記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3802/jgo.2023.34.e34

PubMed

記述言語：英語   出版者・発行元：Pediatric Surgery International  

Purpose: This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH). Methods: A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed. Results: A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 [95% confidence interval (CI) 4.65–30.89], 11.14 (95% CI 5.19–23.89), and 10.28 (95% CI 3.38–31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position. Conclusions: This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH.

DOI： 10.1007/s00383-022-05232-w

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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：Cancer Medicine  

Background: Choriocarcinoma is a rare and aggressive gynecological malignancy. The standard treatment is systemic chemotherapy as choriocarcinoma exhibits high chemosensitivity. However, refractory choriocarcinoma exhibits chemoresistance; thus, the prognosis remains very poor. This study aimed to identify novel therapeutic agents for choriocarcinoma by utilizing a drug repositioning strategy. Methods: Three choriocarcinoma cell lines (JAR, JEG-3, and BeWo) and a human extravillous trophoblast cell line (HTR-8/SVneo) were used for the analyses. The growth inhibitory effects of 1,271 FDA-approved compounds were evaluated in vitro screening assays and selected drugs were tested in tumor-bearing mice. Functional analyses of drug effects were performed based on RNA sequencing. Results: Muti-step screening identified vorinostat, camptothecin (S, +), topotecan, proscillaridin A, and digoxin as exhibiting an anti-cancer effect in choriocarcinoma cells. Vorinostat, a histone deacetylase inhibitor, was selected as a promising candidate for validation and the IC50 values for choriocarcinoma cells were approximately 1 μM. RNA sequencing and subsequent pathway analysis revealed that the ferroptosis pathway was likely implicated, and key ferroptosis-related genes (i.e., GPX4, NRF2, and SLC3A2) were downregulated following vorinostat treatment. Furthermore, vorinostat repressed tumor growth and downregulated the expression of GPX4 and NRF2 in JAR cell-bearing mice model. Conclusion: Vorinostat, a clinically approved drug for the treatment of advanced primary cutaneous T-cell lymphoma, showed a remarkable anticancer effect both in vitro and in vivo by regulating the expression of ferroptosis-related genes. Therefore, vorinostat may be an effective therapeutic candidate for patients with choriocarcinoma.

DOI： 10.1002/cam4.5243

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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：PLoS ONE  

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.

DOI： 10.1371/journal.pone.0273876

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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：Journal of Gynecologic Oncology  

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.

DOI： 10.3802/jgo.2022.33.e40

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記述言語：英語   出版者・発行元：Children  

Background: Treatment modalities for neonates with congenital diaphragmatic hernia (CDH) have greatly improved in recent years, with a concomitant increase in survival. However, long-term outcomes restrict the identification of optimal care pathways for CDH survivors in adolescence and adulthood. Therefore, we evaluated the long-term outcomes within the Japanese CDH Study Group (JCDHSG). Methods: Participants were born with CDH between 2006 and 2018 according to the JCDHSG. Participants were enrolled in the database at 1.5, 3, 6, and 12 years old. Follow-up items included long-term complications, operations for long-term complication, and home medical care. Results: A total of 747 patients were included in this study, with 626 survivors (83.8%) and 121 non-survivors (16.2%). At 1.5, 3, 6, and 12 years old, 45.4%, 36.5%, 34.8%, and 43.6% developed complications, and 20.1%, 14.7%, 11.5%, and 5.1% of participants required home care, respectively. Recurrence, pneumonia, pneumothorax, gastroesophageal reflux disease, and intestinal obstruction decreased with age, and thoracic deformity increased with age. Conclusions: As CDH survival rates improve, there is a need for continued research and fine-tuning of long-term care to optimize appropriate surveillance and long-term follow-up.

