Details of a Researcher - Oya, Mototsugu

Papers - Oya, Mototsugu

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Kidney cancer working group report

Naito Seiji, Tomita Yoshihiko, Rha Sun Young, Uemura Hirotsugu, Oya Mototsugu, Song He Zhi, Zhong Li Han, Wahid Mohamed Ibrahim Bin A

Japanese Journal of Clinical Oncology 40 ( SUPPL. 1 ) 2010.09

ISSN 0368-2811

Kidney cancer accounts for approximately 2% of all cancers worldwide, with renal cell carcinoma being the most common form and this report is focused on renal cell carcinoma. Globally, the incidence and mortality rates are increasing by 2-3% per decade. Kidney cancer is less common in Asia compared with the West. Cigarette smoking, obesity, acquired cystic kidney disease and inherited susceptibility are known risk factors for kidney cancer. The National Comprehensive Cancer Network Guidelines recommend surgical excision as first line of treatment for Stage I, II or III kidney cancer patients and Stage IV patients with resectable tumours. Immunotherapy has a 20-year history in treatment of metastatic kidney cancer. Highdose interleukin-2 (IL-2) is administered in some countries, whereas low-dose IL-2 and interferon-alpha (IFN-α) are popular in Japan. Molecular-targeted drugs, including sunitinib, bevacizumab and sorafenib, are being used for previously untreated and refractory patients. Asian and non-Asian populations have shown large differences in the incidences of adverse events with sorafenib and sunitinib. Consensus Statement: Kidney cancer is relatively uncommon in Asia compared with the West, but its incidence is increasing in more developed Asian nations. Guidelines from the National Comprehensive Cancer Network, etc., for treating metastatic renal cell carcinoma are based on Phase III clinical trials conducted primarily in Western patients. Targeted therapies are now becoming primary recommendations, but efficacy/toxicity data from Asian patients are lacking. Some drugs cause adverse effects in Asians because their recommended dosages are optimal for Caucasians but may be too high for Asians. Further research is necessary to develop optimal treatment strategies for Asians.

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Kidney Cancer Working Group Report

Naito Seiji, Tomita Yoshihiko, Rha Sun Young, Uemura Hirotsugu, Oya Mototsugu, Song He Zhi, Zhong Li Han, Wahid Mohamed Ibrahim Bin A.

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 40 i51 - i56 2010.09

Research paper (scientific journal), Joint Work, ISSN 0368-2811

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Preimplant factors affecting postimplant CT-determined prostate volume and the CT/TRUS volume ratio after transperineal interstitial prostate brachytherapy with I-125 free seeds

Sugawara Akitomo, Nakashima Jun, Kunieda Etsuo, Nagata Hirohiko Asakura Hirotaka, Oya Mototsugu, Shigematsu Naoyuki

RADIATION ONCOLOGY 5 619 - 624 2010.09

Research paper (scientific journal), Joint Work, ISSN 1748-717X

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Regulation of human dendritic cells by a novel specific nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin

Shinoda Kazunobu, Nakagawa Ken, Kosaka Takeo, Tanaka Nobuyuki, Maeda Takahiro, Kono Hidaka, Mizuno Ryuichi, Kikuchi Eiji, Miyajima Akira, Umezawa Kazuo, Oya Mototsugu

