oxyntomodulin and Neoplasms

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs, but there is concern that they may increase the risk of malignant neoplasia. The present meta-analysis examined the safety of GLP-1 receptor agonists with regard to malignant neoplasia.. We analyzed data from randomized controlled trials with a minimum duration of 24 weeks that assessed the incidence of neoplasms in type 2 diabetes patients receiving GLP-1 receptor agonists compared with placebo or other hypoglycemic drugs. We searched the MEDLINE, Embase, and Cochrane databases with a language restriction of English through October 1, 2018, and carried out a meta-analysis of the available trial data using a fixed effects model to calculate odds ratios (ORs) for neoplasia.. Thirty-four relevant articles, providing data for 50452 patients, were included in the meta-analysis. Compared with the incidence of malignant neoplasia with placebo or other interventions, no increase in malignant neoplasm formation was observed with the use of GLP-1 receptor agonists (OR 1.04, 95% confidence interval (CI) 0.94-1.15;. GLP-1 receptor agonists can be used without safety concerns related to malignant neoplasia in patients with type 2 diabetes.

Topics: Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Incidence; Liraglutide; Neoplasms; Risk Factors

Apoptosis is a complicated process that involves activation of a series of intracellular signaling. Tissue injuries from diabetes mellitus mostly occur as a consequence of higher rate of apoptosis process due to activation of a series of molecular mechanisms. Several classes of anti-hyperglycaemic agents have been developed which could potentially modulate the apoptotic process resulting in fewer tissue damages. Novel types of anti-hyperglycaemic medications such as sodium glucose cotransporters-2 inhibitors, glucagon like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have shown to provide potent anti-hyperglycaemic effects, but their influences on diabetes-induced apoptotic injuries is largely unknown. Therefore, in the current study, we reviewed the published data about the possible effects of these anti-hyperglycaemic agents on apoptosis in diabetic milieu as well as in cancer cells.

Topics: Apoptosis; Blood Glucose; Deafness; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Hypoglycemic Agents; Mitochondrial Diseases; Neoplasms; Sodium-Glucose Transporter 2 Inhibitors

Stem cell research provides a foundation for therapeutic advancement in oncology, clinical genetics and a diverse array of degenerative disorders. For example, the elucidation of pathways governing proliferative regulation and differentiation within cellular systems will result in medical strategies aimed at the root cause of cancer. At present the characterization of reliable stem cell markers is the immediate aim in this particular field. Over the past 30 years investigators have determined many of the physical and functional properties of stem cells through careful and imaginative experimentation. Intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt. They readily undergo altruistic apoptosis in response to toxic stimuli although their progeny are hardier and will regain stem cell function to repopulate the tissue compartment, giving rise to the concept of a proliferative hierarchy. Contention exists when deciding whether the full complement of cells within a crypt is derived from either a single or multiple stems. Evidence has also arisen to challenge the long held view that colorectal tumours arise from a single mutated stem cell, as early adenomas from a human XO/XY mosaic contained distinct clones. Mechanisms governing the stem cell cycle and subsequent proliferative activity largely remain obscure. The adenomatous polyposis coli gene product has, however, been shown to promote the degradation of beta-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.

Topics: Adenomatous Polyposis Coli; Animals; Cell Differentiation; Cell Division; Colorectal Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Cyclooxygenase 2; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Intestines; Isoenzymes; Membrane Proteins; Neoplasms; Peptides; Prostaglandin-Endoperoxide Synthases; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Stem Cells; Transforming Growth Factor beta; Tumor Suppressor Protein p53

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Liraglutide; Neoplasms; Randomized Controlled Trials as Topic

Intestinal dysfunction is frequent in cancer and during anti-cancer treatment. Glucagon-like peptide-2 (GLP-2) is secreted in a nutrition-dependent manner from the intestinal enteroendocrine L-cells. It accelerates crypt cell proliferation and nutrient absorption, inhibits enterocyte apoptosis and decreases mucosal permeability. Lack of GLP-2 may increase the risk of malabsorption and intestinal bacterial translocation. The aim of this study is to evaluate meal stimulated secretion of GLP-2 in children with cancer undergoing anti-cancer treatment.. Plasma-GLP-2 analysis after an overnight fast and 1 hour after intake of a mixed test meal. Data on gastrointestinal toxicity, blood neutrophile counts and food records were included in the analysis.. Forty-four meal stimulation tests were performed in 25 children (median age, 6.0 years; range, 2.5-19) during anti-cancer treatment. Median GI toxicity score was 5 (range, 0-15), and mean energy intake was 62.4% of recommended values. P-GLP-2 values increased from mean (SD) 38 (18) to 63 (51) pmol/l (P < 0.0001). Twelve of the meal stimulation tests (28%) resulted in a p-GLP-2 increase >2 fold, which is assumed to be the lower limit of normal values. The increase was strongly dependent on the energy intake (r = 0.62, P < 0.0001), while toxicity score and neutrophile count had no significant influence (multiple regression).. In children treated with anti-cancer therapy, GLP-2 secretion seems to be normal if the enteral energy intake is sufficient. Insufficient GLP-2 secretion could influence the gastrointestinal problems seen in the children with a low enteral energy intake.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Diet Records; Energy Intake; Enteral Nutrition; Female; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Humans; Male; Neoplasms; Neutrophils; Nutritional Requirements; Nutritional Status; Peptides

