Updated on 2024/03/11

写真a

 
IKEDA Yoshiki
 
Organization
Nagoya University Hospital Obstetrics and Gynecology Lecturer of hospital
Title
Lecturer of hospital
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Degree 2

  1. 博士(医学) ( 2022.4   名古屋大学 ) 

  2. Master of Engineering ( 2001.3   The University of Tokyo ) 

Research Interests 4

  1. Ovarian tumors

  2. Artificial intelligence

  3. 低侵襲手術

  4. 婦人科腫瘍

Research Areas 1

  1. Life Science / Obstetrics and gynecology

Current Research Project and SDGs 1

  1. 医療技能のデジタル化で実現する卵巣腫瘍の革新的診断システムの開発

Research History 5

  1. Nagoya University   Nagoya University Hospital Obstetrics and Gynecology   Lecturer of hospital

    2022.4

  2. Nagoya University   Nagoya University Hospital Obstetrics and Gynecology   Lecturer of hospital

    2022.4

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  3. Nagoya University   Nagoya University Hospital, Department of Obstetrics and Gynecology   Assistant Professor

    2021.4 - 2022.3

  4. Nagoya University   Nagoya University Hospital, Department of Obstetrics and Gynecology   Assistant professor of hospital

    2020.4 - 2021.3

  5. Nagoya University   Graduate School of Medicine, Department of Obstetrics and Gynecology   Designated assistant professor

    2018.2 - 2020.3

Education 3

  1. University of Fukui

    2004.10 - 2009.3

  2. The University of Tokyo

    1999.4 - 2001.3

  3. The University of Tokyo

    1995.4 - 1999.3

Professional Memberships 8

  1. 日本産科婦人科学会

  2. 日本婦人科腫瘍学会

  3. 日本産科婦人科内視鏡学会

  4. 日本婦人科ロボット手術学会

  5. 日本内視鏡外科学会

  6. 日本ロボット外科学会

  7. 日本遺伝性腫瘍学会

  8. 日本女性医学学会

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Committee Memberships 4

  1. Nature Publishing Group   Editorial Board Member, Scientific Reports  

    2022.8   

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    Committee type:Other

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  2. 日本産科婦人科内視鏡学会   ガイドライン委員  

    2022.4   

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    Committee type:Academic society

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  3. 日本婦人科腫瘍学会   代議員・査読委員  

    2022.1   

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    Committee type:Academic society

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  4. 日本産科婦人科学会   産科婦人科用語集・用語解説集委員会 編集委員  

    2021.6   

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Papers 63

  1. An update of oncologic and obstetric outcomes of radical trachelectomy for early-stage cervical cancer: The need for further minimally invasive treatment

    Tamauchi, S; Iyoshi, S; Yoshihara, M; Yoshida, K; Ikeda, Y; Shimizu, Y; Yokoi, A; Niimi, K; Yoshikawa, N; Kajiyama, H

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 50 ( 2 ) page: 175 - 181   2024.2

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    Aims: To investigate the oncologic and obstetric outcomes of radical trachelectomy (RT) in patients with early-stage cervical cancer and to evaluate the potential role of fertility-preserving treatments in improving pregnancy outcomes while oncologic status is stable. Methods: In this single-institution study, we analyzed the oncologic and obstetric outcomes of 67 patients with early-stage cervical cancer who underwent RT at Nagoya University Hospital. Results: The cancer recurrence rate (6.0%) and the mortality rate (1.5%) were comparable with those of previous studies. Of the 46 patients who attempted to conceive after RT, 19 (41.3%) became pregnant, and 16 gave birth. Of these 37.5% delivered at term, and delivery at less than 28 weeks of gestation occurred in 31.3% of pregnancies. Conclusions: RT is a viable treatment option for selected patients with early-stage cervical cancer. However, the use of less invasive techniques, such as conization/simple trachelectomy and pelvic lymph node dissection, may improve pregnancy outcomes while oncologic status is stable.

    DOI: 10.1111/jog.15824

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  2. Effect of radical trachelectomy on ovarian reserve: A single-institute prospective study

    Nakagawa, A; Tamauchi, S; Sato, M; Yoshihara, M; Yokoi, A; Shimizu, Y; Ikeda, Y; Yoshikawa, N; Niimi, K; Osuka, S; Kajiyama, H

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 50 ( 2 ) page: 212 - 217   2024.2

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    Aim: Reduced responses to controlled ovarian stimulation (COS) after radical trachelectomy (RT) have been previously reported. We aimed to assess the effect of RT on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels before and after the procedure in this prospective study. Methods: We included 12 patients who underwent RT between September 2019 and December 2021 in this study. Serum AMH levels were measured preoperatively, 1 month postoperatively, and 6 months postoperatively. Differences in the AMH levels were assessed using a paired t-test. Results: The median age of the patients was 30.6 years, and the median follow-up time was 30.1 months. AMH levels at 1 and 6 months postoperatively did not show a consistent trend. At 1 month postoperatively, the average AMH level decreased insignificantly but returned to preoperative levels at 6 months. The differences in AMH levels before and after RT were insignificant. Conclusion: Our findings indicate that RT did not affect ovarian reserve as measured by AMH levels. However, the relationship between unchanged ovarian reserve and reduced response to COS remains unclear. Further research with larger sample sizes and additional measures of ovarian function is needed to corroborate these results and investigate the long-term effects of RT on ovarian reserve. Understanding these mechanisms will help guide surgical practices and provide patients with valuable information about their reproductive outcomes after RT.

    DOI: 10.1111/jog.15828

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  3. Feasibility study of applying an online video communication system in tele-mentoring for guided robotic surgery

    Niwa Yuri, Asai Hidekazu, Ikeda Yoshiki, Matsushita Hidenobu, Isogai Yoshifumi

    JAPANESE JOURNAL OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY   Vol. 39 ( 2 ) page: 129 - 134   2024

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    Language:Japanese   Publisher:JAPAN SOCIETY OF GYNECOLOGIC AND OBSTETRIC ENDOSCOPY AND MINIMALLY INVASIVE THERAPY  

    <p> Although various types of surgeries have recently been performed using robotic surgery, experienced doctors who can provide guidance are few. The introduction of a tele-mentoring system under the guidance of experienced physicians can provide good medical care regardless of the location and is expected to improve patient outcome. However, many medical institutions are reluctant to introduce such systems owing to weak network systems and complicated procedures. Therefore, we devised a new online video guidance system using Zoom video communications that can be easily implemented by anybody. Additionally, we examined the feasibility of our new system in this study.</p><p> In our hospital, five surgeries were performed using an internet connection with an experienced physician at a remote site sharing images identical to those of the surgeon through Zoom video communication.</p><p> No line delays were observed and communication between the physicians was satisfactory. This system allows physicians to draw lines or letters on the shared screen through a Zoom video communications tool during the operation, which helps in verbal guidance. The robotic surgery was completed in all patients with safe outcomes.</p><p> In conclusion, our new system is feasible and is expected to be a method of improving physicians' skills and providing high-quality medical care regardless of location.</p>

    DOI: 10.5180/jsgoe.39.2_129

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  4. Mean platelet volume as a potential biomarker for survival outcomes in ovarian clear cell carcinoma

    Yoshikawa, N; Matsukawa, T; Hattori, S; Iyoshi, S; Yoshida, K; Yoshihara, M; Tamauchi, S; Shimizu, Y; Ikeda, Y; Yokoi, A; Niimi, K; Kawai, M; Kajiyama, H

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 28 ( 12 ) page: 1680 - 1689   2023.12

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    Language:English   Publisher:International Journal of Clinical Oncology  

    Objective: This study aimed to explore the prognostic value of mean platelet volume (MPV) in patients with ovarian clear cell carcinoma (OCCC) and evaluate the predictive performance of a random forest model incorporating MPV and other key clinicopathological factors. Methods: A total of 204 patients with OCCC treated between January 2004 and December 2019 were retrospectively analyzed. Clinicopathological characteristics and preoperative laboratory data were collected, and survival outcomes were evaluated using the Kaplan–Meier method and Cox proportional hazards models. An optimal MPV cutoff was determined by receiver operating characteristic (ROC) curve analysis. A random forest model was then constructed using the identified independent prognostic factors, and its predictive performance was evaluated. Results: The ROC analysis identified 9.3 fL as the MPV cutoff value for predicting 2-year survival. The MPV-low group had lower 5-year overall survival and progression-free survival rates than the MPV-high group (p = 0.003 and p = 0.034, respectively). High MPV emerged as an independent prognostic factor (p = 0.006). The random forest model, incorporating the FIGO stage, residual tumors, peritoneal cytology, and MPV, demonstrated robust predictive performance (area under the curve: 0.905). Conclusion: MPV is a promising prognostic indicator in OCCC. Lower MPV correlated with worse survival rates, advocating its potential utility in refining patient management strategies. The commendable predictive performance of the random forest model, integrating MPV and other significant prognostic factors, suggests a pathway toward enhanced survival prediction, thereby warranting further research.

    DOI: 10.1007/s10147-023-02417-8

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  5. Establishment and characterization of a non-gestational choriocarcinoma patient-derived xenograft model

    Oda, Y; Niimi, K; Yoshida, K; Tamauchi, S; Yokoi, A; Yasui, Y; Nishiko, Y; Shibata, M; Shimizu, Y; Yoshihara, M; Ikeda, Y; Yoshikawa, N; Nishino, K; Yamamoto, E; Kajiyama, H

    BMC CANCER   Vol. 23 ( 1 ) page: 1103   2023.11

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    Background: Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. Methods: Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdc scid 1l2rg tm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. Results: The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P < 0.001). Finally, we demonstrated that the PDX tumour was sensitive to cisplatin and methotrexate; therefore, its clinical response to the agents was similar to that of the primary tumour. Conclusions: We successfully established a PDX model of NGC, to the best of our knowledge, for the first time. The established PDX retained the molecular and transcriptome characteristics of the primary tumour and can be used to predict drug effects. It may facilitate further research and the development of novel therapeutic agents for NGC.

