研究者詳細 - 中村　圭一郎

論文 - 中村　圭一郎

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Three histologically distinct cancers of the uterine corpus: A case report and review of the literature. 国際誌

Hisashi Masuyama, Junko Haraga, Takashi Nishida, Chikako Ogawa, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Hiroyuki Yanai, Yuji Hiramatsu

Molecular and clinical oncology 4 ( 4 ) 563 - 566 2016年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Collision tumors, which are characterized by the coexistence of two or more completely distinct and independent tumors in the uterine corpus, are very rare. A collision tumor is mainly composed of two distinct tumor types, epithelial and mesenchymal. To the best of our knowledge, there has only been a single case in which a choriocarcinoma with an endometrial carcinoma were coexistent but histologically distinct. We herein report the first case of a collision tumor in a 52-year-old woman, with a history of two pregnancies and two deliveries. The collision tumor was composed of three histologically distinct neoplasms in the uterine corpus, namely an endometrioid carcinoma, an undifferentiated carcinoma and a choriocarcinoma. The patient underwent hysterectomy, bilateral adnexectomy and pelvic lymph node dissection, followed by six cycles of adjuvant chemotherapy with paclitaxel/carboplatin due to the high risk of endometrial cancer, and an additional five cycles of chemotherapy with methotrexate, as the β-human chorionic gonadotropin level was beyond the normal range. Following adjuvant chemotherapy, the tumor markers were within normal limits and no relapses of the cancer have been observed during 1 year of follow-up. Diagnosing a collision tumor prior to surgery is difficult if the neoplasms are in close proximity, or if one of the tumors predominates. Careful pathological examination is crucial for accurately diagnosing the neoplasms in a collision tumor and ensuring appropriate management and a favorable prognosis.

Pregnancy complications and glucose intolerance in women with polycystic ovary syndrome

Mari Sawada, Hisashi Masuyama, Kei Hayata, Yasuhiko Kamada, Keiichiro Nakamura, Yuji Hiramatsu

ENDOCRINE JOURNAL 62 ( 11 ) 1017 - 1023 2015年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN ENDOCRINE SOC

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance and hyperandrogenism. The interaction of these factors might result in increased risks of miscarriage and pregnancy complications such as gestational diabetes mellitus (GDM). To examine the pregnancy risks in women with PCOS, we compared obstetrical outcomes between patients with and without PCOS. We also studied the differences in maternal characteristics, glucose intolerance and pregnancy complications between PCOS patients with and without GDM, with and without obesity, and between successful pregnancies and miscarriages. We observed a high incidence of GDM and prevalence of GDM diagnosis in the first trimester in PCOS. Patients with GDM had higher body mass index (BMI) and lower homeostasis model assessment of beta-cell function (HOMA-beta) at preconception than those without GDM. Obese pregnant women with PCOS demonstrated a high incidence of GDM with severe insulin resistance, including high fasting insulin, HOMA of insulin resistance (HOMA-IR), and HOMA-beta at preconception compared with normal-weight patients. BMI was significantly correlated with HOMA-IR or HOMA-beta, and both indices were lower in PCOS patients with than without GDM for the same BMI. There were no significant differences in maternal characteristics (excluding maternal age) between PCOS patients with successful pregnancy and PCOS patients with miscarriages. Our data suggest that pregnant women with PCOS have an increased risk of GDM, especially if they have obesity and/or poorer insulin secretion. Measure of beta-cell function, such as HOMA-beta, at preconception might be a useful predictor of the risk of GDM in pregnant PCOS patients.

DOI： 10.1507/endocrj.EJ15-0364

The Glasgow Prognostic Score Determined During Concurrent Chemoradiotherapy Is an Independent Predictor of Survival for Cervical Cancer

Takeshi Nishida, Keiichiro Nakamura, Junko Haraga, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Hisashi Masuyama, Norihisa Katayama, Susumu Kanazawa, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER 25 ( 7 ) 1306 - 1314 2015年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMJ PUBLISHING GROUP

