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S Isaka

Publications and source records attributed to S Isaka.

At least 19 recordsLinked to original sources
PubMed2001

Site-dependent effect of O-glycosylation on the conformation and biological activity of calcitonin.

We synthesized seven O-glycosylated calcitonin derivatives, each with a single GalNAc residue attached to either Ser or Thr, and studied their three-dimensional structure and biological activity to examine site-dependent effects of O-glycosylation. The CD spectra in an aqueous trifluoroethanol solution showed that the GalNAc attachment at Thr6 or Thr21 reduced the helical content of calcitonin, indicating that the O-glycosylated residue functions as a stronger helix breaker than the original amino acid residue. Only the GalNAc attachment at Ser2 or Thr21 retained the hypocalcemic activity of calcitonin. This result corresponded well to that of the calcitonin-receptor binding assay. The GalNAc attachment other than Ser2 or Thr21 perturbed the interaction with the receptor, resulting in the loss of the hypocalcemic activity. The biodistribution did not change much among the seven derivatives, but some site dependency could also be observed. Thus, we can conclude that the O-glycosylation affects both the conformation and biological activity in a site-dependent manner.

Acetylgalactosamine↗
PubMed2000

Isolation and characterization of a novel TP53-inducible gene, TP53TG5, which suppresses growth and shows cell cycle-dependent transition of expression.

Through a strategy of direct cloning of TP53-binding DNA sequences from human genome DNA, we have identified a novel TP53-target gene, termed TP53TG5 (TP53-target gene 5). This gene, localized to chromosome band 20q13.1 by fluorescence in situ hybridization, encodes a 290-amino-acid peptide with no significant homology with any known proteins in the public database. A colony-formation assay using human glioblastoma cell line T98G, which lacks wild-type TP53 and expresses no endogenous TP53TG5, revealed a growth-suppressive effect of the TP53TG5 gene product. Furthermore, immunohistochemical studies, following transfection of T98G with plasmid designed to express green fluorescent protein-fused TP53TG5, revealed cell cycle-dependent intracellular localization of this protein. Our results suggest that functional studies of TP53TG5 may provide new insights into the complex physiological activities of TP53.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗
PubMed1999

Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group.

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Aged↗
PubMed1999

[Cyclophosphamide-induced bladder cancer in a patient with Wegener granuromatosis].

Cyclophosphamide (CPM) has been considered to be a factor of bladder carcinogen. A 60-years old woman had been received a total dose of 370 g of CPM for the treatment of Wegener's granulomatosis since August, 1977. She was consulted to our department with chief complaint of macrohematuria in August, 1986. Hemorrhage cystitis was diagnosed and cystoscopy and urine cytology were performed as follow-up schedule in every year. In 1996, urine cytology showed class IV and cystoscopy revealed multiple nonpapillary tumors. Abdominal computerized tomography demonstrated a low density mass on the posterior wall of the bladder. A transurethral cold cup biopsy showed G3 transitional cell carcinoma (TCC). Radical cystectomy and tubeless cutaneous ureterostomy was performed on December 6, 1996 and histopathological diagnosis was TCC, G 3, pT3 bNXM0. She died of liver failure due to metastatic bladder cancer after seven months postoperatively.

Carcinoma, Transitional Cell↗
PubMed1998

[Bilateral pheochromocytomas with von Hippel-Lindau's disease: a case report].

A case of bilateral pheochromocytomas with von Hippel-Lindau's disease (VHL) is reported. A 46-year-old woman who had hyperglycemia was admitted to our hospital because of abdominal tumors. Her elder sister and niece had been diagnosed as VHL. Ultrasonography, CT, and MRI revealed bilateral adrenal tumors. Noradrenaline levels in serum and urine were elevated and 131I-MIBG scintigraphy showed accumulation in bilateral adrenal glands. Moreover, she had bilateral renal cysts and cerebellar hemangioblastoma. Bilateral adrenalectomies were performed and pathological diagnosis was pheochromocytoma. This is the seventh case of bilateral pheochromocytomas with VHL reported in Japan.

Adrenal Gland Neoplasms↗
PubMed1997

Surgical approach to tumor thrombus of renal cell carcinoma at the level between hepatic vein and diaphragm.

BACKGROUND: The curative resection of tumor thrombus of renal cell carcinoma often provides a good prognosis, but the best surgical method for resection at the level between hepatic vein and diaphragm is still a matter of controversy. METHODS: We performed transabdominal surgery without cardio-pulmonary bypass on 4 patients with tumor thrombus at the level between hepatic vein and diaphragm. The surgical procedures were as follows: The right lobe of the liver was separated and detached from the retroperitoneum, and then the vena cava was clamped just below the diaphragm simultaneous with clamping the porta hepatis. After complete circulatory isolation of the vena cava, the tumor thrombus was resected. RESULTS: There were no severe complications postoperatively. Two patients died of cancer 18 and 38 months after surgery, and the other 2 are alive without evidence of disease after 62 and 66 months. CONCLUSION: This anatomically rational approach is thought to be a good alternative to the pull-through method or cardio-pulmonary bypass for removing a tumor thrombus at this level.

