Biomedical subjects
T Kotake
Publications and source records attributed to T Kotake.
Correlation of c-myc expression with nuclear pleomorphism in human renal cell carcinoma.
The expression of the c-myc gene product in renal cell carcinomas was examined by immunostaining with monoclonal antibody (mAb) MYC-1. The effects of preservation and fixation of tissues on staining were first examined. In cryostat sections fixed with 4% buffered formalin for 15 min, staining was observed in the nucleus. On the other hand, in paraffin sections after fixation with 10% formalin, staining was observed in the cytoplasm, but not in the nucleus. Because c-myc protein has been shown to be a nuclear protein, the finding that c-myc protein was not detectable in the nucleus appeared to be due to the preservation or fixation procedures used. Therefore, cryostat sections fixed with 4% formalin were used to investigate the correlation between the reaction of MYC-1 mAb and nuclear pleomorphism in primary and metastatic renal cell carcinomas. Among 41 primary tumors, positive staining was observed in 2 of 17 tumors (12%) of grade 1, 17 of 21 (81%) of grade 2, and all 3 (100%) of grade 3. Among 17 metastatic tumors, positive staining was not observed in any of the 5 (0%) of grade 1 but was observed in 2 of 4 (50%) of grade 2 and all 8 (100%) of grade 3. Thus, the frequency of the positive reaction with MYC-1 mAb was correlated with nuclear pleomorphism in primary and metastatic renal cell carcinomas. The reaction of Ki-67 mAb, which recognized a nuclear antigen present in proliferating cells, was also correlated with nuclear pleomorphism. These findings suggest that the c-myc gene product plays a role in cell proliferation in renal cell carcinomas.
Phase II trial of carboplatin in patients with advanced germ-cell testicular tumors and transitional cell carcinomas of the urinary tract.
Carboplatin, an analog of cisplatin, was evaluated in a phase II study involving 25 patients with advanced testicular tumor and 45 with transitional cell carcinoma (TCC) of the urinary tract; 21 and 38 cases, respectively, were evaluable for response. Prior treatment with cisplatin-based chemotherapy had occurred in 7 of the testicular cancer patients and in 11 with TCC. The response rate (complete + partial response) in testicular tumors was 47.6%. The best response rate was observed in seminomas (70.0%), whereas the response rate in nonseminomas was 27.3%. The seminoma patients had mainly stage IIIA or less than IIIA disease, with metastatic lesions restricted to the lymph nodes. Three responses were seen in patients previously treated with cisplatin. In TCC, the response rate was 18.4%. Good-risk patients were treated with a dose of 400 mg/m2 every 4 weeks, whereas poor-risk patients received a lower dose of 300 mg/m2. The response rates for good-risk patients were 50.0% in testicular lesions and 26.1% in TCC. For poor-risk patients, the response rates were 40.0% and 6.7%, respectively. Carboplatin was well tolerated, with no significant renal impairment or ototoxicity detected. Nausea and vomiting were experienced by 51.7% of patients, but the severity was low; half of these patients demonstrated WHO grade I toxicity. However, myelosuppression was severe. In conclusion, carboplatin demonstrated activity in both testicular tumors and TCC and is worthy of further study, especially in combination with other active drugs.
[Reduction of urinary oxalate excretion by administration of calcium and citrate].
Oxalic acid seems to be more important for the formation of calcium oxalate stone than calcium. Three grams of calcium lactate and 3 g of uraly U were administered to 35 urolithiasis patients, whose stones were mainly composed of calcium oxalate. Urinary oxalate level was reduced significantly without raising urinary calcium level by the administration of the two drugs for two weeks. The reduction of oxalic acid was particularly remarkable in patients without hypercalciuria. The mechanism of action of these drugs and the relation to dietary management were discussed.
[VM-26 and VP-16 salvage therapy for refractory germinal testicular cancers].
