Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to detect regions of DNA containing tumor suppressor genes involved in the development of gastric cancer, we performed an allelotype study on 78 gastric adenocarcinomas from a population composed largely of Texan Hispanics and Anglos, two ethnic groups that have a ratio of incidence rates of gastric cancer of approximately 2:1. In total, 42 microsatellite markers were employed, which detected at least one site per arm of each autosome in the human genome. These included several markers linked to known tumor suppressor genes (TP53, APC, DCC, RB1, and BRCA1). Sites showing quantitative allelic imbalance (AI) greater than 30% were located on 3p (36%), 11q (31%), 12q (38%), 13q (33%), 17p near TP53 (74%), and 17q near BRCAI (32%). Among the 22% of cases showing microsatellite instability (MI), a subset (4 of 17) showed instability at 59% or more of sites tested. No ethnic bias was detected in cases showing MI or in cases with AI at sites with rates of AI above 30%. Tumors of the intestinal subtype were significantly more likely than diffuse tumors to show AI at DI3S170 (P = 0.01). A deletion map of chromosome arm 3p was prepared for tumors with AI at D3S1478. These data indicate that a tumor suppressor gene on chromosome arm 3p is involved in the development of a subset of gastric cancers.
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PMID:Allelic imbalance in gastric cancer: an affected site on chromosome arm 3p. 754 34

Colorectal cancer affect the 15% of general population in developed countries. Cancer is a multistep process in which multiple genetic alterations must usually occur in several years. The premalignant step consists of one or multiple aberrant crypts due to hyperproliferation of cells and its shift from the deep third of the crypt to its surface. It has been suggested that abnormality in the APC gene is responsible for this. Furthermore, there exists DNA hypometilation, activation of the gene K-ras and ornithine decarboxylase activity. There is also a loss of MCC gene, that seems to interact with the APC gene. Entire alterations described make possible the Class I adenoma formation. This adenoma, needs the loss of the DCC gene (late stage in the carcinogenesis process), to become a Class II adenoma. The following alteration is deleted and mutation of the p53 gene. There is also an activation of the c-myc oncogene. These two genes are important mechanisms for the conversion of a benign adenoma to a malignant one, adenoma with in situ carcinoma or Class III adenoma. This type of adenoma becomes carcinoma and metastatic stage, throughout inactivation of several tumor suppressor genes. Besides the hereditary APC alteration and other acquired genetic changes as described above there are other associated genetics, antigenics, and enzymes that have an important role in the adenoma-carcinoma sequence. Several carcinogenic factors have been described which also contribute in the adenoma and carcinoma formation: ulcerative colitis, acromegaly, familial history of colonic neoplasia, certain professions, smoking and drinking, consumption of red or processed meat, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Etiology of colorectal cancer]. 755 83

Min (multiple intestinal neoplasia) is a mutant allele of the murine Apc (adenomatous polyposis coli) locus, encoding a nonsense mutation at codon 850. Like humans with germline mutations in APC, Min/+ mice are predisposed to intestinal adenoma formation. The number of adenomas is influenced by modifier loci carried by different inbred strains. One modifier locus, Mom-1 (modifier of Min-1), maps to distal chromosome 4. Intestinal tumours from both B6 (C57BL/6J) and hybrid Min/+ mice show extensive loss of the wild-type allele at Apc. B6 Min/+ female mice are predisposed to spontaneous mammary tumours. The incidence of both intestinal and mammary tumours can be increased in an age-specific manner by treatment with ethylnitrosourea (ENU). Min mice provide a good animal model for studying the role of Apc and interacting genes in the initiation and progression of intestinal and mammary tumorigenesis.
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PMID:ApcMin: a mouse model for intestinal and mammary tumorigenesis. 757 92

