Prostatic Neoplasms: Matsuda T

Tanaka M, Ono Y, Matsuda T, Terachi T, Suzuki K, Baba S, Hara I, Hirao Y, Anonymous00107. · Department of Urology, Fukuoka University Faculty of Medicine, Fukuoka, Japan. ~u.ac.jp · Int J Urol. · Pubmed #19228223 No free full text.

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Yamamoto N, Kinoshita H, Inoue T, Kawakita S, Oguchi N, Muguruma K, Kawa G, Sakaguchi Y, Adachi Y, Sakaida N, Uemura Y, Matsuda T. · The Department of Urology and Andrology, Kansai Medical University. · Hinyokika Kiyo. · Pubmed #17933147 No free full text.

Abstract: A 76-year-old man had been treated with maximum androgen blockade therapy for a poorly-differentiated prostate adenocarcinoma (T3cN1M0, prostate specific antigen (PSA) 65 ng/ml, Gleason Score 4+5=9) since September 2002. By August 2003, his serum PSA levels were undetectable and the lymph node swelling had vanished. However, in December 2004, his serum PSA levels started rising gradually up to 0.66 ng/ml. Radiation therapy on the prostate was then performed (66 Gy). At that time, no metastasis was detected by computed tomography and bone scintigraphy. In August 2005, multiple bone metastases were detected. Immunohistochemical examination of a biopsy specimen from the bone lesion revealed a small cell carcinoma/neuroendocrine cell carcinoma. He died with undetectable PSA levels (less than 0.008 ng/ml) in December 2005. The autopsy showed multiple organ metastases including bone, liver, lungs and others. The immunohistochemical examination revealed pure small cell carcinoma in all metastatic lesions. A precise histological examination of the lungs using a 1 cm serial section could not reveal any tumors compatible with primary lung cancer. We concluded from the clinical history and autopsy findings that his initial poorly-differentiated adenocarcinoma of the prostate dedifferentiated into a pure small cell carcinoma with neuroendocrine differentiation.

Karasawa K, Kaizu T, Niibe Y, Igaki H, Shinohara M, Tanaka Y, Matsuda T. · Department of Radiology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan. · Int J Radiat Oncol Biol Phys. · Pubmed #12694840 No free full text.

Abstract: BACKGROUND AND PURPOSE: In our institution, rotational 3D-conformal radiation therapy (also called conformation therapy) has been applied since the late 1970s to conform the target volume of high-dose radiation to the cancerous tissue while minimizing radiation to the surrounding normal tissues. This technique has been used most commonly to treat prostate cancers in combination with hormonal therapy. The results of Stage B2/C prostate cancer treated with this method were analyzed. PATIENTS AND METHODS: Between 1987 and 1997, 33 cases of prostate cancer were definitively treated with this method: 9 Stage B2 tumors and 24 Stage C tumors. Of these 33 tumors, 3 were well differentiated, 18 were moderately differentiated, and 12 were poorly differentiated. The average patient age was 75.6 years. The median pretreatment PSA value was 23.8 ng/ml. The total radiation dose ranged from 60 Gy to 70 Gy (average: 63.5 Gy) with conventional fractionation. Hormone therapy was administered permanently; the primary hormonal agent was diethylstilbestrol phosphate. RESULTS: The overall survival rate after 5 years was 58.2% and that after 10 years was 29.6%. The biochemical relapse-free rate after 5 years was 87.0% and that after 10 years was still 87.0%. There were 4 cases of biochemical failure, but no cases of death from prostate cancer. Stage, differentiation, and pretreatment PSA value were not prognostic factors. One of the 2 cases with delayed complications was a case of RTOG Grade 3 gastrointestinal complication. CONCLUSIONS: Rotational 3D-conformal radiation therapy combined with hormone therapy might be promising for the treatment of prostate cancer.

Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. · Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan. · Jpn J Clin Oncol. · Pubmed #15020659 links to  free full text

Abstract: OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level <or=4 ng/ml) rate, the 12 week overall tumor response rate (proportion with a partial response or better) and the proportion of withdrawals due to adverse drug reactions (ADRs) at follow-up. This interim analysis was undertaken after a minimum of 6 months' follow-up (median 15 months). RESULTS: The 12 week PSA normalization rate was 79.4% for MAB and 38.6% for LHRH agonist monotherapy (P < 0.001). The 12 week overall tumor response rate was 77.5 and 65.3%, respectively (P = 0.063). The withdrawal rate due to ADRs was 8.8% and 10.9%, respectively. There were differences in favor of MAB over monotherapy with respect to time to treatment failure (TTTF) (P = 0.038) and time to progression (TTP) (P = 0.016). There have been too few deaths (n = 10) to analyze survival. The profiles of adverse events and ADRs were broadly similar in the two treatment groups. CONCLUSION: In Japanese patients with advanced prostate cancer, first-line treatment with bicalutamide 80 mg in combination with an LHRH agonist is superior to LHRH agonist monotherapy in terms of the antitumor response at 12 weeks, and also time to treatment failure and progression, and does not compromise treatment safety. The study is ongoing.

Matsuda T, Saika K. · Cancer Information Services, Surveillance Division, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan. · Jpn J Clin Oncol. · Pubmed #19553401 No free full text.

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Suzuki H, Okihara K, Miyake H, Fujisawa M, Miyoshi S, Matsumoto T, Fujii M, Takihana Y, Usui T, Matsuda T, Ozono S, Kumon H, Ichikawa T, Miki T, Anonymous00323. · Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan. · J Urol. · Pubmed #18635218 No free full text.

Abstract: PURPOSE: Large meta-analyses have documented that maximum androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer confers survival benefits, although it remains controversial. Also, we and others have reported the effectiveness of second line hormonal therapy for prostate cancer that relapses after initial hormone therapy. However, there is little clinical evidence of the effectiveness of the latter treatment strategy. Therefore, in this multicenter trial in Japan we analyzed clinical outcomes following alternative changing from 1 nonsteroidal antiandrogen to another, ie bicalutamide to flutamide and flutamide to bicalutamide, for advanced prostate cancer that relapsed after initial maximum androgen blockade. MATERIALS AND METHODS: The study included 232 patients with advanced prostate cancer who were initially treated with maximum androgen blockade, including surgical or medical castration combined with nonsteroidal antiandrogens. If a patient relapsed while on first line therapy, we discontinued antiandrogen and evaluated the patient for antiandrogen withdrawal syndrome. We then administered an alternative antiandrogen and evaluated its effect. RESULTS: The incidence of antiandrogen withdrawal syndrome after initial maximum androgen blockade was 15.5% for bicalutamide and 12.8% for flutamide. A prostate specific antigen decrease after antiandrogen withdrawal was a prognostic factor. Nonsteroidal antiandrogens as alternative therapy in patients with relapse after the initial maximum androgen blockade were effective (prostate specific antigen decrease greater than 50%) as second line maximum androgen blockade. Of 232 patients 142 (61.2%) showed a prostate specific antigen decrease in response to an alternative antiandrogen. These responders had significantly better survival than nonresponders, suggesting that responsiveness to second line therapy predicts increased survival. CONCLUSIONS: Following maximum androgen blockade with an alternative nonsteroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial maximum androgen blockade. Even a partial response to second line maximum androgen blockade was associated with improved survival. Our data support the notion that responders to second line regimens are androgen independent but still hormonally sensitive.

Kinoshita H, Kamoto T, Nishiyama H, Nakamura E, Matsuda T, Ogawa O. · Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan. · Int J Urol. · Pubmed #17880291 No free full text.

