Faculty Profiles - HIRASAWA Akira

Papers - HIRASAWA Akira

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Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer

Kouji Banno, Megumi Yanokura, Nobuyuki Susumu, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Katsumi Tsukazaki, Daisuke Aoki

ONCOLOGY REPORTS 16 ( 6 ) 1189 - 1196 2006.12

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the. hypermethylation of the promoter regions of five genes: hMLH1, APC, E-cadherin, RAR-beta and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E-cadherin, and 2.3% (1/44) in RAR-beta in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the frequencies of aberrant methylation were 14.3% (2/14) in hMLH1 and 7.3% (1/14) in APC, whereas normal endometrial cells showed no aberrant hypermethylation of any of the five genes. The high frequencies of the aberrant DNA hypermethylation of hMLH1, APC and E-cadherin suggest that the methylation of the DNA mismatch repair and Wnt signal-related genes may be associated with endometrial carcinogenesis.

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Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer Reviewed

Kouji Banno, Megumi Yanokura, Nobuyuki Susumu, Makiko Kawaguchi, Nobumaru Hirao, Akira Hirasawa, Katsumi Tsukazaki, Daisuke Aoki

ONCOLOGY REPORTS 16 ( 6 ) 1189 - 1196 2006.12

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

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卵巣明細胞腺癌におけるシアリダーゼ発現の多寡が腹膜播種形成に及ぼす影響の検討

野村弘行, 玉田裕, 鈴木淳, 平沢晃, 進伸幸, 宮城妙子, 入村達郎, 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 26回 28 - 29 2006.9

子宮体癌における腫瘍マーカーの意義

AOKI DAISUKE

産婦人科の実際 55 ( 5 ) 753-762 - 762 2006.5

コルポスコピー、コルポ下狙い生検

AOKI DAISUKE

臨床婦人科産科 60 ( 4 ) 369-375 - 375 2006.4

Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer. International journal

Wataru Yamagami, Nobuyuki Susumu, Kouji Banno, Takeshi Hirao, Fumio Kataoka, Akira Hirasawa, Nao Suzuki, Daisuke Aoki, Shiro Nozawa

The journal of obstetrics and gynaecology research 31 ( 5 ) 444 - 51 2005.10

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

AIM: The number of patients under 40 years of age with early-onset endometrial cancer is on the rise in Japan. Preservation of fertility in younger patients is a critical issue. In order to examine the clinical and pathological characteristics of these patients, cases of early-onset endometrial cancer at a single hospital were analyzed. METHODS: Seventy-four patients were diagnosed with endometrial cancer before age 40 and included in this study after obtaining informed consent. RESULTS: The clinical characteristics included a significantly higher prevalence of complications such as nulligravidity and nulliparity (P < 0.001). Pathologically, well-differentiated endometrial carcinoma was significantly more frequent (P = 0.011). The 5-year survival rate was high (98.7%). In regards to the relationship between clinicopathological features and grade of differentiation, the prevalence of G2 and G3 carcinoma was not significantly lower (P = 0.24) in patients with obesity. Although the frequency of G2 and G3 carcinoma was significantly higher in patients with a family history of cancer (P = 0.02), their 5-year survival rate was not significantly lower (100%). CONCLUSION: This study found that these two types of early-onset endometrial cancer are clinicopathologically different. In patients with a family history of cancer, their body mass index was lower, and the frequency of G2 and G3 carcinoma was significantly higher, but their 5-year disease-free survival rate was not significantly lower.

DOI： 10.1111/j.1447-0756.2005.00318.x

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実地臨床応用が期待される新たな腫瘍マーカー−バイオマーカーとしてのゲノム変化を中心に−

AOKI DAISUKE

臨床婦人科産科 59 ( 10 ) 1383-1387 - 1387 2005.10

[Diagnostic significance of tumor markers for gynecologic malignancies].

Daisuke Aoki, Akira Hirasawa, Nobuyuki Susumu

Gan to kagaku ryoho. Cancer & chemotherapy 32 ( 3 ) 411 - 6 2005.3

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

Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms. With ovarian tumors, due to their location within the abdominal cavity, it is difficult to make a preoperative pathological diagnosis of cancer without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA 125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, there are no useful tumor markers for endometrial cancer that exhibit both high sensitivity and specificity, although CA 125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of post-molar disease as well as with the overall decrease in the number of pregnancies.