DOI： 10.3390/children9060856

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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：Clinical Cancer Research  

Purpose: Uterine leiomyosarcoma is among the most aggressive gynecological malignancies. No effective treatment strategies have been established. This study aimed to identify novel therapeutic targets for uterine leiomyosarcoma based on transcriptome analysis and assess the preclinical efficacy of novel drug candidates. Experimental Design: Transcriptome analysis was performed using fresh-frozen samples of six uterine leiomyosarcomas and three myomas. The Ingenuity Pathway Analysis (IPA) was used to identify potential therapeutic target genes for uterine leiomyosarcoma. Afterward, our results were validated using three independent datasets, including 40 uterine leiomyosarcomas. Then, the inhibitory effects of several selective inhibitors for the candidate genes were examined using SK-UT-1, SK-LMS-1, and SKN cell lines. Results: We identified 512 considerably dysregulated genes in uterine leiomyosarcoma compared with myoma. The IPA revealed that the function of several genes, including CHEK1 and PLK1, were predicted to be activated in uterine leiomyosarcoma. Through an in vitro drug screening, PLK1 or CHEK1 inhibitors (BI-2536 or prexasertib) were found to exert a superior anticancer effect against cell lines at low nanomolar concentrations and induce cell-cycle arrest. In SK-UT-1 tumor-bearing mice, BI-2536 monotherapy remarkably suppressed tumorigenicity. Moreover, the prexasertib and cisplatin combination therapy inhibited tumor proliferation and prolonged the time to tumor progression. Conclusions: We identified upregulated expressions of PLK1 and CHEK1; their kinase activity was activated in uterine leiomyosarcoma. BI-2536 and prexasertib demonstrated a significant anticancer effect. Therefore, cell-cycle–related kinases may present a promising therapeutic strategy for the treatment of uterine leiomyosarcoma.

DOI： 10.1158/1078-0432.CCR-22-0100

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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：International Journal of Gynecology and Obstetrics  

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.

DOI： 10.1002/ijgo.13844

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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：Matrix Biology  

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.

DOI： 10.1016/j.matbio.2022.03.003

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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 Women's Health  

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.

DOI： 10.1186/s12905-022-01642-z

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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：Scientific Reports  

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.

DOI： 10.1038/s41598-022-08503-7

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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：International Journal of Clinical Oncology  

Background: Previous studies on adjuvant chemotherapy for patients with ovarian clear cell carcinoma (OCCC) have included a limited number of Asian patients with surgical stage I OCCC, despite differences in OCCC survival by race and stage. The aim of this study was to estimate the survival effect of the number of cycles of adjuvant taxane plus carboplatin chemotherapy in Asian patients with surgical stage I OCCC. Methods: We retrospectively identified 227 patients with surgical stage I OCCC at 14 institutions from 1995 to 2017. Kaplan–Meier analysis and Cox proportional hazard regression with inverse probability of treatment weighting (IPTW) adjustment were performed to evaluate overall survival (OS) and recurrence-free survival (RFS) in patients receiving ≤ 3 and 4–6 cycles of taxane plus platinum adjuvant chemotherapy. Results: Eighty-nine and 138 patients received ≤ 3 and 4–6 cycles of adjuvant chemotherapy, respectively. There was no between-group difference in OS or RFS with or without IPTW adjustment. In Cox proportional hazards analysis, 4–6 cycles of adjuvant chemotherapy were not associated with improved OS (HR 1.090; 95% CI 0.518–2.291; p = 0.821) or RFS (HR 1.144; 95% CI 0.619–2.114; p = 0.669) compared to ≤ 3 cycles, even with IPTW adjustment. Subgroup analysis in different substages of stage I OCCC showed that the number of cycles of adjuvant chemotherapy had no impact on OS or RFS. Conclusion: Three or fewer cycles of taxane plus carboplatin chemotherapy may be a reasonable treatment regime for patients with surgical staging I OCCC.

DOI： 10.1007/s10147-021-02075-8

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その他リンク： https://link.springer.com/article/10.1007/s10147-021-02075-8/fulltext.html

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出版者・発行元：Cold Spring Harbor Laboratory  

