Details of a Researcher - Kosaka, Takeo

Papers - Kosaka, Takeo

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Safety and efficacy of teneligliptin

Otsuki Hideo, Kosaka Takeo, Nakamura Kenzo, Shimomura Fumihiko, Kuwahara Yoshitaka, Tsukamoto Takuji

International Urology and Nephrology 46 ( 2 ) 427 - 432 2014.02

ISSN 0301-1623

Purpose: Teneligliptin is a novel DPP-4 inhibitor in development for treating type 2 diabetes mellitus that does not require dose adjustment for diabetic patients with end-stage renal disease; however, it had not been known whether or not teneligliptin is safe or potent in dialysis patients. We conducted a prospective study to assess the utility of teneligliptin for diabetic patients undergoing hemodialysis. Methods: Blood glucose, glycated albumin, and HbA1c were measured every 4 weeks, at 4, 12, 20, and 28 weeks, and every 8 weeks, respectively, for patients treated with teneligliptin (n = 14; 7 patients newly started and 7 that switched from other medications) and patients of a control group who continued ongoing antidiabetic therapy (n = 29). Results: Blood glucose level showed a 36.7 mg/dl decrease from 4 weeks in the teneligliptin group (p < 0.05). The differences in glycated albumin (at 28 w) and HbA1c (at 24 w) between the teneligliptin group and the control group were -3.1 % (p < 0.05) and -0.57 % (p = 0.057), respectively. These parameters also decreased in patients who switched from voglibose 0.2 mg t.i.d. or vildagliptin 50 mg qd after teneligliptin administration. No case with hypoglycemia was identified. One patient had the dose of a laxative administered for constipation increased; however, no patient ceased teneligliptin due to side effects. Conclusion: Teneligliptin 20 mg is well tolerated, safe, and significantly improves glycemic control in diabetic patients with end-stage renal disease. Teneligliptin 20 mg once daily was considered to be more potent than voglibose 0.2 mg t.i.d. or vildagliptin 50 mg qd.

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The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma

Tanaka Nobuyuki, Kikuchi Eiji, Kanao Kent, Matsumoto Kazuhiro, Shirotake Suguru, Kobayashi Hiroaki, Miyazaki Yasumasa, Ide Hiroki, Obata Jun, Hoshino Katsura, Hayakawa Nozomi, Kosaka Takeo, Oyama Masafumi, Miyajima Akira, Momma Tetsuo, Nakagawa Ken, Jinzaki Masahiro, Nakajima Yosuke, Oya Mototsugu

Urologic Oncology: Seminars and Original Investigations 32 ( 1 ) 2014.01

ISSN 1078-1439

Background and objective: Few studies have addressed the predictive value of positive urine cytology for prognosis in patients with upper tract urothelial carcinoma (UTUC). We investigated whether the status of preoperative urine cytology could provide additional prognostic information following radical nephroureterectomy (RNU). Materials and methods: The study included 474 patients with primary nonmetastatic UTUC (pTa-4N0M0) from a retrospective multi-institutional cohort. The median follow-up period was 35 months. Associations between the status of urine cytologic evaluation and outcomes were analyzed using multivariate Cox regression models. Urine cytology was evaluated preoperatively using voided samples. Disease recurrence was defined as any relapse in nonbladder lesions and was coded separately from intravesical recurrence. Results: Positive urine cytology was detected in 184 patients (38.8%) preoperatively. Disease recurrence occurred in 127 patients, while intravesical recurrence occurred in 219 patients; 83 patients died of UTUC during follow-up. Kaplan-Meier analysis revealed that only the incidence of intravesical recurrence was significantly associated with the status of urine cytologic evaluation (P = 0.024); the intravesical recurrence-free survival rates at 1 and 3 years following RNU were 61.4% and 46.2% in patients with positive urine cytology and 71.1% and 51.6% in their counterparts, respectively. Multivariate analysis showed that gender (hazard ratio [HR] = 1.74, 95% confidence interval [CI]; 1.28-2.43), tumor multifocality in RNU specimens (HR = 1.64, 95% CI; 1.09-2.47), and positive urine cytology (HR = 1.41, 95% CI; 1.08-1.85) were independent risk factors for subsequent intravesical recurrence. Conclusions: The results showed the prognostic value of positive urine cytology in patients with primary UTUC, and preoperative positive urine cytology may be associated with a significant increase in the prevalence of intravesical recurrence following RNU.