Numerous molecular genetic events occurring in the development of sporadic colorectal neoplasia have been previously defined. The most frequent genetic alterations are mutations of the APC, KRAS, and TP53 genes, as well as loss of the DCC gene and of the second TP53 allele. The data from several groups indicate that these genes play an important role in ulcerative colitis-associated dysplasias and cancer, as they do in sporadic colorectal adenomas and carcinomas. KRAS and TP53 mutations were detected in dysplasia, but also in villous regeneration and active colitis, and affect a subpopulation of the cells composing these lesions. We conclude that in histologically defined dysplasia, clones can be found that genetically represent precancerous lesions in ulcerative colitis. Seen in this way, part of the active colitis and villous regeneration lesions might be considered as preneoplastic. When present, KRAS mutation is an excellent genetic marker to map populations of preneoplastic cells.
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PMID:Molecular genetics of dysplasia in ulcerative colitis. 757 15

Mice heterozygous for the dominant Min mutation in their Apc gene develop multiple intestinal neoplasia. Analogously, family members from familial adenomatous polyposis kindreds inheriting mutations in their human APC homologue develop a similar phenotype. Quantitative trait loci studies have identified the Mom1 locus (for modifier of Min-1), which is responsible for part of the genetic variability in polyp number found among inbred mouse strains. The secretory type II phospholipase [nonpancreatic Pla2s (type II Pla2s or Pla2s-II)] has been demonstrated to be a candidate for Mom1, and a mutation in Pla2s-II in mice carrying the Min mutation has been proposed to account for an increased polyp number compared to mice without the Pla2s-II mutation. In this study, we have mapped the chromosomal position of the human homologue of Pla2s-II. We have identified 3 mega-yeast artificial chromosomes that carry PLA2S-II and localized one of them by fluorescence in situ hybridization to the border between 1p35 and 1p36.1. The presence of the microsatellite marker D1S199 in all three clones integrates PLA2S-II into different genetic maps. This highly polymorphic CA repeat D1S199 has previously been shown by us to identify loss of heterozygosity in 48% of sporadic colorectal tumors, indicating that the human homologue of the Pla2s-II/Mom1 locus might be related to human colorectal cancer.
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PMID:Human homologue of a candidate for the Mom1 locus, the secretory type II phospholipase A2 (PLA2S-II), maps to 1p35-36.1/D1S199. 758 22

The correlation between the mutation spectra of tumor suppressor genes Rb, p53, APC and MCC in human esophageal cancer (EC) and in human and monkey esophageal epithelium treated with N-Methyl-N-Benzyl nitrosamine (NMBzA) was studied using PCR amplification and direct sequencing methods. The results showed that in 40.9% (9/22) of the specimen examined, the mutation spectrum of p53 in primary EC was similar to that in the esophageal epithelium of human fetus (in vitro) and monkey (in vivo) treated with NMBzA. The same mutational spectra of tumor suppressor genes Rb, APC, MCC in esophageal epithelium cells of human and monkey treated with NMBzA were also found in some human primary EC. The correlation observed in the mutation spectra of multiple tumor suppressor genes between human primary EC and the esophageal epithelia of human and monkey origin treated with NMBzA wouldsuggest that NMBzA may be the esophageal etiological agent for human esophageal cancer in China.
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PMID:[Correlation studies on the alterations of multiple tumor suppressor genes in human esophageal cancer and in human and monkey esophageal epithelial cells treated with N-methyl-N-benzyl nitrosamine]. 758 88

PDGF-B released from colon tumor cells regulated tumor growth in athymic mice in a paracrine manner by inducing blood vessel formation. A positive correlation was found between expression of PDGF B-chain in cells grown in vitro and the number of factor VIII-positive blood vessels in tumors induced by three classes of colon carcinoma cell lines. Elevated expression of PDGF-B was also correlated with tumor size. Each cell line had the same mutations in the colon cancer genes APC, DCC, and p53 and had wild type c-K-ras genes (Huang et al. [1994] Oncogene, 9:3701-3706.) eliminating the possibility that any differences in tumor blood vessel formation were due to mutations and/or deletions in these genes. Colon carcinoma cells released biologically active PDGF capable of stimulating the growth of NIH3T3 cells, which was inhibited by neutralizing antisera to PDGF-AB chains. An inverse correlation was found between induction of factor VIII-positive blood vessels and expression of vascular endothelial growth factor (VEGF), while no correlation was seen with expression of either TGF alpha or k-FGF. Basic fibroblast growth factor (FGF) expression was not detected in these tumor cells. TGF beta 1 was capable of inducing PDGF-B expression in the undifferentiated U9 colon carcinoma cell line, but this sensitivity was not seen in differentiated cells. In contrast, TGF beta 1 inhibited VEGF expression in both undifferentiated cells and differentiated colon cancer cells. Thus, TGF beta 1 has two roles in the growth of undifferentiated U9 colon carcinoma cells in vivo: direct stimulation of cell proliferation as we have showed in earlier studies, and an increase in angiogenesis by inducing PDGF-B.
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PMID:Platelet-derived growth factor-B increases colon cancer cell growth in vivo by a paracrine effect. 759 1