Purpose: Uterine leiomyosarcoma is among the most aggressive gynecological malignancies. No effective treatment strategies have been established. This study aimed to identify novel therapeutic targets for uterine leiomyosarcoma based on transcriptome analysis and assess the preclinical efficacy of novel drug candidates.
Experimental Design: Transcriptome analysis was carried out using fresh-frozen samples of six uterine leiomyosarcomas and three myomas. The Ingenuity Pathway Analysis was then used to identify potential therapeutic target genes for uterine leiomyosarcoma. Moreover, our results were validated using three independent datasets, including 40 uterine leiomyosarcomas. Then, the inhibitory effects of several selective inhibitors for the candidate genes were examined using the SK-UT-1, SK-LMS-1, and SKN cell lines.
Results: We identified 512 considerably dysregulated genes in uterine leiomyosarcoma compared with myoma. The Ingenuity Pathway Analysis showed that the function of several genes, including CHEK1 and PLK1, were predicted to be activated in uterine leiomyosarcoma. Through an in vitro drug screening, PLK1 or CHEK1 inhibitors (BI 2536 or prexasertib) were found to exert a superior anti-cancer effect against cell lines at low nanomolar concentrations and induced cell cycle arrest. In SK-UT-1 tumor-bearing mice, BI 2536 monotherapy demonstrated a marked tumor regression. Moreover, the prexasertib and cisplatin combination therapy also reduced tumorigenicity and prolonged survival.
Conclusion: We identified the upregulated expression of PLK1 and CHEK1; their kinase activity was considered to be activated in uterine leiomyosarcoma. BI 2536 and prexasertib demonstrate a significant anti-cancer effect; thus, cell cycle-related kinases may represent a promising therapeutic strategy for treating uterine leiomyosarcoma.

DOI： 10.1101/2022.01.06.22268775

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

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.

DOI： 10.1038/s41598-021-02635-y

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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：Cancer Science  

High-grade serous ovarian carcinoma is a leading cause of death in female patients worldwide. MicroRNAs (miRNAs) are stable noncoding RNAs in the peripheral blood that reflect a patient’s condition, and therefore, they have received substantial attention as noninvasive biomarkers in various diseases. We previously reported the usefulness of serum miRNAs as diagnostic biomarkers. Here, we investigated the prognostic impact of the serum miRNA profile. We used the GSE106817 dataset, which included preoperative miRNA profiles of patients with ovarian malignancies. Excluding patients with other malignancy or insufficient prognostic information, we included 175 patients with high-grade serous ovarian carcinoma. All patients except four underwent surgery and received chemotherapy as initial treatment. The median follow-up period was 54.6 months (range, 3.5-144.1 months). Univariate Cox regression analysis revealed that higher levels of miR-187-5p and miR-6870-5p were associated with both poorer progression-free survival (PFS) and overall survival (OS), and miR-1908-5p, miR-6727-5p, and miR-6850-5p were poor prognostic indicators of PFS. The OS and PFS prognostic indices were then calculated using the expression values of three prognostic miRNAs. Multivariate Cox regression analysis showed that both indices were significantly independent poor prognostic factors (hazard ratio for OS and PFS, 2.343 [P =.015] and 2.357 [P =.005], respectively). In conclusion, circulating miRNA profiles can potentially provide information to predict the prognosis of patients with high-grade serous ovarian carcinoma. Therefore, there is a strong demand for early clinical application of circulating miRNAs as noninvasive biomarkers.

DOI： 10.1111/cas.15154

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/cas.15154

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Seminars in Cancer Biology  

Extracellular vesicles (EVs) such as exosomes are released by all living cells and contain diverse bioactive molecules, including nucleic acids, proteins, lipids, and metabolites. Accumulating evidence of EV-related functions has revealed that these tiny vesicles can mediate specific cell-to-cell communication. Within the tumor microenvironment, diverse cells are actively interacting with their surroundings via EVs facilitating tumor malignancy by regulating malignant cascades including angiogenesis, immune modulation, and metastasis. This review summarizes the recent studies of fundamental understandings of EVs from the aspect of EV heterogeneity and highlights the role of EVs in the various steps from oncogenic to metastatic processes. The recognition of EV subtypes is necessary to identify which pathways can be affected by EVs and which subtypes can be targeted in therapeutic approaches or liquid biopsies.

