Faculty Profiles - NASU Yasutomo

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前立腺癌に対する遺伝子治療の現況と展望 : 自殺遺伝子治療を中心に

那須保友

日本化学療法学会雜誌 = Japanese journal of chemotherapy 47 31 - 31 1999.11

より安全にPNLを行うために細径尿管鏡を用いたsafety guide wire挿入法

渡辺豊彦, 佐々木克己, 門田晃一, 津川昌也, 那須保友, 公文裕巳

Japanese Journal of Endourology and ESWL 12 ( 2 ) 157 - 157 1999.10

Metastasis-related genes in prostate cancer

CH Bangma, Y Nasu, CZ Ren, TC Thompson

SEMINARS IN ONCOLOGY 26 ( 4 ) 422 - 427 1999.8

CURRENT STATUS AND FUTURE ASPECTS OF PROSTATE CANCER GENE THERAPY : WILL IT BE A REVOLUTIONARY THERAPY?

NASU YASUTOMO, KUSAKA NOBUYUKI, KAKU HARUKI, ARATA RYOUJI, YAMAMOTO YASUO, TSUSHIMA TOMOYASU, KUMON HIROMI, EBARA SHIN, THOMPSON TIMOTHY C.

61 ( 5 ) 405 - 411 1999.5

Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model

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

GENE THERAPY 6 ( 3 ) 338 - 349 1999.3

Language：English Publisher：STOCKTON PRESS

Interleukin-12 (IL-12) can elicit potent antitumoral effects that involve the recruitment of specific immune effector cells. We investigated the efficacy of a single injection of a recombinant adenovirus expressing murine IL-12 (AdmIL-12) directly into orthotopic mouse prostate carcinomas generated from a poorly immunogenic cell line (RM-9) derived from the mouse prostate reconstitution system. Significant growth suppression (>50% reduction of tumor weight) and increased mean survival time (23.4 to 28.9 days) were observed compared with controls. Suppression of pre-established lung metastases was also observed following the injection of AdmIL-12 into the orthotopic tumor. Cytolytic natural killer cell activity was markedly enhanced 1-2 days after virus injection. Immunohistochemical analysis showed significantly elevated intratumoral infiltration of CD4(+) and CD8(+) T cells 7 days after virus injection. However, splenocyte-derived cytotoxic T lymphocytes were not defected during the 14 days following treatment. Increased numbers of nitric oxide synthase-positive macrophages were seen in the AdmIL-12 treated group 7 days following injection. Systemic inhibition of natural killer cells with anti-asialo-GM1 serum led to increased numbers of lung metastases in AdmIL-12-treated orthotopic tumors but did not affect local tumor growth. In this model system the anti-tumor effects of a single injection of adenovirus-mediated IL-12 appears to be based to a large extent on the activation of nitric oxide synthase in macrophages and possibly T cell activities, whereas the relatively early cytolytic activity of natural killer cells are largely but not exclusively responsible for the antimetastatic effects.

DOI： 10.1038/sj.gt.3300834

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Cooperative therapeutic effects of androgen ablation and adenovirus-mediated herpes simplex virus thymidine kinase gene and ganciclovir therapy in experimental prostate cancer

SJ Hall, SE Mutchnik, G Yang, TL Timme, Y Nasu, CH Bangma, SLC Woo, M Shaker, TC Thompson

CANCER GENE THERAPY 6 ( 1 ) 54 - 63 1999.1

Language：English Publisher：STOCKTON PRESS

Adenovirus-mediated transduction of the herpes simplex thymidine kinase gene (HSV-tk) in conjunction with ganciclovir (GCV) has been shown to result in significant growth suppression and to enhance survival in a model of mouse prostate cancer. However, this therapeutic activity is not sustained, because in most cases tumors eventually regrow and ultimately cause the death of the host. Androgen ablation, an inducer of apoptosis in prostate cells which is used widely as palliative therapy in patients with prostate cancer, was combined with HSV-tk plus GCV using an androgen-sensitive mouse prostate cancer cell line. The combination of castration and HSV-tk plus GCV led to markedly enhanced tumor growth suppression in both subcutaneous and orthotopic models compared with either treatment alone and resulted in an enhanced survival in which combination-treated animals lived twice as long as controls in the subcutaneous model and over 50% longer than controls in the orthotopic model. Further analysis of apoptotic activity demonstrated high levels of apoptosis only in combined androgen ablation and HSV-tk plus GCV-treated tumors after 14 days of growth in an androgen-depleted environment and 8 days after HSV-tk plus GCV therapy. At this time, the apoptotic index, but not the percent of necrotic tissue, was significantly higher for combination therapy-treated tumors relative to control-treated tumors or either treatment alone. These data indicate that the therapeutic effects of androgen ablation and HSV-tk plus GCV are cooperative and that increased apoptosis may, in part, underlie these activities.