Abstract: OBJECTIVES: We examined whether the prostate specific antigen (PSA) nadir is a good predictor of biochemical failure after radical prostatectomy. METHODS: We retrospectively reviewed clinico-pathological data in 257 patients who underwent radical prostatectomy. Twenty-nine patients of whom PSA nadir did not reach 0.1 ng/mL and three patients in whom second line therapy was started before biochemical failure were excluded, and 225 patients were subject to this study. We evaluated the changes in PSA value at very low (from less than 0.01-0.10 ng/mL) levels using an ultra-sensitive PSA assay after radical prostatectomy. Biochemical failure was defined as three consecutive elevations of PSA to above 0.1 ng/mL. RESULTS: Biochemical failure-free survival was attained by 89.9% of patients at 1 year, 83.0% at 2 years, and 81.0% at 5 years. PSA nadir more than 0.01 ng/mL was strongly associated with biochemical failure after radical prostatectomy (P < 0.0001). Mean time to reach PSA nadir was 3.1 months. Preoperative PSA > 20 ng/mL (P = 0.0013), clinical T stage = T2 (P = 0.0462), Gleason score 8-10 (P = 0.0243) were also independent predictors of biochemical progression. CONCLUSIONS: Prostate specific antigen nadir determined by ultra-sensitive PSA assay is an important parameter that is objective, reliable, and easily measured, and useful for predicting the subgroups of patients both most likely and unlikely to exhibit biochemical progression.

Matsuda T, Saika K. · Cancer Information Services and Surveillance Division, Center for Cancer Control and Information Services, National Cancer Center. · Jpn J Clin Oncol. · Pubmed #17720742 links to  free full text

This publication has no abstract.

Shimada O, Wu X, Jin X, Nouh MA, Fiscella M, Albert V, Matsuda T, Kakehi Y. · Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan. · Urology. · Pubmed #17320696 No free full text.

Abstract: OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumor cells through two of its receptors: TRAIL-R1 and TRAIL-R2. In this study, we investigated the susceptibility of human prostate cancer and bladder cancer cells to HGS-ETR2, a human monoclonal agonistic antibody specific for TRAIL-R2. METHODS: The cell surface expression of TRAIL-R1 and TRAIL-R2 on prostate cancer and bladder cancer cells was determined using flow cytometry. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and caspase activities were measured by a quantitative colorimetric assay. RESULTS: HGS-ETR2 effectively induced apoptotic cell death in DU145, PC3, and LNCaP human prostate cancer cells and J82 and T24 human bladder cancer cells. The increased effectiveness of HGS-ETR2 for inducing cell death might have been affected by differences in the cell surface expression of the two TRAIL receptors, in that TRAIL-R2, but not TRAIL-R1, was frequently expressed in the prostate cancer and bladder cancer cells. HGS-ETR2 significantly activated the caspase cascade, including caspase-3, -6, -8, and -9, which were the downstream molecules of the death receptors in prostate cancer cells. Caspase-3, -6, and -9 were also significantly activated with HGS-ETR2-induced apoptosis in the bladder cancer cells. CONCLUSIONS: These findings suggest the potential utility of TRAIL-R2 antibody as a novel therapeutic agent against prostate cancer and bladder cancer.

Nagakawa O, Junicho A, Akashi T, Koizumi K, Matsuda T, Fuse H, Saiki I. · Department of Pathogenic Biochemistry, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. · Oncol Rep. · Pubmed #15870945 No free full text.

Abstract: We investigated the effect of the vasoactive intestinal (VIP) and pituitary adenylate cyclase activating peptides (PACAP) on the production of interleukin-6 (IL-6) in normal prostate epithelial and stromal cells and prostate cancer cells. We performed RT-PCR analysis to assess the expression of VIP receptor (VPAC1, VPAC2 and PAC1) mRNA in normal prostate epithelial and stromal cells and prostate cancer cells, and investigated the effect of VIP and PACAP on the production of IL-6. VPAC1, VPAC2 and PAC1 receptor mRNAs were expressed in LNCaP and DU-145/AR prostate cancer cells and PrEC cells (prostate epithelial cells). VIP stimulated the production of IL-6 in DU-145/AR prostate cancer and PrEC cells. PACAP showed a similar effect on IL-6 production in PrEC cells. VIP stimulated IL-6 promoter transcriptional activity in DU-145/AR cells. These results indicate that VIP and PACAP may modulate the IL-6 production of normal prostate epithelial and prostate cancer cells.

