Nobuo Yaegashi

Tohoku University, Miyagi, Japan

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Publications (393)1002.73 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: This multi-institutional study was conducted to clarify the clinicopathological features of squamous cell carcinomas of the vulva. The medical records of vulvar cancer patients treated between 2002 and 2012 were retrospectively reviewed following approval by the Institutional Review Board of each institution. One hundred and eleven patients with vulvar malignancies were included. Of these, 63 patients had squamous cell carcinoma (57 %). Initial treatment was surgery, radiation therapy (RT), and concurrent chemoradiotherapy (CCRT) in 34 (54 %), 15 (24 %), and 11 (17 %) patients, respectively. Nineteen, 11, 26, and 7 patients had stage I, II, III, and IV disease, respectively. Of the 34 patients who had surgical treatment, 50 % had stage I disease, while 74 % of those who received CCRT had stage III or IV disease. Complete response (CR) rates for the surgery, RT, and CCRT groups were 73, 60, and 64 %, respectively. The 5-year survival rates for stage I/II and III/IV disease were 64 and 39 %, respectively (P = 0.019). The 5-year survival rates for the surgery, RT, and CCRT groups were 53, 38, and 50 %, respectively, and the prognosis of patients treated with surgery or CCRT was significantly better than that of patients who received RT (P < 0.05). In multivariate analysis, clinical response to initial treatment was an independent prognostic factor (P < 0.001). Although many patients had advanced-stage disease in the CCRT group, the therapeutic outcome for the surgery and CCRT groups was similar. Thus, CCRT may be a promising treatment for squamous cell carcinoma of the vulva.
    International journal of clinical oncology. 02/2015;
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    ABSTRACT: In order to determine indications for less radical surgery such as modified radical hysterectomy, the risk of pathological parametrial involvement and prognosis of FIGO stage IB1 cervical cancer patients undergoing standard radical hysterectomy with pre-operatively assessed tumor diameter ≤2cm were investigated. We conducted a retrospective multi-institutional chart review of patients with FIGO stage IB1 cervical cancer who underwent primary surgical treatment between 1998 and 2002. The eligibility criteria for the analyses were (i) histologically-proven squamous cell carcinoma, adenocarcinoma or, adenosquamous cell carcinoma, (ii) radical hysterectomy performed, (iii) clinical tumor diameter data available by MR imaging or specimens by cone biopsy, and (iv) age between 20 and 70. Based on the clinical tumor diameter, patients were stratified into those with the following tumors: i) 2cm or less (cT≤2cm) and ii) greater than 2cm (cT>2cm). We expected 5-year OS of ≥95% and parametrial involvement <2-3% for patients with cT≤2cm who underwent radical hysterectomy. Of the 1269 patients enrolled, 604 were eligible for the planned analyses. Among these, 571 underwent radical hysterectomy (323 with cT≤2cm and 248 with cT>2cm). Parametrial involvement was present in 1.9% (6/323) with cT≤2cm and 12.9% (32/248) with cT>2cm. Five-year overall survivals were 95.8% (95% CI 92.9-97.6%) in cT≤2cm and 91.9% (95% CI 87.6-94.8%) in cT>2cm patients. Patients with cT≤2cm had lower risk of parametrial involvement and more favorable 5-year overall survival. They could therefore be good candidates for receiving less radical surgery. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 02/2015; · 3.69 Impact Factor
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    ABSTRACT: Abstract Plasminogen activator inhibitor (PAI)-1 is predictive of poor outcome in several types of cancer. The present study investigated the biological role for PAI-1 in ovarian cancer and potential of targeted pharmacotherapeutics. In patients with ovarian cancer, PAI-1 mRNA expression in tumor tissues was positively correlated with poor prognosis. To determine the role of PAI-1 in cell proliferation in ovarian cancer, the effects of PAI-1 inhibition were examined in PAI-1-expressing ovarian cancer cells. PAI-1 knockdown by small interfering RNA resulted in significant suppression of cell growth accompanied with G2/M cell cycle arrest and intrinsic apoptosis. Similarly, treatment with the small molecule PAI-1 inhibitor TM5275 effectively blocked cell proliferation of ovarian cancer cells that highly express PAI-1. Together these results suggest that PAI-1 promotes cell growth in ovarian cancer. Interestingly, expression of PAI-1 was increased in ovarian clear cell carcinoma compared with that in serous tumors. Our results suggest that PAI-1 inhibition promotes cell cycle arrest and apoptosis in ovarian cancer and that PAI-1 inhibitors potentially represent a novel class of anti-tumor agents.
