Faculty Profiles - NASU Yasutomo

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進行前立腺癌の治療遺伝子治療

那須保友

第7回大塚泌尿器がん懇話会 8 2002

前立腺疾患の臨床－良性疾患から前立腺癌まで－概論前立腺癌の遺伝子診断と遺伝子治療

那須保友, 公文裕巳

日本臨床 60 ( S-11 ) 28 - 32 2002

前立腺がん手術体験記

那須保友

Medical Tribune 35 ( 4 ) 10 2002

ベッドサイド処置の実際膀胱穿刺・膀胱瘻造設術

井口裕樹, 那須保友

臨床泌尿器科 56 ( 4 ) 108 - 111 2002

BACILLUS CALMETTE-GUERIN THERAPY FOR UPPER URINARY TRACT TRANSITIONAL CELL CARCINOMA USING A TRANSVESICAL SINGLE-J STENT

ARATA RYOJI, TSUSHIMA TOMOYASU, NASU YASUTOMO, TSUGAWA MASAYA, MONDEN KOICHI, EBARA SHIN, KUMON HIROMI

64 ( 1 ) 30 - 34 2002

前立腺癌内分泌療法－臨床評価と課題－前立腺癌治療におけるLH-RH agonist投与中止後のテストステロン値の推移

賀来春紀, 津島知靖, 那須保友, 公文裕巳

日本臨床 60 ( 増1 ) 182 - 187 2002

再燃前立腺癌に対する化学療法Estramustine phosphate, Ifosfamide, Cis-platin併用療法

賀来春紀, 津島知靖, 那須保友, 雑賀隆史, 新良治, 白崎義範, 黒瀬恭平, 中田哲也, 公文裕巳, 大橋輝久, 宮地禎幸

西日本泌尿器科 64 ( 4 ) 236 - 241 2002

根治的前立腺摘除施行症例における危険因子に関する検討高感度PSAによるbiochemical failureを指標として

妹尾孝司, 那須保友, 津島知靖, 公文裕巳, 渡辺豊彦, 朝日俊彦, 林俊秀, 金重哲三, 石井亜矢乃, 高本均

西日本泌尿器科 63 ( 増刊 ) 131 - 131 2001.9

Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells

LK Li, G Yang, S Ebara, T Satoh, Y Nasu, TL Timme, CZ Ren, JX Wang, SA Tahir, TC Thompson

CANCER RESEARCH 61 ( 11 ) 4386 - 4392 2001.6

Language：English Publisher：AMER ASSOC CANCER RESEARCH

Previously, we demonstrated that up-regulation of caveolin-1 (cav-1) was associated with prostate cancer metastasis, biochemical recurrence after radical prostatectomy, and androgen insensitivity, The objective of this study was to characterize the regulation of cav-1 by testosterone (T) and to test the effects of cav-1 on prostate cancer cell survival/clonal growth and metastatic activities. Our results demonstrated that T upregulated cav-1 protein Levels in part through transcriptional regulation and significantly enhanced survival of prostate cancer cell lines ABAC3 and LNCaP after serum starvation (> 40% and >60% increased viability, respectively) and in an extended clonogenic assay (approximately 4-fold and 6-fold increase in colonies, respectively), Importantly, antisense cav-1 inhibited the survival effects of T in these assay systems. Modest but not high levels of adenoviral vector-mediated cav-1 expression alone also significantly increased viability (> 40%) and clonal growth (10-fold increase in colonies) after serum starvation. Analysis of spontaneous metastasis in stably transfected antisense cav-l mouse prostate cancer cell clones demonstrated reduction of spontaneous lymph node metastasis incidence (13%), spontaneous lymph node metastasis volume (46%), and experimental lung metastasis incidence (40%) compared with vector control cell clones, Surgical castration further reduced spontaneous lymph node metastasis incidence and volume (18% and 28%, respectively) in antisense cancer cell clones, but not in vector control clones, Our studies demonstrate that cav-1 is a downstream effector of T-mediated prostate cancer cell survival/clonal growth and that modest levels of cav-1 can independently promote prostate canter cell surival/clonal growth and metastatic activities.

