Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenocarcinoma in Barrett's esophagus is the second most rapidly increasing cancer in western society. The cause and pathogenesis are unknown. Although histological studies suggest that there is successive progression from metaplasia and dysplasia, with a high risk of subsequent invasive carcinoma, at present there is no direct evidence that metaplastic and dysplastic epithelia are clonal precursors of adenocarcinoma. We selected 12 esophagectomy specimens of Barrett's esophagus patients, which showed a spectrum of normal tissue, metaplasia, dysplasia, and invasive carcinoma in each individual biopsy. We applied the microdissection technique to selectively procure microscopic tissue samples from H&E-stained slides for genetic evaluation using polymorphic markers flanking the APC gene locus. Identical APC gene alterations were found in the dysplastic and adenocarcinoma foci of all informative cases. The same changes were observed even in some metaplastic foci adjacent to dysplasia. Furthermore, clonality analysis of X-chromosome inactivation in female cases verified the same X-chromosome inactivation pattern in carcinoma, dysplasia, and metaplasia adjacent to dysplasia. No APC gene alterations were found in the normal epithelium and metaplasia distant from dysplasia. These data show for the first time that a tissue field of genotypic changes precedes the histopathological phenotypic changes of carcinoma in Barrett's esophagus syndrome. Our findings, in conjunction with the applied tissue microdissection technique, may help identify genotypic changes in patients with Barrett's esophagus before phenotypic changes occur. Therefore, genotyping of Barrett's metaplastic epithelium may supplement the histopathological evaluation of Barrett's esophagus.
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PMID:Barrett's esophagus: metaplastic cells with loss of heterozygosity at the APC gene locus are clonal precursors to invasive adenocarcinoma. 861 31

The investigation of molecular evidence of gastric carcinoma will be contributable to the prevention, gene diagnosis and therapy of human gastric neoplasms. To determine the specific genetic change in human gastric cancer (HGC) and precancerous lesions, we analysized FISH, PCR/SSCP, IHC and DNA sequencing by using multiple probes to detect the gene abnormalities (mutation, deletion, amplification or overexpression of genes) of 67 fresh tumors, 63 endoscopic biopsies including 30 dysplasia (DYS) and 33 intestinal metaplasia (IM, and 4 tumor cell lines from HGC patients. Multiple genetic abnormalities including hypomethylation of H-ras gene, amplification and overexpression of met and erbB2, deletion of APC, mts1/p16, p53 and nm23 gene and point mutation of p53 gene were noted in HGC and precancerous lesion of human gastric mucosa. Among these changes, p53 gene was the highest frequence genetic alteration in 39/67 (54-58%) of gastric carcinoma. These results indicate that overexpression of met and H-ras occurs at early stage in progression of neoplasia, amplification of met, erbB2 and akt2 gene occurs at progressing stage of tumorigenesis, deletion of p53, APC, mts1/p16 and nm23 occurs at advanced stage in the progression of cancer. The abnormalities should be associated with malignant phenotypes: poor differentiation, vascular invasion, lymph nodes metastasis, and low survival time. We detected p53 gene mutation in both cancer and precancerous lesions of IM and DYS. These results suggest that p53 may be a susceptible gene and alteration of p53 gene plays an important role in the development of HGC.
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PMID:[Multiple gene alterations involved in the processor of human gastric carcinogenesis]. 869 90

In order to detect loss of heterozygosity (LOH) at APC and MCC genetic loci in gastric carcinoma, the authors established a micro-wax-mediated hot start PCR technique. This method allowed a specific gene amplification, and it was useful especially in the amplification of formalin-fixed or stained tissues. In 44 cases of gastric cancer, 29 cases were informative of the APC locus. LOH was found in 8 cases (27.6%): 2 cases in 2 moderately well-differentiated cancer, 2 cases in 13 differentiated cancer, and 4 cases in poorly-differentiated cancer. One of the 3 cases of gastric cancer at early stage also showed LOH. LOH at MCC locus was detected in only 2 of the 25 (8.0%) gastric cancer patients informative. These data suggest that abnormality of APC gene plays a role in the tumorigenesis of gastric cancer and the change may occur at the early stage of tumor development.
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PMID:[Relation between loss of heterozygosity at APC and MCC genetic loci and biological behaviour of gastric carcinoma]. 873

In general, it is presumed that colonic epithelial stem cells are the principal cell type at risk of incurring the series of somatic mutations leading to carcinoma, since all other epithelial cell types are short-lived. Mutant stem cell clonal expansion increases the risk for subsequent mutations and is therefore a potentially important step in carcinogenesis. The stem cells reside in colonic crypts, simple tubular foldings of the epithelium, and thus counting crypts provides an indirect means to determine stem cell numbers. The normal crypt population is known to expand through a process of crypt replication and this is thought to result in a corresponding expansion of the epithelial stem cell population. A simple mathematical model of the population dynamics of normal and mutant crypts (crypts containing mutant stem cells) is developed and used to estimate a lower bound on the relative rate of expansion of the mutant stem cell population. The model predicts that if mutant and normal crypt populations expand at the same rate, and if the mutation rate is small relative to the rate of growth, then the fraction of clusters of mutant crypts composed of only a single mutant crypt should steadily decrease with age towards one-half. Aberrant crypts are easily recognizable lesions in human colon which have frequently been shown to contain cells with K-ras and occasionally APC gene mutations. Application of the model to recent counts of aberrant crypt cluster sizes indicate that the aberrant crypt population, and the contained mutant stem cell population, is expanding substantially faster than normal.
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PMID:Expansion of mutant stem cell populations in the human colon. 873 77

