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)

Non-small cell lung cancers (NSCLC) comprise 75% of all lung cancers and consist of three major histologic types: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. The histopathology of lung cancer appears to be changing: The incidence of squamous cell carcinoma in the United States is declining, accompanied by the increase in the incidence of adenocarcinoma. Carcinoma of the lung is thought to arise from a pluripotent epithelial cell capable of expressing a variety of phenotypes. Malignant transformation is the end result of multiple events involving the growth control of bronchopulmonary epithelium. It is well known that squamous cell carcinomas are preceded by many years of progressive mucosal changes including squamous metaplasia, dysplasia, and carcinoma in situ. Premalignant changes associated with the other types of NSCLC are less well understood. Recently characterized markers for peripheral airway cell differentiation and selected monoclonal antibodies may be helpful. It is conceivable to identify specific genetic events at the cellular level using in situ hybridization or polymerase chain reaction. Biologic and genetic studies have renewed the awareness of the pleomorphism of NSCLC. Potentially interesting subsets include the following: (1) The expression of neuroendocrine (NE) markers has been demonstrated in selected NSCLC (NSCLC-NE), mostly in adeno- and large cell carcinomas. (2) The presence of K-ras mutations in surgically resected adenocarcinomas has been associated with shortened survival times. (3) Also, the neu gene encoded protein p185 has been associated with a more aggressive clinical course in adenocarcinomas. Further studies are needed to confirm such results and correlate the findings with the current WHO NSCLC classification. Rapid validation of relevant new diagnostic approaches is an enormous challenge. Although selected immunohistochemical and molecular biologic techniques may work on routinely processed paraffin-embedded material obtained from the pathology archives, many of the newest applications require fresh or freshly frozen specimens from large numbers of patients with a computerized clinical data base for adequate clinicopathologic correlations. Establishing such a resource is obviously a team effort requiring close collaboration of the oncologist, pathologist, surgeon, and technicians.
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PMID:Pathology of non-small cell lung cancer. New diagnostic approaches. 196 74

Loss of heterozygosity (LOH) and K-ras mutation were analyzed in 111 colorectal polyps and 26 invasive carcinomas from 40 patients with familial adenomatous polyposis of distinct histopathological types. LOH, being less than 2% in moderate adenomas, was detected on chromosome 5q (20%) in severe adenomas, on 5q (26%) and 17p (38%) in intramucosal carcinomas, and on 5q (52%), 17p (56%), 18 (46%), and 22q (33%) in invasive carcinomas. LOH on chromosome 5q occurred most frequently in the region close to the APC gene both in adenomas and carcinomas, and a loss of the normal allele of the APC gene was demonstrated in 3 cases. K-ras mutation markedly increased in the step of development from moderate (11%) to severe (36%) adenomas. These results suggest the following mechanisms for the development of colon tumors in patients with familial adenomatous polyposis: (a) the heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads to a change from moderate to severe adenoma; (c) LOH on chromosome 17p contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also affect the development of moderate to severe adenoma.
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PMID:Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis. 197 14

A murine keratinocyte cell line that is resistant to the growth-inhibitory effects of transforming growth factor beta 1 (TGF beta 1) was examined for differential gene expression patterns that may be related to the mechanism of the loss of TGF beta 1 responsiveness. Cells that were resistant to the growth-inhibitory effects of TGF beta 1 (KCR cells) were derived from K-ras-transformed BALB/MK keratinocytes (KC cells). Using a subtractive hybridization procedure with KC and KCR mRNAs, we isolated a complementary DNA clone for murine protein disulfide isomerase (PDI). The mRNA for PDI is inhibited by TGF beta 1 treatment in the parental KC cells, but not in the TGF beta 1-resistant KCR cells. Similar PDI down-regulation also occurs in other TGF beta-sensitive cells, but not in a human pancreatic carcinoma cell line which is insensitive to the growth-inhibitory effects of TGF beta 1. The results suggest that misregulation of PDI, an important component of co- and posttranslational modification systems, may be involved in the mechanism by which some cells escape from the growth-inhibitory effects of TGF beta 1.
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PMID:Altered regulation of protein disulfide isomerase in cells resistant to the growth-inhibitory effects of transforming growth factor beta 1. 208 67