Thirteen evaluable patients with germinal testicular cancers failing to be cured with first-line therapy (refractory) were treated by salvage chemotherapy. Ten patients received salvage chemotherapy with VM-26 (50 mg/m2, twice a week X 6 weeks) and cisplatin (CDDP, 20 mg/m2 for 5 consecutive days every 3 weeks for 3-4 times) (P-VM), 3 patients were also treated by radiation therapy, and 3 patients received VP-16 (100 mg/m2) and CDDP (20 mg/m2) (P-VP), all given daily for 5 consecutive days every 3-4 weeks for 4-5 courses. Of 13 evaluable patients, 6 (46%) had complete response (CR) (three cases were also treated with radiation therapy), 4 (31%) achieved partial response (PR), and 3 (23%) had no response. Limited to 7 patients treated with only P-VM therapy, there were 3 (43%) CR and 4 (57%) PR. Nine patients (69%) remained alive and were continuously disease free 18 to 84 months (median 48 months). Hematologic toxicity was severe, but with no death related to sepsis. Salvage chemotherapy with VM-26 or VP-16 and cisplatin offers potentially curative treatment to patients with refractory testicular cancer. The addition of radiation therapy to salvage chemotherapy was also effective.
[Development of a serum-free medium and primary culture of human renal cell carcinomas by serum-free culture].
Ovomacroglobulin and LDL fraction of egg yolk were effective to maintain the growth of established human cancer cell lines (Kato III, QG-90, Raji). A serum-free medium (BEM-841) containing 10 mM HEPES, 50 micrograms/ml of ovomacroglobulin, 0.1% (V/V) of LDL fraction of egg yolk, 10(-8) M catalase, 5 micrograms/ml of insulin, 5 micrograms/ml of transferrin, 5 ng/ml of selenium, 1 mg/ml of BSA, and 0.5% (V/V) of trace elements was developed. Primary culture of renal cell carcinoma cells was successful in 3 cases out of 6 by using BEM-841 medium without overgrowth of the fibroblast.
[Primary culture of human bladder carcinomas and establishment of human bladder carcinoma cell line by serum-free culture].
It was possible to cultivate cells from bladder carcinoma tissues in 4 cases out of 6 without the overgrowth of fibroblast. A new human transitional cell carcinoma cell line (HAMT-1) was established in longterm tissue culture by using serum-free medium (BEM-841) which had been developed by us. The tissue for culture was taken from a 61-year-old Japanese male with grade 3 transitional cell carcinoma of the bladder. The microscopic features of the cell in cultures and of the tumors developed in nude mice resembled closely that of the original tumor. Electron microscopy of the cultured cells and the tumors developed in nude mice revealed characteristics of the epithelial origin of these cells with microvilli, junctional complex and scarce filament formation. Blood TPA level of the nude mouse with the transplanted tumor was equally high as that of the patient from whom the original tumor had been taken. The cells were anchorage independent in the serum-free medium but anchorage dependent in the medium containing 5% FCS. Anchorage dependency could not be restored by the addition of collagen and fibronectin. The doubling time of the cells were 18-20 hours. The chromosome counts of the cell line ranged from 59-78 with a modal count of 74.
[Transurethral treatment of bladder diverticulum].
13 patients with bladder diverticula underwent transurethral diverticulectomy. Follow-up cystograms were obtained six months after surgery. The diverticulum had shrunk in all cases and had totally disappeared in 11 (85%). Transurethral diverticulectomy is a simple, effective, and safe procedure. It takes only a short time and can easily be combined with transurethral operations for obstructions of the lower urinary tract.
[Multidisciplinary treatment of advanced testicular tumors].