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Dual PI3K/mTOR Inhibitor NVP-BEZ235 Sensitizes Docetaxel in Castration Resistant Prostate Cancer

Yasumizu, Yota, Miyajima, Akira, Kosaka, Takeo, Miyazaki, Yasumasa, Kikuchi, Eiji, Oya, Mototsugu

JOURNAL OF UROLOGY 191 ( 1 ) 227 - 234 2014.01

Research paper (scientific journal), ISSN 0022-5347

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The predictive value of positive urine cytology for outcomes following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma: A multi-institutional study

Tanaka, Nobuyuki, Kikuchi, Eiji, Kanao, Kent, Matsumoto, Kazuhiro, Shirotake, Suguru, Kobayashi, Hiroaki, Miyazaki, Yasumasa, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Hayakawa, Nozomi, Kosaka, Takeo, Oyama, Masafumi, Miyajima, Akira, Momma, Tetsuo, Nakagawa, Ken, Jinzaki, Masahiro, Nakajima, Yosuke, Oya, Mototsugu

UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 32 ( 1 ) 247 - 251 2014.01

Research paper (scientific journal), ISSN 1078-1439

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Dual PI3K/mTOR inhibitor NVP-BEZ235 sensitizes docetaxel in castration resistant prostate cancer

Yasumizu Yota, Miyajima Akira, Kosaka Takeo, Miyazaki Yasumasa, Kikuchi Eiji, Oya Mototsugu

Journal of Urology 191 ( 1 ) 227 - 234 2014.01

ISSN 0022-5347

Purpose: Effective therapeutic strategies that can achieve long-term improvement in patients with castration resistant prostate cancer are urgently needed. We recently reported that the activated PI3K/Akt/mTOR signaling pathway induced by docetaxel explains resistance to docetaxel in castration resistant prostate cancer. In this study we explored the efficacy of NVP-BEZ235, a dual PI3K and mTORC1/2 inhibitor, for docetaxel resistant castration resistant prostate cancer. Materials and Methods: We used the 2 human castration resistant prostate cancer cell lines C4-2 and C4-2AT6. At our laboratory C4-2AT6 cells were established from C4-2 under androgen ablated treatment for 6 months. We investigated the efficacy of NVP-BEZ235 monotherapy and NVP-BEZ235 combined with docetaxel in vitro and in vivo. Results: Increased phosphorylated Akt in C4-2AT6 cells was significantly inhibited by NVP-BEZ235 in a dose and time dependent manner. WST cell proliferation assay results in C4-2AT6 cells revealed that combined administration of NVP-BEZ235 and docetaxel had significant, synergistically greater cytotoxicity than NVP-BEZ235 or docetaxel monotherapy. Combined NVP-BEZ235 (40 mg/kg) and docetaxel (4 mg/kg) in vivo in a castrated mouse xenograft model inhibited C4-2AT6 tumor growth to a greater degree than in the monotherapy groups. Also, NVP-BEZ235 showed significant efficacy with docetaxel at a low concentration in vivo, suggesting that NVP-BEZ235 effectively decreased resistance to docetaxel. Conclusions: Results suggest that inhibition of the PI3K/Akt/mTOR signaling pathway by NVP-BEZ235 can overcome docetaxel resistance in human castration resistant prostate cancer. Our findings provide a molecular basis for the clinical use of combined administration of NVP-BEZ235 and docetaxel in patients with castration resistant prostate cancer.

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The predictive value of C-reactive protein for prognosis in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy

Tanaka Nobuyuki, Kikuchi Eiji, Shirotake Suguru, Kanao Kent, Matsumoto Kazuhiro, Kobayashi Hiroaki, Miyazaki Yasumasa, Ide Hiroki, Obata Jun, Hoshino Katsura, Hayakawa Nozomi, Ito Yujiro, Kosaka Takeo, Kodaira Kiichiro, Oyama Masafumi, Miyajima Akira, Momma Tetsuo, Nakagawa Ken, Ueno Munehisa, Oya Mototsugu

