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Background: Platinum chemotherapy is the cornerstone of treatment for high‐grade serous ovarian cancer (HGSOC); however, validated biomarkers that can accurately predict platinum response are lacking. Based on their roles in the underlying pathophysiology, circulating microRNAs are potential, noninvasive biomarkers in cancer. In the present study, we aimed to evaluate the circulating miRNA profiles of patients with HGSOC and to assess their potential utility as biomarkers to predict platinum response. Methods: Pretreatment serum samples collected from patients who received platinum chemotherapy for Stage III–IV HGSOC between 2008 and 2016 were analyzed using miRNA microarray. LASSO logistic regression analysis was used to construct predictive models for treatment‐free interval of platinum (TFIp). Results: The median follow‐up was 54.6 (range, 3.5–144.1) months. The comprehensive analysis of 2588 miRNAs was performed in serum samples of 153 eligible patients, and predictive models were constructed using a combination of circulating miRNAs with an area under the receiver operating characteristic curve of 0.944 for TFIp >1 month, 0.637 for TFIp ≥6 months, 0.705 for TFIp ≥12 months, and 0.938 for TFIp ≥36 months. Each predictive model provided a significant TFIp classification (p = 0.001 in TFIp >1 month, p = 0.013 in TFIp ≥6 months, p < 0.001 in TFIp ≥12 months, and p < 0.001 in TFIp ≥36 months). Conclusion: Circulating miRNA profiles has potential utility in predicting platinum response in patients with HGSOC and can aid clinicians in choosing appropriate treatment strategies. [ABSTRACT FROM AUTHOR]

Aim: Prenatal maternal depression is known to affect the neurodevelopment of offspring. This study aimed to investigate the profile of umbilical cord serum in mothers with major depressive disorder (MDD). Methods: Liquid chromatography–tandem mass spectrometry (LC–MS) was conducted using umbilical cord serum from mothers with MDD (n = 5) and controls (control, n = 5). The levels of several differentially expressed proteins in umbilical cord serum were compared between the MDD (n = 10) and control groups (n = 10) by enzyme‐linked immunosorbent assay. Results: The proteomic profiles in the umbilical cord serum were different between the MDD and control groups, including the pathways of regulation of plasma lipoprotein particle levels, and synapse organization. Only apolipoprotein A4 (APOA4) was significantly higher in the cord blood of MDD group. APOA4 levels in maternal serum were also significantly higher in the MDD group than those in the control group. The APOA4 levels in the umbilical cord serum were higher than that in the maternal serum. Conclusions: The levels of APOA4, a biomarker of depression, in the umbilical cord serum at birth were elevated in the neonates of MDD mothers. It is, therefore, likely that fetuses of MDD mothers were exposed to higher APOA4 levels in utero and this could have developmental and mental health implications for the offspring. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the safety and effectiveness of high‐dose oral medroxyprogesterone acetate (MPA) therapy as a fertility‐sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. Methods: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post‐MPA therapy pregnancies were examined. Results: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post‐CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. Conclusions: High‐dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment. [ABSTRACT FROM AUTHOR]