The activity of Protein C in the blood of the patients with prostatic carcinoma and benign prostatic hyperplasia was examined. It was observed a slightly decrease of activity of protein C in the blood the patients with prostatic carcinoma. The observation of the activity of Protein C is useful because it allow to differentiate from patients with prostatic carcinoma a group of high risk of haemorrhagic complications. The activity of Protein C may be a prognostic factor of a progress of a prostatic carcinoma.
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PMID:[Activity of protein C in blood of patients with prostatic carcinoma]. 875 42

We reported on a 74 year old patients with local advanced prostatic carcinoma. Following prostatic surgery an increased bleeding tendency was observed. The patients showed clinical and laboratory evidence for consumption coagulopathy with hyperfibrinolysis. The laboratory data were: marked decrease of AT III, Protein C, increase of thrombin/AT III complex level, fibrin degradation products (FDP) and antigen of t-PA. The treatment was ended successful.
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PMID:[Disseminated intravascular coagulation syndrome with secondary fibrinolysis activation in prostatic carcinoma]. 875 45

Current histopathological evidence suggests that gall-bladder cancer has two main morphological pathways for its development: de novo (ab initio) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested polymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunohisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of invasion, but not in 16 tumors of carcinoma-in-pyloric-gland-type adenoma, or in 51 adenomas (47 pyloric gland-type and 4 intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, all four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carcinoma-in-pyloric-gland-type adenoma develops from p53-, K-ras-, and APC-gene-unrelated, as yet unknown, alteration.
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PMID:APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis. 880 79

The cooked meat mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) produces tumors at multiple sites in the F344 rat, including adenocarcinomas of the colon. In the present study, the development of IQ-induced colorectal tumors was shown to be accompanied by the progressive inhibition of programmed cell death. This was associated with increased expression of the antiapoptosis protein Bcl-2 and decreased expression of bax, a known activator of apoptosis. Carcinomas bearing high levels of bcl-2 expression exhibited low levels of p53, the tumor suppressor protein that in some circumstances has been shown to down-regulate bcl-2. Because they lack mutations in the genes commonly associated with increased cell proliferation (APC, Ki-ras, and p53) and show no evidence of microsatellite instability, IQ-induced colon tumors might arise via the deregulation of bcl-2 expression, leading to inhibition of programmed cell death.
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PMID:Inhibition of apoptosis in colon tumors induced in the rat by 2-amino-3-methylimidazo[4,5-f]quinoline. 881 12

Neoplastic cells can activate the clotting system directly, thereby generating thrombin, or indirectly, by stimulating mononuclear cells to synthesize and express various procoagulants. Clinical manifestations of increased thrombin generation may be accentuated by down-regulation of endothelial cell counterregulatory mechanisms, such as decreased hepatic synthesis of antithrombin III and protein C. Cancer cells and chemotherapeutic agents can injure endothelial cells, thereby intensifying hypercoagulability. In addition, normal endothelial cell function. may be disrupted by various defects in platelet function. Currently, primary prevention of venous thrombosis should be considered for cancer patients (1) during and immediately after chemotherapy, (2) when long-term indwelling central venous catheters are placed; or (3) when hospitalization for cancer is characterized by prolonged immobilization, trauma, or surgery. Secondary prevention of recurrent venous thrombosis usually necessitates anticoagulation. In some patients with cancer, the condition is resistant to warfarin, and long-term adjusted high-dose heparin is required. For patients unable to tolerate heparin or warfarin because of major bleeding problems, placement of an inferior vena caval filter should be considered. The diagnosis of venous thrombosis may help to uncover previously occult carcinoma by prompting a complete physical examination, chest roentgenography, and mammography. However, extensive cancer screening with total-body computed tomography or magnetic resonance imaging has not been shown to be cost effective for patients with venous thrombosis.
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PMID:Cancer and venous thromboembolism. 883 76

It is currently accepted that colorectal tumorigenesis results from accumulation of multiple mutations in certain genes. This concept prompted us to search for possible mutations in the APC, k-ras, and p53 genes in an advanced cancer coexisting with a large villous adenoma of the rectum in a 54-year-old patient with no family history of colorectal cancer. Genomic DNA extracted from multiple subregions of the tumor and surrounding normal mucosa was studied by polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. Both the adenoma and carcinoma had abnormal PCR-SSCP for APC (exon 11) and k-ras, irrespective of the location within the tumors. However, p53 abnormality (exon 7) was detected only in samples taken from the carcinoma. Subsequent sequencing revealed a TTG to TAG mutation at codon 479 of APC, a GGT to GAT mutation at codon 12 of k-ras in both the adenoma and carcinoma, and a CGG to TGG mutation at codon 248 of p53 (exon 7) in the carcinoma. These findings were in accord with the current concept of colorectal tumor progression whereby genetic alteration of APC and k-ras occurs relatively early while that of p53 is rather late and is possibly a decisive event in relation to malignancy.
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PMID:A very large villous adenoma with an adjacent cancer of the rectum: an informative case for testing the proposed molecular basis of colorectal tumorigenesis. 889 82


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