DOI： 10.1016/j.semcancer.2021.03.032

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.celrep.2021.109549

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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：Cancer Cell International  

Background: Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. The characteristics of metastatic cancer may differ from those of primary ovarian cancer and reflect the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers. Methods: Patients with advanced epithelial ovarian cancer were eligible for this study. Five patients underwent surgery and resection of paired primary ovarian and omental metastatic cancer at Nagoya University. Metabolome analysis was performed in these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch’s t-test was used for comparisons between two independent groups. Results: Metabolite profiles were all different, which reflects diversity among these cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, in some cases, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers. With regard to histological subtype, the total levels of amino acids, especially the percentage of glutamine, were significantly enriched in serous carcinomas compared with nonserous carcinomas (p = 0.004 and p = 0.001). Moreover, the reduced forms of glutathione and polyamines were also more abundant in serous carcinomas than in nonserous carcinomas (p = 0.025 and 0.048). Conclusions: The metabolite profiles differed depending on tumor location and histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers.

DOI： 10.1186/s12935-021-02014-7

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Current Oncology  

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

DOI： 10.3390/curroncol28030155

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Experimental and Clinical Cancer Research  

MicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer. The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial–mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888–892 group are considered to be cell type- or tissue-specific. In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.

DOI： 10.1186/s13046-021-01910-0

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncogene  

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.

DOI： 10.1038/s41388-020-01595-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.celrep.2021.108726

PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Web of Science

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Web of Science

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Web of Science

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Web of Science

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

Ovarian clear cell carcinoma (OCCC) has been treated with surgery and chemotherapy; however, the prognosis remains poor because of chemoresistance. Therefore, immunotherapies are attracting attention, including the GPC3 peptide vaccine, which improves overall survival. However, the response rate is limited and there are no sufficient predictive biomarkers that can identify responders before treatment. Our purpose was to identify circulating serum miRNAs as predictive biomarkers for response to GPC3 peptide vaccine. Eighty-four patients in a phase II trial of a GPC3 peptide vaccine were enrolled and miRNA sequencing was performed on their serum samples. Candidate miRNAs were selected from a group of 14 patients for whom treatment was responsive and validated in an independent group of 10 patients for whom treatment was responsive. Three markedly upregulated miRNAs, miR-375-3p, miR-193a-5p, and miR-1228-5p, were identified, and the combination of those miRNAs demonstrated high value in the prediction of the response. The origin of these miRNAs was assessed by referring to OCCC tissue miRNA profiles, and they were not identified as cancer tissue-related miRNAs. Functional annotation analysis suggested that they were associated with interferon-related pathways. The miRNAs identified herein have great potential to allow the realization of liquid biopsy for predicting the immunotherapy response and precision medicine.

DOI： 10.3390/cancers13030550

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PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Web of Science

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Web of Science

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Web of Science

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：F and S Science  

Objective: To establish and characterize cell lines derived from human endometrial epithelial cells (ECs) and mesenchymal cells (MCs) from patients with and without endometriosis. Design: In vitro experimental study. Setting: University and national cancer center research institute. Patient(s): Two women with endometriosis and two women without endometriosis. Intervention(s): Sampling of endometrial ECs and MCs. Main Outcome Measure(s): Establishing immortalized endometrial ECs and MCs with quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunocytochemical analysis, and RNA sequence profiling performed to characterize the immortalized cells and a cell proliferation assay, three-dimensional culture, and assays for hormone responses performed to characterize the features of ECs. Result(s): The qRT-PCR, immunocytochemical analysis, and Western blot analysis revealed that the ECs and MCs maintained their original features. Moreover, the immortalized cells were found to retain responsiveness to sex steroid hormones. The ECs formed a gland-like structure in three-dimensional culture, indicating the maintenance of normal EC phenotypes. The RNA sequence profiling, principal component analysis, and clustering analysis showed that the gene expression patterns of the immortalized cells were different from those of cancer cells. Several signaling pathways that were statistically significantly enriched in ECs and MCs with endometriosis were revealed. Conclusion(s): We successfully obtained four paired immortalized endometrial ECs and MCs from patients with and without endometriosis. Using these cells could help identify diagnostic and therapeutic targets for endometriosis. The cell lines established in this study will thus serve as powerful experimental tools in the study of endometriosis.