    DOI: 10.1186/s12885-023-11626-3

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  6. 9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins

    Mogi, K; Koya, Y; Yoshihara, M; Sugiyama, M; Miki, R; Miyamoto, E; Fujimoto, H; Kitami, K; Iyoshi, S; Tano, S; Uno, K; Tamauchi, S; Yokoi, A; Shimizu, Y; Ikeda, Y; Yoshikawa, N; Niimi, K; Yamakita, Y; Tomita, H; Shibata, K; Nawa, A; Tomoda, Y; Kajiyama, H

    SCIENTIFIC REPORTS   Vol. 13 ( 1 ) page: 19208   2023.11

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    Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25–50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.

    DOI: 10.1038/s41598-023-44365-3

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  7. Small Extracellular Vesicles from adipose-derived stem cells suppress cell proliferation by delivering the let-7 family of microRNAs in ovarian cancer

    Suzuki, H; Yokoi, A; Uno, K; Yoshida, K; Kitagawa, M; Asano-Inami, E; Matsuo, S; Nagao, Y; Suzuki, K; Nakamura, K; Yoshihara, M; Tamauchi, S; Shimizu, Y; Ikeda, Y; Yoshikawa, N; Kajiyama, H; Yamamoto, Y

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 680   page: 211 - 219   2023.11

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    Introduction: Ovarian cancer is the leading cause of death among women with gynecological cancer, and novel treatment options are urgently needed. Extracellular vesicles (EVs), including exosomes, may be one of the most promising therapeutic tools for various diseases. In this study, we aimed to investigate the therapeutic effects of adipose-derived stem cell-derived EVs (ADSC-EVs) on ovarian cancer cell lines. Materials and methods: ADSCs and the ovarian cancer cell lines SKOV3 and OV90 were used for analysis. ADSC-EVs were isolated through ultracentrifugation and validated using a cryotransmission electron microscope, nanoparticle tracking analysis, and western blotting. Then, the effect of ADSC-EVs on ovarian cancer cells was investigated using IncuCyte and microRNA sequencing. Moreover, the potential functions of miRNAs were evaluated by gain-of function analysis and in silico analysis. Results: ADSC-EVs suppressed SKOV3 and OV90 cell proliferation. In particular, small EVs (sEVs) from ADSCs exhibited a stronger antitumor effect than ADSC-medium/large EVs (m/lEVs). Comparison of the miRNA profiles between ADSC-sEVs and ADSC-m/lEVs, along with downstream pathway analysis, suggested the involvement of the let-7 family. Overexpression of hsa-let-7b-5p and hsa-let-7e-5p significantly suppressed the proliferation of SKOV3 cells. In silico analysis revealed that four potential target genes of hsa-let-7b-5p and hsa-let-7e-5p were significantly associated with the prognoses of the patients. Conclusion: ADSC-sEVs had a stronger antitumor effect than ADSC-m/lEVs. Hsa-let-7b-5p and hsa-let-7e-5p, which are highly abundant in ADSC-sEVs, suppressed cell proliferation. These findings may open up new possibilities for therapeutic approaches using ADSC-sEVs.

    DOI: 10.1016/j.bbrc.2023.09.022

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  8. The sarcopenia index measured using the lumbar paraspinal muscle is associated with prognosis in endometrial cancer

    Uno, K; Yoshikawa, N; Kitami, K; Mori, S; Shibata, T; Iyoshi, S; Fujimoto, H; Mogi, K; Yoshihara, M; Tamauchi, S; Ikeda, Y; Yokoi, A; Kato, K; Hoshiba, T; Oguchi, H; Kajiyama, H

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   Vol. 53 ( 10 ) page: 942 - 949   2023.10

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    Objective: The number of type-II endometrial cancer patients has been increasing and the prognosis is not favorable. We aim to investigate whether sarcopenia index in any of several different muscles could serve as a novel biomarker of prognosis in patients with type-II endometrial cancer. Methods: We retrospectively investigated a total of 194 patients at four hospitals. Ninety patients were treated as derivation set and the other 104 patients as validation set. Using preoperative computed tomography images, we measured the horizontal cross-sectional area at the third lumbar spine level: the (i) psoas major, (ii) iliac and (iii) paraspinal muscle. The clinical information including recurrence-free survival and overall survival were retrospectively collected. These results were validated with external data sets of three hospitals. Results: The median values of the sarcopenia index (cm2/m2) ± standard deviation with the first data of 90 patients using the psoas, iliac and paraspinal muscle were 3.4 ± 1.0, 1.7 ± 0.6 and 12.6 ± 3.2, respectively. In univariate analyses, the sarcopenia indexes measured using the psoas or paraspinal muscle were associated with recurrence-free survival and overall survival. On the other hand, in multivariate analyses, only the sarcopenia index using paraspinal muscle was significantly related to recurrence-free survival (hazard ratio = 3.78, 95% confidence intervals = 1.29-5.97, P = 0.009) and overall survival (hazard ratio = 3.13, 95% confidence interval = 1.18-8.26, P = 0.022). Paraspinal sarcopenia index was also related to overall survival (hazard ratio = 3.74, 95% confidence interval = 1.31-10.72, P = 0.014) even in patients with advanced stage. Serum albumin was significantly correlated with the sarcopenia index (P = 0.012). Within the analysis of the validation set, sarcopenia index using paraspinal muscle was related to recurrence-free survival (hazard ratio = 2.06, P = 0.045) in multivariate analysis and recurrence-free survival (P = 0.009) in patients with advanced stage. Conclusions: The sarcopenia index using the paraspinal muscle, not psoas, could be a suitable index to predict recurrence-free survival and overall survival in patients with type-II endometrial cancer even in advanced stage.

    DOI: 10.1093/jjco/hyad086

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  9. Unclear tumor border in magnetic resonance imaging as a prognostic factor of squamous cell cervical cancer

    Sato, M; Tamauchi, S; Yoshida, K; Yoshihara, M; Ikeda, Y; Yoshikawa, N; Kajiyama, H

    SCIENTIFIC REPORTS   Vol. 13 ( 1 ) page: 15392   2023.9

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    Magnetic resonance imaging (MRI) is used for pretreatment staging in cervical cancer. In the present study, we used pretreatment images to categorize operative cases into two groups and evaluated their prognosis. A total of 53 cervical cancer patients with squamous cell carcinoma who underwent radical hysterectomy were included in this study. Based on MRI, the patients were classified into two groups, namely clear and unclear tumor border. For each patient, the following characteristics were evaluated: overall survival; recurrence-free survival; lymph node metastasis; lymphovascular space invasion; and pathological findings, including immunohistochemical analysis of vimentin. The clear and unclear tumor border groups included 40 and 13 patients, respectively. Compared with the clear tumor border group, the unclear tumor border group was associated with higher incidence rates of recurrence (3/40 vs. 3/13, respectively), lymphovascular space invasion (24/40 vs. 13/13, respectively), lymph node metastasis (6/40 vs. 10/13, respectively), and positivity for vimentin (18/40 vs. 10/13, respectively). Despite the absence of significant difference in recurrence-free survival (p = 0.0847), the unclear tumor border group had a significantly poorer overall survival versus the clear tumor border group (p = 0.0062). According to MRI findings, an unclear tumor border in patients with squamous cell cervical cancer is linked to poorer prognosis, lymph node metastasis, and distant recurrence of metastasis.

    DOI: 10.1038/s41598-023-42787-7

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  10. DDIT4 Facilitates Lymph Node Metastasis via the Activation of NF-kB Pathway and Epithelial-Mesenchymal Transition

    Lin, XX; Yoshikawa, N; Liu, WT; Matsukawa, T; Nakamura, K; Yoshihara, M; Koya, Y; Sugiyama, M; Tamauchi, S; Ikeda, Y; Yokoi, A; Shimizu, Y; Kajiyama, H

    REPRODUCTIVE SCIENCES   Vol. 30 ( 9 ) page: 2829 - 2841   2023.9

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    This study was aimed to identify a novel metastasis-promoting molecule and elucidate its functional and prognostic roles in cervical cancer. DDIT4 (DNA-damage-inducible transcript 4), a hypoxia-inducible gene, was identified by analyzing multiple microarray databases. The correlation between DDIT4 expression in immunohistochemistry and clinicopathological characteristics in the public database and our cohort was evaluated by statistical analysis. Transwell® assay and wound-healing assay to determine cell migration and invasion were performed. DDIT4 was knocked down using siRNA or lentiviral vectors. The potential downstream pathways of DDIT4 were explored and verified by a gene set enrichment analysis and western blotting. The in vivo metastatic capability was determined with the use of an intraperitoneal injection mouse model. In the analysis of the public database and our cohort, DDIT4 high expression was significantly related to short overall survival and lymph node metastasis in patients with early-stage cervical cancer. The knockdown of DDIT4 attenuated the migration and invasion activity of tumor cells in vitro and reduced the expression of epithelial–mesenchymal transition (EMT)-related proteins and the NF-κB pathway in cervical cancer cells. DDIT4 also promoted tumor progression in the mouse model. Our results indicate that DDIT4 can be a prognostic indicator in cervical cancer and promote lymph node metastasis, augmenting malignancy via the EMT and NF-kB pathways.

