Microencapsulated mitomycin-C therapy in renal-cell carcinoma.
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Biomedical subjects
Publications and source records attributed to R Nemoto.
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In vitro sensitivity of an established cell line from human urinary bladder cancer to various chemotherapeutic agents was determined by 14C-leucine incorporation into the target cells. Of 12 drugs tested, Carboquone, Neocarzinostatin, Actinomycin D, Adriamycin, Mitomycin C and Chromomycin A3 produced intensive cytotoxic effects, while Thio-Tepa, Bleomycin, 5-Fluorouracil and Vincirstine were less cytotoxic, Intravesical instillation of Carboquone, one of the most toxic agents in vitro, resulted in complete or partial tumor remission in 6 of 9 patients with bladder cancer. Prophylactic effects of periodic intravesical Carboquone were also indicated in 7 of 8 patients who had experienced recurring superficial bladder tumors.
Microencapsulated Mitomycin C with ethylcellulose was infused into isolated dog kidneys through the renal artery. The capsules were lodged mainly at cortico-medullary junction, where the drug was released from the capsules. Vascularity of kidney was reduced moderately.
While lymphocytes from normal persons exhibited cytotoxicity against T24 cells, prednisolone at a concentration as low as 10(-7) M significantly inhibited the cytotoxic reactions and almost complete inhibition was observed at the concentration of 10(-4) M. The inhibitory effect was shown to be progressively decreased when prednisolone was added during the cytotoxicity assay of normal human lymphocytes. These findings suggest that the cytotoxicity of lymphocytes from normal persons can be suppressed by immunosuppressive effect of prednisolone and that the early phase in the cytotoxic reaction is considerably sensitive to prednisolone.
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Two cell lines, T24 and MGH-U1, established from human urinary bladder carcinoma showed typically epithelial features. Although the proliferating cell population presented a polymorphic appearance including polygonal and elongated cells, ultrastructural studies failed to identify different types of cells in each cell line. Extensive cytoplasmic organelles, microvilli on the cell surface and cell continuity with the junctional complex were common findings in both the cell lines. Virus-like particle was not detected. Chromosome numbers of these cell lines were distributed from hypertriploidy to hypertetraploidy. T24 cell line contained a large number of elongated cells and well developed microvilli as compared with MGH-U1 cell line. The present results suggest that T24 cell line has been transformed to a relatively uniform cell population during the long-term culture as referred to in a previous report.
The cell cycle of the human bladder carcinoma cell line (MGH-U1 cells) was prolonged immediately after low dose of triethylene thiophosphoramide (Thio Tepa). Although the elongated cell cycle time seemed to return to the control level 48 hr following the treatment, there still remained postsynthetic accumulation and postmitotic diminution in the cell population and the cells were insensitive to high dose of the agent. The present results suggest that Thio Tepa is less effective for G2 cells, but more effective for G1 or S cells.
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A case of hemodialysis for acute renal failure during the thirty-fourth week of gestation is reported. Subsequently, the patient delivered a normal viable baby, weighing 1,790 gm. Maternal renal function returned to normal after delivery.
The first case of primary hyperparathyroidism associated with renal cell carcinoma, nasopharynx carcinoma and thyroid carcinoma is reported. Selective venous sampling with radioimmunoassays for parathyroid hormone was helpful in the differentiation of primary hyperparathyroidism from hypercalcemia associated with malignancy.
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A comparison was made of 14C-leucine incorporation and cell viability of T24 human bladder carcinoma cells after treatment with Thio-Tepa, a potent alkylating agent. It was found that Thio-Tepa produced concentration-dependent damage in these cells and also that 14C-leucine incorporation correlated well with cell viability. 14C-leucine incorporation can be used as a reliable and rapid screening test for the assessment of the relative potencies of anticancer drugs.
Stimulation of normal peripheral blood lymphocytes (PBL) by phytohemagglutinin (PHA) and production of PHA-induced cytotoxicity were investigated. PBL transformation stimulated by PHA was measured by 3H-thymidine incorporation, and the cytotoxicity was assayed by measuring the reduction of 14C-leucine incorporation in to target cells after interaction with PHA-treated PBL. The cytotoxicity of PHA-treated PBL showed dose response curves which corresponded with that of PBL transformation. Reduced 14C-leucine incorporation of target cells caused by cytotoxic PBL would be a reliable measure of immune reactions.
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