    Cancer biology & therapy 01/2015; · 3.29 Impact Factor
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    ABSTRACT: The aim of this study was to investigate prognostic factors, including postoperative chemotherapy regimen, for the treatment of ovarian yolk sac tumour (YST), and resulting fertility outcome.
    European Journal of Cancer 01/2015; · 4.82 Impact Factor
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    ABSTRACT: Hachimijiogan (HJG), Ba-Wei-Di-Huang-Wan in Chinese, is one of the most popular herbal medicines in Japanese Kampo. HJG is often prescribed for the prevention and treatment of age-related diseases. Muscle atrophy plays an important role in aging-related disabilities such as sarcopenia. The purpose of this study was to investigate the possible beneficial effect of HJG on skeletal muscle. Cells of murine skeletal muscle myoblast cell line C2C12 were used as an in vitro model of muscle cell proliferation and differentiation. The effect of HJG on C2C12 cell proliferation and differentiation was assessed. We counted the number of myotubes morphologically to assess the degree of differentiation. HJG treatment (200 μg/mL) for 3 days significantly increased C2C12 cell number by 1.23-fold compared with that of the control. HJG promoted the proliferation of C2C12 cells through activation of the ERK1/2 signaling pathway without affecting the Akt signaling pathway. HJG did not affect the differentiation of C2C12 cells. HJG had beneficial effects on skeletal muscle myoblast proliferation. These findings may provide a useful intervention for the prevention and treatment of sarcopenia.
    Clinical Interventions in Aging 01/2015; 10:445-51. · 2.65 Impact Factor
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    ABSTRACT: To the Editor: The global population is aging.1 Pneumonia is a leading cause of death in elderly adults, especially those with dysphasia and microaspiration.2 Because aspiration pneumonia is related to impairment of the swallowing and cough reflex,3 the development of preventive strategies is needed to improve such protective reflexes to reduce the incidence of pneumonia in older people. In Japan, pneumonia is the third leading cause of death.4 It was previously reported that acupuzncture at two points on the legs (ST36 and KI3) improved the swallowing reflex after stroke5 and reduced pharyngeal retention and aspiration.6 To investigate the effectiveness of acupuncture with press needles in improving the swallowing reflex in elderly adults with cerebrovascular disease, a three-arm randomized double-blind controlled multicenter trial was conducted by incorporating sham patches and sham points. Individuals aged 65 and older who had had a stroke and had dysphasia were recruited consecutively from two hospitals and two nursing homes in Sendai, Japan. The purpose and design of the study were explained to each individual, and informed consent was obtained. The Tohoku University ethics committee approved the study protocol. Twenty-nine individuals (10 men, 19 women; mean age � SD 82.2 � 7.1) were recruited and assigned randomly to three groups: group 1, press needles (Pyonex; Seirin Corporation, Shizuoka, Japan) on the ST36 and KI3; group 2, sham patches on the acupuncture points; and group 3, press needles on sham points. The needles were 0.2 mm in diameter and 0.6 mm long. The design of the sham patch was identical to that of the press needle except most of the needle had been cut off, so that only the head of the needle remained in the resin. Patches were applied and changed every day for 4 weeks. Latent time of swallowing reflex (LTSR), plasma substance P (SP), Barthel Index, Mini-Mental State Examination, and days of fever were measured at baseline and 4 weeks later. Table 1 shows the outcomes of this study. The primary outcome was change in LTSR. A statistically significant shortening of LTSR was evident in Group 1 (6.9 � 2.3 vs 2.5 � 0.3 seconds, P = .005), whereas no statistically significant difference was observed in the other two groups. There was a significant difference between the three groups in change in LTSR (P = .009). Change in LTSR in Group 1 was significantly different from that in Group 2 (P = .008) but not Group 3 (P > .99). There was a significant difference in LTSR at day 28 between Groups 1 and 2 (P = .001), but no significant difference between Groups 1 and 3 (P = .51). Plasma SP did not change significantly during the study in any group, and no differences in secondary outcomes were observed in any group. between baseline and Day 