    DOI: 10.1007/s43032-023-01230-y

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  11. Niraparib as a therapeutic agent for the treatment of ovarian cancer meningeal dissemination with <i>BRCA1</i> mutation

    Nei, T; Tamauchi, S; Ikeda, Y; Yoshikawa, N; Niimi, K; Kajiyama, H

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 49 ( 7 ) page: 1875 - 1879   2023.7

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    This study analyzed a 63-year-old woman with hereditary BRCA1 mutation. She underwent interval debulking surgery after neoadjuvant chemotherapy for high-grade serous ovarian carcinoma (HGSOC). After 2 years of postoperative chemotherapy, she developed headache and dizziness, and a suspected metastatic cerebellar mass in left ovary was detected. Pathological analysis of the mass revealed HGSOC, which was removed surgically. Eight months and another 6 months after the surgery, local recurrence was noted; hence, she underwent CyberKnife treatment. After 3 months, cervical spinal cord metastasis was found, evidenced by left shoulder pain. Moreover, meningeal dissemination was present around the cauda equina. Chemotherapy treatment, including bevacizumab, was ineffective and increased lesions were observed. After CyberKnife treatment for the cervical spinal cord metastasis, niraparib was initiated for the meningeal dissemination. The cerebellar lesions and meningeal dissemination improved within 8 months of niraparib treatment. Although meningeal dissemination is challenging to treat, niraparib may be useful in BRCA-mutated HGSOC.

    DOI: 10.1111/jog.15663

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  12. Downregulating vaccinia-related kinase 1 by luteolin suppresses ovarian cancer cell proliferation by activating the p53 signaling pathway

    Chang, X; Tamauchi, S; Yoshida, K; Yoshihara, M; Yokoi, A; Shimizu, Y; Ikeda, Y; Yoshikawa, N; Kiyono, T; Yamamoto, Y; Kajiyama, H

    GYNECOLOGIC ONCOLOGY   Vol. 173   page: 31 - 40   2023.6

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    Language:English   Publisher:Gynecologic Oncology  

    Objectives: Ovarian cancer constitutes one of the most common causes of cancer-related deaths, and preventing chemotherapy resistance and recurrence in patients with ovarian cancer remains a challenge. Herein, we aimed to identify the effect of luteolin, a novel therapeutic agent targeting vaccinia-related kinase 1 (VRK1), on high-grade serous ovarian cancer (HGSOC). Methods: Phosphokinase array, RNA sequencing, and cell cycle and apoptosis assays were conducted to determine the underlying mechanism of the effect of luteolin on HGSOC cells. The anticancer effects of oral and intraperitoneal luteolin administration were assessed in patient-derived xenograft models via several methods, including the assessment of tumor size and immunohistochemistry of phospho-p53, phosphor-HistoneH3 and cleaved caspase 3. Results: Luteolin reduced HGSOC cell proliferation and increased apoptosis and cell cycle arrest at G2/M. Compared with controls, several genes were dysregulated in luteolin-treated cells, and luteolin activated the p53 signaling pathway. The human phosphokinase array revealed distinct p53 upregulation in luteolin-treated cells, as confirmed by p53 phosphorylation at ser15 and ser46 using western blot analysis. In patient-derived xenograft models, oral or intraperitoneal luteolin administration substantially suppressed tumor growth. Moreover, combination treatment involving luteolin and cisplatin inhibited tumor cell proliferation, especially in cisplatin-resistant HGSOC cell lines. Conclusions: Luteolin demonstrated considerable anticancer effect on HGSOC cells, reduced VRK1 expression, and activated the p53 signaling pathway, thereby inducing apoptosis and cell cycle arrest in G2/M and inhibiting cell proliferation. Furthermore, luteolin exhibited a synergistic effect with cisplatin both in vivo and in vitro. Thus, luteolin can be considered a promising cotreatment option for HGSOC.

    DOI: 10.1016/j.ygyno.2023.04.003

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  13. Novel therapeutic strategies targeting UCP2 in uterine leiomyosarcoma

    Nagao, Y; Yokoi, A; Yoshida, K; Sugiyama, M; Watanabe, E; Nakamura, K; Kitagawa, M; Asano-Inami, E; Koya, Y; Yoshihara, M; Tamauchi, S; Shimizu, Y; Ikeda, Y; Yoshikawa, N; Kato, T; Yamamoto, Y; Kajiyama, H

    PHARMACOLOGICAL RESEARCH   Vol. 189   page: 106693   2023.3

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    Uterine leiomyosarcoma (ULMS) is a malignant stromal tumor arising from the myometrium with a poor prognosis and very limited response to current chemotherapy. This study aimed to identify novel targets for ULMS through a three-step screening process using a chemical library consisting of 1271 Food and Drug Administration-approved drugs. First, we evaluated their inhibitory effects on ULMS cells and identified four candidates: proscillaridin A, lanatoside C, floxuridine, and digoxin. Then, we subcutaneously or orthotopically transplanted SK-UT-1 cells into mice to establish mouse models. In vivo analyses showed that proscillaridin A and lanatoside C exerted a superior antitumor effect. The results of mRNA sequencing showed that uncoupling protein 2 (UCP2) was suppressed in the sirtuin signaling pathway, increasing reactive oxygen species (ROS) and inducing cell death. Moreover, the downregulation of UCP2 induced ROS and suppressed ULMS cell growth. Furthermore, analyses using clinical samples showed that UCP2 expression was significantly upregulated in ULMS tissues than in myoma tissues both at the RNA and protein levels. These findings suggested that UCP2 is a potential therapeutic target and can contribute to the development of novel therapeutic strategies in patients with ULMS.

    DOI: 10.1016/j.phrs.2023.106693

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  14. The prognostic significance of DDIT4 in endometrial cancer

    Yoshikawa, N; Yoshida, K; Liu, WT; Matsukawa, T; Hattori, S; Yoshihara, M; Tamauchi, S; Ikeda, Y; Yokoi, A; Shimizu, Y; Niimi, K; Kajiyama, H

    CANCER BIOMARKERS   Vol. 37 ( 4 ) page: 217 - 225   2023

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    Language:English   Publisher:Cancer Biomarkers  

    BACKGROUND: Despite extensive research on endometrial cancer and tumor hypoxic microenvironment, there are no reports exploring the role of DDIT4 in endometrial cancer. OBJECTIVE: This study aimed to elucidate the significance of DDIT4, as a prognostic biomarker for endometrial cancer by immunohistochemical staining and statistical analysis. METHODS: Four endometrial cancer cells were cultured under normoxia and hypoxia, and the differentially expressed genes were examined using RNA-seq. Immunohistochemical staining for DDIT4 and HIF1A was performed in 86 patients with type II endometrial cancer treated at our hospital, and their correlation with other clinicopathological factors and the prognostic role was analyzed using statistical methods. RESULTS: The expression analysis of hypoxia-inducible genes using four types of endometrial cancer cells revealed that DDIT4 was among the 28 genes that were upregulated in all cells. Based on our results of immunohistochemistry of DDIT4 expression in endometrial cancer tissues, univariate and multivariate analyses based on COX regression analysis showed that high DDIT4 expression significantly correlated to favorable prognosis in both progression-free survival and overall survival. Limited to recurrent cases, metastasis to only lymph nodes was significantly related to high DDIT4 expression, whereas metastasis to other parenchymal organs was significantly dominant in patients with low DDIT4 expression. CONCLUSIONS: The expression of DDIT4 enables to predict survival and recurrence in type II endometrial cancer.

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  15. Development of an Artificial Intelligence Assisted Preoperative Diagnosis System for Ovarian Tumors

    INABA Daiki, KOIZUMI Norihiro, MUKASA Annju, ONODERA Yusuke, SASAKI Kaho, KUNISHIMA Atsushi, GOTO Mayuko, MURAMATSU Reina, IKEDA Yoshiki

    The Proceedings of JSME annual Conference on Robotics and Mechatronics (Robomec)   Vol. 2023 ( 0 ) page: 2P1-B16   2023

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    <p>It is difficult to diagnose benign, borderline, or malignant nature of ovarian tumors preoperatively. Problems often arise because physicians determine the extent of resection based on presumed diagnosis. There is an urgent need to improve the accuracy of preoperative diagnosis. In this study, we developed a three-level classification system for serous ovarian tumors using blood test data and machine learning. The effectiveness of combining data sets and training models was examined by learning and estimating for four different data sets and a control group using three different models: random forest, logistic regression analysis, and linear SVC. The results showed that only LR-D4 outperformed the control group in all categories, but other combinations improved in some category. This suggests that the content and combination of the data set are effective in improving precision and specificity of the estimation.</p>

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  16. Hypoalbuminemia for the prediction of survival in patients with stage IVB cervical cancer

    Yoshikawa, N; Yoshihara, M; Tamauchi, S; Ikeda, Y; Yokoi, A; Kajiyama, H

    PLOS ONE   Vol. 17 ( 9 ) page: e0273876   2022.9

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    We evaluated the prognostic significance of malnutrition in patients with metastatic cervical cancer. In this study, we retrospectively analyzed the cases of 43 patients with stage IVB (FIGO2018) cervical cancer treated at our institute from December 2004 to December 2017. We determined the correlation between clinicopathological characteristics and survival by performing univariate and multivariate analyses. The serum albumin value at diagnosis was used as an index of malnutrition. The median follow-up period was 16.4 months (range, 0.9–91.4 months). On Kaplan-Meier analysis, the 1- and 2-year overall survival (OS) rates for all patients were 61.6% and 48.6%, respectively. The optimal serum albumin for predicting 1-year survival was 3.3 g/dL, as determined by the receiver operating characteristic curve to maximize the area under the curve. The OS of the patients with albumin >3.3 g/ dL (n = 28) was significantly better than that of the patients with albumin ≤3.3 g/dL (n = 15) (p = 0.004). The univariate and multivariate analyses revealed that pretreatment serum albumin and mode of primary treatment were significantly associated with survival in patients with stage IVB cervical cancer. Hypoalbuminemia was an unfavorable prognostic factor for patients with metastatic cervical cancer.

