Faculty Profiles - HIRASAWA Akira

Papers - HIRASAWA Akira

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miR-152 Is a Tumor Suppressor microRNA That Is Silenced by DNA Hypermethylation in Endometrial Cancer

Tomohiko Tsuruta, Ken-ichi Kozaki, Atsushi Uesugi, Mayuko Furuta, Akira Hirasawa, Issei Imoto, Nobuyuki Susumu, Daisuke Aoki, Johji Inazawa

CANCER RESEARCH 71 ( 20 ) 6450 - 6462 2011.10

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

The etiology and development of human cancers that remain little understood might be enlightened by defining tumor suppressor microRNAs (TS-miRNA). In this study, we identified TS-miRNAs silenced by aberrant DNA hypermethylation in endometrial cancer. Functional screening of 327 synthetic miRNAs in an endometrial cancer cell proliferation assay identified 103 miRNAs that inhibited cell growth. We then determined the sequence, DNA methylation status, and expression levels of these miRNAs in endometrial cancer cell lines and primary tumors. These determinations led to the identification of miR-152 as a candidate TS-miRNA gene in endometrial cancer. Epigenetic silencing documented in miR-152 was consistent with its location at 17q21.32 in intron 1 of the COPZ2 gene, which is also silenced often in endometrial cancer by DNA hypermethylation, and also with evidence that miR-152 targets the DNA methyltransferase DNMT1. Notably, restoration of miR-152 expression in endometrial cancer cell lines was sufficient to inhibit tumor cell growth in vitro and in vivo. We identified E2F3, MET, and Rictor as novel candidate targets of miR-152, suggesting how its epigenetic silencing can drive endometrial carcinogenesis. Our findings define a central role for miR-152 in endometrial cancer, and they also suggest its use in new therapeutic strategies to treat this cancer. Cancer Res; 71(20); 6450-62. (C) 2011 AACR.

DOI： 10.1158/0008-5472.CAN-11-0364

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妊産婦への向精神薬の投与

AOKI DAISUKE

産婦人科治療 103 ( 4 ) 417-421 - 421 2011.10

Magnifying hysteroscopy with narrow-band imaging for visualization of endometrial lesions

Kisu I, Banno K, Kobayashi Y, Ono A, Masuda K, Ueki A, Nomura H, Hirasawa A, Abe T, Kouyama K, Susumu N, Aoki D

Int J Gynaecol Obstet 115 ( 1 ) 74-75 2011.10

miR-152 Is a Tumor Suppressor microRNA That Is Silenced by DNA Hypermethylation in Endometrial Cancer Reviewed

Tomohiko Tsuruta, Ken-ichi Kozaki, Atsushi Uesugi, Mayuko Furuta, Akira Hirasawa, Issei Imoto, Nobuyuki Susumu, Daisuke Aoki, Johji Inazawa

CANCER RESEARCH 71 ( 20 ) 6450 - 6462 2011.10

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

DOI： 10.1158/0008-5472.CAN-11-0364

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遺伝性乳癌・卵巣がんの取扱いとリスク低減卵管卵巣摘出術

AOKI DAISUKE

産科と婦人科 78 ( 9 ) 1064-1068 - 1068 2011.9

婦人科疾患と遺伝カウンセリング

AOKI DAISUKE

産婦人科の実際 60 ( 9 ) 1331-1338 - 1338 2011.9

遺伝性腫瘍の基礎知識と遺伝子診断および予防法～遺伝性乳がん・卵巣がんに着目して～．

AOKI DAISUKE

がん看護 16 ( 6 ) 631-635 - 635 2011.9

発現解析による子宮体癌の再発予測モデルの開発

津田浩史, 井口蓉子, 片岡史夫, 野村弘行, 田中英雄, 千代田達幸, 平沢晃, 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 31回 68 - 69 2011.9

発現解析による子宮体部癌肉腫の生物学的特性の解明

千代田達幸, 津田浩史, 片岡史夫, 野村弘行, 田中英雄, 平沢晃, 進伸幸, 佐谷秀行, 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 31回 46 - 47 2011.9

