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

The distribution of the neu protein has been studied with two monoclonal antibodies in a post-embedding immunogold method on glycolmethacrylate sections. Labeling of the cytoplasm was due to binding to mitochondrial cristae. The detection of label at the plasma membrane was optimized by selectively staining the plasma membrane with phosphotungstic acid at low pH. Strong labeling was observed in breast carcinoma cells and faint labeling in other tissues. Brush borders were also found to be reactive. neu protein can thus be localized to baso-lateral and apical cell membranes. An important homology exists with a mitochondrial protein.
 ...
PMID:The selective counterstaining of the plasma membrane improves the immunoelectron microscopic detection of neu protein at the cell border. 198 65

Hematopoietic growth factors have recently been well characterized by complementary DNA cloning. For human epidermal growth factor, granulocyte-macrophage colony-stimulating factor recombinant proteins have been expressed in Escherichia coli. To reduce the toxic side effects of chemotherapy on the bone marrow, recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human interleukin 3 were applied to patients suffering of gastrointestinal cancers. To determine the influence of recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human interleukin 3 on human pancreas and gastric cancer cell cells in vitro, a sensitive microculture test system was established that allows precise quantification of proliferation. A more than twofold enhancement of proliferation was observed by interleukin 3 and granulocyte-macrophage colony-stimulating factor in two of two cell cultures derived from gastric carcinoma cells, while two of nine cultures from pancreas carcinoma cells have shown enhanced cell growth in the presence of recombinant human interleukin 3 or recombinant human granulocyte-macrophage colony-stimulating factor. In comparison, recombinant human epidermal growth factor increased cell growth in two of two gastric and in five of nine pancreas carcinoma cultures. In general, 1-10 ng/mL of the growth factors yielded the highest growth rate, but even 1-pg amounts produced increased cell growth. Expression of messenger RNA for granulocyte-macrophage colony-stimulating factor, interleukin 3, and the oncogene HER2/neu remained undetectable in all of the tested cell lines, while the various abundance of messenger RNA for the epidermal growth factor receptor was different in each cell line. The reported results imply that the hematopoietic growth factors interleukin 3 and granulocyte-macrophage colony-stimulating factor influence cellular growth of pancreas and gastric carcinoma cells by a paracrine mechanism and may possess a more general regulatory function than originally anticipated.
 ...
PMID:Stimulation of pancreas and gastric carcinoma cell growth by interleukin 3 and granulocyte-macrophage colony-stimulating factor. 201 78

More than 60 breast cancer specimens were screened for their expression status of 25 different proto-oncogenes. The screening method is based on in vitro synthesis of a radioactive cDNA copied from the total cellular RNA of tumor tissue. This cDNA is hybridized to cloned oncogene probes which are immobilized to a GeneScreen membrane. Frequently multiple oncogenes were found expressed although expression levels were rather moderate. 25-30% of the analyzed tumors showed significant expression of either erbB, src, raf1, lck or H-ras. Although neu expression--an oncogene believed to be particular relevant as prognostic parameter for mamma carcinoma--was screened for most of the tumors with a heterologous gene probe, expression signals could be detected in about 20% cases. The only notable correlation with classical clinical parameters such as tumor size and proliferation stage, hormone receptor status and different DNA indices was the observation that tumors lacking the progesterone receptor frequently express multiple oncogenes. Advantages and limitations of the cDNA/dot-blot screening for oncogene expression are discussed.
 ...
PMID:Expression of oncogenes in human breast cancer specimens. 201 53

The neu oncogene codes for a cell surface protein that has a high degree of homology with the epidermal growth factor receptor. Amplification of this oncogene in breast carcinoma and ovarian carcinoma is correlated with a poorer prognosis. The c-myc oncogene codes for a DNA binding protein and is believed to regulate cellular proliferation. Sixteen primary endometrial adenocarcinomas were analyzed for c-myc and c-neu amplification. Eleven of sixteen tumor samples exhibited amplification of the neu gene. Four of these eleven patients died of disease an average of 16 months after diagnosis. The five patients without tumor amplification of the c-neu gene have been followed an average of 31.2 months without evidence of recurrent disease. Ten of fifteen tumor samples exhibited amplification of the c-myc gene. Five of the ten patients died of disease an average of 13.4 months after diagnosis. The remaining five patients have been followed for an average of 31.2 months and are free of disease. Six of the sixteen tumor specimens exhibited amplification of the both c-neu and c-myc genes, and four of these patients died of recurrent disease. Amplification of the c-neu or c-myc oncogene correlated with advanced-stage disease and poorly differentiated lesions, suggesting that oncogene amplification may predict biologically aggressive adenocarcinomas of the endometrium.
 ...
PMID:Oncogene alterations in endometrial carcinoma. 222 49

