Faculty Profiles - HIRASAWA Akira

Papers - HIRASAWA Akira

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Blood-direct InvaderPlus (R) as a new method for genetic testing Reviewed

Akira Hirasawa, Tomoko Akahane, Yusuke Tanigawara, Daisuke Aoki

PERSONALIZED MEDICINE 9 ( 6 ) 657 - 663 2012.8

Language：English Publishing type：Research paper (scientific journal) Publisher：FUTURE MEDICINE LTD

Aim: This study compared the efficiency of Blood-direct InvaderPlus (R) with existing methods for detecting genetic polymorphisms by using clinical samples, and to determine whether this new method can be used for future clinical studies. Materials & methods: We developed a new method, called Blood-direct InvaderPlus, for detecting genetic polymorphisms. Whole-blood samples were subjected to genetic analysis with the new method and also the conventional method. Results: The results obtained with the new method were consistent with those of direct sequencing. Blood-direct InvaderPlus was able to detect gene polymorphisms of UGT1A1*6, *2Z *28, *60, VKORC1 -1639G>A, VKORC1 1173T>C and CYP2C9 *2 and *3 much faster than the conventional methods. Conclusion: Blood-direct InvaderPlus allowed accurate, simple and rapid detection of genetic polymorphisms.

DOI： 10.2217/PME.12.71

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Blood-direct InvaderPlus (R) as a new method for genetic testing

Akira Hirasawa, Tomoko Akahane, Yusuke Tanigawara, Daisuke Aoki

PERSONALIZED MEDICINE 9 ( 6 ) 657 - 663 2012.8

Language：English Publishing type：Research paper (scientific journal) Publisher：FUTURE MEDICINE LTD

DOI： 10.2217/PME.12.71

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当科健康維持外来受診者における大腿骨近位部骨密度の検討

AOKI DAISUKE

Osteoporosis Japan 20 ( 3 ) 489 - 491 2012.7

子宮体癌の家族発生と遺伝子診断

AOKI DAISUKE

日本臨床婦人科がん－最新の研究動向－ 70 ( 増刊号4 ) 292-296 - 296 2012.6

[Hereditary endometrial cancer and genetic testing].

Akira Hirasawa, Tomohiko Tsuruta, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 4 292 - 6 2012.6

[Hereditary endometrial cancer and genetic testing].

Hirasawa Akira, Tsuruta Tomohiko, Banno Kouji, Susumu Nobuyuki, Aoki Daisuke

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 4 292 - 296 2012.6

EGRI and FOSB gene expressions in cancer stroma are independent prognostic indicators for epithelial ovarian cancer receiving standard therapy

Fumio Kataoka, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Hideo Tanaka, Hiroyuki Nomura, Tatsuyuki Chiyoda, Akira Hirasawa, Tomoko Akahane, Hiroshi Nishio, Kazuto Nishio, Daisuke Aoki

GENES CHROMOSOMES & CANCER 51 ( 3 ) 300 - 312 2012.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Stromal components interact with cancer cells to promote growth and metastasis. The purpose of this study was to identify genes expressed in stroma, which could provide prognostic information in epithelial ovarian cancer (EOC). Seventy-four patients were included. We performed gene expression profiling and confirmed array data using RT-PCR and immunohistochemistry. By microarray analysis, 52 candidate genes associated with progression free survival (PFS) were identified (P < 0.005). Expression of the early growth response 1 (EGR1) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) genes was further analyzed. Array data were confirmed by RT-PCR and multivariate analysis demonstrated that both EGR1 and FOSB expression in cancer stroma, and EGR1 expression in cancer are independent prognostic factors in EOC. Immunohistochemically, EGR1 protein is localized in cancer cells and a-smooth muscle actin positive stromal fibroblasts. The EGR1 and FOSB expression in stromal cells and EGR1 expression in cancer cells are prognostic indicators in EOC. (c) 2011 Wiley Periodicals, Inc.

