Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A poly(ADP-ribose) polymerase inhibitor, benzamide (BA), was found to induce flat revertants of NIH 3T3 cells that had been transformed by human Ha-ras, rat Ki-ras, rat c-raf, and human ret-II. These genes had been amplified in original transformants, but they were completely eliminated by BA. Contrary to this, endogenous activated Ha-ras in a human bladder carcinoma cell line, T24, was not eliminated by BA. The gene loss seemed to be restricted to exogenous and/or amplified sequences. BA also eliminated the amplified c-myc gene in HL-60 cells, concomitant with differentiation into granulocytes. We demonstrated that the amplified c-myc gene was not present as episomes. It is probably present as double minutes or a homogeneously staining region. Dimethylsulfoxide also induced differentiation at a concentration that did not inhibit poly(ADP-ribose) polymerase. The cell lost the c-myc gene in association with this differentiation. The amplified c-myc gene in a colon adenocarcinoma cell line, COLO 320HSR, and the amplified mdr-1 gene in an adriamycin-resistant myelogenous leukemia cell line, K562/ADM, were not eliminated by BA. Various poly(ADP-ribose) polymerase inhibitors also eliminated human Ha-ras in the NIH 3T3 transformant and the c-myc gene in HL-60 cells.
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PMID:Loss of amplified genes by poly(ADP-ribose) polymerase inhibitors. 177 88

Ras gene protein products (p21) reacting with the monoclonal antibodies ras 11, DWP, R256 and E184 were studied with an immunohistochemical method which was applied to 17 normal and 79 colorectal adenocarcinoma specimens. Normal colorectal epithelium showed positive staining for ras 11 in 35% of the cases, but not for DWP, R256 and E184. The antibodies showed positive staining in colorectal adenocarcinomas in 76, 53, 29 and 35% of the cases respectively. The degree of staining for ras 11 was significantly related to the grade of differentiation and increased from Dukes stage A to C. Strong staining for ras 11 predicted a significantly shorter recurrence-free interval (p less than 0.001). In Cox's regression analysis, the degree of staining for ras 11 was a prognostic factor independent of the grade of differentiation and Dukes stage (p less than 0.01). The results indicate that the enhanced expression of pan ras p21 may provide an important biological marker for determining prognosis in colorectal adenocarcinomas.
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PMID:Ras p21 expression in relation to histopathological variables and prognosis in colorectal adenocarcinoma. 177 45

ras p21 expression, as indicated by the monoclonal antibody ras 11, was estimated using immunohistochemistry on 69 primary colorectal adenocarcinomas. Also, DNA ploidy and S-phase fraction (SPF) were analysed with flow cytometry. Positive staining for ras 11 tended to be more common in DNA non-diploid tumours (P = 0.11), but was significantly correlated with high SPF (P = 0.038). Positive ras 11 staining, Dukes' stage, DNA ploidy and SPF were related to the recurrence-free interval of patients with Dukes' A-C tumours (P = 0.0014, P = 0.023, P = 0.035 and P = 0.040, respectively). ras 11 staining was a prognostic factor independent of both Dukes' stage and DNA ploidy (P = 0.011). The results indicate that pan ras p21 expression is associated with proliferative activity and has an independent prognostic value in colorectal adenocarcinoma.
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PMID:ras p21 expression in relation to DNA ploidy, S-phase fraction and prognosis in colorectal adenocarcinoma. 178 77

Expression of protooncogenes c-myc, N-myc, c-fos, Ha-ras 1, Ki-ras 2, yes, abl, src, N-ras, met and mos was studied in human gastric tumors and in rat gastric mucosal membrane during gastric carcinogenesis induced in rats by means of N-methyl-N'-nitro-N-nitroso guanidine (MNNG). Elevated expression of protooncogenes c-myc, c-fos, Ha-ras 1, Ki-ras 2, N-myc and Raf 1 was observed in carcinomas of human stomach. Amplification of Ha-ras 1 protooncogene was found in the human gastric tumor and metastasis. Point mutation was not detected in 12 the codon of Ha-ras I protooncogene. Expression of these protooncogenes was not altered during gastric carcinogenesis induced by MNNG in rats. However, within early steps of cancerogenesis (9 days, 3 months) amplification of ribosomal genes occurred in rat gastric mucosal membrane and in adenocarcinoma developed, while the tumor growth was accompanied by activation of mitochondrial genes.
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PMID:[Biochemical and molecular biological aspects of stomach cancer development in human and animal]. 181 23