28. Peripheral blood tests were performed to assess inflammatory and nutritional status. No statistically significant differences were observed in white blood cell count, C-reactive protein, total protein, albumin, or total cholesterol between baseline and Day 28. There were no significant differences in any parameters. Neither press needle nor sham needle treatment caused any side effects. Attachment of press needles at the two leg acupuncture points improved the swallowing reflex of elderly adults with cerebrovascular disease. Lack of a significant difference between acupuncture points and sham points indicates that the attachment of the fine needle itself has some effect on the swallowing reflex. Even if the press needles are placed at positions that deviate from the acupoints (e.g., sham points in this study), LTSR may improve, which is clinically convenient. This type of acupuncture may become a new adjuvant method for the prevention and treatment of pneumonia in elderly adults. The limitations of the present study were the small sample size and short follow-up time. In addition, only Group 3 included participants with extremely poor LTSR at baseline, which could have been why there was no difference between Groups 1 and 3 in LTSR at Day 28. Further studies are required to investigate the effect of the press needle on swallowing function.
    Journal of the American Geriatrics Society 12/2014; 62(12):2438. · 4.22 Impact Factor
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    ABSTRACT: Endometrial carcinoma, especially endometrioid endometrial adenocarcinoma, is an estrogen-dependent tumor that is similar to breast cancer. Androgen is closely associated with other steroid hormones, but its correlation with endometrioid endometrial adenocarcinoma remains largely unclear. We previously demonstrated the expression of the androgen receptor, 5α-reductase type 1, and 5α-reductase type 2 in endometrioid endometrial adenocarcinoma tissue, but androgen action and its correlation with prognosis are unknown. In this study, we measured the tissue and serum concentrations of androgen and performed immunohistochemical analyses of androgen-associated factors in 41 patients. In 86 additional patients, we performed the same immunohistochemical analyses to identify correlations associated with prognosis. We found that 5α-reductase type 1 was associated with intratumoral dihydrotestosterone concentrations, and it was an independent prognostic factor in endometrioid endometrial adenocarcinoma. The poor prognosis of patients negative for both androgen receptor and 5α-reductase type 1 suggests that androgens have inhibitory effects on tumor growth. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Molecular and Cellular Endocrinology 12/2014; · 4.24 Impact Factor
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    ABSTRACT: This study aimed to evaluate surgical, pregnancy, and prognostic outcomes of radical abdominal trachelectomy (RAT) for Japanese patients with early-stage cervical cancer.
    International Journal of Clinical Oncology 11/2014; · 2.17 Impact Factor
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    ABSTRACT: AimThe aim of this study was to investigate the long-term fertility prognosis after B-Lynch sutures for post-partum hemorrhage (PPH).MethodsA retrospective observational study was conducted on patients who underwent B-Lynch sutures in our hospital between 2005 and 2010. Patient data was collected from hospital records. Information regarding subsequent pregnancies and menstrual complications were obtained by posted questionnaires and telephone interviews with patients who avoided hysterectomy.ResultsA total of 28 B-Lynch sutures were performed in 3976 deliveries, all in patients that underwent cesarean section. Twenty-two of the 26 patients who avoided hysterectomy answered our questionnaire or took part in an interview. All patients recovered regular menstruation with no severe complications. Of the 19 patients who wanted another child, 12 patients (63.2%) had 14 subsequent pregnancies in a mean follow-up period of 52.1 months. The results of pregnancies were nine uncomplicated term pregnancies, all delivered by elective cesarean section, two artificial abortions and three miscarriages. A significant difference was observed in the age of patients with subsequent pregnancies and those without pregnancies (30.8 vs 34.6 years, P = 0.04).ConclusionB-Lynch sutures for PPH do not appear to jeopardize fecundity. An older age was a risk factor for achieving subsequent pregnancies.
