研究者詳細 - 坂井　健良

坂井　健良（サカイ　ケンスケ）

Sakai, Kensuke

写真a

所属（所属キャンパス）: 医学部産婦人科学教室（信濃町）

職名: 専任講師（有期）

Scopus 論文情報

Click to view the Scopus page. The data was downloaded from Scopus API inApril 26, 2026, via http://api.elsevier.com and http://www.scopus.com .

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Identification of sentinel lymph nodes in gynecologic surgery

Sakai K., Yamagami W., Susumu N., Aoki D., Fluorescence Guided Surgery from Lab to Operation Room, 2023年11月

　概要を見る

Gynecologic malignancies, especially cervical, endometrial, and vulvar cancers, mainly progress by lymphatic metastasis, and therefore, systematic lymph node dissection is performed in many patients. On the other hand, the rates of lymph node metastasis in pT1 and pT2 patients are about 15.8% in cervical cancer, 5.9% in endometrial cancer, and 25% in vulvar cancer [1, 2]. Therefore, the decrease in QOL due to postoperative lymphedema and lymphatic cysts caused by lymph node dissection is becoming a growing issue corresponding to the improvement of long-term outcomes.
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Elevated 18F-FDG uptake in non-metastatic lymph nodes of POLE-mutated endometrial cancer on PET/CT

Kurihara M., Iwabuchi Y., Yamada Y., Shimizu A., Yoshimura T., Sakai K., Chiyoda T., Nakamura K., Nishihara H., Yamagami W., Jinzaki M.

European Journal of Radiology 195 2026年02月

ISSN 0720048X

　概要を見る

Purpose DNA polymerase epsilon ( POLE ) exonuclease domain-mutated endometrial cancer (EC) is associated with a favorable prognosis and significant immune cell infiltration. Cancers with significant immune cell infiltration often exhibit higher maximum standardized uptake value (SUVmax) on <sup>18</sup>F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT). This study aimed to evaluate the correlation between POLE status and FDG-PET/CT imaging in patients with EC. Methods This retrospective study enrolled 102 patients (mean age, 56.2 ± 11.8 years) with EC who underwent preoperative FDG-PET/CT between July 2018 and August 2023. Patients were categorized into molecular subtypes based on molecular profiling. SUVmax of the primary tumor and lymph nodes was measured, and correlations with molecular subtypes were examined. Results The SUVmax in the primary tumor of POLE -mutated ECs was higher than that in non- POLE -mutated ECs (mean ± SD, 13.21 ± 4.78 vs 9.82 ± 3.78; p = 0.001). Multiple regression analysis showed that POLE status was associated with SUVmax in primary tumors (B = 2.30, p = 0.031). The SUVmax in non-metastatic lymph nodes of POLE -mutated ECs was higher than that in non -POLE- mutated ECs (median SUVmax, 1.31 [IQR, 1.05–2.21] vs. 1.06 [IQR, 0.91–1.20]; p = 0.003). Multiple regression analysis revealed that POLE status was the only factor associated with SUVmax in non-metastatic lymph nodes (B = 0.339, p = 0.046), while age, BMI, blood glucose level, histological type, and primary tumor size showed no significant association. Conclusion Patients with POLE -mutated EC exhibit high SUVmax in primary tumors and also tend to show elevated uptake in non-metastatic lymph nodes.
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Prognostic Biomarker of Fertility-Preserving Hormonal Therapy Based on Multigene Panel Testing for Endometrial Cancer

Hirano T., Sakai K., Yoshimura T., Chiyoda T., Nakamura K., Aimono E., Kawaida M., Nishihara H., Susumu N., Aoki D., Yamagami W.

Cancer Science 117 （ 1 ） 236 - 245 2026年01月

ISSN 13479032

　概要を見る

In this study, we identified prognostic biomarkers that predict treatment outcome in patients receiving fertility-preserving high-dose medroxyprogesterone acetate (MPA) therapy through comprehensive multigene panel testing. A total of 38 patients (20 atypical endometrial hyperplasia and 18 stage IA G1 without myometrial invasion) who received first-line MPA therapy were enrolled. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples, and PleSSision-Rapid multigene panel testing was performed. Of the 38 patients, 31 (82%) achieved complete response (CR), 2 (5%) had stable disease (SD), and 5 (13%) had progressive disease (PD) following initial treatment. The median duration to achieve tumor disappearance was 7 months (range: 4–14 months). Following initial treatment, 25 of 32 patients (78%) experienced recurrence, with a median recurrence-free survival (RFS) of 21 months (range: 2–84 months). The most frequently observed actionable gene mutations were PTEN (68.4%), CTNNB1 (55.2%), and PIK3CA (33.3%). Patients harboring PTEN mutations in EMG1 required a significantly longer duration to achieve tumor disappearance (p = 0.011). In addition, the presence of PIK3CA mutations in AEH was significantly associated with shorter RFS (p = 0.048). Molecular classification identified 34 patients (89%) with no specific molecular profile (NSMP), 1 patient (3%) with POLE mutation, and 3 patients (8%) with deficient mismatch repair (d-MMR). Most patients undergoing MPA therapy were classified as having NSMP. Genetic alterations, specifically mutations in PTEN and PIK3CA, were significantly associated with treatment outcomes, highlighting their potential as prognostic biomarkers.
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Up-to-Date Chemotherapy for Endometrial Cancer

Sakai K., Yamagami W.

