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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparative investigation of the one- and two-dimensional electrophoretic keratin polypeptide patterns of various keratinizing epithelial tissues and of benign and malignant tumors of these tissues in the rodent species mouse, rat and hamster was undertaken. Keratin polypeptides of all normal epithelia investigated (vaginal, anal and forestomach epithelium) appear in a molecular weight range of about 40 K--70 K daltons and can be divided according to molecular weight and electrical charge into three groups. The large keratins (group A) have a basic character, while the lower molecular weight components of groups B and C are acidic in nature. The tissue-specific variations within one species are minimal and, apart from minor quantitative differences, mainly concern differing numbers of components within groups A and B, whereas the species-specific variations are more pronounced and apply to all three groups of keratins, which show a variable number of individual polypeptides differing in molecular weights and/or electrical charge. Independent of the tissue- and species-specific differences, keratins of epithelial carcinomas exhibit a special pattern differing from that of their corresponding intact tissues, as well as from benign tumors, by the lact of the large keratin polypeptides of group A. These characteristic differences in the keratin polypeptide composition of normal epithelia and of benign and malignant tumors may be useful for the diagnosis of epithelial tumors.
Carcinogenesis 1981
PMID:Carcinoma-specific keratin polypeptide patterns in keratinizing epithelia of rodents : independence of species- and tissue-specific variations. 616 11

In order to investigate the role that hyperplasia plays in the induction of the keratin modifications by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the effects of several inhibitors of tumor promotion and cycloheximide on the TPA-induced protein changes were studied. The antiinflammatory steroid fluocinolone acetonide and cycloheximide, which prevent the induction of hyperplasia, were found to prevent the appearance of the TPA-induced keratin modifications. Retinoic acid and tosylphenylalanylchloromethyl ketone, which have minor influence on hyperplasia, were found to have essentially no effect on these protein changes. These results provided further evidence that the TPA-induced epidermal keratin changes were associated with the induction of hyperplasia by TPA and not necessarily related to promoting ability.
Carcinogenesis 1982
PMID:Effects of inhibitors of tumor promotion on 12-O-tetradecanoylphorbol-13-acetate-induced keratin modification in mouse epidermis. 618 46

Human epithelial cells contain, intermediate-sized filaments formed by polypeptides related to epidermal alpha-keratin ("cytokeratins") which are expressed in different combinations in different epithelia. Using cytoskeletal proteins from human biopsies and autopsies we have examined, by two-dimensional gel electrophoresis and immunoblotting experiments, the cytokeratin polypeptide patterns of diverse primary and metastatic carcinomas and have compared them with those of corresponding normal epithelial tissues and cultured cells. Five groups of carcinoma cytokeratin patterns can be discriminated. (1) Cytokeratins typical of simple epithelia (polypeptides Nos. 7, 8, 18, 19) are expressed, in various combinations, by many adenocarcinomas, for example those of gastrointestinal tract. (2) Cytokeratins typical of stratified epithelia (Nos. 1, 5, 6, 10, 11, 14-17) are found, in various combinations, in squamous cell carcinomas of skin and tongue. (3) Complex patterns showing polypeptides Nos. 7, 8, 18, 19, and one basic component (No. 5 or 6) are detected in certain carcinomas of the respiratory tract and the breast. (4) Complex patterns containing cytokeratins widespread in stratified epithelia (Nos. 4-6, 14-17) as well as components Nos. 8 and 19 occur in diverse squamous cell carcinomas derived from non-cornified stratified epithelia, with or without additional small amounts of cytokeratin No. 18. (5) Patterns of unusually high complexity can be found in some rare tumors as is shown for a cloacogenic carcinoma. No significant qualitative changes of expression of cytokeratins were found when primary tumors and metastases were compared. When compared with cytokeratin patterns of normal epithelia, carcinomas of the first type usually display a high degree of relatedness to the tissue of origin. Other carcinomas do not express some of the cytokeratins present in the tissue of their origin and, vice versa, certain components which are minor or apparently absent in normal tissue are major cytokeratins in the corresponding tumor. These differences may be explained by cell type selection during carcinogenesis, but changes of expression during tumor development cannot be categorically excluded. The possibility of cell type heterogeneity within a given tumor is also discussed. Similarly complex patterns of cytokeratin polypeptides have been noted in certain cultured human carcinoma cell lines (e.g., A-431, RPMI 2650, Detroit 562, A-549) and can also be observed in cell clones. The possible value of analyses of cytokeratin patterns, by gel electrophoresis or specific monoclonal antibodies, in distinguishing different carcinomas by non-morphologic criteria is discussed.
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PMID:Complex cytokeratin polypeptide patterns observed in certain human carcinomas. 618 57

