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H Akaza

Publications and source records attributed to H Akaza.

At least 19 recordsLinked to original sources
PubMed2007

Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients.

To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A alone in Japanese men with untreated advanced prostate cancer. A total of 205 patients with stage C/D prostate cancer were randomized to either LHRH-A+once-daily oral bicalutamide 80 mg or placebo. Primary study variables have been reported previously. Secondary variables included: time to achieve prostate-specific antigen < or = 4 ng/ml, time-to-treatment failure (TTTF), time-to-disease progression (TTP), overall survival (OS), adverse events and adverse drug reactions. Following combination therapy with bicalutamide 80 mg, there were significant (P<0.001) advantages over LHRH-A alone in terms of TTTF and TTP, but the difference in the interim OS was not statistically significant. First-line combination therapy with bicalutamide 80 mg in Japanese patients with advanced prostate cancer offers significant benefits over LHRH-A alone, with respect to TTTF and TTP. Follow-up for OS continues.

Aged↗
PubMed2006

Incidence of venous thromboembolism following major abdominal surgery: a multi-center, prospective epidemiological study in Japan.

BACKGROUND: Venous thromboembolism (VTE) has been considered to be a rare surgical complication in Japan. AIM: To investigate the incidence and risk factors of VTE in Japanese patients undergoing major abdominal surgery. METHODS: A prospective, multi-center epidemiological study was conducted from December, 2001 to August 2002 in 39 medical institutes throughout Japan. A total of 173 patients with general (n = 128), gynecologic (n = 23), and urologic (n = 22) surgery were analyzed. For the diagnosis of deep vein thrombosis (DVT), bilateral venography was performed in all patients. Lung ventilation/perfusion scintigraphy was carried out in patients suspected of pulmonary thromboembolism (PTE). RESULTS: There were 36 patients with distal DVT (20.8%) and five patients with proximal DVT (2.9%). One patient was diagnosed as PTE. Overall, VTE was diagnosed in 42 patients (24.3%). By univariate analysis, only age (60 years or older) was identified as a significant risk factor in the whole study population. When analyzed by the stepwise multiple logistic regression model, female gender, operation site, age, and operation time were four risk factors found to be significant. The incidence of VTE was closely related to the number of risk factors that patients had. As many as 44% of patients with three or four risk factors developed VTE while those with one or two risk factors showed about a 17% incidence of VTE. Four patients lacking any risk factors did not develop VTE. CONCLUSIONS: Venous thromboembolism is common in Japanese patients undergoing major abdominal surgery. Pharmacologic thromboprophylaxis is considered essential, particularly in those patients with multiple, potential risk factors.

Abdomen↗
PubMed2004

Adjuvant goserelin improves clinical disease-free survival and reduces disease-related mortality in patients with locally advanced or localized prostate cancer.

This article reviews the clinical disease-free survival (DFS) and disease-related mortality (DRM) data from published prospective, randomized trials of goserelin, given alone as adjuvant treatment or combined with a nonsteroidal antiandrogen as neoadjuvant treatment in patients with locally advanced or localized prostate cancer. Four trials were of radiotherapy and one of radical prostatectomy. The five trials included > 3500 patients and the median follow-up was 4.8-7.1 years. There were statistically significant improvements in clinical DFS with goserelin support relative to the control treatment in all five trials (each log-rank P </= 0.004). Reductions in the risk of DRM were statistically significant with adjuvant goserelin vs no adjuvant treatment to support radiotherapy in one trial, and with adjuvant goserelin or bilateral orchidectomy vs no adjuvant treatment to support radical prostatectomy in another (each log-rank P </= 0.001). Time-point estimates of the rates of clinical DFS and DRM were in favour of goserelin support vs control in all five trials at 5 years and in the three trials for which data were available at 8 years. Goserelin support therefore improves clinical DFS and reduces DRM after radiotherapy or radical prostatectomy. Adjuvant goserelin may offer greater clinical benefits than neoadjuvant hormonal treatment.