Nagakawa O, Akashi T, Hayakawa Y, Junicho A, Koizumi K, Fujiuchi Y, Furuya Y, Matsuda T, Fuse H, Saiki I. · Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. · Oncol Rep. · Pubmed #15375509 No free full text.

Abstract: We have established a clonal DU-145 prostate cancer cell line (DU-145/AR) stably transfected with androgen receptor cDNA. We investigated the expression of integrin subunits, adhesion to extracellular matrices, the invasion of DU-145/AR prostate cancer cells. The expression of various integrin subunits and adhesion to various extracellular matrices in DU-145, DU-145/Neo and DU-145/AR cells were examined. The haptoinvasion and the haptotactic migration of these cells were investigated using a Transwell cell culture chamber assay. DU-145/AR cells exhibited lower expression of alpha6 and beta4 integrin subunits and higher expression of alpha2 and alpha5 than DU-145 cells. DU-145/AR cells showed significantly lower adhesion to fibronectin, laminin-1 and laminin-5 than DU-145/ Neo cells, whereas DU-145/AR cells showed higher adhesion to type I and type IV collagen. Haptoinvasion of DU-145/AR cells into Matrigel/fibronectin-coated filter was significantly reduced as compared with DU-145/Neo or DU-145 cells, but there was no significant difference between DU-145/AR and control cells in the haptotactic migration to fibronectin. Dihydrotestosterone (DHT) inhibited the invasive ability of DU-145/AR cells. These results indicate that androgen receptor may play a role in the regulation of adhesion to the extracellular matrices and invasion of prostate cancer cells through influencing the expression of specific integrin subunits.

Sant M, Aareleid T, Berrino F, Bielska Lasota M, Carli PM, Faivre J, Grosclaude P, Hédelin G, Matsuda T, Møller H, Möller T, Verdecchia A, Capocaccia R, Gatta G, Micheli A, Santaquilani M, Roazzi P, Lisi D, Anonymous00160. · Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. · Ann Oncol. · Pubmed #14684501 links to  free full text

Abstract: EUROCARE-3 analysed the survival of 1815584 adult cancer patients diagnosed from 1990 to 1994 in 22 European countries. The results are reported in tables, one per cancer site, coded according to the International Classification of Diseases (ICD)-9 classification. The main findings of the tables are summarised and commented on in this article. For most solid cancers, wide differences in survival between different European populations were found, as also reported by EUROCARE-1 and EUROCARE-2, despite a remarkable (10%) overall increase in cancer survival from 1985 to 1994. Survival was highest in northern Europe (Sweden, Norway, Finland and Iceland), and fairly good in central-southern Europe (France, Switzerland, Austria and Spain). Survival was particularly low in eastern Europe, low in Denmark and the UK, and fairly low in Portugal and Malta. The mix of tumour stage at diagnosis explains much of the survival differences for cancers of the digestive tract, female reproductive system, breast, thyroid, and also skin melanoma. For tumours of the urinary tract and prostate, the differences were explained mainly by differences in diagnostic criteria and procedures. The case mix by anatomic subsite largely explains differences in survival for head and neck cancers. For oesophagus, pancreas, liver and brain cancer, with poor prognoses, survival differences were limited. Tumours, for which highly effective treatments are available, such as testicular cancer, Hodgkin's lymphoma and some haematological malignancies, had fairly uniform survival across Europe. Survival for all tumours combined (an indicator of the overall cancer care performance of a nation's health system) was better in young than old patients, and better in women than men. The affluence of countries influenced overall cancer survival through the availability of adequate diagnostic and treatment procedures, and screening programmes.

Arai Y, Egawa S, Terachi T, Suzuki K, Gotoh M, Kawakita M, Tanaka M, Terada N, Baba S, Okumura K, Hayami S, Ono Y, Matsuda T, Naito S. · Department of Urology, Kurashiki Central Hospital, Kurashiki, Japan. · Int J Urol. · Pubmed #12887364 No free full text.

