[Intermittent androgen suppression for prostate cancer].
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Androgen Antagonists↗
Biomedical subjects
K Akakura
Publications and source records attributed to K Akakura.
Advances in genetic aspects of cystinuria.
Cystinuria has been clinically classified into three subtypes (I, II, and III) by Rosenberg and associates. In 1994, the SLC3A1 (rBAT) genes which is one of the genes responsible for cystinuria, was located on chromosome 2(2p21). However, it was demonstrated that rBAT is responsible only for Type I cystinuria. At present, 43 mutations, including 5 discovered in our laboratory, have been reported in the rBAT gene of patients with cystinuria. Recent studies suggest that the rBAT-encoded protein was not a transporter itself; rather, the protein represented a specific "guidance molecule" for a selected amino acid transporter. In 1999, the SLC7A9 (BAT1) gene was located on chromosome 19(19q13) by us and by a European group. It seemed that the BAT1 gene is responsible for non-Type I cystinuria and that its protein was a subunit linked to the rBAT protein via a disulfide bond. Mutational, structural, and functional analyses of the gene have been performed by several groups, including our laboratory. It is expected that the roles of these genes in cystinuria will be clarified further, and genetic diagnosis and therapy of patients with cystinuria may be facilitated in the future.
Amino Acid Transport Systems, Basic↗
[A study on parameters to predict tumor volume for stage T1c prostate cancers of Gleason score 6 or less].
The number of cases of stage T1c prostate cancer has dramatically been increasing since the introduction of PSA as a screening test. The patients with T1c prostate cancer are usually treated by radical prostatectomy. In this group, however, some cancers are of small tumor volume and with a Gleason score of less than 7. These cancers are considered to be good candidates for watchful waiting management. We have investigated 40 patients with T1c prostate cancer treated by radical prostatectomy between 1996 and 1998. All 9 patients harboring tumors of Gleason score 7 or greater had tumors larger than 0.5 cm3. We have investigated PSA-related parameters including total PSA (PSA), PSA density (PSAD), free PSA, and % free PSA in 31 patients with T1c cancers of Gleason score 6 or less in order to clarify good preoperative predictors of tumor volume. We compared the distribution of PSA, PSAD, free PSA, and % PSA between the larger and smaller tumor groups. There was no significant difference in PSA, PSAD, or free PSA value. The small tumor group had a greater mean % free PSA than the larger tumor group (23.27 versus 11.88, p = 0.007). Areas under receiver operating characteristic curves were 0.715, 0.794, 0.636, and 0.842 for PSA, PSAD, free PSA and % free PSA. In stage T1c prostate cancer of Gleason score 6 or less, % free PSA may be the most useful preoperative predictor for tumor volume of 0.5 cm3 or greater.
Aged↗
Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer.
AIM: To identify the metastasis suppressor genes for prostate cancer. METHODS: A copy of human chromosomes was introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediated chromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained the metastasis suppressor gene(s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ hybridization analysis, and polymerase chain reaction analysis were performed. RESULTS: Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity. This demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively. CONCLUSION: This assay system is useful to identify metastasis suppressor gene (s) for prostate cancer.
Animals↗
Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.
BACKGROUND: Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. METHODS: The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. RESULTS: The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. CONCLUSIONS: These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.
Aged↗
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↗
The change in free-to-total prostate-specific antigen during progression to androgen-independent state in prostate cancer patients: utilization for intermittent androgen suppression therapy.
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Journal Article↗
Pattern of progression and survival in hormonally treated metastatic prostate cancer.
BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.
Aged↗
External beam radiation monotherapy for prostate cancer.
BACKGROUND: To clarify the implications and limitations of external beam radiation monotherapy for localized prostate cancer, the long-term outcomes and prognostic factors were investigated. METHODS: Between 1976 and 1994, 91 patients with untreated prostate cancer were treated with external beam radiation therapy alone. Thirty-two were classified as T1b, eight were T2a, four were T2b and 47 were T3. Pelvic lymphadenectomy was carried out in 69 cases; 57 were staged as pN0, eight were pN1, four were pN2 and 22 were pNX. Linac X-rays were used in 55 cases, fast neutron in 15 and a combination of the two in 21. No other therapy was given until relapse and when relapse was evident endocrine therapy was started. RESULTS: The observation period ranged from 3 to 206 months with a median of 78 months. Local control rate and disease-free, cause-specific and overall survivals at 10 years were 74.0, 49.6, 74.2 and 39.2%, respectively. By univariate analysis, T category, pN category and histologic grade were significant prognostic indicators for disease-free survival. Multivariate analysis revealed that T category was an independent prognostic factor. In T2b and T3 diseases, pN0/1 patients demonstrated significantly better disease-free survival than pNX. CONCLUSIONS: A favorable long-term outcome was achieved by external beam radiation monotherapy in patients with minimally extended prostate cancer (T1b and T2a). For locally advanced disease (T2b and T3), staging pelvic lymphadenectomy would be useful for the selection of patients.