Regarding to the pancreatic cancer, outcomes of the patients surgically treated have been poor. By using polymerase chain reaction (PCR), paraffin-embedded specimens of the pancreatic carcinoma were confined point mutation in Kirsten (K)-ras codon 12. Then, incidence and type of point mutation of this oncogene and correlative studies with stage, T or N factor of pancreatic cancer were analysed. Extremely high incidence of K-ras gene mutation was shown in present report. The highest mode of point mutation of K-ras oncogene was GGT to GAT coded aspartic acid. Cases without point mutation in K-ras codon 12 were significantly frequent in papillary adenocarcinoma than in tubular type. There were not correlative result among mutation types, stage and T factor of pancreatic cancer. Most patients with pancreatic cancer who survived more than 2 years have not shown mutation to aspartic acid. Four cases including two cases of mucin producing pancreatic cancer did not have point mutation in K-ras codon 12. Pathogenesis of mucin producing cancer can be distinguished from typical pancreatic cancer by detection of point mutation in K-ras codon 12 using PCR.
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PMID:[Detection of point mutation of Kirsten ras oncogene in pancreatic carcinoma by polymerase chain reaction]. 187 May 74

The presence of point mutation at codons 12, 13 and 61 of the c-Ki-ras oncogene was investigated in 7 cases of gastric adenoma and 35 cases of gastric adenocarcinoma using DNA samples from formalin-fixed and paraffin-embedded tissues. Oligonucleotides encompassing the three codons were amplified by using the polymerase chain reaction (PCR), and then examined for point mutation by the selective oligonucleotide hybridization technique. Point mutation was detected in three of the 7 adenomas (43%) and three of the 35 carcinomas (9%). All the gastric adenomas showed the histology of tubular adenoma, being very similar to that of colonic adenoma. The 35 cases of gastric adenocarcinoma were classified into 17 cases of differentiated type and 18 cases of undifferentiated type including signet-ring cell carcinoma. The point mutation of c-Ki-ras oncogene was detected only in the differentiated type (3/17, 18%), and there was no case with point mutation in the undifferentiated type. These results suggest that the genetic mechanism of carcinogenesis differs between the differentiated type and the undifferentiated type of gastric adenocarcinoma, and also that c-Ki-ras activation is possibly involved in a relatively early step of the "adenoma-carcinoma sequence," which leads to the development of a portion of differentiated adenocarcinomas in the stomach.
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PMID:Point mutation of c-Ki-ras oncogene in gastric adenoma and adenocarcinoma with tubular differentiation. 190 52

Most pancreatic adenocarcinomas are known to have ras gene (oncogene) mutations. The site of the mutations is localized in codon 12 of K-ras gene. Such high incidence and localization of the ras gene mutations have not been observed in any other human malignancies. Polymerase chain reaction and direct sequencing method enabled us to analyze DNA sequence around codon 12 of K-ras gene in small quantities of specimens obtained from needle biopsies and aspirate samples for pathological diagnosis. All the materials obtained from 12 patients with pancreatic adenocarcinoma showed the mutations, whereas those obtained from 6 patients with chronic pancreatitis showed no mutations. In several cases using the mutations of K-ras gene as a marker, this analysis supplemented conventional pathology and cytology in making the diagnosis of pancreatic adenocarcinoma. The analysis of ras-gene mutations was useful for the clinical diagnosis of pancreatic adenocarcinoma.
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PMID:Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. 198 26