Abstract: AIM: Laparoscopic radical prostatectomy is being evaluated throughout the world. The aim of the present study is to report early multi-institutional experience of the procedure in Japan. METHODS: A total of 148 men who were diagnosed with clinically localized prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early complications (within 30 days postoperatively) and postoperative convalescence were reviewed retrospectively. The median age of patients was 68.0 years (range, 51-80). RESULTS: The median operative time was 403 minutes (range, 167-925; average, 427). Blood loss ranged from 50 to 5000 mL (median, 540; average, 856). A total of 66 complications were reported in 55 patients (37.2%). Intraoperative complications were noted in 25 of 148 patients (16.9%): 10 rectal injuries (6.8%); five bladder injuries (3.4%); five cases of subcutaneous emphysema (3.4%); two intestinal injuries (1.4%); one major vessel injury (0.7%); one ureteral injury (0.7%); and one obturator nerve injury (0.7%). Overall, 16 of 148 patients (10.8%) required open conversion or postoperative open surgical repair. The most common postoperative complications were anastomotic leakage (6.8%), wound-related complications (4.7%) and perineal pain (4.7%). The bladder catheter was removed on day 7 or earlier in 73 cases (49.3%). The median time to ambulation was 1 day (mean 1.4, range 1-5). Oral intake was started on postoperative day 1 in 67 patients (45.2%) and on postoperative day 2 in 65 (43.9%). CONCLUSION: Although laparoscopic radical prostatectomy is technically demanding, reduced blood loss and shorter convalescence periods can be expected from the procedure. Surgeons should be aware of the disturbingly high morbidity rate related to early experience. By mastering laparoscopic skills and sharing knowledge, surgeons could reduce the impact of the learning curve required to complete this procedure competently.

Egawa S, Arai Y, Kawakita M, Matsuda T, Tanaka M, Naito S, Okumura K, Terachi T, Hayami S, Suzuki K, Gotoh M, Ono Y, Baba S. · Department of Urology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. · Int J Clin Oncol. · Pubmed #12720102 No free full text.

Abstract: BACKGROUND: Because laparoscopic radical prostatectomy requires significant laparoscopic expertise, it needs to be evaluated critically before being accepted as a standard therapeutic option for localized prostate cancer. METHODS: A total of 148 men diagnosed as having clinically resectable prostate cancer underwent laparoscopic radical prostatectomy at seven different institutions in Japan. Early biochemical and oncological outcomes were investigated. RESULTS: Policies underlying the selection of laparoscopic radical prostatectomy did not appear to be consistent among the participating institutions. Pathologically organ-confined disease was found in 64.0% of the patients who had undergone neoadjuvant therapy and in 77.2% of those who had not. Positive surgical margins were found in 36.0% and 34.1%, respectively, of the specimens. The most common site was the apex, which accounted for 77.8% of positive margins in patients who had undergone neoadjuvant therapy and 50.0% in those who had not. Seven patients have experienced biochemical failure at a median follow-up of 9.0 months. No clinical progression has been reported. CONCLUSIONS: Continuing improvements in each step of laparoscopic radical prostatectomy, especially apical dissection, should be sought as we pursue the goal of still better oncological outcomes. A systematic approach and therapeutic guidelines should help to reduce the learning curve for competent performance of this procedure.

Hisatomi H, Nagao K, Kawakita M, Matsuda T, Hirata H, Yamamoto S, Nakamoto T, Harasawa H, Kaneko N, Hikiji K, Tsukada Y. · Center for Molecular Biology and Cytogenetics, SRL, Inc, Hino, Tokyo, Japan. · Int J Mol Med. · Pubmed #12373303 No free full text.

