Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosomal proteins from rat liver have been assessed immunologically for changes in specific cytokeratins or primary tumor nonhistone proteins during treatment with an azo dye hepatocarcinogen (3'-methyl-4-dimethylaminoazobenzene), (3'-Me-DAB) or the hepatotoxin alpha-naphthyl-iso-thiocyanate (alpha-NIT). Fisher rats were fed laboratory diets supplemented with either agent and sacrificed sequentially at various intervals. Chromosomal proteins from these livers were electrophoresed in the presence of sodium dodecyl sulfate, transferred to nitrocellulose sheets and reacted with rabbit antisera to Novikoff hepatoma cytokeratin or 3'-Me-DAB induced primary hepatoma dehistonized chromatin. Livers from carcinogen-fed animals exhibited distinct, sequential changes in antigenic nonhistone proteins until the immunological specificity characteristic of the hepatoma was achieved concomitant with the induction of neoplasia. No antigenic changes were observed to occur in hepatotoxin-fed animals. The rat carcinoma-specific cytokeratin antigens p39 and p49 in Novikoff hepatoma were observed to appear as early as three weeks after the start of carcinogen feeding and were present maximally in 23 week livers with in situ carcinoma. These cytokeratins were not detected in alpha-NIT-fed animals. Our results support the concept that the carcinogenic process can be related to temporal changes in the expression of cell-specific cytokeratins in addition to nonhistone chromosomal proteins. Furthermore, these data suggest the expression of these antigenic species to not be the direct result of changes in liver structure and cellular composition associated with carcinogen toxicity; rather, neoplastic transformation is apparently required.
Carcinogenesis 1983
PMID:Cytokeratin and nonhistone protein antigenic changes in rat liver during azo dye but not hepatotoxin feeding. 619 May 86

Biliary glycoprotein (BGP) is the human homologue of a cell adhesion molecule (CAM) of the rat designated Cell-CAM. The BGP gene is a member of the carcinoembryonic antigen gene family, which belongs to the immunoglobulin superfamily. BGP is expressed in cells of epithelial and myeloid origin. In granulocytes, BGP is a main antigen of the CD66 cluster of differentiation antigens that mediate the binding to endothelial E-selectin. Since BGP is a major human CAM, the expression of BGP was studied in 21 colorectal carcinoma tissue specimens and in the respective adjacent normal mucosae. As an internal control for epithelial mRNA, the expression of cytokeratin 18 was evaluated in parallel. In addition, the expression of carcinoembryonic antigen and nonspecific crossreacting antigen, which are highly homologous to BGP, was investigated. Two BGP mRNAs of 3.9 and 1.5 kilobases were detected in the normal colonic mucosa samples. The median of the tumor-to-normal ratios of mRNA expression was 0.2 for both BGP mRNAs. In contrast, the median was 1.2 for cytokeratin, 1.0 for carcinoembryonic antigen, and 1.4 for nonspecific crossreacting antigen. Relative to cytokeratin 18 expression, the expression of BGP was reduced to < or = 0.1 in half of the tumors and to < or = 0.4 in > 80% of the tumors. These findings indicate that the loss or reduced expression of the adhesion molecule BGP is a major event in colorectal carcinogenesis.
 ...
PMID:Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas. 750 81