Human Immunology 71 ( 8 ) 763 - 770 2010.08

ISSN 0198-8859

Regulation of antigen-presenting cells (APC) is crucial in controlling allograft rejection. Dendritic cells (DC) are the most potent APC and must mature to present antigens to T-cell receptors. During DC maturation, nuclear factor-κB (NF-κB) is a key transcriptional factor. We synthesized dehydroxymethylepoxyquinomicin (DHMEQ), which specifically inhibits the final step of nuclear translocation of activated NF-κB proteins and examined its immunoregulatory effects on human monocyte-derived DC (Mo-DC). Regulatory Mo-DC were generated by pretreatment with DHMEQ before LPS stimulation, which were termed dl-DC. DHMEQ pretreatment (5 μg/ml) completely inhibited nuclear translocation of activated NF-κB. DHMEQ significantly inhibited DC production of κproinflammatory cytokines (IL-6, TNF-α, and IL-12 p70) in a dose-dependent manner. IL-12 was most potently inhibited. However, IL-10 production by dl-DC was only moderately affected by DHMEQ. Although CD40 and the expression of HLA-DR (HLA-DR) expression on dl-DC was downregulated, CD80 and CD86 expression was moderately upregulated. Induction of T helper 1 cell responses was efficiently impaired by dl-DC. This confirmed that DHMEQ-treated Mo-DC exhibited immunoregulatory effects. These findings suggest that DHMEQ has potential as an immunosuppressive drug for human immune cells.

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Regulation of human dendritic cells by a novel specific nuclear factor-kappa B inhibitor, dehydroxymethylepoxyquinomicin

Shinoda Kazunobu, Nakagawa Ken, Kosaka Takeo, Tanaka Nobuyuki, Maeda Takahiro, Kono Hidaka, Mizuno Ryuichi, Kikuchi Eiji, Miyajima Akira, Umezawa Kazuo, Oya Mototsugu

HUMAN IMMUNOLOGY 71 ( 8 ) 763 - 770 2010.08

Research paper (scientific journal), ISSN 0198-8859

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Long-term results of children with renal cell carcinoma

Asanuma Hiroshi, Mizuno Ryuichi, Kono Hidaka, Shinoda Nobuyuki, Kikuchi Eiji, Satoh Hiroyuki, Muramatsu Masaki, Matsui Zenichi, Nagara Hirohiko, Miyajima Akira, Nakagawa Ken, Oya Mototsugu

INTERNATIONAL JOURNAL OF UROLOGY 17 A141 - A141 2010.08

Research paper (scientific journal), Joint Work, ISSN 0919-8172

[Genitourinary cancers].

Mizuno Ryuichi, Oya Mototsugu

Nippon rinsho. Japanese journal of clinical medicine 68 Suppl 8 485 - 488 2010.08

ISSN 0047-1852

Risk classification for non-muscle invasive bladder cancer

Kikuchi Eiji, Oya Mototsugu

Japanese Journal of Clinical Urology 64 ( 9 ) 633 - 638 2010.08

ISSN 0385-2393

Retroperitoneal mixed-type perinephric liposarcoma

Daimon Tatsuaki, Maeda Takahiro, Shirakawa Hiroshi, Mikami Shuji, Mukai Makio, Oya Mototsugu

Japanese Journal of Clinical Urology 64 ( 9 ) 665 - 668 2010.08

ISSN 0385-2393

A 66-year-old man, with abdominal distention, was referred to our department for the treatment of an abdominal tumor. Contrast computed tomogram and magnetic resonance imaging revealed a large retroperitoneal fatty tissue mass with calcification measured about 25 cm in diameter. The tumor, displacing the jejunum and the descending colon, was diagnosed as a liposarcoma. The previous contrast computed tomogram showed the abnormal signal in the left renal capsule, suggesting that the tumor was originated from the perinephric tissue. A complete excision of the tumor with concomitant resection of the left kidney was performed in September, 2009. The tumor did not involve other organs and weighed 5.88 kg. Histological examination disclosed retroperitoneal mixed-type liposarcoma composed of well-differentiated and dedifferentiated type. The patient did not consent to receive any adjuvant therapy. Neither local recurrence nor metastasis has been seen at 5 months after the operation.

How do young residents practice laparoscopic surgical skills?