家系内の遺伝子検査が契機となり早期介入を行ったLynch症候群の1例

AOKI DAISUKE

東京産科婦人科学会会誌 60 ( 2 ) 293-297 - 297 2011.6

産婦人科臨床における遺伝性乳癌卵巣癌の位置づけ

AOKI DAISUKE

家族性腫瘍 11 ( 2 ) 48-51 - 51 2011.5

老人性腟炎

AOKI DAISUKE

臨床婦人科産科 65 ( 4(増大号) ) 568-571 2011.4

Flexible hysteroscopy with narrow band imaging (NBI) for endoscopic diagnosis of malignant endometrial lesions

Iori Kisu, Kouji Banno, Yusuke Kobayashi, Asuka Ono, Kenta Masuda, Arisa Ueki, Hiroyuki Nomura, Akira Hirasawa, Takayuki Abe, Keisuke Kouyama, Nobuyuki Susumu, Daisuke Aoki

INTERNATIONAL JOURNAL OF ONCOLOGY 38 ( 3 ) 613 - 618 2011.3

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

Narrow band imaging (NBI) for detection of blood vessels and microstructures on the mucosal surface is used in gastrointestinal endoscopy since it can improve qualitative diagnosis and detection of lesion. However, there are no studies on flexible hysteroscopy using NBI. We performed flexible hysteroscopy with NBI for outpatients to investigate the sensitivity and specificity of endoscopic diagnosis of malignant endometrial lesions. Of patients who attended our hospital for suspected lesions in the uterine cavity between April 2009 and May 2010, 104 subjects underwent hysteroscopy with NBI, in addition to white light. Using the pathological diagnosis as the gold-standard, we evaluated the sensitivity and specificity of NBI hysteroscopy for detecting atypical endometrial hyperplasia (AEH) or carcinoma. The results were also compared with historical data (n=209) for conventional hysteroscopy using white light only in 2008. The sensitivities were 97.2% [95% confidence interval (95% CI): 90.3-99.7%] and 82.6% (95% Cl: 74.4-89.0%) for NBI hysteroscopy and conventional hysteroscopy, respectively. The 95% CIs for the two methods did not overlap and the sensitivity of lesion detection was higher with NB! hysteroscopy. Specificities were comparable, 90.6% (95% CI: 75.0-98.0%) and 85.1% (95% CI: 76.3-91.6%) between the methods. NBI hysteroscopy has increased sensitivity for detection of atypical endometrial hyperplasia (AEH) or carcinoma. A comparison with historical data suggested that NBI may be useful for diagnosis of malignant endometrial lesions. As far as we are aware, this is the first evaluation of flexible hysteroscopy with NBI for diagnosis of malignant endometrial lesions.

DOI： 10.3892/ijo.2011.903

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Flexible hysteroscopy with narrow band imaging (NBI) for endoscopic diagnosis of malignant endometrial lesions. International journal

Iori Kisu, Kouji Banno, Yusuke Kobayashi, Asuka Ono, Kenta Masuda, Arisa Ueki, Hiroyuki Nomura, Akira Hirasawa, Takayuki Abe, Keisuke Kouyama, Nobuyuki Susumu, Daisuke Aoki

International journal of oncology 38 ( 3 ) 613 - 8 2011.3

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

Narrow band imaging (NBI) for detection of blood vessels and microstructures on the mucosal surface is used in gastrointestinal endoscopy since it can improve qualitative diagnosis and detection of lesion. However, there are no studies on flexible hysteroscopy using NBI. We performed flexible hysteroscopy with NBI for outpatients to investigate the sensitivity and specificity of endoscopic diagnosis of malignant endometrial lesions. Of patients who attended our hospital for suspected lesions in the uterine cavity between April 2009 and May 2010, 104 subjects underwent hysteroscopy with NBI, in addition to white light. Using the pathological diagnosis as the gold-standard, we evaluated the sensitivity and specificity of NBI hysteroscopy for detecting atypical endometrial hyperplasia (AEH) or carcinoma. The results were also compared with historical data (n=209) for conventional hysteroscopy using white light only in 2008. The sensitivities were 97.2% [95% confidence interval (95% CI): 90.3-99.7%] and 82.6% (95% CI: 74.4-89.0%) for NBI hysteroscopy and conventional hysteroscopy, respectively. The 95% CIs for the two methods did not overlap and the sensitivity of lesion detection was higher with NBI hysteroscopy. Specificities were comparable, 90.6% (95% CI: 75.0-98.0%) and 85.1% (95% CI: 76.3-91.6%) between the methods. NBI hysteroscopy has increased sensitivity for detection of atypical endometrial hyperplasia (AEH) or carcinoma. A comparison with historical data suggested that NBI may be useful for diagnosis of malignant endometrial lesions. As far as we are aware, this is the first evaluation of flexible hysteroscopy with NBI for diagnosis of malignant endometrial lesions.