Objective The Glasgow prognostic score (GPS) determined at pretreatment is important in the prediction of prognosis in various cancers. We investigated if the GPS used both at pretreatment and during concurrent chemoradiotherapy (CCRT) could predict the prognosis of patients with cervical cancer.Methods We collected GPS and clinicopathological data from the medical records of 91 patients who underwent CCRT for cervical cancer; their GPSs at pretreatment and during CCRT were retrospectively analyzed for correlations with recurrence and survival. Statistical analyses were performed using the Mann-Whitney U test. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses.Results The median follow-up for all patients who were alive at the time of last follow-up was 38.0 months (range, 1-108 months). The DFS and OS rates of patients with a high GPS during CCRT (GPS 1 + 2; 55 patients; 60.4%) were significantly shorter than those for patients with a low GPS (GPS 0; 36 patients; 39.6%) (DFS, P < 0.001; OS, P < 0.001). Furthermore, multivariate analyses showed that high GPS during CCRT was an independent prognostic factor of survival for OS (P = 0.008).Conclusions During CCRT, a high GPS was revealed to be an important predictor of survival for cervical cancer.

DOI： 10.1097/IGC.0000000000000485

Pretreatment platelet-lymphocyte ratio is an independent predictor of cervical cancer recurrence following concurrent chemoradiation therapy. 国際誌

Keiichiro Nakamura, Takeshi Nishida, Tomoko Haruma, Junko Haraga, Chiaki Omichi, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Hisashi Masuyama, Yuji Hiramatsu

Molecular and clinical oncology 3 ( 5 ) 1001 - 1006 2015年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The aim of the present study was to identify the correlations between inflammation markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and C-reactive protein (CRP) and the prognosis in patients with recurrent cervical cancer. The associations among NLR, PLR and CRP and clinical characteristics and prognosis were examined in 32 patients receiving chemotherapy with recurrent cervical cancer following concurrent chemoradiation therapy (CCRT). The patient median survival time was 198 days (range, 42-1,022 days). Pretreatment NLR and PLR were significantly correlated with the recurrence of cervical cancer following CCRT (R=-0.538, P=0.002; and R=-0.542, P=0.001, respectively). Pretreatment PLR >322.0 was significantly associated with a poor prognosis for recurrent cervical cancer following CCRT by univariate and multivariate analyses (P=0.015 and P=0.029). These findings indicate that pretreatment PLR is an important predictor of prognosis in patients with recurrent cervical cancer following CCRT.

子宮子宮体がんの病理と診断子宮体癌におけるMSIおよびMMR deficiencyの頻度・相関とその臨床像

春間朋子, 永坂岳司, 中村圭一郎, 原賀順子, 西田傑, 小川千加子, 楠本知行, 関典子, 平松祐司

日本癌治療学会誌 50 ( 3 ) 988 - 988 2015年9月

妊娠17週にて子宮破裂を発症した既往帝王切開後妊娠の1例

光井崇, 西田傑, 中村圭一郎, 早田桂, 谷和祐, 河原義文, 衛藤英理子, 延本悦子, 瀬川友功, 増山寿, 平松祐司

日本産科婦人科学会雑誌 67 ( 2 ) 907 - 907 2015年2月

Pre-treatment neutrophil to lymphocyte ratio is a predictor of prognosis in endometrial cancer

Tomoko Haruma, Keiichiro Nakamura, Takeshi Nishida, Chikako Ogawa, Tomoyuki Kusumoto, Noriko Seki, Yuji Hiramatsu

Anticancer Research 35 ( 1 ) 337 - 344 2015年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Institute of Anticancer Research

Background/Aim: Inflammation and tumor immunology are important in the prognosis of various cancers. We herein investigated whether pre-treatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and serum cancer antigen 125 (CA125) predict recurrence and survival in patients with endometrial cancer (EC).
Patients and Methods: We collected complete blood counts and clinicopathological data from medical records of 320 patients with EC
their pre-treatment NLR, PLR and CA125 were analyzed for correlations with recurrence and survival, retrospectively.
Results: Disease-free survival (DFS) and overall survival (OS) rates of patients with high NLR and CA125 were significantly shorter than those for patients with low NLR and CA125 (DFS: p=0.002 and p&lt
0.001
OS: p&lt
0.001 and p&lt
0.001, respectively). Furthermore, NLR was also an independent predictive factor for mortality in multivariate analysis (hazard ratio (HR)=3.318
95% confidence interval (CI)=1.154-9.538
p=0.026).
Conclusion: Pre-treatment NLR is a predictor of poor prognosis in EC.

