Fengjun Cao

Metformin therapy associated with survival benefit in lung cancer patients with diabetes

The purpose of this study is to summarize the currently available evidence regarding the concerned issue by performing a comprehensive meta-analysis. Relevant publications reporting the association of metformin use with survival of lung cancer patients with diabetes were electronically searched to identify eligible studies. The meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures for disease-free survival(DFS) and overall survival(OS) estimates. A total of 17 individual studies from 10 publications were included in the meta-analysis. Overall, the results revealed a significant association of metformin use with a better survival of lung cancer patients with diabetes(for DFS: HR = 0.65, 95%CI = 0.52-0.83; for OS: HR = 0.78, 95%CI = 0.64-0.93). The subgroup analyses showed similar association in Asian region(for DFS:HR = 0.69, 95%CI = 0.59-0.80; for OS: HR = 0.55, 95%CI = 0.46-0.67) but not in Western region. Such association was also presented in small cell lung cancer (for DFS: HR = 0.54, 95%CI = 0.38-0.77; for OS: HR = 0.52, 95%CI = 0.39-0.69) and in non-small cell lung cancer(for DFS: HR = 0.70, 95%CI = 0.51-0.96; for OS: HR = 0.75, 95%CI = 0.58-0.97). Analyses stratified by treatment strategy showed a reduction in the risk of cancer-related mortality in patients receiving chemotherapy(for DFS: HR = 0.71, 95%CI = 0.64-0.83; for OS: HR = 0.58, 95%CI = 0.47-0.71) but not in patients receiving chemoradiotherapy. The meta-analysis demonstrated that metformin use was significantly associated with a favorable survival outcome of lung cancer patients with diabetes.

Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

BACKGROUND The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. METHODS A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. RESULTS Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. CONCLUSION The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma.

Elevated YKL-40 expression is associated with a poor prognosis in breast cancer patients

Numerous studies have investigated the prognostic role of YKL-40 in breast cancer, but yielded inconsistent results. To derive a more precise evaluation, relevant publications assessing the association between YKL-40 expression and clinical outcome of breast cancer patients were electronically searched and identified. A combined analysis of included studies was performed using fixed- or random-effect model to calculate the pooled hazard ratio (HR) or odds ratio(OR) and 95% confidence interval (95%CI) for the assessment of the association. Ten eligible studies involving 1250 patients were ultimately included in the meta-analysis. Overall, the pooled analysis showed that elevated YKL-40 expression was significantly associated with a poor overall survival(OS: HR=1.48, 95%CI= 1.11-1.97) and disease-free survival(DFS: HR=1.51, 95%CI= 1.10-2.07). The subgroup analysis by detection methods revealed an unfavorable OS in breast cancer patients with elevated YKL-40 expression evaluated by IHC(HR=1.39, 95%CI=1.12-1.71) but not by ELISA/RIA. Also, the stratification analysis by ethnicity showed a significant association between increased YKL-40 expression and shorter OS of breast cancer patients in western population(HR=1.51, 95%CI=1.03-2.21) as well as Asian population (HR=1.40, 95%CI= 1.05-1.86). Similarly, the subgroup analysis by detection methods revealed a significantly inferior DFS in breast cancer patients with increased YKL-40 expression disregarding the use of IHC(HR=2.02, 95%CI=1.47-2.79) or ELISA/RIA(HR=1.06, 95%CI= 1.02 -1.10). Additionally, increased YKL-40 expression was found to significantly correlate with larger tumor size (OR=2.38, 95%CI=1.41-4.05).The present meta-analysis indicate that elevated YKL-40 expression is associated with a poor prognosis in breast cancer patients. YKL-40 may serve as a promising predictive biomarker of prognosis of breast cancer.

Associations between FAS rs2234767 and FASL rs763110 polymorphisms and the risk of lung cancer: a meta-analysis of 39,736 subjects

Background Previous studies have investigated the associations between the common polymorphisms in FAS/FASL genes and lung cancer risk; however, the results remain inconsistent and inconclusive. Hence, we performed a meta-analysis to reassess the relationships between FAS rs2234767 and FASL rs763110 polymorphisms and the risk of lung cancer. Methods Eligible studies retrieved by an electronic search were pooled to calculate the strength of the associations using the odds ratio (OR) and 95% confidence interval (95% CI). Results A total of 13 case–control studies involving 39,736 subjects (9,237 cases and 10,838 controls on FAS rs2234767 and 8,957 cases and 10,704 controls on FASL rs763110) were included in the meta-analysis. The results showed a significant association between FAS rs2234767 polymorphism and increased risk of lung cancer (A vs G: OR =1.07, 95% CI =1.01–1.13; AA vs GG: OR =1.23, 95% CI =1.06–1.43; AA vs GA + GG: OR =1.24, 95% CI =1.08–1.43). Similar association was also observed in Asian population (AA vs GA + GG: OR =1.30, 95% CI =1.01–1.67) and in the studies with large sample size (A vs G: OR =1.07, 95% CI =1.00–1.14; AA vs GG: OR =1.30, 95% CI =1.07–1.58). However, no significant association between FASL rs763110 polymorphism and lung cancer risk was found other than in the Asian population (CC vs TC + TT: OR =1.35, 95% CI =1.01–1.80). Conclusion The meta-analysis indicated that FAS rs2234767 polymorphism was significantly associated with an increased risk of lung cancer and FASL rs763110 polymorphism may not contribute to susceptibility to lung cancer other than in Asian population.

