[Subrenal capsule assay--host reaction and tumor size].
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Biomedical subjects
Publications and source records attributed to R Nemoto.
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A model system of human prostate carcinoma in nude mice for searching out a method to protect the bone from cancer cells is described, in which the transplanted human prostate cancer cells were inoculated subcutaneously over the calvaria in nude mice after the periosteum wa disrupted. The tumor induced osteolysis associated with osteoclast proliferation accompanied with reactive new bone formation. This osteolysis was evaluated by measuring the increased area of bone resorption by its reduced opacity to X-ray, and histology. Etidronate disodium, a diphosphonate derivative, at a dose of three mg./kg. and 10 mg./kg. s.c. protected the bone by decreasing the extent of osteolysis as judged by the above criteria. This inhibition was obtained with no apparent effect on the growth of the tumor. These results are discussed in light of recent clinical work, showing that this animal model is a useful tool to test the effect of new drugs against osteolysis of cancer as well as to study the biology of local interaction between bone and cancer cell.
A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10 per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0 per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0 per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10 per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10 per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.
The high incidence of metastatic bone resorption in urological cancer makes it necessary for clinicians to look for a valid experimental model to investigate basic interaction between cancer cells and bone in order to improve the treatment. A new model of bone resorption has been defined, namely the subcutaneous injection of tumor cell suspensions of invasive transitional cell carcinoma of the bladder (MBT-2) into mice after the periosteum of the calvaria has been disrupted. The tumor induced osteolysis associated with osteoclast proliferation with reactive bone formation. Moreover, we were able to show hypercalcemia accompanied with local bone resorption in this model.
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Intra-arterial infusion chemotherapy with adriamycin (ADM) was carried out in 32 patients with bladder cancer prior to total cystectomy. An oblique incision approximately 12 cm long was made in the gluteal region to expose either the superior or inferior gluteal artery, into which a Teflon catheter was inserted and fixed. The distal end of the catheter was taken out from under the skin in the precordial region. Via this catheter, a single dose of 10 mg ADM was injected twice a week. Superior-gluteal-artery infusion chemotherapy was performed in 7 patients; the 5-year survival rate was 14.3%, which was not as high as expected. Inferior-gluteal-artery infusion chemotherapy was performed in 25 patients. Cisplatin (CDDP) was used with ADM in 8 patients. Radiation and/or hyperthermia were used in 11 patients. The 5-year survival rate in these 25 patients was 58.4%, which was considered to be satisfactory. Of these 25 patients, 5 were stage-T4 cases; for these, the treatment was ineffective, and all 5 died within 2 years. Of the 6 patients at stage T2, 1 died, as did 1 patient with carcinoma in situ (CIS). Of the 13 patients with bladder cancer at stage T3, 3 died; lymph-node metastases were found in all 3 of these cases. Of the 25 patients who received inferior-gluteal-artery infusion chemotherapy, 9 died of cancer; all 9 died within 2 years due to distant metastases. There was no evidence of recurrence in any patient who survived for 2 years or more after total cystectomy. Therefore, inferior-gluteal-artery infusion chemotherapy may be effective as a preoperative adjuvant therapy with no serious side effects.
A new experimental method to test the effect of drugs on tumor-induced osteolysis using a bladder tumor in mice has been designed. The method consisted of inoculating MBT-2 tumor cells s.c. over the calvaria in mice, resulting in a local tumor causing fragmentation of the bone. This was accompanied by adjacent osteoplastic changes, which were evaluated by X-ray and histological examination. Etidronate disodium (EHDP), a diphosphonate derivative, at a dose of 3 mg/kg to 30 mg/kg s.c. protected the bone by decreasing the extent of osteolysis as judged by the same criteria. Therapy with EHDP prolonged the survival period. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumor.
Histologic characteristics of prostate cancer in Japan were evaluated in a retrospective analysis of 267 cases. These specimens were graded by the Gleason histopathologic grading system, and the proportional distribution of histologic features and the death rate were compared with those of Gleason's results in the literature. The system demonstrates significant correlation with mortality rates for each grade group in our cases, and it was also found that the death rates as obtained by our figures were comparable to those of Gleason in each category. The results help to provide the basis for future comparative multinational trials of prostate cancer.
The high incidence of metastatic bone disease in urological cancer makes it necessary for clinicians to look for a valid experimental model to investigate the basic interactions between cancer cells and bone in order to improve the treatment. A new model of bone resorption was defined, namely the subcutaneous injection of tumor cell suspensions of serially transplanted renal cell carcinoma in nude mice after disruption of the periosteum of the calvaria. The tumor induced osteolysis associated with osteoclast proliferation with reactive bone formation. The X-p film from nude mice calvaria showed the same multiple osteolytic punched-out lesions as those of the patient's skull.
The detection and recording systems for urethral sounds during micturition were developed. This procedure was termed as "urophonography" and its recording as "urophonogram". Classification of urophonograms was undertaken on the basis of analyzing normal healthy male volunteers, and patients with benign prostatic hyperplasia. Four types of urophonogram were demonstrated. Urophonography was useful for investigation of dysfunctional voiding, and lower urinary tract obstruction. Urophonography will be a new approach to urodynamic investigations.
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