Faculty Profiles - NASU Yasutomo

MISC - NASU Yasutomo

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Prostate cancer gene therapy: Comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines

GW Hull, MA McCurdy, Y Nasu, CH Bangma, G Yuang, S Shimura, HM Lee, JX Wang, J Albani, S Ebara, T Sato, TL Timme, TC Thompson

CLINICAL CANCER RESEARCH 6 ( 10 ) 4101 - 4109 2000.10

Language：English Publisher：AMER ASSOC CANCER RESEARCH

We have documented previously that adenovirus-mediated interleukin 12 (IL-12) gene therapy is effective for orthotopic tumor control and suppression of pre-established metastases in a preclinical prostate cancer model (Y, Nasu et at, Gene Ther,, 6: 338-349, 1999), In this report, we directly compare the effectiveness of an adenovirus that expresses both IL-12 and the costimulatory molecule B7-1 (AdmIL-12/B7) with one that expresses IL-12 alone (AdmIL-12) using the poorly immunogenic RM-9 orthotopic murine model of prostate cancer. We document AdmIL-12/B7-mediated secretion of IL-12 and increased surface expression of B7-1 in infected RM-9 tumor cells, A significant reduction in orthotopic tumor size and increased survival was demonstrated in mice treated with a single orthotopic injection of AdmIL-12/B7 compared with AdmIL-12 or controls, Six of 19 animals treated with AdmIL-12/B7 survived long term with apparent eradication of the primary tumor in contrast to one of 38 animals in the Admit-12-treated group. Orthotopic treatment of tumors with both vectors led to an infiltration of both CD4+ and CD8+ immunoreactive cells, with AdmIL-12/B7 treatment having a more prolonged infiltration of CD8+ cells. AdmIL-12/B7 was also more effective than AdmIL-12 or controls at suppression of pre-established metastases, We further developed a vaccine model based on s,c, injection of infected, irradiated RM-9 cells and found that both AdmIL-12 and AdmIL-12/B7 are effective at suppressing the development and growth of challenge orthotopic tumors using this protocol.

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Epidermal growth factor in urine from patients with bladder cancer

T Saika, T Tsushima, Y Nasu, H Kumon, H Ohmori

UROLOGICAL RESEARCH 28 ( 4 ) 230 - 234 2000.8

Language：English Publisher：SPRINGER-VERLAG

Epidermal growth factor (EGF), a mitogenic polypeptide with a molecular weight of 6000, is excreted in human urine in nanomolar quantities. Recently, some reports showed that urothelial neoplasm was related to the concentration of EGF in urine. In this study, EGF concentration in urine was measured by enzyme-linked immunosorbent assay (ELISA) in 207 samples from 112 male patients (30-90 years old, median 66.2) who had previously been treated for bladder cancer. Then, we tried to clarify the significance of urinary EGF as a marker for recurrence of bladder cancer in comparison with urine cytology. The samples were collected on occasional follow up cystoscopy. Urine from nine age-adjusted males without urological disease was also measured to obtain normal control values. In 123 samples from patients without tumors, EGF concentrations in urine decreased with age. In 84 samples obtained from patients with recurrent tumor, EGF concentrations were significantly lower than those in 123 samples from patients without tumors (P < 0.001) Furthermore, EGF concentrations in longitudinal samples collected the same patients during tumor recurrence and at the times when no tumor was detected were measured in 56 patients. EGF concentrations in the samples collected during tumor recurrence was significantly lower than that in specimens collected when there was no tumor (P < 0.01). There were no significant differences between the same samples collected during tumor recurrence with regard to tumor grade, stage shape and number of tumors. However, EGF concentration in urine from patients with carcinoma in situ (CIS) was lower than that in specimens from patients without CIS. These results indicate the usefulness of determining the EGF concentration as a marker for detecting bladder cancer recurrence. Urine cytology was also examined in the same series and findings were compared with those of urinary EGF. On cytology, class IV and V were considered positive, and on urinary EGF, less than 10 ng/mgCr were considered positive. Sensitivity was 25% for cytology and 57% for urinary EGF, while specificity was 98% and 66%, respectively. The predictive positive value was 0.88 and 0.53, respectively. With the combined use of urinary EGF and cytology, the sensitivity, specificity and predictive positive value were 68%, 64% and 0.92, respectively. In conclusion, urinary EGF seems to be a useful marker for detecting bladder cancer recurrence if performed in addition to cytology.

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Analysis of Caveolin Expression in the Development of Drug Resistance in Bladder Cancer Cell

NASU Yasutomo, WATANABE Masami, KUSAKA Nobuyuki, TSUSHIMA Tomoyasu, KUMON Hiromi

19 ( 2 ) 84 - 84 2000.6

Chromosomal numerical aberrations of exfoliated cells in the urine detected by fluorescence in situ hybridization: clinical implication for the detection of bladder cancer

T Inoue, Y Nasu, T Tsushima, Y Miyaji, T Murakami, H Kumon

UROLOGICAL RESEARCH 28 ( 1 ) 57 - 61 2000.1

Language：English Publisher：SPRINGER VERLAG

Numerical aberrations of chromosomes 7 and 9 of exfoliated cells from the urinary tract were examined using fluorescence in situ hybridization (FISH). To minimize contamination with inflammatory, squamous and normal transitional cells all samples were stained using Giemsa's solution and clusters of transitional cells were selected for FISH analysis. Samples collected from 21 patients who had cystoscopic monitoring for bladder cancer were used in this study. Cystoscopy was positive in seven patients and five biopsy-proven transitional cell carcinomas were identified. Among the patients with cancer recurrence, numerical chromosomal aberrations were detected in four cases (sensitivity: 80%) and positive cytology in two cases. This preliminary pilot study shows FISH can be a useful tool for the detection of recurrence during a follow up of bladder cancer.

