Prostatic Neoplasms: Tanaka M

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.

This publication has no abstract.

Sato N, Akakura K, Isaka S, Nakatsu H, Tanaka M, Ito H, Masai M, Anonymous00258. · Department of Urology, Ichihara Hospital, Teikyo University School of Medicine, Chiba, Japan. · Urology. · Pubmed #15302491 No free full text.

Abstract: OBJECTIVES: To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL). METHODS: Patients with locally advanced or metastatic prostate cancer were treated with a combination of leuprolide acetate and flutamide for 36 weeks. When the serum prostate-specific antigen (PSA) levels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until the PSA level reached 15 ng/mL or the pretreatment level. This cycle of on-treatment and off-treatment was repeated until PSA failure (three consecutive increases in PSA level greater than 4.0 ng/mL during the on-treatment period) or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire. RESULTS: Forty-nine patients (26 with T3N0M0, 8 with T2-T3N1M0, 2 with T4N0M0, and 13 with T2-T3N0M1) were enrolled. The mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1, six finished cycle 2, and three finished cycle 3. The mean off-treatment duration in cycles 1, 2, and 3 was 46.1, 36.9, and 23.3 weeks, respectively. In the off-treatment period, statistically significant improvements in the QOL score were observed in the categories of potency (11.4 versus 2.4) and social/family well-being (20.3 versus 16.1) compared with those in the on-treatment period. PSA failure occurred in 6 patients (3 with T3N0M0 and 3 with T2-T3N1M0), and all patients were alive at last follow-up. CONCLUSIONS: Our interim analysis indicated that QOL is remarkably improved during the off-treatment period. Intermittent androgen suppression would be a viable option for treatment of advanced prostate cancer, although a randomized controlled study is required to determine whether intermittent androgen suppression prolongs the time to androgen-independent cancer. We will continue follow-up in this study to a minimum of 3 years.

Tanaka M, Murakami S, Suzuki N, Hamano S, Kinsui H, Oikawa T, Shimazaki J. · Department of Urology, Asahi General Hospital. · Hinyokika Kiyo. · Pubmed #10723657 No free full text.

Abstract: Patients with Stage D2 prostate cancer were treated with surgical or medical (LHRH analog) castration combined with either estrogen, chlormadinone acetate or flutamide as initial therapy. The effect of each medication was compared. The overall survival, cause-specific survival and relapse-free survival were not different among the three medications. Patients given each medication were divided into two groups each according to grade, extent of diseases on bone metastases, and levels of tumor marker. Survivals of the corresponding two groups were compared with each other among different medications. No differences were revealed with any medication. There were no serious side effects in whole patients, except that grade 2 liver dysfunction was accompanied in 12% of flutamide-treated group. It is concluded that the three drugs used with castration did not make any difference in the survival of stage D2 patients, and differences between medications were seen in the frequency of side effects.

Nakai Y, Tanaka M, Yoshikawa M, Tanaka N, Hirayama A, Fujimoto K, Hirao Y, Inoue T, Akiyama T. · Department of Urology, Nara Medical University. · Hinyokika Kiyo. · Pubmed #19227214 No free full text.

Abstract: We report a case of prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. A 62-year-old man was admitted to our hospital for treatment of prostate cancer with cyst formation. On the rectal examination, a cystic tumor was palpable on the left side of prostate. The left kidney was not detected by intravenous pyelography and ultrasonography. Magnetic resonance imaging revealed a retrovesical cystic lesion in the left side. Total prostatectomy and left ureterectomy were performed under the diagnosis of clinical T1cN0M0 prostate cancer and left ectopic ureter opening to seminal vesicle with left renal agenesis. The pathological findings showed well differentiated adenocarcinoma, Gleason score 3 + 3, and left ectopic ureter entering into the seminal vesicle and left renal agenesis. The patient was well 39 months after the total prostatectomy and left ureterectomy without evidence of recurrence. There have been no cases of the association of this urogenital anomaly, such as ectopic ureter opening to seminal vesicle with renal agenesis and prostate cancer and the combined management of both. Our case seems to be first case in the Japanese literature.