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婦人科腫瘍

AOKI DAISUKE

癌と化学療法 32 ( 33 ) 411-416 2005.3

Diagnostic significance of tumor markers for gynecologic malignancies

Aoki Daisuke, Hirasawa Akira, Susumu Nobuyuki

Gan to kagaku ryoho. Cancer & chemotherapy 32 ( 3 ) 411 - 416 2005.3

Language：English

<p>Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms. With ovarian tumors, due to their location within the abdominal cavity, it is difficult to make a preoperative pathological diagnosis of cancer without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA 125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, there are no useful tumor markers for endometrial cancer that exhibit both high sensitivity and specificity, although CA 125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of post-molar disease as well as with the overall decrease in the number of pregnancies.</p>

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子宮体癌手術症例における傍大動脈リンパ節廓清の検討.

HIRASAWA AKIRA

日本産科婦人科学会東京地方部会会誌 54 ( 2 ) 219-222 - 222 2005

Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer

W Yamagami, N Susumu, K Banno, T Hirao, F Kataoka, A Hirasawa, N Suzuki, D Aoki, S Nozawa

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 31 ( 5 ) 444 - 451 2005

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

Aim: The number of patients under 40 years of age with early-onset endometrial cancer is on the rise in Japan. Preservation of fertility in younger patients is a critical issue. In order to examine the clinical and pathological characteristics of these patients, cases of early-onset endometrial cancer at a single hospital were analyzed.
Methods: Seventy-four patients were diagnosed with endometrial cancer before age 40 and included in this study after obtaining informed consent.
Results: The clinical characteristics included a significantly higher prevalence of complications such as nulligravidity and nulliparity (P < 0.001). Pathologically, well-differentiated endometrial carcinoma was significantly more frequent (P = 0.011). The 5-year survival rate was high (98.7%). In regards to the relationship between clinicopathological features and grade of differentiation, the prevalence of G2 and G3 carcinoma was not significantly lower (P = 0.24) in patients with obesity. Although the frequency of G2 and G3 carcinoma was significantly higher in patients with a family history of cancer (P = 0.02), their 5-year survival rate was not significantly lower (100%).
Conclusion: This study found that these two types of early-onset endometrial cancer are clinicopathologically different. In patients with a family history of cancer, their body mass index was lower, and the frequency of G2 and G3 carcinoma was significantly higher, but their 5-year disease-free survival rate was not significantly lower.

DOI： 10.1111/j.1447-0756.2005.00318.x

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Clinicopathologic manifestations of early-onset endometrial cancer in Japanese women with a familial predisposition to cancer Reviewed

W Yamagami, N Susumu, K Banno, T Hirao, F Kataoka, A Hirasawa, N Suzuki, D Aoki, S Nozawa

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 31 ( 5 ) 444 - 451 2005

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

DOI： 10.1111/j.1447-0756.2005.00318.x

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Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines. Reviewed International journal

Hideaki Tanami, Issei Imoto, Akira Hirasawa, Yasuhiro Yuki, Itaru Sonoda, Jun Inoue, Kohichiro Yasui, Akiko Misawa-Furihata, Yutaka Kawakami, Johji Inazawa

Oncogene 23 ( 54 ) 8796 - 804 2004.11

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

Comparative genomic hybridization (CGH) using 40 cell lines derived from malignant melanomas (MMs) revealed frequent amplification at 7q33-q34 containing BRAF gene, which often is mutated in MM. We found this gene to be amplified to a remarkable degree in the MM cell lines that exhibited high-level gains at 7q33-q34 in CGH. Among 40 cell lines, the eight lines that revealed neither BRAF nor NRAS mutations showed even higher levels of BRAF mRNA expression than the 32 mutated lines, although DNA amplification at 7q33-q34 was not detected in every lines overexpressing BRAF. MM cells that carried wild-type BRAF and NRAS showed constitutive overexpression of B-Raf protein and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), even after serum starvation. Not only downregulation of the endogenously overexpressed wild-type B-Raf by antisense oligonucleotide but also a treatment with an inhibitor of mitogen-activated protein kinase kinase (MAPKK, MEK) reduced phosphorylated ERK1/2 and cell growth, whereas the exogenously expressed wild-type B-Raf promoted cell growth in MM cells. Our results provide the evidence that overexpression of wild-type B-Raf, in part but not always as a result of gene amplification, is one of the mechanisms underlying constitutive activation of the MAPK pathway that stimulates growth of MM cells.

