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H Akaza

Publications and source records attributed to H Akaza.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Management of non-seminomatous germ cell tumors of the testes].

Since the advent of cisplatin-based chemotherapy in the 1970s, testicular cancer has become a model for curable cancer. We review the current treatment options for non-seminomatous germ cell tumors (NSGCT) of the testes. Surveillance is considered to be the most widely accepted option for stage I NSGCT in Japan. Because of the high relapse rate of about 30% in this setting, the establishment of a risk-adapted treatment protocol is warranted in stage I NSGCT. In early stage II NSGCT, both the primary RPLND and the primary chemotherapy show equivalent cure rates. These options give different balances of toxicity; namely, ejaculation disorders and drug induced infertility. In the treatment for NSGCT with good prognosis, both three courses of BEP and four courses of etoposide and cisplatin are appropriate and standard chemotherapy regimens.

Antineoplastic Agents, Phytogenic↗
PubMed2000

[Assessment of quality of life as an endpoint of cancer treatment].

In order to evaluate the efficacy of cancer therapy, it is important to assess quality of life (QOL) as an endpoint in addition to tumor size reduction and survival. Thus, assessment of QOL has been included in many clinical trials of cancer therapy. These studies use various multiple QOL scales. We have translated the English version of the FACT-BL (Functional Assessment of Cancer Therapy for Bladder Cancer) questionnaire into Japanese. In the process, we performed a comparative study simultaneously using this questionnaire and EORTC QLQ-C30J which is generally used for various cancer patients. We found that FACT-BL provides a more sensitive assessment of the QOL of patients with advanced bladder cancer than EORTC QLQ-C30J. This means that we should carefully choose a questionnaire which is directly related to disease site, symptoms and treatment and can be conducted clinically. In the future, the assessment of QOL will have an important role as an endpoint of cancer treatment if the methodology and infrastructure, such as coordinators and data centers, are established in Japan.

Clinical Trials as Topic↗
PubMed2000

Transgenic rats carrying copies of the human c-Ha-ras proto-oncogene exhibit enhanced susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine bladder carcinogenesis.

We have established a transgenic rat line carrying three copies of the human c-Ha-ras proto-oncogene with its own original promoter region, Jcl/SD-TgN(HrasGen)128Ncc (Hras128) rat. c-Ha-ras protein from expression of transduced and endogenous c-Ha-ras genes could be detected in the bladder epithelium of untreated transgenic rats. To examine their susceptibility to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis, male transgenic and wild-type littermates were treated with 0.05% BBN in their drinking water for 10 weeks and then killed at week 20. The numbers and volumes of total macroscopic bladder tumors including both transitional cell papillomas and carcinomas (TCC) per rat were much greater in Hras128 rats than in their wild-type counterparts. The numbers of carcinomas per rat were also significantly greater in Hras128 rats. Two cases of TCC exhibiting invasion of the bladder muscle layer, which is extremely rare in the wild-type animals under the experimental conditions used, were also observed in Hras128 rats. The GGC-->GAC mutations at codon 12 of the transgene were observed in only two TCC out of 21 bladder tumors (9.5%), assessed by RFLP analysis and direct sequencing. SSCP analysis did not show any endogenous c-Ha-ras gene mutations. One of 25 tumors (4.0%) in wild-type rats had an endogenous c-Ha-ras gene mutation at codon 12 that was detected (GGA-->GAA) by single-strand conformation polymorphism and direct sequencing. These results indicate that the Hras128 rat is highly susceptible to BBN carcinogenesis and may be utilized as a rat model for analysis of bladder tumor development. The mutation findings indicate that the enhanced tumor development is not primarily due to mutations occurring in the transgene.

Animals↗
PubMed2000

[Development of molecular targeting drugs for the treatment of cancer-therapeutic potential and issues to be addressed in global development].