Recent advances in the biology of the epidermis increase our understanding of skin cancer. Epidermal tissue culture demonstrates that cells from epidermal malignancies retain their malignant characteristics. Some epidermal tumors contain a low molecular weight keratin as a major structural protein; a low molecular weight keratin is a characteristic of fetal epidermis as well. Certain epidermal cell-surface antigens, such as the pemphigus antigen, may be absent in skin cancers. A population of long-lived skin cells may be the site for genetic alterations that eventually produces skin cancers. A population of basal "dark" cells is increased after treatment with tumor promoting agents such as phorbol esters. Two-stage (initiation, promotion) epidermal carcinogenesis can now be studied in tissue culture. Several components of the complex multilayered basement membrane zone are produced by epidermal cells. Malignancies of epidermal cells may extend beyond the basement membrane zone by disordered synthesis of the zone or by producing enzymes including collagenases that alter the zone.
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PMID:Recent advances in epidermal biology: relevance to epidermal malignancies. 619 44

Eight cell lines exhibiting resistance to Ca2+ induced terminal differentiation were derived from primary mouse epidermal cultures and their properties analyzed. The lines developed either spontaneously (2 lines) or after exposure of primary cultures to carcinogens or carcinogens and tumor promoter. All but one of the lines were of epithelial or epitheloid morphology but 3 of the 8 lines lacked desmosomes, keratin filaments and immunoprecipitable keratin proteins, and thus could not be defined as keratinocytes. Two of the 5 keratinocyte lines were tumorigenic in syngeneic Balb/c newborns after 4 months in medium containing 1.2 mM Ca2+, and 3 lines remained non-tumorigenic even after 11 months in 1.2 mM Ca2+. All three of the non-keratinizing lines were tumorigenic. Tumorigenic potential of the 5 keratinocyte lines did not correlate with ploidy (as determined by DNA content), transglutaminase activity or growth in soft agar. However, the 2 tumorigenic keratinocyte lines contained cells which stained intensely red for gamma glutamyl transpeptidase activity, while the non-tumorigenic keratinocyte lines did not. Only those lines lacking desmosomes and keratin filaments grew in soft agar, but these lines were negative for gamma glutamyl transpeptidase activity. Ploidy and transglutaminase activity did not correlate with tumorigenicity in these non-keratinizing lines. These results show that cell lines derived from cultured mouse epidermal cells and selected on the basis of their resistance to Ca2+ induced terminal differentiation may be preneoplastic. Furthermore the association of additional markers with malignant change in these cell lines depended on whether or not the cells were keratinizing.
Carcinogenesis 1983 Nov
PMID:Properties of carcinogen altered mouse epidermal cells resistant to calcium-induced terminal differentiation. 619 37

A method is proposed for the simultaneous staining of neutral and acidic, periodate reactive and nonperiodate reactive mucosubstances, glycogen and keratin in paraffin sections. Briefly, sections are stained by the Alcian blue (pH 2.5)-PAS method, followed by a peroxidase-antiperoxidase immunohistochemical stain for keratin. The proposed method modifies an existing method, and expands the range of polysaccharides and mucosubstances which may be demonstrated. The proposed method is easily performed within a single working day and promises to be of value in surgical pathology as well as in studies of bronchial carcinogenesis.
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PMID:An Alcian blue (pH 2.5)-PAS-keratin immunoperoxidase method for the simultaneous demonstration of keratin and neutral and acidic mucosubstances. 619 75

The human keratinocyte line SCC-13, derived from a squamous cell carcinoma of epidermis, was examined for effects on growth and differentiation upon treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition of growth was observable at 0.1 nM and maximal in the concentration range of 1-100 nM TCDD, but was completely antagonized by addition of hydrocortisone to the growth medium. TCDD was found to inhibit several aspects of keratinocyte differentiation that are stimulated by hydrocortisone. In confluent cultures, accumulation of keratin protein and transglutaminase activity were suppressed as well as spontaneous envelope formation and envelope competence. This phenomenon occurred without significant effect of TCDD on depletion of hydrocortisone from the medium. We conclude that the response of SCC-13 cells to TCDD depends upon hormonal conditions in culture and that this agent can interfere with cellular responses to normal physiological conditions, thereby altering the differentiation program ordinarily observed.
Carcinogenesis 1984 Mar
PMID:Opposing effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone on growth and differentiation of cultured malignant human keratinocytes. 620 Feb 49

