Details of a Researcher - Masuda, Kenta

Papers - Masuda, Kenta

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Glycan profiling of gestational choriocarcinoma using a lectin microarray.

Kobayashi Y, Masuda K, Banno K, Kobayashi N, Umene K, Nogami Y, Tsuji K, Ueki A, Nomura H, Sato K, Tominaga E, Shimizu T, Saya H, Aoki D

Oncology reports (Oncology Reports) 31 ( 3 ) 1121 - 6 2014.03

ISSN 1021-335X

Glycosylation is an important post-translational modification, in which attachment of glycans to proteins has effects on biological functions and carcinogenesis. Analysis of human chorionic gonadotropin, a glycoprotein hormone produced by placental trophoblasts and trophoblastic tumors, has contributed to the diagnosis and treatment of trophoblastic disease, resulting in reduced incidence and mortality. However, alterations of the glycan structure itself in choriocarcinoma have not been characterized. We established a new choriocarcinoma cell line, induced choriocarcinoma cell-1 (iC3-1), which mimics the clinical pathohistology in vivo, to examine the tumorigenesis and pathogenesis of choriocarcinoma. In this study, the alterations of glycan structures in the development of choriocarcinoma were examined by performance of comprehensive glycan profiling in clinical samples and in iC3-1 cells using a conventional microarray and the recently introduced lectin microarray. Microarray comparison showed significant upregulation of several characteristic glycogenes in the iC3-1 cells as compared to the parental HTR8/SVneo cells. The lectin array showed increased α-2-6-sialic acid, Galβ1-4GlcNAc, GlcNAcβ1-3GalNAc, and decreased α-1-6 core fucose, high mannose, GalNacβ1-4Gal, GALNAc (Tn antigen) and Galβ-3Gal in choriocarcinoma tissue compared to normal villi. This is the first report of a lectin array analysis in choriocarcinoma and provides useful information for understanding of the disease.

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A tumor of the uterine cervix with a complex histology in a Peutz-Jeghers syndrome patient with genomic deletion of the STK11 exon 1 region.

Kobayashi Y, Masuda K, Kimura T, Nomura H, Hirasawa A, Banno K, Susumu N, Sugano K, Aoki D

Future oncology (London, England) (Future Oncology) 10 ( 2 ) 171 - 7 2014.02

ISSN 1479-6694

Patients with Peutz-Jeghers syndrome (PJS) have a risk of complicating malignant tumors, including cancer of the uterine cervix. Mutations in the STK11 gene have been identified as being responsible for PJS. However, the genotype-phenotype correlation in PJS is poorly understood, especially with respect to malignant tumors. Here, we report a detailed analysis of a case of a cervical tumor in a PJS patient showing a large genomic deletion in exon 1 of STK11 without human papillomavirus infection. Histological examination revealed a complex histology consisting of three components: lobular endocervical gland hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA) and mucinous adenocarcinoma. Immunohistochemistry for STK11 was positive in the LEGH and MDA components, while that of the mucinous adenocarcinoma stained very faintly. These findings support a close relationship among LEGH, MDA and mucinous adenocarcinoma and imply that inactivation of STK11 may occur during progression from MDA to mucinous adenocarcinoma. © 2014 Future Medicine Ltd.

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Application of FDG-PET in cervical cancer and endometrial cancer: utility and future prospects.

Nogami Y, Iida M, Banno K, Kisu I, Adachi M, Nakamura K, Umene K, Masuda K, Tominaga E, Tanaka K, Aoki D

Anticancer research (Anticancer Research) 34 ( 2 ) 585 - 92 2014.02

ISSN 0250-7005

© 2014, International Institute of Anticancer Research. All rights reserved. Positron-emission tomography (PET), a diagnostic imaging technique using an agent labeled with a positron-emitting radionuclide, may facilitate improved diagnosis and treatment in gynecological fields. A combined PET/computerized tomography (CT) scan can identify the precise anatomical location of a lesion based on accumulation of 18F-fluoro-D-glucose (FDG). FDG-PET and PET/CT have been used for detecting metastatic lesions and predicting prognosis in uterine cancer. PET has higher reliability in diagnosing lymph node metastases of uterine cancer than CT or MRI, and is considered most useful among non-invasive diagnostic imaging methods. Accumulation of FDG in lesions is indicative of a poor prognosis. Due to its limited spatial resolution, PET is not suitable has lower utility for detecting small lesions, and is not suitable for early-stage screening, and diagnosing primary lesions. Further improvements in diagnostic technology, including PET/MRI, investigation of new positron tracers, and analysis of data from various combinations of tracers are likely to make PET particularly useful for diagnosis and therapeutic strategy planning.