Antineoplastic Agents, Hormonal↗
PubMed2003

Effects of combination therapy with a luteinizing hormone-releasing hormone agonist and chlormadinone acetate on rat prostate weight and plasma testosterone levels.

We investigated whether the combination of chlormadinone acetate (CMA) and a luteinizing hormone releasing hormone (LH-RH) agonist, leuprorelin acetate (leuprorelin), more markedly decreased ventral prostate and seminal vesicle weights and plasma sex hormone levels in male rats. Four weeks after administration of 0.28, 0.84 or 2.8 mg/kg of leuprorelin, ventral prostate weights significantly decreased (53.8, 54.4 and 64.1%) and the plasma testosterone levels significantly lowered, but not dose-dependently. After repetitive administrations of 3 and 30 mg/kg/day of CMA, the rates of ventral prostatic atrophy were 37.1 and 65.9%, respectively. Although there was no change in the plasma testosterone level at 3 mg/kg, 30 mg/kg of CMA significantly decreased the level. A combination of leuprorelin (0.28 mg/kg) and CMA (3 or 30 mg/kg) more potently induced ventral prostatic and seminal vesicle atrophy than leuprorelin alone. Furthermore, a combination of leuprorelin and CMA (30 mg/kg) more markedly decreased the plasma testosterone level. According to the pharmacokinetic data for CMA in male rats, the doses of CMA correspond to the clinical dose. These findings suggest that combination therapy with an LH-RH agonist and CMA is more useful than therapy with the agonist alone in the treatment of prostate cancer.

Androgen Antagonists↗
PubMed2003

Clinical course and immune response of a renal cell carcinoma patient to adoptive transfer of autologous cytotoxic T lymphocytes.

The cytotoxic T lymphocyte (CTL) is a promising candidate for an effector cell in adoptive immunotherapy for renal cell carcinoma (RCC). Here we report the clinical course and in vivo immune responses of a RCC patient with bulky retroperitoneal lymph node (RPLN) metastases who received adoptive autologous CTL therapy. A 56-year-old woman diagnosed with RCC with multiple RPLN metastases underwent unilateral nephrectomy. Autologous RCC cells were primary-cultured from surgical specimens. Before addition of peripheral blood mononuclear cells (PBMC) for CTL induction, subconfluent RCC cells were irradiated with 50 Gy. The PBMCs were then cultured on RCC cells in the induction medium supplemented with four kinds of interleukins. The induced CTLs showed the potent killing activity against autologous RCC cells in a typical MHC-class I-restricted manner. The patient received three courses of CTL therapy with a total of 10.2 x 10(9) cells, and the RPLN mass decreased markedly in size after the second course. Eosinophilia and enhanced CTL inducibility from peripheral blood were observed after CTL administrations. The patient was progression free without further treatment; however, she developed rapidly progressive glomerulonephritis more than 1 year after the last treatment. The patient died of newly developed metastases 27 months after the start of CTL therapy. At autopsy, viable RCC cells were found in multiple metastatic sites. However, only diffuse fibrous tissue was observed in the responding RPLN mass. Apparent histological divergence was observed between primary and metastatic sites.

Carcinoma, Renal Cell↗
PubMed2003

A prospective and randomized study of primary hormonal therapy for patients with localized or locally advanced prostate cancer unsuitable for radical prostatectomy: results of the 5-year follow-up.

OBJECTIVE: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer. PATIENTS AND METHODS: Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years. RESULTS: The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively. CONCLUSION: The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.

Aged↗
PubMed2003

Induction of potent antitumour natural-killer cells from peripheral blood of patients with advanced prostate cancer.

