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)

We previously reported (Cancer Res., 50:6139-6145, 1990) a significant frequency of activating point mutations in codon 12 of the K-ras oncogene in endometrial adenocarcinomas of the uterine corpus (series 1). To further define the role of ras activation in the development of endometrial adenocarcinoma, we surveyed cystic, adenomatous, and atypical hyperplasias of uterine endometrium and additional cases of endometrial and cervical carcinoma (series 2) for the presence of activating mutations in cellular protooncogenes of the ras family. Polymerase chain reaction was performed from deparaffinized sections of formalin-fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13, and 61 of the K-, H-, and N-ras genes by dot blot hybridization analysis with mutation-specific oligomers. Mutations in K-ras were also confirmed by direct genomic DNA sequencing. Of 19 endometrial adenocarcinomas in series 2, point mutations in ras genes were found in 7 tumors. Six contained single-base substitutions, five in codon 12 of K-ras and one in codon 12 of N-ras. The seventh tumor contained two different point mutations in codon 12 of K-ras. In one endometrial adenocarcinoma, tumor cells with point mutations in K-ras were predominantly localized to a portion that had a more aggressive histological pattern. In endometrial hyperplasia, K-ras mutations, one in codon 12 and one in codon 13, were found in 2 of 16 hyperplasias histologically classified as atypical and clinically considered premalignant. None of 6 adenomatous hyperplasias and none of 12 cystic hyperplasias, the latter of which is considered clinically benign, contained any detectable ras mutations. No mutations in H-ras were detected in either carcinomas or hyperplastic tissue.
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PMID:K-ras activation in premalignant and malignant epithelial lesions of the human uterus. 191 54

In the present paper we review the results of our study on the use of monoclonal antibodies Y13,259 to the ras p21 and MYC1 9E10 to the c-myc p62 oncoprotein products in human tumors and tumorlike conditions of the colorectum. A total of 78 tissue sections were analyzed immunohistochemically and revealed the following: 42 adenocarcinomas with 8 normal mucosae adjacent to the tumor, 25 adenomas (with or without dysplasia and with in situ carcinoma) and 3 hyperplastic polyps. Parallel tissue sections were used in order to compare ras and c-myc oncoproteins. Reviewing our results we made the following remarks: 1. All adenocarcinomas but one were expressed with both oncoproteins, most of them being strongly positive. 2. All adenomas were positive for ras p21, and all but two were also positive for c-myc p62. An interesting point is that the degree of staining intensity increased in accordance with the degree of dysplasia and/or in situ carcinoma association. 3. The hyperplastic polyps, as well as all normal mucosae were negative.
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PMID:Immunohistochemical detection of ras p21 and c-myc p62 in colonic adenomas and carcinomas. 193 63

It has been reported that mutations in the human ras gene family convert these genes into active oncogenes. In the present study using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the oligonucleotide hybridization assay, a total of 86 colorectal cancers were analyzed for the point mutations at codon 12 and 13 of K-ras genes. Mutations were present in 33 of the 86 colorectal cancers examined; 32 of the 33 mutations were at codon 12 of this gene and one of them was at codon 13. There was no apparent correlation between the presence of a ras gene mutation in a carcinoma and its anatomical location, level of differentiation, depth of invasion, degree of lymphnode metastasis or stage of progression, however, the high incidence of K-ras mutations was observed in early stage carcinomas (depth m and sm). This results support the concept that the point mutation of K-ras gene is early event in tumorigenesis of colorectal cancer.
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PMID:[Prevalence of K-ras gene mutations in human colorectal cancers]. 194 8