    Journal of Obstetrics and Gynaecology Research 11/2014; · 0.84 Impact Factor
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    ABSTRACT: This study aimed to evaluate the efficacy of paclitaxel and carboplatin in patients with completely or optimally resected uterine carcinosarcoma.
    International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 10/2014;
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    ABSTRACT: Ischemic reperfusion (IR) during the perinatal period is a known causative factor of fetal brain damage. So far, both morphologic and histologic evidence has shown that fetal brain damage can be observed only several hours to days after an IR insult has occurred. Therefore, to prevent fetal brain damage under these circumstances, a more detailed understanding of the underlying molecular mechanisms involved during an acute response to IR is necessary. In the present work, pregnant mice were exposed to IR on day 18 of gestation by clipping one side of the maternal uterine horn. Simultaneous fetal electrocardiography was performed during the procedure to verify that conditions resulting in fetal brain damage were met. Fetal brain sampling within 30 minutes after IR insult revealed molecular evidence that a fetal response was indeed triggered in the form of inhibition of the Akt-mTOR-S6 synthesis pathway. Interestingly, significant changes in mRNA levels for both HIF-1α and p53 were apparent and gene regulation patterns were observed to switch from a HIF-1α-dependent to a p53-dependent process. Moreover, pre-treatment with pifithrin-α, a p53 inhibitor, inhibited protein synthesis almost completely, revealing the possibility of preventing fetal brain damage by prophylactic pifithrin-α treatment.
    PLoS ONE 10/2014; 9(10):e110577. · 3.53 Impact Factor
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    Journal of Clinical Medicine Research 10/2014; 6(5):392-4.
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    ABSTRACT: This study explores the correlation between the impact of the Great East Japan Earthquake and the incidence of postpartum depression in Miyagi prefecture, Japan. The design used was a cross-sectional study with self-administered questionnaires, 6-9 months after the disaster. The results showed the prevalence of postnatal women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥9 to be 21.3 %. Multivariate analysis showed that exposure to tsunami (odds ratio, 1.80; 95 % confidence interval, 1.16-2.78) was significantly and independently associated with an EPDS score of ≥9. Postnatal women and their children should be treated as a vulnerable population, and a protective framework must be established to prepare for future devastating disasters.
    Archives of Women s Mental Health 09/2014; · 1.96 Impact Factor
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    ABSTRACT: Background To improve lymph node (LN) metastasis identification for patients with endometrial cancer (EC), this study assessed the usefulness of molecular biologic techniques using a one-step nucleic acid amplification (OSNA) assay. Methods Using quantitative reverse transcription polymerase chain reaction (qRT-PCR), an optimal mRNA marker was selected, and its expression was compared between histopathologically positive and negative LNs using an OSNA assay. The authors determined copy number cutoff values and evaluated the diagnostic performance of this OSNA assay using sentinel lymph nodes (SLNs). They also investigated whether an OSNA assay could detect LN metastases with sensitivity and specificity equivalent to the 2-mm-interval histopathology method. Results For analysis of EC samples, cytokeratin 19 (CK19) was selected as a useful mRNA marker for the OSNA assay. When the cutoff value was set at 250 copies (using 215 LNs from 70 patients), an OSNA assay using CK19 mRNA had a sensitivity of 93.3 %, a specificity of 99.5 %, and a concordance rate of 99.1 %. For performance evaluations using SLNs (120 histopathologically negative LNs and 17 histopathologically positive LNs from 35 patients), a OSNA assay using CK19 mRNA had a sensitivity of 82.4 %, a specificity of 99.2 %, a positive predictive value of 93.3 %, and a concordance rate of 97.1 %. Thus, an OSNA assay using CK19 mRNA provided results equivalent to those with the 2-mm-interval histopathology method. Conclusions The study data demonstrated that an OSNA assay using CK19 mRNA was applicable for detecting LN metastases in EC. Combined analysis using an OSNA assay and SLNs may improve individualized treatments according to LN metastatic status.
