Faculty Profiles - NASU Yasutomo

Papers - NASU Yasutomo

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前立腺癌に対するHybrid radical prostatectomyのOncological outcomes

雑賀隆史, 小林泰之, 上原慎也, 荒木元朗, 高尾彰, 上杉達也, 那須保友, 公文裕巳

日本癌治療学会誌 44 ( 2 ) 428 - 428 2009.9

進行性尿路上皮癌に対するGCP療法の検討

枝村康平, 雑賀隆史, 谷本竜太, 高尾彰, 小林泰之, 上杉達也, 賀来春紀, 那須保友, 公文裕巳

日本癌治療学会誌 44 ( 2 ) 593 - 593 2009.9

上部尿路疾患に対する腎盂尿管鏡の有用性に関する検討

高尾彰, 雑賀隆史, 枝村康平, 小林泰之, 小武家誠, 上杉達也, 上原慎也, 賀来春紀, 門田晃一, 那須保友, 公文裕巳

日本癌治療学会誌 44 ( 2 ) 763 - 763 2009.9

The role of hepatocyte growth factor activator inhibitor-1(HAI-1)as a prognostic indicator in cervical cancer

Nakamura K, Abarzua F, Hongo A, Kodama J, Nasu Y, Kumon H, Hiramatsu Y

Int J Oncol 35 ( 2 ) 239 - 248 2009.8

Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways

Chung S, Furihata M, Tamura K, Uemura M, Daigo Y, Nasu Y, Miki T, Shuin T, Fujioka T, Nakamura Y, Nakagawa H

Oncogene 28 ( 32 ) 2849 - 2859 2009.8

Prospective Longitudinal Comparative Study of Health-Related Quality of Life in Patients Treated with Radical Prostatectomy or Permanent Brachytherapy for Prostate Cancer Reviewed

Makoto Kobuke, Takashi Saika, Yoshiko Nakanishi, Shin Ebara, Daisuke Manabe, Tatsuya Uesugi, Hiroyuki Nose, Ryoji Arata, Tomoyasu Tsushima, Yasutomo Nasu, Hiromi Kumon

ACTA MEDICA OKAYAMA 63 ( 3 ) 129 - 135 2009.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

To determine health-related quality of life (HRQOL) after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (BT), third party-conducted QOL surveys were prospectively compared. Between 2004 and 2005, 37 patients underwent RRP and 36 were treated with BT. A QOL survey consisting of the Medical Outcomes Study 36-Item Short Form (SF-36), the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and the International Prostate Symptoms Score (IPSS) was completed prospectively by a research coordinator at baseline, and at 1, 3, 6 and 12 months after treatment. The RRP patients scored well in general QOL except at I month after surgery, with their mental health better than at baseline by 6 months after surgery. Disease-specific QOL in RRP patients received a low score at I month for both urinary and sexual function, though urinary function rapidly recovered to baseline levels. BT patient QOL was not affected by the therapy except in the IPSS score. However, general and mental health scores in BT patients were inferior to those in RRP patients. This prospective study revealed differences in QOL after RRP and BT. These results will be helpful in making treatment decisions.

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Overexpression of REIC/Dkk-3 in Normal Fibroblasts Suppresses Tumor Growth via Induction of Interleukin-7

Masakiyo Sakaguchi, Ken Kataoka, Fernando Abarzua, Ryuta Tanimoto, Masami Watanabe, Hitoshi Murata, Swe Swe Than, Kaoru Kurose, Yuji Kashiwakura, Kazuhiko Ochiai, Yasutomo Nasu, Hiromi Kumon, Nam-ho Huh

JOURNAL OF BIOLOGICAL CHEMISTRY 284 ( 21 ) 14236 - 14244 2009.5

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

We previously showed that the tumor suppressor gene REIC/Dkk-3, when overexpressed by an adenovirus (Ad-REIC), exhibited a dramatic therapeutic effect on human cancers through a mechanism triggered by endoplasmic reticulum stress. Adenovirus vectors show no target cell specificity and thus may elicit unfavorable side effects through infection of normal cells even upon intra-tumoral injection. In this study, we examined possible effects of Ad-REIC on normal cells. We found that infection of normal human fibroblasts (NHF) did not cause apoptosis but induced production of interleukin (IL)-7. The induction was triggered by endoplasmic reticulum stress and mediated through IRE1 alpha, ASK1, p38, and IRF-1. When Ad-REIC-infected NHF were transplanted in a mixture with untreated human prostate cancer cells, the growth of the cancer cells was significantly suppressed. Injection of an IL-7 antibody partially abrogated the suppressive effect of Ad-REIC-infected NHF. These results indicate that Ad-REIC has another arm against human cancer, an indirect host-mediated effect because of overproduction of IL-7 by mis-targeted NHF, in addition to its direct effect on cancer cells.