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  17. Survival benefits of retroperitoneal lymphadenectomy for optimally-resected advanced ovarian high-grade serous carcinoma: a multi-institutional retrospective study Reviewed International journal

    Ikeda Yoshiki, Yoshihara Masato, Tamauchi Satoshi, Yokoi Akira, Yoshikawa Nobuhisa, Kajiyama Hiroaki

    JOURNAL OF GYNECOLOGIC ONCOLOGY   Vol. 33 ( 4 ) page: e40   2022.7

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    OBJECTIVE: The survival benefits of retroperitoneal lymphadenectomy (RLNA) for epithelial ovarian cancer (EOC) remain controversial because clinical behaviors differ among subtypes. The purpose of the present study was to clarify whether RLNA increases the survival rate of advanced high-grade serous carcinoma (HGSC). METHODS: This was a retrospective cohort analysis of 3,227 patients with EOC treated between 1986 and 2017 at 14 institutions. Among them, 335 patients with stage IIB-IV HGSC who underwent optimal cytoreduction (residual tumor of <1 cm) were included. Patients were divided into the RLNA group (n=170) and non-RLNA group (n=165). All pathological slides were assessed based on a central pathological review. Oncologic outcomes were compared between the two groups in the original and weighted cohorts adjusted with the inverse probability of treatment weighting. RESULTS: The median observation period was 49.8 (0.5-241.5) months. Overall, 219 (65%) out of 335 patients had recurrence or progression, while 146 (44%) died of the disease. In the original cohort, RLNA was a significant prognostic factor for longer progression-free survival (PFS) (hazard ratio [HR]=0.741; 95% confidence interval [CI]=0.558-0.985) and overall survival (OS) (HR=0.652; 95% CI=0.459-0.927). In the weighted cohort in which all variables were well balanced as standardized differences decreased, RLNA was also a significant prognostic factor for more favorable oncologic outcomes (PFS, adjusted HR=0.742; 95% CI=0.613-0.899) and OS, adjusted HR=0.620; 95% CI=0.488-0.787). CONCLUSION: The present study demonstrated that RLNA for stage III-IV HGSC with no residual tumor after primary debulking surgery contributed to better oncologic outcomes.

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  18. Peritoneal restoration by repurposing vitamin D inhibits ovarian cancer dissemination via blockade of the TGF-beta 1/thrombospondin-1 axis Reviewed International journal

    Kitami Kazuhisa, Yoshihara Masato, Tamauchi Satoshi, Sugiyama Mai, Koya Yoshihiro, Yamakita Yoshihiko, Fujimoto Hiroki, Iyoshi Shohei, Uno Kaname, Mogi Kazumasa, Ikeda Yoshiki, Yokoi Akira, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Nawa Akihiro, Enomoto Atsushi, Kajiyama Hiroaki

    MATRIX BIOLOGY   Vol. 109   page: 70 - 90   2022.5

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    Ovarian cancer (OvCa), a lethal gynecological malignancy, disseminates to the peritoneum. Mesothelial cells (MCs) act as barriers in the abdominal cavity, preventing the adhesion of cancer cells. However, in patients with OvCa, they are transformed into cancer-associated mesothelial cells (CAMs) via mesenchymal transition and form a favorable microenvironment for tumors to promote metastasis. However, attempts for restoring CAMs to their original state have been limited. Here, we investigated whether inhibition of mesenchymal transition and restoration of MCs by vitamin D suppressed the OvCa dissemination in vitro and in vivo. The effect of vitamin D on the mutual association of MCs and OvCa cells was evaluated using in vitro coculture models and in vivo using a xenograft model. Vitamin D restored the CAMs, and thrombospondin-1 (component of the extracellular matrix that is clinically associated with poor prognosis and is highly expressed in peritoneally metastasized OvCa) was found to promote OvCa cell adhesion and proliferation. Mechanistically, TGF-β1 secreted from OvCa cells enhanced thrombospondin-1 expression in CAMs via Smad-dependent TGF-β signaling. Vitamin D inhibited mesenchymal transition in MCs and suppressed thrombospondin-1 expression via vitamin D receptor/Smad3 competition, contributing to the marked reduction in peritoneal dissemination in vivo. Importantly, vitamin D restored CAMs from a stabilized mesenchymal state to the epithelial state and normalized thrombospondin-1 expression in preclinical models that mimic cancerous peritonitis in vivo. MCs are key players in OvCa dissemination and peritoneal restoration and normalization of thrombospondin-1 expression by vitamin D may be a novel strategy for preventing OvCa dissemination.

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  19. Is cystectomy an option as conservative surgery for young patients with borderline ovarian tumor? A multi-institutional retrospective study Reviewed International journal

    Ikeda Yoshiki, Yoshihara Masato, Yoshikawa Nobuhisa, Tamauchi Satoshi, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS   Vol. 157 ( 2 ) page: 437 - 443   2022.5

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    OBJECTIVE: To investigate the impact of cystectomy for borderline ovarian tumor (BOT) on tumor recurrence compared with salpingo-oophorectomy using inverse probability of treatment weighting (IPTW). METHODS: A central pathologic review and a search of the medical records from 14 collaborating institutions from 1986 to 2017 identified 4708 women with a malignant ovarian neoplasm. Data for young women with Stage I BOT were extracted. To compare recurrence-free survival between the surgery groups, Cox regression analyses and the IPTW-adjusted Kaplan-Meier method were employed. RESULTS: During a median follow-up of 62.0 (1.2-270.4) months, 10 of the 285 patients identified (3.5%) developed recurrence. In multivariate analysis, the practice of cystectomy was not a significant prognostic indicator of recurrence-free survival (hazard ratio [95% confidence interval] 1.276 [0.150-10.864]; P = 0.823). In the IPTW-adjusted cohort, the 5-year recurrence-free survival rates were 95.8% and 96.0% in patients receiving cystectomy and salpingo-oophorectomy, respectively (P = 0.378). CONCLUSION: If patients are selected appropriately, cystectomy in itself may not increase tumor recurrence in young women with early-stage BOT. A large-scale prospective clinical study is necessary to validate this finding.

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  20. Is adjuvant chemotherapy necessary for young women with early-stage epithelial ovarian cancer who have undergone fertility-sparing surgery?: a multicenter retrospective analysis Reviewed International journal

    Ikeda Yoshiki, Yoshihara Masato, Yoshikawa Nobuhisa, Yokoi Akira, Tamauchi Satoshi, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    BMC WOMENS HEALTH   Vol. 22 ( 1 ) page: 80 - 80   2022.3

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    OBJECTIVE: In young patients with early-stage epithelial ovarian carcinoma (EOC) who were received fertility-sparing surgery (FSS), the role of adjuvant chemotherapy is unclear. Here, we performed a multicenter study using inverse probability of treatment weighting (IPTW) to explore the effect of chemotherapy on patients' survival. METHODS: Between 1987 and 2015, a retrospective study was carried out, including 1183 patients with stage I EOC. Among them, a total of 101 women with stage I EOC who underwent FSS were investigated, including 64 and 37 patients with or without adjuvant chemotherapy, respectively. Oncologic outcomes were compared between the two arms using original and IPTW cohorts. RESULTS: During 62.6 months (median) of follow-up, recurrence was noted in 11 (17.2%) women in the chemotherapy arm and 6 (16.2%) patients in the observation arm. In the unweighted cohort, the 5-year overall and recurrence-free survival (OS/RFS) rates of chemotherapy and observation arms were 86.3/80.8 and 90.2/79.8%, respectively. There was no significant difference between the two groups {Log-rank: P = 0.649 (OS)/P = 0.894 (RFS)}. In the IPTW cohort after adjusting for various clinicopathologic covariates, we also failed to identify a difference in RFS/OS between the two groups {RFS (chemotherapy vs. observation), HR: 0.501 (95% CI 0.234-1.072), P = 0.075: OS (chemotherapy vs. observation), HR: 0.939 (95% CI 0.330-2.669), P = 0.905}. CONCLUSIONS: Even after adjusting clinicopathologic covariates, performing adjuvant chemotherapy may not improve the oncologic outcome in young patients who have undergone FSS.

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  21. Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy Reviewed International journal

    Uno Kaname, Yoshikawa Nobuhisa, Tazaki Akira, Ohnuma Shoko, Kitami Kazuhisa, Iyoshi Shohei, Mogi Kazumasa, Yoshihara Masato, Koya Yoshihiro, Sugiyama Mai, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Kikkawa Fumitaka, Kato Masashi, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 12 ( 1 ) page: 4513 - 4513   2022.3

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    Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with "platinum-resistant recurrence". Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.

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  22. A case of fistula cancer in Crohn's disease indistinguishable preoperatively from Bartholin's adenocarcinoma

    Matsui Mami, Niimi Kaoru, Yoshihara Masato, Tamauchi Satoshi, Yokoi Akira, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Kajiyama Hiroaki

    Japanese Journal of Gynecological Oncology   Vol. 40 ( 1 ) page: 10 - 16   2022.1

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    <p>Adenocarcinoma of the vulva is rare. Lesions of the posterior vaginal vestibule are often assumed to be primary lesions of the Bartholin's glands. We report a case where vulvar adenocarcinoma in a Crohn's disease patient was diagnosed as cancer arising from an anal fistula following resection. A 48-year-old woman received treatment for Crohn's disease. Six months prior, she had a tumor of the left vulvar area, close to the vaginal vestibule. Adenocarcinoma was confirmed based on biopsy results. Upper and lower gastrointestinal endoscopy performed was negative. Accordingly, Bartholin's adenocarcinoma was suspected. On the first visit, a 4 cm mass was found in the left Bartholin's gland area. CT revealed mild bilateral inguinal lymph node hypertrophy. We performed simple vulvectomy and bilateral inguinal lymph node sampling for biopsy. The pathological diagnosis was moderately different from adenocarcinoma. A continuity was observed between the colonic mucosal epithelium and the adenocarcinoma. Accordingly, anal fistula cancer was confirmed. The excision margin was positive on the deep exfoliated surface of the left vaginal wall. Subsequently, robot-assisted laparoscopic abdominal perineal resection, vaginal perineal resection, colon stoma construction, and inguinal lymph node dissection were performed. Capecitabine plus oxaliplatin (CAPOX) chemotherapy is currently being administered to the patient. Vulvar adenocarcinoma with Crohn's disease should be scrutinized with suspicion of anal fistula cancer.</p>