Ishizaka K, Machida T, Tanaka M, Kawamura N, Nakamura K, Kihara K. · Department of Urology, Kanto Central Hospital, Tokyo, Japan. · Int J Urol. · Pubmed #19207610 No free full text.

Abstract: OBJECTIVE: The management of lower urinary tract symptoms that persist after radical prostatectomy remains to be established. We investigated whether an alpha1-blocker, naftopidil, improves LUTS in patients >or=1 year after radical prostatectomy. METHODS: A total of 29 male patients received 25 mg/day of naftopidil for the first week, then 75 mg/day for 4 weeks. The frequency-volume chart, international prostate symptom score and quality of life index (QOL) were examined before and at the end of the 5-week administration in all subjects. RESULTS: Total international prostate symptom score (I-PSS) and I-PSS subtotals associated with voiding symptoms and storage symptoms were significantly decreased at 5 weeks compared with baseline (P < 0.001 each). QOL index was significantly improved with naftopidil for 5 weeks (P < 0.001). From analyses of the frequency-volume chart, mean and maximum volume/void were significantly increased (P < 0.05 each). CONCLUSION: Lower urinary tract symptoms detected in patients >or=1 year after radical prostatectomy were markedly improved with administration of naftopidil at 75 mg/day. These symptoms could represent a novel target for medical treatment by improved understanding of the symptom pathology in the near future.

Tanaka N, Asakawa I, Kondo H, Tanaka M, Fujimoto K, Hasegawa M, Konishi N, Hirao Y. · Department of Urology, Nara Medical University, Kashihara, Nara, Japan. · Int J Urol. · Pubmed #19120529 No free full text.

Abstract: OBJECTIVES: To assess our initial experience in the treatment of localized prostate cancer using low-dose-rate brachytherapy (LDR-brachytherapy) with iodine-125. METHODS: One-hundred consecutive patients received LDR-brachytherapy between July 2004 and October 2006. Seventy-six patients were treated with seed implantation alone, whereas 24 patients were treated with a combination of brachytherapy and external beam radiotherapy. The minimal percentage of the dose received by 90% of the prostate gland (%D90), the percentage prostate volume receiving 100% of the prescribed minimal peripheral dose (V100), and the operation time were compared among every 10 consecutive patients. RESULTS: The means of %D90 and V100 were 109.6% and 93.4%, respectively. When compared with the first 10 patients, both D90 and V100 showed significant improvement in the following 10 consecutive patients. Similarly, the mean operation time decreased significantly according to the accumulated number of patients. CONCLUSIONS: Our initial experience with the first 100 cases suggests that LDR-brachytherapy needs accumulation of many more patients to obtain high-quality post-implant dosimetric outcomes.

Haga K, Tomioka A, Liao CP, Kimura T, Matsumoto H, Ohno I, Hermann K, Logg CR, Jiao J, Tanaka M, Hirao Y, Wu H, Kruse CA, Roy-Burman P, Kasahara N. · Department of Medicine, University of California-Los Angeles, California, USA. · J Urol. · Pubmed #19010487 No free full text.

Abstract: PURPOSE: Testing immunotherapeutic strategies for prostate cancer has been impeded by the lack of relevant tumor models in immunocompetent animals. This opportunity is now provided by the recent development of prostate specific PTEN knockout mice, which show spontaneous development of true adenocarcinoma arising from prostate epithelium and more faithfully recapitulate the human disease than any previous model. We investigated the feasibility of using tumor cells derived from this model to test tumor vaccination and adoptive immunotherapeutic strategies for prostate cancer. MATERIALS AND METHODS: PTEN-CaP8 adenocarcinoma cells derived from the biallelic PTEN knockout prostate cancer model were used to vaccinate nontumor bearing litter mates. Tumor specific effector cells were generated from splenocytes of vaccinated mice by mixed lymphocyte-tumor reactions, and antiproliferative effects and cytokine generation were examined in vitro. The effect of vaccination or adoptive immunotherapy on luciferase marked PTEN-CaP8 subcutaneous tumors was monitored by tumor volumetric measurements and noninvasive bioluminescence imaging. RESULTS: Vaccination of litter mate mice with irradiated PTEN-CaP8 cells showed a significant prophylactic effect against the subsequent tumor challenge. Effector cells harvested from vaccinated litter mates showed significant interferon-gamma secretion upon co-incubation with PTEN-CaP8 target cells and they were capable of efficient target cell growth inhibition in vitro. Intratumor adoptive transfer of effector cells resulted in significant growth inhibition of preestablished prostate tumors in vivo. CONCLUSIONS: The PTEN knockout model serves as a highly useful model in which to investigate tumor cell vaccination and adoptive immunotherapeutic strategies in the context of true adenocarcinoma of the prostate. This model should accelerate efforts to develop effective immunotherapies for human prostate cancer.

