Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0001430 (adenoma)
21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gut microbiota plays important roles in many diseases, including cancer. It may promote carcinogenesis by inducing oxidative stress, genotoxicity, host immune response disturbance, and chronic inflammation. Colorectal cancer, hepatocellular carcinoma, and gastric cancer are the major gastrointestinal tract cancers in Taiwan. The microbiota detected in patients with tubular adenoma and villous/tubulovillous polyps is different from that in healthy controls and patients with hyperplastic polyps. Normalization of the microbiota is observed in patients after colorectal cancer treatment. Furthermore, the liver is exposed to microbiota-associated molecular patterns (MAMPs), bacterial metabolites, and toxins, as it is anatomically connected to the gut via the portal vein. Patients with cirrhosis have significantly higher plasma endotoxin levels than healthy controls. Helicobacter pylori is a well-established risk factor for gastric cancer. Some nitrosating bacteria convert nitrogen compounds in gastric fluid to potentially carcinogenic N-nitroso compounds, which also contribute to gastric cancer development. Growing evidence demonstrates that gut microbiota promotes carcinogenesis. In this review, we discuss the mechanisms and types of microbiota changes involved in these gastrointestinal cancers and the future treatment choices.
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PMID:Microbiota and gastrointestinal cancer. 3065 33

TFF1 is a peptide of the gastric mucosa co-secreted with the mucin MUC5AC. It plays a key role in gastric mucosal protection and repair. Tff1-deficient (Tff1^KO) mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas. Thus, these mice represent a model for gastric tumorigenesis. Here, we compared the expression of selected genes in Tff1^KO mice and the corresponding wild-type animals (RT-PCR analyses). Furthermore, we systematically investigated the different molecular forms of Tff1 and its heterodimer partner gastrokine-2 (Gkn2) in the stomach (Western blot analyses). As a hallmark, a large portion of murine Tff1 occurs in a monomeric form. This is unexpected because of its odd number of seven cysteine residues. Probably the three conserved acid amino acid residues (EEE) flanking the 7th cysteine residue allow monomeric secretion. As a consequence, the free thiol of monomeric Tff1 could have a protective scavenger function, e.g., for reactive oxygen/nitrogen species. Furthermore, a minor subset of Tff1 forms a disulfide-linked heterodimer with IgG Fc binding protein (Fcgbp). Of special note, in Tff1^KO animals a homodimeric form of Gkn2 was observed. In addition, Tff1^KO animals showed strongly reduced Tff2 transcript and protein levels, which might explain their increased sensitivity to Helicobacter pylori infection.
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PMID:Molecular Alterations in the Stomach of Tff1-Deficient Mice: Early Steps in Antral Carcinogenesis. 3196 21

TFF1 is a protective peptide of the Trefoil Factor Family (TFF), which is co-secreted with the mucin MUC5AC, gastrokine 2 (GKN2), and IgG Fc binding protein (FCGBP) from gastric surface mucous cells. Tff1-deficient mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas, indicating that Tff1 is a tumor suppressor. As a hallmark, TFF1 contains seven cysteine residues with three disulfide bonds stabilizing the conserved TFF domain. Here, we systematically investigated the molecular forms of TFF1 in the human gastric mucosa. TFF1 mainly occurs in an unusual monomeric form, but also as a homodimer. Furthermore, minor amounts of TFF1 form heterodimers with GKN2, FCGBP, and an unknown partner protein, respectively. TFF1 also binds to the mucin MUC6 in vitro, as shown by overlay assays with synthetic ¹²⁵I-labeled TFF1 homodimer. The dominant presence of a monomeric form with a free thiol group at Cys-58 is in agreement with previous studies in Xenopus laevis and mouse. Cys-58 is likely highly reactive due to flanking acid residues (PPEEEC⁵⁸EF) and might act as a scavenger for extracellular reactive oxygen/nitrogen species protecting the gastric mucosa from damage by oxidative stress, e.g., H₂O₂ generated by dual oxidase (DUOX).
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PMID:The Tumor Suppressor TFF1 Occurs in Different Forms and Interacts with Multiple Partners in the Human Gastric Mucus Barrier: Indications for Diverse Protective Functions. 3226 Mar 57


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