Family history and BRCA1/BRCA2 status among Japanese ovarian cancer patients and occult cancer in a BRCA1 mutant case.

Hirasawa A, Masuda K, Akahane T, Ueki A, Yokota M, Tsuruta T, Nomura H, Kataoka F, Tominaga E, Banno K, Makita K, Susumu N, Sugano K, Kosaki K, Kameyama K, Aoki D

Japanese journal of clinical oncology (Japanese Journal of Clinical Oncology) 44 ( 1 ) 49 - 56 2014.01

ISSN 0368-2811

Background: This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. Methods: One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. Results: Nine of 102 (8.8%) families were regarded as having hereditary breast-ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingooophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. Conclusions: Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations. © The Author 2013. Published by Oxford University Press. All rights reserved.

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Application of microRNA in diagnosis and treatment of ovarian cancer.

Banno K, Yanokura M, Iida M, Adachi M, Nakamura K, Nogami Y, Umene K, Masuda K, Kisu I, Nomura H, Kataoka F, Tominaga E, Aoki D

BioMed research international (BioMed Research International) 2014 232817 2014

ISSN 2314-6133

Ovarian cancer has a poor prognosis because early detection is difficult and recurrent ovarian cancer is usually drug-resistant. The morbidity and mortality of ovarian cancer are high worldwide and new methods of diagnosis and therapy are needed. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression that are involved in carcinogenesis, metastasis, and invasion. Thus, miRNAs are likely to be useful as diagnostic and prognostic biomarkers and for cancer therapy. Many miRNAs have altered expression in ovarian cancer compared to normal ovarian tissues and these changes may be useful for diagnosis and treatment. For example, deficiencies of enzymes including Dicer and Drosha that are required for miRNA biogenesis may be adverse prognostic factors; miRNAs such as miR-214 and miR-31, which are involved in drug resistance, and the miR-200 family, which is implicated in metastasis, may serve as biomarkers; and transfection of downregulated miRNAs and inhibition of upregulated miRNAs may be effective for treatment of ovarian cancer. Chemotherapy targeting epigenetic mechanisms associated with miRNAs may also be effective to reverse gene silencing. © 2014 Kouji Banno et al.

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Indocyanine green fluorescence imaging in the pregnant cynomolgus macaque: childbearing is supported by a unilateral uterine artery and vein alone?

Kisu I, Banno K, Yanokura M, Nogami Y, Umene K, Tsuji K, Masuda K, Ueki A, Kobayashi Y, Aoki D

Archives of gynecology and obstetrics (Archives of Gynecology and Obstetrics) 288 ( 6 ) 1309 - 15 2013.12

ISSN 0932-0067

Purpose: Uterine blood flow is required for the maintenance of uterine viability in pregnancy and delivery, but it is unknown how many vessels are necessary for maintenance of uterine viability. The objective of this study was to examine whether unilateral uterine vessels provide sufficient nutrition in pregnancy in a cynomolgus macaque and to evaluate hemodynamics of pregnant uterus by indocyanine green (ICG) fluorescence imaging. Methods: A cynomolgus macaque with uterine blood flow maintained by the right uterine artery and vein alone was made pregnant. Hemodynamics of the uterus in the third trimester was evaluated by ICG fluorescence imaging. Results: Pregnancy was maintained with the right uterine artery and vein. An appropriate-for-date infant was delivered by Cesarean section. ICG fluorescence imaging showed that the uterine body was imaged from the right side to the center; furthermore, collateral circulation was present from the right uterine artery toward the left uterine artery, with expanded blood flow to the left uterine body. Conclusion: Pregnancy and delivery were achieved in a cynomolgus macaque with a unilateral right uterine artery and vein. Blood flow to the side without the artery was complemented by vascularization of collateral circulation to the uterine artery. © 2013 Springer-Verlag Berlin Heidelberg.