Abstract: RT-nested PCR has been introduced as a highly specific and sensitive assay method to detect the prostate-specific membrane antigen (PSM) mRNA in peripheral blood. However, appreciable percentages of false-positive cases have been reported. Additionally, primer sets reported previously could not discriminate between PSM and PSM', an alternatively spliced variant, mRNA. These isoforms can be produced from a single gene. Switches in alternative splicing patterns are often controlled with strict cell-type or developmental-stage specificity. Therefore, it is most important to discriminate between PSM mRNA and PSM' mRNA. Using our highly specific primer sets, PSM mRNA was detected in 3 of 24 peripheral blood samples of normal male volunteers (12.5%) and was not detected in peripheral blood of 11 normal female volunteers. PSM' mRNA was detected in 5 of 24 peripheral blood samples of normal male volunteers (20.8%) and in 4 of 11 of normal female volunteers (36.4%). PSM' mRNA induced false-positive results, it is important for genetic diagnosis of prostate cancer to discriminate between PSM and PSM' using our primer sets with high specificity. The advances in the uniquely designed primer sets may allow researchers to detect a real PSM mRNA without PSM' mRNA.

Muramoto S, Uematsu H, Kimura H, Ishimori Y, Sadato N, Oyama N, Matsuda T, Kawamura Y, Yonekura Y, Okada K, Itoh H. · Department of Radiology, Fukui Medical University, 23 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193, Japan. · Eur J Radiol. · Pubmed #12350413 No free full text.

Abstract: OBJECTIVE: To investigate the usefulness of dynamic contrast magnetic resonance (MR) imaging in the differentiation of prostate cancer (PC) from benign prostate hypertrophy (BPH). MATERIALS AND METHODS: Eleven PC patients and 13 BPH patients were entered into the analysis. The mean gradient (MG) was calculated from the T2* term-eliminated time-signal intensity curve obtained from dynamic contrast MR data, and the MG of PC and that of BPH were compared. RESULTS: The MG of PC was significantly higher than that of BPH. When the threshold value was set to 1.88% per s for discriminating PC from BPH, the sensitivity, specificity, and accuracy were 100, 85, and 92%, respectively. CONCLUSION: The MG, which is derived from the T2* term-eliminated time-signal intensity curve, may be a useful index for differentiating PC from BPH.

Muramoto S, Uematsu H, Sadato N, Tsuchida T, Matsuda T, Hatabu H, Yonekura Y, Itoh H. · Department of Radiology, Fukui Medical University, Fukui, Japan. · J Comput Assist Tomogr. · Pubmed #12218810 No free full text.

Abstract: PURPOSE: Information regarding prostate blood flow as determined by positron emission tomography (PET) with H 0 may provide useful information about tumor diagnosis; however, PET requires a cyclotron for the production of an extremely short half-life (2 minutes) tracer. Therefore, the aim of this study was to propose a complementary index for blood flow as determined by MRI to validate the results and compare them with PET, especially for prostate tissue. METHODS: Six consecutive patients with prostate disease were studied. The two semiquantitative indices for tumor blood flow were calculated from the time-concentration curve measured from double-echo MR images. The theory of nondiffusible tracers by means of indicator dilution theory was applied to MR data. The relative regional blood flow (rrBF) was calculated as the ratio of the relative regional blood volume to relative regional mean transit time. Another proposed index was the maximum height of the time-concentration curve. PET studies were also performed, and absolute blood flow values were calculated for each subject. These indices calculated from different modalities were then compared. RESULTS: A significant correlation was found between the rrBF and the absolute blood flow as determined by PET (r = 0.69, p < 0.005). A significant correlation was also found between the maximum height of the time-concentration curve and the absolute blood flow (r = 0.85, p < 0.0001). CONCLUSIONS: The semiquantitative tumor blood flow indices measured with MRI have a good correlation with the corresponding measurements by PET; therefore, these indices may provide useful information about tumor diagnosis in clinical settings.

Kawa G, Hiura Y, Satoh H, Sugi M, Fujita I, Oguchi N, Doi H, Ashida M, Okada H, Muguruma K, Murota T, Koyama Y, Kawamura H, Ohara T, Kawakita M, Matsuda T. · Kansai Medical University, Prostate Study Group. · Hinyokika Kiyo. · Pubmed #11993205 No free full text.