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Prostate cancer gene therapy: Outcome of basic research and clinical trials

Y. Nasu, B. Djavan, M. Marberger, H. Kumon

Techniques in Urology 5 ( 4 ) 185 - 190 1999

Language：English Publishing type：Book review, literature introduction, etc.

With the advances in genetic engineering, tumor biology, and immunology, gene therapy has been recognized as a promising new treatment option for cancer, including prostate cancer. Several clinical trials of prostate cancer gene therapy currently underway are using therapeutic genes, including suicide genes, immunomodulatory genes, tumor suppressor genes, and antioncogenes. Although gene therapy for prostate cancer as a clinical alternative is still at an early stage that requires several technological breakthroughs, information obtained from clinical trials indicates the full potential of prostate cancer gene therapy. Concordant progress in basic research and gene therapy technology will ready prostate cancer gene therapy for widescale use in the future. In this report, the general concept and current progress in prostate cancer gene therapy are summarized.

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PubMed

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RETROPERITONEAL RELAPSE UNDER POST-ORCHIECTOMY SURVEILLANCE IN STAGE I TESTICULAR SEMINOMA : A REPORT OF TWO CASES

KAKU HARUKI, KUSAKA NOBUYUKI, MURAKAMI TAKANORI, YAMAMOTO YASUO, MIYAJI YOSHIYUKI, NASU YASUTOMO, TSUSHIMA TOMOYASU, KUMON HIROMI

61 ( 5 ) 463 - 465 1999

ワークショップ：腹腔鏡下手術－Borderless時代を迎えて泌尿器科医はいかにあるべきか？－UPJ形成－Ureterovascular hydronephrosisに対する後腹膜鏡下手術－

永井敦, 橋本英昭, 津川昌也, 那須保友, 公文裕巳

西日本泌尿器科 61 ( 4 ) 308 - 312 1999

A comparative study of a thick and standard loop in transurethral resection of the prostate

45 ( 6 ) 397 - 401 1999

泌尿器科画像診断 Ⅰ．画像診断の基礎知識検査法別にみた適応と禁忌

那須保友, 公文裕巳

臨床泌尿器科 53 ( 4 ) 43 - 47 1999

PULMONARY HAMARTOMA MIMICKING METASTATIC PULMONARY TUMOR ARISING FROM UROLOGICAL CANCER : A REPORT OF TWO CASES

FUJITA RYUJI, MIYAJI YOSHIYUKI, MONDEN KOUICHI, NASU YASUTOMO, TSUSHIMA TOMOYASU, OHMORI HIROYUKI, KUMON HIROMI

61 ( 1 ) 63 - 65 1999

腎盂尿管移行部狭窄症に対する経皮的腎盂切開術における crossing vessel の検討

橋本英昭, 津川昌也, 那須保友, 公文裕巳

Japanese Journal of Endourology and ESWL 12 ( 1 ) 66 - 72 1999

Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells

Y Nasu, TL Timme, G Yang, CH Bangma, LK Li, CZ Ren, SH Park, M DeLeon, JX Wang, TC Thompson

NATURE MEDICINE 4 ( 9 ) 1062 - 1064 1998.9

Language：English Publisher：NATURE AMERICA INC

Although prostate cancer cells are often initially sensitive to androgen ablation, they eventually lose this response and continue to survive, grow and spread in the absence of androgenic steroids. The mechanism(s) that underlie resistance to androgen ablation therapy remain mostly unknown. We have demonstrated that elevated caveolin protein levels are associated with human prostate cancer progression in pathological specimens(1). Here we show that suppression of caveolin expression by a stably transfected antisense caveolin-1 cDNA vector converted androgen-insensitive metastatic mouse prostate cancer cells to an androgen-sensitive phenotype. Orthotopically grown tumors and low-density cell cultures derived from antisense caveolin clones had increased apoptosis in the absence of androgenic steroids, whereas similarly grown tumors and cells from vector (control) clones and parental cells were not sensitive to androgens. Studies using a representative antisense caveolin clone showed that selection for androgen resistance in vivo correlated with increased caveolin levels, and that adenovirus-mediated caveolin expression blocked androgen sensitivity. Our results identify a new candidate gene for hormone-resistant prostate cancer in man and indicate that androgen insensitivity can be an inherent property of metastatic prostate cancer.