K-ras gene mutation in colorectal tumors from patients with familial polyposis coli were investigated using oligonucleotide probes specific for a mutation at codon 12, 13, or 61 of the K-ras gene. The authors examined 22 colorectal carcinomas and 51 colorectal adenomas from 41 familial polyposis coli patients and observed mutations at codons 12 and 13 in eight of 22 colorectal carcinomas (36%) and six of 51 colorectal adenomas (12%). Thus, the frequency and sites of K-ras gene mutation in colorectal carcinoma from familial polyposis coli patients are similar to those in cases of sporadic colorectal carcinoma and may not be the first genetic event linked to the tumorigenesis.
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PMID:K-ras activation in colorectal tumors from patients with familial polyposis coli. 215 40

Ras gene is one of the oncogenes most commonly detected in human cancers and consists of three families (H-ras, K-ras, N-ras) that are converted to active oncogenes by point mutations occurring in codon 12, 13, or 61. The authors analyzed mutations of these codons in 12 extrahepatic bile duct carcinomas, nine gallbladder carcinomas, and 20 pancreatic tumors (18 pancreatic adenocarcinomas and two islet cell tumors) by a method to directly sequence nucleotides, using polymerase chain reaction and a direct sequencing method. Point mutations at K-ras codon 12 were found in all of 18 pancreatic adenocarcinomas and in one bile duct carcinoma, but there were no mutations in the remaining 11 bile duct carcinomas, in all of 9 gallbladder carcinomas, or in two islet cell tumors. A very high incidence of ras gene mutations may be used clinically for the diagnosis of debatable cases of pancreatic adenocarcinoma.
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PMID:Analysis of ras gene mutations in biliary and pancreatic tumors by polymerase chain reaction and direct sequencing. 216 48

High mol. wt genomic DNA was prepared from normal hamster pancreas and the solid and ascites variants of two different hamster transplantable carcinomas, one induced by N-nitrosobis(2-oxopropyl)amine and the other spontaneously occurring. This DNA was transfected into NIH/3T3 cells and resulted in cells that were capable of forming tumors when injected into nude mice. Analysis of the nude mouse tumors by Southern blotting revealed the presence of a band specific for hamster K-ras. Polymerase chain reaction (PCR)-mediated amplification of the K-ras codon 12-13 region of genomic DNA prepared from the transplantable tumors produced a 117 bp fragment which was analyzed by both allele-specific oligonucleotide hybridization and direct DNA sequencing. Oligonucleotide hybridization with probes specific for changes in the first or second position of codons 12 or 13 detected a G to A transversion in the second position of codon 12 in the chemically induced transplantable tumor, and a G to A change in the second position of codon 13 in the spontaneously occurring transplantable carcinomas. The result obtained for the chemically induced tumor was confirmed by direct dideoxy sequencing of the PCR-amplified product. These findings are the first to show a specific oncogene activation in an experimental pancreatic tumor model and also parallel the results recently reported for K-ras mutations in human pancreatic carcinoma.
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PMID:Activation of K-ras in transplantable pancreatic ductal adenocarcinomas of Syrian golden hamsters. 217 98

Remarkable advances in the understanding of specific inherited and acquired genetic events that are important in colonic carcinogenesis have occurred in the last several years. Studies of the population genetics of colon cancer have determined that the gene responsible for familial adenomatous polyposis (FAP), and Gardner's syndrome has been localized on the long arm of chromosome 5 and have more clearly defined the importance of genetic influences in 'sporadic' colon cancer. Studies of the molecular genetics of colon cancer have identified acquired alterations in oncogenes such as the K-ras gene and in putative tumor suppressor genes such as the FAP gene on chromosome 5, the p53 gene on chromosome 17, and the DCC gene on chromosome 18, which appear to mediate important steps in the adenoma-dysplasia-carcinoma sequence. Some of these research advances (FAP gene carriage) are already being used clinically to identify individuals at risk for colon cancer, and they offer great promise for the future of both prevention and therapeutic programs.
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PMID:Lessons from the genetics of colon cancer. 217 30