A tumorigenicity assay was performed using DNA extracted from the human mammary carcinoma cell line MCF-7. Seven nude mouse tumors were obtained and were analyzed for the presence of human sequences and known activated oncogenes. The c-erbB.2/neu gene was identified in two tumors and two ras oncogenes in two other tumors. In order to characterize the mechanism of activation of the c-erbB.2/neu oncogene, we isolated and analyzed this gene from one of the tumors. The cloned gene did not present any rearrangement. c-erbB.2/neu transcripts from the nude mice tumors were of normal size. In one case overexpression was observed.
 ...
PMID:Tumorigenicity assay of the human mammary carcinoma cell line MCF-7. 256 Jun 22

We have investigated the biological function of an unidentified human growth factor, the ligand of the putative HER2 receptor, by characterizing the signalling properties of its receptor. HER2 (or c-erbB-2), the human homolog of the rat neu proto-oncogene, encodes a transmembrane glycoprotein of the tyrosine kinase family that appears to play an important role in human breast carcinoma. Since a potential ligand for HER2 has not yet been identified, it has been difficult to analyze the biochemical properties and biological function of this cell surface protein. For this reason, we replaced the HER2 extracellular domain with the closely related ligand binding domain sequences of the epidermal growth factor (EGF) receptor, and examined the ligand-induced biological signalling potential of this chimeric HER1-2 protein. This HER1-2 receptor is targetted to the cell surface of transfected NIH 3T3 cells, forms high and low affinity binding sites, and generates normal mitogenic and cell transforming signals upon interaction with EGF or TGF alpha. The constitutive activation of wild-type HER2 in transfected NIH 3T3 cells suggests the possibility that these cells synthesize the as yet unidentified HER2 ligand and activate HER2 by an autocrine mechanism.
 ...
PMID:HER2 cytoplasmic domain generates normal mitogenic and transforming signals in a chimeric receptor. 256 8

The expression of the neu oncogene product was investigated in invasive and non-invasive ductal carcinomas of the breast, non-neoplastic lesions of the breast, fragments of normal adult and fetal breasts and in several other normal and fetal tissues at different weeks of pregnancy by means of an immunohistochemical study with monoclonal antibodies. The staining pattern along the cytoplasmic membrane was specific for malignancy and occurred in 29% of the breast carcinomas. It was observed in invasive carcinomas as well as in ductal carcinoma in situ and it showed a significantly higher expression in premenopausal women than in postmenopausal women. This higher expression was also present in oestrogen receptor-negative tumours. The tubules of the fetal and adult kidney, the absorption cells of the fetal and adult small and large intestine, the sebaceous glands of the fetal and adult small and large intestine, the sebaceous glands of the fetal and adult skin, the adult endocervix, the endometrium, the C-cells of the thyroid, hepatocytes and all ductal cells of the fetal breast showed a constant diffuse intracytoplasmic granular staining. staining. The same granular intracytoplasmic staining pattern was focally observed in rare cases of normal breast tissue in adults and in some cases of epitheliosis, aprocrine metaplasia and some breast carcinoma cells, which did not express neu oncogene product on their membrane. Western blot experiments showed that the cytoplasmic protein had a molecular weight of 155 kD (kilodaltons); the membrane protein is the known 185 kD neu protein.
 ...
PMID:The expression of the neu oncogene product in breast lesions and in normal fetal and adult human tissues. 257 31

