Biomedical subjects
Publications and source records attributed to D Haagensen.
We cared for a 64-year-old woman who experienced increased serum creatinine levels after 8 days of ciprofloxacin therapy. She had previously received a course of several antibiotics, including gentamicin. Renal function returned to normal 18 days after the ciprofloxacin was discontinued. This is the eighth reported case of nephrotoxicity associated with this agent. The mechanism and predisposing factors have not been defined.
Three [35S]methionine-labeled polypeptides released by T47D human breast cancer cells have been identified as corresponding to two proteins previously described in breast gross cystic disease fluid. A Mr 43,000 protein was immunoprecipitated by polyclonal antibodies to the Zn-alpha 2-glycoprotein. A Mr 18,000 and a Mr 13,000 polypeptide were both immunoprecipitated by four monoclonal antibodies directed against four separate epitopes of Mr 15,000 gross cystic disease fluid protein, a major protein that is characteristic of apocrine gland secretions. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, purified Mr 15,000 gross cystic disease fluid protein migrated at the level of the Mr 18,000 protein of T47D cells. The proteins were regulated by androgens and progestins. In addition to a general stimulation of protein secretion, 5 alpha-dihydrotestosterone (DHT) specifically increased, by 2- to 20-fold, the release of the Mr 43,000 and Mr 18,000 proteins into the medium. DHT also increased the cellular level of the Mr 18,000 protein, as shown by immunoprecipitation with a Mr 15,000 gross cystic disease fluid protein antibody, which suggests a stimulation of protein synthesis. The progestin 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione also increased the release in the medium of the Mr 43,000 and Mr 18,000 proteins, but higher molar concentrations were required than in the case of DHT. The induction of these proteins by DHT and 17,21-dimethyl-19nor,4,9-pregnadiene-3,20-dione was specifically inhibited by the antiandrogen flutamide which has no effect on other progestin-regulated proteins. This suggests an effect mediated by the androgen receptor. This is the first report on the identification of two proteins induced by androgens in a human breast cancer cell line. These proteins should be useful in studying the role of androgens in human mammary tumors and their mechanism of action in cell culture.
Preliminary clinical trials indicate that transient stimulation of breast and prostate cancer growth by hormonal means may enhance tumor sensitivity to chemotherapy. In none of these studies, however, has an attempt been made to measure parameters that might reflect perturbations in cell kinetics induced by the treatment schedules. While conducting two, controlled, randomized clinical trials in advanced breast cancer and prostate cancer using a similar approach, we have measured plasma levels of two tumor markers, carcinoembryonic antigen (CEA) and breast gross cystic disease fluid protein (GCDFP-15). These served as a possible means of monitoring hormonal stimulation of tumor growth. Both markers failed to increase following administration of estrogens to patients with breast cancer and of androgens to men with prostatic carcinoma. In contrast, transient stimulation of tumor growth probably occurred as shown by exacerbation of symptoms and, in patients with prostate cancer, rise in acid phosphatase. We conclude that CEA and GCDFP-15 are not useful for monitoring pertubations in tumor cell kinetics induced by hormone stimulative protocols.
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