Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemopreventive effect of the nonsteroidal anti-inflammatory drug indomethacin (IMC) on 1-hydroxyanthraquinone (1-HA)-induced carcinogenesis was investigated in a total of 69 male ACI/N rats. Animals in Group 1 were fed the diet containing 1.5% 1-HA for 48 weeks. The rats in Group 2 were given the 1-HA diet together with 16 ppm IMC in the drinking water for 48 weeks. Group 3 was given IMC alone throughout the study. Group 4 was served as an untreated control. At the end of the study, the incidences of large bowel and forestomach tumors in Group 2 were significantly smaller than those in Group 1 (large bowel tumors: 0/14 rats, 0% in Group 2 versus 12/27 rats, 44% in Group 1, p < 0.002; forestomach tumors: 2/14 rats, 14% in Group 2 versus 14/27 rats, 52% in Group 1, p < 0.01). Also, the incidences of inflammatory changes including ulcerative colitis and melanosis coli in colonic mucosa of rats of given 1-HA together with IMC were significantly reduced compared with those in rats given 1-HA alone (ulcerative colitis: 2/14 rats, 14% in Group 2 versus 20/27 rats, 74% in Group 1, p < 0.004). Concurrent administration of IMC with 1-HA caused a significant decrease in the bromodeoxyuridine labeling index of the colonic mucosa. These results indicate that the nonsteroidal anti-inflammatory drug IMC inhibits 1-HA-induced carcinogenesis and that this effect in decreasing the cell proliferation.
 ...
PMID:Chemoprevention of the naturally occurring carcinogen 1-hydroxyanthraquinone-induced carcinogenesis by the nonsteroidal anti-inflammatory drug indomethacin in rats. 758 28

Chronic sennoside use induces melanosis coli (MC) and possibly increases colorectal cancer risk. Sennosides alter colonic crypt length, proliferative activity, and bcl-2 expression 18 h after administration. To investigate possible mechanisms for carcinogenesis, the effects of acute sennoside use and the presence of MC on colorectal epithelium were studied. Colorectal biopsies from 15 subjects receiving sennosides 6 h before sigmoidoscopy (Sen), 15 controls (NSen), and 27 with MC [11 moderate (MMC) and 16 severe (SMC)]. were analysed for degree of apoptosis (H&E staining), immunohistochemical p53, p21/WAF and bcl-2 expression, and proliferative activity (labelling index, LI). Apoptosis (p=0.0004), intensity of p53 staining (p=0.01), and p21/WAF expression (p=0.008) were increased in Sen and SMC compared with NSen and MMC. p53 expression was increased in Sen (p=0.004). No difference in bcl-2 expression or LI was observed. Crypts were shorter in Sen (p=0.05) and longer in SMC (p=0.04) than in NSen. It is concluded that sennosides acutely induce apoptosis of colonic epithelial cells, presumably by a p53, p21/WAF-mediated pathway, resulting in shorter crypts. In severe melanosis coli, apoptosis seems to be delayed, causing longer crypts without a rise in proliferative activity or bcl-2 expression. This escape from a presumably protective mechanism may enhance the risk of carcinogenesis during chronic sennoside use.
 ...
PMID:Apoptosis induction by sennoside laxatives in man; escape from a protective mechanism during chronic sennoside use? 1152 59

This study aims to reveal the biological relevancy between melanosis coli (MC) with colon cancer by analyzing the proteomics differences of tissues of melanosis coli, colon cancer, and normal ones to probe into the causes and development mechanisms of MC from the perspective of biomolecules. Fourteen differential protein spots were found in the study after using two-dimensional gel electrophoresis (2-DE) and bio-mass spectrometry (MALDI-TOF/TOF-MS). Specifically, six and eight differential protein spots in the melanosis coli tissues were detected, respectively, compared with the normal tissues and colon cancer tissues. Eight kinds of proteins, including keratin 8 (KRT8), keratin 18 (KRT18), fibrinogen beta chain isoform 2 preproprotein (FGB), catalase (CAT), 26s protease regulatory subunit 10b (PSMC6), isoform 1 of tropomyosin alpha-4 chain (TPM4), carbonic anhydrase 1 (CA1), isoform of prelammin-A/C (LMNA), were retrieved through the mass spectral database, which could be deemed as associated proteins of MC and colon cancer. The different expressions in the disease tissues indicate that these proteins may be connected with the carcinogenesis of MC as well as the malignant proliferation, development, differentiation, and diffusion of cancer cells.
 ...
PMID:Differential proteomics mass spectrometry of melanosis coli. 3277 90