European Urology 65 ( 1 ) 227 - 234 2014.01

ISSN 0302-2838

Background: Few studies have discussed the prognostic impact of serum C-reactive protein (CRP) level in upper tract urothelial carcinoma (UTUC). Objective: To investigate whether the perioperative level of CRP provides additional prognostic information following radical nephroureterectomy (RNU). Design, setting, and participants: A total of 564 patients with UTUC from a retrospective multi-institutional cohort were included. The median follow-up was 32 mo. Intervention: All patients underwent RNU without neoadjuvant chemotherapy, while 106 patients (18.8%) received adjuvant chemotherapy. Outcome measurements and statistical analysis: Associations between perioperative CRP level and outcome were assessed using multivariate analysis. A serum CRP level >0.50 mg/dl was defined as elevated. Results and limitations: Preoperative CRP (pre-CRP) level was elevated in 136 patients (24.1%). Multivariate analysis showed that pre-CRP elevation was an independent predictor of subsequent disease recurrence (hazard ratio [HR]: 1.47 for CRP 0.51-2.00; HR: 1.89 for CRP >2.00). Five-year recurrence-free survival rates were 69.2% in patients with pre-CRP levels ≤0.50 mg/dl, 54.3% in patients with pre-CRP levels between 0.51 and 2.00 mg/dl, and 35.4% in patients with pre-CRP levels >2.00 mg/dl (p < 0.001). Similar results were found in cancer-specific mortality, showing that pre-CRP elevation was an independent predictor of worse outcome (HR: 1.74 for CRP 0.51-2.00; HR: 2.31 for CRP >2.00). In a subgroup analysis of the elevated pre-CRP group, postoperative normalisation of CRP level was an independent predictor of better outcome. This study is limited by its retrospective nature as well as its heterogeneous group of patients and variable follow-up protocols resulting from the multi-institution design. Conclusions: Serum CRP may become a possible biomarker in UTUC, suggesting that patients with an elevated pre-CRP level could be predicted to have subsequent disease recurrence and cancer-specific mortality, while postoperative normalisation of CRP level was an independent predictor for prognosis.

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Ureteral metastasis from prostate cancer

Hongo Hiroshi, Kosaka Takeo, Yoshimine Shunsuke, Oya Mototsugu

BMJ Case Reports 2014 2014

A 59-year-old man had an elevated prostate-specific antigen (PSA) concentration (439 ng/mL) in December 2008. We diagnosed prostatic adenocarcinoma by prostate needle biopsy. CT and MRI showed a prostatic tumour with bone and lymph node metastases. Combined androgen blockade therapy reduced the PSA level temporarily. After the PSA level gradually started to increase again and reached 27.27 ng/mL in October 2010, the patient was diagnosed with castration-resistant prostate cancer and treated with docetaxel chemotherapy. Radiological examination detected left hydronephrosis and a tumour in the left lower ureter in March 2011. Retrograde pyelography and urine cytology of class 3 from the left ureter indicated that the ureteral mass was a urothelial carcinoma. A left nephroureterectomy was performed. After the operation, the pathological examination showed a metastatic prostate carcinoma, accompanied by a decrease in the serum PSA level from 59.56 to 45.33 ng/mL.

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Complete response to bicalutamide withdrawal prolonged for almost 2 years in patients with metastatic prostate cancer

Hongo Hiroshi, Kosaka Takeo, Oya Mototsugu

Urology Case Reports 2 ( 5 ) 150 - 151 2014

ISSN 2214-4420

This is the first case report describing a complete response to bicalutamide withdrawal that lasted for almost 2years in a patient with metastatic prostate cancer. An 80-year-old man who had prostate-specific antigen (PSA) level elevation (168.1ng/mL) visited our hospital in February 2010. Bone scintigraphy showed pelvic metastases. We started hormonal therapy with leuprorelin and bicalutamide. The PSA concentration decreased to <0.1ng/mL but started increasing again and reached 1.64ng/mL in October 2012, at which time bicalutamide administration was discontinued. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2years.

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Independent predictors for bladder outcomes after treatment of intravesical recurrence following radical nephroureterectomy in patients with primary upper tract urothelial carcinoma

Tanaka Nobuyuki, Kikuchi Eiji, Kanao Kent, Matsumoto Kazuhiro, Shirotake Suguru, Kobayashi Hiroaki, Miyazaki Yasumasa, Ide Hiroki, Obata Jun, Hoshino Katsura, Hayakawa Nozomi, Hagiwara Masayuki, Kosaka Takeo, Oyama Masafumi, Miyajima Akira, Momma Tetsuo, Nakagawa Ken, Jinzaki Masahiro, Hasegawa Shintaro, Nakajima Yosuke, Oya Mototsugu