Adenocarcinoma↗
Radiotherapy for local progression in patients with hormone-refractory prostate cancer.
PURPOSE: The aim of the present study was to investigate the effect of radiotherapy on the local progression of hormone-refractory prostate cancer. METHODS: From 1986 to 1995, 38 patients were diagnosed with local progression without distant progression after hormonal therapy at Chiba University Hospital. Eleven cases were treated with irradiation for local progression. External beam irradiation was delivered to the prostate at a dose of 50-66.6 Gy. RESULTS: In patients treated with radiotherapy, the duration from initial treatment to local recurrence was 6-80 months (mean +/- SD: 33.9 +/- 22.9 months). The follow-up period after irradiation was 7-64 months (mean +/- SD; 25.4 +/- 18.8 months). Three and 5 year cause-specific survival rates from radiotherapy were 46.2 and 23.1%, respectively. Radiotherapy had a marked effect on symptoms associated with local progression and no patients suffered from the symptoms after the radiotherapy. Complications of radiotherapy were limited. CONCLUSIONS: In patients with hormone refractory local progression without distant progression, low morbidity, low mortality radiotherapy offers a variable therapy to other palliative treatments because radiotherapy is able to control local symptoms for a long period of time.
Aged↗
Prognosis of patients with T4 prostate carcinoma.
BACKGROUND: The clinical course of patients with T4 prostate carcinoma was examined in order to consider whether there are alternative treatment options besides androgen ablation therapy. METHODS: From 1986 to 1995 at Chiba University Hospital, there were 22 cases of T4 prostate carcinoma. Sixteen cases had no bone metastasis at initial diagnosis. Tumor grade and response of prostate-specific antigen (PSA) to endocrine treatment were evaluated in these 16 cases. RESULTS: Four patients had moderately differentiated and 12 had poorly differentiated adenocarcinoma. For initial treatment, all patients received endocrine therapy. Anti-androgen therapy was effective in 15 cases and the 5 year cause-specific and progression-free survival rates were 72.1 and 38.1%, respectively. Patients with moderately differentiated tumors tended to have a longer disease-free period than those with poorly differentiated tumors (P = 0.047). CONCLUSIONS: Endocrine therapy was effective in patients with T4 tumors. It was suggested that aggressive local treatment (i.e. radiotherapy) in combination with endocrine therapy may be considered if the patients had no distant metastases and had a long life expectancy.
Adenocarcinoma↗
Vitamin D receptor gene polymorphism in Japanese patients with prostate cancer.
Vitamin D receptor gene polymorphism was determined in 66 and 60 Japanese patients with prostate cancer and non cancer controls, respectively. In contrast to previous reports showing an association between vitamin D receptor polymorphism of a TaqI restriction fragment length polymorphism at codon 352 (genotype tt) and prostate cancer in an American population, the frequency of genotype tt is less than one percent in the Japanese population. There was no difference between the patients and the controls in the vitamin D receptor TaqI genotype. In patients with metastatic prostate cancer, genotype TT had a tendency to shorter progression free survival compared to genotype Tt, but the number of patients was limited.
Aged↗
[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↗
[The evaluation of methods for determinations of urinary oxalate].
BACKGROUND: Estimation of urinary oxalate is one of important tools for the diagnosis and treatment of urolithiasis. And more precise, simple and inexpensive method is desirable. In the present study, we evaluated three methods which were clinically well-used. METHODS: From October 1996 to June 1997, 146 acidified urine samples were collected for 24 hours from 144 urolithiasis patients. We determined the urinary oxalates by three methods; the colorimetric method, the enzymic method and the ion chromatography (IC method). And we evaluated the correlations of these methods. RESULTS: Correlation coefficients in the urine oxalate concentration were, 0.86 with the colorimetric method and the IC method, 0.91 with the enzymic method and the IC method, 0.90 with the colorimetric method and the enzymic method. The coefficients in the 24 hours-urinary excretion of oxalate (0.76, 0.87, 0.82) were lower than those in the urine oxalate concentration. The correlation coefficients with the colorimetric method and the IC method were, 0.58 in hyperoxaluric group, 0.34 in normooxaluric group. The coefficients with the enzymic method and the IC method, 0.93 in hyperoxaluric group, 0.71 in normooxaluric group. CONCLUSION: The colorimetric method is least expensive, but is less useful. The enzymic method is less expensive, and is as useful as the IC method.
Adolescent↗
Identification of a I-cM region of common deletion on 13q14 associated with human prostate cancer.