Utilizing the polymerase chain reaction (PCR), we studied the presence and pattern of mutations in the Kirsten (Ki)-ras oncogene, using paraffin-embedded sections of pancreatic carcinoma tissue from 53 patients. Mutations in the Ki-ras oncogene were evident in 46 of the 53 patients (87%) in codon 12. The predominant mutation was from glycine (GGT) to aspartic acid (GAT). Among the 46, one had an additional mutation in Ki-ras codon 13, and no mutation was found in codon 61. These oncogenetic mutations were observed even in early stage pancreatic carcinoma, and there was no statistically significant difference in the rate or positivity of mutations among the stages of the disease. With regard to patient survival, statistical analysis comparing 37 patients with mutations in the Ki-ras oncogene and four patients without mutations revealed no significant difference. These results suggest that mutations in the Ki-ras oncogene may be related to the initiation of carcinogenesis, but are not linked to malignant potential or promotion of human pancreatic cancer.
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PMID:Mutations in the Kirsten-ras oncogene are common but lack correlation with prognosis and tumor stage in human pancreatic carcinoma. 196 23

Molecular biological analysis plays an important role for understanding of cancer pathogenesis. For example, accumulation of oncogene and anti-oncogene changes is necessary for cancer development. Molecular pathology is defined as a study field examining clinical materials using molecular biological technique. Even though mechanisms of cancer development and progression has much complexity, molecular pathological findings give a crucial information on clinical medicine, as Ki-ras point mutation and certain allelic loss may convert colon adenoma into carcinoma. Overexpression of EGF/receptor in gastric cancer is a biologic marker for high malignancy. More accumulation of molecular pathological informations will provide a new approach for prospective molecular diagnosis.
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PMID:[Molecular pathological diagnosis of cancer]. 197 45

We have reported the presence of c-K-ras oncogenes activated by single point mutations at codon 12 in a vast majority of human pancreatic carcinomas. Formalin-fixed, paraffin-embedded specimens from surgical resections, autopsies and biopsies were used as well as snap frozen surgical specimens. The high oncogene incidence has been confirmed in other studies and indicate that somatic mutational activation of the c-K-ras gene is an important event in the development, maintenance or progression of cancer of the exocrine pancreas. While the role that these point mutations play in any or all of these processes remains to be determined, their presence is useful clinically for the diagnosis of pancreatic carcinoma at the molecular genetic level. The detection of mutated c-K-ras oncogenes in fine needle aspirates of pancreatic masses, that by cytomorphology may be suspicious but not diagnostic of malignant disease, increases the sensitivity of the diagnosis for this cancer. The identification of codon 12 mutations in the c-K-ras gene in pancreatic adenocarcinomas has been possible by advances in recombinant DNA techniques, especially by the development of in vitro gene amplification by the polymerase chain reaction (PCR). The possibility of analysing formalin-fixed, paraffin-embedded tissue for the presence of genetic alterations as small as single point mutations by PCR in concert with other mutation detection techniques, should facilitate the molecular genetic analysis of pancreatic carcinoma. Retrospective studies using stored specimens are now feasible with the technology described and should yield important information on the molecular epidemiology and aetiology of this and other diseases.
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PMID:Mutational activation of the c-K-ras gene in human pancreatic carcinoma. 197 94

By using recombinant plasmid PHS-49 as a probe, BamHI restriction fragment length polymorphisms (RFLPs) was studied in tumour DNAs of 36 gastric carcinoma patients and normal tissue DNAs of 25 unaffected Chinese individuals. Ten alleles and eighteen genotypes for Ha-ras gene were found. Four "rare" restriction fragments of size less than 6 kilobase pairs (kb) are first reported for Ha-ras locus in present paper, we inferred that these alleles might be one of the characteristics of genetic polymorphisms in Chinese population. Moreover, the frequency of some "rare" alleles and genotypes occurred in gastric carcinoma samples is significantly higher than that occurred in normal individuals. The results of pedigree analysis for two patients showed that some heterozygotes carried three or four alleles. It suggested that there may be more than one copy of Ha-ras gene sequence existed in a chromosome. The possible causes of the phenomenon mentioned above were discussed.
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PMID:[Study on Ha-ras RFLPs in gastric carcinoma and normal tissue DNAs of Chinese individuals]. 197 86

