出版者・発行元：(有)科学評論社  

DOI： 10.69337/d202604-094-05

CiNii Research

記述言語：日本語   出版者・発行元：公益社団法人 日本婦人科腫瘍学会  

<p>概要：妊娠性絨毛性腫瘍（GTN）は，胎盤栄養膜細胞の異常増殖を来す腫瘍性疾患であり，絨毛癌診断スコア・FIGO 2000リスク分類を用いた診断が行われる．これらの診断法では，臨床的絨毛癌はHigh-risk GTNに，臨床的侵入奇胎はLow-risk GTNに対応するが，診断の不一致症例も存在する．本研究は，1991～2023年に当院で治療を受けたGTN 273例を対象とし，両診断法の相関性と治療成績を報告する．結果として，臨床的絨毛癌かつHigh-risk GTN，臨床的侵入奇胎かつLow-risk GTNとなる症例の割合は92.2％であった．また，病理学的診断と絨毛癌診断スコアの一致率は92.7％であった．治療方針は，病理学的診断・絨毛癌診断スコアによって決定され，全生存率は絨毛癌群で84.9％，非絨毛癌群で99.5％であった．なお，絨毛癌かつLow-risk GTN症例は多剤併用療法を，侵入奇胎かつHigh-risk GTN症例は単剤療法を受け，全生存率は100％であった．総じて，両診断法は概ね一致するが，絨毛癌診断スコアの方が病理学的診断との一致率が高く，有用性が高いと考えられる．</p>

DOI： 10.57291/jsgo.44.2_146

CiNii Research

記述言語：英語   出版者・発行元：Frontiers in Oncology  

Small-cell carcinoma of the cervix (SCCC) is a rare and highly aggressive histological subtype of cervical cancer, associated with poor prognosis. SCCC is histologically classified as a neuroendocrine tumor and has the potential to produce ectopic hormones, leading to various paraneoplastic syndromes. This report is a rare case of recurrent SCCC presenting with psychiatric symptoms due to endogenous Cushing’s syndrome caused by ectopic adrenocorticotropic hormone (ACTH) production. The patient initially developed mood and behavioral disturbances as the disease progressed, leading to hospitalization under the suspicion of a primary psychiatric disorder. However, further evaluation, prompted by the discovery of severe hypokalemia, revealed Cushing’s syndrome associated with clinically diagnosed ectopic ACTH production in the setting of recurrent disease. Her psychiatric symptoms rapidly remitted following the administration of a cortisol synthesis inhibitor. This case highlights the importance of considering endocrine disorders as potential causes of psychiatric manifestations in patients with cancer, particularly those with neuroendocrine tumors such as SCCC. Acute and marked elevation of endogenous cortisol can induce distinct psychiatric symptoms, such as manic features and grandiose delusions, that often respond better to endocrine treatment aimed at normalizing cortisol levels rather than to antipsychotic therapy alone. Clinicians should be aware of this rare but important clinical presentation as timely diagnosis and management can improve patient outcomes.

DOI： 10.3389/fonc.2026.1684861

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PubMed

記述言語：英語   出版者・発行元：Placenta  

Objective: Choriocarcinoma is a rare cancer associated with antecedent pregnancy. Therefore, its development may be influenced by an immune-evasive tumor microenvironment. In this study, we focused on natural killer (NK) cells to elucidate the immune microenvironment of choriocarcinoma. Methods: Peripheral blood and intratumoral NK cells were isolated from six samples of four patients with choriocarcinoma. Flow cytometry was used to analyze the NK cell proportion. Immunohistochemistry was performed to assess the expression of NK cell inhibitory ligands using choriocarcinoma tissues from 17 patients. In addition, choriocarcinoma cell lines (JAR, BeWo, and JEG-3) were cocultured with interleukin-2-stimulated NK cells, and loss-of-function analyses of HLA-E were conducted to investigate the impact of NK cells on choriocarcinoma cells. Results: Flow cytometry revealed that NK cells were more abundant in choriocarcinoma tissues than in the peripheral blood. Immunohistochemistry confirmed the expression of NK cell inhibitory ligands, including HLA-E. Moreover, JAR cells were cocultured with NK cells, and viable JAR cells were isolated by flow cytometry. Subsequent mRNA sequencing showed that HLA-E was upregulated, and multiple cytokine-related pathways were activated in the cocultured JAR cells compared with monocultured JAR cells. Functional assays demonstrated that HLA-E knockdown enhanced NK-cell-mediated cytotoxicity, whereas interferon-gamma treatment increased HLA-E expression and promoted tumor cell survival. Conclusion: These findings suggest that NK cells may play an important role in the tumor immune microenvironment of choriocarcinoma through HLA-E expression.