Kusumi T, Koie T, Tanaka M, Matsumoto K, Sato F, Kusumi A, Ohyama C, Kijima H. · Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan. · Pathol Int. · Pubmed #18844933 No free full text.

Abstract: Following hormone therapy, residual carcinoma is frequently difficult to identify on HE-stained prostatectomy specimens. The aim of the present study was therefore to investigate whole-mounted specimens obtained by radical prostatectomy from patients who had undergone hormone therapy. Formalin-fixed and paraffin-embedded specimens were immunostained with prostate secretory cell markers including prostate-specific antigen (PSA), P504S (alpha-methylacyl-coenzyme A racemase, AMACR), P501S (prostein), and prostate-specific membrane antigen (PSMA). Residual carcinoma was detected in 250 histological slides of 42 patients in a total of 497 slides from 45 patients. In five of 250 slides (2%), carcinoma was not able to be recognized on HE-stained slides, but was found on the immunohistochemistry slides. PSMA had reacted positively beyond a moderate degree in carcinoma from all patients. PSA was positive for carcinoma in most of the patients, while negative or minimal staining was observed in a small number of patients. Carcinoma was positively reactive with P504S and P501S in most of the patients, but was negatively reactive in a few. The Gleason score for a pretreatment needle biopsy correlated with P504S staining of the prostatectomy specimens. P504S and P501S had limited ability to identify degenerated carcinoma. PSMA was the most useful marker to identify carcinoma after hormone therapy.

Tomioka A, Tanaka M, De Velasco MA, Anai S, Takada S, Kushibiki T, Tabata Y, Rosser CJ, Uemura H, Hirao Y. · Department of Urology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. · Mol Cancer Ther. · Pubmed #18644998 links to  free full text

Abstract: The tumor suppressor gene MMAC/PTEN located on chromosome10q23.3 has dual phosphatase activity in the phosphoinositide-3-kinase signaling pathway and inhibits Akt activation, a serine-threonine kinase, which is involved in proliferative and antiapoptotic pathways. Furthermore, MMAC/PTEN is frequently inactivated in a variety of tumors including prostate cancer. In this study, we generated a new type of gene transfer drug, GelaTen, which is a microsphere of cationized gelatin hydrogels incorporating PTEN plasmid DNA. Using our previously reported radiation-resistant PC3-Bcl-2 human prostate cancer cells (PTEN deleted), we examined the efficacy of GelaTen to force the expression of PTEN in vivo to inhibit tumor growth after intratumoral injection alone or with irradiation. Combinational therapy with GelaTen and irradiation improved both the in vitro and in vivo efficacy of growth inhibition compared with GelaTen or irradiation alone. These data show that GelaTen gene therapy, enabling radiosensitization, can potentially treat prostate cancers that have MMAC/PTEN gene alterations associated with radioresistance.

Nakagawa M, Oda Y, Eguchi T, Aishima S, Yao T, Hosoi F, Basaki Y, Ono M, Kuwano M, Tanaka M, Tsuneyoshi M. · Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. · Oncol Rep. · Pubmed #17786334 No free full text.

