥64% tumor cells), H3K18Ac (<74% or ≥74% tumor cells), and H4K20triMe (<75% or ≥75% tumor cells). The 10 groups were associated with significantly different progression-free (P < 0.0001) and overall survival (P < 0.0001). Cox proportional hazards models including age, sex, WHO grade, histology, extent of tumor resection, Karnofsky performance status score, and RPA groups retained age and RPA groups as the sole independent factors significantly influencing overall survival. For progression-free survival, RPA grouping was the only independent prognostic factor.Conclusions: Multiple histone modifications seem to have prognostic relevance in glioma. Impact: Further evaluation of histone modifications as prognostic markers of treatment and predictors of chemotherapy response using histone deacetylase inhibitors is warranted. Cancer Epidemiol Biomarkers Prev;

BackgroundMany physicians are reluctant to treat elderly glioblastoma (GBM) patients as aggressively as younger patients, which is not evidence based due to the absence of validated data from primary studies. We conducted a meta-analysis to provide valid evidence for the use of the aggressive combination of radiotherapy (RT) and temozolomide (TMZ) in elderly GBM patients.MethodsA systematic literature search was conducted using the PubMed, EMBASE and Cochrane databases. Studies comparing combined RT/TMZ with RT alone in elderly patients (≥65 years) with newly diagnosed GBM were eligible for inclusion.ResultsNo eligible randomized trials were identified. Alternatively, a meta-analysis of nonrandomized studies (NRSs) was performed, with 16 studies eligible for overall survival (OS) analysis and nine for progression-free survival (PFS) analysis. Combined RT/TMZ was shown to reduce the risk of death and progression in elderly GBM patients compared with RT alone (OS hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.48–0.72; PFS: HR 0.58, 95% CI 0.41–0.84). Evaluable patients were reported to tolerate combined treatment but certain toxicities, and especially hematological toxicities, were more frequently observed. Limited data on O6-methylguanine-DNA methyltransferase (MGMT) promoter status and quality of life were reported.ConclusionThe meta-analysis of NRSs provided level 2a evidence (Oxford Centre for Evidence-Based Medicine) that combined RT/TMZ conferred a clear survival benefit on a selection of elderly GBM patients who had a favorable prognosis (e.g., extensive resection, favorable KPS). Toxicities were more frequent but acceptable. Future randomized trials are warranted to justify a definitive conclusion.

BackgroundHealth-related quality of life (HRQOL) has been increasingly emphasized in cancer patients. There are no reports comparing baseline HRQOL of different subgroups of glioma patients prior to surgery.MethodsHRQOL assessments by the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0), the Mini-Mental State Examination and Karnofsky Performance Status were obtained from glioma patients prior to surgery.ResultsNinety-two pathologically confirmed glioma patients were recruited. There were 84.8% patients with emotional impairment, 75% with social and cognitive impairment, 70.7% with physical impairment, and 50% with role impairment. Eighty-two percent of patients reported fatigue symptoms, 72.8% reported pain, 50% reported appetite loss, 39.1% reported insomnia, and 36.9% reported nausea/vomiting, whereas other symptoms (dyspnea, diarrhea, constipation) in the QLQ-C30 were reported by fewer than 30% of patients. Fatigue and pain symptoms and all "functioning" scales were strongly correlated with global health status/quality of life (QoL). Fatigue was strongly related to all functioning scales, pain, appetite loss, and global health status/QoL. No difference in baseline HRQOL prior to surgery was reported between females and males, among different lesion locations, or between normal- and abnormal-cognition subgroups of glioma patients. Age, KPS, WHO grade, and tumor recurrence significantly affected HRQOL in glioma patients.ConclusionsThese data provided the baseline HRQOL in glioma patients prior to surgery in China. Most pre-surgery glioma patients indicated emotional, social, cognitive, physical, and role impairment. Fatigue, pain, appetite loss, insomnia, and nausea/vomiting were common in these patients. The fatigue and pain symptoms and all types of functioning strongly affected global health status/QoL. Old age, worse performance status, WHO grade IV and tumor recurrence had deleterious effects on HRQOL.

BackgroundThe clinical implication of O6-methylguanine-DNA methyltransferase (MGMT) promoter status is ill-defined in elderly glioblastoma patients. Here we report a meta-analysis to seek valid evidence for its clinical relevance in this subpopulation.MethodsLiterature were searched and reviewed in a systematic manner using the PubMed, EMBASE and Cochrane databases. Studies investigating the association between MGMT promoter status and survival data of elderly patients (≥65 years) were eligible for inclusion.ResultsTotally 16 studies were identified, with 13 studies included in the final analyses. The aggregate proportion of MGMT promoter methylation in elderly patients was 47% (95% confidence interval [CI]: 42–52%), which was similar to the value for younger patients. The analyses showed differential effects of MGMT status on overall survival (OS) of elderly patients according to assigned treatments: methylated vs. unmethylated: (1) temozolomide (TMZ)-containing therapies: hazard ratio [HR] 0.49, 95% CI 0.41–0.58; (2) TMZ-free therapies: HR 0.97, 95% CI 0.77–1.21. More importantly, a useful predictive value was observed by an interaction analysis: TMZ-containing therapies vs. RT alone: (1) methylated tumors: HR 0.48, 95% CI 0.36–0.65; (2) unmethylated tumors: HR 1.14; 95% CI 0.90–1.44.ConclusionThe meta-analysis reports an age-independent presence of MGMT promoter methylation. More importantly, the study encouraged routine testing of MGMT promoter status especially in elderly glioblastoma patients by indicating a direct linkage between biomarker test and individual treatment decision. Future studies are needed to justify the mandatory testing in younger patients.

No abstract

Temozolomide (TMZ) alone has been proposed as a promising alternative to radiotherapy (RT) in elderly glioblastoma (GBM) patients. We report a meta-analysis to systematically evaluate TMZ monotherapy in older GBM patients. A systematic literature search was performed using PubMed, EMBASE and the Cochrane database. Studies comparing TMZ versus RT in elderly patients (≥ 65 years) with newly diagnosed GBM were eligible for inclusion. Two randomized clinical trials (RCTs) and three comparative studies were included in the analyses, which revealed an overall survival (OS) advantage for TMZ compared with RT (HR [hazard ratio] 0.86, 95 % CI [confidence interval] 0.74-1.00). However, a sensitivity analysis of 2 RCTs only supported its non-inferiority (HR 0.91, 95 % CI 0.66-1.27). Most elderly patients tolerated TMZ despite an increased risk of grade 3-4 (G3-4) toxicities, especially hematological toxicities. The quality of life was similar between the groups. In the MGMT analysis, methylated tumors were associated with a longer OS than unmethylated tumors among elderly patients receiving TMZ monotherapy (HR 0.50, 95 % CI 0.35-0.70). Moreover, in patients with methylated tumors, TMZ was more beneficial than RT alone in improving OS (TMZ vs. RT: HR 0.66, 95 % CI 0.47-0.93) whereas the opposite was true for those with unmethylated tumors (HR 1.32, 95 % CI 1.00-1.76). Although the meta-analysis demonstrated the non-inferiority to RT in improving OS, TMZ alone was not a straightforward solution for elderly GBM patients because of an increased risk of G3-4 toxicities, especially hematological toxicities. MGMT testing might be helpful for determining individualized treatment.