DOI： 10.1016/j.placenta.2025.11.012

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

Background: Uterine sarcoma has an inferior prognosis and high recurrence rate among gynecological malignancies, even in early-stage cases with complete resection. However, the risk factors for recurrence remain poorly understood. This study aimed to identify risk factors associated with recurrence in early-stage uterine sarcoma. Methods: Among 97 patients with uterine sarcoma treated at our institution between January 2007 and June 2023, we retrospectively investigated 55 patients of the following five histological types: uterine leiomyosarcoma (ULMS), low- or high-grade endometrial stromal sarcoma (LG-ESS or HG-ESS), adenosarcoma, and smooth muscle tumor of uncertain malignant potential (STUMP). Risk factors were compared between the recurrence and non-recurrence groups using univariate analysis, and recurrence rates, time to recurrence, progression-free survival (PFS), and overall survival (OS) were examined. Results: The median age of 55 patients was 48 years, and the most common initial symptom was abdominal pain or abdominal mass awareness (29.4%), followed by abnormal bleeding in 25.5% of the patients. The median tumor size was 9.7 cm, and stage I cases were 64.8% of the total. Histological types were 28 ULMS, 13 LG-ESS, 8 STUMP, 5 HG-ESS, and one adenosarcoma. Among stage I cases, ULMS had a recurrence rate of 81.3% with a median time to recurrence of 12.4 months, while LG-ESS had a recurrence rate of 30% with a median time to recurrence of 41.1 months. A high mitotic count was significantly associated with recurrence in stage I ULMS (p = 0.044). Other surgical pathological findings, such as lymphovascular space invasion, MIB-1 positive rate, and necrosis, and surgical factors, such as myomectomy and ovarian preservation, showed no statistically significant differences but were higher in the recurrence cases. The 5-year PFS rates in stage I ULMS and LG-ESS groups were 31.3% and 75%, and the 5-year OS rates were 68.5% and 100%, respectively. Conclusions: In stage I ULMS, a high mitotic count was associated with an increased risk of recurrence after complete surgical resection.

DOI： 10.1186/s12885-026-15618-x

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記述言語：英語   出版者・発行元：Cancer Science  

Choriocarcinoma is a rare gynecologic malignancy. MicroRNAs, which are noncoding RNAs approximately 22 nucleotides in length, are known to regulate gene expression and play important roles in various cancers; however, their functions in choriocarcinoma remain largely unknown. This study aimed to identify disease-specific microRNAs involved in choriocarcinoma development. Eleven cases of choriocarcinoma and five cases of complete hydatidiform mole treated at our institution were analyzed. Total RNA was extracted from trophoblast cells in formalin-fixed, paraffin-embedded specimens using laser capture microdissection, and microRNA sequencing was performed. The analysis revealed that 87 microRNAs were significantly upregulated, whereas 28 were downregulated in choriocarcinoma compared to complete hydatidiform mole. Notably, 13 of the 28 downregulated microRNAs belonged to the chromosome 19 microRNA cluster. In vitro experiments demonstrated that overexpression of miR-517a-3p, a representative member of this cluster, significantly suppressed cell proliferation, migration, and invasion in JEG-3 and BeWo cell lines. Further transcriptome sequencing and computational analysis identified SRSF1 as a target gene of miR-517a-3p, which was validated by dual-luciferase reporter assays. Knockdown of SRSF1 also led to significant reductions in proliferation, migration, and invasion, supporting its functional relevance. Immunohistochemical analysis confirmed that SRSF1 protein was highly expressed in choriocarcinoma tissues compared to complete hydatidiform mole. These findings indicate that downregulation of the chromosome 19 microRNA cluster is a characteristic feature of choriocarcinoma and that miR-517a-3p functions as a tumor suppressor by directly regulating SRSF1 expression.

DOI： 10.1111/cas.70207

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記述言語：英語   出版者・発行元：Npj Precision Oncology  

Poly(ADP-ribose) polymerase inhibitors (PARPis) have improved the prognosis of patients with high-grade serous ovarian carcinoma (HGSOC). However, PARPis are not effective for all HGSOC patients. Spatial transcriptomics is a powerful tool for characterizing the tumor microenvironment. We used Visium to analyze eight tumor samples from HGSOC patients with clinical information on PARPi sensitivity. Two complementary analyses were performed: an integrated analysis across all samples, without considering spatial information, and an analysis with spatial information within each sample. Both approaches indicated that midkine (MDK) signaling is involved in PARPi resistance. Furthermore, we identified receptors that enhance MDK signaling in cancer cells. To assess the generalizability of this finding, we deconvolved bulk RNA-sequencing data using single-cell RNA-sequencing data as a reference to examine the relationship between receptor expression levels and overall survival (OS). This analysis revealed that high SDC4 expression in cancer cells is associated with poor OS in HGSOC patients.

DOI： 10.1038/s41698-025-01122-1

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記述言語：英語   出版者・発行元：Scientific Reports  

Malignant ovarian tumors (MOTs) and borderline ovarian tumors (BOTs) differ in treatment strategies and prognosis. However, accurate preoperative diagnosis remains challenging, and improving diagnostic accuracy is crucial. We developed and validated a system using artificial intelligence (AI) to integrate machine learning (ML) models based on blood test data and deep learning (DL) models based on magnetic resonance imaging (MRI) findings to distinguish between MOT and BOT. We analyzed 78 patients with malignant serous ovarian tumors and 31 with borderline serous ovarian tumors treated at our institution. A classification model was developed using ML for blood test data, and a DL model was constructed using MRI data. By integrating these models, we developed three fusion models as multimodal diagnostic AI and compared them with standalone models. The performance was evaluated using precision, recall, and accuracy. The classification model using Light Gradient Boosting Machine achieved an accuracy of 0.825, and the DL model using Visual Geometry Group 16-layer network achieved an accuracy of 0.722 for discriminating BOT from MOT. The intermediate, late, and dense fusion models achieved accuracies of 0.809, 0.776, and 0.825, respectively. Integrating multimodal information such as blood test and imaging data may enhance learning efficiency and improve diagnostic accuracy.