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TREATMENT WITH INTERFERON-α FOR METASTATIC RENAL CELL CANCER

SHIRASAKI YOSHINORI, TSUSHIMA TOMOYASU, KURASHIGE TAKUSHI, KUSAKA NOBUYUKI, ARATA RYOUJI, KAKU HARUKI, SAIKA TAKASHI, NASU YASUTOMO, KUMON HIROMI

西日本泌尿器科 63 ( 5 ) 344 - 346 2001.5

Transrectal ultrasound for monitoring murine orthotopic prostate tumor

N Kusaka, Y Nasu, R Arata, T Saika, T Tsushima, R Kraaij, CH Bangma, H Kumon

PROSTATE 47 ( 2 ) 118 - 124 2001.5

Language：English Publisher：WILEY-LISS

BACKGROUND. The mouse orthotopic prostate tumor model has been recognized as an ideal preclinical animal model simulating the anatomical and biological milieu of the prostate. In comparison with the subcutaneous tumor model, the only disadvantage of this model is the difficulty of chronological tumor growth monitoring. We have applied recent endoluminal ultrasound technology, transrectal ultrasonography (TRUS), to the monitoring of mouse orthotopic prostate tumors.
METHODS. A 6 Fr. 20 MHz catheter-based radial scan probe was used and TRUS was performed without any prior preparation including anesthesia. Orthotopic tumors were initiated by inoculation of 5000 RM-9 cells into the dorsal prostate of 12-week-old C57BL/6 male mice. The tumor growth was monitored by TRUS from day 3 to day 21. In addition, TRUS was performed to detect tumor growth suppression after intraperitoneal administration of cis-diamminedichloroplatinum (CDDP).
RESULTS. By ultrasound, tumors became detectable 7 days after tumor cell inoculation. TRUS images were clear and parallel to actual tumor growth. The tumor volume (X) calculated by TRUS correlated significantly with the actual tumor weight (Y) measured at autopsy; Y = 101.653 + 1.174X (R = 0.930, P < 0.001). Similarly, tumor growth suppression induced by CDDP was clearly detected by TRUS with reasonable accuracy.
CONCLUSIONS. A high resolution TRUS allows simple and reliable monitoring of in situ tumor growth and growth suppression, making the mouse orthotopic prostate tumor model more efficient. Prostate 47:118-124, 2001. (C) 2001 Wiley-Liss, Inc.

DOI： 10.1002/pros.1054

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Combination gene therapy with adenoviral vector-mediated HSV-tk plus GCV and IL-12 in an orthotopic mouse model for prostate cancer

Y Nasu, CH Bangma, GW Hull, G Yang, J Wang, S Shimura, MA McCurdy, S Ebara, HM Lee, TL Timme, TC Thompson