OBJECTIVE: To examine whether antitumour natural-killer (NK) cells can be induced from peripheral blood mononuclear cells (PBMCs) of patients with advanced prostate cancer, as cell therapy using antitumour immune cells is a promising candidate treatment but such patients generally have a suppressed immune response against cancer cells. PATIENTS AND METHODS: PBMCs were obtained from 10 patients (four with stage D2 and six with stage B or C disease). For the NK cell expansion, PBMCs were co-cultured with irradiated HFWT cells, a cell line originating from Wilms' tumour, in RHAM alpha culture medium supplemented with 5% autologous plasma and interleukin-2 (200 U/mL) for 2 weeks. RESULTS: When PBMCs were co-cultured with HFWT cells, lymphocytes from all patients had a 20- to 130-fold expansion after 2 weeks of culture. The CD16+ CD56+ cells constituted >70% of the proliferated lymphocyte population. The induced NK cells had significantly greater cytotoxicity against a prostate cancer cell line (PC-3) than lymphocytes cultured with no HFWT cells. There was no significant difference in growth and phenotypes of lymphocytes and the induced NK cell activity between patients with stage D2, B or C. CONCLUSION: NK cells with potent cytotoxic activity against prostate cancer cell lines from patients with advanced prostate cancer were selectively expanded. Further investigation is needed to determine whether this approach could be a candidate for cell therapy for advanced prostate cancer.

Aged↗
PubMed2001

Genetic heterogeneity of surgically resected prostate carcinomas and their biopsy specimens is related to their histologic differentiation.

BACKGROUND: In human prostate carcinogenesis, many genetic analyses including conventional loss of heterozygosity (LOH) studies and microsatellite LOH analyses using the polymerase chain reaction method have revealed frequent LOH events at specific regions on chromosomes 3p, 7q, 8p, 10q, 16q, 17q, and 18q. METHODS: Using the laser-captured microdissection method, the authors extracted genomic DNA from 23 cases of prostate carcinomas including 59 different lesions and 8 biopsy specimens. Using (32)P-labeled primers, the authors analyzed six microsatellite loci (D3S647, D3S1228, D7S522, D8S137, NEFL, and D10S190) at which frequent LOH events have been reported. RESULTS: Of 10 cases in which the authors found LOH at any of the loci, 8 cases showed a heterogeneous LOH pattern. In four cases, the authors also found replication error (RER) at some of the loci examined. There was no significant relation between histologic differentiation and frequency of LOH or RER events. The overall LOH rate was found to be significantly lower in foci at classification pT2 (1 of 28 foci, 3%) compared with those at classification pT3 (13 of 44 foci, 30%). In pT3 samples, LOH events in extraglandular foci (9 of 23 foci, 39%) tended to be more frequent compared with those in intraglandular foci (8 of 41 foci, 20%). The patterns of LOH events in biopsy specimens correlated well with those in foci from surgical material showing the same histologic characteristics. CONCLUSIONS: Prostate carcinoma is a genetically multicentric carcinoma, and the genetic heterogeneity is well correlated with histologic differentiation. The frequency of LOH events increased according to the degree of tumor progression.

DNA Replication↗
PubMed2001

Treated natural history of superficial bladder cancer.

BACKGROUND: The present study was conducted to examine the natural history of superficial bladder cancer. METHODS: One hundred and forty-four patients with superficial bladder cancer who had been treated with transurethral resection of bladder tumor (TURBt) alone were analyzed. RESULTS: The non-recurrence rate was 64.8% at 36 months and 61.2% at 60 months after TURBt. When the non-recurrence rate after TURBt was analyzed by background variables, the rate differed significantly between the solitary tumor group and the multiple tumor group. The tumor recurrence hazard curves for the entire population had one high peak before 500 days and another slight peak around 1500 days after TURBt. CONCLUSIONS: These results will provide basic information useful when evaluating new regimens of intravesical instillation therapy for prophylaxis of superficial bladder cancer after our complete TURBt in the Nara Uro-Oncology Research Group.

Aged↗
PubMed2001

Detection and cloning of a protein recognized by anti-human prostate-specific antigen (PSA) antibody in the rat ventral prostate.