DOI： 10.1074/jbc.M808002200

Expression of Matriptase and Clinical Outcome of Human Endometrial Cancer Reviewed

Keiichiro Nakamura, Atsushi Hongo, Junichi Kodama, Fernando Abarzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

ANTICANCER RESEARCH 29 ( 5 ) 1685 - 1690 2009.5

Language：English Publishing type：Research paper (scientific journal) Publisher：INT INST ANTICANCER RESEARCH

Background: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix and in progression of some epithelial cancers. The purpose of the present study was to examine matriptase expression and evaluate its clinicopathological significance in endometrial cancer. Patients and Methods: Matriptase expression was examined in normal endometrium (n=20), endometrial hyperplasia (n=11) and endometrial cancer (n=65) samples. The distribution of cases that scored positive for each of the biological parameters examined was correlated with matriptase expression status obtained by immunohistochemistry. Results: Matriptase was found to be significantly overexpressed in endometrial cancer as compared with normal endometrium and endometrial hyperplasia. Interestingly, matriptase expression is associated with stage (p=0.010), grade (p=0.021), depth of myometrial invasion (p=0.004), cervical involvement (p=0.021), lymph node metastasis (p=0.009), LVS involvement (p=0.041) and peritoneal cytology (p=0.045). The high matriptase expression was a significant predictor for poor prognosis when compared with low matriptase expression (Disease-free survival rate; p=0.032, Overall survival rate; p=0.011). Conclusion: High matriptase expression in endometrial cancer may be associated with poor prognosis.

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Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer

Tamura K, Furihata M, Chung S.Y, Uemura M, Yoshioka H, Iiyama T, Ashida S, Nasu Y, Fujioka T, Shuin T, Nakamura Y, Nakagawa H

Cancer Sci 100 ( 5 ) 914 - 919 2009.5

Prostate-specific antigen 'bounce' after permanent 125I -implant brachytherapy in Japanese men:a multi-institutional pooled analysis

Satoh T, Ishiyama H, Matsumoto K, Tsumura H, Kitano M, Hayakawa K, Ebara S, Nasu Y, Kumon H, Kanazawa S, Miki K, Egawa S, Aoki M, Toya K, Yorozu A, Nagata H, Saito S, Baba S

BJU International 103 ( 8 ) 1064 - 1068 2009.4

Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression

Masami Watanabe, Yuji Kashiwakura, Peng Huang, Kazuhiko Ochiai, Junichiro Futami, Shun-Ai Li, Munenori Takaoka, Yasutomo Nasu, Masakiyo Sakaguchi, Nam-Ho Huh, Hiromi Kumon

INTERNATIONAL JOURNAL OF ONCOLOGY 34 ( 3 ) 657 - 663 2009.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The REIC/Dkk-3 gene has been reported to be a tumor suppressor and the expression is significantly down-regulated in a broad range of cancer cell types. The protein is secretory, but the physiological function remains unclear. This study demonstrated that recombinant REIC/Dkk-3 protein induced the differentiation of human CD14(+) monocytes into a novel cell type ((REIC/Dkx-3)Mo). (REIC/Dkk-3)Mo resembles immature dendritic cells generated with IL-4 and GM-CSF. Both these cell populations exhibit similar proportions of CD11c(+), CD40(+), CD86(+) and HLA-DR(+) cells and endocytic capacity, but (REIC/Dkk-3)Mo is negative for CD1a antigen. An analysis of the signal transducers and activators of transcription (STAT) pathways revealed that REIC/Dkk-3 induces phosphorylation of STAT 1 and STAT 3. Furthermore, intratumoral administration of REIC/Dkk-3 protein significantly suppressed tumor growth with CD11c(+) and CD8(+) (dendritic and killer T cell marker, respectively) cell accumulation and enhanced anticancer cytolytic activity of splenocytes. These data indicated a cytokine-like role of REIC/Dkk-3 protein in monocyte differentiation that might be exploited therapeutically.