Pancreatic islets isolated from juvenile but not aging adult mice, when infected with a retrovirus carrying polyomavirus middle T oncogene, produced cell lines, mPAC, with characteristics both of pancreatic ductal epithelium and neuroendocrine cells of the islets. Following three cycles of single cell cloning, mPAC cells consisted of two subtypes, a null cell, and a double-positive cell that co-expressed cytokeratin, a marker of ductal epithelium, and A2B5, a neuroendocrine ganglioside expressed in developing islet cells. Two islet cell genes, encoding somatostatin and pancreatic polypeptide, were transcribed at low levels in most mPAC clones, whereas the insulin and glucagon genes were not. Upon inoculation of mice, mPAC cells rapidly formed well-differentiated ductal adenocarcinomas that expressed cytokeratin but not the islet cell markers. The mPAC phenotype may result from a specific dedifferentiation of juvenile islet cells or ductal epithelium induced by middle T protein. Alternatively, mPAC cells may arise by transformation of a multipotential progenitor present within or in juxtaposition to juvenile islets. This cell type could therefore represent one of the targets in human cancers of the pancreatic duct. Moreover, signal transduction systems modulated by middle T, including src-related kinases, phosphatidylinositol kinase, and protein phosphatase 2A, may be involved in pancreatic carcinogenesis.
 ...
PMID:Murine pancreatic ductal adenocarcinoma produced by in vitro transduction of polyoma middle T oncogene into the islets of Langerhans. 752 78

Expression of cytoskeletal proteins has been shown to be dependent on the differentiation status of the tissue. In the present study, expression of two cytoskeletal proteins normally present in terminally differentiated keratinocytes, namely cytokeratin types 10/11 and involucrin, were studied in different stages of tumour progression in the oral mucosa. Results showed that cytokeratins 10/11 and involucrin strongly correlated with the differentiation status of cells. High expression was observed in non-dysplastic hyperplastic epithelium as compared to normal, dysplastic and neoplastic epithelium. In addition, various grades of dysplasia showed an inverse correlation with expression of these proteins. Statistical analysis of the results also showed a negative correlation between the differentiation of upper spinal cells and the stage of tumour progression. It therefore appears that the proteins studied may be useful as markers for epithelial carcinogenesis.
 ...
PMID:Alterations in expression of terminal differentiation markers of keratinocytes during oral carcinogenesis. 752 29

To begin delineating the cellular and molecular events that are important in ovarian carcinogenesis, we have developed a simple and rapid method for the establishment of primary cultures derived from benign tumors, malignant tumors, and ascites of the ovary that are representative of the original clinical material from which they are derived. From 23 ovarian epithelial ascites collected, 13 were successfully established in culture and cells survived an average of 7 to 8 passages. From 65 solid epithelial ovarian tumors (benign and malignant) 36 were cultured for an average of 6 passages for cultures derived from benign tumors and 11 or 12 passages in the case of malignant tumors. Cells were scored as epithelial in nature by morphology and histochemical analysis using anti-cytokeratin antibodies. Cultures, especially those derived from solid tumors, sometimes displayed fibroblastic-like contamination which was quickly resolved. We include limited molecular analyses both to characterize the origin of the populations we have established as well as to demonstrate the usefulness of these cultures in molecular studies.
 ...
PMID:Primary cultures of normal and tumoral human ovarian epithelium: a powerful tool for basic molecular studies. 752 92

Nodularin and microcystin-LR are cyanobacterial toxins and environmental hazards. Nodularin inhibits protein phosphatases 1 and 2A with the same potency as does microcystin-LR, which has recently been identified as a potent tumor promoter in rat liver. Our results suggested that nodularin is also a new tumor promoter in rat liver. A two-stage carcinogenesis experiment in rat liver initiated with diethylnitrosamine and without partial hepatectomy revealed that nodularin stimulated glutathione S-transferase placental form-positive foci in rat liver more effectively than did microcystin-LR, and that nodularin alone induced glutathione S-transferase placental form-positive foci as well as did diethylnitrosamine alone. Thus, nodularin itself is a new liver carcinogen, and microcystin-LR is a tumor promoter rather than a carcinogen. Nodularin induced hyperphosphorylation of cytokeratin peptides 8 and 18 in primary cultured rat hepatocytes 20% more effectively than did microcystin-LR, suggesting that nodularin penetrates more easily into the hepatocytes than does microcystin-LR. Nodularin up-regulated induction of c-jun, jun-B,jun-D,c-fos,fos-B, and fra-1 mRNA transcripts in rat liver after i.p. administration, and the accumulation of the mRNA transcripts was sustained for over 9 h after treatment. The environmental hazards of cyanobacterial toxins are discussed in relation to human primary liver cancer in Qidong county in the People's Republic of China. Our results support this hypothesis and indicate the need for prevention measures against cyanobacterial toxins.
 ...
PMID:Nodularin, a potent inhibitor of protein phosphatases 1 and 2A, is a new environmental carcinogen in male F344 rat liver. 752 97