Abstract: To search for a more suitable qualification indicating watchful waiting, we performed a retrospective study against early-stage prostate cancer patients managed without initial treatment. Thirty-three patients who had not been treated for more than 6 months after diagnosed as T1c or T2 prostate cancer were studied. The median values of total observation period, age at diagnosis, and initial PSA were 27.0 months, 69.0 years old, and 7.0 ng/ml, respectively. Among 28 patients who had had measurement of serum PSA at least three times, seven patients showed a significant PSA elevation when transition of PSA level was analyzed using linear regression analysis. The other patients had been stable or PSA level declined. Between these two groups, there was no significant difference regarding age, initial PSA, PSA density, Gleason score, number of cancer-positive core, and cancer-occupying rate in biopsy specimen. The median PSA doubling time in patients showing PSA elevation was 36.3 months. There were no patients showing PSA elevation among those with a cancer-occupying rate of less than 5%. Clinical disease progression was obviously observed in two cases although one did not show PSA elevation. During the observation period, treatment was eventually started in seven patients. The 5-year rate of no treatment was 53.8%. Although a significant independent factor predicting the future treatment was not identified, univariate analysis revealed that the initial PSA value in patients undergoing treatment was significantly higher than that of those without treatment (p = 0.032). We concluded that early-stage prostate cancer has clinical variability, and regular clinical evaluations as digital rectal examination should be performed when the patient was managed with watchful waiting.

Nagakawa O, Murata J, Junicho A, Matsuda T, Fujiuchi Y, Fuse H, Saiki I. · Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. · Cancer Lett. · Pubmed #11790458 No free full text.

Abstract: We established a clonal DU-145 prostate cancer cell line (DU-145/AR) stably transfected with androgen receptor (AR) cDNA and investigated the expression of type 1 vasoactive intestinal peptide (VIP) receptor (VIP1R) and type 2 VIP receptor (VIP2R) mRNA in these cells by reverse transcriptase-polymerase chain reaction analysis and the effect of VIP on the invasion and the haptotactic migration of these cells. DU-145/AR cells constitutively expressed both VIP1R and VIP2R mRNA, but the parent DU-145 cells did not. VIP increased the invasive capacity of DU-145/AR cells. VIP also enhanced the haptotactic migration of these cells to fibronectin. However, the growth of these tumor cells was not affected by VIP at any concentrations used in this study. These results indicate that VIP may play a role in the regulation of the invasion of prostate cancer.

Kawakita M, Sato M, Oguchi N, Muguruma K, Murota T, Matsuda T. · Department of Urology, Kansai Medical University, Moriguchi, Japan. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #11449701 No free full text.

Abstract: PURPOSE: In 1998 Guillonneau et al reported feasible and safe technique for laparoscopic radical prostatectomy. Herein we review initial 5 cases with using the Montsouris technique. MATERIALS AND METHODS: Between January and April 2000, 5 patients underwent transperitoneal laparoscopic radical prostatectomy. Clinical stages were T1c in 2, T2a in 1 and T2b in 2 patients. Preoperative PSA levels and Gleason grades in needle biopsies ranged from 7.9 to 39 ng/ml and from 2 to 6, respectively. Under general anesthesia 5 to 6 trocars were introduced and the patient was placed in the exaggerated Trendelenburg position. In 2 patients bilateral obturator lymph nodes were dissected for frozen pathological examination. Antegrade prostatectomy was performed initiating with the transperitoneal dissection of seminal vesicles. A watertight vesicourethral anastomosis was made with 8 to 10 interrupted sutures. RESULTS: Operating time and blood loss ranged from 505 to 925 minutes and from 100 to 700 gm, respectively. There were no intraoperative complications and one postoperative complication of prolonged urinary leakage, which was spontaneously closed. In other 4 patients Foley catheters were removed on postoperative day 6 to 10. CONCLUSIONS: Laparoscopic radical prostatectomy provides better visualization, inducing meticulous surgical procedures and less blood loss. More sophisticated maneuver would be required in dissection between the prostate and the bladder neck.

Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A. · Department of Immunology, Department of Urology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194, Japan. · Biochem Biophys Res Commun. · Pubmed #11322786 No free full text.