DOI： 10.1016/j.xfss.2020.09.001

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PubMed

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

Ovarian cancer is the most lethal gynecological cancer due to lack of early screening methods and acquired drug resistance. MicroRNAs (miRNAs) are effective post-transcriptional regulators that are transferred by extracellular vesicles, such as exosomes. Numerous studies have revealed that miRNAs are differentially expressed in epithelial ovarian cancer and act either as oncogenes or tumor suppressor genes. Cancer cells secrete exosomes containing miRNAs, which exert various effects on the components of the tumor microenvironment, including cancer-associated fibroblasts, macrophages, and adipocytes. Conversely, cancer cells also receive exosomes from these cells. As a result of cell-to-cell communication, epithelial ovarian cancer acquires a more aggressive phenotype and resistance to multiple drugs. In addition, some circulating miRNAs are protected from RNase degradation in the peripheral blood and can be potential non-invasive biomarkers. In particular, the combination of several circulating miRNAs enhances the accuracy of cancer screening. Likewise, comprehensive analyses revealed specific miRNA signatures in non-epithelial ovarian tumors and several miRNAs contributing to alterations of carcinogenic pathways. Overall, miRNAs play a crucial role in ovarian cancer progression. In this review, we discuss the emerging roles of intra- and extracellular miRNAs in ovarian cancers. In the near future, miRNAs will be practical biomarkers and computational deep learning will help in the clinical application of miRNAs. Moreover, miRNAs are potential therapeutic targets and agents, and there are ongoing clinical trials of miRNA replacement therapy. Therefore, accelerating research on miRNA might improve the prognosis of patients with ovarian cancer.

DOI： 10.1111/cas.14599

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Cancer  

Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell-to-cell crosstalk or phenotypic alterations including the acquisition of platinum-resistance in OvCa cells. Herein, we report how OvCa-associated mesothelial cells (OCAMs) induce platinum-resistance in OvCa cells through direct cell-to-cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF-β1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum-sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell-to-cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF-β1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell-to-cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum-resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination.

DOI： 10.1002/ijc.32854

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Clinical Oncology  

Background: The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. Methods: We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Results: Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P = 0.696) and recurrence-free survival (P = 0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. Conclusions: The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.

DOI： 10.1093/jjco/hyz163

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

Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated.

DOI： 10.1111/cas.14215

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Carcinogenesis  

Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle'. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.

DOI： 10.1093/carcin/bgz135

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1126/sciadv.aax8849

PubMed

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/ijgc-2019-ESGO.1079

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41388-019-0832-4

PubMed

記述言語：英語  

DOI： 10.1038/s41598-019-45001-9

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.canlet.2019.03.002

PubMed

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

The mesothelium, covered by a continuous monolayer of mesothelial cells, is the first protective barrier against metastatic ovarian cancer. However, mesothelial cells release tumor-promoting factors that accelerate the process of peritoneal metastasis. We identified cancer-associated mesothelial cells (CAMs) that had tumor-promoting potential. Here, we found that plasminogen activator inhibitor-1 (PAI-1) induced the formation of CAMs, after which CAMs increasingly secreted the oncogenic factors interleukin-8 (IL-8) and C-X-C motif chemokine ligand 5 (CXCL5), further promoting the metastasis of ovarian cancer cells in a feedback loop. After the formation of CAMs, PAI-1 activated the nuclear factor kappa B (NFκB) pathway in the CAMs, thus transcriptionally upregulating the expression of the downstream NFκB targets IL-8 and CXCL5. Moreover, PAI-1 correlated with peritoneal metastasis in ovarian cancer patients and indicated a poor prognosis. In both ex vivo and in vivo models, after PAI-1 expression was knocked down, the metastasis of ovarian cancer cells decreased significantly. Therefore, targeting PAI-1 may provide a potential target for future therapeutics to prevent the formation of CAMs and alleviate peritoneal metastasis in ovarian cancer patients.