A survey of cancer treatment in a sample of hospitals > 100 beds conducted in 1998 compared with experience in the US showed that good progress has been achieved in Japan in the screening and early treatment of gastric cancer, and that the prognosis for breast cancer is better than in the West. Although in the past, the cytotoxic therapies available to physicians in Japan vs the West have been different, recent acceleration of regulatory review will result in a convergence of treatment paradigms and some improvement in acute response in many tumour types. However, world wide there is a need for new improved therapies in all cancers evaluated. Particular needs are in the management of NSCLC, advanced disease and cancers which form micrometastases. The eventual hope is that cancer can be turned from a lethal disease into a chronic disease where patients maintain a good QOL. Apart from anti hormonal therapies, the usual approach has been to kill the cancerous cells. However, the new approaches to intervening in the growth and migration of cancerous cells or the host tissue response by molecular targeting offer the promise of achieving a step change in therapy. Although EGF tyrosine Kinase inhibitors such as ZD 1839 have been shown to cause a conventional tumour response in NSCLC, many of these new approaches are unlikely to show a short term response even if they have the capacity to affect tumour development and increase disease free survival. Some compounds will require combination therapy with a conventional cytotoxic or radiotherapy to show their full benefit. For conventional cytotoxics, the usual approach to development has been to select the maximum tolerated dose and then evaluate the efficacy in advanced disease. However, for the new approaches which will not have such severe dose limiting toxicities, it will be necessary to select a surrogate marker of the intended biological effect to select the optimal biological dose (OBD) and dose regimen in phase I/II studies for further evaluation in phase II or III studies which are designed to show the expected patient benefit. The tumour target, the stage of the disease and the possible need for concomitant therapy will also have to be considered according to the mechanism of action of the product.

Angiogenesis Inhibitors↗
PubMed2000

[A randomized long-term comparative study of clinical efficacy of alpha 1-blocker with or without antiandrogen therapy for benign prostatic hyperplasia: focusing on improvement of I-PSS].

This study was conducted to examine the efficacy of administration of tamsulosin hydrochloride alone or in combination with chlormadinone acetate (CMA) against lower urinary tract symptoms for a period of 52 weeks in 33 patients with benign prostatic hyperplasia. The patients were randomly allocated into a group administered tamsulosin alone and a group administered tamsulosin in combination with CMA. Based on the assessment of the total I-PSS (International Prostate Symptom Score), significant symptomatic improvement was noted 4 weeks after the commencement of drug administration in the tamsulosin + CMA group, whereas no significant improvement was observed in the tamsulosin group. Both irritative and obstructive bladder symptoms improved significantly at any time of assessment after 4 weeks of drug administration in the tamsulosin + CMA group; however, significant improvement was noted only at week 16 and week 52 for irritative symptoms and at week 16 for obstructive symptoms in the tamsulosin group. In particular, obstructive symptoms showed significant improvement at week 4 in the tamsulosin + CMA group, as compared with that in the tamsulosin group. The average value of peak urinary flow rate was significantly increased in the tamsulosin + CMA group (10.4 ml/s to 15.6 ml/s) as compared with that in the tamsulosin group (8.5 ml/s to 10.5 ml/s). These findings indicate that combined administration of tamsulosin and CMA resulted in early improvement of lower urinary tract symptoms in these patients. Long-term combined administration of tamsulosin and CMA thus appears to be a promising treatment strategy for the improvement of obstructive symptoms and peak urinary flow rate, particularly, 16 weeks onward after administration in patients with benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗
PubMed1999

Intravesical chemotherapy for maximum prophylaxis of new early phase superficial bladder carcinoma treated by transurethral resection: a combined analysis of trials by the Japanese Urological Cancer Research Group using smoothed hazard function.