Pure choriocarcinoma of the ovary in silver-russell syndrome

Tomoko Haruma, Chikako Ogawa, Takeshi Nishida, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Takaaki Katayama, Yuji Hiramatsu

Acta Medica Okayama 69 ( 3 ) 183 - 188 2015年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Okayama University

Pure ovarian choriocarcinoma is an extremely rare malignancy that can be gestational or non-gestational in origin. Silver-Russell syndrome (SRS) is a rare congenital developmental disorder characterized by pre- and postnatal growth failure, relative macrocephaly, a triangular face, hemihypotrophy, and fifth-finger clinodactyly. We report a rare case of pure ovarian choriocarcinoma occurring in a 19-year-old woman with SRS. Following surgery, multiple chemotherapy courses were effective and she was free of disease at the 10-month follow-up.

後腹膜desmoid型線維腫症の症例

西條昌之, 中村圭一郎, 安藤まり, 依田尚之, 岡本和浩, 樫野千明, 谷和祐, 松岡敬典, 春間朋子, 福島千加子, 楠本知行, 関典子, 平松祐司, 佃和憲

現代産婦人科 62 ( 2 ) 263 - 267 2014年4月

記述言語：日本語出版者・発行元：中国四国産科婦人科学会

Desmoid線維腫症は100万人あたり2.4〜4.3例の稀な疾患で、線維腫症の1つであるが、周囲に浸潤性増殖しやすく、根治術を行っても局所再発を繰り返す難治性疾患であることが知られている。症例は22歳、0経妊0経産。4月某日に下腹部痛、軽度の悪心・嘔吐を主訴に近医受診し、巨大骨盤内腫瘤を指摘、精査加療目的に当科を紹介された。MRIでは多房性で一部充実部分を伴った26×24cmの腫瘤を認め、悪性腫瘍も危惧されたため、5月某日に開腹術を施行した。子宮・卵巣は正常であり、腫瘍は後腹膜由来で、回盲部を含め、横行結腸や脾臓下極に浸潤しており、腫瘍摘出とともに横行結腸部分切除吻合、脾臓の部分切除を行った。摘出した腫瘍は2980gで、内容は血性混濁液が存在し、総重量は5kgに達した。病理組織検査にてDesmoid-type fibromatosisと診断され、術後経過は良好で手術後13日目に退院した。後腹膜desmoid線維腫症の1症例を経験したので、若干の文献的考察を加えて報告する。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J05038&link_issn=&doc_id=20140620430022&doc_link_id=%2Fcv0mtrob%2F2013%2F006202%2F022%2F0263-0267%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcv0mtrob%2F2013%2F006202%2F022%2F0263-0267%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Maximum standardized lymph node uptake value could be an important predictor of recurrence and survival in patients with cervical cancer. 国際誌

Keiichiro Nakamura, Ikuo Joja, Takeshi Nagasaka, Tomoko Haruma, Yuji Hiramatsu

European journal of obstetrics, gynecology, and reproductive biology 173 77 - 82 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: To investigate prognostic values of maximum standardized lymph node (LN) uptake (SUVmax), minimum apparent LN diffusion coefficient (ADCmin), and LN short-axis length in women with cervical cancer. STUDY DESIGN: Retrospective review of diffusion-weighted magnetic resonance imaging (DWI) and positron emission tomography/computed tomography (PET/CT) of LN confined to the pelvis in 80 cervical cancer patients before undergoing radiotherapy (RT) with or without concurrent chemotherapy. Optimal cut-off values for disease-free survival (DFS) and overall survival (OS) were determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether LN SUVmax, LN ADCmin and LN short-axis length predicted risk of recurrence or survival. RESULTS: Median DFS and OS for all patients were 18.97 and 22.28 months, respectively. DFS and OS rates of patients with high LN SUVmax was significantly lower than those of patients exhibiting low LN SUVmax (P=0.003 and P=0.019). Patients with low LN ADCmin had poorer DFS and OS than those with high LN ADCmin (P=0.033 and P=0.005). DFS for patients exhibiting longer LN short-axis length was significantly lower than those of patients exhibiting shorter LN short-axis length (P=0.018). Multivariate analyses indicated that high LN SUVmax was an independent predictor for both DFS and OS (P=0.0231 and P=0.0146). CONCLUSIONS: LN SUVmax could be an important predictor of recurrence and survival in patients with cervical cancer confined to the pelvis.

