論文 - 大家　基嗣

Activation of signal transducer and activator of transcription 3 in renal cell carcinoma

Horiguchi Akio, Oya Mototsugu, Shimada Tetsuya, Uchida Atsushi, Marumo Ken, Murai Masaru

Journal of Urology 168 （ 2 ） 762 - 765 2002年

ISSN  0022-5347

　概要を見る

<p>Purpose: Signal transducer and activator of transcription 3 (STAT3) is known to have an important role in cytokine and growth factor signaling pathways. In various types of human malignant tumors STAT3 has been shown to be constitutively activated due to aberrant production of cytokines and growth factors. We examined the presence of STAT3 activation and its association with pathological features and clinical outcome in renal cell carcinoma cases. Materials and Methods: We examined 48 paraffin embedded renal cell carcinoma specimens and corresponding nonneoplastic kidney tissues for the activation status of STAT3 on immunohistochemistry using anti-phospho-specific (p)-STAT3 antibody, which recognizes only activated STAT3. Based on the percent of cells with positive nuclear staining the activation status of STAT3 was determined and categorized into 2 groups, including low-less than 10% and high90% or more tumor cells positive. The associations of the activation status of STAT3 with pathological features and clinical outcome were analyzed. Results: Of 48 tumors 24 (50%) demonstrated high levels of nuclear immunostaining for p-STAT3, while the other 24 (50%) showed low levels. Adjacent nonneoplastic kidney tissues showed only little immunostaining for p-STAT3. A significant association of high levels of p-STAT3 with metastasis was observed (p = 0.0094). No significant associations of p-STAT3 immunostaining with pathological stage or grade were observed. A high level of p-STAT3 was a significant indicator of a poor prognosis on univariate and multivariate analysis (p = 0.0117 and 0.0439, respectively) Conclusions: Our results indicate a high frequency of STAT3 activation in renal cell carcinoma, especially in metastatic disease. STAT3 activation was an independent prognostic variable in renal cell carcinoma cases. Our results strongly suggest that the activation of STAT3 contributes to the development and progression of renal cell carcinoma.</p>

勃起障害患者治療における血清テストステロン値の意義

丸茂健，堀口裕，中川健，大家基嗣，大東貴志，中島淳，村井勝

日本性機能学会雑誌 3 （ 16 ） 273-277 2001年12月

研究論文（学術雑誌）, 共著

マルチスライスCTによる三次元再構築画像を用いた腎病変の評価

水野隆一，中川健，大家基嗣，大東貴志，中島淳，丸茂健，村井勝

腎移植・血管外科 13 （ 1 ） 48-54 2001年12月

研究論文（学術雑誌）, 共著

高齢者における勃起障害の治療

佐藤全伯，丸茂健，堀口裕，中川健，大家基嗣，大東貴志，中島淳，村井勝

日本性機能学会雑誌 16 （ 3 ） 321-325 2001年10月

研究論文（学術雑誌）, 共著

腎細胞癌治療における腎保存手術

大家基嗣

慶應医学 78 （ 5 ） 159-160 2001年09月

研究論文（学術雑誌）, 単著

Constitutive activation of nuclear factor-κB prevents TRAIL-induced apoptosis in renal cancer cells

Oya Mototsugu, Ohtsubo Masafumi, Takayanagi Atsushi, Tachibana Masaaki, Shimizu Nobuyoshi, Murai Masaru

Oncogene 20 （ 29 ） 3888 - 3896 2001年06月

ISSN  0950-9232

　概要を見る

<p>TRAIL has gained much attention for its specific induction of apoptosis in cancer cells but not in normal cells. This phenomenon has been explained thus: that cancer cells dominantly express death receptors while normal cells express decoy receptors. However, recent reports have shown that some cancer cell lines are resistant to TRAIL-induced apoptosis despite the absence of decoy receptors and the presence of death receptors. This suggested the existance of an inhibitory factor. We herein showed that NF-κB is a key molecule underlying the TRAIL-resistant mechanism in renal cell carcinoma (RCC) cell lines. We observed that NF-κB is constitutively activated in resistant cell lines. Forced expression of antisense cDNA of IκBα, a specific inhibitor of NF-κB, in TRAIL-sensitive cell lines with a low NF-κB activity result in constitutive activation of NF-κB and resistance to TRAIL-induced apoptosis. Adenoviral expression of a stable form of IκBα in the TRAIL-resistant cell lines induced apoptosis. These data suggest that RCC can be classified into two subsets: TRAIL-sensitive RCC with a low NF-κB activity and TRAIL-resistant RCC with constitutively activated NF-κB. In the former group TRAIL can be a treatment option, while in the latter group a molecular approach targeting NF-κB appears to be a promising therapy.</p>