DOI： 10.1016/j.canlet.2018.10.027

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記述言語：日本語   出版者・発行元：一般社団法人 日本助産学会  

<p><b>目　的</b></p><p>バースセンター（以下BC）は，総合周産期母子医療センターに併設する院内助産施設である。BCでは妊娠分娩経過は正常であっても，出産後に予期せぬ多量出血を経験することがある。生殖補助医療（以下ART）妊娠は癒着胎盤のリスク因子と言われており，且つ癒着胎盤は産科危機的出血の原因となり得る。当施設ではART妊娠であっても院内助産分娩希望があれば，産科医許可のもとBCで分娩を取扱っている。本研究ではART妊娠（新鮮胚移植妊娠，融解胚移植妊娠）の産後過多出血（以下PPH）を検証し，院内助産におけるリスク評価，及び対応を検討した。</p><p><b>対象と方法</b></p><p>研究デザインは症例対照研究である。対象は2013年4月から2016年3月の調査期間中にBCで取り扱った分娩604例で，うち非ART妊娠は567例，ART妊娠は37例（新鮮胚移植9例，融解胚移植28例）であった。非ART妊娠と新鮮胚移植妊娠，融解胚移植妊娠で分娩後出血量，産褥24時間出血量，及びPPH（分娩後出血500ml以上，産褥24時間出血800ml以上）頻度の統計解析を行った。分娩後出血量，産褥24時間出血量を重回帰分析で，PPH頻度を多変量ロジスティック分析により検証した。</p><p><b>結　果</b></p><p>融解胚移植妊娠は分娩後出血量，産褥24時間出血量が非ART妊娠より有意に多く，PPHの頻度は非ART妊娠より有意に高かった。PPHのうち4例が産科危機的出血であったが，うち3例は融解胚移植のART妊婦であった。</p><p><b>結　論</b></p><p>ART妊婦の中でも融解胚移植妊娠はPPHのリスク因子になることが示唆された。融解胚移植妊娠については医師と速やかな医療連携がとれる体制の確立，及び将来的に院内助産分娩の対象から除外すべきか検討するための調査が必要と考える。</p>

DOI： 10.3418/jjam.jjam-2017-0048

CiNii Research

掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

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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：Nature Communications  

A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.

DOI： 10.1038/s41467-018-06434-4

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掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：生命科学系学会合同年次大会運営事務局  

記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oncotarget  

Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine.

DOI： 10.18632/oncotarget.20688

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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：Nature Communications  

Advanced ovarian cancers are highly metastatic due to frequent peritoneal dissemination, resulting in dismal prognosis. Here we report the functions of cancer-derived extracellular vesicles (EVs), which are emerging as important mediators of tumour metastasis. The EVs from highly metastatic cells strongly induce metastatic behaviour in moderately metastatic tumours. Notably, the cancer EVs efficiently induce apoptotic cell death in human mesothelial cells in vitro and in vivo, thus resulting in the destruction of the peritoneal mesothelium barrier. Whole transcriptome analysis shows that MMP1 is significantly elevated in mesothelial cells treated with highly metastatic cancer EVs and intact MMP1 mRNAs are selectively packaged in the EVs. Importantly, MMP1 expression in ovarian cancer is tightly correlated with a poor prognosis. Moreover, MMP1 mRNA-carrying EVs exist in the ascites of cancer patients and these EVs also induce apoptosis in mesothelial cells. Our findings elucidate a previously unknown mechanism of peritoneal dissemination via EVs.

DOI： 10.1038/ncomms14470

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記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

DOI： 10.11241/jsmtmr.32.27

CiNii Research

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(一社)日本がん・生殖医療学会  

記述言語：日本語   出版者・発行元：(一社)日本がん・生殖医療学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

外陰部腺癌は稀であり、腟前庭後部の病変はバルトリン腺原発と考えやすい。今回クローン病罹患中の外陰部腺癌が、術後に痔瘻癌と判明した症例を経験したので報告する。症例は48歳の女性で、クローン病で内科的治療を継続していた。前医を受診する6ヵ月前に左腟前庭部に腫瘤が出現し前医を受診した。生検でadenocarcinomaと診断された。腸管由来の可能性も示唆されたため、上下部消化管内視鏡精査を行ったが悪性腫瘍を認めず、バルトリン腺癌疑いで当院を紹介受診した。初診時、左バルトリン腺領域に4cm大、その腹側の陰核左側に1.5cm大の腫瘤を認めた。CT検査で両側鼠径リンパ節の軽度腫大を認めた。2週間後に単純外陰切除術、両側鼠径リンパ節生検を施行した。病理診断は中分化腺癌であり、大腸粘膜上皮と腺癌との連続性が確認できたため痔瘻癌と診断した。切除断端は左腟壁深部剥離面が陽性であり、両側鼠径リンパ節にも転移を認めた。前手術から3ヵ月後に外科にてロボット支援腹腔鏡下腹会陰式直腸切除術、腟会陰切除術、大腸ストーマ造設術、鼠径リンパ節郭清術を施行され、現在化学療法(CAPOX療法)を行っている。外陰部は痔瘻が発生する場所として矛盾しないため、クローン病既往の外陰部腺癌は痔瘻由来の可能性を積極的に考慮し、術前に痔瘻の精査を十分に行う必要がある。(著者抄録)