BACKGROUND: The effect of intravesical instillation of doxorubicin or epirubicin after transurethral resection (TUR) was estimated from the data of five randomized clinical trials in Japan. The authors provided the estimated hazard function plots with a smoothing technique, to evaluate the prophylactic effect of an intravesical therapy over time and to estimate the natural history of superficial bladder carcinoma. METHODS: Data on a total of 1732 patients from 5 studies of the Japanese Urological Cancer Research Group who were eligible to receive doxorubicin and epirubicin were analyzed. The patients were divided into four subgroups based on their background characteristics. Their tumors were categorized as "primary and solitary," "primary and multiple," "recurrent and solitary," or "recurrent and multiple." RESULTS: Multivariate analysis revealed that intravesical instillation reduced the risk of recurrence to about one-half to two-thirds compared with the controls. The shapes of the graphs that estimated the hazard function for patients with no prophylaxis indicated that multiple tumors showed an earlier peak of recurrence than solitary tumors and recurrent tumors had a higher hazard of recurrence than primary tumors. Graphic presentation of the hazard function in each subgroup suggested that the effect of prophylaxis continued for 500 days after TUR but not for longer. CONCLUSIONS: This analysis indicated that there are two patterns of tumor recurrence of superficial bladder carcinoma after TUR, namely, early phase and late phase. Intravesical chemotherapy may be effective mainly in reducing the hazard for recurrence in the early phase.

Administration, Intravesical↗
PubMed1999

Early results of radical prostatectomy and adjuvant endocrine therapy for prostate cancer with or without preoperative androgen deprivation. The Prostate Cancer Study Group.

BACKGROUND: The effects of preoperative androgen deprivation were explored in the patients who received radical prostatectomy and subsequent adjuvant endocrine therapy for prostate cancer. METHODS: Stage A2, B or C prostate cancers were randomized to one of two groups: (i) group I (n=90), who received androgen deprivation (leuploride and chlormadinone acetate) for 3 months preoperatively followed by radical prostatectomy and adjuvant endocrine therapy (leuploride only); and (ii) group II (n=86), who underwent the surgery followed by 3 month androgen deprivation and subsequent adjuvant endocrine therapy. The effects of preoperative androgen deprivation on clinical relapse (serum prostate specific antigen (PSA) > 1.98 ng/mL, local recurrence or distant metastasis) and PSA relapse (PSA >0.2ng/mL) were evaluated at 2 years after randomization. RESULTS: There was no significant difference in clinical or PSA relapse-free survival and quality of life measures between the two groups, although relapses occurred significantly more frequently in patients who had more advanced stages, higher pretreatment PSA values or lower histologic differentiation in either group. Subgroup analysis indicated that clinical relapse-free survival in stage C cancer tended to be better in patients with preoperative androgen deprivation than in those patients without it (P< 0.1). CONCLUSIONS: Preoperative androgen deprivation may be beneficial for stage C prostate cancer patients receiving radical prostatectomy and adjuvant endocrine therapy over the 2 year observation period. A longer follow up is needed to clarify the exact extent of benefit in terms of survival and quality of life.

Aged↗
PubMed1999

Effect of recombinant human granulocyte colony stimulating factor (lenograstim) on chemotherapy induced neutropenia in patients with urothelial cancer.

BACKGROUND: A multicenter cooperative study to evaluate clinical usefulness of recombinant human granulocyte colony stimulating factor (rG-CSF; lenograstim) in the treatment of neutropenia associated with cancer chemotherapy was conducted in patients with urothelial cancer. METHODS: Therapeutic responses were compared within each patient between the observation and study treatment phases. RESULTS: Treatment with rG-CSF raised the nadir of the neutrophil count (343 to 3015/mm3), reduced the duration of neutropenia (6.2 to 0.4 days) and hastened recovery from the neutropenic state (23.5 to 5.5 days). Febrile neutropenia was encountered in 12 patients during the observation phase alone and in only one patient during the study treatment phase alone. The mean duration of febrile neutropenia was also shortened (0.39 to 0.12 days). In addition, the duration of antibiotic therapy was significantly reduced during treatment. The percentage of patients completing the chemotherapeutic regimens of combination M-VAC therapy was markedly increased to 81.0% as a result of rG-CSF therapy compared with 44.8% in the observation phase. Adverse reactions were observed in four patients and abnormal laboratory values were found in nine patients. None of these adverse events was of a serious nature. CONCLUSIONS: These results indicate that rG-CSF is a useful drug for the treatment of neutropenia associated with chemotherapy in urothelial cancer.

