Chemopreventive Effect of Metformin on Gastric Cancer Development

Cheung, Ka Shing; Chung, Kit Lam; Leung, Wai K.

doi:10.5009/gnl210132

Cited by 4 publications

(1 citation statement)

References 101 publications

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“…Metformin inhibits the 5'-AMP-activated protein kinase (AMPK)/mTOR pathway and activates phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase (PTEN) to inhibit the PI3K/Akt pathway [447][448][449][450], which are important in the metabolic regulation and pluripotency maintenance of PSCs [451]. It is associated with reduced cancer risk and/or attenuation of cancer symptoms in a variety of cancers [452][453][454][455][456][457][458][459][460], as well as improvements in many inflammatory and age-related diseases, as well as lifespan and other hallmarks of aging [447][448][449][461][462][463].…”

Section: Possible Role Of Pgrmc1 Effects On Metabolism and Metformin ...mentioning

confidence: 99%

Quo vadis PGRMC? Grand-Scale Biology in Human Health and Disease

Cahill

2022

Front. Biosci. (Landmark Ed)

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The title usage of Latin Quo vadis 'where are you going' extends the question Unde venisti from where 'did you come?' posed in the accompanying paper and extends consideration of how ancient eukaryotic and eumetazoan functions of progesterone receptor membrane component (PGRMC) proteins (PGRMC1 and PGRMC2 in mammals) could influence modern human health and disease. This paper attempts to extrapolate to modern biology in terms of extensions of hypothetical ancestral functional states from early eukaryotes and the last eumetazoan common ancestor (LEUMCA), to relativize human metabolic physiology and disease. As novel cell types and functional specializations appeared in bilaterian animals, PGRMC functions are hypothesized to have continued to be part of the toolkit used to develop new cell types and manage increasingly complex tasks such as nerve-gut-microbiome neuronal and hormonal communication. A critical role of PGRMC (as one component of a new eumetazoan genetic machinery) is proposed in LEUMCA endocrinology, neurogenesis, and nerve-gut communication with possible involvement in circadian nicotinamide adenine dinucleotide synthesis. This model would explain the contribution of PGRMC to metabolic and differentiation/behavioral changes observed in age-related diseases like diabetes, cancer and perhaps aging itself. Consistent with proposed key regulation of neurogenesis in the LEUMCA, it is argued that Alzheimer's disease is the modern pathology that most closely reflects the suite of functions related to PGRMC biology, with the 'usual suspect' pathologies possibly being downstream of PGRMC1. Hopefully, these thoughts help to signpost directions for future research.

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Section: Possible Role Of Pgrmc1 Effects On Metabolism and Metformin ...mentioning

confidence: 99%

Quo vadis PGRMC? Grand-Scale Biology in Human Health and Disease

Cahill

2022

Front. Biosci. (Landmark Ed)

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Haemoglobin A1c and serum glucose levels and risk of gastric cancer: a systematic review and meta-analysis

et al. 2022

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Background This systematic review and meta-analysis examined associations between serum levels of haemoglobin A1c (HbA1c) and glucose and the risk of gastric cancer. Methods MEDLINE, Embase, and Cochrane Library were searched for studies examining associations between serum levels of HbA1c or glucose and the risk of gastric cancer. Inclusion of studies, quality assessment, and data extraction were conducted independently by two authors. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were synthesised using random-effects models. Cochran’s Q test and I2 statistic were used to assess heterogeneity. Results Among 3473 identified studies, 12 were included. Of these, 5 studies examined HbA1c levels and 7 studies examined serum glucose levels. Serum HbA1c levels >6% were associated with an increased risk of gastric cancer (HR 1.36, 95% CI 1.06–1.74). When compared with the lowest glucose categories, the highest glucose categories were associated with a borderline increased risk of gastric cancer (HR 1.11, 95% CI 0.98–1.26). In subgroup analyses, studies that adjusted for Helicobacter pylori infection indicated stronger associations between elevated HbA1c levels and gastric cancer (HR 2.08, 95% CI 1.46–2.98) than those without such adjustment (HR 1.10, 95% CI 0.91–1.32). Conclusions Long-standing poor glycaemic control may increase the risk of gastric cancer. Registration number PROSPERO CRD42020157453.

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Inosine, gut microbiota, and cancer immunometabolism

Samami

Aleebrahim-Dehkordi

Mohebalizadeh

et al. 2023

American Journal of Physiology-Endocrinology and Metabolism

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This article briefly reviews cancer immunity and the role of gut microbiota in carcinogenesis, followed by an understanding of mechanisms by which inosine is involved in cancer immunometabolism. Constitutional cells of immune systems play a paradoxical role in cancer treatment. Anti-tumor immunity depends on the T-cell priming against tumor antigens, while the pro-tumor signaling is triggered by inflammatory mediators present in the tumor microenvironment. Studies link the microbiome with metabolism and immunity-two main factors implicated in carcinogenesis. Gut microbiota has been shown to affect both anti-tumor immunity and pro-tumor immune signaling. Additionally, there is mounting evidence that the human microbiome can play a role in the immunotherapeutic effects, both response and resistance. Inosine-5'-monophosphate dehydrogenase (IMPDH) is a highly conservative enzyme widely expressed in mammals. Cell signaling pathways utilize molecular inosine, which is a crucial secondary metabolite in purine metabolism and a molecular messenger in the process. Recent research has identified inosine as a critical regulator of immune checkpoint inhibition (ICB) therapeutic response in various tumor types. Three bacterial species, Bifidobacterium pseudopodium, Lactobacillus, and Olsenella, were found to produce inosine or its metabolite hypoxanthine and induce Th1 differentiation and effector functions via the inosine-A2AR-cAMP-PKA pathway upon ICB initiation, after being injected into the systemic circulation. Moreover, inosine acts as a substitute carbon source for T cell metabolism in glucose-restricted environments, i.e., the tumor microenvironment, assisting T cell proliferation and differentiation while enhancing sensitivity to ICB, reinforcing the notion that inosine metabolism may contribute to anti-tumor immunity. Also, inosine is a strong agonist of the adenosine receptor, A2AR, and A2AR signaling can affect T cell responses and anti-tumor immunity, making the inosine-A2AR pathway blockage a candidate for cancer treatment. Further research is required to investigate inosine as a cancer immunometabolism therapy.

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Chemopreventive Effect of Metformin on Gastric Cancer Development

Cited by 4 publications

References 101 publications

Quo vadis PGRMC? Grand-Scale Biology in Human Health and Disease

Quo vadis PGRMC? Grand-Scale Biology in Human Health and Disease

Haemoglobin A1c and serum glucose levels and risk of gastric cancer: a systematic review and meta-analysis

Inosine, gut microbiota, and cancer immunometabolism

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