PROSTATE CANCER AND PROSTATIC DISEASES 4 ( 1 ) 44 - 55 2001

Language：English Publisher：NATURE PUBLISHING GROUP

We previously demonstrated significant therapeutic activities associated with adenoviral vector-mediated Herpes Simplex Virus/thymidine kinase (AdHSV-tk) with ganciclovir (GCV) in situ gene therapy in the RM-1 orthotopic mouse prostate cancer model and interleukin-12 (AdmIL-12) in situ gene therapy in the RM-9 orthotopic mouse prostate model for prostate cancer. In both protocols, local cytotoxicity and activities against pre-established lung metastases were demonstrated. To test whether combined AdHSV-tk + GCV + IL-12 gene therapy would lead to enhanced therapeutic effects when compared to either treatment alone, we used RM-9 mouse prostate cancer cells in both orthotopic and preestablished lung metastases models of prostate cancer. Combined treatment with a single injection of optimal doses of AdHSV-tk + GCV or AdmIL-12 led to significantly increased suppression of orthotopic tumor growth. IL-12 gene therapy alone was more effective than AdHSV-tk + GCV in suppressing spontaneous lymph node metastases and pre-established lung metastases but combination gene therapy did not result in additional anti-metastatic activities. Combination gene therapy also did not achieve significantly better animal survival compared to AdHSV-tk + GCV or AdmIL-12 alone. Analysis of localized antitumor activities demonstrated that AdHSV-tk + GCV therapy induced higher levels of necrosis compared to AdmIL-12 or combination therapy. However, both treatments alone and combination therapy produced similar increases in apoptotic index. To address the possible mechanisms of locally co-operative cytotoxic activities, we analyzed the systemic natural killer (NK) response and the numbers of tumor-infiltrating immune cells using quantitative immunohistochemical analysis. AdHSV-tk + GCV therapy alone led to detectable increases in iNOS-positive cells, CD4 + and CD8 + T-cells and moderately increased numbers of F4/80 (macrophage selective)-positive cells within treated tumors. In contrast, AdmIL-12 elicited a highly robust pattern of tumor infiltration for all four of these immune cells that was in general mimicked by combination therapy. Further analysis of the accumulation of transforming growth factor-beta1 (TGF-beta1) immunohistochemical staining demonstrated that AdHSV-tk + GCV treatment, but not AdmIL-12 treatment, produced cancer cell-associated increases in this cytokine relative to control Ad-beta -gal injections. Interestingly, local injection with AdHSV-tk + GCV induced significant splenocyte-derived NK cell cytolytic activities with maximal response 7 days following treatment, whereas AdmIL-12 injection produced significantly higher NK activity with maximal response 2 days following injection. The combined treatment produced a higher systemic NK response over the 14-day treatment period. Depletion of NK cells in vivo demonstrated that this immunocyte subpopulation was responsible for early locally cytotoxic activities induced by AdHSV-tk + GCV but not AdmIL-12 and that NK activities were largely responsible for activities against pre-established metastases generated by both gene therapy protocols.

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根治的前立腺全摘除術後患者の経時的QOL変化

新良治, 国富公人, 渡辺豊彦, 小野憲昭, 日下信行, 白崎義範, 賀来春紀, 雑賀隆史, 那須保友, 津島知靖, 公文裕巳, 真鍋大輔

日本泌尿器科学会雑誌 92 ( 2 ) 287 - 287 2001

特集遺伝子治療臨床研究の動向前立腺癌に対する自殺遺伝子治療

那須保友, 公文裕巳

カレントテラピー 19 ( 1 ) 33 - 37 2001

泌尿器科手術における合併症管理のすべてⅣ.術後合併症とその管理無気肺

日下信行, 那須保友

臨床泌尿器科 55 ( 4 ) 284 - 285 2001

セミナー－泌尿生殖器におけるバイオマーカーの新展開－前立腺癌のバイオマーカーの現況と展望－PSAの時代におけるバイオマーカーの意義－

那須保友, 倉繁拓志

臨床泌尿器科 55 ( 7 ) 539 - 544 2001

前立腺癌のアンドロゲン依存性とカベオリン

那須保友

Urological Review 3 ( 3 ) 2 - 5 2001

前立腺癌治療の最近の話題３遺伝子治療

那須保友

診療手帖 ( 152 ) 19 - 22 2001

特集遺伝子治療はどこまで進んでいるのか泌尿器科領域のがん

那須保友

分子がん治療 2 ( 2 ) 92 - 98 2001

The absorption of pirarubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer

Y Yamamoto, Y Nasu, T Saika, T Akaeda, T Tsushima, H Kumon

BJU INTERNATIONAL 86 ( 7 ) 802 - 804 2000.11

Language：English Publisher：BLACKWELL SCIENCE LTD

Objectives To assess the validity of the prophylactic use of pirarubicin ([2'R]-4-O-tetrahydropyranyl-doxorubicin) immediately after transurethral resection of bladder tumour (TURBT), using pharmacodynamic studies.
Patients and methods The study included 20 consecutive patients with superficial bladder cancer. Pirarubicin (30 mg/50 mL or 30 mg/100 mL, 10 patients each) was instilled immediately after TURBT and retained in the bladder for 1 h. Blood samples were obtained before and at 15, 30, 60 and 120 min after the instillation. After retaining the drug for 1 h all the intravesical fluid was collected and assayed for pirarubicin.
Results The plasma pirarubicin concentration in those receiving either dose was below detectable levels at any time after instillation. The mean recovery rate of pirarubicin in the drained fluid was 73%.
Conclusion The intravesical instillation of pirarubicin immediately after TURBT caused no detectable plasma concentration and few systemic side-effects.

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