Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report reviews the literature on the genotoxicity of mainstream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it has been tested, with the base/neutral fractions being the most mutagenic. In rodents, cigarette smoke induces sister chromatid exchanges (SCEs) and micronuclei in bone marrow and lung cells. In humans, newborns of smoking mothers have elevated frequencies of HPRT mutants, translocations, and DNA strand breaks. Sperm of smokers have elevated frequencies of aneuploidy, DNA adducts, strand breaks, and oxidative damage. Smoking also produces mutagenic cervical mucus, micronuclei in cervical epithelial cells, and genotoxic amniotic fluid. These data suggest that tobacco smoke may be a human germ-cell mutagen. Tobacco smoke produces mutagenic urine, and it is a human somatic-cell mutagen, producing HPRT mutations, SCEs, microsatellite instability, and DNA damage in a variety of tissues. Of the 11 organ sites at which smoking causes cancer in humans, smoking-associated genotoxic effects have been found in all eight that have been examined thus far: oral/nasal, esophagus, pharynx/larynx, lung, pancreas, myeoloid organs, bladder/ureter, uterine cervix. Lung tumors of smokers contain a high frequency and unique spectrum of TP53 and KRAS mutations, reflective of the PAH (and possibly other) compounds in the smoke. Further studies are needed to clarify the modulation of the genotoxicity of tobacco smoke by various genetic polymorphisms. These data support a model of tobacco smoke carcinogenesis in which the components of tobacco smoke induce mutations that accumulate in a field of tissue that, through selection, drive the carcinogenic process. Most of the data reviewed here are from studies of human smokers. Thus, their relevance to humans cannot be denied, and their explanatory powers not easily dismissed. Tobacco smoke is now the most extreme example of a systemic human mutagen.
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PMID:Genotoxicity of tobacco smoke and tobacco smoke condensate: a review. 1557 90

Hereditary non-polyposis colorectal carcinoma (Lynch syndrome) is among the most common hereditary cancers in man and a model of cancers arising through deficient DNA mismatch repair (MMR). Lynch syndrome patients are predisposed to different cancers in a non-random fashion, the basis of which is poorly understood. We addressed this issue by determining the molecular profiles for different tumors from a nationwide cohort of Lynch syndrome families (approximately 150 tumors in total). We focused on some less prevalent cancers, affecting the brain (n = 7) and urinary tract (five bladder and five ureter uroepithelial cancers and four kidney adenocarcinomas), and compared their molecular characteristics to those of the most common cancers, colorectal, gastric and endometrial adenocarcinomas, from the same families. Despite origin from verified MMR gene mutation carriers, the frequency of high-level microsatellite instability in tumors varied between high (100-96% for ureter, stomach and colon), intermediate (63-60% for endometrium and bladder) and low (25-0% for kidney and brain). In contrast to gastrointestinal and endometrial carcinomas, active (nuclear) beta-catenin was rare and KRAS mutations were absent in brain and urological tumors. Compared with other tumors, frequent stabilization of p53 protein characterized urinary tract cancers. Promoter methylation of tumor suppressor genes discriminated the tumors in an organ-specific manner. Our findings suggest that different Lynch syndrome tumors develop along different routes. Uroepithelial cancers of the ureter (and bladder to lesser extent) share many characteristics of MMR deficiency-driven tumorigenesis, whereas brain tumors and kidney adenocarcinomas follow separate pathways.
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PMID:Differential cancer predisposition in Lynch syndrome: insights from molecular analysis of brain and urinary tract tumors. 1855 May 72

A 65-year-old woman who was diagnosed with unresectable Stage IV sigmoid colon cancer underwent transverse colostomy with double orifices. Although KRAS gene mutation was observed, we could not administer bevacizumab because of the risk of bleeding from the primary tumor and peritumoral abscess. We started bi-weekly XELOX therapy but bloody bowel discharge continued. We planned extended resection of the primary tumor in order to control the bleeding and perforation. Sigmoidectomy, partial resection of the left ureter and small intestine, partial hysterectomy, bilateral salpingo-oophorectomy, and umbilical tumor resection were performed and the patient was discharged on the 10th day after surgery. After surgery, bloody bowel discharge disappeared and bevacizumab was administered in the 55th day. Extended resection for a primary tumor may contribute to bleeding control and broaden treatment options.
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PMID:[Unresectable Stage IV Sigmoid Colon Cancer with Extended Resection for Primary Tumor - A Case Report]. 2813 11