RESUMEN
The immune system is the key player in a wide range of responses in normal tissues and tumors to anticancer therapy. Inflammatory and fibrotic responses in normal tissues are the main limitations of chemotherapy, radiotherapy, and also some newer anticancer drugs such as immune checkpoint inhibitors (ICIs). Immune system responses within solid tumors including anti-tumor and tumor-promoting responses can suppress or help tumor growth. Thus, modulation of immune cells and their secretions such as cytokines, growth factors and epigenetic modulators, pro-apoptosis molecules, and some other molecules can be suggested to alleviate side effects in normal tissues and drug-resistance mechanisms in the tumor. Metformin as an anti-diabetes drug has shown intriguing properties such as anti-inflammation, anti-fibrosis, and anticancer effects. Some investigations have uncovered that metformin can ameliorate radiation/chemotherapy toxicity in normal cells and tissues through the modulation of several targets in cells and tissues. These effects of metformin may ameliorate severe inflammatory responses and fibrosis after exposure to ionizing radiation or following treatment with highly toxic chemotherapy drugs. Metformin can suppress the activity of immunosuppressive cells in the tumor through the phosphorylation of AMP-activated protein kinase (AMPK). In addition, metformin may stimulate antigen presentation and maturation of anticancer immune cells, which lead to the induction of anticancer immunity in the tumor. This review aims to explain the detailed mechanisms of normal tissue sparing and tumor suppression during cancer therapy using adjuvant metformin with an emphasis on immune system responses.
RESUMEN
BACKGROUND: Recent studies suggest that individuals who underwent noncurative endoscopic resection for gastric cancer may require additional surgery. We conducted a comprehensive systematic review and meta-analysis to investigate the risk of lymph node metastasis in these cases. METHODS: We comprehensively examined relevant literature by extensively reviewing electronic databases such as PubMed, Cochrane Library, and Google Scholar. Subsequently, we analyzed clinicopathological outcomes and calculated pooled odds ratios and 95 percent confidence intervals using diverse effects models. RESULTS: This analysis included 12 papers with 4808 individuals who underwent additional surgery after noncurative endoscopic resection for early gastric cancer. The results indicated significant associations between lymph node metastasis and submucosal invasion (Odd ratio 2.04, 95% (CI): 1.58-2.63, I 2 = 88.7%; p<0.001), vertical margin (Odd ratio 6.11, 95% (CI): 1.94-19.23, I 2 = 0%; p<0.001), lymphatic invasion (Odd ratio 10.02, 95% (CI): 7.57-13.27, I 2 = 92%; p<0.000), and vascular invasion (Odd ratio 7.11, 95% (CI): 5.49-9.22, I 2=92%; p<0.000). CONCLUSIONS: When choosing factors for surgical treatment, it is essential to thoroughly consider the invasion of lymph nodes, vascular system, submucosa, and positive vertical margin.