Annals of Surgical Oncology 21 ( 9 ) 3151 - 3158 2014

ISSN 1068-9265

Background. Few studies have described the clinical courses and outcomes in the bladder after treatment of intravesical recurrence after radical nephroureterectomy (RNU) in patients with primary upper tract urothelial carcinoma (UTUC). We investigated the indicators for predicting subsequent bladder outcomes after treatment of intravesical recurrence after RNU. Methods. A total of 241 patients with primary UTUC (pTa-4N0M0) who experienced intravesical recurrence after RNU were included. Of these patients, 101 (41.9 %) underwent Bacillus Calmette-Guérin treatments, whereas 49 (20.3 %) underwent intravesical chemotherapy. The median follow-up period after initial transurethral resection of the bladder tumor was 33 months. Relationships with bladder outcomes were analyzed by using multivariable analysis. Results. Ninety-six patients experienced intravesical recurrence, and bladder progression was observed in 13. Cumulative incidence rates of intravesical recurrence at 1 and 5 years after treatment of the first intravesical recurrence were 31.0 and 48.4 %, whereas those of bladder progression at 1 and 5 years thereafter were 2.4 and 8.0 %. Multivariate analysis showed that the number of recurrent tumors and pT1 tumors at the time of the first intravesical relapse were independent risk factors for subsequent intravesical recurrence. With respect to bladder progression, multivariate analysis showed that pT1 tumors, the appearance of concomitant carcinoma-in situ at the time of the first intravesical relapse, and the absence of the Bacillus Calmette-Guérin treatment were independent risk factors. Conclusions. This retrospective study presents a detailed picture of further bladder outcomes after intravesical recurrence after RNU in primary UTUC patients. The results may assist physicians to develop a more rational protocol in bladder surveillance.

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Invasion and metastasis of renal cell carcinoma

Mikami Shuji, Oya Mototsugu, Mizuno Ryuichi, Kosaka Takeo, Katsube Ken Ichi, Okada Yasunori

Medical Molecular Morphology 47 ( 2 ) 63 - 67 2014

ISSN 1860-1480

Renal cell carcinoma (RCC) represents over 80 % of kidney cancer, and about 30 % of the patients with RCC develop metastasis after the surgery. Invasion of basement membrane (BM) and extracellular matrix (ECM) is an essential event in tumor invasion and metastasis. Matrix metalloproteinases (MMPs), which digest the main components of BM and ECM, are expressed in RCC. Heparanase, which degrades heparan sulfate proteoglycans, is predominantly expressed in high-grade RCCs with a positive correlation with pathological tumor stage and poor prognosis. Bone metastasis is common among the patients with RCC, and increased osteoclastic activity was observed at metastatic sites. Receptor activator of nuclear factor κB ligand (RANKL), which plays an important role in osteoclastogenesis, is predominantly expressed in high-grade RCC and its expression level is associated with bone metastasis and prognosis. Epithelial-mesenchymal transition (EMT), a switch of epithelial cells to sarcomatoid phenotype, is considered to be critical step during metastasis, and Snail, a major regulator of EMT, is predominantly expressed in high-grade RCC, and high Snail expression is a worse prognostic factor. Accordingly, heparanase, RANKL and Snail may be targets for the development of anti-tumor therapies for RCCs.

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Is DHT production by 5a-reductase friend or foe in prostate cancer?

Kosaka Takeo, Miyajima Akira, Oya Mototsugu

2014

ISSN 2234-943X

The first advance in the history of studies on prostate cancer (PCa) and androgens was the development of treatment with castration and administration of estrogen by Charles B. Huggins, who won the Nobel Prize in Physiology and Medicine. Since then, and for 70 years, androgen deprivation therapy has been the standard therapy for advanced PCa and the center of studies on PCa. However, recent advances have shed light on the relationship between androgens and the development or the progression of PCa. The use of 5AR inhibitors to prevent progression of PCa continues to be widely discussed. Discussion has been fueled by the findings of two large randomized, placebo-controlled trials: the Prostate Cancer Prevention Trial with finasteride and the Reduction by Dutasteride of Prostate Cancer Events trial. Does the development of PCa or progression to castration-resistant PCa depend on dihydrotestosterone (DHT)? Here, we summarize and discuss recent topics of local androgen production of DHT in PCa.

