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Introduction: The aim of the present study was to assess the efficacy of molecularly targeted agents (MTAs) in the treatment of elderly patients with metastatic oesophago-gastric cancer (mOGC).Material and Methods: We systematically searched electronic databases and abstracts presented at American Society of Clinical Oncology (ASCO) meetings up to January 31, 2017. Hazard ratios (HRs) were used to estimate overall survival (OS) and progression-free survival (PFS). Subgroup analysis and publication bias were also evaluated. All statistical analysis was conducted using Comprehensive Meta Analysis software (Version 2.0).Results: A total of 2,149 elderly patients with mOGC from thirteen trials were included. Compared to non-MTA-containing regimens, OS was significantly improved in the MTA-containing regimens (HR = 0.86, 95% CI: 0.75-0.99, p = 0.037), but not for PFS (HR = 1.05, 95% CI: 0.85-1.30, p = 0.67). In addition, subgroup analysis indicated that MTA-containing regimens as second-line therapy in elderly mOGC patients significantly improved PFS (HR = 0.58; 95% CI: 0.39-0.85, p = 0.005) and OS (HR = 0.82, 95% CI: 0.70-0.96, p = 0.016), but did not significantly improve PFS (HR = 1.36; 95% CI: 1.06-1.76, p = 0.017) and OS (HR = 0.98, 95% CI: 0.77-1.27, p = 0.90) for MTA-containing regimens as first-line therapy in these patients. No publication bias was detected by Begg's and Egger's tests for OS and PFS.Conclusions: Our results indicate that the MTA-containing therapies significantly improve OS but not for PFS in elderly mOGC patients. Sub-group analysis shows that improved efficacy is only observed in the second-line setting and not in the first-line setting. Our findings support the use of angiogenesis as second-line treatment for elderly mOGC patients. [ABSTRACT FROM AUTHOR]

Aim:To investigate the role of LKB1 in regulation of mTOR signaling in non-small cell lung cancer (NSCLC) cells.Methods:LKB1 protein expression and phosphorylation of AMPK, 4E-BP1 and S6K in the cells were assessed using Western blotting in various NSCLC cell lines (A549, H460, H1792, Calu-1 and H1299). Energy stress was mimicked by treating the cells with 2-deoxyglucose (2-DG). Compound C was used to inhibit AMPK activity. Cell growth was measured using the MTS assay.Results:LKB1 protein was expressed in LKB1 wild-type Calu-1, H1299 and H1792 cells, but it was undetected in LKB1 mutant A549 and H460 cells. Treatment of the LKB1 wild-type cells with 2-DG (5, 10 and 25 mmol/L) augmented the phosphorylation of AMPK in dose- and time-dependent manners. In the LKB1 wild-type cells, 2-DG dramatically suppressed the phosphorylation of two mTOR targets, 4E-BP1 and S6K, whereas the LKB1 mutant A549 and H460 cells were highly resistant to 2-DG-induced inhibition on mTOR activity. In addition, stable knockdown of LKB1 in H1299 cells impaired 2-DG-induced inhibition on mTOR activity. Pretreatment of H1299 and H1792 cells with the AMPK inhibitor compound C (10 μmol/L) blocked 2-DG-induced inhibition on mTOR activity. 2-DG inhibited the growth of H1299 cells more effectively than that of H460 cells; stable knockdown of LKB1 in H1299 cells attenuated the growth inhibition caused by 2-DG.Conclusion:In non-small cell lung cancer cells, LKB1/AMPK signaling negatively regulates mTOR activity and contributes to cell growth inhibition in response to energy stress. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have been widely used in a variety of solid malignancies. Concerns have arisen regarding the risk of severe infections (≥grade 3) with use of these drugs, but the contribution of VEGFR-TKIs to infections is still unknown., Methods: The databases of PubMed and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to December 2014. Summary incidences, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies., Results: A total of 16,488 patients from 27 randomized controlled trials were included. The risk of developing severe (Peto OR 1.69, 95% CI: 1.45-1.96, P<0.001) and fatal infections (Peto OR 1.78, 95% CI: 1.13-2.81, P=0.013) was significantly increased in patients treated with VEGFR-TKIs when compared to controls. Exploratory subgroup analysis showed no effect of tumor types, phase of trials, or agent used on the Peto OR of severe infections. When stratified according to specific infectious events, the risks of high-grade febrile neutropenia, pneumonia, fever, and sepsis were increased compared with controls, with Peto ORs of 1.57 (95% CI: 1.30-1.88, P<0.001), 1.79 (95% CI: 1.29-2.49, P<0.001), 5.35 (95% CI: 1.47-19.51, P=0.011), and 3.68 (95% CI: 1.51-8.99, P=0.004), respectively. Additionally, VEGFR-TKIs significantly increased the risk of fatal sepsis (OR 3.66, 95% CI: 1.47-9.13, P=0.005) but not fatal pneumonia (OR 1.34, 95% CI: 0.80-2.25, P=0.26)., Conclusion: The use of VEGFR-TKIs significantly increases the risk of developing severe and fatal infectious events in cancer patients. A close monitoring for any signs of infections is recommended for patients treated with VEGFR-TKIs.