• Access to Document (DOI)

Constitutive activation of nuclear factor-kB prevents TRAIL-induced apoptosis in renal cancer cells

Oya Mototsugu, Ohtsubo Masafumi, Takayanagi Atsushi, Tachibana Masaaki, Shimizu Nobuyoshi, Murai Masaru

Oncogene 20 （ 29 ） 3888-3896 2001年06月

研究論文（学術雑誌）, 共著

Constitutive activation of nuclear factor-κB prevents TRAIL-induced apoptosis in renal cancer cells

Oya Mototsugu, Ohtsubo Masafumi, Takayanagi Atsushi, Tachibana Masaaki, Shimizu Nobuyoshi, Murai Masaru

Oncogene 20 （ 29 ） 3888-3896 2001年06月

研究論文（学術雑誌）, 共著

前立腺癌診断におけるPSA関連マーカーの有用性

中島淳，菊地栄次，石橋みどり，大家基嗣，大東貴志，丸茂健，村井勝

泌尿器外科 14   445-446 2001年

研究論文（学術雑誌）, 共著

勃起障害治療における陰茎締めつけバンドの有用性

丸茂健，堀口裕，中川健，大家基嗣，大東貴志，中島淳，村井勝

日本性機能学会雑誌 16   15-19 2001年

研究論文（学術雑誌）, 共著

Serum interleukin 6 as a prognostic factor in patients with prostate cancer

Nakashima Jun, Tachibana Masaaki, Horiguchi Yutaka, Oya Mototsugu, Ohigashi Takashi, Asakura Hirotaka, Murai Masaru

Clinical Cancer Research 6 （ 7 ） 2702 - 2706 2000年07月

ISSN  1078-0432

　概要を見る

<p>The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning ≥1, IL-6 ≥7 pg/ml, PS ≥1, PSA &gt;100 ng/ml, and ALP &gt;620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD ≥1, IL-6 ≥7 pg/ml, PS ≥1, PSA &gt;100 ng/ml, LDH &gt;200 IU/liter, and ALP &gt;620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD ≥1 and IL-6 ≥7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.</p>

Serm interleukin 6 as a prognostic factor in patients with prostatic cancer

Nakashima Jun, Tachibana Masaaki, Horiguchi Yutaka, Oya Mototsugu, Ohigashi Takashi, Asakura Hirotaka, Murai Masaru

Clinical Cancer Research 6 （ 7 ） 2702-2706 2000年07月

研究論文（学術雑誌）, 共著

Appricationof condetionally replicating herpes vector for gene therapy treatment of urologic neoplasms

Oyama Masafumi, Yazaki Takahito, Ohigashi Takashi, Hoshi Michio, Horiguchi Yutaka, Oya Mototsugu, Asakura Hirotaka, Nakashima Jun, Tachibana Masaaki, Uyemura Keiichi, Murai Masaru

Molecular Urology 4 （ 2 ） 83-87 2000年07月

研究論文（学術雑誌）, 共著

Complications of laparoscopic and retroperotoneoscopic adrenalectomies in 370 cases in Japan: a multi-institutional study

Terachi Toshiro, Yoshida Osamu, Matsuda Tadashi, Orikasa Seiichi, Chiba Yutaka, Takahashi Kota, Takeda Masayuki, Higashihara Eiji, Murai Masaru, Baba Shiro, Fujita Kimio, Suzuki Koji, Ohshima Shinichi, Ono Yoshinari, Kumazawa Joichi, Naito Seiji