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  23. Laparoscopic pelvic surgery after reconstructive surgery with vertical rectus abdominis muscle flap: A case report. Reviewed International journal

    Nishino K, Ikeda Y, Kitami K, Niimi K, Kajiyama H

    International journal of surgery case reports   Vol. 90   page: 106706 - 106706   2022.1

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    INTRODUCTION: Patients who have experienced vertical rectus abdominis muscle (VRAM) flap reconstruction are under risk of the abdominal incisional hernia (donor site hernia), and laparotomy increases the risk. PRESENTATION OF THE CASE: We present the case of a 71-year-old nulliparous woman who experienced radical vulvectomy against extramammary Paget disease and reconstructive surgery with VRAM flap 7 years ago and developed right ovarian tumor. In this case, right ovarian tumor was removed with laparoscopic surgery, instead of laparotomy, and the risk of incisional hernia was successfully minimized. DISCUSSION: Incisional (donor site) hernia after reconstructive surgery using VRAM flap has been reported in between 2 and 10%. While VRAM flap can fill larger amount of skin and subcutaneous tissue to recipient site, the risk of postoperative incisional hernia of abdominal wall is substantial. CONCLUSION: Reconstructive surgery of with VRAM flap is required for extramammary vulvar Paget disease expanding wide range, and develops the risk of incisional hernia. Laparoscopic surgery should be applied in patients who have experienced VRAM flap reconstruction and developed pelvic tumor for avoiding the risk of incisional hernia as long as it can be allowed on oncologic aspects such as recurrence.

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  24. Clinical effects of cervical conization with positive margins in cervical cancer Reviewed International journal

    Nagao Yukari, Yokoi Akira, Yoshida Kosuke, Sumi Masanori, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 23288 - 23288   2021.12

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    Radical surgery after cervical conization is a common approach for the treatment of cervical cancer. In some cases, disease progression is observed after positive margins at conization, but the effect of conization on disease progression remains unclear. Thus, the aim of this study was to investigate the clinical outcomes of positive margins at conization in cervical cancer. A total of 101 patients who underwent cervical conization before radical hysterectomy and pelvic lymph node dissection were considered eligible by reviewing medical records. The association between the positive margins and patient outcomes, including subsequent lymph node metastasis, was evaluated. The rate of lymphovascular space invasion (LVSI) positivity at radical surgery was significantly higher in patients with positive margins (p = 0.017) than in those with negative margins, although there was no significant difference in the rate of pelvic lymph node metastasis (p = 0.155). Moreover, there was no significant difference in the overall survival or progression-free survival between the two groups (p = 0.332 and 0.200, respectively). A positive margin at conization presented no significant prognostic disadvantage; thus, diagnostic conization is one of the most suitable treatment options for early-stage cervical cancer that is difficult to accurately assess.

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  25. Achievement of live birth after overcoming two gynecological malignancies treated with radical trachelectomy and medroxyprogesterone acetate therapy Reviewed

    Tamauchi Satoshi, Moriyama Yoshinori, Suzuki Shiro, Ikeda Yoshiki, Yoshikawa Nobuhisa, Kajiyama Hiroaki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 47 ( 11 ) page: 4101 - 4105   2021.11

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  26. Core 2 beta 1,6-N-acetylglucosaminyltransferases accelerate the escape of choriocarcinoma from natural killer cell immunity Reviewed International journal

    Nakamura Kenichi, Niimi Kaoru, Yamamoto Eiko, Ikeda Yoshiki, Nishino Kimihiro, Suzuki Shiro, Kajiyama Hiroaki, Kikkawa Fumitaka

    BIOCHEMISTRY AND BIOPHYSICS REPORTS   Vol. 26   page: 100951 - 100951   2021.7

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    Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted from choriocarcinoma and contains a core2 O-glycan formed by core2 β1,6-N-acetylglucosaminyl transferase (C2GnT). Choriocarcinoma is considered immunogenic as it is gestational and contains paternal chromosomal components. Here we examined the function of C2GnT in the evasion of choriocarcinoma cells from natural killer (NK) cell-mediating killing. We determined that C2GnT is highly expressed in malignant gestational trophoblastic neoplasms. C2GnT KO downregulates core2 O-glycan expression in choriocarcinoma cells, which are more efficiently killed by NK cells than control cells. C2GnT KO cell containing tumor necrosis factor-related apoptosis inducing ligand have lower viability than control cells. Additionally, poly-N-acetyllactosamine in core2 branched oligosaccharides on MHC class I-related chain A (MICA) and mucin1 (MUC1) is significantly reduced in C2GnT KO cells. Meanwhile, the cumulative survival rate of nude mice inoculated with C2GnT KO tumors was higher than that of the control group. These findings suggest that choriocarcinoma cells may escape NK cell-mediated killing via glycosylation of MICA and MUC1.

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  27. Metabolome analysis reveals a diversity of cancer tissues in advanced epithelial ovarian cancer Reviewed

    Yoshida Kosuke, Yoshikawa Nobuhisa, Kitami Kazuhisa, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Kajiyama Hiroaki

    CANCER CELL INTERNATIONAL   Vol. 21 ( 1 ) page: 314   2021.6

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  28. Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer Reviewed

    Hattori Satomi, Yoshikawa Nobuhisa, Mogi Kazumasa, Yoshida Kosuke, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yokoi Akira, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kajiyama Hiroaki

    CURRENT ONCOLOGY   Vol. 28 ( 3 ) page: 1663 - 1672   2021.6

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  29. A poor prognostic metastatic nongestational choriocarcinoma of the ovary: a case report and the literature review Reviewed International journal

    Nishino Kimihiro, Yamamoto Eiko, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Toshimichi, Kajiyama Hiroaki

    JOURNAL OF OVARIAN RESEARCH   Vol. 14 ( 1 ) page: 56 - 56   2021.4

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    BACKGROUND: Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis. CASE PRESENTATION: A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma. CONCLUSION: Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.

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  30. Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance Reviewed International journal

    Yoshida Kosuke, Yokoi Akira, Sugiyama Mai, Oda Shingo, Kitami Kazuhisa, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka, Yokoi Tsuyoshi, Kajiyama Hiroaki

    ONCOGENE   Vol. 40 ( 7 ) page: 1255 - 1268   2021.2

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    Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer and exhibits dismal prognosis due to chemoresistance. Moreover, only few effective therapeutic options exist for patients with recurrent OCCC, and an understanding of its molecular characteristics is essential for the development of novel therapeutic approaches. In the present study, we investigated unique MicroRNAs (miRNA) profiles in recurrent/metastatic OCCC and the role of miRNAs in cisplatin resistance. Comprehensive miRNA sequencing revealed that expression of several miRNAs, including miR-508-3p, miR-509-3p, miR-509-3-5p, and miR-514a-3p was remarkably less in recurrent cancer tissues when compared with that in paired primary cancer tissues. These miRNAs are located in the chrXq27.3 region on the genome. Moreover, its expression was negative in omental metastases in two patients with advanced OCCC. In vitro analyses revealed that overexpression of miR-509-3p and miR-509-3-5p reversed cisplatin resistance and yes-associated protein 1 (YAP1) was partially responsible for the resistance. Immunohistochemistry revealed that YAP1 expression was inversely correlated with the chrXq27.3 miRNA cluster expression. In conclusion, these findings suggest that alteration of the chrXq27.3 miRNA cluster could play a critical role in chemoresistance and miRNAs in the cluster and their target genes can be potential therapeutic targets.

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  31. Establishment of a patient-derived xenograft model and cell line of malignant transformation of mature cystic teratoma of the ovary Reviewed

    Tamauchi Satoshi, Suzuki Shiro, Xuboya Chang, Yoshihara Masato, Yoshida Kosuke, Ikeda Yoshiki, Yoshikawa Nobuhisa, Kajiyama Hiroaki, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 47 ( 2 ) page: 713 - 719   2021.2

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  32. A uterine pseudotumor of immunoglobulinG4-related disease Reviewed

    Senda Yasutaka, Ikeda Yoshiki, Tamauchi Satoshi, Yoshikawa Nobuhisa, Kikkawa Fumitaka, Kajiyama Hiroaki

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 47 ( 1 ) page: 430 - 435   2021.1

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  33. Does uterine preservation affect survival outcomes of patients with stage I ovarian sex cord-stromal cell tumours? A multi-institutional study Reviewed International journal

    Yoshihara Masato, Tamauchi Satoshi, Iyoshi Shohei, Kitami Kazuhisa, Uno Kaname, Yoshikawa Nobuhisa, Ikeda Yoshiki, Kawai Michiyasu, Nagasaka Tetsuro, Kajiyama Hiroaki

    EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY   Vol. 254   page: 52 - 56   2020.11

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    OBJECTIVE: Sex cord-stromal tumours of the ovary are relatively uncommon neoplasms that account for 3 % of all ovarian cancers. Uterine preservation with careful staging is achievable; however, conservative surgery remains controversial. This study examined the prognostic effects of uterine preservation in patients with stage I sex cord-stromal tumours. STUDY DESIGN: This retrospective cohort study was undertaken between January 1986 and February 2019, and the clinicopathological data of 4897 women with malignant ovarian tumours were collected. Seventy-seven patients with stage I sex cord-stromal tumours were eligible for inclusion. The characteristics and survival outcomes of these patients were examined. To investigate the prognostic effects of uterine-preserving surgery, baseline imbalances between patients with and without uterine-preserving surgery were adjusted using an inverse probability of treatment weighting with propensity scores composed of independent clinical variables. RESULTS: The mean ages of patients in the uterine-preserving surgery and non-uterine-preserving surgery groups were 39.8 and 57.8 years, respectively. After inverse probability of treatment weighting adjustments, no significant differences in overall survival (p = 0.205) or recurrence-free survival (p=0.071) were observed between the uterine-preserving surgery and non-uterine-preserving surgery groups. Estimated 10-year overall survival rates were 98.7 % in the uterine-preserving surgery group and 95.9 % in the non-uterine-preserving surgery group, and 10-year recurrence-free survival rates were 87.2 % in the uterine-preserving surgery group and 78.2 % in the non-uterine-preserving surgery group. Uterine-preserving surgery did not significantly affect the site of tumour recurrence. CONCLUSION: Uterine-preserving surgery may be a feasible surgical option for patients with stage I sex cord-stromal tumours. Further research is needed to guarantee prognostic accuracy and develop effective therapeutic approaches for sex cord-stromal tumours.