Abstract: Histone deacetylase (HDAC) activity is one of the widely used and well-established mechanisms for regulation of various genes in cancer. To identify which subtype of class I HDACs are overexpressed in cancers, we analyzed the expression of class I HDAC isotypes composed of HDAC1, 2, 3 and 8 in several cell lines and human cancer tissues, including cancer of the stomach, esophagus, colon, prostate, breast, ovary, lung, pancreas and thyroid. The results showed that >75% of human cancer tissues and their corresponding non-cancerous epithelium showed high expression of these class I HDACs. However, the immunoreactivity of HDAC8 in both prostatic cancer tissue and non-cancerous prostate glands was lower than that in other cancer tissues. Furthermore, 5-40% of cancer tissues overexpressed class I HDACs, when compared with normal epithelium. The results suggest the potential usefulness of HDAC inhibitors for the treatment of a wide variety of human cancers.

Tanaka N, Fujimoto K, Yoshikawa M, Tanaka M, Hirao Y, Kondo H, Saito I. · Department of Urology, Nara Medical University. · Hinyokika Kiyo. · Pubmed #17702178 No free full text.

Abstract: We examined the usefulness of the volume-adjusted prostate-specific antigen (PSA) parameters for prediction of T1c prostate cancer on 210 patients who had abnormal PSA levels but no abnormal findings in digital transrectal examination (DRE) or transrectal ultrasonography (TRUS). PSA, prostate volume (PV), transition zone volume (TZV), PSAD (PSA/PV) and PSATZD (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and stepwise logistic regression models were used to calculate the odds ratios of these parameters. Fifty-three (25.2%) of all 210 patients and 31 (19.9%) of 156 patients with intermediate PSA levels had biopsy-proved prostate cancer. The ROC curves of all patients revealed that PSA, PV, TZV, PSAD and PSATZD had significant predictive values, while AUCs of PV, PSAD and PSATZD had significant predictive values as compared to that of PSA. In the patients with intermediate PSA levels, the ROC curves revealed that PV, TZV, PSAD and PSATZD had significant predictive values, but there were no significant differences in AUCs among these parameters. The stepwise logistic regression analysis showed that PV and PSATZD were significant predictive parameters in all patients and that PSATZD was the only significant predictive parameter in the patients with intermediate PSA levels. In conclusion, not only PSAD and PSATZD but also PV and TZV had significant predictive values in discriminating prostate cancer. However, the multivariate analysis showed that PSATZD had the strongest predictive value in all patients and in those with intermediate PSA levels.

Tanaka M, Komatsu N, Terakawa N, Yanagimoto Y, Oka M, Sasada T, Mine T, Gouhara S, Shichijo S, Okuda S, Itoh K. · Department of Immunology, Kurume University School of Medicine, Kurume 830-0011, Japan. · Oncol Rep. · Pubmed #17549363 No free full text.

Abstract: One of the longstanding challenges in the treatment of pancreatic cancer, the fifth most common cancer worldwide, is to establish a simple and reliable diagnostic marker for the disease. This study examined whether or not the plasma levels of IgG antibodies (IgGs) reactive to peptides derived from the prostate stem cell antigen (PSCA), which is highly expressed in pancreatic cancer cells, were elevated in patients with pancreatic cancer. Fifty-seven kinds of peptides encoded by PSCA were tested for their reactivity to plasma IgGs of pancreatic cancer patients. The results showed that the levels of IgGs specific to each of the 10 different peptides in the plasma of pancreatic cancer patients were significantly higher than those of non-cancer subjects. Eighty percent of subjects with and 18% of subjects without pancreatic cancer were diagnosed as having pancreatic cancer, respectively, when those cases showing significantly elevated levels of IgGs against at least one of the three peptides of PSCA at positions 2-11, 85-95, and 109-118 were judged as positive for pancreatic cancer. These results indicate that the measurement of IgGs reactive to these PSCA-derived peptides can provide novel information on the host-tumor interaction in pancreatic cancer, and could potentially be used as a new diagnostic tool to screen for pancreatic cancer.

Anai S, Tanaka M, Shiverick KT, Kim W, Takada S, Boehlein S, Goodison S, Mizokami A, Rosser CJ. · Division of Urology, University of Florida, Jacksonville, Florida 32209, USA. · J Urol. · Pubmed #17437847 No free full text.