DOI： 10.1038/2048

Elevated expression of caveolin is associated with prostate and breast cancer

G Yang, LD Truong, TL Timme, CZ Ren, TM Wheeler, SH Park, Y Nasu, CH Bangma, MW Kattan, PT Scardino, TC Thompson

CLINICAL CANCER RESEARCH 4 ( 8 ) 1873 - 1880 1998.8

Language：English Publisher：AMER ASSOC CANCER RESEARCH

To identify genes associated with prostate cancer progression, we developed a strategy involving the use of differential display-PCR with a panel of genetically matched primary tumor- and metastasis-derived mouse prostate cancer cell lines. We isolated a cDNA fragment with homology to the mouse caveolin-1 gene. Northern blotting with this fragment revealed increased caveolin expression in metastasis-derived cell lines relative to primary tumor-derived cell lines, Western blotting with a polyclonal caveolin antibody confirmed increased caveolin protein in metastasis-derived mouse cell lines and expression in three of four human prostate cancer cell lines. Immunohistochemical analysis of a human prostate cancer cell line demonstrated a prominent granular pattern of caveolin accumulation. Subsequent analysis of mouse and human prostate specimens revealed minimal caveolin expression in normal epithelium with abundant staining of smooth muscle and endothelium. The frequency of caveolin-positive cells was increased in prostate cancer with markedly increased accumulation of caveolin and a granular staining pattern in lymph node metastatic deposits. In human breast cancer specimens, increased caveolin staining was detected in intraductal and infiltrating ductal carcinoma as well as nodal disease, Caveolin therefore appears to be associated with human prostate cancer progression and is also present in primary and metastatic human breast cancer.

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COMBINATION CHEMOTHERAPY WITH CIS-PLATINUM AND IFOSFAMIDE FOR HORMONE UNRESPONSIVE PROSTATE CANCER

MAKI Yoshio, TSUSHIMA Tomoyasu, NASU Yasutomo, KUMON Hiromi, OHMORI Hiroyuki, TANAHASHI Toyoko, NANBA Katsuichi, OHASHI Teruhisa, KONDO Katsuyoshi, SAIKA Takashi, ASAHI Toshihiko, SAEGUSA Michinao, OZAKI Yujiro, YAMASHITA Yoshitaka, KATAYAMA Yasuhiro, KOBUKE Makoto, UNO Satoshi, OCHI Junzo, KOBASHI Kenji, HATA Kazuhiro

The Japanese Journal of Urology 89 ( 7 ) 657 - 664 1998.7

Language：Japanese Publisher：The Japanese Urological Association

(Purpose) There is no effective therapy against hormone refractory prostate cancer. This led us to evaluate the effectiveness and toxicity of cis-platinum (CDDP) and ifosfamide (IFM) combination chemotherapy in the patients with hormone-unresponsive carcinoma of the prostate. (Methods) Patients with hormone-unresponsive prostate cancer were scheduled to receive CDDP 70mg/m2 intravenously on day 1 and IFM 1.2g/m2/day intravenously on day 1 through day 5 of 28-day cycle. (Results) Twenty seven patients with hormone unresponsive prostate cancer were enrolled onto this trial. Of these patients, seven (26%) demonstrated a partial objective response (PR), and ten (37%) a stable disease (ST). The response duration of PR cases lasted from 6 to 49 months with a median of 16 months and the response duration of PR+ST cases lasted from 3 to 36 months with a median of 10 months. Subjective improvement was obtained in 11 patients (41%). Survival duration of all cases were 4 to 89 months with a median of 23 months and probabilities of survival at 3 years and 5 years were 36% and 24%, respectively. The toxicity of this treatment was mostly mild to moderate, anemia (96%), leukocytopenia (89%), anorexia (81%), alopecia (67%), thrombocytopenia (44%), hematuria (38%), renal dysfunction (19%) and liver dysfunction (7%) were noticed. Severe toxicity was observed in two cases, one acute renal failure and one endotoxin shock. (Conclusion) We conclude that CDDP and IFM combination chemotherapy was active regimen for hormone unresponseive prostate cancer.

DOI： 10.5980/jpnjurol1989.89.657

CiNii Article

CiNii Books

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Experimental gene therapy for prostate cancer: Treatment of mouse prostate cancer with adenovirus mediated interleukin-12 gene transduction alone and in combination with herpes simplex virus thymidine kinase gene transduction and ganciclovir therapy

Y Nasu, CH Bangma, GW Hull, JC Hu, JX Wang, TL Timme, TC Thompson

JOURNAL OF UROLOGY 159 ( 5 ) 1 - 1 1998.5

シンポジウムⅡ 泌尿器科悪性腫瘍における臓器温存治療の適応と限界浸潤性膀胱癌に対する膀胱部分切除術の治療成績

津島知靖, 村上貴典, 江原伸, 日下信行, 郭春鋼, 宮地禎幸, 山本康雄, 那須保友, 公文裕巳, 大森弘之

西日本泌尿器科 60 ( 5 ) 397 - 401 1998

前立腺癌の画像診断 MRIとPET 前立腺癌の画像診断におけるMRIの特徴，有用性および限界

那須保友, 村上貴典

日本臨牀 56 ( 8 ) 2042 - 2045 1998

ステロイド療法が著効を示した小児膀胱後部Inflammatory pseudotumorの１例

郭春鋼, 津島知靖, 津川昌也, 那須保友, 公文裕巳, 大森弘之

西日本泌尿器科 60 ( 9 ) 669 - 672 1998

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