Carcinoma, Renal Cell↗
PubMed1997

[Prostate cancer].

Up to stage B1 or prostate cancer with N0-1 positive lymph node may be curable by monotherapy of either radical prostatectomy or irradiation. Localized but more advanced stages (B2 and C), however, are difficult to cure. To further improve the prognosis in these stages, a new treatment modality is proposed; pelvic lymphadenectomy, followed by irradiation with neoadjuvant and adjuvant endocrine therapy. An average 2-year followup is favorable. Further studies is awaited to make conclusion.

Androgen Antagonists↗
PubMed1996

Recommended dose of flutamide with LH-RH agonist therapy in patients with advanced prostate cancer.

BACKGROUND: In a recent study by the Casodex Combination Study Group, USA, patients in a flutamide (750 mg/day) plus LH-RH agonist group showed a high treatment failure rate, mainly due to flutamide-induced diarrhea and hepatotoxicity. Our current study was conducted to determine the optimal dose of flutamide for use in this type of combination therapy. METHODS: In a randomized, multicenter study, 30 patients (hormone untreated; stage C or D) were divided into 2 groups: flutamide 250 mg (125 mg x 2; 14 patients) and flutamide 375 mg (125 mg x 3; 16 patients, and each dose combined with either goserelin acetate (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin and leuprolide were administered to patients in a 1:1 ratio. Flutamide monotherapy at a daily dose of 375 mg was determined to be the optimal dose in Japan in our previous phase II study. The endpoints of this pilot study were the objective response and adverse events during the 12-week treatment. RESULTS: The objective response rate was 83.3% in the flutamide 250 mg group and 85.7% in the flutamide 175 mg group according to the Japanese response criteria for prostate cancer. Elevated PSA levels fell to within the normal range in 83.3% of the patients in the former group and in 93.3% of the patients in the latter group. One patient administered 250 mg of flutamide experienced diarrhea, while the serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide and 4 patients administered 375 mg of flutamide. CONCLUSIONS: Based on the findings of this pilot study of maximal androgen-depletion therapy for advanced prostate cancer, 375 mg/day of flutamide is recommended in combination with an LH-RH agonist. Assessment of the effects of our recommended regimen on longer term survival, quality of life and antiandrogen withdrawal syndrome of patients treated requires additional patients and time for follow-up.

Aged↗
PubMed1996

[Prognostic factors in patients with non-metastatic renal cell carcinoma].

BACKGROUND: The objective of this study is to evaluate prognostic factors of non-metastatic renal cell carcinoma using univariate and multivariate statistical methods. METHODS: 390 patients who were performed radical surgery in our hospital between 1960 and 1994 were entered to this study. Kaplan-Meier method with log-rank test and Cox's proportional hazard model were used for statistical analysis. RESULTS: Chief complaints, tumor localization on kidney, tumor size, fever, hemoglobin, C-reactive protein, erythrocyte sedimentation rate, immunosuppressive acidic protein, operative method, blood loss, histologic grade, cell type, pT, pN and pV revealed to have prognostic statistical significance in the univariate analysis. Whereas, sex, age, blood type, hypertension, affected side and preoperative embolization did not. In the multivariate analysis of the preoperatively evaluable factors, CRP, tumor size and tumor localization proved to be significant prognostic predictors in this order. When the pathological factors were included to the multivariate analysis, pV, historogic grade and pN revealed to be significant prognostic predictors in this order. CONCLUSION: These results suggest that pathological factors were significant prognostic predictors for non-metastatic renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1996

[QOL assessment in the treatment of prostate cancer].

It has been stressed that evaluation of QOL is an essential part of a clinical trial. We started a prospective randomized trial for advanced prostate cancer comparing various types of endocrine therapies which included QOL study in 1992. The QOL was evaluated before, one month after, three months after, and 12 months after the start of therapy. An EO-RTC questionnaire system was translated into Japanese and its reproducibility was assessed before the study. Eighty-four patients who were registered to the trial replied before the start of therapy. Endocrine therapies showed good effects on patients' QOL, especially in the domains of disease-related symptoms, physical feelings, mental distress and social life, which were improved significantly three months after the start of therapy. Sex life was seen to deteriorate from the therapies. In conclusion, the results of our QOL study reflected well the effects of endocrine therapy, and are expected to provide useful information for evaluation of the different effects of each treatment group.

Antineoplastic Agents, Hormonal↗
PubMed1996

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral↗
PubMed1996

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral↗
PubMed1996

[Bilateral renal cell carcinoma with extension into the vena cava associated with von Hippel-Lindau disease: a case report and review of the literature].

