Biomedical subjects
Publications and source records attributed to M Osafune.
Late recurrence of renal cell carcinoma is unusual. Of 43 patients who underwent curative nephrectomy more than 10 years before, 2 cases (4.7%) had late recurrence. The 2 cases, both female patients, had late recurrence 12 and 19 years from the date of nephrectomy. The clinical aspects of late recurrence are discussed briefly.
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The anti-tumor effect of twice a week instillation of 30 mg mitomycin C combined with 200 mg cytosine arabinoside dissolved in 30 ml saline was studied in 37 bladder tumor patients. Endoscopic or histological disappearance of the tumor was observed in 19 cases, average instillation being 16.4 times. Small (less than 1 cm in diameter), low grade, low stage and villous-surfaced tumors were more sensitive to this therapy. Further more, in the cases showing a complete response, frequency of the intravesical tumor recurrence significantly decreased compared with the cases showing no response. The clinical results of this therapy are compared mainly with those of TUR performed at our hospital, and the usefulness and clinical limitation of this kind of management in the treatment of bladder tumors are discussed.
Ten patients with advanced transitional cell carcinoma were treated with the combination chemotherapy (CISCAF) consisting of cis-platinum (CDDP), cyclophosphamide (CPM), adriamycin (ADM) and 5-fluorouracil (5-FU). There were 8 males and 2 females with a median age of 57 years (range 33-76). Prior to this chemotherapy, all primary lesions were resected surgically; one patient received irradiation, one interferon. CDDP (15 mg/m2) with mannitol diuresis and ADM (7 mg/m2) were given daily for 5 days. CPM (200-300 mg/m2) was given on day one, and 5-FU (200-300 mg/m2) on day 2. Courses were repeated every 3-4 weeks for 3 courses and later every 2 months. All patients were evaluable for toxicity and 9 for response. There were 3 (33%) partial and 2 minor responses. Survival difference between responders (PR + MR) vs non-responders (NC + PD) was significant during the 30-120 days of observation, but not significant throughout the whole period (generalized Wilcoxon test). The overall toxicity due to chemotherapy was generally mild, except for one irreversible nephrotoxicity and one gastric hemorrhage treated surgically.
Thirty-three patients with advanced transitional cell carcinoma of the urinary tract (23 bladder cases, 8 ureter cases, and 2 renal pelvis cases) were treated by three-drug combination chemotherapy using two protocols (protocol I: Adriamycin 50 mg/m2, cyclophosphamide 500 mg/m2, and 5-fluorouracil 500 mg/m2, protocol II: Adriamycin 50 mg/m2, cyclophosphamide 500 mg/m2, and cis-platinum 50 mg/m2). Protocol I induced responses in three of 19 patients (16%), (1 complete response, 2 partial responses), and protocol II (I complete response, 4 partial responses) in five of 14 patients (36%). The overall response rate was 24%. The duration of response was relatively short (median duration 5.1 months). The combination therapy was relatively well tolerated except in three patients, including two mortalities. In our study, three-drug combination chemotherapy with Adriamycin, especially that including cis-platinum, was effective against transitional cell carcinoma of the urinary tract, but the results were not completely satisfactory.
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The circulating anti-RCC cytotoxic antibodies of eighteen RCC patients, preoperatively, and one inoperable case were studied by 51Cr release CDC and ADCC assays, using the cultured human RCC cell line, OUR-10. Circulating cytotoxic anti-RCC antibodies were detected in eight patients as CDC antibodies. The patients with a low pathological grade had a significantly higher percentage (P less than 0.05) of positive antibody responses.
In vitro cultivated cells derived from normal human renal cortex were characterized morphologically and biochemically. Although the epithelial monolayer was composed of heterogeneous cells, it included cells with a surface structure similar to microvilli as well as some resembling the desmosome between neighboring cells. Enzymatic studies revealed a marked decrease in alkaline phosphatase activity, and the activity of gamma-glutamyl transpeptidase was also reduced to about one-fifth of that in the original tissue. The electrophoretic mobility of the enzyme was not identical with that of normal kidney or of the novel enzyme in renal neoplastic tissue. Lactate dehydrogenase activity was similar to that of normal kidney tissue but the isozyme pattern was completely inverted. These cells responded to the addition of 10 ng per ml of parathyroid hormone in culture medium and there was a 33 fold increase in intracellular cyclic adenosine monophosphate. Estrogen specific binding protein was not detectable in the monolayer cells. These results clearly indicated that the biologic transformation observed in the cultivated normal cells was not attributable to simple fetalism or dedifferentiation, but was a more complicated process.