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  34. Adjusted multiple gases in the plasma flow induce differential antitumor potentials of plasma-activated solutions Reviewed

    Nakamura Kae, Yoshikawa Nobuhisa, Yoshihara Masato, Ikeda Yoshiki, Higashida Akihiro, Niwa Akihiro, Jindo Takahiro, Tanaka Hiromasa, Ishikawa Kenji, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

    PLASMA PROCESSES AND POLYMERS   Vol. 17 ( 10 )   2020.10

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  35. The Preoperative Prognostic Nutritional Index for the Prediction of Outcomes in Patients with Early-Stage Ovarian Clear Cell Carcinoma Reviewed

    Yoshikawa Nobuhisa, Yoshida Kosuke, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 7135   2020.4

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  36. The Therapeutic Effects of Goreisan, a Traditional Japanese Herbal Medicine, on Lower-Limb Lymphedema after Lymphadenectomy in Gynecologic Malignancies: A Case Series Study Reviewed International journal

    Yoshikawa Nobuhisa, Kajiyama Hiroaki, Otsuka Naoki, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Utsumi Fumi, Shibata Kiyosumi, Kikkawa Fumitaka

    EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE   Vol. 2020   page: 6298293 - 6298293   2020.4

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    BACKGROUND: Lower-limb lymphedema (LLL) is a chronic and progressive complication of gynecologic cancer treatment, including pelvic lymphadenectomy. This study aims to investigate the therapeutic effect of goreisan, a traditional Japanese medicine, which has been used for hydrostatic modulation on patients with LLL. METHODS: Patients diagnosed with LLL in our hospital in 2018 were included and principally treated with complex decongestive therapy (CDT), including elastic clothing and lymph drainage. The patients who received a combination therapy of CDT and goreisan (CDT-G group) were prescribed goreisan extract granules, with a dose of 7.5 g per os daily in three doses. Patients who were not prescribed goreisan received CDT alone (CDT group). The severity of lymphedema was evaluated by the estimated limb volume calculated by limb circumferences and the ratio of extracellular water (ECW) to total body water (TBW). RESULTS: Nineteen women with LLL after pelvic lymphadenectomy were included in the study. The number of patients in the CDT and CDT-G groups was 8 and 11, respectively. There were no statistically significant differences between the CDT and CDT-G groups in terms of patient characteristics and severity of LLL before treatment. Reduction in ECW/TBW in the CDT-G group (in the whole body and the affected lower limb) after the intervention was significantly more remarkable than that in the CDT group. CONCLUSIONS: Goreisan-based Japanese herbal therapy may be effective in patients with LLL after retroperitoneal lymphadenectomy.

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  37. The role of additional hysterectomy after concurrent chemoradiation for patients with locally advanced cervical cancer Reviewed

    Yoshida Kosuke, Kajiyama Hiroaki, Yoshihara Masato, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 25 ( 2 ) page: 384 - 390   2020.2

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    DOI: 10.1007/s10147-019-01551-6

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  38. Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway Reviewed

    Yoshikawa Nobuhisa, Liu Wenting, Nakamura Kae, Yoshida Kosuke, Ikeda Yoshiki, Tanaka Hiromasa, Mizuno Masaaki, Toyokuni Shinya, Hori Masaru, Kikkawa Fumitaka, Kajiyama Hiroaki

    SCIENTIFIC REPORTS   Vol. 10 ( 1 ) page: 1614   2020.1

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    DOI: 10.1038/s41598-020-58667-3

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  39. Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer Reviewed International journal

    Yoshida Kosuke, Kajiyama Hiroaki, Inami Eri, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Nawa Akihiro, Kikkawa Fumitaka

    IN VIVO   Vol. 34 ( 1 ) page: 109 - 116   2020.1

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    BACKGROUND: Ubiquitin-associated protein 2-like (UBAP2L) has been demonstrated to be associated with the progression of multiple types of cancer. However, the function of UBAP2L in uterine cervical cancer remains unclear. MATERIALS AND METHODS: Between 2005 and 2015, 84 patients who underwent surgery were included in this study. The patients were stratified into two groups on the basis of immunohistochemical staining for UBAP2L, and survival analysis was performed. Moreover, loss-of-function analysis was performed using the cervical cancer cell lines CaSki and SiHa. RESULTS: Based on immunohistochemistry, the overall survival in patients with low UBAP2L expression was significantly longer than that of those with high UBAP2L expression (p=0.045). The in vitro experiment revealed that knockdown of UBAP2L remarkably inhibited cell proliferation in both live cell imaging and the MTS assay. CONCLUSION: Patients with high UBAP2L expression had unfavorable prognosis and UBAP2L appears to play an important role in proliferation.

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  40. Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age Reviewed

    Hanatani Maya, Yoshikawa Nobuhisa, Yoshida Kosuke, Tamauchi Satoshi, Ikeda Yoshiki, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kawai Michiyasu, Kajiyama Hiroaki, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 25 ( 1 ) page: 187 - 194   2020.1

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  41. Expression of connective tissue growth factor as a prognostic indicator and its possible involvement in the aggressive properties of epithelial ovarian carcinoma Reviewed International journal

    Shimbo Akiko, Kajiyama Hiroaki, Tamauchi Satoshi, Yoshikawa Nobuhisa, Ikeda Yoshiki, Nishino Kimihiro, Suzuki Shiro, Niimi Kaoru, Sakata Jun, Kikkawa Fumitaka

    ONCOLOGY REPORTS   Vol. 42 ( 6 ) page: 2323 - 2332   2019.12

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    Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarify its molecular mechanism and clinical significance. Paraffin sections from clinical samples of EOC (N=104) were immunostained with the CTGF antibody, and then the staining positivity was semiquantitatively examined. Moreover, we explored the role of CTGF expression in the migration‑promoting effect on and chemoresistance of EOC cells. The results revealed that of the 104 EOC patients, the low and high CTGF staining expression rates were 65 (62.5%) and 39 (37.5%), respectively. Patients belonging to the higher‑level CTGF group showed poorer progression‑free (PFS) and overall survival (OS) rates than those in the lower‑level group [PFS (log‑rank: P=0.0076) and OS (log‑rank: P=0.0078), respectively]. Multivariable analysis showed that CTGF expression was a significant predictor of poorer PFS and OS [PFS: HR (high vs. low): 1.837, 95% CI: 1.023‑3.289 (P=0.0418); OS: HR: 2.141, 95% CI: 1.077‑4.296 (P=0.0300)]. In in vitro studies, in acquired paclitaxel (PTX)‑resistant EOC cells, the silencing of CTGF expression led to the restoration of PTX sensitivity. Furthermore, we confirmed that the TGF‑β‑dependent migration‑promoting effect on these CTGF‑depleted cells was completely inhibited. In conclusion, the results of the present study suggest the possible involvement of CTGF in the migration‑promoting effect and chemoresistance of EOC, suggesting that it may be a target for overcoming the malignant properties of EOC.

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  42. Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background Reviewed

    Yoshida Kosuke, Yokoi Akira, Kagawa Takumi, Oda Shingo, Hattori Satomi, Tamauchi Satoshi, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Shibata Kiyosumi, Kajiyama Hiroaki, Yokoi Tsuyoshi, Kikkawa Fumitaka

    CARCINOGENESIS   Vol. 40 ( 12 ) page: 1435 - 1444   2019.12

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  43. COMPREHENSIVE MIRNA SEQUENCING OF SQUAMOUS CELL CARCINOMA ARISING FROM OVARIAN MATURE TERATOMA Reviewed

    Yoshida K, Yokoi A, Tamauchi S, Ikeda Y, Yoshikawa N, Nishino K, Niimi K, Suzuki S, Kajiyama H, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 29   page: A544 - A545   2019.11

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    DOI: 10.1136/ijgc-2019-ESGO.1079

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  44. REDUCED RESPONSE TO CONTROLLED OVARIAN STIMULATION AFTER RADICAL TRACHELECTOMY Reviewed

    Tamauchi S, Kajiyama H, Osuka S, Moriyama Y, Yoshihara M, Iyoshi S, Yoshida K, Ikeda Y, Yoshikawa N, Nishino K, Niimi K, Suzuki S, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 29   page: A269 - A270   2019.11

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  45. Relationship between preexisting mental disorders and prognosis of gynecologic cancers: A case-control study Reviewed International journal

    Tamauchi Satoshi, Kajiyama Hiroaki, Moriyama Yoshinori, Yoshihara Masato, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH   Vol. 45 ( 10 ) page: 2082 - 2087   2019.10

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    AIM: Cancer treatment involves long-term therapy and follow-up, with mental disorders (MD) often affecting the treatment process. Hence, in this study, we retrospectively analyze cases involving gynecologic cancer with MD and clarify the relationship between psychosis and cancer prognosis. METHODS: Patients with both gynecologic cancer and MD from January 2003 to August 2016 were recruited in this study. Cases were limited to those whose MD had been diagnosed before their cancer. Control patients without MD were also analyzed. Both cases and controls were adjusted for age, cancer type, and cancer stage. RESULTS: A total of 54 patients with gynecologic cancer and MD, as well as 108 controls without MD, were included. The median age of the patients was 52 years. Details regarding cancer type were as follows: 11 ovarian cancers, 26 uterine corpus cancers and 17 cervical cancers. Among these, 25 schizophrenia cases, 15 depressive disorders, 4 bipolar disorders and 10 other MD were recorded. No significant differences in the 5-year survival rate were found between patients and controls. In advanced-stage cervical cancer, however, the prognosis was significantly poor given the low rate of initial treatment completion. Moreover, patients with advanced-stage cervical cancer had significantly lower chemotherapy completion rates compared to those with other gynecologic malignancies. CONCLUSION: Mental disorders do not affect the prognosis of gynecologic cancers, except for advanced cervical cancer. Accordingly, improving the low rate of initial treatment completion seems to be a focal point for better prognosis in advanced cervical cancer.