DOI： 10.1002/gcc.21916

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EGRI and FOSB gene expressions in cancer stroma are independent prognostic indicators for epithelial ovarian cancer receiving standard therapy Reviewed

Fumio Kataoka, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Hideo Tanaka, Hiroyuki Nomura, Tatsuyuki Chiyoda, Akira Hirasawa, Tomoko Akahane, Hiroshi Nishio, Kazuto Nishio, Daisuke Aoki

GENES CHROMOSOMES & CANCER 51 ( 3 ) 300 - 312 2012.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

DOI： 10.1002/gcc.21916

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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誌 27 23-34 - 24 2012

Aberrant DNA Methylation in Endometrial Cancer

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

Epigenetics in Human Disease 471 - 480 2012

遺伝性乳癌卵巣癌 Invited Reviewed

平沢晃, 青木大輔

日本産科婦人科学会雑誌 64 ( 4 ) 292 - 296 2012

発現解析による子宮体癌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誌 27 45-46 - 46 2012

子宮体がんの術後補助療法

AOKI DAISUKE

腫瘍内科 8 ( 6 ) 563-571 - 571 2011.12

Immunofluorescence-Detected Infiltration of CD4(+)FOXP3(+) Regulatory T Cells is Relevant to the Prognosis of Patients With Endometrial Cancer Reviewed

Wataru Yamagami, Nobuyuki Susumu, Hideo Tanaka, Akira Hirasawa, Kouji Banno, Nao Suzuki, Hiroshi Tsuda, Katsumi Tsukazaki, Daisuke Aoki

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 21 ( 9 ) 1628 - 1634 2011.12

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

Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8(+) cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.
Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4(+) FOXP3(+) cells were identified as Tregs in this study. The numbers of CD8(+) cells, CD4(+) cells, and Tregs as well as the Treg/CD8(+) and Treg/CD4(+) ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis.
Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8(+) and CD4(+) cell counts, Treg count, and Treg/CD8(+) and Treg/CD4(+) ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8(+) ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8(+) ratios (P < 0.05).
Conclusions: The Treg count and Treg/CD8(+) ratio may be new prognostic factors for endometrial cancer.

DOI： 10.1097/IGC.0b013e31822c271f

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Immunofluorescence-Detected Infiltration of CD4(+)FOXP3(+) Regulatory T Cells is Relevant to the Prognosis of Patients With Endometrial Cancer

Wataru Yamagami, Nobuyuki Susumu, Hideo Tanaka, Akira Hirasawa, Kouji Banno, Nao Suzuki, Hiroshi Tsuda, Katsumi Tsukazaki, Daisuke Aoki

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 21 ( 9 ) 1628 - 1634 2011.12

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

Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8(+) cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4(+) FOXP3(+) cells were identified as Tregs in this study. The numbers of CD8(+) cells, CD4(+) cells, and Tregs as well as the Treg/CD8(+) and Treg/CD4(+) ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis.Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8(+) and CD4(+) cell counts, Treg count, and Treg/CD8(+) and Treg/CD4(+) ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8(+) ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8(+) ratios (P < 0.05).Conclusions: The Treg count and Treg/CD8(+) ratio may be new prognostic factors for endometrial cancer.

DOI： 10.1097/IGC.0b013e31822c271f

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Immunofluorescence-detected infiltration of CD4+FOXP3+ regulatory T cells is relevant to the prognosis of patients with endometrial cancer. International journal

Wataru Yamagami, Nobuyuki Susumu, Hideo Tanaka, Akira Hirasawa, Kouji Banno, Nao Suzuki, Hiroshi Tsuda, Katsumi Tsukazaki, Daisuke Aoki

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 21 ( 9 ) 1628 - 34 2011.12

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

OBJECTIVE: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8 cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients. METHODS: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4FOXP3 cells were identified as Tregs in this study. The numbers of CD8 cells, CD4 cells, and Tregs as well as the Treg/CD8 and Treg/CD4 ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis. RESULTS: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8 and CD4 cell counts, Treg count, and Treg/CD8 and Treg/CD4 ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8 ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8 ratios (P < 0.05). CONCLUSIONS: The Treg count and Treg/CD8 ratio may be new prognostic factors for endometrial cancer.

