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)

The effects of four isomeric forms of aminophenols, ortho-, meta-, para-aminophenol and acetaminophen (o-, m-, p-AP and AAP, respectively) on liver and kidney carcinogenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested. Rats were given 0.1% EHEN (in their drinking water for 2 weeks) and then diet containing these compounds at concentrations of 0.8% for 49 weeks. Administration of o-AP and AAP significantly decreased the number and area of preneoplastic foci staining immunohistochemically for glutathione S-transferase placental type (GST-P) per unit area of liver section as compared with the values for rats given EHEN alone. o-AP and AAP also significantly decreased the incidence of hepatocellular carcinoma. In contrast, p-AP and AAP significantly increased quantitative values for kidney preneoplastic lesions and renal cell adenoma. It is suggested that the cytotoxic effects of these chemicals preferentially suppressed the proliferation of preneoplastic liver cells, but stimulated the mitotic activity of preneoplastic tubular lesions in the kidney.
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PMID:Reciprocal modifying effects of isomeric forms of aminophenol on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine. 362 66

Studies were made on the effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium L-ascorbate (SA), ethoxyquin (EQ) and acetaminophen (AAF) on the induction of neoplastic lesions in the liver, kidney or urinary bladder of rats initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN), diethylnitrosamine (DEN) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The number and area of histochemical gamma-glutamyltranspeptidase-positive (gamma-GT+) foci per unit area of liver section in rats given BHA, BHT, EQ or AAP, but not SA, were significantly less than in rats given EHEN or DEN alone. Similarly, the number of hyperplastic nodules (HN) in groups given BHA or AAP and their area in groups given BHA, EQ or AAP were significantly less than in control groups. Induction of hepatocellular carcinoma (HCC) was also clearly inhibited by these three chemicals. In contrast, the incidence and quantitative values of preneoplastic lesions and renal cell adenoma in the group given EHEN were significantly increased in groups given BHA, EQ or AAP administration. For assesing the influence of BHA and BHT on urinary bladder carcinogenesis, rats received BHA or BHT after treatment with BBN. The incidences and the number per unit length of basement membrane of papilloma and carcinomas were significantly increased in rats given BHA. BHT also showed significant increase but values were less than with BHA. These results clearly demonstrated that BHA, BHT, EQ and AAP inhibit the development of gamma-GT+ foci, or HN and HCC, whereas BHA, EQ and AAP enhance the appearance of preneoplastic and neoplastic lesions in the kidney, BHA and BHT also enhancing urinary bladder carcinogenesis.
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PMID:Modification of carcinogenesis by antioxidants and other compounds. 614 34

The glycolytic enzyme pyruvate kinase (PK) is required for cancer development, and has been implicated in the metabolic transition from oxidative to fermentative metabolism, the Warburg effect. However, the global metabolic response that follows changes in PK activity is not yet fully understood. Using shotgun proteomics, we identified 31 yeast proteins that were regulated in a PK-dependent manner. Selective reaction monitoring confirmed that their expression was dependent on PK isoform, level and activity. Most of the PK targets were amino acid metabolizing enzymes or factors of protein translation, indicating that PK plays a global regulatory role in biosynthethic amino acid metabolism. Indeed, we found strongly altered amino acid profiles when PK levels were changed. Low PK levels increased the cellular glutamine and glutamate concentrations, but decreased the levels of seven amino acids including serine and histidine. To test for evolutionary conservation of this PK function, we quantified orthologues of the identified PK targets in thyroid follicular adenoma, a tumor characterized by high PK levels and low respiratory activity. Aminopeptidase AAP-1 and serine hydroxymethyltransferase SHMT1 both showed PKM2- concentration dependence, and were upregulated in the tumor. Thus, PK expression levels and activity were important for maintaining cellular amino acid homeostasis. Mediating between energy production, ROS clearance and amino acid biosynthesis, PK thus plays a central regulatory role in the metabolism of proliferating cells.
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PMID:Pyruvate kinase is a dosage-dependent regulator of cellular amino acid homeostasis. 2315 38