The expression pattern of cytokeratin filaments in epithelia has been shown to be dependent on their type and grade of differentiation. The type of expression of cytokeratin in a cell may also be altered during carcinogenesis or other pathological conditions. The present study examined the alterations in expression of various cytokeratin types during different stages of tumour progression in the oral mucosa. Six monoclonal anti-cytokeratin antibodies were used for the study. Conspicuous staining differences with these antibodies were evident between normal keratinizing and non-keratinizing mucosa. These differences can be correlated to the differentiation pattern of the normal mucosa types. Antibodies specific to cytokeratin types 10/11, 19 and 14 showed significant correlation with stage of tumour progression. In addition cytokeratin type 18 also showed prominent differences in expression between different stages of tumour progression. These alterations in cytokeratin expression suggest that the terminal differentiation pathway of keratinocytes is disturbed during oral carcinogenesis. The results of the present study also emphasize the potential of using cytokeratin filaments as markers in the biological staging of oral premalignant and malignant lesions.
 ...
PMID:Differential expression of cytokeratin proteins during tumour progression in oral mucosa. 752 4

Tautomycin isolated from Streptomyces spiroverticillatus is an inhibitor of protein phosphatases 1 and 2A. Tautomycin induced hyperphosphorylation of cytokeratin peptides in human keratinocytes (PHK 16-I cells) 30 times less strongly than did okadaic acid. Repeated applications of tautomycin (30 micrograms, 40 nmol/application) did not induce tumor promotion in a two-stage carcinogenesis experiment on mouse skin initiated with 7,12-dimethylbenz[a]anthracene, whereas okadaic acid (1 microgram, 1.2 nmol/application) as a control induced tumor promotion strongly. As for mucosa of rat glandular stomach, tautomycin induced ornithine decarboxylase 4 h after intubation into the stomach. The tumor-promoting activity of tautomycin was next studied in the glandular stomach initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administration of tautomycin in the diet (1 mg rat-1 day-1), from week 9 to week 52 of the experiment, inhibited rather than enhanced tumor development in the glandular stomach initiated with MNNG. The percentages of tumor-bearing rats of the groups treated with MNNG plus tautomycin, MNNG alone, and tautomycin alone were 20.0%, 40.6%, and 0% respectively in week 52. The reason for the absence of tumor-promoting activity of tautomycin was studied in relation to tumor necrosis factor alpha (TNF alpha), an endogenous tumor promoter. We found that tautomycin neither enhanced TNF alpha mRNA expression in mouse skin nor induced TNF alpha release in a human stomach cancer cell line (KATO III cells), whereas okadaic acid did both. These results indicate that not all inhibitors of protein phosphatases are tumor promoters, and suggest that tumor promotion of the okadaic acid class of compounds is mediated by TNF alpha.
 ...
PMID:Tautomycin: an inhibitor of protein phosphatases 1 and 2A but not a tumor promoter on mouse skin and in rat glandular stomach. 755 47