Gan to Kagaku Ryoho Cancer Chemotherapy 52 （ 12 ） 864 - 868 2025年12月

ISSN 03850684

　概要を見る

For many years, drug therapy for endometrial cancer has centered on chemotherapy regimens such as adriamycin+cisplatin(AP)or paclitaxel+carboplatin(TC). In recent years, however, the introduction of immune checkpoint inhibitors(ICIs)has dramatically changed the treatment landscape. Multiple phase Ⅲ trials(eg, NRG-GY018, DUO-E)have demonstrated that adding ICIs to TC chemotherapy improves prognosis, and in 2024 combination therapies with pembrolizumab or durvalumab were approved in Japan for advanced or recurrent endometrial cancer. Additionally, development of antibody-drug conjugates(ADCs)is underway, and ADCs targeting HER2, TROP2, and other tumor-specific antigens are anticipated to become new therapeutic options.
Characteristics of endometrial cancer progressed to extrauterine lesions following fertility preserving medroxyprogesterone acetate therapy for young endometrial cancer patients

Kitazawa S., Sakai K., Kawaida M., Chiyoda T., Nishio H., Banno K., Susumu N., Yamagami W.

Journal of Gynecologic Oncology 36 （ 6 ） 2025年11月

ISSN 20050380

　概要を見る

Objective: Medroxyprogesterone acetate (MPA) is an effective fertility-preserving treatment for early endometrial cancer and atypical endometrial hyperplasia (AEH), and rarely leads to the development of extrauterine lesions (ELs). We aimed to clarify the characteristics of patients who developed ELs post-MPA therapy. Methods: We analyzed the clinicopathological factors and prognoses of 319 patients with endometrioid carcinoma grade 1 (EMG1) and AEH treated with MPA at our institution. All patients underwent imaging before MPA treatment to rule out ELs. Results: Seven patients (2.2%) with EMG1 showed EL after MPA treatment. Two patients developed EL during the initial treatment, 2 during repeated treatment, and 3 during follow-up. Two patients had peritoneal dissemination, 3 had regional lymph node metastasis, 1 had distant metastasis at the Virchow lymph node, and 1 had ovarian metastasis. ELs were diagnosed using imaging tests in 6 patients and elevated tumor markers in 3 (overlapping) patients. One patient was diagnosed with ELs pathologically after hysterectomy. Upon EL diagnosis, patients underwent standard treatment, including hysterectomy and chemotherapy, that was followed by a diagnosis of EMG1 for 5, EMG2 for 1, and EMG3 for 1 patient. One patient died 15 months after start of therapy and another died 119 months post-treatment initiation, while the others have been survived. Conclusion: Only 2.2% of all patients developed ELs post-MPA treatment, but some cases were fatal. It is essential to conduct imaging tests and screen for tumor markers during and after MPA treatment regularly and also when cancer progression is suspected.
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High-Throughput Drug Screening of Clear Cell Ovarian Cancer Organoids Reveals Vulnerability to Proteasome Inhibitors and Dinaciclib and Identifies AGR2 as a Therapeutic Target

Yoshimura T., Kamatani T., Ookubo A., Takahashi M., Itoh M., Ebisudani T., Masugi Y., Toyonaga T., Hamamoto J., Saotome K., Sakai K., Yoshihama T., Moritoki N., Shibata S., Yasuda H., Sato T., Sato T.A., Aoki D., Yamagami W., Tsunoda T., Chiyoda T.

Cancer Research Communications 5 （ 6 ） 1018 - 1033 2025年06月

　概要を見る

There are currently no effective treatments available for clear cell ovarian cancer (CCC). In this study, we aimed to identify effective drugs for CCC through high-throughput drug screening (HTDS) using ovarian cancer organoids and determine novel therapeutic targets based on the biological characteristics of CCC through omics analysis. An ovarian cancer organoid biobank was established, and HTDS was conducted using CCC organoids based on libraries of 361 and 4,560 compounds. The efficacy of the identified drugs was verified in in vitro and in vivo experiments using a patient-derived organoid xenograft mouse model. Transcriptome analysis was performed to identify genes related to the pathways targeted by the identified drugs in CCC and to assess their potential as therapeutic targets. Proteasome inhibitors and dinaciclib were extracted using HTDS and shown to inhibit tumorigenesis in vitro and in vivo. CCC, like multiple myeloma, exhibited activated endoplasmic reticulum (ER) stress and unfolded protein response (UPR), and treatment with proteasome inhibitors further enhanced ER stress and UPR, ultimately leading to cell death. Transcriptome analysis identified anterior gradient-2 (AGR2) as a key gene involved in UPR in CCC. CRISPR knockout of AGR2 suppressed cell proliferation, increased sensitivity to proteasome inhibitors, and reversed platinum resistance in CCC. AGR2 knockout also upregulated Schlafen 11, contributing to platinum sensitivity. ER stress and the UPR are activated in CCC, and proteasome inhibitors disrupt this balance, ultimately leading to cell death. AGR2 may serve as a potential therapeutic target in CCC.
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