DOI： 10.1016/j.ejogrb.2013.10.030

子宮頸癌心臓転移の一例

岡本和浩, 楠本知行, 安藤まり, 依田尚之, 樫野千明, 西條昌之, 谷和祐, 春間朋子, 福島千加子, 関典子, 中村圭一郎, 増山寿, 平松祐司

現代産婦人科 62 ( Suppl. ) S46 - S46 2013年9月

婦人科癌大量胸腹水に対して利尿剤の大量投与が有効であった2症例

谷川真奈美, 関典子, 春間朋子, 福島千加子, 楠本知行, 中村圭一郎, 平松祐司, 市原英基, 松岡順治

現代産婦人科 62 ( Suppl. ) S54 - S55 2013年9月

Three Cases of Struma Ovarii Underwent Laparoscopic Surgery with Definite Preoperative Diagnosis

Nurliza Binti Md Nor, Tomoyuki Kusumoto, Seiji Inoue, Keiichiro Nakamura, Noriko Seki, Atsushi Hongo, Junichi Kodama, Yuji Hiramatsu

ACTA MEDICA OKAYAMA 67 ( 3 ) 191 - 195 2013年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Struma ovarii is a rare neoplasm that accounts for approximately 0.3% of ovarian tumors. Due to its ultrasound morphology, which is quite similar to that of malignant ovarian carcinoma, most struma ovarii cases are open operated with laparotomy rather than laparoscopy. We present 3 cases of struma ovarii, which were diagnosed preoperatively by imaging studies and removed by laparoscopic surgery. All patients were premenopausal women between ages 31-50. The magnetic resonance imaging (MRI) findings were complex masses composed of multiple cysts and solid components with T2-hypointense regions as well as multiple T1-hyperintense cystic areas, findings that are typical for struma ovarii. A combination of plain computed tomography (CT), positron emission tomography (PET)-CT, and scintigraphy was useful for diagnosis. Laboratory examination revealed elevated serum thyroglobulin, which led to the diagnosis of struma ovarii. Laparoscopic surgeries were performed without rupturing the tumors. Although it has been difficult to differentiate between struma ovarii and malignant tumors by conventional methods, recently MRI techniques appear make it possible to diagnose struma ovarii preoperatively from the abovementioned imaging characteristic, together with laboratory data. As for treatment, we think laparoscopy could be successful for struma ovarii, but the surgeon must be careful not to rupture the tumor intra-abdominally in order to prevent dissemination, which could lead to malignancy.

The mean apparent diffusion coefficient value (ADCmean) on primary cervical cancer is a predictive marker for disease recurrence. 国際誌

Keiichiro Nakamura, Ikuo Joja, Takeshi Nagasaka, Chikako Fukushima, Tomoyuki Kusumoto, Noriko Seki, Atsushi Hongo, Junichi Kodama, Yuji Hiramatsu

Gynecologic oncology 127 ( 3 ) 478 - 83 2012年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The purpose of this study is to investigate the correlation of the max, mean and minimal apparent diffusion coefficient values (ADCmax, ADCmean, and ADCmin) on diffusion weighted imaging findings with prognostic factors in cervical cancer. METHODS: A cohort of 80 cervical cancer patients underwent pelvic magnetic resonance imaging (MRI) within the 2 to 4 weeks prior to radical hysterectomy. The optimal cutoff value for segregating disease free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. We used ROC curve analyses to evaluate whether preoperative ADCmax, ADCmean, ADCmin on MRI predicted the risk group of recurrence. RESULTS: Analyses of ROC curves identified an optimal The ROC curves identified an optimal ADCmax, ADCmean, and ADCmin cutoff values of 1.122 × 10(-3)mm(2)/s, 0.852 × 10(-3)mm(2)/s, 0.670 × 10(-3)mm(2)/s and for predicting the recurrence of cervical cancer. The patients categorized into the lower ADCmean or ADCmin groups showed the shorter disease free survivals compared with the higher ADCmean or ADCmin, respectively (P<0.0001 or P=0.0210). In particular, the ADCmean of primary cervical cancer was an independent predictive factor for disease recurrence by a multivariate analysis (P=0.0133). CONCLUSIONS: The ADCmean of primary cervical cancer calculated by MRI could be an important factor for identifying patients with a risk of disease recurrence.