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

The C57BL/6 x C3H F1 (hereafter called B6C3F1) mouse is an important animal model for long-term carcinogenesis studies. Maintained under normal laboratory conditions, these mice develop various types of spontaneous tumors during their lifetime. Activated Ha-ras genes have been detected in 66% of spontaneous hepatocellular tumors in the B6C3F1 mouse [Reynolds et al., Science (Washington DC), 237:1309, 1988]. In this study 49 spontaneous non-liver tumors were investigated for oncogene activation by DNA transfection techniques. Of the 49 tumor DNAs analyzed, only 5 yielded multiple foci in the NIH 3T3 focus assay: 2 of 10 pulmonary adenocarcinomas; 0 of 25 lymphomas; 2 of 2 Harderian gland adenomas; 0 of 1 adenocarcinoma of the small intestine; 1 of 6 malignant skin tumors; 0 of 4 hemangiosarcomas; and 0 of 1 lung metastasis of a hepatocellular carcinoma. DNA from six lymphomas which were negative in the NIH 3T3 focus assay were further analyzed for transforming genes by the nude mouse tumorigenicity assay. One of the five lymphomas tested positive with this assay. Southern blot analysis identified five activated ras genes: H-ras in two Harderian gland adenomas; K-ras in one pulmonary adenocarcinoma and in one s.c. adenocarcinoma; and N-ras in one lymphoma. The mutations involved were CG to AT and AT to TA in codon 61 of the Ha-ras genes, GC to AT or TA in codon 12 of the K-ras genes, and a GC to AT mutation in codon 12 of the N-ras gene. Transformant DNA from a pulmonary adenocarcinoma which yielded multiple foci in the transfection assay did not hybridize to DNA probes specific for the K-, H-, and N-ras, raf, neu, and met genes. Thirteen additional tumor DNAs yielded a single focus in the NIH 3T3 transfection assay. The transformant DNAs retransmitted in a second cycle transfection assay. Rearranged and/or amplified raf genes were detected in six of the transformant DNAs. At present we do not know whether these activated raf genes were present in the original tumor DNA. The other seven transformant DNAs did not hybridize with any of the above mentioned specific DNA probes utilized in Southern blot analysis. Unlike liver tumors, the activation of ras protooncogenes is not a frequent event in the development of spontaneous non-liver tumors of the B6C3F1 mouse. The results from this study should aid in understanding the neoplastic development associated with exposure to chemical carcinogens in the B6C3F1 mouse.
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PMID:Activation of protooncogenes in spontaneously occurring non-liver tumors from C57BL/6 x C3H F1 mice. 199 58

Point mutations in codons 12, 13 or 61 of the oncogenes Ha-ras, Ki-ras or N-ras have been identified in human malignancies of many types. Using the PCR (polymerase chain reaction) technique for DNA amplification in vitro and stringent probing of the amplified DNA on dot blots with a library of specific oligonucleotides, we have screened for the presence of ras mutations in oral and para-oral malignancies and some associated lesions. The material, from UK patients, consisted of 22 oral squamous-cell carcinomas including 5 neck metastases, 1 oral mucosal dysplasia, 1 proliferative verrucous leukoplakia, 1 antral and 1 tonsillar carcinoma, 1 basal-cell carcinoma, 1 salivary adenocarcinoma, 1 salivary adenoid cystic carcinoma and 1 lung adenocarcinoma metastatic to the gingiva. Genomic DNA was extracted from tissues which were fresh or preserved in liquid nitrogen. Two DNA samples contained point mutations in codon 61 of Ki-ras. One of these mutations was in the lymphocytes infiltrating a retromolar SCC. The other mutation (CAA to CAU; substitution of glutamine by histidine) was in the lung adenocarcinoma metastasis. The absence of ras mutations in the epithelium of primary oral squamous-cell carcinomas is of considerable interest as other work in our Department on Indian cases of oral carcinomas associated with chewing tobacco (quid) revealed that 35% of these had a codon 12, 13 or 61 mutation in Ha-ras. While ras activations arising from point mutations may occur in a high proportion of oral malignancies associated with chewing tobacco (quid), this was not the case in UK oral malignancies, even where tobacco was smoked.
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PMID:Ras mutations in United Kingdom examples of oral malignancies are infrequent. 204 May 36


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