DOI： 10.1038/sj.onc.1208152

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Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines

H Tanami, Imoto, I, A Hirasawa, Y Yuki, Sonoda, I, J Inoue, K Yasui, A Misawa-Furihata, Y Kawakami, J Inazawa

ONCOGENE 23 ( 54 ) 8796 - 8804 2004.11

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

DOI： 10.1038/sj.onc.1208152

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[Outline of treatment for endometrial cancer].

Daisuke Aoki, Akira Hirasawa, Nobuyuki Susumu, Shiro Nozawa

Nihon rinsho. Japanese journal of clinical medicine 62 Suppl 10 324 - 8 2004.10

子宮体癌の治療治療概論

青木大輔, 平沢晃, 進伸幸, 野澤志朗

日本臨床 62 ( 増刊 ) 324-328 - 328 2004.10

Two Japanese kindreds occurring endometrial cancer meeting new clinical criteria for hereditary non-polyposis colorectal cancer (HNPCC), Amsterdam Criteria II Reviewed

K Banno, N Susumu, T Hirao, M Yanokura, A Hirasawa, D Aoki, Y Udagawa, K Sugano, S Nozawa

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH 30 ( 4 ) 287 - 292 2004.8

Language：English Publishing type：Research paper (scientific journal) Publisher：BLACKWELL PUBLISHING ASIA

Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, is an autosomal dominantly inherited disorder of cancer susceptibility. Patients with HNPCC exhibit an increased risk for HNPCC-associated extracolonic tumors such as cancer of the endometrium. HNPCC is associated with germline mutations in DNA mismatch repair (MMR) genes: hMLH1, hMSH2 and hMSH6.
Here, we describe two Japanese kindreds (0.5%) who met the new clinical criteria for HNPCC, Amsterdam criteria II, from among 375 endometrial cancer patients treated at Keio University Hospital from 1990 to 2002. From these results, it was found that female HNPCC patients comprised approximately 0.5% of all endometrial cancer patients. Decreased expression of two MMR gene protein products (hMLH1 and hMSH6) was confirmed immunohistochemically in these two endometrial tumors in HNPCC kindreds. This case report provides important information on Japanese HNPCC patients occurring endometrial cancer.

DOI： 10.1111/j.1447-0756.2004.00195.x

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Association of HNPCC and endometrial cancers.

Kouji Banno, Nobuyuki Susumu, Megumi Yanokura, Takeshi Hirao, Takashi Iwata, Akira Hirasawa, Daisuke Aoki, Kokichi Sugano, Shiro Nozawa

International journal of clinical oncology 9 ( 4 ) 262 - 9 2004.8

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

Hereditary nonpolyposis colorectal cancer (HNPCC) is among the representative familial cancers that are autosomally dominant inherited disorders. Because endometrial cancers develop at high rates in women with HNPCC, it is suggested that some endometrial cancers are familial cancers that are induced by mutations of the DNA mismatch repair (MMR) genes, as in HNPCC. To understand the clinical pathology of familial endometrial cancers that are associated with HNPCC, we surveyed the family histories of 385 patients with endometrial cancer and found that 0.5% of endometrial cancers met the new diagnostic criteria of HNPCC. From molecular and biological analyses, we found microsatellite instability in 30.8% of endometrial cancers and germline mutations of MMR genes in 8.3%. These results suggest a close relationship of MMR gene mutations to the development of endometrial cancers. For a better understanding of the clinical pathology of HNPCC-associated familial endometrial cancers, it is critical for gynecologists to perform a large multicenter study, including detailed family histories.

DOI： 10.1007/s10147-004-0402-8

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Association of HNPCC and endometrial cancers

Kouji Banno, Nobuyuld Susumu, Megumi Yanokura, Takeshi Hirao, Takashi Iwata, Akira Hirasawa, Daisuke Aoki, Kokichi Sugano, Shiro Nozawa

International Journal of Clinical Oncology 9 ( 4 ) 262 - 269 2004.8

Language：English

DOI： 10.1007/s10147-004-0402-8

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