Present status and problems of multidisciplinary treatment for advanced testicular tumors were reviewed. In this paper, we presented the treatment results of 69 patients with advanced testicular cancer treated by multidisciplinary treatment. The primary PVB therapy induced a CR in 39 patients (56.5%), and 8 patients of them relapsed. After primary chemotherapy 40 patients, incomplete responders and relapsed cases, underwent salvage therapy. Salvage chemotherapy with CDDP and VM-26 or VP-16 was performed in 19 patients, and induced a CR in 10 (58.5%). Salvage surgery was done in 29, and produced NED in 22 patients (75.9%). As overall results of salvage therapy, 25 of 40 patients are living with NED, 3 are alive with tumors, and 12 patients died of the disease. As final results of the multidisciplinary treatment, of 69 patients with advanced testicular tumors 48 patients are living with NED and 3 patients with tumors, and 18 patients died of the disease. A overall cure rate was 73.9%. The overall 8-year survival rates of the 69 patients was 70.5%. The survival rate of 39 CR-patients, 23 PRs and 7 NRs was 94.9%, 45.7% and 0% at 4 years, respectively. The 8-year survival rates according to clinical stage for the last 10 years were 100% in stage I, 74.0% in stage II, and 70% in stage III. The survival rates for 10 years from 1968 to 1978 were 88.3% in stage I. 60% in stage II, and 33.3% in stage III. The treatment results were so satisfactory. To reach the treatment goal for advanced testicular tumors, importance of aggressive multidisciplinary treatment was emphasized.
[Clinical evaluation of chemotherapy in urologic cancer].
In this paper, we will attempt to place the current status of the chemotherapy for testicular cancer, urothelial tumors and penile cancer in perspective. Perhaps the most exciting development in the past decade has been the demonstration of a significant number of complete responders (CR) to CDDP combined chemotherapy in patients with advanced testicular cancers. A CR rate of 60% was observed in the PVB therapy or VAB-6 therapy and no evidence of disease (NED) increased to 80% with salvage therapy. In our study of 43 evaluable patients, the CR rate was 60% and the NED rate was 81%. The activity of salvage chemotherapy with VP-16 for refractory testicular cancer has been well known with a CR rate of 19-38%. Among 13 evaluable patients with refractory cases, the CR rate was 46% with VP-16 or VM-26 salvage chemotherapy. The chemotherapeutic results of advanced urothelial cancers were also reviewed. In the present time, M-VAC therapy is thought to be the most effective regimen with a CR rate of 37%. In the chemotherapy of the primary lesion of penile cancer, bleomycin is most effective with a response rate of 60-70%. But for the primary lesion, there has been no effective chemotherapy.
[The significance of serum prostate-specific antigen, gamma-seminoprotein and prostatic acid phosphatase as prostate cancer markers].
Prostate-specific antigen (PA), gamma-seminoprotein (gamma-Sm) and prostatic acid phosphatase (PAP) have been evaluated in patients with prostate cancer, benign prostatic hyperplasia (BPH), chronic prostatitis and acute prostatitis. PA has proved to be diagnostically more sensitive than PAP and gamma-Sm for the detection of prostatic cancer. Although PA may be elevated more frequently than PAP and gamma-Sm in patients with BPH, there are possibilities that these patients with elevated PA and normal PAP and gamma-Sm may have prostatic cancer or precancerous conditions not detectable in our routine diagnostic procedures. We report two cases of prostatic cancer with persistently elevated PA and diagnosed after repeated biopsies. Our data suggest that PA is a sensitive and useful tumor marker for the diagnosis of prostatic cancer. PAP and gamma-Sm in combination with PA may serve as more useful for differential diagnosis and confirmation of prostatic cancer.
[A case of exohepatic pedunculated hepatocellular carcinoma suspected of adrenal tumor].
A case of exohepatic pedunculated hepatocellular carcinoma that was clinically diagnosed as nonfunctioning adrenal tumor is reported. A 66-year-old man was admitted to our hospital for further examination of unstable angina pectoris. Abdominal echogram and CT scan revealed a large tumor in the right retroperitoneal space. Selective right renal arteriography demonstrated that the tumor was fed by the capsular branch of right renal artery and the right adrenal artery. Adrenal function was normal. Preoperative diagnosis of right nonfunctioning adrenal tumor was made. On operation we found that the tumor was pedunculated from the liver and adhered massively to both right kidney and vena cava. The tumor and right kidney were removed. A histopathological examination demonstrated well differentiated hepatocellular carcinoma (Edmondson's grade II type).
