研究者詳細 - 那須　保友

MISC - 那須　保友

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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年11月

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年10月

Metastasis-related genes in prostate cancer

CH Bangma, Y Nasu, CZ Ren, TC Thompson

SEMINARS IN ONCOLOGY 26 ( 4 ) 422 - 427 1999年8月

前立腺癌遺伝子治療の現状と展望 : 将来の新しい治療法となりうるか?

那須保友, 日下信行, 賀来春紀, 新良治, 山本康雄, 津島知靖, 公文裕巳, 江原伸, THOMPSON TIMOTHY C.

西日本泌尿器科 61 ( 5 ) 405 - 411 1999年5月

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年3月

記述言語：英語出版者・発行元：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年1月

記述言語：英語出版者・発行元：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年

記述言語：英語掲載種別：書評論文，書評，文献紹介等

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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Surveillance 後に後腹膜リンパ節転移が認められた seminoma の２例

賀来春紀, 日下信行, 村上貴典, 山本康雄, 宮地禎幸, 那須保友, 津島知靖, 公文裕巳

西日本泌尿器科 61 ( 5 ) 463 - 465 1999年

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年

新しい幅広型ループを用いた経尿道的前立腺切除術と従来型のループを用いた経尿道的前立腺切除術の比較試験

橋本英昭, 津川昌也, 那須保友, 公文裕巳, 村田匡, 武田克治, 入江伸, 白崎義範, 赤枝輝明, 大橋輝久, 近藤捷嘉, 高本均, 水野全裕, 小武家誠, 西光雄

泌尿器科紀要 45 ( 6 ) 397 - 401 1999年

記述言語：日本語出版者・発行元：泌尿器科紀要刊行会

TURPにおける幅広型ループの有用性を検討するため,従来の細い針金状のループを用いたTURPとの無作為比較試験を行った. 1)手術時間,術中出血量,使用灌流液量,術前・術直後の血清Na値の変化は両群間に有意差は認めなかった. 2)合併症として被膜穿孔,低Na血症,後出血,術後尿道狭窄の発症頻度は両群間に有意差を認めなかった. 3)臨床効果は両群共に著明に改善しており,両群間に有意差は認めなかった. 4)幅広型ループを用いたTURPは従来のループを用いたTURPに比較して術中出血量の軽減,切除時間の短縮という点では必ずしも優れてはいなかったWe compared the safety and efficacy of transurethral resection of the prostate (TURP) with a thick loop and with a standard loop. We compared 36 consecutive men (median age, 70 years) with symptomatic benign prostatic hyperlasia (BPH) treated by TURP with a thick loop to a cohort of 36 men (median age, 72 years) treated by TURP with a standard loop. The safety parameters of evaluation included the operative time, blood loss, chronological changes in serum sodium, and complications. The efficacy parameters of evaluation included International Prostate Symptom Score, quality of life assessment, peak urinary flow rate, and post-void residual urine volume. The operative time (median, 49.5 versus 43.5 minutes), blood loss (median, 179 versus 127 ml), and change in serum sodium (median, -4.0 versus -6.0 mEq/L) were not significantly greater in the thick loop group than in the standard loop group, respectively. There were no major complications in either group. Clinically significant improvement was observed in all efficacy parameters in both groups, with no difference between the two groups. These results suggest that TURP with a thick loop is not necessarily superior to TURP with a standard loop in terms of decreasing the blood loss and decreasing the operative time.

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その他リンク： http://search.jamas.or.jp/link/ui/1999263631

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年

尿路癌よりの肺転移を疑わせた肺過誤腫の２例

藤田竜二, 宮地禎幸, 門田晃一, 那須保友, 津島知靖, 大森弘之, 公文裕巳

西日本泌尿器科 61 ( 1 ) 63 - 65 1999年

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年

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年9月

記述言語：英語出版者・発行元：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年8月

記述言語：英語出版者・発行元：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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内分泌療法不応前立腺癌に対する CDDP,IFM 併用療法

牧佳男, 津島知靖, 那須保友, 公文裕巳, 大森弘之, 棚橋豊子, 難波克一, 大橋輝久, 近藤捷嘉, 雑賀隆史, 朝日俊彦, 三枝道尚, 尾崎雄治郎, 山下良孝, 片山泰弘, 小武家誠, 宇埜智, 越智淳三, 小橋腎二, 畠和宏

日本泌尿器科学会雑誌 89 ( 7 ) 657 - 664 1998年7月

記述言語：日本語出版者・発行元：社団法人日本泌尿器科学会

(目的) 再燃前立腺癌に対して現在のところ有効な治療法はない. そこで我々は内分泌療法不応性前立腺癌に対してシスプラチナム, イフォスファミド併用療法の有効性と安全性を検討した. (方法) 内分泌療法不応性前立腺癌に対してシスプラチンを治療第1日に70mg/m2静脈内投与, イフォスファミドを治療第1日から第5日に1.2g/m2/日を静脈内投与し4週毎に繰返した. (結果) 27例の内分泌療法不応性前立腺癌が登録された. 27例中7例 (26%) に部分寛解 (PR), 10例 (37%) に不変 (ST) を認めた. PR 7例の効果持続期間は6から49ヵ月, 中央値16ヵ月, PR+ST 17例の効果持続期間は3から36ヵ月, 中央値10ヵ月であった. 自覚症状の改善が11例 (41%) に認められた. 全症例の生存期間は4から89ヵ月で, 3年生存率36%, 5年生存率24%, 50%生存期間23ヵ月であった. 副作用は殆どが軽度から中等度で, 貧血 (96%), 白血球減少 (89%), 食欲不振 (81%), 脱毛 (67%), 血小板減少 (44%), 血尿 (38%), 腎機能障害 (19%), 肝機能障害 (7%) が認められた. 重篤な副作用が2例に認められ, 1例は急性腎不全, もう1例はエンドトキシンショックであった. (結論) シスプラチン, イフォスファミド併用化学療法は, 内分泌療法不応性前立腺癌に対して有効であり, 考慮してよい治療法と考えられた.

DOI： 10.5980/jpnjurol1989.89.657

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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年5月

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年

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年

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年

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