Zhiheshouwu ethanol extract induces intrinsic apoptosis and reduces unsaturated fatty acids via SREBP1 pathway in hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is the major incidence and one of the most life-threatening cancer. How to conquer HCC is a worldwide issue for patients. Zhiheshouwu (Polygoni multiflori Radix Praeparata) is a Chinese medicinal herb exhibiting both lowering lipid and inhibiting cancer cells. However, it remains a matter if its inhibiting cancer cells is related to its lowering lipid. In this study, we investigate the effects of Zhiheshouwu ethanolic extract (HSWE) on apoptosis and the underlying mechanisms in Bel-7402 cells. The results showed that HSWE inhibited the proliferation with an increased level of ALT and AST in Bel-7402 cells. The decreased mitochondrial membrane potential (ΔΨm) was observed in HSWE-treated Bel-7402 cells. The flow cytometry results showed that HSWE triggered apoptosis. Since mitochondrial injury is characterized as intrinsic apoptotic cell death, these data indicated that HSWE may induce intrinsic apoptosis in Bel-7402 cells. In addition, HSWE decreased the production of unsaturated fatty acids, and inhibited the mRNA and protein of SCD1 and its up-stream factor, sterol-regulatory element binding proteins 1 (SREBP1), a master transcriptional regulator of lipogenic gene. Taken together, these data suggest that HSWE induces an intrinsic apoptosis, and reduced unsaturated fatty acids by blocking SREBP1 in hepatocellular carcinoma cells.

Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis

Background/Aims: Previous studies on the effect of metformin therapy on survival of pancreatic cancer patients obtained inconsistent findings. To reevaluate the prognostic value of metformin adjuvant treatment, a meta-analysis was carried out. Methods: Relevant articles addressing the association between metformin use and pancreatic cancer survival were electronically searched to identify eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Results: Totally, seventeen studies involving 36791 participants were included. Overall, metformin use was found to be significantly associated with a favorable OS (HR=0.88, 95% CI=0.80-0.97). Subgroup analyses by ethnicity showed a significantly reduced risk of death for metformin users compared with non-users in Asians (HR=0.74, 95% CI=0.58-0.94) but nonsignificant in Caucasians. When stratified by clinical stage, a remarkable reduction of mortality risk in patients at stage I-II treated with metformin (HR=0.76, 95% CI=0.68-0.86) was found as well as the group at stage I-IV (HR=0.88, 95% CI=0.79-0.99), but not in patients at stage III-IV. In the stratification analyses based on treatment strategy, metformin therapy was found to be associated with a better clinical outcome in patients receiving surgery or comprehensive therapy (HR=0.73, 95% CI=0.62-0.87; HR=0.88, 95% CI=0.79-0.97) but not chemotherapy. However, the overall analysis failed to show a significant association between metformin use and DFS (HR=1.54, 95% CI=0.94 -2.50) with only 2 studies enrolled. Conclusion: The current study has evidenced a significant association of metformin adjuvant treatment with the survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment. Further investigation is needed.

Ethyl 1-benzyl-5-{[(isopropyl-amino)(3-nitro-phen-oxy)methyl-idene]amino}-1H-1,2,3-triazole-4-carboxyl-ate.

In the title compound, C22H24N6O5, the triazole ring is essentially planar with a maximum deviation of 0.005 (2) Å and forms dihedral angles of 79.78 (11) and 86.22 (11)° with the phenyl and benzene rings, respectively. In the crystal, molecules are linked by intermolecular N—H⋯N, C—H⋯O and C—H⋯π interactions into a three-dimensional network.

Ethyl (2,5-dioxo-1-phenyl-2,3-dihydro-1H,5H-1-benzofuro[3,2-d]imidazo[1,2-a]pyrimidin-3-yl)acetate

In the title compound, C22H17N3O5, synthesized via the aza-Wittig reaction of ethyl 3-(phenyliminomethyleneamino)benzofuran-2-carboxylate, benzene isocyanate and diethyl 2-aminosuccinate, the imidazo[1,2-a]benzo[4,5]furo[2,3-d]pyrimidine ring system is essentially planar (r.m.s. deviation for all 16 non-H atoms = 0.020 Å). The phenyl ring is twisted with respect to this ring system, making a dihedral angle of 54.23 (4)°. The crystal packing is stabilized by weak intermolecular C—H⋯O interactions.

3-Benzyl-6-isopropyl-5-phen-oxy-3H-1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-one.

In the title compound, C20H19N5O2, all atoms of the 1,2,3-triazolo[4,5-d]pyrimidine ring system are essentially coplanar [maximum deviation = 0.015 (2) Å], indicating the existence of a conjugate system in which each carbon and nitrogen atom is sp 2 hybridized and ten π electrons (three from carbon atoms and seven from nitrogen atoms) constitute an aromatic heterocycle. The ring system forms dihedral angles of 68.37 (10) and 71.57 (9)° with the phenyl rings. The crystal packing is stabilized by van der Waals interactions and intermolecular C—H⋯π interactions.