[Clinical problems in patients who were exposed to carcinogens].
The study of carcinogenesis is most advanced in bladder cancer through the study of what is called aniline bladder cancer. Bladder cancer has also played a key role in introducing the concept of 'occupational' cancer. Industrial Safety and Health Law defines various chemical substances as carcinogens of 'occupational' cancer, many of which are related to the urinary tract tumor, including benzidine, beta-naphthylamine, alpha-naphthylamine, 4-aminodiphenyl, 4-netrodiphenyl, auramine, magenta, orthotolidine, dianisidine, dichlorobenzidine and paradimethylaminoazobenzene. When a patient has been exposed to any of these substances, a diagnosis of 'occupational' cancer is made after consultation in the Central Labor Standards Council. Few bladder cancer patients are acknowledged as victims of 'occupational' cancer. In most cases the cause of bladder cancer remains unknown. However, cases of cancer caused by chemical substances are increasing, and many other chemical substances are probably carcinogenic. Although regulations on 'occupational' cancer have been completed, there are many cases of inconvenience in practice. In this report I investigated into such clinical problems and also studied the above-mentioned carcinogens.
[Clinical statistics on inpatients and operations at the Department of Urology, the Center for Adult Diseases, Osaka, 1984-1988].
Statistical observation on inpatients and operations at our department between January 1984 and December 1988 revealed the following results: 1) The total number of inpatients was 1962 (male: 1658, female: 304). The most frequent diseases were bladder cancer (30.0%), benign prostatic hypertrophy (19.2%), prostatic cancer (10.6%) and renal cancer (6.7%). 2) The total number of operations was 1699. The most frequent operations were transurethral resection (TUR) of bladder tumor (22.8%), TUR prostate (20.7%), TUR biopsy (6.5%) and total cystectomy (5.4%).
[A case of primary ureteral squamous cell carcinoma associated with calculus].
A case of primary squamous cell carcinoma of the ureter associated with ureteral calculus is presented. A 66-year-old woman was admitted to our hospital, with the chief complaint of macroscopic hematuria in October, 1985. A kidney-ureter-bladder X-ray and drip intravenous pyelography failed to reveal the calculus shadow clearly. However, computerized tomographic scan revealed the calculus shadow clearly adjacent to the ureteral tumor, and retrograde pyelography revealed the filling defect on a third lower portion of the left ureter. She was diagnosed with tumor of the ureter associated with the calculus. She underwent complete nephroureterectomy with excision of a periureteral cuff of the bladder. The tumor was diagnosed histologically as squamous cell carcinoma. Metastases and recurrence of tumor have never occurred on July, 1987. Forty-four cases of the primary ureteral squamous cell carcinoma could be collected in the Japanese literature. Moreover, we deal with this disease associated with the ureteral calculus.
The treatment of advanced renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine.
Explore the source record for details and available documents.
[CT in the diagnosis of squamous cell carcinoma of the urinary bladder].
Explore the source record for details and available documents.
Comparative analysis of growth factors in normal and pathologic human prostates.
Growth factors, as detected by DNA synthesis stimulating activity for BALB/c 3T3 cells, in normal, benign hypertrophic and cancerous human prostates were analyzed. The total content (units per gram of tissue) in benign hypertrophic prostate was two to four times higher than those in normal and cancerous prostates. In all the three groups, heparin-binding growth factor, growth factor adsorbed to heparin-Sepharose in the presence of 0.5 NaCl. accounted for about 80-95% of the total growth factor content. Qualitative analysis using a heparin-Sepharose column revealed two types of heparin-binding growth factor in the prostates, one eluted from the column at 1.2-1.3 M NaCl and the other at 1.5-1.8 M NaCl. The latter was the predominant type in all groups. In addition to the growth factors detected with BALB/c 3T3, a growth factor with specific action upon MC3T3-E1 mouse osteoblasts was found in prostatic cancer, but not in normal and benign hypertrophic prostates.