Adjuvants, Immunologic↗
PubMed1999

Hamartoma of the urinary bladder.

BACKGROUND: Hamartomas of the urinary bladder are extremely rare. We report on a case in a 58-year-old female who presented with the chief complaint of pain on urination. METHODS/RESULTS: Cystoscopy revealed a solid tumor on the left posterior wall of the bladder. Transurethral resection of the tumor failed to provide a definitive pathological diagnosis of the tumor. Thus, we performed partial cystectomy. The pathological diagnosis was hamartoma arising from the urinary bladder. CONCLUSION: This is the ninth case diagnosed as urinary bladder hamartoma to be reported in the literature.

Cystoscopy↗
PubMed1999

Urinary nuclear matrix protein 22 as a new marker for the screening of urothelial cancer in patients with microscopic hematuria.

PURPOSE: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. METHODS: Patients with microscopic hematuria detected at a health examination, who were advised by a consulted urologist to have a cystoscopical examination, were asked to enter this study. Urine samples were collected before cystoscopy and divided into two portions for NMP22 test and voided urine cytology. RESULTS: Of the 309 patients with microscopic hematuria, 22 cases (7.1%) of urothelial cancer and one case of prostate cancer were detected. For the other cases, 128 (41.4%) were of benign diseases and 158 (51.1%) were designated as having no evidence of disease (NED). The median NMP22 values for urothelial cancer, other diseases and NED were 35.5, 6.7 and 6.0 U/mL, respectively, with 95% confidence intervals of 19.9-228.2, 5.1-9.3 and 5.4-7.2, respectively. The sensitivity of the NMP22 test for urothelial cancer was 90.9% (20/22), whereas the sensitivity of voided urine cytology was only 54.5% (12/22). CONCLUSIONS: The present study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.

Adult↗
PubMed1999

Lower urinary tract function after intra-arterial chemotherapy with concurrent pelvic radiotherapy for invasive bladder cancer.

BACKGROUND: Intra-arterial chemotherapy with concurrent pelvic radiotherapy as a bladder-sparing regimen for invasive bladder cancer is highly promising for selected patients. However, lower urinary tract function after this treatment has not been fully investigated. METHODS: The urodynamic effects of intra-arterial chemotherapy with concurrent pelvic radiotherapy were retrospectively evaluated in 14 patients with organ-confined invasive bladder cancer. The post-treatment urodynamic findings were compared with the pretreatment ones (n = 7), and a comparison was made between the serial urodynamic findings after the treatment in another seven patients who were able to undergo the pretreatment urodynamic study (UDS). RESULTS: The median follow-up period up to the latest UDS was 34 months. Of the 14 patients, the latest UDS revealed some storage dysfunctions in 11 (79%) and some emptying dysfunctions in three (23%). Uninhibited detrusor contraction and decreased bladder compliance were recorded in 29 and 43% at the pretreatment UDS and approximately 50-60 and 20-60% in the serial follow-up studies, respectively (n = 7). Impaired detrusor contractility lasted in one patient. In the seven patients without the pretreatment UDS, decreased maximum cystometric capacity and decreased compliance were recorded in approximately 50-60 and 20-60% at the serial UDS, respectively. Detrusor contractility was aggravated in one patient and completely lost in one with time. CONCLUSIONS: The urodynamic findings indicate that the bladder-sparing regimen might result in perpetuating the lower urinary tract dysfunctions due to invasive bladder cancer itself and/or transurethral surgery and might injure the infrasacral autonomic nerves and the bladder itself.

Aged↗
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

Antiemetic efficacy of granisetron: a randomized crossover study in patients receiving cisplatin-containing intraarterial chemotherapy.