Prostate-specific antigen (PSA), a 33 kDa glycoprotein produced in the epithelium of the human prostate, has become established as a useful tumor marker for prostate cancer in man. Since reports of homologous proteins in animals other than primates have been lacking, the present investigation was carried out to identify any PSA-like protein in rats. Immunoblot analysis using a specific monoclonal anti-human PSA antibody detected a 32 kDa immunoreactive protein in the ventral lobe of the rat prostate, but not in other lobes or in other tissues. Positive immunostaining was observed only for the luminal surface of the glandular epithelium and the intraductal fluid in the ventral prostate. Sequence analysis of a cDNA for the rat PSA-like protein, cloned by immunoscreening of an expression cDNA library prepared from the ventral lobe, revealed identity to the rat submaxillary gland S3 kallikrein. Human PSA also belongs to the kallikrein family. Thus, this protein produced in the rat ventral prostate was suggested to be a possible counterpart of human PSA.

Amino Acid Sequence↗
PubMed2001

AgNOR count in resting cells (resting NOR) is a new prognostic marker in invasive bladder tumor.

PURPOSE: We have previously demonstrated that the AgNOR count in proliferating cells is a predictor of tumor recurrence in superficial bladder tumor (J. Urol. 162 (1999), 63-68). In the present study, we evaluate the type of AgNOR associated with cell cycles as a prognostic factor in invasive bladder tumor using a double staining technique employing both AgNOR and MIB-1 labelling. MATERIALS AND METHODS: Forty-four paraffin sections of invasive bladder tumors were stained simultaneously with AgNOR and MIB-1. The number of AgNORs in proliferating (MIB-1 positive) or resting (MIB-1 negative) cells were counted from a total of 100 nuclei. Correlations between MIB-1 associated AgNOR count and clinicopathological parameters were statistically analyzed. RESULTS: The AgNOR count in proliferating cells (proliferating NOR) was significantly higher than that in resting cells (resting NOR) (p<0.01). The resting NOR in tumors with distant metastases was significantly higher than that in tumors without metastases (p<0.05). Patients with a low resting NOR tumor had a better prognosis than those with a high resting NOR tumor, whereas the proliferating NOR was not associated with survival. Survival analysis revealed that the resting NOR was the most powerful prognostic marker in patients with invasive bladder tumor (p<0.05). CONCLUSIONS: Resting NOR had a predictive value in the prognosis of patients with invasive bladder tumor.

Adult↗
PubMed2001

Long-term results of donor-specific blood transfusion with cyclosporine in living related kidney transplantation.

Donor-specific blood transfusion (DST) was introduced to achieve better graft survival. However, its benefits are controversial considering the immunosuppression of cyclosporine (CYA) or tacrolimus (Tac), and its long-term effects have not been well discussed. Of the 40 patients who received DST with CYA, 3 (7.5%) became cross-match positive. Of the 37 patients with negative cross-match, 34 patients received a one-haplotype-matched kidney and were compared to patients with one-haplotype-matched kidney transplant without preoperative DST (n = 13). Acute rejection within 3 months after transplant was 29.4% in the DST group, and 15.4% in the non-DST group. All rejection episodes were steroid resistant in the non-DST group. If the graft survival rates were calculated excluding non-immunological graft loss, graft survival rate was 91.0 and 72.8% at 5 and 10 years in the DST group, and 83.3% at 5 and 10 years in the non-DST group, respectively. The two graft survival lines converged 7 years and 7 months after transplantation. No beneficial effect of DST was statistically evident under CYA immunosuppression. In terms of the severity of acute rejection or the onset of chronic rejection, DST induced a small benefit, however, which seemed to disappear within 8 years after transplantation.

Acute Disease↗
PubMed2001

[Platinum compounds in cancer therapy--past, present, and future].