DOI： 10.1016/j.ygyno.2012.07.123

Antitumor effects of novel shorter truncated insulin-like growth factor I receptors

Yojiro Ojima, Atsushi Hongo, Yixuan Liu, Lisha Zhu, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Junichi Kodama, Yuji Hiramatsu

CANCER BIOLOGY & THERAPY 13 ( 7 ) 559 - 566 2012年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LANDES BIOSCIENCE

We generated novel truncated insulin-like growth factor I receptors (IGF-IRs) designated as 126/STOP, 223/STOP and 325/STOP in order to establish shorter soluble IGF-IRs than previously reported 486/STOP without abrogating the same antitumor effects. Stable transfection of 223/STOP and 325/STOP, but not 126/STOP caused inhibition of anchorage-independent growth of CaOV-3 ovarian cancer cells in vitro. This antitumor effect was reproduced when we used recombinant proteins of these constructs, suggesting a bystander effect of these shorter truncated IGF-IRs. Tumorigenesis in vivo of CaOV-3 cells tranfected with 223/STOP or 325/STOP was strictly inhibited, and inoculation of these cells in nude mice caused massive apoptosis exclusively in vivo. Phosphorylations of IGF-IR and Akt, but not Erk were attenuated in 223/STOP- or 325/STOP-transfected CaOV-3 cells and downregulations of IGF-IR and Akt phosphorylation seemed to play at least a partial role in the antitumor effect of these novel truncated IGF-IRs. Since 223/STOP and 325/STOP are smaller in size than previously reported 486/STOP, and they retain the same antitumor effects, they could be good candidates for clinical application in the future.

DOI： 10.4161/cbt.19609

α-fetoprotein-producing endometrial adenocarcinoma without an obvious hepatoid component 査読

Junichi Kodama, Noriko Seki, Hiroyuki Yanai, Tomoyuki Kusumoto, Keiichiro Nakamura, Atsushi Hongo, Yuji Hiramatsu

Oncology Letters 1 ( 2 ) 243 - 245 2010年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Endometrial carcinomas producing α-fetoprotein (AFP) are extremely rare. We report a case of AFP-producing, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. A 59-year-old multiparous woman presented with abdominal swelling. The serum level of AFP was 1292.8 ng/ml. Magnetic resonance images of the pelvis showed a markedly enlarged uterus, with a tumor growing exophytically within the endometrial cavity. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. The histopathological examination demonstrated a Stage IIA, Grade 2 endometrioid adenocarcinoma without an obvious hepatoid component. The endometrioid adenocarcinoma cells were partly positive for AFP immunoreactivity. The patient received adjuvant chemotherapy and was disease-free 60 months after the operation. This case confirms the existence of AFP-producing endometrioid adenocarcinomas without hepatoid features.

DOI： 10.3892/ol_00000043

Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are potential targets in uterine leiomyosarcoma

Keiichiro Nakamura, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

International Journal of Oncology 37 ( 3 ) 605 - 614 2010年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Spandidos Publications

Hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) are Kunitz-type serine protease inhibitors that have a broad inhibitory spectrum against serine proteases. This study examined the role of HAI-1 and HAI-2 in uterine leiomyosarcoma (LMS) patients, and in vitro. HAI-1 and HAI-2 was examined in uterine normal smooth muscle, leiomyoma and LMS specimens using immunohistochemistry. We investigated biological functions and inhibitory effects of HAI-1 and HAI-2 using uterine LMS cell line SK-LMS-1 and SKN. The expression levels of HAI-1 and HAI-2 were significantly decreased in uterine LMS specimens relative to corresponding uterine normal smooth muscle and leiomyoma specimens. Furthermore, the low HAI-1 and HAI-2 expression was a significant predictor for poor prognosis when compared with high HAI-1 and HAI-2 expression (disease-free survival rate
p=0.024 and p=0.045, overall survival rate
p=0.043 and p=0.009). HAI-1 and HAI-2 showed potential inhibitory effects that mediated cell proliferation, migration and cellular invasion which led to apoptosis and necrosis through a reduction of HGFA, matriptase and hepsin expression. These findings indicate that HAI-1 and HAI-2 may be possible tumor suppressor genes for uterine LMS and thus, both could be considered therapeutic agents for the treatment of LMS.