BACKGROUND: Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed. METHODS: CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion. RESULTS: Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P < 0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P < 0.0001). CONCLUSION: A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.

Adolescent↗
PubMed1999

Argyrophilic nucleolar organizer region in proliferating cell has a predictive value for local recurrence in superficial bladder tumor.

PURPOSE: It has been shown in many carcinomas that the proliferation rate and number of argyrophilic nucleolar organizer regions (AgNOR) are associated with tumor aggressiveness. However, in bladder tumor the significance of the correlation between the number of AgNOR and tumor behavior remains controversial. Therefore, it would be helpful if a new technique could be developed that would allow for more accurate AgNOR counting in association with tumor behavior. We established the simultaneous staining technique of AgNOR with Ki-67 labeling to reveal the significance of AgNOR count in superficial bladder tumor. MATERIALS AND METHODS: A total of 50 paraffin sections of superficial bladder tumor were stained with AgNOR and Ki-67 (MIB-1). The numbers 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 was significantly higher than that in resting cells (p<0.01), and the count significantly increased with tumor grade (p<0.01). Based on recurrence-free survival analyses the local recurrence rate was significantly higher in patients with high proliferating cell NOR but not for those with resting or whole cells. However, no AgNOR score helped to select patients at high risk for disease progression. CONCLUSIONS: Proliferating cell NOR had a predictive value for local recurrence in patients with superficial bladder tumor.

Adult↗
PubMed1999

Effects of a soybean isoflavone mixture on carcinogenesis in prostate and seminal vesicles of F344 rats.

Several epidemiological studies have suggested an inverse association between the risk of prostate cancer and intake of soybeans and their products. In vitro data pointing to possible anti-carcinogenic properties of the soybean isoflavone, genistein, led us to investigate the chemopreventive potential of soybean isoflavones in a rat carcinogenesis model induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP). Animals received DMAB s.c. injections at 2-week intervals for the first 20 weeks and implanted silicon tubes containing 40 mg of TP, replaced at 6-week intervals throughout the experiment. The soybean isoflavone mixture consisting of 74% genistein and 21% daidzein was mixed in basal diet (AIN-76A) at concentrations of 100 and 400 ppm and fed to F344 male rats throughout the experiment. Rats treated with carcinogens and administered isoflavone mixture at 100 and 400 ppm developed adenocarcinomas at incidences of 35% and 29%, respectively, in the prostate and seminal vesicles, whereas the figure was 60% for those maintained on control diet. Feeding of the isoflavone mixture at 100 and 400 ppm significantly inhibited the number of argyrophilic nucleolar organizer regions (AgNORs) in adenocarcinomas of the accessory sex glands as compared to those of rats fed control diet. No influence on the development of neoplastic lesions originating in other organs was noted. The results of this study provide evidence that soybean isoflavones may have potential as chemopreventive agents against carcinogenesis in the prostate.

Aminobiphenyl Compounds↗
PubMed1999

YM116, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole, decreases adrenal androgen synthesis by inhibiting C17-20 lyase activity in NCI-H295 human adrenocortical carcinoma cells.

The concentrations of androstenedione and dehydroepiandrosterone, products of C17-20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased by YM116 (2-(1H-imidazol-4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and ketoconazole (IC50: 54.9 and 54.2 nM). 17Alpha-hydroxyprogesterone, a product of 17alpha-hydroxylase, was increased by YM116 (1-30 nM) and by ketoconazole (10-300 nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were 50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than 17alpha-hydroxylase. Compatible with these findings, progesterone, a substrate of 17alpha-hydroxylase, was increased by these agents. Cortisol production was inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116 was a 14-fold more potent inhibitor of androstenedione production than cortisol production, whereas ketoconazole was a nonselective inhibitor of the production of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results demonstrate that YM116 reduces the synthesis of adrenal androgens by preferentially inhibiting C17-20 lyase activity.

Adrenal Cortex Hormones↗