記述言語：日本語   出版者・発行元：(一社)日本がん・生殖医療学会  

記述言語：日本語   出版者・発行元：(一社)日本がん・生殖医療学会  

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

記述言語：日本語   出版者・発行元：東海産婦人科内視鏡手術研究会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：日本語   出版者・発行元：(一社)日本産科婦人科内視鏡学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：英語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：英語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(公社)日本婦人科腫瘍学会  

記述言語：日本語   出版者・発行元：(一社)日本産科婦人科内視鏡学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：日本語   出版者・発行元：愛知産科婦人科学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：英語   出版者・発行元：(一社)日本癌学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(株)医学書院  

＜文献概要＞●血液中を循環するマイクロRNAをバイオマーカーとして臨床応用することを目的とした取り組み.●卵巣がん患者群において有意に変化する複数のマイクロRNAを同定し,それらの組み合わせにより,早期から高精度でがんの存在を検出できる診断モデルを作成.●卵巣がん診断血液スクリーニングの実現に大きな前進をもたらす成果である.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01564&link_issn=&doc_id=20191202060012&doc_link_id=10.11477%2Fmf.1409209874&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1409209874&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：日本語   出版者・発行元：(一社)日本助産学会  

目的 バースセンター(以下BC)は、総合周産期母子医療センターに併設する院内助産施設である。BCでは妊娠分娩経過は正常であっても、出産後に予期せぬ多量出血を経験することがある。生殖補助医療(以下ART)妊娠は癒着胎盤のリスク因子と言われており、且つ癒着胎盤は産科危機的出血の原因となり得る。当施設ではART妊娠であっても院内助産分娩希望があれば、産科医許可のもとBCで分娩を取扱っている。本研究ではART妊娠(新鮮胚移植妊娠、融解胚移植妊娠)の産後過多出血(以下PPH)を検証し、院内助産におけるリスク評価、及び対応を検討した。対象と方法 研究デザインは症例対照研究である。対象は2013年4月から2016年3月の調査期間中にBCで取り扱った分娩604例で、うち非ART妊娠は567例、ART妊娠は37例(新鮮胚移植9例、融解胚移植28例)であった。非ART妊娠と新鮮胚移植妊娠、融解胚移植妊娠で分娩後出血量、産褥24時間出血量、及びPPH(分娩後出血500ml以上、産褥24時間出血800ml以上)頻度の統計解析を行った。分娩後出血量、産褥24時間出血量を重回帰分析で、PPH頻度を多変量ロジスティック分析により検証した。結果 融解胚移植妊娠は分娩後出血量、産褥24時間出血量が非ART妊娠より有意に多く、PPHの頻度は非ART妊娠より有意に高かった。PPHのうち4例が産科危機的出血であったが、うち3例は融解胚移植のART妊婦であった。結論 ART妊婦の中でも融解胚移植妊娠はPPHのリスク因子になることが示唆された。融解胚移植妊娠については医師と速やかな医療連携がとれる体制の確立、及び将来的に院内助産分娩の対象から除外すべきか検討するための調査が必要と考える。(著者抄録)

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02875&link_issn=&doc_id=20190107430008&doc_link_id=130007549960&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007549960&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

Web of Science

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

Web of Science

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY  

Web of Science

記述言語：日本語   出版者・発行元：(株)東京医学社  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：英語   出版者・発行元：日本癌学会  

記述言語：日本語   出版者・発行元：日本分子腫瘍マーカー研究会  

記述言語：日本語   出版者・発行元：(株)篠原出版新社