Miyajima Akira, Hasegawa Masanori, Takeda Toshikazu, Tamura Kouetsu, Kikuchi Eiji, Nakagawa Ken, Oya Mototsugu

Urology 76 ( 2 ) 352 - 356 2010.08

ISSN 0090-4295

Objectives: To investigate whether a training system using a dry box is feasible for training young urologists. Despite laparoscopic surgery being widely indicated for several urological diseases, a laparoscopic training system for young urologists has not been fully established yet. However, the learning curve for laparoscopic surgery has not yet been ascertained. Methods: We continued to test 11 sixth-year residents (postgraduate year: PGY6) and third-year residents (PGY3) in our department in terms of surgical skills using a dry box. We gave them several tasks (cutting and suturing) and let them practice until task completion. We continued to test all participants by these tasks for 16 weeks. Results: At the beginning of the present study, the PGY6 residents achieved significantly better scores than the PGY3 residents. However, the difference between the 2 groups became insignificant over time. Furthermore, statistical analysis revealed that a practice time of 100 minutes per week was the only significant factor affecting the last test score. For the final test, the mean practice time for all participants was 79.1 minutes per week. Conclusions: These results suggest that laparoscopic surgical skills can definitely be polished by adequate voluntary practice.

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Characteristics and management of erectile dysfunction after various treatments for prostate cancer

Soh Jintetsu, Kaiho Yasuhiro, Kikuchi Eiji, Oya Mototsugu, Yoshioka Kunihiko, Nakagami Yoshihiro, Hatano Tadashi, Ozu Choichirou, Horiguchi Yutaka, Namiki Kazunori, Tachibana Masaaki, Hisasue Shin Ichi, Tanaka Nobumichi, Asakawa Isao

International Journal of Urology 17 ( 8 ) 689 - 697 2010.08

ISSN 0919-8172

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How do young residents practice laparoscopic surgical skills?

Miyajima A., Hasegawa M., Takeda T., Tamura K., Kikuchi E., Nakagawa K., Oya M.

International Braz J Urol 36 ( 4 ) 502 2010.07

ISSN 1677-5538

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mTOR inhibitors

Oya Mototsugu

Nippon rinsho. Japanese journal of clinical medicine 68 ( 6 ) 1067 - 1071 2010.06

ISSN 0047-1852

Mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving proliferation, cell survival, and angiogenesis. These pathways are frequently abnormally regulated in cancer. Notably, Akt is an upstream molecule which is over-expressed and/or activated in several cancers. Therefore, mTOR inhibitors can be options for the treatment of cancers. At present, mTOR inhibitors are applied to treat patients with metastatic renal cell carcinoma (RCC). Temsirolimus is indicated as the first line therapy for RCC patients with poor prognosis, whereas everolimus as the second line for those refractory to sorafenib or sunitinib. Interstitial pneumonia is the most serious adverse event for both agents. Clinical trials are under way to explore indications for various cancers.

Late Recurrence and Progression in Non-muscle-invasive Bladder Cancers After 5-year Tumor-free Periods

Matsumoto Kazuhiro, Kikuchi Eiji, Horiguchi Yutaka, Tanaka Nobuyuki, Miyajima Akira, Nakagawa Ken, Nakashima Jun, Oya Mototsugu

UROLOGY 75 ( 6 ) 1385 - 1390 2010.06

Research paper (scientific journal), Joint Work, ISSN 0090-4295

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The clinical significance of urine cytology after a radical cystectomy for urothelial cancer

Yoshimine Shunsuke, Kikuchi Eiji, Matsumoto Kazuhiro, Ide Hiroki, Miyajima Akira, Nakagawa Ken, Oya Mototsugu

INTERNATIONAL JOURNAL OF UROLOGY 17 ( 6 ) 527 - 532 2010.06

Research paper (scientific journal), ISSN 0919-8172

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Impact of Tumor Location on Prognosis for Patients with Upper Tract Urothelial Carcinoma Managed by Radical Nephroureterectomy

Raman Jay D., Ng Casey K., Scherr Douglas S., Margulis Vitaly, Lotan Yair, Bensalah Karim, Patard Jean Jacques, Kikuchi Eiji, Montorsi Francesco, Zigeuner Richard, Weizer Alon, Bolenz Christian, Koppie Theresa M., Isbarn Hendrik, Jeldres Claudio, Kabbani Wareef, Remzi Mesut, Waldert Mathias, Wood Christopher G., Roscigno Marco, Oya Mototsuga, Langner Cord, Wolf J. Stuart, Ströbel Philipp, Fernández Mario, Karakiewcz Pierre, Shariat Shahrokh F.