Abstract: PURPOSE: Cyclooxygenase-2 functions as a survival factor by protecting cells from apoptosis. We analyzed cyclooxygenase-2 expression in LNCaP-COX-2 and LNCaP-Neo cell lines treated with irradiation. MATERIALS AND METHODS: LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 500 microM celecoxib and a dose response curve was generated. A clonogenic assay was performed in which cells were subjected to irradiation (0 to 6 Gy) with or without celecoxib. Cyclooxygenase-2 protein and other relevant proteins were measured by immunohistochemistry Western blot analysis after irradiation and celecoxib treatment. RESULTS: The 2 studied cell lines experienced cytotoxic effects of celecoxib in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to radiation therapy than LNCaP-Neo cells. Furthermore, the addition of celecoxib sensitized LNCaP-Neo and LNCaP-COX-2 cells to the cytocidal effects of radiation. Moreover, cyclooxygenase-2 over expression was associated with the over expression of pAkt and carbonic anhydrase. In this cell line irradiation alone was associated with increased expression of cyclooxygenase-2 and carbonic anhydrase. Combination therapy with irradiation and celecoxib down-regulated cyclooxygenase-2, pAKT and carbonic anhydrase. LNCaP-Neo cells expressed carbonic anhydrase and pAkt. Irradiation of these cells increased carbonic anhydrase and pAkt expression. Combination therapy with irradiation and celecoxib down-regulated carbonic anhydrase and pAkt. CONCLUSIONS: Cyclooxygenase-2 expression is also associated with pAkt and carbonic anhydrase expression. Down-regulation of cyclooxygenase-2 by celecoxib is associated with decreased expression of cyclooxygenase-2, pAkt and carbonic anhydrase, and eventual radiation sensitization, which is a phenomenon that may have clinical usefulness.

Anai S, Goodison S, Shiverick K, Iczkowski K, Tanaka M, Rosser CJ. · Department of Urology, University of Florida, Gainesville 32610, USA. · Hum Gene Ther. · Pubmed #16984224 No free full text.

Abstract: The resistance of prostate cancers to radiation therapy has been linked to abnormalities in overexpression of Bcl-2, an oncogene associated with inhibition of apoptosis. In this study, we evaluated whether the combination of the overexpression of phosphatase and tensin homolog (PTEN), a protein known to inhibit Bcl-2 expression, and radiation therapy would inhibit proliferation of Bcl-2-expressing human prostate cancer cells inoculated into the subcutis of athymic mice. Compared with either treatment alone, the combination of adenoviral vector-expressed PTEN (AdPTEN) and radiation (5 Gy) significantly inhibited xenograft tumor growth. Median tumor size on day 48 was 1030 mm3 in untreated controls, 656 mm3 in mice treated with radiation (5 Gy) alone, 640 mm3 in mice treated with AdPTEN alone, and 253 mm3 in mice treated with the combination (p<0.001). Treatment was well tolerated in all cases. Combination treatment also enhanced apoptosis (p=0.048), inhibited cellular proliferation (p=0.005), and inhibited tumor-induced neovascularity (p=0.030). Interestingly, this treatment increased apoptosis not only in tumor cells but also in tumor-associated endothelial cells. Together, these findings indicate that AdPTEN strongly inhibits the growth of human prostate tumors, especially when combined with radiation therapy, and that this effect is mediated by the induction of apoptosis and by the inhibition of angiogenesis and cellular proliferation.

Minami T, Matsueda S, Takedatsu H, Tanaka M, Noguchi M, Uemura H, Itoh K, Harada M. · Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Fukuoka, Japan. · Cancer Immunol Immunother. · Pubmed #16937115 No free full text.