Malignant lymphoma of mucosa-associated lymphoid tissue involving the renal pelvis and the entire ureter

Otsuki Hideo, Ito Keiichi, Sato Ken, Kosaka Takeo, Shimazaki Hideyuki, Kaji Tatsumi, Asano Tomohiko

Oncology Letters 5 ( 5 ) 1625 - 1628 2013.10

ISSN 1792-1074

Mucosa-associated lymphoid tissue (MALT) lymphoma occurs in various sites, but rarely in the urinary tract. Imaging studies of a 69-year-old male revealed a left hydronephrosis and diffuse thickening of the renal pelvic and upper ureteral wall. Retrograde pyelography revealed a narrowing in this region, and brush cytology specimens contained atypical cells. As the lesion was considered to be malignant, surgical excision was performed. Histological analysis revealed an intense lymphoid infiltrate mainly consisting of B cells. The immunohistochemistry results demonstrated that the lesion was positive for CD20 and CD79a and negative for CD5 and cyclin D1. These findings led to a diagnosis of MALT lymphoma. Pathological exploration disclosed a focally dense invasion of lymphoma cells into not only the renal pelvis, but the whole ureteral wall and surrounding tissue; therefore, the patient underwent eight courses of rituximab treatment. Diffuse invasion of lymphoma cells into the whole ureter was rarely observed. Since the surgery, the patient has survived for 78 months without evidence of a recurrence of lymphoma.

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Editorial Comment to Circulating immunosuppressive cells of prostate cancer patients before and after radical prostatectomy

Kosaka Takeo

International Journal of Urology 20 ( 10 ) 979 2013.10

ISSN 0919-8172

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Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming

Kosaka, Takeo, Nagamatsu, Go, Saito, Shigeru, Oya, Mototsugu, Suda, Toshio, Horimoto, Katsuhisa

CANCER SCIENCE 104 ( 8 ) 1017 - 1026 2013.08

Research paper (scientific journal), ISSN 1347-9032

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Patient characteristics and outcomes in metastatic upper tract urothelial carcinoma after radical nephroureterectomy

Tanaka Nobuyuki, Kikuchi Eiji, Kanao Kent, Matsumoto Kazuhiro, Kobayashi Hiroaki, Miyazaki Yasumasa, Ide Hiroki, Obata Jun, Hoshino Katsura, Shirotake Suguru, Hayakawa Nozomi, Kosaka Takeo, Miyajima Akira, Momma Tetsuo, Nakagawa Ken, Hasegawa Shintaro, Nakajima Yosuke, Oya Mototsugu

BJU International 112 ( 2 ) 2013.07

ISSN 1464-4096

Objectives To investigate oncological outcomes and prognostic factors in patients with upper tract urothelial carcinoma (UTUC) who experienced disease recurrence after radical nephroureterectomy (RNU). Few studies have focused on the clinical courses of patients who experienced disease recurrence after RNU. Patients and Methods A total of 204 UTUC patients who experienced disease recurrence from a retrospective multi-institutional cohort were included in the present study. Associated patient outcomes were analyzed using multivariate analysis. Results The mean time from RNU to first disease recurrence was 15.0 months and ≈90% of patients experienced disease recurrence within the first 3 years after RNU. During a median follow-up of 8.1 month after disease recurrence, 165 patients died from UTUC and five patients died from other causes. In the 204 cohorts, 1- and 3-year cancer-specific survival rates were 40.2% and 9.7%, respectively, and 1- and 3-year overall survival rates were 39.5% and 9.4%, respectively. After disease recurrence, 132 patients underwent systemic chemotherapy, and a subgroup analysis of patients who underwent systemic chemotherapy multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently prognostic of cancer-specific and overall survival after relapsing. According to three significant variables, 1- and 3-year cancer-specific survival rates were 72.7% and 20.8% in patients with no risk factors, 46.5% and 7.5% in patients with one risk factor, and 26.4% and 4.4% in patients with two or three risk factors, respectively (P < 0.001). Conclusions Most patients died from UTUC within 3 years, even though systemic chemotherapies were administered after relapsing. Multivariate analysis showed that performance status, the presence of liver metastasis and the number of recurrence sites were independently related to poor survival after systemic chemotherapy.

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Patient characteristics and outcomes in metastatic upper tract urothelial carcinoma after radical nephroureterectomy: the experience of Japanese multi-institutions

Tanaka, Nobuyuki, Kikuchi, Eiji, Kanao, Kent, Matsumoto, Kazuhiro, Kobayashi, Hiroaki, Miyazaki, Yasumasa, Ide, Hiroki, Obata, Jun, Hoshino, Katsura, Shirotake, Suguru, Hayakawa, Nozomi, Kosaka, Takeo, Miyajima, Akira, Momma, Tetsuo, Nakagawa, Ken, Hasegawa, Shintaro, Nakajima, Yosuke, Oya, Mototsugu

BJU INTERNATIONAL 112 ( 2 ) E28 - E34 2013.07

Research paper (scientific journal), ISSN 1464-4096

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Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelial carcinoma

Yoshimine S., Kikuchi E., Kosaka T., Mikami S., Miyajima A., Okada Y., Oya M.