    Annals of Surgical Oncology 09/2014; 22(3). · 3.94 Impact Factor
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    ABSTRACT: Vasohibin-1 (VASH1) and vasohibin-2 (VASH2), the 2 members of the vasohibin family, have been identified as novel regulators of angiogenesis. VASH1 ceases angiogenesis, whereas VASH2 stimulates sprouting. Here we characterized their functional role in the placenta. Immunohistochemical analysis of human placental tissue clarified their distinctive localization; VASH1 in endothelial cells and VASH2 in trophoblasts. We then used a mouse model to explore their function. Wild-type, Vash1(-/-), and Vash2(-/-) mice on a C57BL6 background were used in their first pregnancy. As expected, the fetal vascular area was increased in the Vash1(-/-) mice, whereas it was decreased in the Vash2(-/-) mice relative to wild-type. In addition, we noticed that the Vash2(-/-) mice at 18.5dpc displayed thinner villi of the labyrinth and larger maternal lacunae. Careful observation by an electron microscopy revealed that the syncytiotrophoblast formation was defective in the Vash2(-/-) mice. To test the possible involvement of VASH2 in the syncytiotrophoblast formation, we examined the fusion of BeWo cells, a human trophoblastoid choriocarcinoma cell line. The forskolin treatment induced the fusion of BeWo cells, and the knockdown of VASH2 expression significantly inhibited this cell fusion. Conversely, the overexpression of VASH2 by the infection with adenovirus vector encoding human VASH2 gene significantly increased the fusion of BeWo cells. Glial cell missing-1 and endogenous retrovirus envelope glycoprotein Syncytin 1 and Syncytin 2 are known to be involved in the fusion of trophoblasts. However, VASH2 did not alter their expression in BeWo cells. These results indicate that VASH1 and VASH2 showed distinctive localization and opposing function on the fetoplacental vascularization. Moreover, our study shows for the first time that VASH2 expressed in trophoblasts is involved in the regulation of cell fusion for syncytiotrophoblast formation.
    PLoS ONE 09/2014; 9(9):e104728. · 3.53 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks' gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation-appropriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intraamniotic AZ dose, or repeated maternal IV AZ doses, would safely yield therapeutic levels of AZ in an 80 d gestation (term=150 d) ovine fetus.
    Antimicrobial Agents and Chemotherapy 08/2014; · 4.45 Impact Factor
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    ABSTRACT: We have developed a collaborative hospital-based approach to monitoring the impact of a human papillomavirus vaccine on cervical cancer, its precursor lesions and human papillomavirus type-specific prevalence in Japan. The monitoring will be conducted for a total period of 21 years on women aged <40 who are newly diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia or adenocarcinoma in situ at 21 participating institutes. Women are monitored to determine their vaccine history and will be human papillomavirus-genotyped each year. The primary endpoint is the human papillomavirus16/human papillomavirus18-positive rate in women aged 16-25 who are diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia grade 2/3 and adenocarcinoma in situ. The major secondary endpoints are the number of women aged <40 who are diagnosed with invasive cervical cancer, cervical intraepithelial neoplasia grade 2/3 and adenocarcinoma in situ, the human papillomavirus type-specific prevalence, and the number of deaths from invasive cervical cancer in women aged <40. Long-term surveillance for human papillomavirus-associated cervical diseases in young females is important for the development of future strategies for cervical cancer prevention in Japan.
    Japanese Journal of Clinical Oncology 08/2014; · 1.75 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate prognostic factors including efficacy of postoperative chemotherapy in Japanese patients with uterine carcinosarcoma.
    International Journal of Clinical Oncology 07/2014; · 2.17 Impact Factor
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    ABSTRACT: Predictive factors of the efficacy of chemotherapy for Japanese patients with recurrent cervical cancer who have been previously treated with concurrent chemoradiotherapy (CCRT) are currently unknown, and hence we aimed to investigate this.