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  46. Comparison of long-term oncologic outcomes between metastatic ovarian carcinoma originating from gastrointestinal organs and advanced mucinous ovarian carcinoma Reviewed

    Kajiyama Hiroaki, Suzuki Shiro, Utsumi Fumi, Yoshikawa Nobuhisa, Nishino Kimihiro, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Eiko, Kawai Michiyasu, Shibata Kiyosumi, Nagasaka Tetsuro, Kikkawa Fumitaka

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 24 ( 8 ) page: 950 - 956   2019.8

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    BACKGROUND: Occasionally, ovarian tumors are found to have originated from non-ovarian organs as metastatic lesions since the ovary is a common site of metastasis from many cancers. The aim of the current study was to estimate the long-term oncologic outcome of patients with metastatic mucinous ovarian carcinoma (MmOC) in comparison with those with primary mucinous ovarian carcinoma (PmOC) at an advanced stage. MATERIALS AND METHODS: The data of one hundred and sixty-seven patients with mucinous ovarian cancer, including 91 patients with MmOC from the digestive organs and 76 patients with stage III-IV PmOC, were retrospectively analyzed. The prognostic significances of clinicopathologic factors were evaluated employing both uni- and multivariable analyses. Pathological slides were evaluated based on centralized pathological review. RESULTS: The median age of patients with PmOC and MmOC was 55 (18-81) and 51 years (30-82), respectively. With follow-up of a total of 167 patients, 145 patients (86.8%) developed recurrence. In addition, 122 patients (73.0%) died of the disease. Regardless of the residual tumor status, patients with PmOC did not a show a significantly poorer OS than those with MmOC. Furthermore, in a Cox multivariable hazard model, after adjustment for various clinicopathologic confounders, a gastric cancer (GC)-originated tumor and larger residual tumor were significant predictors of poorer OS [GC (vs. PmOC): HR (95% CI) 2.205 (1.303-3.654), P = 0.0036]. CONCLUSION: The oncologic outcome of patients with MmOC was extremely poor; however, it was almost the same as that of those with PmOC. We should recognize MmOC derived from gastric carcinoma as a highly aggressive malignancy.

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  47. Does postoperative prophylactic irradiation of para-aortic lymph nodes reduce the risk of recurrence in uterine cervical cancer with positive pelvic lymph nodes? Reviewed

    Yoshida K, Kajiyama H, Yoshihara M, Ikeda Y, Yoshikawa N, Nishino K, Utsumi F, Niimi K, Suzuki S, Kikkawa F

    International journal of clinical oncology   Vol. 24 ( 5 ) page: 567 - 574   2019.5

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    DOI: 10.1007/s10147-018-1376-2

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  48. Reproductive outcomes of 105 malignant ovarian germ cell tumor survivors: a multicenter study Reviewed International journal

    Tamauchi Satoshi, Kajiyama Hiroaki, Yoshihara Masato, Ikeda Yoshiki, Yoshikawa Nobuhisa, Nishino Kimihiro, Utsumi Fumi, Niimi Kaoru, Suzuki Shiro, Kikkawa Fumitaka

    AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY   Vol. 219 ( 4 ) page: 385.e1 - 385.e7   2018.10

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    BACKGROUND: Malignant ovarian germ cell tumors usually occur in young women. Until the 1970s, before establishment of systemic chemotherapy, malignant ovarian germ cell tumors had a very poor prognosis. Recently, prognosis has improved, and fertility-sparing treatment is being adopted in patients who desire to become pregnant. However, the number of malignant ovarian germ cell tumor survivors who actually became pregnant remains unknown. OBJECTIVE: The present study aimed to clarify the reproductive outcomes in malignant ovarian germ cell tumor survivors by using data from a multicenter database and an additional survey on reproductive outcomes. STUDY DESIGN: The study used the Tokai Ovarian Tumor Study Group database on ovarian cancer patients. We assessed the database from 1986 through 2016 and selected malignant ovarian germ cell tumor patients <40 years of age who received fertility-sparing treatment. Questionnaires on reproductive outcomes were sent to the registered facilities. The following data were collected and used in this study: age, date of onset, surgical procedure, chemotherapy regimen, tumor type, International Federation of Gynecology and Obstetrics stage, survival outcome and period, number of pregnancies and childbirths, marital status, childbearing desire, method of pregnancy, gestational weeks at delivery, birthweight of the baby, obstetric complications, and menstrual status after fertility-sparing treatment. RESULTS: A total of 110 malignant ovarian germ cell tumor patients who received fertility-sparing treatment were identified. The median follow-up period was 10.4 years. Five patients were excluded because of death or loss of fertility after treatment for recurrence. Thus, 105 patients were finally included. The additional survey revealed that 42 of 45 patients who desired childbirth became pregnant. The total number of pregnancies was 65, and 56 babies were born to 40 malignant ovarian germ cell tumor survivors. CONCLUSION: The reproductive outcomes of malignant ovarian germ cell tumor survivor are promising with fertility-sparing treatment. Malignant ovarian germ cell tumor survivors can become pregnant and give birth if they desire.

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  49. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY Reviewed

    NIimi Kaoru, Ikeda Yoshinori, Nishino Kimihiro, Yamamoto Eiko, Kikkawa Fumitaka

    PLACENTA   Vol. 69   page: E29 - E29   2018.9

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  50. GENETIC STUDY ON ORIGINS OF CHORIOCARCINOMAS BY SHORT TANDEM REPEAT ANALYSIS Reviewed

    Nishino Kimihiro, Nakamura Kenichi, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Eiko, Yamamoto Toshimichi, Kikkawa Fumitaka

    PLACENTA   Vol. 69   page: E88 - E89   2018.9

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  51. CLINICAL CHARACTERISTICS OF PSTT AND ETT IN JAPAN Reviewed

    Niimi K., Yamamoto E., Nishino K., Nakamura K., Ikeda Y., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 919 - 919   2018.9

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  52. SHORT TANDEM REPEAT ANALYSIS DISTINGUISHING THE GENOTYPE OF CHORIOARCINOMA Reviewed

    Nishino K., Yamamoto E., Watanabe E., Nakamura K., Ikeda Y., Niimi K., Yamamoto T., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 920 - 920   2018.9

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  53. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY Reviewed

    Nakamura K., Kaoru N., Ikeda Y., Nishino K., Yamamoto E., KIkkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 195 - 195   2018.9

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  54. PROPENSITY SCORE ADJUSTED ANALYSIS OF PROPHYLACTIC IRRADIATION TO PARA-AORTIC LYMPH NODE AFTER RADICAL HYSTERECTOMY FOR UTERINE CERVICAL CANCER. Reviewed

    Yoshida K., Yoshihara M., Ikeda Y., Yoshikawa N., Nishino K., Utumi F., Niimi K., Suzuki S., Kajiyama H., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 447 - 447   2018.9

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  55. EFFECT OF CONCURRENT CHEMO-RADIOTHERAPY ON CLINICAL OUTCOMES IN SMALL CELL CARCINOMA OF THE UTERINE CERVIX Reviewed

    Ikeda Y., Kajiyama H., Yoshida K., Yoshikawa N., Nishino K., Utsumi F., Niimi K., Suzuki S., Kawai M., Kikkawa F.

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 294 - 294   2018.9

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  56. CLINICAL CHARACTERISTICS OF PSTT AND ETT IN JAPAN Reviewed

    Niimi K, Yamamoto E, Nishino K, Nakamura K, Ikeda Y, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 919 - 919   2018.9

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  57. SHORT TANDEM REPEAT ANALYSIS DISTINGUISHING THE GENOTYPE OF CHORIOARCINOMA Reviewed

    Nishino K, Yamamoto E, Watanabe E, Nakamura K, Ikeda Y, Niimi K, Yamamoto T, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 920 - 920   2018.9

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  58. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY Reviewed

    Nakamura K, Kaoru N, Ikeda Y, Nishino K, Yamamoto E, KIkkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 195 - 195   2018.9

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  59. ROLE OF CORE 2 beta 1, 6-N ACETYLGLCOSAMINYL TRANSFERASE IN EVASION MECHANISM THROUGH NK CELL IMMUNITY Reviewed

    NIimi Kaoru, Ikeda Yoshinori, Nishino Kimihiro, Yamamoto Eiko, Kikkawa Fumitaka

    PLACENTA   Vol. 69   page: E29-E29   2018.9

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  60. PROPENSITY SCORE ADJUSTED ANALYSIS OF PROPHYLACTIC IRRADIATION TO PARA-AORTIC LYMPH NODE AFTER RADICAL HYSTERECTOMY FOR UTERINE CERVICAL CANCER. Reviewed

    Yoshida K, Yoshihara M, Ikeda Y, Yoshikawa N, Nishino K, Utumi F, Niimi K, Suzuki S, Kajiyama H, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 447 - 447   2018.9

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  61. GENETIC STUDY ON ORIGINS OF CHORIOCARCINOMAS BY SHORT TANDEM REPEAT ANALYSIS Reviewed

