Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attempts by early workers to induce liver tumours by the local implantation of carcinogens had by and large not been successful, so that the liver came to be viewed as being "resistant" to tumourigenesis by this means. A review of these early studies showed not only that fibrosarcomas could be easily induced by the local application of 3-methylcholanthrene (3-M.C.), but that there were also reasons why the apparently low susceptibility of the liver to the localised induction of hepatocellular tumours should not be accepted as established dogma. In an attempt to re-investigate this problem pellets made of cholesterol (CHOL), anthracene (ANT), alpha-naphthylisothiocyanate (ANIT), 3-M.C. or 4-dimethylaminoazobenzene (DAB) were implanted into the livers of male litter-mate weanling rats. The evolution of the response was studied by histological examination of the implantation site at varying intervals. In each instance the liver responded with the formation of a firm, complete connective tissue capsule which, however, did not prevent the gradual degradation of the implants. No tumours or other significant changes were observed with the control implants of CHOL or ANT. ANIT, known to damage biliary ducts, elicited what appeared to be an intense serous exudation which was separated from the adjacent parenchyma by a shell-like deposition of calcium in the connective tissue capsule. No significant biliary changes were observed, however, and no tumours were produced. Attention should be drawn to this reproducible, regularly occurring, in vivo model of extra-osseous calcification. The 3-M.C. induced a high incidence of large solitary bosselated tumours associated with the carcinogenic pellet which was found embedded in the tumour mass. The architectural arrangement and bizarre cytological appearance of the tumours led to the currently widely used diagnosis of malignant fibrous histiocytoma (M.F.H.) rather than the fibrosarcoma or rhabdomyosarcoma of the early workers. Some tumours produced large numbers of implantation metastases in the peritoneal cavity, but no distant metastases were observed in this series. Of particular interest is the fact that it was not possible to determine the site of origin of these tumours despite histological sampling at intervals of the site of implantation of the pellets. In contrast to these pleomorphic, clearly mesenchymal tumours reliably produced by 3-M.C., the implantation of pellets of DAB produced fewer tumours which were classified as large, singly occurring hepatocellular carcinomas (H.C.C.).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Localized hepatocarcinogenesis: the response of the liver and kidney to implanted carcinogens. 311 99

In an attempt to induce adenocarcinoma containing myoepithelial cells (MECs) in the rat submandibular gland, we injected 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in acetone into the glands of rat pups at the age of 10 days. In both male and female pups, the glands, including their developing terminal secretory units, contained far greater numbers of cells positive for proliferating cell nuclear antigen (PCNA) than did adult glands. A single administration of 1% DMBA (0.05 ml/130 g b.w.) did not produce adenocarcinoma, but did induce occasional sarcomas, such as rhabdomyosarcoma and fibrosarcoma, in 2 months. Most glands regenerated with minimal scar formation. Microscopically, these glands were atypical in that they contained increased numbers of PCNA-positive cells, underdeveloped granular ducts, and striated ducts surrounded by MECs positive for alpha smooth muscle actin (alphaSMA). Though these features were also observed in the regenerated glands after acetone injection, the number of PCNA-positive cells was relatively high in the glands of DMBA-treated females, especially in the terminal secretory unit. The second DMBA injection at 10 weeks of age produced adenocarcinoma made up of alphaSMA-positive MECs and keratin 19-positive duct cells. Such MEC-associated adenocarcinoma was induced in the glands of more than half the female but not the male animals. Replacement of either of the double DMBA treatments with acetone, or DMBA treatment, single or double, of adult glands did not produce adenocarcinoma, but did produce sarcoma and squamous cell carcinoma. These results suggest that (1) at least two genetic mutations are necessary for induction of adenocarcinoma with MECs in the rat submandibular gland, (2) the mutation is efficiently introduced to pup glands whose terminal secretory units exhibit extreme proliferative activity, and (3) the second mutation is difficult to introduce in male glands, whose proliferative activity is relatively low, and/or transformed cells need some female hormone after the mutation to propagate.
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PMID:Induction of adenocarcinoma containing myoepithelial cells in rat submandibular gland by 7,12-dimethylbenz(a)anthracene. 1103 53