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Suicide gene therapy for urogenital cancer: Current outcome and prospects

Y. Nasu, N. Kusaka, T. Saika, T. Tsushima, H. Kumon

Molecular Urology 4 ( 2 ) 67 - 71 2000

Language：English Publisher：Mary Ann Liebert Inc.

Viral-mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene has been demonstrated by several investigators to confer sensitivity to nucleoside analogs such as ganciclovir (GCV) in a variety of tumor cells including brain, prostate, bladder, kidney, ovary, head and neck, lung, pancreas, and liver cancers. Fourteen suicide gene clinical protocols using adenovirus vectors have been conducted, including four in prostate cancer. Two additional protocols for prostate cancer are in preparation in Japan and the Netherlands. A study conducted at Baylor College of Medicine was the first to demonstrate the safety of HSV-tk plus GCV therapy for human prostate cancer and the anticancer activity of gene therapy in this disease. However, it is still in the early stage of its development, with a number of problems to be overcome. Systemic delivery, specific introduction, and specific expression of the target gene are the major issues to be managed in order to establish a clinically relevant treatment strategy.

DOI： 10.1089/10915360050138611

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シンポジウム Ⅲ.膀胱 5.QOLからみた回腸利用代用膀胱とS状結腸利用代用膀胱の比較

新良治, 雑賀隆史, 那須保友, 津島知靖, 公文裕巳

第27回尿路悪性腫瘍研究会記録 QOLを考慮した尿路悪性腫瘍の治療法 49 - 51 2000

T1-T2腎細胞癌の腫瘍径と予後についての検討

津島知靖, 那須保友, 日下信行, 新良治, 賀来春紀, 山本康雄, 宮地禎幸, 岸幹雄, 公文裕巳

西日本泌尿器科 62 ( 2 ) 55 - 58 2000

前立腺癌；アンドロゲン感受性逸脱機構の新しい治験特集アンドロゲン受容体以外の機序：カベオリンなど

那須保友

Biotherapy 14 ( 7 ) 697 - 701 2000

第98回岡山医学会総会ワークショップ前立腺癌遺伝子治療の現況と展望

那須保友

岡山医学会雑誌 112 ( 1 ) 12 2000

話題前立腺癌に対する遺伝子治療－HSV-tk遺伝子を用いた自殺遺伝子治療

那須保友, 公文裕巳

医学のあゆみ 192 ( 2 ) 184 - 185 2000

特集急性腎不全のすべて-2000 急性腎不全の画像診断

那須保友, 荒木元朗

病因・病態 49 ( 3 ) 391 - 395 2000

SEXUAL DYSFUNCTION FOLLOWING CYSTECTOMY : A SURVEY USING QUESTIONNAIRES

ARATA RYOJI, KUSAKA NOBUYUKI, NAGAI ATSUSHI, NASU YASUTOMO, TSUSHIMA TOMOYASU, KUMON HIROMI, TAKEDA KATSUJI, ASAHI TOSHIHIKO, TAKENAKA TADASU, NASU YOSHITSUGU, MITSUHATA NAOKI, MIZUNO AKIHIRO, NISHI MITSUO, SAIKA TAKASHI, SUYAMA BUNZO, KISHI MIKIO

62 ( 5 ) 290 - 296 2000

前立腺癌の診断と治療－最新の研究動向－Ⅴ.前立腺癌の治療新しい治療法・新薬開発動向遺伝子治療

那須保友, 公文裕巳

日本臨床 58 ( 増刊 ) 299 - 302 2000

経皮的針生検にて診断し得た副腎原発悪性リンパ腫の２例

真鍋大輔, 永井敦, 津島知靖, 石井和史, 門田晃一, 那須保友, 公文裕巳

西日本泌尿器科 62 ( 3 ) 136 - 139 2000

泌尿器科外来診療－私はこうしている－V.外来診療のポイント尿路感染症

那須保友

臨床泌尿器科 54 ( 4 ) 191 - 196 2000

前立腺の遺伝子治療

那須保友

臨床と研究 77 ( 3 ) 536 - 540 2000

シンポジウム：泌尿器科先端技術：その習得と応用【上部尿路内視鏡の実際】上部尿路病変に対する内視鏡的検査と手術－手技習得と応用－

津川昌也, 那須保友, 公文裕巳

西日本泌尿器科 62 ( 4 ) 147 - 152 2000

泌尿器科外来診療－私はこうしている－メディカルエッセイ膀胱鏡検査－あなたが患者なら進んで受けますか？－

那須保友

臨床泌尿器科 54 ( 4 ) 110 2000

シンポジウム Ⅲ.前立腺癌 1.カベオリン(Caveolin)－前立腺癌のprogressionに関与した新しいbiomarker－

那須保友, 津島知靖, 公文裕巳

第26回尿路悪性腫瘍研究会記録尿路悪性腫瘍における新しいbiomarker 89 - 91 2000

シンポジウム：泌尿器科先端技術：その習得と応用【超音波の新しい応用】前立腺生検ならびに経尿道的前立腺高温度治療における超音波診断用造影剤の有用性

津川昌也, 佐々木克己, 妹尾孝司, 新良治, 那須保友, 公文裕巳

西日本泌尿器科 62 ( 4 ) 176 - 181 2000

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