Abstract: SART3-derived peptides applicable to prostate cancer patients with HLA-A3 supertype alleles were identified in order to expand the possibility of an anti-cancer vaccine, because the peptide vaccine candidates receiving the most attention thus far have been the HLA-A2 and HLA-A24 alleles. Twenty-nine SART3-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were first screened for their recognizability by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific cytotoxic T lymphocytes (CTLs) from HLA-A3 supertype(+) prostate cancer patients. As a result, five SART3 peptides were frequently recognized by IgG, and two of them-SART3 (511-519) and SART3 (734-742)-efficiently induced peptide-specific and cancer-reactive CTLs. Their cytotoxicity toward prostate cancer cells was ascribed to peptide-specific and CD8(+) T cells. These results indicate that these two SART3 peptides could be promising candidates for peptide-based immunotherapy for HLA-A3 supertype(+) prostate cancer patients.

Kakuta Y, Kobayashi Y, Tanaka M, Yazawa K, Harada Y, Itoh K. · The Department of Urology, Osaka General Medical Center. · Hinyokika Kiyo. · Pubmed #16440737 No free full text.

Abstract: Sarcomas and related proliferative lesions of specialized prostatic stroma are rare. Lesions have been classified into prostatic stromal tumor of uncertain malignant potential (P-STUMP) and prostatic stromal sarcoma based on the degree of stromal cellularity, presence of mitotic figures, necrosis, and stromal overgrowth. STUMPs are considered neoplastic, based on the observations that they may diffusely infiltrate the prostate gland and extend into adjacent tissues, and often recur. Although most cases of STUMPs do not behave in an aggressive fashion, occasional cases have been documented to recur rapidly after resection and a minority have progressed to stromal sarcoma. Here we describe a case of P-STUMP. A 57-year-old male went to his family doctor because of pollakisuria. Digital examination revealed abnormal findings in the prostate, then he was referred to our medical center. The mass was palpable in the left lobe of the prostate; it was elastic hard, surface smooth, about 2 cm in diameter. Serum PSA was elevated slightly (5.42 mg /dl). We diagnosed firstly leiomyosarcoma by transrectal ultra sound guided needle biopsy of the prostate. Then we performed radical prostatectomy. Finally we made the pathological diagnosis of P-STUMP. After 11 months, there is no sign of metastasis or recurrence.

Matsueda S, Takedatsu H, Yao A, Tanaka M, Noguchi M, Itoh K, Harada M. · Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan. · Clin Cancer Res. · Pubmed #16203785 links to  free full text

Abstract: PURPOSE: The peptide vaccine candidates identified to date have been focused on the HLA-A2 and HLA-A24 alleles. The HLA-A11, HLA-A31, and HLA-A33 alleles share binding motifs and belong to an HLA-A3 supertype family. In this study, we attempted to identify CTL-directed peptide candidates, derived from prostate-related antigens and shared by HLA-A11+, HLA-A31+, and HLA-A33+ prostate cancer patients. EXPERIMENTAL DESIGN: Based on the binding motif to the HLA-A3 supertype alleles, 42 peptides were prepared from prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and prostatic acid phosphatase (PAP). These peptides were first screened for their ability to be recognized by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific and prostate cancer-reactive CTLs from peripheral blood mononuclear cells (PBMC) of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. RESULTS: Five peptide candidates, including the PSA(16-24), PAP(155-163), PAP(248-257), PSMA(207-215), and PSMA(431-440) peptides, were frequently recognized by IgGs of prostate cancer patients. These peptides efficiently induced peptide-specific and prostate cancer-reactive CTLs from PBMCs of cancer patients with the HLA-A11, HLA-A31, and HLA-A33 alleles. Antibody blocking and cold inhibition experiments revealed that the HLA-A3 supertype-restricted cytotoxicity against prostate cancer cells could be ascribed to peptide-specific and CD8+ T cells. CONCLUSIONS: We identified prostate-related antigen-derived new peptide candidates for HLA-A11-, HLA-A31-, and HLA-A33-positive prostate cancer patients. This information could facilitate the development of a peptide-based anticancer vaccine for patients with alleles other than HLA-A2 and HLA-A24.

Tanaka M, Rosser CJ, Grossman HB. · Department of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. · Cancer Detect Prev. · Pubmed #15829377 No free full text.