Mutations of the APC gene play a critical role in both sporadic and familial forms of colorectal cancer. The vast majority of these mutations result in the loss of the carboxyl terminus of the protein. To further elucidate the function of APC, we searched for cellular proteins that associate with its carboxyl terminus. One million human cDNA clones were screened with the use of the interaction trap two-hybrid system, and 67 clones were found to have a phenotype suggestive of an APC-interacting protein. Nucleotide sequence analysis revealed that 48 of these clones were derived from a single novel named EBI. The association of APC and EB1 proteins was confirmed with in vitro binding assays. mAbs against EB1 were then produced and used to demonstrate the association of APC and EB1 in vivo. The EB1 gene was predicted to encode a 268-amino acid protein without significant homology to proteins with known function. However, searches of nucleotide databases did identify evidence for at least two related human genes and a yeast homologue. This conservation suggests an essential function for EB1 that might provide clues to the mechanism through which APC suppresses colonic neoplasia.
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PMID:APC binds to the novel protein EB1. 760 12

The mutation and deletion of APC, MCC genes in human esophageal cancer were analyzed by PCR amplification and direct sequencing assay. In PCR amplification analysis, one of 10 cases of esophageal cancer was found to have APC gene deletion in exon 11; one of 10 cases of EC was found to have MCC gene deletion in exon 12; one case of EC was found to have MCC gene deletion in exon 12. One of adjacent non-tumor tissue was also found to have deletion at exon 12 of MCC. In PCR direct sequencing analysis, two of 10 cases of EC were found to contain APC gene mutation in exon 11, two of 7 cases of EC were found to contain MCC genes mutation in exon 12. The results confirmed that mutation of APC and MCC genes exists in human esophageal cancer. It gives new clues to the understanding of carcinogenesis of human esophageal cancer. The mechanism of mutation or deletion of APC and MCC genes in EC needs further study.
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PMID:[Mutation of tumor suppressor genes APC and MCC in human esophageal cancer]. 765 96

Results of epidemiological studies have shown that nitrosamine-induced carcinogensis is involved in esophageal cancer in China. In order to demonstrate the mechanism at molecular level, Multiple tumor suppressor genes Rb, p53, APC and MCC in human fetus esophageal epithelium treated with NMBzA (in vitro) for 24 hours or three weeks and esophageal carcinoma induced by NMBzA were analyzed with PCR amplification and direct sequencing. In PCR amplification analysis. Rb, p53, APC and MCC deletions in esophageal carcinoma of human fetus induced by NMBzA were found, but no deletions of these genes was demonstrated in NMBzA-treated human fetal esophageal epithelium. PCR direct sequencing analysis revealed mutation of p53, Rb and MCC genes in human fetal esophageal epithelium treated with NMBzA for three weeks. The results first confirmed (in vitro) that nitrosamine can cause mutations and deletions of multiple tumor suppressor genes in human esophageal epithelium. The mutations of tumor suppressor genes in nitrosamine-induced esophageal carcinoma may occur in the early stage, while deletions in late stage of carcinogenesis.
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PMID:[Multiple tumor suppressor genes in esophageal carcinoma induced in human fetus esophageal epithelium by NMBzA]. 765 18


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