Hongqing Zhuang

Vascular damage is followed by vascular endothelial growth factor (VEGF) expression at high levels, which is an important mechanism forradiation brain necrosis development. Bevacizumab alleviates brain edema symptoms caused by radiation brain necrosis through inhibiting VEGF and acting on vascular tissue around the brain necrosis area. Many studies have confirmed that bevacizumab effectively relieves symptoms caused by brain necrosis, improves patients' Karnofsky performance status (KPS) scores and brain necrosis imaging. However, necrosis is irreversible, and hypoxia and ischemia localized in the brain necrosis area may easily lead to radiation brain necrosis recurrence after bevacizumab is discontinued. Further studies are necessary to investigate brain necrosis diagnoses, bevacizumab indications, and the optimal mode of administration, bevacizumab resistance and necrosis with a residual or recurrent tumor.

BACKGROUND: Transient elastography is a non-invasive method for staging liver fibrosis. The meta-analysis using the hierarchical models to evaluate the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B was rarely reported. AIM: A meta-analysis using the hierarchical models was performed to assess transient elastography for diagnosing and stage liver fibrosis in patients with chronic hepatitis B. METHODS: Electronic databases were searched and studies were identified to assess the diagnostic accuracy of transient elastography in CHB patients for staging fibrosis F ≥ 2, F ≥ 3 and F = 4 with liver biopsy as a reference standard. The hierarchical summary receiver operating characteristic curve and the bivariate models were performed to evaluate the diagnostic accuracy of transient elastography, and meta-regression analyses were performed to explore the heterogeneity. The quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of studies. RESULTS: Twenty-seven studies with a total of 4386 patients were included in the meta-analysis. The summary sensitivity of transient elastography for staging fibrosis F ≥ 2, F ≥ 3 and F = 4 was 0.806 (95% CI, 0.756-0.847), 0.819 (95% CI, 0.748-0.874) and 0.863 (95% CI, 0.818-0.898), respectively, and the summary specificity was 0.824 (95% CI, 0.761-0.873), 0.866 (95% CI, 0.824-0.899) and 0.875 (95% CI, 0.840-0.903), respectively. The corresponding area under the summary receiver operating characteristic curve was 0.88 (95% CI, 0.85-0.91), 0.91 (95% CI, 0.88-0.93) and 0.93 (95% CI, 0.91-0.95), respectively. Meta-regression showed that patient age contributed to heterogeneity. CONCLUSIONS: Transient elastography performs well to diagnose liver fibrosis in patients with chronic hepatitis B, which may reduce the use of liver biopsy.

BACKGROUND/AIMS: Gastric cancer (GC) is an important health problem. Classification based on molecular subtypes may help to determine the prognosis of patients with GC. Tumor invasion and metastasis are important factors affecting the prognosis of cancer. We aimed to identify genes related to tumor invasion and metastasis, which may serve as indicators of good GC prognosis. METHODS: Tumor tissues and adjacent normal tissues were collected from 105 patients with primary GC who were treated by undergoing radical surgery. Samples were used for tissue microarray analysis. Identified genes with altered expression were further analyzed using the Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression levels of THBS2, COL1A2 and SPP1 were analyzed by RT-PCR, western blot and immunohistochemistry. The overall survival curves of patients with high and low expression of each gene of interest were plotted and compared. RESULTS: Forty-three genes were identified. THBS2, COL1A2 and SPP1 were selected for further analysis. Altered expression levels of THBS2, COL1A2 and SPP1 in tumor tissues were confirmed. Patients with low THBS2 expression had a better prognosis; the expression of COL1A2 and SPP1 might not affect the prognosis of patients with GC. CONCLUSION: THBS2, but not COL1A2 and SPP1, may serve as an indicator of GC prognosis.

PURPOSE: To investigate the potential roles that p16 (CDKN2A) and RB activation have in sensitization to MEK inhibitor in resistant KRAS-mutant non-small cell lung cancer cells (NSCLC) in vitro and in vivo. EXPERIMENTAL DESIGN: Cell viability was measured with MTS assays. Effects of administration of radiation and combination drug treatments were evaluated by clonogenic assay, flow cytometry, and Western blots. DNA repair was assessed using immunofluorescent analysis. Finally, lung cancer xenografts were used to examine in vivo effects of drug treatment and radiation therapy. RESULTS: In this study, we showed that sensitivity to MEK inhibitor correlated to the RB/p16/CDK4 pathway and knockdown of RB induced resistance in cell lines sensitive to MEK inhibitor. Also, overexpression of p16 and inhibition of CDK4 had the ability to sensitize normally resistant cell lines. Our data indicated that the MEK inhibitor (trametinib, GSK112012) cooperated with the CDK4/6 inhibitor (palbociclib, PD0332991) to strongly reduce cell viability of KRAS-mutant NSCLCs that were resistant to the MEK inhibitor in vitro and in vivo. In addition, we report for the first time that resistance of KRAS-mutant NSCLCs to MEK inhibitor is, at least partly, due to p16 mutation status, and we described a drug combination that efficiently reactivates the RB tumor suppressor pathway to trigger radiosensitizing effects, apoptosis, and cell-cycle arrest. CONCLUSIONS: Our findings suggest that MEK inhibitor in combination with CDK4/6 inhibitor has significant anti-KRAS-mutant NSCLC activity and radiosensitizing effect in preclinical models, potentially providing a novel therapeutic strategy for patients with advanced KRAS-mutant NSCLCs.