Abstract: The PTEN gene, located on chromosome 10, is a phosphatase in the phosphatidylinositol 3'-kinase (PI3'K)-mediated signal transduction pathway. PTEN inhibits the activation of Akt, a serine-threonine kinase involved in proliferative metabolic and anti-apoptotic pathways, and has tumor suppressor properties. We used a PTEN adenoviral vector, Ad-MMAC, to assess the role of PTEN in the treatment of prostate cancer. Infection of Ad-MMAC in PC-3 and LNCaP prostate cancer cells (PTEN deleted, up-regulation of phosphorylated Akt) resulted in PTEN expression and significantly decreased growth compared with Ad-CTR or mock infected cells. Infection of Ad-MMAC did not inhibit the growth of DU-145 cells (wild-type PTEN). Combination therapy with Ad-MMAC and doxorubicin improved the efficacy of PTEN gene therapy in PC-3 and DU-145 cells. These data demonstrate that PTEN gene therapy can effectively treat some prostate cancers that have genomic alterations in PTEN. In others, PTEN gene therapy combined with chemotherapy is more effective.

Rosser CJ, Tanaka M, Pisters LL, Tanaka N, Levy LB, Hoover DC, Grossman HB, McDonnell TJ, Kuban DA, Meyn RE. · Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer Gene Ther. · Pubmed #14765130 No free full text.

Abstract: Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bcl-2 expression, and potentiate the G2M block induced by radiation. Four cell lines - PC-3-Bcl-2 (Bcl-2 overexpression, deleted PTEN), PC-3-Neo (wild-type Bcl-2, deleted PTEN), LNCaP (Bcl-2 overexpression, deleted PTEN), and DU-145 (wild-type Bcl-2 and PTEN) - were transduced with a recombinant adenovirus-5 vector expressing the human wild-type PTEN cDNA under the control of a human cytomegalovirus promoter (Ad-MMAC). After correction for the effect of Ad-MMAC on plating efficiency, Ad-MMAC treatment reduced the surviving fractions after 2 Gy as follows: PC-3-Bcl-2, from 60.5 to 3.6%; PC-3-Neo, no reduction; LNCaP, from 29.6 to 16.3%; and DU-145, from 32.7 to 25.7%. PTEN expression was associated with the downregulation of Bcl-2 expression in PC-3-Bcl-2 and LNCaP cell lines. Ad-MMAC plus radiotherapy potentiated the G2M block seen with radiotherapy alone only in PC-3-Bcl-2 cells. These findings suggest that overexpression of Bcl-2 result in radioresistance and inability of radiation to cause its typical G2M cell-cycle arrest.

Tanaka M, Grossman HB. · Department of Urology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. · Oncol Rep. · Pubmed #14719096 No free full text.

Abstract: Connexin 26 (Cx26) encodes a gap junction protein and is a putative tumor suppressor gene. We evaluated the effect of forced expression of Cx26 on three human prostate cancer cell lines, PC-3, LNCap, and DU-145. The three cell lines were infected with a Cx26 adenovirus vector (Ad-Cx26) or a control vector or were mock infected. We tested cell growth, cell cycle, apoptosis, and the efficacy of combined treatment with doxorubicin. Ad-Cx26 infection suppressed the growth of all the cell lines compared with controls and induced cell cycle arrest at the G2/M phase and apoptosis. Ad-Cx26 decreased the expression of Bcl-2. LNCaP cell growth was dramatically suppressed by Ad-Cx26 alone. PC-3 and DU-145 had greater growth suppression with combined gene therapy and chemotherapy than with either Ad-Cx26 or doxorubicin alone. Forced expression of Cx26 suppresses the growth of prostate cancer cells and decreases the expression of Bcl-2. Combining Cx26 gene therapy with doxorubicin results in greater growth suppression.

Tanaka M, Suzuki N, Nakatsu H, Murakami S, Matsuzaki O, Shimazaki J. · Department of Urology, Asahi General Hospital. · Hinyokika Kiyo. · Pubmed #14655599 No free full text.