DOI： 10.3892/ijo_00000191

Expression of hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) in ovarian cancer

Nakamura K, Abarzua F, Kodama J, Hongo A, Nasu Y, Kumon H, Hiramatsu Y

Int J Oncol 34 ( 2 ) 345 - 353 2009.2

エンドユロロジー・腹腔鏡領域腎癌に対するCTガイド下経皮的ラジオ波焼灼療法

小林泰之, 郷原英夫, 枝村康平, 小武家誠, 上杉達也, 雑賀隆史, 那須保友, 金澤右, 公文裕巳

日本泌尿器科学会雑誌 100 ( 2 ) 77 - 77 2009.2

Hepatocyte growth factor activator inhibitor-2(HAI-2)is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer

Nakamura K, Abarzua F, Hongo A, Kodama J, Nasu Y, Kumon H, Hiramatsu Y

Annals of Oncology 20 ( 1 ) 63 - 70 2009.1

OP-209 限局性前立腺癌に対する高密度焦点式超音波(HIFU)による治療成績(前立腺腫瘍/HIFU,一般演題口演,第97回日本泌尿器科学会総会)

津川昌也, 中村あや, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 100 ( 2 ) 241 - 241 2009

OP-303 岡山大学病院におけるI125前立腺癌永久密封小線源療法の治療成績(前立腺腫瘍/放射線治療3,一般演題口演,第97回日本泌尿器科学会総会)

上杉達也, 小武家誠, 藤尾圭, 谷本竜太, 小林泰之, 賀来春紀, 雑賀隆史, 那須保友, 公文裕巳, 小林知子, 江原伸

日本泌尿器科学会雑誌 100 ( 2 ) 264 - 264 2009

APP-031-PM 上部尿路上皮癌に対する腎尿管全摘除術術後の膀胱内再発に関する検討 : 早期尿管結紮は膀胱内再発のリスクを軽減するか?(総会賞応募ポスター,第97回日本泌尿器科学会総会)

小林泰之, 雑賀隆史, 江原伸, 宮地禎幸, 倉繁拓志, 津島知靖, 那須保友, 公文裕巳

日本泌尿器科学会雑誌 100 ( 2 ) 140 - 140 2009

A comparison of proteomic profiles changes during 17β-estradiol treatment in human prostate cancer PC-3 cell line Reviewed

Jie Chen, Peng Huang, Haruki Kaku, Kai Zhang, Masami Watanabe, Takashi Saika, Yasutomo Nasu, Hiromi Kumon

Cancer Genomics and Proteomics 6 ( 6 ) 331 - 335 2009

Language：English Publishing type：Research paper (scientific journal) Publisher：International Institute of Anticancer Research

Human telomerase reverse transcriptase (hTERT) is overexpressed in prostate cancer. Estrogen plays a central role in the development of prostate cancer. hTERT activity has been shown to be increased after estrogen treatment. Although significant efforts have been made to understand the role of estrogen, the telomerase connection with estrogen is poorly understood. In this report, we describe a proteomics approach for investigating the global changes in protein expression in estrogen-treated human prostate cancer PC-3 cells. PC-3 cells were seeded in medium and then treated with estrogen
the protein extract from these cells was used for two-dimensional (2D) gel electrophoresis. The protein spots were subjected to comparative analysis by liquid chromatography/mass spectrometry (LC/MS). We observed that the expression of 17 proteins, including stress-induced phosphoprotein 1 and lamin-A/C was down-regulated, and that the expression of proteins such as subunit a of T-complex protein 1, tubulin alpha-1B, and other 13 proteins was up-regulated. These proteins may have been closely associated with estrogen-induced hTERT activity. The expression level of these proteins could be a useful parameter for evaluating the estrogen-induced hTERT activity in clinical specimens of human prostate cancer.

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Initial report of hybrid radical prostatectomy for prostate cancer: reduced bleeding, clear vision, and secure surgical margins. Reviewed

Saika T, Kobayashi Y, Watanabe T, Manabe D, Ebara S, Uehara S, Nasu Y, Kumon H

Acta medica Okayama 62 ( 6 ) 379 - 384 2008.12

Language：English Publishing type：Research paper (scientific journal)

To evaluate morbidity in Hybrid Radical Prostatectomy (HRP, hybridized laparoscopic and open retropubic radical prostatectomy). The operative and pathological outcomes obtained in 25 consecutive patients who underwent HRP were reviewed. The median operating time was 220 min, median blood loss was 550 ml, and no patient required an allogenic blood transfusion. No severe postoperative complications were observed. The surgical margin was positive in 12% of all patients, and in 1 patient with pT2 or less (4.5%). These results indicate that HRP is safe and may be able to combine the benefits of both laparoscopic and open procedures.

DOI： 10.18926/AMO/30950

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Mechanistic analysis of resistance to REIC/Dkk-3-induced apoptosis in human bladder cancer cells. Reviewed

Kobayashi T, Sakaguchi M, Tanimoto R, Abarzua F, Takaishi M, Kaku H, Kataoka K, Saika T, Nasu Y, Miyazaki M, Kumon H, Huh NH

Acta medica Okayama 62 ( 6 ) 393 - 401 2008.12

Language：English Publishing type：Research paper (scientific journal)

We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.

DOI： 10.18926/AMO/30945

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