European Urology 57 ( 6 ) 1072 - 1079 2010.06

ISSN 0302-2838

Background: There is a lack of consensus regarding the prognostic significance of ureteral versus renal pelvic upper tract urothelial carcinoma (UTUC). Objective: To investigate the association of tumor location on outcomes for UTUC in an international cohort of patients managed by radical nephroureterectomy (RNU). Design, setting, and participants: A retrospective review of institutional databases from 10 institutions worldwide identified patients with UTUC. Intervention: The 1249 patients in the study underwent RNU with ipsilateral bladder cuff resection between 1987 and 2007. Measurements: Data accrued included age, gender, race, surgical approach (open vs laparoscopic), tumor pathology (stage, grade, lymph node status), tumor location, use of perioperative chemotherapy, prior endoscopic therapy, urothelial carcinoma recurrence, and mortality from urothelial carcinoma. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the dominant tumor. Results and limitations: The 5-yr recurrence-free and cancer-specific survival estimates for this cohort were 75% and 78%, respectively. On multivariate analysis, only pathologic tumor (pT) classification (p < 0.001), grade (p < 0.02), and lymph node status (p < 0.001) were associated with disease recurrence and cancer-specific survival. When adjusting for these variables, there was no difference in the probability of disease recurrence (hazard ratio [HR]: 1.22; p = 0.133) or cancer death (HR: 1.23; p = 0.25) between ureteral and renal pelvic tumors. Adding tumor location to a base prognostic model for disease recurrence and cancer death that included pT stage, tumor grade, and lymph node status only improved the predictive accuracy of this model by 0.1%. This study is limited by biases associated with its retrospective design. Conclusions: There is no difference in outcomes between patients with renal pelvic tumors and with ureteral tumors following nephroureterectomy. These data support the current TNM staging system, whereby renal pelvic and ureteral carcinomas are classified as one integral group of tumors.

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Adrenocortical zonation in humans under normal and pathological conditions

Nishimoto Koshiro, Nakagawa Ken, Li Dan, Kosaka Takeo, Oya Mototsugu, Mikami Shuji, Shibata Hirotaka, Itoh Hiroshi, Mitani Fumiko, Yamazaki Takeshi, Ogishima Tadashi, Suematsu Makoto, Mukai Kuniaki

Journal of Clinical Endocrinology and Metabolism 95 ( 5 ) 2296 - 2305 2010.05

ISSN 0021-972X

Context: Aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) catalyze the terminal steps for aldosterone and cortisol syntheses, respectively, thereby determining the functional differentiationofhumanadrenocortical cells. Little isknown, however, about how the cells expressing the enzymes are actually distributed in the adrenals under normal and pathological conditions. Objective: The objective of the study was to determine the localization of CYP11B2 and -B1 in human adrenal specimens by using developed antibodies capable of distinguishing the two enzymes from each other. Results: Under normal conditions, CYP11B2 was sporadically detected in the zona glomerulosa, whereas CYP11B1 was entirely detected in the zonae fasciculata-reticularis. Adrenocortical cells lacking both enzymes were observed in the outer cortical regions. In addition to conventional zonation, we found a variegated zonation consisting of a subcapsular cell cluster expressing CYP11B2, which we termed aldosterone-producing cell cluster,andaCYP11B1- expressing area. Aldosterone-producing adenomas differed in cell populations expressing CYP11B2 from one another, whereas CYP11B1-expressing and double-negative cells were also intermingled. Adenomas from patients with Cushing's syndrome expressed CYP11B1 entirely but not CYP11B2, resulting in atrophic nontumor glands. The nontumor portions of both types of adenomas bore frequently one or more aldosterone-producing cell clusters, which sustained CYP11B2 expression markedly under the conditions of the suppressed renin-angiotensin system. Conclusion: Immunohistochemistry of the human normal adrenal cortex for CYP11B2 and CYP11B1 revealed a variegated zonation with cell clusters constitutively expressing CYP11B2. This technique may provide a pathological confirmatory diagnosis of adrenocortical adenomas.

