Management of gastric cancer in Asia: Resource-stratified guidelines

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
The Lancet Oncology (Impact Factor: 24.69). 11/2013; 14(12):e535-47. DOI: 10.1016/S1470-2045(13)70436-4
Source: PubMed


Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.

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Available from: Kun-Huei Yeh, Aug 19, 2014
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    • "The prevalence of gastric cancer (GC) is particularly serious in Asian countries (Leung et al., 2008). Newly diagnosed GC cases in Asian countries accounted for about three-quarters of the world total in 2008 (Shen et al., 2013). To date, the 5-year survival rate of GC patients is less than 15% (Correa, 2004). "
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    ABSTRACT: Oxidative stress is linked to increased risk of gastric cancer (GC). Recent reports have found that hsa-let-7g microRNA (miRNA) has properties of anti-tumor and resistance to damages induced by oxidized low-density lipoprotein (ox-LDL). Dysregulation of hsa-let-7g was present in GC in vivo and in vitro under exogenous stress. However, we didn't know whether there are regulatory mechanisms of hsa-let-7g in GC under oxidative stress. This study was aimed at investigating the effects of hsa-let-7g microRNA (miRNA) on GC under oxidative stress. The results showed that H2O2 induced the increase of DNA damage response (DDR) genes (ATM, H2AX and Chk1) and downregulation of hsa-let-7g in GC cells. Further study confirmed Hsa-let-7g caused the apoptosis and loss of proliferation in GC cells exposed to H2O2 associated with repression of DDR system. Yet, we found let-7g didn't target DDR genes (ATM, H2AX and Chk1) directly. In addition, data revealed hsa-let-7g miRNA increased the sensitivity of GC to X-rays involving in ATM regulation as well according to application of X-rays (another DDR inducer). In conclusion, Hsa-let-7g miRNA increased the sensitivity of GC to oxidative stress by repression activation of DDR indirectly. Let-7g improved the effects of X-rays on GC cells involving in DDR regulation as well.
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    • "Gastric cancer is an important health problem around the world and the cause of 12% of all cancer-related deaths each year [1,2], especially in China, which accounts for 42% of the global total cases [3]. Carcinogenesis is a multistep process involving the transformation, survival, proliferation, invasion, angiogenesis, and metastasis of tumor. "
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    ABSTRACT: Sirtuin-1 (SIRT1) possesses apparently dual roles in regulation of tumor. Previous reports have documented the crosstalk between SIRT1 with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB) signaling in leukemia, lymphoma and myeloma. In this study, the purpose was to survey the regulatory effects of SIRT1 on gastric cancer (GC) cells (AGS and MKN-45) and the relationships between SIRT1 and activation of STAT3 and NF-κB in GC cells. We found the SIRT1 activator (resveratrol RSV) contributed to the repression of viability and increase of senescence, which were rescued by SIRT1 inhibitor (nicotinamide NA) and SIRT1 depletion by CCK-8 assay and SA-β-gal assay respectively. Further study found SIRT1 activation (RSV supplement) not only inhibited the activation of STAT3 including STAT3 mRNA level, c-myc mRNA level phosphorylated STAT3 (pSTAT3) proteins and acetylizad STAT3 (acSTAT3) proteins, but also repression of pNF-κB p65 and acNF-κB p65. NA reversed the effects of RSV. In addition, either RSV or NA application could not change the cellular viability and senescence in MKN-45 cells with STAT3 knockdown or NF-κB knockdown. Overall, our findings suggested SIRT1 activation could induced the loss of viability and increases of senescence in GC in vitro. Moreover, our observations revealed SIRT1 displayed growth inhibitory activity in GC cells highly associated with causing repression of activation of STAT3 and NF-κB proteins via deacetylation.
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