Abstract: Interleukin 6 (IL-6) plays important roles in the immune system, hematopoiesis, as well as the growth of various tumors. Androgens are important in the initiation and progression of prostate cancer and their effects are mediated by androgen receptor (AR). Here we present a molecular mechanism for the effects of IL-6 on prostate cancer cells through a cross-talk between IL-6 and AR signaling pathways. IL-6-induced activation of signal transducer and activator of transcription 3 (STAT3) was augmented by AR in the presence of dihydrotestosterone (DHT). In addition, DHT treatment augmented endogenous STAT3-mediated gene expression by IL-6. Conversely, DHT-induced AR activity was increased by IL-6, and a dominant negative form of STAT3 inhibited AR activation. In contrast, DHT-mediated enhancement of STAT3 activation was inhibited by flutamide, an AR antagonist. We provide evidence that these activities are due to direct physical interactions between STAT3 and AR in prostate cancer cells.

Junicho A, Matsuda T, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A. · Department of Urology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. · Biochem Biophys Res Commun. · Pubmed #11071847 No free full text.

Abstract: Protein inhibitor of activated STAT3 (PIAS3) is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3). PIAS3 binds to STAT3 and inhibits its DNA-binding activity, and thereby STAT3-mediated gene activation. PIAS1, another member of the PIAS family, was recently shown to interact with the androgen receptor (AR), a nuclear hormone receptor that has an important role in both physiological and pathological processes, and acts as a cofactor for AR. Here we demonstrate that PIAS3 is expressed in prostate cancer cells and its expression is induced in response to dihydrotestosterone (DHT) treatment. Ectopic overexpression of PIAS3 suppressed AR-mediated gene activation induced by DHT-stimulation in LNCaP cells. We provide evidence that these activities were due to direct physical interactions between PIAS3 and AR. These results indicate that PIAS3 acts as a coregulator of AR signaling pathway in prostate cancer cells.

Arai Y, Egawa S, Tobisu K, Sagiyama K, Sumiyoshi Y, Hashine K, Kawakita M, Matsuda T, Matsumoto K, Fujimoto H, Okada T, Kakehi Y, Terachi T, Ogawa O. · Departments of Urology, Kurashiki Central Hospital, Kurashiki, Japan. · BJU Int. · Pubmed #10671883 No free full text.

Abstract: OBJECTIVES: To assess the time trends, morbidity and mortality of contemporary anatomical radical retropubic prostatectomy (RRP) in a multi-institutional study in Japan, where RRP has become more popular in the last decade. PATIENTS AND METHODS: Between January 1991 and August 1998, 638 patients underwent RRP at seven urological centres in Japan. Major complications (within 30 days of surgery) and the 30-day mortality were reviewed retrospectively. Of the patients, 12.9% were < 60 years old, 56.3% were 60-69 years old and 30.9% were >/= 70 years old (median age 67). Results The number of RRPs increased markedly, by more than sevenfold, from 1991-92 to 1996-97, mainly because there were more patients undergoing RRP in their sixth decade. The contribution of T1c disease increased in absolute and relative terms, from 13.9% in 1991-92 to 37.9% in 1997-98. Over time, the mean blood loss and the allogeneic transfusion rate decreased steadily. There was a trend toward more favourable outcomes for pathological variables (an increased percentage of organ-confined disease, decreased margin positivity and a decreased incidence of positive lymph node metastasis). The most common complications were wound-related (7.5%), or anastomotic leakage (4.1%). Major cardiopulmonary complications occurred in only two patients (0.31%, both pulmonary embolisms). One patient died from cerebral haemorrhage within 30 days of surgery, giving a mortality rate of 0.16%. CONCLUSION: s This study indicates a trend towards selecting patients most likely to benefit from RRP. Although the procedure is technically demanding, it can have an acceptably low rate of early complications, little mortality and need for allogeneic transfusion. The assessment of morbidity suggests a lower incidence of catastrophic thrombo-embolic and cardiac complications in Japanese patients than in Western men. The present data may be useful in decision-analysis models evaluating the role of therapy for Asian men with early-stage prostate cancer.