In a study of the relation between chronic inflammation and carcinogenesis, C3H mouse fibroblasts of the 10T 1/2 clone 8 line (10T 1/2 cells) were exposed to human neutrophils stimulated to synthesize reactive oxygen intermediates or to a cell-free enzymatic system generating superoxide (xanthine oxidase plus hypoxanthine). After exposure, the 10T 1/2 cells were either placed in tissue culture or immediately injected into athymic nude mice. Both malignant and benign tumors developed in the mice injected with treated cells, but not in those injected with control cells; in one instance cells grown from one of the benign tumors subsequently developed a malignant phenotype. Malignant transformation was also observed in treated cells in the experiments in vitro.
Newly diagnosed breast cancer patients (N = 494) aged 45-90 years were studied to determine if age was associated with appropriate diagnostic and prognostic evaluations, and initial definitive therapy. Women 75 years of age and older were less likely to receive an appropriate diagnostic evaluation than were younger women, but age was not associated with an appropriate prognostic evaluation. Older patients with local disease who were undergoing lumpectomy were less likely to receive follow-up radiation; older patients with regional disease undergoing mastectomy were less likely to receive adjuvant chemotherapy (including hormonal therapy). Physicians' attitudes about appropriateness of therapy appear to be the major determinant of what treatment is received.
2',3'-didehydro-3'-deoxythymidine (d4T) is a pyrimidine analogue and inhibitor of reverse transcriptase with potent in vitro activity against human immunodeficiency virus (HIV). A phase I trial of d4T was conducted in 41 HIV-infected patients, 12 with AIDS and 29 with AIDS-related complex (ARC). Thirty-six patients were evaluatable. The maximum tolerated dose was 2 mg/kg/day. The dose-limiting toxicity was sensory peripheral neuropathy, which occurred in 20 patients (55%). Four patients (11%) developed hepatotoxicity. Five (14%) developed anemia requiring a transfusion but not discontinuation of drug. The mean +/- SE plasma elimination half-life at all dose levels was 1.2 +/- 0.09 h. Increased or stable absolute CD4 counts were seen in most patients. The majority of patients with detectable serum p24 antigen levels had a persistent decrease by 6 months. d4T is a promising drug for patients with AIDS or ARC. This clinical trial is continuing to determine the minimal effective dose.
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