DOI： 10.3892/ijo_00000709

Expression of Matriptase and Clinical Outcome of Human Endometrial Cancer 査読

Keiichiro Nakamura, Atsushi Hongo, Junichi Kodama, Fernando Abarzua, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

ANTICANCER RESEARCH 29 ( 5 ) 1685 - 1690 2009年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：INT INST ANTICANCER RESEARCH

Background: Matriptase, a type II transmembrane serine protease is involved in angiogenesis, degradation of extracellular matrix and in progression of some epithelial cancers. The purpose of the present study was to examine matriptase expression and evaluate its clinicopathological significance in endometrial cancer. Patients and Methods: Matriptase expression was examined in normal endometrium (n=20), endometrial hyperplasia (n=11) and endometrial cancer (n=65) samples. The distribution of cases that scored positive for each of the biological parameters examined was correlated with matriptase expression status obtained by immunohistochemistry. Results: Matriptase was found to be significantly overexpressed in endometrial cancer as compared with normal endometrium and endometrial hyperplasia. Interestingly, matriptase expression is associated with stage (p=0.010), grade (p=0.021), depth of myometrial invasion (p=0.004), cervical involvement (p=0.021), lymph node metastasis (p=0.009), LVS involvement (p=0.041) and peritoneal cytology (p=0.045). The high matriptase expression was a significant predictor for poor prognosis when compared with low matriptase expression (Disease-free survival rate; p=0.032, Overall survival rate; p=0.011). Conclusion: High matriptase expression in endometrial cancer may be associated with poor prognosis.

The role of hepatocyte growth factor activator inhibitor-1 (HAI-1) as a prognostic indicator in cervical cancer

Keiichiro Nakamura, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

International Journal of Oncology 35 ( 2 ) 239 - 248 2009年

記述言語：英語掲載種別：研究論文（学術雑誌）

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a Kunitz-type serine protease inhibitor that has a broad inhibitory spectrum against serine proteases. This is the first study to investigate the role of HAI-1 and its clinical importance in cervical cancer. We attempted to investigate the inhibitory effects of HAI-1 using cervical carcinoma cell lines SiHa with integrated human papillomavirus (HPV) 16 and HeLa with integrated HPV 18. HAI-1 expression in cervical cancer (n=91) were assessed by immunohistochemistry. HAI-1 was found to be a potential inhibitory effects mediated by reduction of hepsin, matriptase and prostasin expression. This led to apoptosis through a reduction in the levels of Bcl-2, Bcl-xL, MUPP-1 and MAGI-3 in cervical cancer cell lines. There were significant correlations between HAI-1 expression and stage (p=0.013), tumor size (p=0.002), stromal invasion (p&lt
0.001), vaginal invasion (p=0.031), parametrial invasion (p=0.012), lymph-node metastasis (p=0.019), and LVS involvement (p=0.002). The disease-free and overall survival rates of patients exhibiting high HAI-1 expression were significantly higher than those of patients exhibiting low HAI-1 expression (p=0.022 and p=0.011, respectively). The present study proposes that these findings may be considered HAI-1 as a therapeutic target for treatment and identify as a favorable prognostic marker for cancer patients of cervical cancer.

DOI： 10.3892/ijo_00000333

Hepsin inhibits the cell growth of endometrial cancer

Keiichiro Nakamura, Norio Takamoto, Fernando Abarzua, Atsushi Hongo, Junichi Kodama, Yasutomo Nasu, Hiromi Kumon, Yuji Hiramatsu

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 22 ( 3 ) 389 - 397 2008年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPANDIDOS PUBL LTD

Currently, several therapeutic approaches including surgery, chemotherapy, and radiation therapy are available for the treatment of endometrial cancer. However, endometrial cancer cells may survive, resulting in relapse of the disease, and ultimately causing demise of the patient. Hepsin is a cell surface-expressed chymotrypsin-like serine protease and a member of the, family of type II transmembrane serine proteases. To date, little is known about its precise mechanisms of action. We investigated the biological functions and effects in vitro and in vivo of Hepsin, using endometrial cancer cell lines transfected with Hepsin. In stably transfected Ishikawa/Hepsin cell lines (Hepsin-10 and -12), we observed a significant inhibitory effect on cell growth in a monolayer culture system and in anchorage-independent cell growth in soft agar in vitro. Furthermore, in a xenograft model, growth inhibitory effects were observed when compared with the effects of mock-transfected cells used as a control. Overall, Hepsin showed potential inhibitory effects mediated by the induction of 14-3-3 sigma expression which leads to both cell cycle arrest at the G(2)/M phase through cyclin B and cyclin A and the p53-dependent pathway activated by increasing the level of Bak and reducing the level of Bcl-2 and Bcl-xL.

DOI： 10.3892/ijmm_00000035

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