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Biomedical subjects

S S Sternberg

Publications and source records attributed to S S Sternberg.

At least 73 records · Page 4Linked to original sources

Tumorigenicity in vivo and induction of malignant transformation and mutagenesis in cell cultures by adriamycin and daunomycin.

The two anthracycline antitumor antibiotics, adriamycin and daunomycin, have been tested for tumorigenic activity, and the results confirm previous findings that they can induce mammary tumors in female rats receiving single i.v. doses. Both substances are highly potent in producing malignant transformation and mutation in mammalian cell systems in vitro. Their transformming activity is comparable to that of the potent carcinogen, N-methyl-N'-nitro-N-nitro-soguanidine. Actinomycin D, although similar to the anthracyclines in having high binding affinity for DNA, is only minimally effective in the same in vitro systems and its direct carcinogenic activity in vivo is moot. These results suggest that satisfactory correlations may be obtainable between tests for tumorigenicity in vivo, and assays for transformation and mutagenesis in vitro, and that adriamycin, and daunomycin may have carcinogenic potential in man.

Adenocarcinoma↗

Carcinoma complicating Crohn's disease. Report of seven cases and review of the literature.

Seven cases of adenocarcinoma complicating Crohn's disease are reviewed. In three of the patients, small bowel cancers developed in association with reginal enteritis. In four patients, carcinoma of the colon was superimposed on Crohn's colitis. In two of these, the adenocarcinoma infiltrated chronic colocutaneous fistulas. Review of the literature shows an increasing number of reports of carcinoma complicating Crohn's disease, with a total of 36 cases of small bowel cancer and 30 cases of colon cancer previously reported. The significane of these and our own cases is discussed. The possibility of carcinoma must be kept in mind by clinicians following patients with Crohn's disease. Adenocarcinoma complicating Crohn's disease occurs at a younger age, on the average, and in areas similar to the distribution of Crohn's disease rather than the usual distribution of the cancer. Preoperative diagnosis is difficult, but changes in the nature of chronic fistulas should be investigated.

Adenocarcinoma↗

Prognostic evaluation of regional lymph node morphology colorectal cancer.

Histologic sections from 143 patients treated with surgery for infiltrating adenocarcinoma of the distal large bowel were studied with emphasis on the morphologic characteristics of the regional lymph nodes. Lymph nodes were classified into four groups designated lymphocyte predominance, germinal center predominance, lymphocyte depletion, and unstimulated. Results were correlated with the extent of disease and five year survival data. There was no significant association between the histologic pattern of the lymph nodes and the extent of the primary lesion. There was a higher survival rate in patients whose nodes showed germinal center predominance (71 per cent) compared with those whose nodes showed lymphocyte predominance or the unstimulated pattern (both 54 per cent), but these results were not statistically significant.

Adenocarcinoma↗

Megalocytosis and other abnormalities expressed during proliferation in regenerating liver of rats treated with methylazoxymethanol acetate prior to partial hepatectomy.

Rats were partially hepactectomized at various intervals after receiving a single injection of the carcinogen, methylazoxymethanol acetate. In treated rats, there was a delay and a reduction in the peak response of hepatic DNA synthesis. At 48 hr after partial hepatectomy, following completion of the first mitoses, almost all hepatocytes were enlarged (megalocytes) and many contained enlarged nuclei. Although at 7 days after the hepatectomy many megalocytes could still be found in centrilobular zones, the majority of the hepatocytes were of normal size or smaller. Abnormal anaphase and telophase figures containing chromosomal bridges and acentric fragments were found during the period of regeneration. In addition, discrete nests of small cells with increased cytoplasmic basophilia were evident. Megalocytes also appeared when rats were partially hepatectomized as late as 26 weeks after injection of the carcinogen. These results show that a single dose of methylazoxymethanol acetate can affect almost all hepatocytes and that latent effects persist for long periods of time.

Age Factors↗

Chronic toxicity study of cyclamate: saccharin (10: 1) in rats.

Chronic rat feeding studies were conducted on a 10: 1 cyclamate/saccharin (C/S) mixture to supplement previous investigations which had established the safety of the individual components. The test mixture was fed at dietary levels designed to furnish 500, 1120, and 2500 mg/kg body weight to groups of 35 male and 45 female rats. The protocol included observations of physical condition, growth response, food efficiency, blood, urine, and postmortem pathology. Reproduction and lactation performance was examined through 2 litters. Teratology was also investigated. Since conversion to cyclohexylamine (CHA) was found to occur in many of the rats, particularly in the higher dosage groups, it was included as an added insult in the diets of about half the animals during the last quarter of the 2-year test period. The only positive finding in these studies which proved to have crucial significance was the occurrence of papillary carcinomas in the bladders of 12 of the 70 rats fed the maximum dietary level of the mixture (equivalent to about 2500 mg/kg body weight) for periods ranging from 78 to 105 weeks (except for one earlier death). This finding was the principal reason for the removal of cyclamates from the "generally recognized as safe" (GRAS) group of non-nutritive sweeteners by the U.S. Department of Health, Education and Welfare. In the opinion of the authors, the sequelae following this precipitate ban on cyclamates, prompted by a verbal report of the preliminary findings, warrant placing the study on record for the information of toxicologists and regulatory agencies throughout the world.

Animals↗

The lethal actions of antitumor agents in proliferating cell systems in vivo.

Antitumor agents cause selective lethal injury in tissues in which there is high proliferative activity. It is a reasonable postulate that the selective pathology is the consequence of interference with the replication of DNA in mitotically active cells. The crypt epithelium of the small intestine of rodents, which is highly susceptible to injury by antitumor agents, has served as a useful object for in vivo study of the relationship between inhibition of DNA synthesis and cell death in proliferating tissues. The lethal effects of highly selective inhibitors of DNA synthesis, such as hydroxyurea and 1-beta-D-arabinofuranosylcytosine, develop rapidly and are restricted to those crypt cells which are committed to DNA synthetic activity. Agents like methotrexate, which concurrently suppress DNA, RNA, and protein synthesis, induce more slowly developing and more persistent alterations. As illustrated in mice treated with 1-beta-D-arabinofuranosylcytosine and polyinosinic-polycytidylic acid, the necrotic process in intestinal epithelial cells involves rapid envelopment of degenerating organelles in cytolysomal vacuoles.

Animals↗

Hereditary hemorrhagic telangiectasia. A case with hepatocellular carcinoma and acquired hepatocerebral degeneration.

A patient with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease), treated with ethinyl estradiol, multiple blood transfusions, and iron-dextran, developed hepatocellular carcinoma and acquired hepatocerebral degeneration. In addition to the carcinoma, the liver contained extensive arteriovenous maliformations, telangiectasis, and changes of Osler atypical cirrhosis. The carcinoma possibly had its genesis in the presence of an ocongenic serum hepatitis virus, or the cirrhosis, or both.

Aged↗

Penetration of somatic mammalian cells by sperm.

Penetration of somatic mammalian cells by spermatozoa occurred after simple admixture in culture. With sperm labeled in vivo, autoradiography revealed incorporation of DNA into nuclei of recipient cells, indicating release of DNA after entrance by sperm. This system provides a new approach to study the molecular biology of information transfer and of haploid gene expression.

Animals↗