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Hereditary gynecological tumors associated with Peutz-Jeghers syndrome (Review).

Banno K, Kisu I, Yanokura M, Masuda K, Ueki A, Kobayashi Y, Hirasawa A, Aoki D

Oncology letters (Oncology Letters) 6 ( 5 ) 1184 - 1188 2013.11

ISSN 1792-1074

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease that is characterized by gastrointestinal hamartomatous polyposis and mucocutaneous melanin spots. The tumor suppressor gene, STK11/LKB1, which is located on chromosome 19p13.3, has been reported to be responsible for this condition. PJS is complicated by benign and malignant tumors of various organs and complications from rare diseases, including sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which have also recently attracted attention in the field of gynecology. Among the total MDA cases, 10% are complications of PJS, and mutations in the STK11 gene are closely associated with the development and prognosis of MDA. Furthermore, a new type of uterine cervical tumor, lobular endocervical glandular hyperplasia (LEGH), has been identified and has been predicted to be a precancerous lesion of MDA. The first case of LEGH induced by a germline STK11 mutation has also been described. A high risk of endometrial cancer in PJS has also been reported. These developments suggest that PJS is an important syndrome of hereditary gynecological tumors that requires further study.

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Current status of molecular-targeted drugs for endometrial cancer (Review).

Nogami Y, Banno K, Kisu I, Yanokura M, Umene K, Masuda K, Kobayashi Y, Yamagami W, Nomura H, Tominaga E, Susumu N, Aoki D

Molecular and clinical oncology 1 ( 5 ) 799 - 804 2013.09

ISSN 2049-9450

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Candidate biomarkers for genetic and clinicopathological diagnosis of endometrial cancer.

Banno K, Nogami Y, Kisu I, Yanokura M, Umene K, Masuda K, Kobayashi Y, Yamagami W, Susumu N, Aoki D

International journal of molecular sciences (International Journal of Molecular Sciences) 14 ( 6 ) 12123 - 37 2013.06

ISSN 16616596

The recent increase in the frequency of endometrial cancer has emphasized the need for accurate diagnosis and improved treatment. The current diagnosis is still based on conventional pathological indicators, such as clinical stage, tumor differentiation, invasion depth and vascular invasion. However, the genetic mechanisms underlying endometrial cancer have gradually been determined, due to developments in molecular biology, leading to the possibility of new methods of diagnosis and treatment planning. New candidate biomarkers for endometrial cancer include those for molecular epigenetic mutations, such as microRNAs. These biomarkers may permit earlier detection of endometrial cancer and prediction of outcomes and are likely to contribute to future personalized therapy for endometrial cancer. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

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Aurora kinase inhibitors: Potential molecular-targeted drugs for gynecologic malignant tumors.

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

Biomedical reports 1 ( 3 ) 335 - 340 2013.05

ISSN 2049-9434

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Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer: comparison of magnetic resonance imaging and frozen sections.

Kisu I, Banno K, Lin LY, Ueno A, Abe T, Kouyama K, Okuda S, Masugi Y, Umene K, Nogami Y, Tsuji K, Masuda K, Ueki A, Kobayashi Y, Yamagami W, Susumu N, Aoki D

Acta obstetricia et gynecologica Scandinavica (Acta Obstetricia et Gynecologica Scandinavica) 92 ( 5 ) 525 - 35 2013.05