DOI： 10.1038/s41598-025-21128-w

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記述言語：英語   出版者・発行元：Journal of Extracellular Biology  

Extracellular vesicles (EVs) are present in body fluids and act as disease biomarkers. Emerging evidence has proven that EVs are released not only from mammalian cells but also from bacteria. Ovarian cancer has a dismal prognosis because of difficulties in early detection. This study aimed to identify bacterial EV (BEV) proteins associated with ovarian cancer. Fifteen patients with ovarian cancer or non-cancer were recruited, and EVs were isolated from the ascites. BEVs were recovered from seven in vitro-cultured strains of bacteria present in the vaginal microbiota, and LC-MS/MS analysis was performed. The detected peptide data were annotated to both human and bacterial references, and the human data showed that the profiles of cancer EVs were distinct from those of patients with non-cancer. As analysed by bacterial proteins, P15636_Protease1 was found as the BEV-associated protein highly expressed in patients with cancer. To distinguish patients with cancer, the area under the curve was 0.88 (95% CI, 0.64–1.00). In addition, homology analysis showed that P15636_Protease1 is a unique protein only detected in bacteria. In this study, ovarian cancer-specific bacterial proteins were identified on EVs, and BEVs in bodily fluids are promising in the discovery of disease biomarkers.

DOI： 10.1002/jex2.70073

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記述言語：英語   出版者・発行元：Journal of Obstetrics and Gynaecology Research  

Objective: To identify preoperative imaging features associated with retroperitoneal growth of large uterine fibroids and evaluate their impact on surgical outcomes. Methods: This retrospective study included 20 patients who underwent hysterectomy for uterine fibroids measuring ≥10 cm between 2014 and 2024. Preoperative CT or MRI was evaluated for four features: bladder displacement, sigmoid colon deviation, cecal displacement, and hydronephrosis. Tumor growth direction (intraperitoneal vs. retroperitoneal) was determined intraoperatively. Operative time, blood loss, and complications were compared between groups. Results: Eight tumors exhibited retroperitoneal growth. Bladder displacement, cecal shift, sigmoid colon deviation, and hydronephrosis were significantly more common in retroperitoneal cases (all p < 0.05). Retroperitoneal tumors were associated with significantly greater median blood loss (1591 mL vs. 651 mL, p = 0.043), although operative time did not differ significantly (301 vs. 232 min, p = 0.237). Organ injury or resection occurred only in the retroperitoneal group. A bubble plot illustrated the trend of increased surgical burden in retroperitoneal cases. Conclusion: Retroperitoneal growth of large uterine fibroids is associated with increased intraoperative blood loss and surgical complexity. Four simple imaging features may serve as reliable indicators of growth direction and help guide preoperative planning.

DOI： 10.1111/jog.70013

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担当区分：筆頭著者   記述言語：日本語   出版者・発行元：公益社団法人 日本婦人科腫瘍学会  

DOI： 10.57291/jsgo.42.2_75

Open Access

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biochimica Et Biophysica Acta Molecular Basis of Disease  

Objective: Uterine leiomyosarcoma (ULMS) is a rare malignant tumor, which is aggressive, and has a poor prognosis even during its early stages. Extracellular vesicles (EVs) carry cargo, such as microRNAs (miRNAs), which are involved in intercellular communication in the tumor microenvironment and other processes. Because there are no studies on EV-related miRNAs in ULMS, we identified EV-related miRNAs in ULMS and examined their function. Methods: Small EVs (sEVs) and medium/large EVs (m/lEVs) were extracted from ULMS cells by ultracentrifugation and their basic characteristics were evaluated. Then, small RNA sequencing was done to obtain EV-related miRNA profiles. Next, miRNA expression levels in sera and tissues of ULMS patients were compared with those of myoma patients. Results: miR-654-3p and miR-369-3p were indicated to be highly expressed in both sera and tissues of ULMS patients. These two miRNAs are also highly expressed in ULMS cell lines and ULMS-derived EVs. Some cancer-associated fibroblast (CAF) markers were increased when fibroblasts were treated with ULMS-derived EVs. Furthermore, fibroblasts took up EVs derived from ULMS as determined by confocal laser microscopy. In addition, the transfection of the two candidate miRNAs into fibroblasts significantly increased some CAF markers, particularly ACTA2. Conclusion: miR-654-3p and miR-369-3p are highly expressed in ULMS-derived EVs, indicating that these EV-related miRNAs induce the formation of cancer-associated fibroblasts.

DOI： 10.1016/j.bbadis.2024.167103

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）