Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues. Increasing evidence suggests that methionine adenosyltransferases play significant roles in the development of cancers. Liver cancers, namely hepatocellular carcinoma and cholangiocarcinoma, involve dysregulation of all three methionine adenosyltransferase genes. MAT1A reduction is associated with increased oxidative stress, progenitor cell expansion, genomic instability, and other mechanisms implicated in tumorigenesis. MAT2A/MAT2B induction confers growth and survival advantage to cancerous cells, enhancing tumor migration. Highlighted examples from colon, gastric, breast, pancreas and prostate cancer studies further underscore methionine adenosyltransferase genes' role beyond the liver in cancer development. In this subset of extra-hepatic cancers, MAT2A and MAT2B are induced via different regulatory mechanisms. Understanding the role of methionine adenosyltransferase genes in tumorigenesis helps identify attributes of these genes that may serve as valuable targets for therapy. While S-adenosylmethionine, and its metabolite, methylthioadenosine, have been largely explored as therapeutic interventions, targets aimed at regulation of MAT gene expression and methionine adenosyltransferase protein-protein interactions are now surfacing as potential effective strategies for treatment and chemoprevention of cancers. Impact statement This review examines the role of methionine adenosyltransferases (MATs) in human cancer development, with a particular focus on liver cancers in which all three MAT genes are implicated in tumorigenesis. An overview of MAT genes, isoenzymes and their regulation provide context for understanding consequences of dysregulation. Highlighting examples from liver, colon, gastric, breast, pancreas and prostate cancers underscore the importance of understanding MAT's tumorigenic role in identifying future targets for cancer therapy.
Background: Chamas for Change (Chamas) is a group-based health education and microfinance program for pregnant and postpartum women that aims to address inequities contributing to high rates of maternal and infant mortality in rural western Kenya. In this prospective matched cohort study, we evaluated the association between Chamas participation and facility-based delivery. We additionally explored the effect of participation on promoting other positive maternal, newborn and child health (MNCH) behaviors. Methods: We prospectively compared outcomes between a cohort of Chamas participants and controls matched for age, parity, and prenatal care location. Between October-December 2012, government-sponsored community health volunteers (CHV) recruited pregnant women attending their first antenatal care (ANC) visits at rural health facilities in Busia County to participate in Chamas. Women enrolled in Chamas agreed to attend group-based health education and microfinance sessions for one year; controls received the standard of care. We used descriptive analyses, multivariable logistic regression models, and random effect models to compare outcomes across cohorts 12 months following enrollment, with α set to 0.05.
A new family planning counseling tool uses the simple mnemonic device “NORMAL” to help family planning counselors and providers communicate to their clients key messages about menstrual bleeding changes associated with use of hormonal contraception and the copper IUD.
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