ISSN 0001-6349

Objective To compare the diagnostic characteristics of the evaluation of myometrial invasion (MI) retrospectively between preoperative magnetic resonance imaging (MRI) and intraoperative frozen sections. Design A retrospective study. Setting University hospital. Sample 201 women diagnosed with endometrial carcinoma. Methods All women underwent preoperative MRI and 111 of them also underwent intraoperative frozen section assessment. The final pathological evaluation was used as the definitive diagnosis. Main outcome measures In women who underwent MRI and frozen sections (n = 111), the accuracies of detection of MI and of deep invasion (defined as ≥50% invasion) were compared. Results The accuracy, sensitivity, and specificity of MRI for detection of MI were 65.8, 58.8, and 88.5%, and those in frozen sections were 90.1, 90.6, and 88.5%, respectively. The accuracy and sensitivity of frozen sections were significantly higher (p < 0.001, p < 0.001), whereas the specificity of the two methods did not differ (p = 1.000). The accuracy, sensitivity, and specificity of MRI for detection of deep invasion were 83.8, 69.2, and 88.2%, and those of frozen sections were 93.7, 73.1, and 100.0%, respectively. The accuracy and specificity of frozen sections were significantly higher (p = 0.007 and p < 0.001, respectively), whereas sensitivity did not show a significant difference (p = 0.999). Conclusion In assessment of MI, the accuracy of frozen sections was significantly higher than that of MRI. Since the diagnostic characteristics differ between two methods, additional intraoperative frozen sections are recommended for more accurate assessment of MI when MRI is negative for the presence of any MI or positive for the presence of deep invasion. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

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Experience of risk-reducing salpingo-oophorectomy for a BRCA1 mutation carrier and establishment of a system performing a preventive surgery for hereditary breast and ovarian cancer syndrome in Japan: our challenges for the future.

Hirasawa A, Masuda K, Akahane T, Tsuruta T, Banno K, Makita K, Susumu N, Jinno H, Kitagawa Y, Sugano K, Kosaki K, Aoki D

Japanese journal of clinical oncology (Japanese Journal of Clinical Oncology) 43 ( 5 ) 515 - 9 2013.05

ISSN 0368-2811

Background: Risk-reducing salpingo-oophorectomy is currently regarded as the most certain primary method for preventing ovarian cancer among BRCA1/2 mutation carriers with hereditary breast and ovarian cancer syndrome. However, risk-reducing salpingo-oophorectomy has rarely been performed in Japan. Methods: We developed the first system in Japan for performing risk-reducing salpingooophorectomy for BRCA1/2 mutation carriers at our university hospital in 2008. Results: The indication for risk-reducing salpingo-oophorectomy for patients with hereditary breast/ovarian cancer syndrome is currently limited in Japan. This situation may be because of the limited number of genetic counseling units, the limited number of facilities that can perform BRCA1/2 genetic testing and the fact that prophylactic surgery is not covered by health insurance in Japan. Conclusions: Recent treatment guidelines for breast cancer in Japan recommended riskreducing salpingo-oophorectomy for BRCA1/2 mutation carriers. Risk-reducing salpingooophorectomy should be performed in the framework of the standard therapeutic modality for BRCA1/2 mutation carriers in the near future. © The Author 2013. Published by Oxford University Press. All rights reserved.

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New candidate therapeutic agents for endometrial cancer: potential for clinical practice (review).

Umene K, Banno K, Kisu I, Yanokura M, Nogami Y, Tsuji K, Masuda K, Ueki A, Kobayashi Y, Yamagami W, Tominaga E, Susumu N, Aoki D

Oncology reports (Oncology Reports) 29 ( 3 ) 855 - 60 2013.03

ISSN 1021-335X

Cases of endometrial cancer have increased in recent years, but the prognosis of patients with this disease has also been improved by combined modality therapy with surgery, radiotherapy and chemotherapy. However, the development of new therapy is required from the perspectives of conservation of fertility and efficacy for recurrent and intractable cancer. New candidate therapeutic agents for endometrial cancer include fourth-generation progestins for inhibition of growth and differentiation of endometrial glands; metformin for reduction of hTERT expression in the endometrium and inhibition of the mTOR pathway by activation of AMPK, with consequent inhibition of the cell cycle; mTOR inhibitors for supressing growth of cancer cells by G1 cell cycle arrest; microRNAs involved in the molecular mechanisms of oncogenesis and progression; and HDAC inhibitors that block the growth of cancer cells by transcriptional elevation of tumor-suppressor genes, cell cycle arrest and induction of apoptosis. In this study, we review the background and early clinical evidence for these agents as new therapeutic candidates for endometrial cancer.

