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)

A two-year mechanistic bioassay in male Crl:CD BR rats was initiated with 50 ppm Wyeth-14,643 (WY) to investigate the relationship between peroxisome proliferating compounds and Leydig cell adenoma formation. After 154 days, the survival rate in the WY group decreased below control levels. After 300 days, the dose was lowered to 25 ppm for the remainder of the study. Gross examination of WY-treated rats either found dead or euthanized in extremis revealed hemorrhages at several sites. To investigate this observation, blood was then collected on test day 281 from 10 randomly selected control and WY-treated rats and a clinical pathological examination was performed. The WY-treated rats had significantly decreased red blood cell count, hemoglobin, and hematocrit, and elevated platelet counts. In the WY-treated rats, prothrombin times in undiluted plasma were similar to the controls, but were markedly prolonged in 2 of 10 rats when the plasma samples were diluted to 25%. Subsequently, blood was collected prior to sacrificing WY-treated rats which were exhibiting clinical signs of anemia. These rats had prolonged prothrombin times, activated partial thromboplastin time, and thrombin clot time when compared to laboratory historical control data (116.7 vs 13.3, 116.4 vs 13.7, and 42.4 vs 25.7 seconds, respectively). In a subsequent, ongoing study, Vitamin K was added to control and WY-treated diets (100 ppm). No survival differences between control and WY-treated rats occurred through 260 days in this second study. These new data suggest that deaths in the WY-treated group in our initial study were due to a vitamin K deficiency. The role of increased serum estradiol, its effects on blood coagulation, and enhanced hepatic cell proliferation in the vitamin K-dependent coagulation processes warrant further investigation.
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PMID:Induction of coagulation effects by Wyeth-14,643 in Crl:CD BR rats. 918 58

Activation of hepatocyte growth factor/scatter factor (HGF/SF) in the extracellular milieu is a critical limiting step in the HGF/SF-induced signaling pathway mediated by Met receptor tyrosine kinase, which has potentially important roles in tumor biology and progression. However, little is known concerning the regulation of HGF/SF activation in tumors. Immunoblot analysis revealed that the activation of HGF/SF was enhanced significantly in colorectal carcinoma tissues compared with the corresponding normal mucosa. Serum-free conditioned media of cultured human colorectal carcinoma cell lines contained HGF/SF-activating activity, and the addition of a single-chain precursor form of HGF/SF to the serum-free culture of these cells resulted in HGF/SF-dependent modulation of cellular phenotypes, such as increased scattering and enhanced secretion of vascular endothelial growth factor. This processing activity was enhanced by thrombin treatment but was inhibited significantly by a neutralizing antibody against HGF activator (HGFA), a factor XIIa-like serine proteinase believed to be expressed mainly in the liver. The activity was also inhibited by recombinant HGFA inhibitor type 1 (HAI-1). The presence of HGFA mRNA and secretion of HGFA protein were confirmed in the cell lines. Therefore, extrahepatic expression of HGFA in the colorectal carcinoma cells could be responsible for the single-chain HGF/SF-processing activity of the cells. We examined the expression of HGFA and HAI-1 in human colorectal mucosa and adenoma-carcinoma sequence. Immunohistochemically, HGFA was stained weakly in the normal enterocytes, and immunoreactivity was increased modestly in the neoplastic differentiation. The subcellular localization of HGFA immunoreactivity was altered in carcinoma cells showing basal or cell-stroma interface staining patterns, compared with normal and adenoma cells with a supranuclear or apical staining pattern. In contrast to HGFA, the expression of HAI-1 decreased significantly in carcinoma cells relative to the adjacent normal or adenoma cells, indicating that the net balance between HGFA and HAI-1 shifts in favor of HGFA in carcinomas. In fact, pro-HGFA and the active form of HGFA proteins increased in carcinoma tissue compared with the corresponding normal mucosa. It was concluded that HGFA is expressed in colorectal mucosa and tumors and could be involved in the activation of HGF/SF in colorectal carcinomas. Therefore, the balance between HGFA and HAI-1 could play an important role in the regulation of HGF/SF activity in colorectal carcinomas.
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PMID:Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma. 1108 39

Background. Although rare, visceral artery pseudoaneurysms often present as surgical emergencies with a specific mortality rate as high as 35% related to aneurysmal rupture. Risk factors for the development of iatrogenic pseudoaneurysms include anticoagulation, female gender, obesity, and vessel calcification. Case Report. We present a case of an elderly female who developed a dissecting pseudoaneurysm of the proper hepatic artery after undergoing routine surgery to resect a large duodenal adenoma. Surgical repair comprised of resection and primary anastomosis was employed resulting in a favourable outcome. Discussion/Conclusion. Surgical management reduces the risk of hepatic ischemia, biliary complications, and abscess formation. Although stenting, coil embolization, and thrombin injection are all plausible options for management, we propose that surgical reconstruction be considered seriously as a treatment for such spontaneous pseudoaneurysms.
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PMID:Dissecting pseudoaneurysm of the proper hepatic artery repaired by primary anastomosis: a case report. 2319 51

The established association between inflammatory bowel disease and colorectal cancer underscores the importance of inflammation in colon cancer development. On the basis of evidence that hemostatic proteases are powerful modifiers of both inflammatory pathologies and tumor biology, gene-targeted mice carrying low levels of prothrombin were used to directly test the hypothesis that prothrombin contributes to tumor development in colitis-associated colon cancer (CAC). Remarkably, imposing a modest 50% reduction in circulating prothrombin in fII+/- mice, a level that carries no significant bleeding risk, dramatically decreased adenoma formation following an azoxymethane/dextran sodium sulfate challenge. Similar results were obtained with pharmacologic inhibition of prothrombin expression or inhibition of thrombin proteolytic activity. Detailed longitudinal analyses showed that the role of thrombin in tumor development in CAC was temporally associated with the antecedent inflammatory colitis. However, direct studies of the antecedent colitis showed that mice carrying half-normal prothrombin levels were comparable to control mice in mucosal damage, inflammatory cell infiltration, and associated local cytokine levels. These results suggest that thrombin supports early events coupled to inflammation-mediated tumorigenesis in CAC that are distinct from overall inflammation-induced tissue damage and inflammatory cell trafficking. That prothrombin is linked to early events in CAC was strongly inferred by the observation that prothrombin deficiency dramatically reduced the formation of very early, precancerous aberrant crypt foci. Given the importance of inflammation in the development of colon cancer, these studies suggest that therapeutic interventions at the level of hemostatic factors may be an effective means to prevent and/or impede colitis-associated colon cancer progression.
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PMID:Thrombin drives tumorigenesis in colitis-associated colon cancer. 2471 Apr 7