    Nishino Kimihiro, Nakamura Kenichi, Ikeda Yoshiki, Niimi Kaoru, Yamamoto Eiko, Yamamoto Toshimichi, Kikkawa Fumitaka

    PLACENTA   Vol. 69   page: E88-E89   2018.9

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  62. EFFECT OF CONCURRENT CHEMO-RADIOTHERAPY ON CLINICAL OUTCOMES IN SMALL CELL CARCINOMA OF THE UTERINE CERVIX Reviewed

    Ikeda Y, Kajiyama H, Yoshida K, Yoshikawa N, Nishino K, Utsumi F, Niimi K, Suzuki S, Kawai M, Kikkawa F

    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER   Vol. 28   page: 294 - 294   2018.9

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  63. Fertility-sparing surgery of malignant transformation arising from mature cystic teratoma of the ovary. Reviewed International journal

    Yoshikawa N, Teshigawara T, Ikeda Y, Nishino K, Sakata J, Utsumi F, Niimi K, Sekiya R, Suzuki S, Kawai M, Shibata K, Kikkawa F, Kajiyama H

    Oncotarget   Vol. 9 ( 44 ) page: 27564 - 27573   2018.6

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    BACKGROUND: The purpose of this study was to evaluate the long-term clinical outcome of young women with malignant transformation arising from mature cystic teratoma of the ovary (MT-MCT) by comparing radical surgery and fertility-sparing surgery (FSS). PATIENTS AND METHODS: All patients treated with radical surgery or FSS for MT-MCT in multiple institutions were registered in this analysis. Univariate and multivariate analyses were performed to evaluate clinical outcome, including overall survival (OS) and disease-free survival (DFS). RESULTS: From 1986 to 2016, 62 patients with MT-MCT were treated in our group. The median follow-up period was 38.0 (2.0-227.9) months, and the median age was 54 (17-82) years old. Multivariate analysis revealed that only advanced stage was significantly correlated with poorer prognosis of patients [hazard ratio (HR) for death: 6.58, 95% confidence interval (CI): 1.82-24.78, P = 0.0048; HR for recurrence: 5.59, 95% CI: 1.52-21.83, P = 0.01]. Of a total of 13 women with stage I-II disease at less than 45 years old, 7 were treated with FSS, and there was no recurrence except for in one woman with stage II MT-MCT. There was no significant difference in long-term oncological outcome between radical surgery and FSS. CONCLUSION: FSS may be indicated for patients with stage I MT-MCT, who hope to preserve fertility, as no relapse was found after FSS.

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Books 1

  1. FUSE資格者が教える電気メス

    渡邊 祐介(エネルギーデバイス用語集 フェーズ2 エディター)

    メジカルビュー社  2022.4  ( ISBN:978-4-7583-0468-9

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KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 臨床情報と人工知能を基盤とした卵巣腫瘍診断システムの構築

    Grant number:23K08795  2023.4 - 2026.3

    科学研究費助成事業  基盤研究(C)

    池田 芳紀, 小泉 憲裕

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    本研究の目的は、医療技能のデジタル化(医デジ化)により卵巣腫瘍の革新的診断システムを開発することである。卵巣腫瘍の確定診断は手術以外には困難である。病歴、腫瘍マーカー、超音波検査、MRI、CT等の情報から、手術前に卵巣腫瘍の良・悪性や病理組織型を医師が勘や経験に基づき推定している。本研究で構築するのは、人工知能(AI)技術を用いてこの医師の技能をデジタルに再現し、術後に確定した病理組織型の情報から学習を積むことによって、人間を超える高い精度で卵巣腫瘍の良・悪性、病理組織型を術前に診断するシステムである。卵巣悪性腫瘍の早期発見手法として研究を発展させ、最終的には卵巣悪性腫瘍の死亡率低下を目指す。

  2. 医療技能のデジタル化で実現する卵巣腫瘍の革新的診断システムの開発

    Grant number:20K09667  2020.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    池田 芳紀, 小泉 憲裕

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    Authorship:Principal investigator 

    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    本研究の目的は、医療技能のデジタル化(医デジ化)により卵巣腫瘍の革新的診断システムを開発することである。卵巣腫瘍の確定診断は手術以外には困難である。病歴、腫瘍マーカー、超音波検査、MRI、CT等の情報から、手術前に卵巣腫瘍の良・悪性や病理組織型を医師が勘や経験に基づき推定している。本研究で提案するのは、人工知能(AI)技術を用いてこの医師の技能をデジタルに再現し、術後に確定した病理組織型の情報から学習を積むことによって、人間を超える高い精度で卵巣腫瘍の良・悪性、病理組織型を術前に診断するシステムである。卵巣悪性腫瘍の早期発見手法として研究を発展させ、最終的には卵巣悪性腫瘍の死亡率低下を目指す。
    本研究の目的は、医療技能のデジタル化により、卵巣腫瘍の革新的診断システムを開発することである。卵巣腫瘍の術前診断は、臨床情報、各種検査データを参考に、医師が良・悪性を推定している。熟練した画像診断医は、画像読影時に卵巣腫瘍の病理組織型まで推定している。人工知能技術を用いてこの医師の技能をデジタル化し機能としてシステムに実装し、学習を積むことで、人間を超える高い診断精度を実現する。卵巣悪性腫瘍の早期発見手法として発展・確立し、ゴールは卵巣悪性腫瘍の死亡率減少である。本研究は下記の4つのステップで卵巣腫瘍の診断システムの開発を行う。本研究期間においては1~2のステップを繰り返してシステムの性能を高め、有効性を検証する。当該年度は1の段階で最初の目標である約200症例分のデータの抽出を終え、研究分担者のグループにデータを集積した。複数の機械学習モデルで学習し評価を行った。問題点を抽出し、1~2のステップを繰り返して診断精度の向上を図っている最中である。
    1.名古屋大学産婦人科で治療した卵巣腫瘍症例の診療情報、検査データの抽出・解析;名古屋大学産婦人科で治療した卵巣腫瘍症例の患者臨床情報、血液・画像検査データ、摘出物の最終病理組織型の情報を抽出する。研究分担者のグループに集積して解析し、システムの枠組みを構築する。
    2.システムの性能の評価;上記で使用していない卵巣腫瘍症例のデータをシステムに入力し、出力された良性・境界悪性・悪性の診断と病理組織型の正診率を評価する。
    3.症例数を拡大し診断精度の向上を図る;名古屋大学産婦人科と複数の関連病院で組織する東海卵巣腫瘍研究会の登録症例へとデータの集積を拡大する。
    4.卵巣悪性腫瘍の早期発見に向けてシステムの発展・確立;一般的な検診で収集可能な臨床情報・血液検査データと経腟超音波データのみで診断を可能にし、早期発見手法として実用化を検討する。
    進捗状況としては大幅に遅れている。COVID-19感染症の流行により本研究期間のスタート時点からすでに研究活動に制限がかかっていたことが最大の原因である。昨年度で、名古屋大学産婦人科で治療した卵巣腫瘍症例の患者臨床情報、血液・画像検査データ、摘出物の最終病理組織型の情報を抽出し、研究分担者のグループに集積して解析し、システムの枠組みを構築する予定であった。まず初めに必要な作業としては、多数例の臨床情報、検査データ、画像データを匿名化して収集することである。データ収集のためには研究補助員が電子カルテシステムを参照する必要があり、施設に出勤しての作業がどうしても必要なため、テレワーク下では作業困難であった。データ収集作業が当初の予定通りスタートできず計画より大幅に遅れを生じた。一昨年度から昨年度で、最初の目標であった約200症例分の患者臨床情報、血液・画像検査データ、摘出物の最終病理組織型の情報の抽出を終え、昨年度から今年度にかけて研究分担者のグループへのデータ集積作業を行った。また、今年度は複数の機械学習モデルで学習、評価を行い、機械学習モデルの再検討を繰り返し行っているがまだ十分な診断精度が得られていない。研究分担者のグループでのデータ解析・システムの枠組みの構築を次年度も引き続き行っていく。
    最初の目標であった約200症例分の患者臨床情報、血液・画像検査データ、摘出物の最終病理組織型の情報の抽出を終え、研究分担者のグループへのデータ集積作業を行い、複数の機械学習モデルで学習、評価を行った。まだ十分な診断精度が得られておらず、機械学習モデルの再検討が必要な状況で、今後も引き続き学習、評価を繰り返していく必要がある。また、臨床情報・血液検査データと同じ機械学習モデルで画像検査データを扱うために、どのような手法で画像検査データを処理するかが大きな課題となっている。次年度は研究代表者のグループで機械学習を用いた研究経験がある研究補助員を確保しており、データ解析作業を推進する。今後の研究の進捗をみながら、さらに研究分担者のグループで本研究に携わる大学院生の増員も視野に入れ、研究分担者と綿密に相談・検討しながら本研究を推進していく。

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  3. Development of novel intraperitoneal therapy based on atmospheric pressure plasma for complete removal of peritoneal dissemination

    Grant number:19K21346  2019.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    Ikeda Yoshiki

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    Authorship:Principal investigator 

    Grant amount:\2990000 ( Direct Cost: \2300000 、 Indirect Cost:\690000 )

    Anti-tumor effects of plasma-activated medium (PAM) on endometrial cancer remain unknown. Our results demonstrated that PAM inhibited cell viabilities by inducing autophagic cell death in endometrial cancer cells. We investigated the inhibitory effect of PAM on the viabilities of endometrial cancer cells in vitro. Our data showed that the viabilities of AMEC and HEC50 endometrial cancer cell lines were decreased by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. In addition, we evaluated the molecular mechanism of PAM activity and found that PAM treatment in both HEC1A and HEC50 endometrial cancer cells increased the protein expression of LC3B which is a biomarker of autophagy.

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Teaching Experience (On-campus) 4

  1. 産婦人科学

    2023

  2. 産婦人科学

    2022

  3. 現代医療と生命科学

    2021

  4. 産婦人科学

    2021