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Gene expression profile of a newly established choriocarcinoma cell line, iC<sup>3</sup>-1, compared to existing choriocarcinoma cell lines and normal placenta

Kobayashi Y., Banno K., Shimizu T., Ueki A., Tsuji K., Masuda K., Kisu I., Nomura H., Tominaga E., Nagano O., Saya H., Aoki D.

Placenta (Placenta) 34 ( 2 ) 110 - 118 2013.02

ISSN 01434004

Gestational choriocarcinoma is a malignant trophoblastic tumor that usually occurs in the uterus after pregnancy. The tumor is curable with advanced chemotherapy, but the molecular mechanism of choriocarcinoma tumorigenesis remains unclear. This is partly because the low incidence makes it difficult to obtain clinical samples for investigation and because an appropriate choriocarcinoma cell model to study the tumorigenesis has not been developed. We have established a new choriocarcinoma cell line, induced choriocarcinoma cell-1 (iC3-1), that possesses unique characteristics compared to other choriocarcinoma cell lines, including production of tumors that consist of the two types of cells commonly found in choriocarcinoma and mimicking of the clinical pathology. Existing trophoblast cell lines utilized in previous choriocarcinoma studies have had significantly dissimilar gene expression profiles. Therefore, it is important to choose an appropriate cell line for a particular study based on the characteristics of the cell line. In this study, to clarify the genetic characteristics of iC3-1 and to explore the tumorigenesis mechanism, we examined the gene profile of iC3-1 compared to those of existing cell lines and normal placental tissue. Bioinformatics analysis showed that several characteristic genes, IGF1R, CHFR, MUC3A, TAF7, PARK7, CDC123 and PSMD8, were significantly upregulated in iC 3-1 compared to BeWo and JEG3 cells. Interestingly, HAS2, CD44 and S100P were significantly upregulated in iC3-1 compared to parental HTR8/SVneo cells and normal third trimester placenta. Choriocarcinoma samples also showed immunoreactivity to HAS2, CD44 and S100. In summary, the gene expression profile of iC3-1 suggests that studies using this cell line can make an important contribution to improved understanding of choriocarcinoma tumorigenesis. © 2012 Elsevier Ltd. All rights reserved.

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The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells.

Naoe H, Chiyoda T, Ishizawa J, Masuda K, Saya H, Kuninaka S

Biochemical and biophysical research communications (Biochemical and Biophysical Research Communications) 430 ( 2 ) 757 - 62 2013.01

ISSN 0006-291X

Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1GT/GT) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1GT/GT TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation. © 2012 Elsevier Inc.

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Aberrant DNA Methylation in Endometrial Cancer

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

Epigenetics in Human Disease (Epigenetics in Human Disease) 471 - 480 2012.12

ISSN 9780123884152

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Relationship of lower uterine segment cancer with Lynch syndrome: a novel case with an hMLH1 germline mutation.

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

Oncology reports (Oncology Reports) 28 ( 5 ) 1537 - 43 2012.11

ISSN 1021-335X

Lynch syndrome is a genetic disease that often develops in patients with endometrial cancer and is caused by abnormal DNA mismatch repair (MMR) genes. In the United States, it was recently reported that the prevalence of Lynch syndrome with an hMSH2 mutation in patients with endometrial cancer in the lower uterine segment (LUS) is much greater than that in patients with endometrial cancer, although no such reports have been published in Asia. In this study, we examined the correlation between endometrial cancer in LUS and abnormalities in MMR genes. We examined 625 patients, who were diagnosed with endometrial cancer and underwent a hysterectomy. Nine patients (1.4%) had cancer based on pathological confirmation of a tumor in the lower part of the uterus and no cancer in the upper part. These cases were compared with 27 cases of sporadic endometrial (non-LUS) cancer. The age and BMI of the patients with LUS cancer were significantly lower than those of the patients with non-LUS cancer. No differences were observed in the pathological characteristics. The microsatellite instability (MSI)-positive rates were similar. Immunohistochemistry showed a decreased expression of hMLH1 and hMSH6 in patients with LUS cancer. In contrast with earlier reports from the United States, hMSH2 was expressed in all the cases. Of the 2 patients with LUS cancer who exhibited high MSI, 1 patient showed abnormal methylation of hMLH1, while the other patient was diagnosed with Lynch syndrome with a mutation in the hMLH1 gene. This is the second report on the relationship of LUS cancer and Lynch syndrome, and the first to describe an Asian patient with LUS cancer with Lynch syndrome induced by an hMLH1 mutation.