British Journal of Cancer 108 ( 11 ) 2312 - 2320 2013.06

ISSN 0007-0920

Background: Bcl-xL has an important role in the control of cell death through its inhibition of apoptosis. The aim of this study was to investigate the clinicopathological significance of Bcl-xL in upper urinary tract urothelial carcinoma (UTUC) and the therapeutic effect of targeting Bcl-xL protein in urothelial carcinoma (UC) cells. Methods: We evaluated the immunohistochemical expression of Bcl-xL in 175 UTUC patients to determine the clinical role of BclxL expression in clinical outcome. We used bafilomycin A1 (BMA) as a specific inhibitor of Bcl-xL to examine the biological effects in UC cells in vitro and in vivo. Results: Immunohistochemical analysis of Bcl-xL expression revealed that patients with a high Bcl-xL score had a significantly lower 5-year cancer-specific survival (CSS) rate (53.2%) than those with a low Bcl-xL score (77.2%) (P = 0.0011). Multivariate analysis indicated that a high Bcl-xL score was an independent prognostic factor of CSS (P = 0.023). BMA inhibited UMUC-3 cell proliferation in vitro by induction of apoptosis. Treatment with BMA significantly inhibited tumour growth in UMUC-3 tumours in this mouse xenograft model accompanied by an elevated apoptosis induction. Conclusion: Bcl-xL appears to be a significant molecular marker for the prognosis of UTUCs. Targeting Bcl-xL may be a promising therapeutic strategy for patients with UC.

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The prognostic significance of vasohibin-1 expression in patients with prostate cancer

Kosaka T., Miyazaki Y., Miyajima A., Mikami S., Hayashi Y., Tanaka N., Nagata H., Kikuchi E., Nakagawa K., Okada Y., Sato Y., Oya M.

British Journal of Cancer 108 ( 10 ) 2123 - 2129 2013.05

ISSN 0007-0920

Background:We recently isolated vasohibin-1 (VASH1), a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells (ECs), and the status of VASH1 expression has been documented in various cancer angiogenesis. The aim of this study was to assess the prognostic value of VASH1 expression in prostate cancer (PCa).Methods:In this study, we retrospectively analysed the clinical records and evaluated the VASH1 expression of tumour microvessels in 167 patients with PCa who underwent radical prostatectomy. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD) and the microvessels with activated ECs positive for VASH1 density.Results:We found that the VASH1 expression was restricted to ECs in the tumour stroma. VASH1 density was significantly associated with pathological T stage, Gleason score and MVD. The 5-year PSA recurrence-free survival rate was 58.8% in patients with higher VASH1 density (≧12 per mm 2) and 89.1% in patients with lower VASH1 density (<12 per mm 2), respectively (P<0.001). Microvessel density was not an independent predictor of PSA recurrence. Multivariate analysis revealed that high VASH1 density was an independent prognostic indicator of PSA recurrence (P=0.007, HR=2.950).Conclusion:VASH1 density represents a clinically relevant predictor of patient prognosis and can be a new biomarker that would provide additional prognostic information in PCa.

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Malignant lymphoma of mucosa-associated lymphoid tissue involving the renal pelvis and the entire ureter: A case report

Otsuki, Hideo, Ito, Keiichi, Sato, Ken, Kosaka, Takeo, Shimazaki, Hideyuki, Kaji, Tatsumi, Asano, Tomohiko

ONCOLOGY LETTERS 5 ( 5 ) 1625 - 1628 2013.05

Research paper (scientific journal), ISSN 1792-1074

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Efficacy and safety of docetaxel-based chemotherapy in Japanese men over 80 years old with castration-resistant prostate cancer.

Kosaka, Takeo, Yasumizu, Yota, Mizuno, Ryuichi, Miyajima, Akira, Kikuchi, Eiji, Shinya, Morita, Kono, Hidaka, Nakagawa, Ken, Oya, Mototsugu

JOURNAL OF CLINICAL ONCOLOGY 31 ( 15 ) 287 - 295 2013.05

Research paper (international conference proceedings), ISSN 0732-183X

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