We report a case of bilateral renal cell carcinoma with extension into the inferior vena cava associated with von Hippel-Lindau (VHL) disease. A 52-year-old woman was referred to our hospital for further examination of bilateral renal masses which were found on abdominal ultrasound examination. The diagnosis was confirmed with renal angiography, abdominal computed tomography (CT), abdominal magnetic resonance-CT (MRI), cavography and head MRI. Right adjunctive nephrectomy and removal of the tumor thrombus were performed. She has been treated with interferon-alpha after the operation. The analysis of her DNA by using single strand conformational polymorphism revealed a VHL gene abnormality.

Carcinoma, Renal Cell↗
PubMed1996

[Cavernous hemangioma of urinary bladder: a case report and review of the literature].

We report a case of cavernous hemangioma of the urinary bladder treated with transurethral resection (TUR). A 58-year-old woman was admitted to our department with the chief complaint of macroscopic hematuria. Cystoscopy revealed a red sessile tumor 2 cm in diameter, at the internal urethral orifice. The tumor had a mostly low signal intensity, partly high signal intensity, on T1-weighted, coronal magnetic resonance (MR) images. Computed tomography and T2-weighted MR images did not delineate the tumor. TUR was performed, and the specimen was pathologically diagnosed as cavernous hemangioma of the urinary bladder. A brief description of the case is provided and the literature is reviewed.

Female↗
PubMed1995

[Neoadjuvant endocrine therapy prior to nerve-sparing radical prostatectomy in patients with stage T2 prostatic cancer].

Radical prostatectomy is the effective treatment for clinical T2 prostatic cancer. However, clinical T2 stage is often understaged preoperatively. The objective of neoadjuvant therapy is to increase the curability of surgery to understaged patients. The present study was based on patients who had had neoadjuvant endocrine therapy (LH-RH agonist) prior to radical nerve-sparing prostatectomy for T2 prostatic cancer. Sexual function were estimated before and after surgery. Ten patients with a mean age of 64.6 years (range 57-71 years) and biopsy-proven cancer received this treatment modality. No patients had evidence of lymph node metastasis by the pelvic computerized tomography and their bone scan was negative for metastasis. Clinical stage was T2a in 3 patients and T2b in 7. The grade of these tumors as assessed on prostatic biopsy before neoadjuvant endocrine treatment was well differentiated in 3 and moderately differentiated in 7. The duration of neoadjuvant endocrine therapy was 3.6 months (range 2-5 months) in average. Serum levels of prostatic specific antigen (PSA) were examined monthly and prostate volume was measured by transrectal ultrasonography before and after neoadjuvant treatment. Decrease in serum PSA values was observed from an average level of 8.6 ng/ml (range 3.1-17.5 ng/ml) determined prior to neoadjuvant treatment to an average of 1.1 ng/ml (range 0.6-3.3 ng/ml) determined after neoadjuvant treatment. An average reduction of prostatic volume was 25.3% (range 7.4-56.7%) after neoadjuvant therapy. Pathological effects of the neoadjuvant therapy by the criteria proposed by Japanese Urological Association were Grade (G) 0a in 3 patients, G0b in 4, G1 in 2 and G2 in 1. Of patients who had 10 stage T2 cancer before treatment, 4 had pT2 and 6 pT3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Prophylactic chemotherapy with intravesical instillation of adriamycin and oral administration of 5-fluorouracil after surgery for superficial bladder cancer. The Japanese Urological Cancer Research Group for Adriamycin.

The Japanese Urological Cancer Research Group for Adriamycin has conducted a series of clinical trials to investigate the efficacy and safety of prophylactic intravesical chemotherapy for superficial bladder cancer. In the third trial, reported herein, patients with recurrent bladder cancer or multiple primary cancer were selected and randomized to one of four groups using the envelope method after complete resection of the original tumors. Group A was given Adriamycin alone, group B received oral 5-fluorouracil (5-FU), group C was given Adriamycin and oral 5-FU, and group D served as the control group. Of the 544 patients registered, 331 were evaluable for the purpose of this study. The administration of 5-FU (group B) failed to prevent the recurrence of bladder tumors. Although group C (both Adriamycin and 5-FU) did not fare better than group A (Adriamycin only), Adriamycin was effective in preventing the recurrence of tumors, especially in high-risk patients with recurrent and multiple tumors. The risk of recurrence was reduced to 0.21 (95% confidence interval, 0.10-0.44) relative to the control group. There was no indication of a synergistic effect between 5-FU and Adriamycin. As side effects, cystitis syndrome was observed in 23%-30% of the patients in the Adriamycin groups and mild myelosuppression was observed in the 5-FU groups.

Administration, Intravesical↗