    International Journal of Clinical Oncology 07/2014; · 2.17 Impact Factor
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    ABSTRACT: Aims and background. Whilst most uterine smooth muscle neoplasms are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with a high incidence of metastasis and recurrence. Gynecological tumors are often associated with female hormone secretion, but no strong link has been detected between human Ut-LMS and the hormonal environment. In fact, the risk factors for Ut-LMS are poorly understood. In addition, no diagnostic biomarkers for differentiating between leiomyoma, a benign tumor, and malignant Ut-LMS have been found. Interestingly, mice that were homozygously deficient for LMP2/β1i were found to spontaneously develop Ut-LMS and exhibited a Ut-LMS prevalence of ~40% by 14 months of age. Thus, analyzing potential risk factors for Ut-LMS (such as LMP2/β1i) might aid the development of diagnostic biomarkers and clinical treatments for the condition. Methods and study design. Fifty-seven patients (age range: 32-83 years) who had been diagnosed with uterine mesenchymal tumors were chosen from a pathological archive. Tissue samples from these patients were fixed in 10% buffered formalin, incubated in 4% paraformaldehyde for 8 hours, and embedded in paraffin. Tissue sections were stained with hematoxylin and eosin for standard histological examination or were subjected to further processing for immunohistochemical (IHC) examination. Serial Ut-LMS, bizarre leiomyoma, leiomyoma, and myometrium sections were subjected to IHC staining of β-smooth muscle actin, estrogen receptor, cyclin B1, LMP2/β1i, calponin h1, ki-67, tumor protein p53, and progesterone receptor. Results. The Ut-LMS samples were positive for cyclin B1 and negative for LMP2/β1i, while the opposite result was obtained for bizarre leiomyoma, leiomyoma, and myometrium samples. Conclusions. The expression pattern of LMP2/β1i and cyclin B1 might be a diagnostic biomarker for human Ut-LMS. Studies of the biological roles of LMP2/β1i and/or cyclin B1 could lead to the elucidation of new targets for therapies against Ut-LMS.
    Tumori. 07/2014; 100(4):99e-106e.

Publication Stats

5k Citations
1,002.73 Total Impact Points

Institutions

  • 1989–2015
    • Tohoku University
      • • Graduate School of Medicine
      • • Center for Traditional Asian Medicine
      • • Department of Microbiology and Immunology
      • • Department of Medical Genetics
      Miyagi, Japan
  • 2013
    • Fudan University
      • Department of Obstetrics and Gynecology
      Shanghai, Shanghai Shi, China
    • Kinki University
      Ōsaka, Ōsaka, Japan
  • 2003–2013
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 2010–2012
    • University of Tsukuba
      • Institute of Clinical Medicine
      Tsukuba, Ibaraki, Japan
    • Osaka City General Hospital
      Ōsaka, Ōsaka, Japan
    • Osaka City University
      • Graduate School of Medicine
      Ōsaka-shi, Osaka-fu, Japan
    • Tottori University
      TTJ, Tottori, Japan
    • Iwate Prefectural Central Hospital
      Aomori, Aomori Prefecture, Japan
  • 2011
    • University of Western Australia
      • School of Women's and Infants' Health
      Perth, Western Australia, Australia
    • Shinshu University
      • Department of Obstetrics and Gynecology
      Shonai, Nagano, Japan
    • Iwate Medical University
      • Department of Obstetrics and Gynecology
      Morioka, Iwate, Japan
  • 2010–2011
    • Keio University
      • Department of Obstetrics and Gynecology
      Tokyo, Tokyo-to, Japan
  • 2007–2010
    • National Defense Medical College
      • Division of Obstetrics and Gynecology
      Tokorozawa, Saitama-ken, Japan
  • 2008
    • Hirosaki University
      • Department of Obstetrics and Gynecology
      Khirosaki, Aomori Prefecture, Japan
  • 1991–1993
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States