DOI： 10.1097/IGC.0b013e31822c271f

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Narrow band imaging hysteroscopy: A comparative study using randomized video images Reviewed

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 39 ( 5 ) 1057 - 1062 2011.11

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

Narrow band imaging (NBI) has been used in the gastrointestinal endoscopy field as a novel endoscopic imaging technique and has contributed to improved qualitative diagnosis and detection of lesions. However, there are only a few studies of use of NBI in the gynecology field. We applied NBI in flexible hysteroscopy at our outpatient clinic and evaluated the utility of NBI hysteroscopy for diagnosis of malignant endometrial lesions by comparison of the sensitivity and specificity between white light alone and white light+NBI using hysteroscopic video images. The subjects were 65 patients with a suspected endometrial lesion in the uterine cavity. These patients underwent flexible hysteroscopy using NBI in addition to conventional white light. Video images from 65 patients were edited into two groups, white light alone (WL group) and white light+NBI (NBI group) (130 images in total). Computerized block randomization of the order was then performed. Four raters independently diagnosed the images without use of other clinical information. Using the pathological diagnosis as the gold standard, we evaluated the sensitivity and specificity of diagnosis of atypical endometrial hyperplasia (AEH) or endometrial carcinoma compared between the WL and NBI groups. The sensitivity of diagnosis of A EH or endometrial carcinoma was numerically higher in the NBI group for all raters, and the average sensitivity was significantly higher in the NBI group compared to the WL group (78.6% vs. 63.7%, P<0.001). The specificity for each rater and the average specificity were comparable between the two groups. Compared to white light hysteroscopy, NBI hysteroscopy had a higher sensitivity for diagnosis of AEH or endometrial carcinoma without loss of specificity. This suggests that NBI hysteroscopy may be more useful than white light hysteroscopy for endoscopic diagnosis of malignant endometrial lesions.

DOI： 10.3892/ijo.2011.1131

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Narrow band imaging hysteroscopy: A comparative study using randomized video images

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 39 ( 5 ) 1057 - 1062 2011.11

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

DOI： 10.3892/ijo.2011.1131

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Narrow band imaging hysteroscopy: a comparative study using randomized video images. 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 39 ( 5 ) 1057 - 62 2011.11

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

Narrow band imaging (NBI) has been used in the gastrointestinal endoscopy field as a novel endoscopic imaging technique and has contributed to improved qualitative diagnosis and detection of lesions. However, there are only a few studies of use of NBI in the gynecology field. We applied NBI in flexible hysteroscopy at our outpatient clinic and evaluated the utility of NBI hysteroscopy for diagnosis of malignant endometrial lesions by comparison of the sensitivity and specificity between white light alone and white light+NBI using hysteroscopic video images. The subjects were 65 patients with a suspected endometrial lesion in the uterine cavity. These patients underwent flexible hysteroscopy using NBI in addition to conventional white light. Video images from 65 patients were edited into two groups, white light alone (WL group) and white light+NBI (NBI group) (130 images in total). Computerized block randomization of the order was then performed. Four raters independently diagnosed the images without use of other clinical information. Using the pathological diagnosis as the gold standard, we evaluated the sensitivity and specificity of diagnosis of atypical endometrial hyperplasia (AEH) or endometrial carcinoma compared between the WL and NBI groups. The sensitivity of diagnosis of AEH or endometrial carcinoma was numerically higher in the NBI group for all raters, and the average sensitivity was significantly higher in the NBI group compared to the WL group (78.6% vs. 63.7%, P<0.001). The specificity for each rater and the average specificity were comparable between the two groups. Compared to white light hysteroscopy, NBI hysteroscopy had a higher sensitivity for diagnosis of AEH or endometrial carcinoma without loss of specificity. This suggests that NBI hysteroscopy may be more useful than white light hysteroscopy for endoscopic diagnosis of malignant endometrial lesions.

DOI： 10.3892/ijo.2011.1131

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miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. International journal

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

Cancer research 71 ( 20 ) 6450 - 62 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.

DOI： 10.1158/0008-5472.CAN-11-0364

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Papers - HIRASAWA Akira