Differentiation between primary colonic adenocarcinoma arising in flat mucosa and carcinoma metastatic to the colon is often difficult. Examination of the mucosa adjacent to the tumor, the so-called transitional mucosa (TM), may be helpful. The morphologic, ultrastructural, and histochemical characteristics of the TM have been reported previously in detail. In this study the morphologic and immunohistochemical characteristics of the TM have been compared in 18 cases of primary colonic adenocarcinoma and 13 cases of metastasis to the colon. Five immunophenotypic markers were used: carcinoembryonic antigen (CEA), Lewis (x) and (y) blood group antigens, ras oncogene p21, and tumor-associated glycoprotein (TAG-72). Neoplastic transformation of colonic epithelium is associated with altered expression of these antigens. The morphologic and immunohistochemical profile of the TM was similar in both primary colonic adenocarcinomas and metastases to the colon. In some cases the TM adjacent to colonic metastases stained with one or more antibodies while the metastatic tumor was negative. Therefore, in cases where differentiation between primary colonic adenocarcinoma arising in flat mucosa and metastasis is difficult, the use of these reagents, particularly CEA, TAG-72, or ras oncogene p21, may be helpful. The similar immunohistochemical staining pattern of the TM in both primary and metastatic colon lesions supports a reactive, non-neoplastic origin of the TM. Furthermore, expression of these antigens is not limited to neoplastic epithelial cells.
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PMID:Role of the transitional mucosa of the colon in differentiating primary adenocarcinoma from carcinomas metastatic to the colon. An immunohistochemical study. 198 61

Nodules of acinar cells with increased proliferative potential develop in the pancreas of carcinogen-treated rats and in untreated aged rats. Large nodules are classed as adenomas. Phenotypic and genotypic characteristics of nodule cells were compared with normal pancreas and transplantable acinar cell carcinomas by several methods. Nuclei of acinar cells from normal pancreas, adenomas, and three carcinomas in situ had normal diploid DNA content as determined by flow cytometry. One of two primary carcinomas had a hypodiploid DNA content. Two of three transplantable carcinomas were aneuploid with a DNA content in the tetraploid range. Explants from nodules and adenomas failed to grow in soft agar, whereas several carcinomas were positive in this assay. A primary carcinoma was serially transplanted, but transplantation of nodules or adenomas failed. Transfection of DNA from carcinomas in situ yielded a higher frequency of NIH 3T3 transformants than DNA from adenomas. DNAs from the transformants did not contain ras sequences. These studies indicate that cells from nodules and adenomas have low growth potential and lack critical phenotypic and genotypic characteristics of transformed malignant cells that were present in some primary and transplanted carcinomas.
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PMID:Characterization of preneoplastic and neoplastic lesions in the rat pancreas. 199 60

We have previously reported that activated ras oncogenes can simultaneously switch on the metastatic phenotype and increased capability to degrade type IV collagen. Here the relationship between c-H-ras, metalloproteinase expression and metastatic behavior was studied in N-nitrosomethylurea (NMU)-induced rat mammary carcinomas, which are known to possess activated c-H-ras. When comparing normal rat breast tissue to mammary carcinomas there was no direct relationship between ras DNA levels and neoplastic changes. Furthermore, there were no consistent differences between metastatic and non-metastatic carcinomas, or between primary tumors and metastases. The NMU-induced rat mammary carcinomas expressed two major gelatinolytic metalloproteinases (gelatinases) of 65 and 92 kD, but only the 65 kD gelatinase was detected in normal breast tissue and a rat fibroma. Type IV collagenolytic activity per 5 micrograms of protein was two to three times higher in the mammary carcinomas than in the normal breasts, whereas the primary tumors did not differ from the corresponding metastases. This study shows that ras amplification is not necessary for development of the malignant or metastatic phenotype in the NMU-induced rat mammary carcinoma model. We have also found that induction of p21 ras protein synthesis in a v-H-ras transfected NIH/3T3 (433) cell line, containing a glucocorticoid promoter, does not lead to an increase in metastatic capacity.
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PMID:Ras levels and metalloproteinase activity in normal versus neoplastic rat mammary tissues. 203 22


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