Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Stomach cancers are ...90% adenocarcinoma; lymphoma, carcinoid, and stromal tumours may occur. Adenocarcinoma can be subdivided into histological Lauren and the World Health Organization (WHO) classifications, but this information has not led to the development of histologic subtype-specific treatment options. One way to potentially improve treatment for gastric cancers is to better understand the pathogenesis of this disease, the contribution of Helicobacter pylori infection, and host immune response to lead to the development of integrated histological and molecular classification schemes for gastric cancer. The hope is that these studies may facilitate the development of clinical trials to explore therapies in defined sets of patients, ultimately improving survival from this deadly disease.
We previously estimated that 660,000 cases of cancer in the year 2008 were attributable to the bacterium Helicobacter pylori (H. pylori), corresponding to 5.2% of the 12.7 million total cancer cases ...that occurred worldwide. In recent years, evidence has accumulated that immunoblot (western blot) is more sensitive for detection of anti-H. pylori antibodies than ELISA, the detection method used in our previous analysis. The purpose of this short report is to update the attributable fraction (AF) estimate for H. pylori after briefly reviewing new evidence, and to reassess the global burden of cancer attributable to H. pylori. We therefore reviewed the literature for studies comparing the risk of developing non-cardia gastric cancer (NCGC) in cases and controls, using both ELISA and multiple antigen immunoblot for detection of H. pylori. The results from prospective studies were combined, and the new pooled estimates were applied to the calculation of the AF for H. pylori in NCGC, then to the burden of infection-related cancers worldwide. Using the immunoblot-based data, the worldwide AF for H. pylori in NCGC increased from 74.7% to 89.0%. This implies approximately 120,000 additional cases of NCGC attributable to H. pylori infection for a total of around 780,000 cases (6.2% instead of 5.2% of all cancers). These updated estimates reinforce the role of H. pylori as a major cause of cancer. What's new? Some 5.2 percent of the estimated 12.7 million new cancer cases in 2008, including 75% of non-cardia gastric cancer cases (NCGC), were attributed to the bacterium Helicobacter pylori. However, those percentages may be an underestimate, given the low sensitivity of detection of anti-H. pylori antibodies. Here, using improved estimates from prospective studies based on immunoblot, the fraction of all cancers and NCGC attributable to H. pylori was found to be 6.2 and 89% percent, respectively. Our findings reinforce the significance of the bacterium as a major cause of cancer.
Background
Multimodal treatment strategies with surgery as its centerpiece have been accepted as the standard of care in nonmetastatic cardia gastric cancer (CGC). There remains a lack of consensus ...regarding the optimal multimodal treatment strategy.
Method
We queried National Cancer Database from 2004 to 2016 to identify patients with resected nonmetastatic CGC who received perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), or postoperative chemotherapy (POC). A subgroup analysis was performed in optimally treated patients defined as initial chemotherapy within 45 days of diagnosis, resection within 45 days of diagnosis, negative margins, adjuvant chemotherapy within 90 days of resection, and standard radiation dose (45 Gy). Kaplan–Meier, Univariate analysis (UVA), and Multivariable analysis (MVA) were performed.
Results
We identified 2387 patients. Median survival was 38.8 months in the PEC group, 36 months in the POCR group, and 32.3 months in the POC group (p = 0.1025). On UVA, patients treated with PEC had an association with improved survival (HR, 0.83; p = 0.037) when compared with POC. On MVA, no significant difference was noted in overall survival (OS) between PEC, POCR, and POC, similar to subgroup analysis of optimally treated cohort.
Conclusion
OS rate in nonmetastatic CGC is not significantly different between patients receiving PEC, POCR, or POC.
LINKED CONTENT This article is linked to Gong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17676 and https://doi.org/10.1111/apt.17741
LINKED CONTENT This article is linked to Gong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17676 and https://doi.org/10.1111/apt.17691
Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable ...GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.
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