Two rat ascites hepatoma lines, AH130, originating from a azodye-induced liver carcinoma, and AH130F(N), spontaneously derived from the AH130 line during serial i.p. transplantation were analyzed for their intermediate filament protein expression by one and two-dimensional gel electrophoresis, in vitro translation of their mRNAs and immunolocalization using antisera against distinct subunits and compared with intermediate filament expression of normal hepatocytes. Normal rat hepatocytes synthesize mainly two keratin subunits at 55 and 47 kDa. The AH130 hepatoma line maintains the expression of these proteins, however, in addition also synthesizes a 40-kDa keratin subunit and large amounts of vimentin. In contrast, the AH130F(N) hepatoma line has lost the ability to express keratin subunits; its intermediate-sized filament compound is apparently built up only by vimentin. Even by means of the sensitive immunoblotting technique using antisera against the normal hepatocyte keratin subunits, no keratin synthesis can be demonstrated in this line. The marked differences in the metastatic capacity of the two hepatoma lines make them promising tools to investigate a possible involvement of intermediate-sized filament expression in the process of tumor spreading.
Carcinogenesis 1984 Oct
PMID:Differential expression of intermediate filament proteins in two rat ascites hepatoma lines of common origin. 620 51

The present study was concerned with oral reparative and inflammatory reactions, benign epithelial proliferations and malignant lesions including their prestages. Following investigations of normal oral mucosa, biopsy and surgical specimens of diseased human oral mucosa were studied with light and electron microscopical methods. In addition, experimental models of oral wound healing and carcinogenesis were developed. Combining morphological (immunofluorescence, immunocytochemistry, electron microscopy) and biochemical (SDS polyacrylamide gel electrophoresis) techniques differentiation and function of epithelial and non-epithelial cells of the oral mucosa were investigated. Clinical pathology. 725 oral lesions were collected from the files of the Dermatological Clinic of the University of Hamburg. Among these lesions epithelial hyperplasias and neoplasias represented the most frequent alterations of the oral mucosa. The incidence of premalignant lesions (3.7%) was consistent with the percentages reported in the literature. On frozen or glutaraldehyde-fixed tissue samples the value of immunohistological and ultrastructural methods was examined with particular respect to the distinction of reactive inflammatory processes from true premalignant and malignant lesions and with special reference to the differential diagnosis of epithelial and non-epithelial tumours. Examples were given for immunological characterization of inflammatory lesions and for histogenetical typing of neoplasias. Normal oral mucosa. Biochemical and morphological investigations of keratin filaments showed that basal and suprabasal epithelia contain different keratin polypeptides related to the degree of cell differentiation. These cytoskeletal modifications were seen to be associated with cell membrane differentiations which was demonstrated by different lectin affinities to basal and suprabasal compartments of epithelium. At the epithelial-mesenchymal interfaces macromolecular substances appeared (e.g. fibronectin) which are produced by basal epithelia (e.g. laminin) and connective tissue cells leading to the formation of the basement membrane zone. Immune competent cells were seen to be regular components of normal oral mucosa. Within the epithelium Langerhans cells and T lymphocytes of the suppressor/cytotoxic phenotype were shown to be the predominant inflammatory cells. B lymphocytes, T lymphocytes of the suppressor/cytotoxic and helper/inducer phenotypes and typical macrophages represented cellular elements of the connective tissue. All these non-epithelial cells were found to contain vimentin filaments.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Immunopathology of the oral mucosa. Oral immune system--inflammatory reactions--tumor-"marker"--virus identification]. 632 69

Skin tumors experimentally induced by dimethylbenzanthracene (DMBA) are associated with dense subepithelial accumulations of mast cells. To investigate the sequential changes of the mast cell population during carcinogenesis, and to provide a model with which to examine mast cell proliferation, the back skin of 48 Swiss Webster mice was painted with 0.5% DMBA in benzene twice weekly for 12 weeks. Control and DMBA-treated tissues were processed for histological examination. The observed pattern of tissue changes fell into four phases: a) inflammation and necrosis followed by epithelial regeneration and hyperplasia, b) development of localized regions of acanthosis, c) loss of normal organization with downgrowth of epithelial cells and formation of keratin pearls, d) appearance of well-defined nodules resembling verrucous carcinoma. Subepithelial mast cells varied greatly in number during the above sequence of changes. Dense foci of cells were seen, particularly beneath the regions of hyperplastic epithelium. Mast cells may play a role in abnormal epithelial proliferation and, further, DMBA treatment may provide a suitable model with which to examine the origin and kinetics of mast cells.
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PMID:Sequential histological changes and mast cell response in skin during chemically-induced carcinogenesis. 641 83


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