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Epimutation and cancer: a new carcinogenic mechanism of Lynch syndrome (Review).

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

International journal of oncology (International Journal of Oncology) 41 ( 3 ) 793 - 7 2012.09

ISSN 1019-6439

Epimutation is defined as abnormal transcriptional repression of active genes and/or abnormal activation of usually repressed genes caused by errors in epigenetic gene repression. Epimutation arises in somatic cells and the germline, and constitutional epimutation may also occur. Epimutation is the first step of tumorigenesis and can be a direct cause of carcinogenesis. Cancers associated with epimutation include Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC), chronic lymphocytic leukemia, breast cancer and ovarian cancer. Epimutation has been shown for many tumor suppressor genes, including RB, VHL, hMLH1, APC and BRCA1, in sporadic cancers. Methylation has recently been shown in DNA from normal tissues and peripheral blood in cases of sporadic colorectal cancer and many studies show constitutive epimutation in cancers. Epimutation of DNA mismatch repair (MMR) genes (BRCA1, hMLH1 and hMSH2) involved in development familial cancers has also been found. These results have led to a focus on epimutation as a novel oncogenic mechanism.

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Biomarkers in endometrial cancer: Possible clinical applications (Review).

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

Oncology letters (Oncology Letters) 3 ( 6 ) 1175 - 1180 2012.06

ISSN 1792-1074

The number of cases of endometrial cancer has shown a tendency to increase in recent years. Endometrial cancer originates from the endometrium and is classified, based on the development mechanism, into types 1 and 2, which are responsive and non-responsive to estrogen, respectively, and have significantly different gene expression profiles. Studies of genes with abnormal expression in endometrial cancer have identified multiple oncogenes, tumor suppressors, mismatch repair genes, apoptosis-associated genes, levels of hormone receptors and DNA ploidy and aneuploidy as biomarkers of endometrial cancer. The use of these molecules and genes may facilitate accurate diagnosis and prognostic prediction and contribute to individualized treatment. Trials of drugs which target these biomarkers and searches for new biomarkers using cDNA microarrays and RT-qPCR are ongoing and it is likely that these findings can be translated to clinical use.

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Progestin therapy for endometrial cancer: the potential of fourth-generation progestin (review).

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

International journal of oncology (International Journal of Oncology) 40 ( 6 ) 1755 - 62 2012.06

ISSN 1019-6439

Progestin preparations are made of synthetic progesterone and have often been used for hormone therapy in gynecological patients with endometriosis or endometrial cancer. Hormone therapy using progestin is considered to be one of the effective means of treatment particularly when dealing with endometrial cancer (an estrogen-dependent tumor). Numerous reports have been published concerning its efficacy in advanced or recurrent cases of atypical endometrial hyperplasia or endometrial cancer. Dienogest has been developed as a fourth-generation progestin for hormone therapy for endometriosis that can be used with high safety for long periods of time. In Japan, dienogest has been recommended as a first-line drug for endometriosis-associated pain. However, its antitumor activity has also been attracting close attention following a report that this drug suppressed the proliferation in vitro of endometrial cancer-derived cell lines which failed to respond to other progestins such as medroxyprogesterine acetate (MPA). The mechanism for antitumor activity of dienogest is considered to differ from the mechanism for antitumor activity of conventional progestin preparations used for treatment of endometrial cancer. This drug is expected to be clinically applicable as a new drug for the treatment of endometrial cancer.

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