Structural alterations of protooncogene sequences may be involved in the pathogenesis of human neoplasms. We screened 54 thyroid tumors (36 benign and 18 malignant) for gene rearrangements of the protooncogenes c-myc, c-myb, c-fos, c-erb-B1, c-erb-B2, c-erb-A, N-ras, K-ras, and H-ras. Only mutations of H-ras were observed. None of the 15 colloid adenomas examined had detectable H-ras rearrangements. Of the remaining tumors, we observed mutations of H-ras in 4 benign and 4 malignant neoplasms. Gene amplification was found in 5 tumors. An aggressive recurrent papillary carcinoma had a marked amplification of one of the H-ras alleles. The amplified allele was truncated, in that the 3' variable tandem repeat was not a part of the amplification unit, and contained a codon 12 point mutation leading to a valine for glycine substitution. We also observed the association of low copy gene amplification with a codon 12 valine for glycine mutation in a follicular adenoma. Two tumors contained H-ras EcoRI polymorphisms not present in the DNA of normal thyroid from the same individuals, and one follicular carcinoma showed loss of an H-ras allele. Ras protooncogenes may become transforming by quantitative mutations, leading to increased expression, or qualitative mechanisms, through activating point mutations. Both of these appear to coexist in thyroid neoplasms, and it may be that a combination of both mechanisms is capable of inducing a more complete spectrum of neoplastic phenotypes.
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PMID:H-ras protooncogene mutations in human thyroid neoplasms. 219 80

This investigation has employed the NIH 3T3 cell transfection assay in an effort to detect transforming genes in DNA from squamous carcinomas of the head and neck. Of 11 tumor DNAs tested, 1 DNA sample from a gingival squamous carcinoma was able to produce primary and secondary transformants containing the human K-ras oncogene. This is the first report of an activated ras oncogene derived from a carcinoma of the head and neck. Head and neck cancers may possess activated ras oncogenes more often than is indicated by this study because of the relative inefficiency of transfection assays in detecting large transforming genes such as K-ras.
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PMID:A transforming Kirsten ras oncogene in an oral squamous carcinoma. 223 35

Recent studies of colon adenocarcinomas in humans and experimentally induced colonic tumors in rodents have demonstrated selective elevations in the level of N1-acetylspermidine in these malignant tissues. The exact relationship of these alterations in acetylated polyamine levels to the malignant transformation process, however, remains unclear. In order to clarify this issue, rats were given s.c. injections of 1,2-dimethylhydrazine (DMH; 20 mg/kg body wt/week) or diluent for up to 26 weeks. After 10 weeks of carcinogen treatment, one-half of the animals in each group were also concomitantly given i.p. injections of MDL 72527 (20 mg/kg body wt/week), a specific inhibitor of polyamine oxidase, until they were killed. Animals were killed after 15 weeks of DMH treatment and polyamine levels as well as the activities of polyamine oxidase, ornithine decarboxylase and spermidine-N1-acetyltransferase were measured and compared in rat proximal and distal colonic mucosa of each group. Polyamine levels were also assessed in each of these groups after 26 weeks of treatment with this carcinogen +/- MDL 72527. In addition, in view of recent studies that have indicated that polyamines may influence certain oncogenes in human colonic carcinoma cells, tumors from DMH +/- MDL 72527 were analyzed for K-ras mutations. The results of these experiments demonstrated for the first time that: (i) MDL 72527 was a specific inhibitor of polyamine oxidase in normal and malignant colonic tissue; (ii) concomitant administration of this agent with DMH enhanced the elevation of colonic N1-acetylspermidine and significantly reduced the mean colonic tumor burden, as assessed by total tumor area per rat, produced by this carcinogen alone; (iii) analysis of K-ras mutations revealed a similar incidence (62-69%) in adenocarcinomas for both groups (+/- MDL 72527); (iv) however, analysis of the K-ras-mutated and non-mutated tumors revealed that in both carcinogen-treated groups (+/- MDL 72527), tumors with such mutations were smaller than their counterparts without such genetic alterations. Moreover, MDL 72527 reduced the average size of tumors, with and without such mutations, to a similar extent.
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PMID:Effect of polyamine oxidase inhibition on the colonic malignant transformation process induced by 1,2-dimethylhydrazine. 226 65


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