Platinum cytotoxics play an important role globally in the management of solid tumours. Cisplatin sets the standard for efficacy in both regions with careful administration to reduce nephrotoxicity. Carboplatin is associated with neurotoxicity, but has become the leading product in the US due largely to the easier to manage toxicity profile. Both agents have been widely used in both registered and non registered indications and are frequently combined with other cytotoxics. In Japan, cisplatin has been used successfully at low doses in combination with 5-FU based regimens and appears to achieve a synergistic effect, but controlled data are not yet available. More recently oxaliplatin (Europe) and nedaplatin (in Japan) have been introduced, but their clinical roles in therapy have yet to be established. One of the limiting features of the first generation of platinum compounds is that a significant proportion of tumours develop cross resistance to platins due to either changes in uptake or excretion, intracellular detoxification or accelerated DNA repair. The forum discussed the possibility for the development of better new platinum compounds, A new platin agent which had lower toxicity and higher efficacy across a wide range of cancers without the development of resistance would be a significant step forward. If the tolerability profile was suitable, an oral formulation may improve the quality of life for patients but this must not be at the expense of efficacy. Even after the introduction of new target based drugs, platinum cytotoxics are likely to be used to reduce the tumour mass and in some cases can be expected to potentiate the effects of the new agents. In preclinical studies, ZD0473 has been shown to by-pass some major mechanisms of resistance and has the potential to achieve these objectives and is now being evaluated in clinical studies in both Japan and the West.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Clinical effects of a 3-month formulation LH-RH agonist (Zoladex LA 10.8 mg depot) in patients with prostate cancer].

Pharmacodynamics (PD), anti-tumor effects, safety and pharmacokinetics of a 3-month formulation of goserelin (Zoladex LA 10.8 mg depot: "10.8 mg depot") were investigated in a collaborative multicenter study. Study participants were 40 Japanese patients with prostate cancer comprising 20 untreated patients and 20 switch patients who had been receiving Zoladex 3.6 mg depot for 3 months or longer. Serum testosterone levels, serum LH levels, prostate-specific antigen (PSA) levels and drug concentrations were measured until 12 weeks after a single subcutaneous dose of 10.8 mg depot. Anti-tumor effects were evaluated by means of changes in the tumor lesions and the PSA levels at 12 weeks. After administration to the untreated patients, 10.8 mg depot reduced serum testosterone to the castrate range within 4 weeks and the reduction was maintained for up to 12 weeks. In the switch patients, serum testosterone suppression that had been produced by previous treatment with Zoladex 3.6 mg depot was maintained for up to 12 weeks following 10.8 mg depot administration. The anti-tumor effect at 12 weeks was 90.0% including partial response cases. The ratio of PSA normalization at 12 weeks was 75.0%. Fifty-seven adverse reactions were observed in 27 of the 40 patients (67.5%), but none were clinically significant. Although a disease flare presented as urinary retention in 1 of the untreated patients, all patients completed the study. Serum goserelin was detected up to 12 weeks after the administration of 10.8 mg depot. In conclusion a single dose of 10.8 mg depot showed a satisfactory PD-effect and brought about clinical efficacy persisting for at least 12 weeks and was well tolerated in patients with prostate cancer.

Adenocarcinoma↗
PubMed2001

[Management of a hormone dependent cancer with endocrine therapy--prostate cancer].

We offer a historical overview of endocrine therapy for prostate cancer. Hormone therapy remains the cornerstone of treatment for patients with locally advanced or metastatic prostate cancer. Although this therapy has been traditionally performed by oral estrogen or bilateral orchiectomy, there are now two most important pharmacological hormonal therapies: LH-RH agonist and antiandrogen therapy. We do not have yet sufficient data to conclude whether maximal androgen blockade from the combined use of an LH-RH agonist and an antiandrogen will prolong the survival in patients with metastatic prostate cancer, nor to conclude whether neoadjuvant androgen ablation therapy improves the disease-free survival of patients after radical prostatectomy. New treatment strategies and modalities such as LH-RH antagonists, intermittent hormonal therapy, and antiandrogen monotherapy are appearing and being tested in clinical trials. However, to date there is still no effective therapy for patients who have hormone refractory disease.

Androgen Antagonists↗