Abstract: Between 1980 and June, 2002, transurethral resection of prostate was performed against 3294 cases of benign prostatic hyperplasia, and 144 cases of stage A cancer were detected (4.4%). Among these cases, 136 cases which had complete records of examination were studied. Annual number of stage A and A1:A2 ratio were not influenced by introducing PSA determination from 1991, although the number of T1c has been increasing gradually. Since subclassification of stage A is different between Japanese rules (A1; 3 chips of cancer with well-differentiated adenocarcinoma, A2; others) and TNM (T1a; 5% of less number of chips with cancer, T1b; others), two criteria were compared. Coincidence was found with 93.7%, and disagreement was due to ratio of number of chips with cancer to whole number resected, or different grade. The former difference was caused by a larger or smaller prostate. Most cases of A1 and A2 were subjected to watchful waiting or subsequent therapy. PSA was elevated in 10 cases (7%), two of which died from progression of cancer. Other cases were disease-free. Individual pathological findings are important for subclassification of stage A.

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.

Tanaka M, Suzuki N, Nakatsu H, Murakami S, Matsuzaki O, Shimazaki J. · Department of Urology, Asahi General Hospital, Chiba, Japan. · Int J Urol. · Pubmed #12757602 No free full text.

Abstract: BACKGROUND: There is a discrepancy in tumor node metastasis (TNM) staging of capsular attachment and invasion; the condition was classified as pT3 in 1987, then as pT2 in 1992. Because capsular finding associated with radical prostatectomy is an important prognostic factor, the present study was conducted to characterize clinicopathological states of cancer tissues attached to and invading the capsule. METHODS: Specimens removed by radical prostatectomy exhibiting pT2 or pT3 from 90 patients who did not receive any treatment before surgery were classified as Loc (24%, cancer tissues localized and apart from capsule), Inv (59%, attached to and invading but not penetrating capsule) and Pen (17%, penetrating capsule). Their clinicopathological profiles were examined. RESULTS: Gleason score, volume of cancer tissues, seminal vesicle invasion, positive surgical margin and regional lymph node metastasis of Inv were distributed between those of Loc and Pen. Postoperative management was decided as routine check-up or endocrine therapy according to pathological findings. Median follow-up was 59 months. Prostate-specific antigen (PSA) relapse occurred in 13 patients, one of whom died of prostate cancer. The remaining of these patients lived. Rate of PSA relapse was not different between Loc and Inv, mainly due to endocrine therapy to Inv with high risk factors. CONCLUSION: Pathological profile of Inv lies between those of Loc and Pen. Therefore, pT2a (1997) would be subclassified as Loc and Inv. Patients with Inv may be required to receive the respective management according to clinicopathological profile, which would be different to that of Loc.

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.

Tanaka M, Suzuki Y, Takaoka K, Suzuki N, Murakami S, Matsuzaki O, Shimazaki J. · Department of Urology, Asahi General Hospital, Asahi-shi, Chiba-ken, Japan. · Int J Urol. · Pubmed #11555007 No free full text.

Abstract: BACKGROUND: The progression to endocrine therapy-resistant prostate cancer is partly due to clonal change to neuroendocrine cell tumor. To elucidate this pathologic process, the clinical courses of four cases of neuroendocrine cell tumor that were found at autopsy are reported. METHODS: Between 1995 and 1999, autopsies were performed for 20 cases of prostate cancer. Lesions predominantly composed of a neuroendocrine cell tumor (small cell carcinoma) were found in four men. The clinical courses of these cases were compared to 16 other non-neuroendocrine cell tumors (adenocarcinomas). RESULTS: The outstanding features of the neuroendocrine cell tumors were: (i) survival was brief after relapse, although the duration of control by employing endocrine therapy varied; (ii) the prostate-specific antigen level did not increase after relapse; and (iii) the sites of metastasis were similar to those of common adenocarcinomas. CONCLUSION: The progression to a neuroendocrine cell tumor indicated a poor prognosis and slight (if any) changes in the serum prostate-specific antigen level. This tumor might not appear to respond to any therapeutic attempt.