Biomedical subjects
Publications and source records attributed to M Slavik.
We report two cases of breast cancer in whom meningioma subsequently developed and provide a brief review of the literature. A hormonal interrelationship is suggested. The knowledge of this potential association is important in the interpretation and treatment of patients with breast cancer who develop central nervous system manifestations.
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The Mg2+ATPase activity of liver plasma membranes decreases markedly with increasing temperature above 30 degrees. This negative temperature dependency is counteracted by the binding of wheat germ agglutinin, concanavalin A, or Ricinus communis agglutinin (at concentrations greater than or equal 0.5 mg/ml) to membranes prior to assay of the enzyme. With one of these lectins bound, the enzyme has a single energy of activation between 20 degrees and 45 degrees. The binding of dimeric succinyl concanavalin A, soybean agglutinin, fucose-binding lectin from Lotus tetragonolobus, or the leucoagglutinin from Phaseolus vulgaris does not alter the temperature dependency of the enzyme. The latter two lectins, however, do prevent the concanavalin A-induced activation of the enzyme at 37 degrees. At saturating substrate concentrations, the enzyme is not inhibited by any of the lectins tested over a wide range of concentrations. Cytochalasin B and colchicine separately or in combination have little influence on the lectin-induced enhancement of enzyme activity. Chlorpromazine and vinblastine sulfate each partially prevent the activation and in combination do so completely. Treatment of the membranes with the detergent Lubrol-PX or phospholipase A prevents activation of the enzyme by concanavalin A. The results are consistent with a restriction by the lectin of an environment which is normally too disordered for maximal enzyme activity above 30 degrees.
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Daunomycin, like its anthracycline analog adriamycin, is a cardiotoxic antitumor antibiotic. Reports on 5,613 patients receiving daunomycin were reviewed for cardiotoxicity. Two distinct patterns of cardiotoxicity were defined, congestive heart failure (cardiomyopathy) and electrocardiographic changes. Dose-response curves were constructed using the percent incidence of cardiomyopathy versus the total dose of daunomycin in mg/m2. There was a dose-response relationship between the total dose of daunomycin and the development of cardiomyopathy, both in children and adults. The children seem more susceptible to the drug-induced cardiomyopathy. The electrocardiographic changes in the children and adults did not show a dose-dependent relationship, were present consistently even at the lowest dosage levels, and did not predict for subsequent development of cardiomyopathy. The dose-response curves constructed enable the clinician to judge the relative risk of developing cardiomyopathy at a given total dosage level and allows comparison of the human experience with the experimental animal model data.
Estramustine phosphate is a nitrogen mustard derivative of estradiol that has been advocated for the treatment of prostatic cancer. The compound was designed with the hope that the estrogen moiety would direct the alkylating moiety to estrogen-dependent malignancies, where the alkylating moiety would be released specifically. Preclinical and clinical data are reviewed to determine to what extent that challenging concept is fulfilled. In addition, we have examined critically the efficacy of this drug for the treatment of prostatic cancer. From available data it appears that there is no evidence that the alkylating moiety of estramustine phosphate is specifically freed in estrogen-dependent tissues. Estramustine phosphate appears to be an active compound with acceptable toxicity in prostatic cancer. However, further clinical trials must be undertaken to clarify the future role of estramustine phosphate in the treatment of prostatic cancer.
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Cis-diamminedichloroplatinum (II) (DDP) leads the series of platinum coordination complexes, a new class of cytotoxic agents. The antitumor and toxic effects of this drug are discussed. It has displayed encouraging results in testicular tumors. The drug's therapeutic effectiveness has also been recognized in a variety of other solid tumors, particularly ovarian, bladder, and head and neck malignancies. Gastrointestinal, renal, audiologic, and relatively minor hematologic toxicities may be encountered, but promising methods have been developed to increase the therapeutic index of DDP.
A review of 498 patients treated with high-dose methotrexate (MTX) with citrovorum factor rescue revealed 29 drug-related deaths. Until the important factors in those deaths are identified, the use of high-dose MTX should be limited to institutions that possess the necessary supportive facilities and the ability to measure serum levels of the drug.
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Hexamethylmelamine (HMM) has been undergoing clinical trials for about a decade under the sponsorship of the National Cancer Institute. It has been tested in Phase II and III cooperative group studies and has a wide spectrum of activity in solid tumors. Its activity is most marked in ovarian cancer, lymphomas, and carcinoma of the cervix; the drug is also active in bronchogenic carcinoma and carcinoma of the breast. Considerable clinical evidence suggests a lack of cross-resistance between HMM and alkylating agents. the currently popular dose is 300 mg/m2/day p.o. for indefinite periods if tolerated. The dose-limiting toxicity is neurologic, but gastrointestinal side effects and a moderate degree of myelosuppression are also observed. Combination chemotherapy using HMM is underway in ovarian and lung cancer. Futher exploration of its activity as a single agent in tumors such as those of the bladder, prostate, and uterus, and in combination chemotherapy in lymphomas, and mammary, cervical, and pulmonary tumors is warranted.
Nafoxidine is a nonsteroidal antiestrogen available as an investigational agent from the Investigational Drug Branch of the National Cancer Institute. It has been used effectively in the treatment of breast cancer patients. A cumulative response rate of 31% is reported for a total of 200 patients treated with this drug. Most patients have been treated with a dose of 60 mg three times a day. Side effects include dryness of skin, photosensitivity reactions and, less commonly, partial hair loss. There is a strong correlation of response to nafoxidine with the presence of estrogen receptor in the tumor and also with the response to previous hormonal treatment. Nafoxidine is a useful addition to the list of hormonal treatments in the therapy of breast cancer.
A tentative evaluation is proposed for the clinical status of 15 early and investigational drugs in human solid tumors.
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