Various monoclonal antibodies reactive with protooncogene products or tumor-associated antigens have been utilized to investigate breast carcinoma biology or antigen expression with potential prognostic relevance. Murine monoclonal antibody TA1, generated by immunization of BALB/c mice with whole c-erbB-2 (neu) transformed NIH/3T3 cells, recognizes the extracellular domain of the c-erbB-2 protein and binds a Mr 185,000 protein by immunoprecipitation. Using avidin-biotin-peroxidase techniques and monoclonal antibody TA1, 313 archival primary adenocarcinomas of the breast were evaluated for c-erbB-2 overexpression; 290 of these were used for multiparametric statistical analysis. Historical, clinical (age, laterality), histological (nuclear grade, tumor size, lymph node status, lymphatic or blood invasion), and hormone receptor data as well as clinical outcome (minimal follow-up, 6 years; median follow-up, 8.5 years) were compared to TA1 staining. For these 290 patients Cox regression multivariate analysis showed the strongest correlation between lymph node status or estrogen receptor status and overall survival (P = 0.0001 and 0.049, respectively). TA1 staining did not significantly correlate with survival (P = 0.395). However, univariate analysis of certain patient subpopulations showed a significant correlation if the examined tumors were subdivided into negative or focally reactive and those with greater than or equal to 40% cellular reactivity. For T3, T4 patients, strong TA1 immunoreactivity correlated with a shortened disease-free survival (log rank P = 0.0018; Wilcoxon p = 0.0078) and overall survival (log rank P = 0.0002; Wilcoxon P = 0.0013). For these patients the overall survival at 6 years was markedly different between the strongly reactive tumors (0%) and the negative to weakly reactive tumors (55%). In lymph node-positive patients a trend between high TA1 reactivity and a worse overall survival was also noted (log rank P = 0.128; Wilcoxon P = 0.054), with a 6-year survival of 42% in the strongly reactive tumors (n = 16) and 65% in the negative to weakly reactive carcinomas (n = 105). No correlation between TA1 immunoreactivity and other historical, clinical, and histological features were noted. c-erbB-2 overexpression as measured by immunohistochemical techniques, therefore, may have clinical significance in certain patient subpopulations.
 ...
PMID:Analysis of c-erbB-2 expression in breast carcinomas with clinical follow-up. 257 26

Fischer 344/Ncr rats of both sexes were subjected to partial hepatectomy and then initiated 21-24 h later by a single injection of methyl(acetoxymethyl)nitrosamine at 0.1 mmol/kg body weight via the portal vein. Beginning 3 weeks later, development of hepatocellular neoplasms in initiated rats was promoted by feeding 0.05% phenobarbital (PB) in the diet. Not only intrahepatic lesions but also a variety of extrahepatic tumors were induced. High-molecular-weight DNAs were prepared from 67 samples of grossly normal liver containing multiple preneoplastic foci/areas of microscopic dimensions, 137 hepatocellular adenomas (nodules), 93 hepatocellular carcinomas (HCC), 10 cholangiomas, and 25 extrahepatic tumors in 95 rats and tested for transforming activity in the NIH 3T3 transfection assay. DNA preparations from 7 of 93 HCCs, 2 of 10 cholangiomas, 2 of 137 nodules, 1 histiocytic sarcoma, and 1 thyroid carcinoma were positive in the transfection assay. Southern blot analysis showed that NIH 3T3 transformants induced by DNA from 5 HCCs, 1 hepatocellular adenoma, 1 cholangioma, 1 histiocytic sarcoma, and 1 thyroid carcinoma contained an activated K-ras gene of rat origin. Rat-derived H-ras was identified in transformants from 2 additional HCCs and rat c-raf from 1 hepatocellular adenoma. The transforming gene from one cholangioma showed no sequence homology to the ras genes, neu, or c-raf. Immunoprecipitation analysis of ras Mr 21,000 protein in 11 transformants indicated that, based upon protein electrophoretic mobilities, activation of the ras genes consistently resulted from mutations in codon 12 of these genes. Selective oligonucleotide analysis revealed that a G----A transition in the second base of codon 12 of K-ras was present in the 9 K-ras-positive transformants and also in DNAs prepared from the original tumors. In contrast, oligonucleotide hybridization experiments with DNAs from 35 hepatocellular tumors that were negative in transfection assays revealed the presence of mutant K-ras in 1 of 15 HCCs; no mutation could be detected in 20 transfection-negative adenomas. The infrequency of detection of a specific oncogene, more frequent detection of oncogenes in malignant tumors, and failure to observe activated oncogenes in preneoplastic lesions suggest that activation of ras oncogenes may occur as a late and infrequent event in the evolution of some rat hepatocellular neoplasms and that mutation of a specific ras locus is not an obligatory early event in the genesis of these neoplasms.
 ...
PMID:Infrequent activation of K-ras, H-ras, and other oncogenes in hepatocellular neoplasms initiated by methyl(acetoxymethyl)nitrosamine, a methylating agent, and promoted by phenobarbital in F344 rats. 264 46

The research of the past decade has made it clear that aberrant expression of genes that encode growth factors, their receptors, and other genes involved in normal cell growth and differentiation--so-called oncogenes--play important roles in determining the proliferative and invasive characteristics of malignant mammary neoplasms. The authors briefly review the topic of oncogenes and the relevance of oncogenes to breast carcinoma; also included is a description of current techniques commonly employed in the study of aberrant oncogene structure and function. Also presented is the authors' own work on oncogene expression in breast neoplasms, which implicates the neu, fms, PDGF-A and Ki-ras oncogenes in the control of mammary epithelial cell proliferation by autocrine and paracrine mechanisms.
 ...
PMID:Oncogene structure, function, and expression in breast cancer. 266 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>