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Adrenocortical Zonation in Humans under Normal and Pathological Conditions

Nishimoto Koshiro, Nakagawa Ken, Li Dan, Kosaka Takeo, Oya Mototsugu, Mikami Shuji, Shibata Hirotaka, Itoh Hiroshi, Mitani Fumiko, Yamazaki Takeshi, Ogishima Tadashi, Suematsu Makoto, Mukai Kuniaki

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 95 ( 5 ) 2296 - 2305 2010.05

Research paper (scientific journal), Joint Work, ISSN 0021-972X

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Evidence-based Sex-related Outcomes After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: Results of a Large Multicenter Study (vol 73, pg 142, 2009)

Fernandez Mario I., Shariat Shahrokh F., Margulis Vitaly, Bolenz Christian, Montorsi Francesco, Suardi Nazareno, Remzi Mesut, Wood Christopher G., Roscigno Marco, Kikuchi Eiji, Oya Mototsugu, Zigeuner Richard, Langner Cord, Weizer Alon, Lotan Yair, Koppie Theresa M., Raman Jay D., Karakiewicz Pierre, Bensalah Karim, Schultz Marcela, Bernier Pablo

UROLOGY 75 ( 5 ) 1243 - 1243 2010.05

Research paper (scientific journal), Joint Work, ISSN 0090-4295

Potent Cytotoxic Effect of a Novel Nuclear Factor-κB Inhibitor Dehydroxymethylepoxyquinomicin on Human Bladder Cancer Cells Producing Various Cytokines

Kodaira Kiichiro, Kikuchi Eiji, Kosugi Michio, Horiguchi Yutaka, Matsumoto Kazuhiro, Kanai Kunimitsu, Suzuki Eriko, Miyajima Akira, Nakagawa Ken, Tachibana Masaaki, Umezawa Kazuo, Oya Mototsugu

Urology 75 ( 4 ) 805 - 812 2010.04

ISSN 0090-4295

Objectives: To explore the potential therapeutic effects of the nuclear factor-κB (NF-κB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ). KU-19-19 cells, originally derived from a patient with invasive bladder cancer who exhibited marked leukocytosis, produce multiple cytokines. This model of clinically advanced bladder cancer, in which NF-κB is constitutively activated, was used in this study. Methods: Expression of p65 protein in fractionated KU-19-19 cells was determined by Western blotting analysis. DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay. The cytotoxic effects and induction of apoptosis by DHMEQ were analyzed, and cytokines in the supernatant of KU-19-19 cells cultured with or without DHMEQ were measured by enzyme-linked immunosorbent assay (ELISA). Athymic nude mice bearing KU-19-19 subcutaneous tumors were subjected to intraperitoneal administration of 2 mg/kg/d DHMEQ for 3 weeks. Tumor growth was monitored and microvessel density, vascular endothelial growth factor expression, and the apoptotic index of tumors were evaluated by tissue immunohistochemistry. Results: NF-κB was constitutively activated in KU-19-19 cells. DHMEQ reversibly inhibited the DNA-binding activity of NF-κB by blocking its nuclear translocation. Both cell viability and production of cytokines were significantly and dose-dependently suppressed by DHMEQ, and significant apoptosis was also induced. In in vivo studies, the mean tumor volume in mice treated with DHMEQ was significantly smaller than in controls. Immunohistochemical analysis of tumors revealed marked reduction in microvessel density, vascular endothelial growth factor expression, and induction of apoptosis. Conclusions: Blockade of NF-κB function by DHMEQ may be a useful new molecular targeting treatment for highly aggressive bladder cancer.

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