Frequent allelic losses on chromosome arm 13q are observed in carcinomas of the head and neck, breast, ovary, and pituitary gland. We analyzed 59 primary prostate tumors (stage B, 18 patients; C, 12 patients; D1, 4 patients; and endocrine therapy-resistant cancer death, 25 patients), as well as 18 metastatic tissues from 14 of the 25 cancer death patients for loss of heterozygosity (LOH) using 35 microsatellite markers on chromosome arm 13q. Of the 59 primary tumors, 31 (53%) showed LOH involving at least one locus. Detailed deletion mapping identified a distinct commonly deleted region in the I-cM interval flanked by D13S153 and D13S273 on 13q14 and this region overlapped a part of the RB1 gene. Paired DNAs were available from both primary and metastatic tumors in the 14 cases of cancer death; among those pairs, we detected LOH on 13q in seven (50%) primary tumors, and in all metastatic foci (P = 0.0029). Moreover, the regions lost in metastatic tissues were more extensive than those seen in the corresponding primary tumors. These results suggest that inactivation of a putative tumor suppressor gene(s) including the RB1 gene on 13q14 plays an important role in human prostate cancer.
Adrenal Gland Neoplasms↗
Smoking and obesity in relation to the etiology and disease progression of prostate cancer in Japan.
BACKGROUND: Various risk factors have been investigated concerning the etiology of prostate carcinoma, but many questions about the significance of the risk factors remain unanswered. To evaluate the relationship between smoking and obesity in prostate cancer, a case-control study was performed. METHODS: Between 1986 and 1995, 329 patients with untreated prostate cancer and 188 patients with benign prostate hyperplasia (control patients) were evaluated according to their smoking habits and the degree of obesity. Also, the progression of prostate cancer in relationship to smoking and obesity was examined. RESULTS: Smoking and obesity were not risk factors for the development of prostate cancer (odds ratio, 0.986, 0.836; 95% confidence interval, 0.69-1.41, 0.57-1.24, respectively). Nor were smoking or obesity a risk factor for survival in stage D2 patients, however, in stage B1-D1 patients, obese men had a tendency for disease progression. CONCLUSION: This study demonstrated that neither smoking nor obesity increase the risk of developing prostate cancer, or the risk of disease progression in prostate cancer patients. However, obese men have a tendency for progression of stage B1-D1 prostate cancer although further studies are necessary to confirm this finding.
Aged↗
Incidence and characteristics of antiandrogen withdrawal syndrome in prostate cancer after treatment with chlormadinone acetate.
OBJECTIVES: In patients with progressive prostate cancer who have been treated with surgical or medical castration plus an antiandrogen, antiandrogen withdrawal can result in a significant decline in serum prostate-specific antigen (PSA). Although the incidence of antiandrogen withdrawal syndrome after combination treatment with the nonsteroidal antiandrogen flutamide has been thoroughly documented, the phenomenon clearly occurs in many other combination therapies and is presently being widely investigated. This paper would like to contribute to this effort by describing the endocrine withdrawal phenomenon in patients treated with combinations of castration plus chlormadinone acetate, ethynylestradiol or estramustine phosphate. MATERIALS AND METHODS: Clinical records of 68 prostate cancer patients who had been treated with surgical castration plus the administration of chlormadinone acetate, ethynylestradiol or estramustine phosphate, and who had shown clinical progression associated with a steady increase in serum PSA, were investigated. Forty-one cases were evaluable for changes in PSA after discontinuation of the hormonal agents. RESULTS: Of 28 patients who had been treated with chlormadinone acetate, 12 (42.9%) revealed 50% or more decline in PSA level following withdrawal of the agent. Among these, 5 cases (17.9%) showed subjective and/or objective improvements. There was no significant difference in histological grade of the tumor at diagnosis, mode of progression, time interval from the start of endocrine therapy to discontinuation of the hormonal agents, or PSA level at withdrawal of the agents between patients who did develop antiandrogen withdrawal syndrome and those who did not. CONCLUSION: When a steady increase in serum PSA is noted in a prostate cancer patient who has been treated with castration plus a steroidal antiandrogen, discontinuation of the antiandrogen may benefit the patient.
Aged↗
Prognostic value of the serum levels of bone formation and bone resorption markers in prostate cancer patients with bone metastasis.
OBJECTIVE: The aim of the present study was to determine whether the serum levels of a bone formation marker, i.e., the carboxy-terminal propeptide of type I procollagen (PICP), and a bone resorption marker, i.e., the carboxy-terminal telopeptide of type I collagen (ICTP) have prognostic value in prostate cancer patients with bone metastasis, compared with alkaline phosphatase (ALP) and prostate-specific antigen (PSA). METHODS: The serum levels of PICP, ALP, ICTP and PSA were examined in 116 untreated prostate cancer patients (40 patients with bone metastasis, 76 patients without bone metastasis), and the prognoses of the patients with bone metastasis were evaluated using univariate and multivariate analyses. RESULTS: The bone metastasis patients with low PICP or ALP values had significantly better outcomes compared to the bone metastasis patients with high PICP or ALP values. A multivariate analysis of PICP, ICTP, ALP, PSA and the patients' age revealed that PICP and patients' age were important prognostic factors for survival. The pretreatment levels of ICTP and PSA did not show any substantial relation to the prognosis of these patients. CONCLUSIONS: The results suggest that the pretreatment serum bone formation marker is an important prognostic indicator for prostate cancer patients with bone metastasis.
Aged↗