A newly established cell line, OUR-10, from human renal carcinoma seems to have the same gamma-glutamyl transpeptidase as the novel one which was found recently in renal carcinoma tissue; the enzymic properties such as electrophoretic mobility, Km value, molecular weight, thermostability, the effects of urea, sodium dodecyl sulfate and sulfhydryl reagents, the effects of amino acids, cations and EDTA, and the binding behavior to a concanavalin A-Sepharose column were the same as those of the novel gamma-glutamyl transpeptidase found in renal carcinoma tissue. The immunological properties of the gamma-glutamyl transpeptidase (GGTP) of OUR-10 examined by inhibition tests and tests of cross-reactivity with anti-normal kidney GGTP antibody were also the same as those of the novel gamma-glutamyl transpeptidase. These results may mean that the novel gamma-glutamyl transpeptidase originates from the cancer cells, and can be used as a marker for identification of this cell line, OUR-10.
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A case of renal cell carcinoma (RCC) presenting various histologic growth patterns, including papillary, tubular and solid arrangements, and an area resembling sarcoma are described. In order to identify RCC of high versatility of renal carcinosarcoma, electrophoretic studies of tissue alkaline phosphatase (Al-P) and gamma-glutamyl transpeptidase (gamma-GTP), as well as histochemical studies of these enzymes, were conducted. The Al-P was proved to be bond type alone and the gamma-GTP corresponded with the novel isozyme associated with RCC tissue. Moreover, these two enzymes were found to be distributed in every part of different histologic appearance. It was concluded from these results that the histologic pleomorphism of the case herein reported was due to morphologic transformation of the neoplastic cells sharing essentially identical enzymatic nature.
Lactate dehydrogenase (LDH) activity and isoenzyme were determined in 27 human renal carcinoma (RC) tissues. Although LDH-1 and LDH-2 were predominant in the normal kidney, a completely inverted isoenzyme pattern was observed in 16 carcinomas. The others, however, showed either a normal or an incompletely inverted pattern. The LDH activity in the tumours with a completely inverted pattern was significantly higher than the activity of incompletely inverted or normal kidney pattern. It was also found that the isoenzyme pattern was more closely correlated with cell type than the grade of malignancy of the tumour, 14 out of the 16 cases of the completely inverted pattern being of the clear cell type, and 9 out of the 11 cases of incompletely inverted or normal kidney pattern being of either granular cell or mixed cell type. These results seemed to well substantiate an opinion that in clear cells anaerobic glycolysis provides a major energy source, whereas granular cells seek energy source primarily in TCA cycle and subsequent oxidative phosphorylation.
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A case of transitional cell carcinoma arising from a bladder which was left behind for more than 24 years without pyocystis syndrome is described. A search in the literature revealed 10 cases of defunctionalized bladder that developed tumors over a rather short latent period ranging from 3 months to 7 years, and mostly with evidence of severe bladder infection.
Another Kasahara-variant alkaline phosphatase isoenzyme was found in 2 out of 25 human renal cell carcinoma tissues. This enzyme electrophoresed in a single diffuse band which is cathodal to but continuous with the liver alkaline phosphatase. After neuraminidase treatment, this enzyme electrophoresed in the same position as that of neuraminidase-treated Kasahara isoenzyme. The enzymic properties of another neuraminidase-treated Kasahara-variant enzyme such as inhibitions by L-phenylalanine, L-homoarginine, L-tryptophan, and L-leucine, effects of inorganic phosphate, urea, and sodium dodecyl sulfate, heat stability, and the reactivity with concanavalin-A are consistent with those of Kasahara isoenzyme. On Ouchterlony's double diffusion, the precipitin lines of Kasahara and the new variant enzyme produced by antibody to Kasahara isoenzyme fused completely. These facts may indicate the occurrence of another Kasahara-variant isoenzyme.
A cell line, designated as OUR-10, has been established from a renal carcinoma in a Japanese woman. This cell line forms monolayers of polygonal epithelial cells with scattered round or dendritic cells and exhibits multilayering. With electron microscopy, differentiated surface structures that resemble the microvilli characteristic of renal carcinomas can be seen even at the 60th transfer. The cells have a hypodiploid karyotype with modal numbers of 39 and 40. No marker chromosomes were seen, but definite nonrandom loss of three chromosomes in Group D and one in Group E were recognized. The doubling time was estimated as approximately 32 hr in exponentially growing cultures, and the cells formed colonies in soft agar with an average efficiency of 25%. Heterotransplantation into the cheek pouch of immunosuppressed hamsters produced tumors that were histologically similar to the original cancerous tissue. The electrophoretic mobility of gamma-glutamyl transpeptidase extracted from the cells coincided with that of a novel isozyme found in human renal carcinoma tissue, and the genetic phenotype of the glucose-6-phosphate dehydrogenase was proved to be the B phenotype. The antigenic structure of HLA was determined as HLA-A2, 11; B5, 40, which was the same as that of peripheral blood lymphocytes of the woman with renal carcinoma.