DOI： 10.3892/ijo.2011.903

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Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics and Association with Lynch Syndrome

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

CURRENT GENOMICS 12 ( 1 ) 25 - 29 2011.3

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

Endometrial cancer arises from the uterine body and fundus in many cases, but can also originate from the lower region of the uterine body through the upper region of the cervix. Such tumors are referred to as carcinoma of the lower uterine segment (LUS) or isthmus, and account for 3-6.3% of all cases of endometrial cancer. This relatively low incidence has permitted performance of only small-scale studies, but the clinical and pathological characteristics of carcinoma of the LUS in all these reports have differed from those of other endometrial cancers. Generally, endometrial cancer is classified into estrogen-dependent endometrioid adenocarcinoma (designated as type I), and non-endometrioid types that are less associated with estrogen and include poorly differentiated adenocarcinoma (type II). In some reports, carcinoma of the LUS has been found to have type II characteristics. Carcinoma of the LUS has also been associated with Lynch syndrome, a hereditary disease with frequent development of colorectal, endometrial, and ovarian cancers. Lynch syndrome is thought to be induced by mismatch repair gene mutation. The frequency of Lynch syndrome in cases of general endometrial cancer is 1-2%. In contrast, the frequency in patients with carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with Lynch syndrome and a high frequency of hMSH2 mutation found in one study. This suggests that further investigation of the clinical and pathological characteristics of carcinoma of the LUS and the association with Lynch syndrome is required through performance of a large-scale survey.

DOI： 10.2174/138920211794520169

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Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics and Association with Lynch Syndrome. International journal

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

Current genomics 12 ( 1 ) 25 - 9 2011.3

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

DOI： 10.2174/138920211794520169

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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

AOKI DAISUKE

日本分子腫瘍マーカー研究会誌 26 32-33 - 33 2011.1

ホルモン補充療法が腰椎骨密度に及ぼす長期的な効果の検討 -当科健康維持外来における10年継続投与例からの検証- .

牧田和也, 松村聡子, 堀場裕子, 平沢晃, 小川真里子, 弟子丸亮太, 柳本茂久, 高松潔, 青木大輔

Osteoporosis Japan 18 ( 3 ) 83-85 - 539 2011

MicroRNA in endometrial cancer Reviewed

Yanokura M, Banno K, Kisu I, Masuda K, Ueki A, Kobayashi Y, Tsuji K, Yamagami W, Nomura H, Hirasawa A, Susumu N, Aoki D

Trends in Cancer Research 7 49-55 2011

Relationship between DNA Mismatch Repair Deficiency and Endometrial Cancer. Reviewed International journal

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

Molecular biology international 2011 256063 - 256063 2011

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

Some cases of endometrial cancer are associated with a familial tumor and are referred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Lynch syndrome is thought to be induced by germline mutation of the DNA mismatch repair (MMR) gene. An aberration in the MMR gene prevents accurate repair of base mismatches produced during DNA replication. This phenomenon can lead to an increased frequency of errors in target genes involved in carcinogenesis, resulting in cancerization of the cell. On the other hand, aberrant DNA methylation is thought to play a key role in sporadic endometrial carcinogenesis. Hypermethylation of unmethylated CpG islands in the promoter regions of cancer-related genes associated with DNA repair leads to the cell becoming cancerous. Thus, both genetic and epigenetic changes are intricately involved in the process through which cells become cancerous. In this review, we introduce the latest findings on the DNA mismatch repair pathway in endometrial cancer.

DOI： 10.4061/2011/256063

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