Gynecologic oncology

1977 April --- 1981 March

Nagoya University School of Medicine

1982 April --- 1986 March

Nagoya University Graduate School of Medicine

1987 October --- 1988 February

Assistant Staff Doctor, Department of Obstetrics and Gynecology
Nagoya University School of Medicine

1988 February --- 1990 April

Visiting Fellow
National Cancer Institue (USA)

1990 May --- 1998 May

Assistant Professor, Department of Obstetrics and Gynecology
Nagoya University School of Medicine

1998 May --- 1998 April

Associate Professor, Department of Obstetrics and Gynecology
Nagoya University School of Medicine

1999 May --- 1999 December

Assistant Professor, Department of Obstetrics and Gynecology
Nagoya University School of Medicine

1999 December --- 2002 February

Associate Professor,
Department of Maternal and Perinatal Care Medicine
Nagoya University Graduate School of Medicine

2002 March --- 2004 October

Associate Professor, Department of Obstetrics and Gynecology
Nagoya University Graduate School of Medicine

2004 November ---

Professor, Department of Obstetrics and Gynecology
Nagoya University Graduate School of Medicine

Developing molecular target therapy against malignant tumors

Malignant ovarian neoplasm (MON) is the leading cause of mortality among cancers of the female reproductive system. The majority of patients with MON have advanced intraperitoneal metastatic disease at diagnosis since this carcinoma frequently remains clinically silent. Today, paclitaxel-platinum-based chemotherapy has become the standard regimen for MON worldwide. Nevertheless, despite the comparatively high sensitivity of MON to paclitaxel, the prognosis of advanced or recurrent cases remains poor since most deaths are the result of metastasis that is refractory to these chemotherapeutic agents. To improve the prognosis of patients with MON, we would like to examine a variety of additional molecular-targeting therapies combined with paclitaxel have been investigated. We have investigated three major projects as described below; 1) Molecular therapy targeting EMT inducer to overcome metastatic potential and chemoresistance of MON, 2) Oncolytic viral therapy for human ovarian cancer using a novel replication-competent herpes simplex virus type I mutant, and 3) Establishment and characterization of an ovarian yolk sac tumor cell line and molecular-targeting therapy focusing Nkx2.5 in tumor development.

1) In our previous study, we showed a correlation between TWIST, which is one of the major inducer of EMT expression and cellular morphology of epithelial ovarian cancer (EOC). Furthermore, we demonstrated that positive TWIST expression seems to be a useful marker in patients with EOC likely to have an unfavorable clinical outcome. Our aim of this study is to clarify whether reduced expression of TWIST suppresses the multistep process of peritoneal dissemination (detachment from the primary lesion, adhesion to and invasion of mesothelial cells) or chemoresistance of EOC, and may be a potential therapeutic target for the treatment of EOC. Furthermore, we will study whether there is simultaneous induction of cancer metastasis and acquired chemoresistance by EMT.

2) Oncolytic HSV-1 has been developed as a novel anticancer agent. According to the properties and functions of HSV-1 encoded proteins, several genes have been targeted for engineering of oncolytic HSV-1. As a result, a variety of strategies have been applied to the engineering of oncolytic HSV-1. Success in cancer therapy for solid tumors requires a maximal oncolytic effect; however, recombinant HSV-1 that has been adapted to meet neurotoxicity requirements for the treatment of brain tumors may be too highly attenuated for effective use in solid tumors outside the brain. Recently, there has been renewed interest in the high potency of naturally oncolytic viruses. In this review, we will overview the engineered oncolytic HSV developed thus far, as well as its mechanism of selectivity and its mode of spreading within tumors. We are investigating the preclinical and clinical studies of HF-10, a non-engineered oncolytic HSV-1 virus, and its potential for use in ovarian cancer gene therapy.

3) The purpose of this study was to establish a human ovarian YST cell line to be able to identify a target for novel molecular-based therapy. YST cell lines (NOY1 and NOY2) were established from surgical specimens, and NOY1 cells were characterized. Analysis of this new cell line suggested that Nkx2.5 can be a new molecular target in the treatment of ovarian YST. Our future findings will indicate that the oncolytic viral therapy or EMT-targeting therapy possesses significant therapeutic potential for treatment of MON. Such therapy offers a novel approach to reductions in the dissemination of MON.

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1. Ino K et al. Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival. Clin. Cancer Res. 14: 2310-2317 (2008)
2. Kajiyama H et al. Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma. Int. J. Cancer 122: 91-99 (2008)
3. Shibata K et al. Twist expression in patients with cervical cancer is associated with poor disease outcome. Ann. Oncol. 19: 81-85 (2008)
4. Yamamoto E et al. Expression of N-acetylglucosaminyltransferase V in endometrial cancer correlates with poor prognosis. Br. J. Cancer 97: 1538-1544 (2007)
5. Yamashita M et al. Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo. Int. J. Cancer 120: 2243-2250 (2007)
6. Hosono S et al. Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients. Br. J. Cancer 96: 314-320 (2007)
7. Ino K et al. Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer. Br. J. Cancer 95: 1555-1561 (2006)
8. Iwase A et al. Neutral endopeptidase expressed by decidualized stromal cells suppresses akt phosphorylation and deoxyribonucleic acid synthesis induced by endothelin-1 in human endometrium. Endocrinology. 147: 5153-5159 (2006)
9. Kikkawa F et al. Clinical characteristics and prognosis of mucinous tumors of the ovary. Gynecol Oncol. 103: 171-175 (2006)
10. Shido F et al. Endoplasmic reticulum aminopeptidase-1 mediates leukemia inhibitory factor-induced cell surface human leukocyte antigen-G expression in JEG-3 choriocarcinoma cells. Endocrinology 147: 1780-1788 (2006)
11. Ino K et al. Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival. Br. J. Cancer 94: 552-560 (2006)
12. Kondo C et al. A novel role for placental leucine aminopeptidase (P-LAP) as a determinant of chemoresistance in endometrial carcinoma cells. Int. J. Cancer 118: 1390-1394 (2006)
13. Kikkawa F et al. Dipeptidyl peptidase IV in tumor progression. Biochim. Biophys. Acta. 1751: 45-51 (2005)
14. Suganuma T et al. Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells and its blockade therapy resulting in suppression of tumor invasion, angiogenesis, and peritoneal dissemination. Clin. Cancer Res. 11: 2686-2694 (2005)
15. Kajiyama H et al. Neutral endopeptidase 24.11/CD10 suppresses progressive potential in ovarian carcinoma in vitro and in vivo. Clin. Cancer Res. 11: 1798-1808 (2005)