Biomedicine & Pharmacotherapy 54 （ Suppl 1 ） 211-214 2000年06月

研究論文（学術雑誌）, 共著

How to Make Proper Specimens for Surgically Resected Renal Cell Carcinoma

Oya Mototsugu

Japanese Journal of Clinical Urology 54 （ 6 ） 377 - 383 2000年05月

ISSN  0385-2393

Prognositic value of alkaline phosphatase flase in patients with metastatic prostate cancer treated with endocrine therapy

Nakashima Jun, Ozu Choichiro, Nishiyama Toru, Oya Mototsugu, Ohigashi Takashi, Asakura Hirotaka, Tachibana Masaaki, Murai Masaru

Urology 56 （ 5 ） 834-847 2000年05月

研究論文（学術雑誌）, 共著

腎癌切除標本の取り扱い方

大家基嗣，村井勝

臨床泌尿器科 54 （ 6 ） 377-383 2000年05月

研究論文（学術雑誌）, 共著

Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms

Oyama M, Yazaki T, Ohigashi T, Hoshi M, Horiguchi Y, Oya M, Asakura H, Nakashima J, Tachibana M, Uyemura K, Murai M

Molecular Urology 4 （ 2 ） 83-87 2000年05月

研究論文（学術雑誌）, 共著

Decreased expression of p57(KIP2) mRNA in human bladder cancer

Oya M., Schulz W. A.

British Journal of Cancer 83 （ 5 ） 626 - 631 2000年

ISSN  0007-0920

　概要を見る

<p>To identify targets of genetic and epigenetic alterations on chromosome 11p15.5 in human bladder cancer, expression of the imprinted KIP2, IGF2 and H19 genes was studied by quantitative RT-PCR in 24 paired samples of urothelial carcinomas and morphologically normal mucosa obtained by cystectomy, and in bladder carcinoma cell lines. The most frequent alteration in tumour tissue was decreased expression of KIP2 identified in 9/24 (37%) specimens. Decreased IGF2 and H19 mRNA levels were found in five (21%) and three (13%) tumours, respectively. One tumour each overexpressed IGF2 and H19. Loss of H19 expression was only found associated with loss of KIP2 expression, whereas decreased expression of IGF2 mRNA occurred independently. Almost all bladder carcinoma cell lines showed significant changes in the expression of at least one gene with diminished expression of KIP2 mRNA as the most frequent alteration. IGF2 mRNA levels were diminished in several lines, but increased in others. The KIP2 gene could be an important target of genetic and epigenetic alterations in bladder cancer affecting the maternal chromosome 11p15.5. However, reminiscent of the situation in Wilms' tumours, expression of the IGF2 gene on the paternal chromosome can also be disturbed in bladder cancers. (C) 2000 Cancer Research Campaign.</p>

Prognostic value of alkaline phosphatase flare in patients with metastatic prostate cancer treated with endocrine therapy

Nakashima Jun, Ozu Choichiro, Nishiyama Toru, Oya Mototsugu, Ohigashi Takashi, Asakura Hirotaka, Tachibana Masaaki, Murai Masaru

Urology 56 （ 5 ） 843 - 847 2000年

ISSN  0090-4295

　概要を見る

<p>Objectives. To assess the prognostic significance of alkaline phosphatase (ALP) flare in 114 patients with metastatic prostate cancer treated with endocrine therapy.Methods. ALP flare was defined as a transient increase of the serum ALP level to 120% or more of the pretreatment value after the initiation of endocrine therapy, followed by a subsequent decrease.Results. Univariate analysis demonstrated that patients with poorly differentiated adenocarcinoma, an extent of disease of 2 or greater, a serum ALP level above twice the upper limit of normal, a serum prostate-specific antigen level greater than 100 ng/mL, an ALP flare, and a hemoglobin level of 12 g/dL or less had a significantly lower survival rate than their respective counterparts. Multivariate Cox's proportional hazards model analysis demonstrated that tumor histologic features and ALP flare were significant prognostic indicators for survival.Conclusions. The results of the present study suggest that the tumor histologic features and the ALP flare are significant prognostic indicators for survival in patients with metastatic prostate cancer treated with endocrine therapy. Copyright (C) 2000 Elsevier Science Inc.</p>

• Access to Document (DOI)