Macroscopic stomach tumors induced in Sprague-Dawley rats during two chronic bioassays with the acetanilide herbicide butachlor at a dietary concentration of 3000 ppm, were evaluated histologically and immunohistochemically in order to determine their identity and pathogenesis. The tumors, which occurred primarily in female rats, were a heterogeneous series, including a few consisting wholly or partly of classic solid or anaplastic epithelium, but with the majority containing diffusely distributed primitive neoplastic cells. The latter had either the general appearance of undifferentiated epithelium or presented a more "mesenchyme-like" pattern where the cells were epithelioid, blastema-like, neuroendocrine-like or sarcoma-like with fascicular disposition. Gastric glandular profiles were also present, usually located near the periphery of the tumors, but in some cases extending into the diffuse tumor tissue. Most of the tumors displayed variable immunohistochemical reactivity for cytokeratin, vimentin and neuron-specific enolase but were negative for muscle-specific actin or desmin except in the stromal tracts. Detailed examination of all available gastric tissue revealed the presence of additional microscopic neoplasms and precursor hyperplastic lesions. All of these were typical gastric neuroendocrine cell lesions (gastric carcinoids) originating in the fundic mucosa but occasionally invading submucosally, and consisting of epithelial cells in organized clusters, rosettes or primitive tubules. The enterochromaffin-like (ECL) nature of these microscopic neoplasms and precursor lesions was substantiated by strong immunohistochemical reactivity for cytokeratin, neuron-specific enolase and chromogranin A, and a negative reaction for vimentin. One microscopic tumor showed a transition from differentiated neuroendocrine type in the fundic mucosa to a dispersed "mesenchyme-like" pattern in the submucosal extension. An additional finding in the butachlor-treated male and female rats was atrophy of the fundic mucosa involving, in particular, reduction in the numbers of parietal cells. This effect was dose-related, being most severe in the high-dose (3000 ppm) females. On the basis of their morphological characteristics, coupled with the continuity evident in the microscopic lesions, it is concluded that the macroscopic stomach tumors associated with the dietary administration of butachlor are poorly differentiated gastric carcinoids, in some cases admixed with a non-neuroendocrine epithelial element. Fundic ECL and stem cells are known to be under the trophic influence of gastrin, which is apparently responsible for the induction of the tumors associated with butachlor administration. Gastric tumor development involving gastrin is recognized as a secondary, hormonal mechanism of carcinogenesis, demonstrating a dose-threshold phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Identity and pathogenesis of stomach tumors in Sprague-Dawley rats associated with the dietary administration of butachlor. 758 Jan 13

The ability of primary tumours to metastasize accounts for the majority of cancer deaths. The emergence of circulating carcinoma cells in the peripheral blood is supposed to be an indicator for cancer cell spread. We have focused on this phenomenon in order to develop a sensitive technique for enriching epithelial derived cells on the basis of a two-layer density gradient and subsequent immune magnetic cell sorting. Epithelial cells are possess a cytoskeleton containing an assembly of intermediate filaments. During carcinogenesis these filaments do not undergo modifications of antibody binding epitopes such as occur in the protein domains of surface markers. We have developed a two-layer density gradient in which the epithelial cells form a single density band. This was demonstrated by recovery experiments using [3H]thymidine-labelled epithelial cells which showed epithelial cells were enriched within this first step by a factor of 20. In a second step the MACS system was applied. Cells were stained with a performed FITC-conjugated mouse anti-human cytokeratin antibody bound to a rat anti-mouse antibody coupled to superparamagnetic particles (immune paramagnetic separation complex; IPSC) and subjected to high gradient magnetic fields. The two-step procedure was confirmed by dispersing 50 epithelial cells in 5 x 10(5), 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9) peripheral blood leucocytes. Specific binding of the preformed IPSC was demonstrated by flow cytometry, confocal laser, fluorescent and electron microscopy. The specificity of the method was further proved by dual staining with IPSC and anti-human PSA antibody of epithelial prostatic cells separated from peripheral blood in vitro. By means of this double-step separation method it was possible to isolate up to 15-20 cells out of 50 epithelial cells originally suspended into 5 x 10(7) to 5 x 10(9) human peripheral blood leucocytes. This represented an enrichment factor between 20,000 and 200,000, depending on the initial cell number. The immunologically captured epithelial cells can be used for further cytogenetic investigations such as in situ hybridization (ISH) and/or polymerase chain reaction (PCR) to detect cancer cell specific gene aberrations. This sensitive combined buoyant density immune magnetic cell separation technique is capable of detecting free carcinoma cells in the peripheral blood.
 ...
PMID:An immunological enrichment method for epithelial cells from peripheral blood. 760 48


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