Faculty Profiles - HIRASAWA Akira

MicroRNA and endometrial cancer: Roles of small RNAs in human tumors and clinical applications

Megumi Yanokura, Kouji Banno, Yusuke Kobayashi, Iori Kisu, Arisa Ueki, Asuka Ono, Kennta Masuda, Hiroyuki Nomura, Akira Hirasawa, Nobuyuki Susumu, Daisuke Aoki

ONCOLOGY LETTERS 1 ( 6 ) 935 - 940 2010.11

Language：English Publisher：SPANDIDOS PUBL LTD

DOI： 10.3892/ol.2010.173

腫瘍間質の遺伝子発現解析を用いた進行上皮性卵巣癌に対する新規バイオマーカーの探索

片岡史夫, 津田浩史, 野村弘行, 千代田達幸, 平沢晃, 冨永英一郎, 鈴木淳, 進伸幸, 青木大輔

日本分子腫瘍マーカー研究会プログラム・講演抄録 30回 52 - 53 2010.9

女性の片頭痛

AOKI DAISUKE

産婦人科治療 101 ( 2 ) 135-139 - 139 2010.8

Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer. International journal

Ei-ichiro Tominaga, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Masashi Takano, Fumio Kataoka, Hiroyuki Nomura, Akira Hirasawa, Daisuke Aoki, Kazuto Nishio

Gynecologic oncology 118 ( 2 ) 160 - 6 2010.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

OBJECTIVES: The purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy. METHODS: We performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin+paclitaxel) as primary therapy. RESULTS: Microarray analysis identified 50 genes differentially expressed between tumors of patients with no evidence of disease (NED) or evidence of disease (ED) (p<0.001). Six genes (13%) were located at 8q24, and 9 genes (19.6%), at 20q11-13. The ratio of selected gene set/analyzed gene set in chromosomes 8 and 20 are significantly higher than that in other chromosome regions (6/606 vs. 32/13656, p=0.01) and (12/383 vs. 32/13656, p=1.3 x 10(-)(16)). We speculate that the abnormal chromosomal distribution is due to genomic alteration and that these genes may play an important role in aEOC and choose GNAS (GNAS complex locus, NM_000516) on 20q13 based on the p value and fold change. Genomic PCR of aEOC cells also showed that amplification of GNAS was significantly correlated with unfavorable PFS (p=0.011). Real-time quantitative RT-PCR analysis of independent samples revealed that high mRNA expression levels of the GNAS genes, located at chromosome 20q13, was significantly unfavorable indicators of progression-free survival (PFS). Finally, GNAS amplification was an independent prognostic factor for PFS. CONCLUSIONS: Our results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC.

DOI： 10.1016/j.ygyno.2010.03.010

無結紮手術（BiClamp，Ligasure，ハーモニック）－広汎子宮全摘出術におけるBiClamp使用の実際

AOKI DAISUKE

産婦人科の実際 59 ( 8 ) 1195-1200 - 1200 2010.8

A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Reviewed International journal

Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi Hirata, Yusuke Nakamura

Nature genetics 42 ( 8 ) 707 - 10 2010.8

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.

DOI： 10.1038/ng.612

A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese

Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi Hirata, Yusuke Nakamura

NATURE GENETICS 42 ( 8 ) 707 - U88 2010.8

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

DOI： 10.1038/ng.612

Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer Reviewed

Ei-ichiro Tominaga, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Masashi Takano, Fumio Kataoka, Hiroyuki Nomura, Akira Hirasawa, Daisuke Aoki, Kazuto Nishio

GYNECOLOGIC ONCOLOGY 118 ( 2 ) 160 - 166 2010.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Objectives. The purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy.Methods. We performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin + paclitaxel) as primary therapy.Results. Microarray analysis identified 50 genes differentially expressed between tumors of patients with no evidence of disease (NED) or evidence of disease (ED) (p<0.001). Six genes (13%) were located at 8q24, and 9 genes (19.6%), at 20q11-13. The ratio of selected gene set/analyzed gene set in chromosomes 8 and 20 are significantly higher than that in other chromosome regions (6/606 vs. 32/13656, p 0.01) and (12/383 vs. 32/13656, p = 1.3 x 10(-16)). We speculate that the abnormal chromosomal distribution is due to genomic alteration and that these genes may play an important role in aEOC and choose GNAS (GNAS complex locus, NM__000516) on 20q13 based on the p value and fold change. Genomic PCR of aEOC cells also showed that amplification of GNAS was significantly correlated with unfavorable PFS (p = 0.011). Real-time quantitative RT-PCR analysis of independent samples revealed that high mRNA expression levels of the GNAS genes, located at chromosome 20q13, was significantly unfavorable indicators of progression-free survival (PFS). Finally, GNAS amplification was an independent prognostic factor for PFS.Conclusions. Our results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ygyno.2010.03.010

Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer

Ei-ichiro Tominaga, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Masashi Takano, Fumio Kataoka, Hiroyuki Nomura, Akira Hirasawa, Daisuke Aoki, Kazuto Nishio

GYNECOLOGIC ONCOLOGY 118 ( 2 ) 160 - 166 2010.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Objectives. The purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy.
Methods. We performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin + paclitaxel) as primary therapy.
Results. Microarray analysis identified 50 genes differentially expressed between tumors of patients with no evidence of disease (NED) or evidence of disease (ED) (p<0.001). Six genes (13%) were located at 8q24, and 9 genes (19.6%), at 20q11-13. The ratio of selected gene set/analyzed gene set in chromosomes 8 and 20 are significantly higher than that in other chromosome regions (6/606 vs. 32/13656, p 0.01) and (12/383 vs. 32/13656, p = 1.3 x 10(-16)). We speculate that the abnormal chromosomal distribution is due to genomic alteration and that these genes may play an important role in aEOC and choose GNAS (GNAS complex locus, NM__000516) on 20q13 based on the p value and fold change. Genomic PCR of aEOC cells also showed that amplification of GNAS was significantly correlated with unfavorable PFS (p = 0.011). Real-time quantitative RT-PCR analysis of independent samples revealed that high mRNA expression levels of the GNAS genes, located at chromosome 20q13, was significantly unfavorable indicators of progression-free survival (PFS). Finally, GNAS amplification was an independent prognostic factor for PFS.
Conclusions. Our results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ygyno.2010.03.010

Relationship Between ABCF2 Expression and Response to Chemotherapy or Prognosis in Clear Cell Adenocarcinoma of the Ovary Reviewed

Hiroshi Tsuda, Kiyoshi Ito, Nobuo Yaegashi, Akira Hirasawa, Tamotsu Sudo, Tsunekazu Kita, Yoshito Terai, Junzo Kigawa, Toru Sugiyama, Daisuke Aoki

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 20 ( 5 ) 794 - 797 2010.7

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Objectives: The purpose of this study was to evaluate the association of ABCF2 (adenosine triphosphate-binding cassette superfamily F2) protein expression with response to chemotherapy and prognosis in patients with clear cell adenocarcinoma (CCC) of the ovary.Methods: One hundred sixty-five patients with CCC were studied, and cytoplasmic ABCF2 expression was detected by immunohistochemical staining. All patients underwent platinum-based primary chemotherapy followed by primary surgery.Results: Adenosine triphosphate-binding cassette superfamily F2 expression was detected in 118 (71.5%) of 165 patients and was not related to age or clinical stage. The response rate to chemotherapy in 38 patients with measurable disease was 47.3% (18/38). The response rate tended to be higher in patients without ABCF2 expression than in those with ABCF2 expression; however, this difference was not significant (66.7% vs 34.8%, P = 0.096). There was no significant difference in overall survival between ABCF2-positive and ABCF2-negative cases (median survival time, 1175 vs 1257 days; P = 0.24).Conclusions: Adenosine triphosphate-binding cassette superfamily F2 protein was highly expressed in CCC of the ovary, but expression was not related to age, clinical stage, chemoresponse, or prognosis.

DOI： 10.1111/IGC.0b013e3181a835fc

Relationship between ABCF2 expression and response to chemotherapy or prognosis in clear cell adenocarcinoma of the ovary. International journal

Hiroshi Tsuda, Kiyoshi Ito, Nobuo Yaegashi, Akira Hirasawa, Tamotsu Sudo, Tsunekazu Kita, Yoshito Terai, Junzo Kigawa, Toru Sugiyama, Daisuke Aoki

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 20 ( 5 ) 794 - 7 2010.7

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

OBJECTIVES: The purpose of this study was to evaluate the association of ABCF2 (adenosine triphosphate-binding cassette superfamily F2) protein expression with response to chemotherapy and prognosis in patients with clear cell adenocarcinoma (CCC) of the ovary. METHODS: One hundred sixty-five patients with CCC were studied, and cytoplasmic ABCF2 expression was detected by immunohistochemical staining. All patients underwent platinum-based primary chemotherapy followed by primary surgery. RESULTS: Adenosine triphosphate-binding cassette superfamily F2 expression was detected in 118 (71.5%) of 165 patients and was not related to age or clinical stage. The response rate to chemotherapy in 38 patients with measurable disease was 47.3% (18/38). The response rate tended to be higher in patients without ABCF2 expression than in those with ABCF2 expression; however, this difference was not significant (66.7% vs 34.8%, P = 0.096). There was no significant difference in overall survival between ABCF2-positive and ABCF2-negative cases (median survival time, 1175 vs 1257 days; P = 0.24). CONCLUSIONS: Adenosine triphosphate-binding cassette superfamily F2 protein was highly expressed in CCC of the ovary, but expression was not related to age, clinical stage, chemoresponse, or prognosis.

DOI： 10.1111/IGC.0b013e3181a835fc