Chemotherapeutic agents produce cytotoxicity via induction of apoptosis and cell cycle arrest. Rapidly proliferating cells in the bone marrow and intestinal crypts are highly susceptible to chemotherapy, and damage to these cellular compartments may preclude maximally effective chemotherapy administration. Glucagon-like peptide (GLP)-2 is an enteroendocrine-derived regulatory peptide that inhibits crypt cell apoptosis after administration of agents that damage the intestinal epithelium. We report here that a human degradation-resistant GLP-2 analogue, h[Gly2]-GLP-2 significantly improves survival, reduces bacteremia, attenuates epithelial injury, and inhibits crypt apoptosis in the murine gastrointestinal tract after administration of topoisomerase I inhibitor irinotecan hydrochloride or the antimetabolite 5-fluorouracil. h[Gly2]-GLP-2 significantly improved survival and reduced weight loss but did not impair chemotherapy effectiveness in tumor-bearing mice treated with cyclical irinotecan. Furthermore, h[Gly2]-GLP-2 reduced chemotherapy-induced apoptosis, decreased activation of caspase-8 and -3, and inhibited poly(ADP-ribose) polymerase cleavage in heterologous cells transfected with the GLP-2 receptor. These observations demonstrate that the antiapoptotic effects of GLP-2 on intestinal crypt cells may be useful for the attenuation of chemotherapy-induced intestinal mucositis.

Topics: Animals; Antineoplastic Agents; Apoptosis; Bacterial Infections; Camptothecin; Cell Line; Cell Survival; Female; Fluorouracil; Glucagon-Like Peptide 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Humans; Intestines; Irinotecan; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Peptides; Rats; Receptors, Glucagon; Survival Rate; Time Factors; Transfection; Tumor Cells, Cultured

Topics: Carrier Proteins; Conotoxins; Cytokines; DNA-Binding Proteins; Endopeptidases; Glucagon-Like Peptides; Homeostasis; Humans; Inflammatory Bowel Diseases; Mathematics; Models, Biological; Neoplasms; Neuropeptides; Peptides; Transcription Factors

Maintaining tumor-bearing rats on total parenteral nutrition (TPN) for eight days significantly reduced mass, protein, and DNA in small intestine and colon. Coinfusion of glucagon-like peptide 2 (GLP-2) significantly increased each of these variables in the duodenum, jejunum, and ileum, but not in the colon. Histological analysis of tissue revealed normal mucosa thickness and villus height in the small intestine of GLP-2-treated rats, whereas non-treated rats maintained on TPN exhibited villus shortening and thinning of the mucosa. Compared with TPN alone, no significant effects of GLP-2 were noted on tumor growth, liver weight, or heart weight. Coinfusion of GLP-2 with TPN had no significant effect on TPN-associated immunosuppression, as measured by mitogen-induced proliferation of cultured splenocytes. Although translocation of bacteria to the mesenteric lymph nodes appeared to be reduced in GLP-2-treated rats, the difference between groups was not statistically significant. These results suggest that hormonal alterations may be more important than an absence of luminal nutrition in TPN-associated mucosa changes in tumor-bearing rats. Additionally, maintenance of gut integrity during TPN does not appear to be a sufficient condition for the avoidance of the negative sequelae associated with this route of supplemental nutrition.

Topics: Animals; Bacterial Translocation; DNA; Glucagon-Like Peptide 2; Glucagon-Like Peptides; Intestinal Diseases; Intestinal Mucosa; Intestine, Small; Male; Microvilli; Neoplasms; Parenteral Nutrition; Peptides; Rats; Rats, Inbred F344

Topics: Animals; Congresses as Topic; Endocrine System Diseases; Gastric Inhibitory Polypeptide; Gastric Juice; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Glucagon-Like Peptides; Histamine; Humans; Insulin; Insulin Secretion; Motilin; Neoplasms; Neurotransmitter Agents; Pancreatic Hormones; Pancreatic Juice; Pancreatic Polypeptide; Secretin; Somatostatin; Vasoactive Intestinal Peptide