A number of studies have evaluated two functional polymorphisms on p53 Arg72Pro and GSTP1 Ile105Val, in relation to esophageal cancer susceptibility. However, the results remain conflicting rather than conclusive. This meta-analysis on 2919 cases and 4074 controls for p53 Arg72Pro and 1885 cases and 2194 controls for GSTP1 Ile105Val from 13 published case-control studies showed that no significant general main effects for GSTP1 Ile105Val on esophageal cancer risk. However, we found that the p53 Arg72Pro was associated with an increased risk of esophageal cancer ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.20, 95%CI=1.06-1.36) without any between-study heterogeneity.In the stratified analysis by ethnicity, we found that the increased esophageal cancer risk associated with p53 Arg72Pro polymorphism was more evident in Asian group ((Pro/Arg +Pro/Pro) versus Arg/Arg: OR=1.35, 95%CI=1.14-1.60, P=0.09 for heterogeneity test), although we still failed to find any significant association between GSTP1 Ile105Val polymorphism and esophageal cancer risk in different ethnicity. These results suggest that p53 Arg72Pro polymorphism, but not GSTP1 Ile105Val, may contribute to esophageal cancer development, especially in Asian. Additional well-designed large studies were required for the validation of this association.

Gastric cancer (GC) is a severe public health problem worldwide, particularly in China. Radiotherapy is the main locoregional treatment for various types of unresectable tumor, including GC. However, many patients fail to respond to radiotherapy due to the intrinsic radioresistance of cancer cells. This study was designed to investigate the effects and potential mechanism of radiosensitization associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor in human GC cell lines in vitro . Among the six GC cell lines (SGC7901, HGC-27, MKN45, MKN74, BGC823 and MGC803) that were exposed to increasing doses of IR (0, 2, 4, 6 and 8 Gy), the mean lethal dose and quasi-threshold dose measurements indicated that BGC823 and MGC803 were relatively insensitive to ionizing radiation (IR). IR induced significant elevation of γ H2A histone family member X (γH2AX) in MKN45 cells compared with BGC823 cells. DNA-PKcs and phospho-DNA-PKcs protein levels were increased in BGC823 and MGC803 cells compared with other GC cell lines (SGC7901, HGC-27, MKN45 and MKN74). DNA-PKcs inhibition led to increased sensitivity of BGC823 and MGC803 cells to IR. NU7441 increased γH2AX expression in the nuclei of BGC823 cells following IR. Combination of DNA-PKcs and CK2 inhibition further increased the sensitivity of GC cells to IR. The combination of NU7441 and CX4945 increased γH2AX expression in the nucleus of BGC823 cells following IR compared with treatment with NU7441 alone. Taken together, the findings suggest that DNA-PKcs inhibitor increased the sensitivity of radioresistant BGC823 and MGC803 cells to radiotherapy through the cleaved-caspase3/γH2AX signaling pathway, thus presenting a potential treatment method for GC.

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Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumorsuppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.