Background: To investigate the role of CD47 expression and its relationship with tumor‐resident macrophages, specifically at the tumor margin, in patients with type II endometrial cancer. This study aims to elucidate whether CD47 could serve as a prognostic marker and to understand the dynamics between CD47 and macrophages, which could inform new therapeutic strategies. Methods: A retrospective cohort study was conducted involving 75 patients of type II endometrial. Immunohistochemical analysis was performed to assess CD47 expression and macrophage markers (CD68 and CD163). Results: The study found no direct correlation between CD47 expression levels and overall survival (p = 0.32), challenging its role as an independent prognostic marker in type II endometrial cancer. The higher expression of CD47 had significantly less incidence of endometrioid carcinoma G3 (p = 0.047). The negative correlation between CD47 H‐score and the density of CD68‐positive macrophages at tumor margin was statistically significant (p = 0.049). A high density of CD68‐positive macrophages at the tumor margin but a low density of CD163‐positive macrophages at the tumor margin were associated with poorer prognosis (p = 0.036). Conclusions: The complex interaction between CD47 and macrophages, particularly at the tumor margin, suggests new avenues for targeted therapy in type II endometrial cancer. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a life‐threatening condition with high morbidity and mortality rates. The survival rate of neonates with severe CDH is reportedly only 10%–15%. However, prenatal prediction of severe cases is difficult, and the discovery of new predictive markers is an urgent issue. In this study, we focused on microRNAs (miRNAs) in amniotic fluid‐derived small EVs (AF‐sEVs). We identified four miRNAs (hsa‐miR‐127‐3p, hsa‐miR‐363‐3p, hsa‐miR‐493‐5p, and hsa‐miR‐615‐3p) with AUC > 0.8 to classify good prognosis group and poor prognosis group in human study. The AUC for hsa‐miR‐127‐3p and hsa‐miR‐615‐3p, for predicting the poor prognosis, were 0.93 and 0.91, respectively. In addition, in the in vivo study, the miRNA profiles of the lung tissues of CDH rats were different from those of control rats. Additionally, two elevated miRNAs (rno‐miR‐215‐5p and rno‐miR‐148a‐3p) in the lung tissues of CDH rats were increased in the AF‐sEVs of CDH rats. Our results suggest that severe CDH neonates can be predicted prenatally with high accuracy using miRNAs contained in AF‐sEVs. Furthermore, miRNA profile changes in AF‐sEVs reflected the lung status in CDH. Our findings may contribute to the development of advanced perinatal care for patients with CDH. [ABSTRACT FROM AUTHOR]

Background: Poly (ADP‐ribose) polymerase (PARP) inhibitors have been increasingly used in the treatment of ovarian cancer, with BRCA positivity and homologous recombination deficiency (HRD) being common biomarkers used for predicting their efficacy. However, given the limitations of these biomarkers, new ones need to be explored. Methods: This retrospective study included 181 ovarian cancer patients who received olaparib or niraparib at two independent hospitals in Japan between May 2018 and December 2022. Clinical information and blood sampling data were collected. Patient characteristics, treatment history, and predictability of treatment duration based on blood data before treatment initiation were examined. Results: High‐grade serous carcinoma, BRCA positivity, HRD, and maintenance therapy after recurrence treatment were observed more frequently in the olaparib group than in the niraparib group. The most common reasons for treatment interruption were anemia, fatigue, and nausea in the olaparib group and thrombocytopenia in the niraparib group. Regarding response to olaparib treatment, complete response to the most recent treatment, maintenance therapy after the first chemotherapy, high‐grade serous carcinoma, and germline BRCA positivity were observed significantly more frequently among responders than among non‐responders. Furthermore, neutrophil counts were significantly higher among responders than among non‐responders. Conclusions: Inflammation‐related blood data, such as neutrophil count, obtained at the initial pre‐treatment visit might serve as potential predictors for prolonged olaparib treatment. While this study offers valuable insights into potential indicators for prolonged olaparib treatment, it underscores the need for more expansive research to strengthen our understanding of PARP inhibitors and optimize treatment strategies in ovarian cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Systemic sclerosis, an autoimmune disease characterized by fibrosis and vasculopathy of the skin and other multiple organs has been associated with an increased risk of malignancy. We present the case of a 74‐year‐old woman who had diffused cutaneous systemic sclerosis and uterine cervical cancer. The patient was initially diagnosed with stage IIB squamous cell carcinoma and concurrent chemoradiotherapy was planned. However, cisplatin could not be administered due to acute renal failure, so the patient was treated solely with radiotherapy. However, complications of systemic sclerosis progressed rapidly, and the patient died 63 days later from pulmonary edema. An autopsy later revealed that uterine cervix had primary signet ring cell carcinoma. We suspected that this patient had a combination of signet ring cell carcinoma and squamous cell carcinoma, with squamous cell carcinoma disappearing after radiotherapy. This case highlighted the importance of systemic management for cancers associated with systemic sclerosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Development of low‐clearance (CL) compounds that are slowly metabolized is a major goal in the pharmaceutical industry. However, the pursuit of low intrinsic CL (CLint) often leads to significant challenges in evaluating the pharmacokinetics of such compounds. Although in vitro–in vivo extrapolation is widely used to predict human CL, its application has been limited for low‐CLint compounds because of the low turnover of parent compounds in metabolic stability assays. To address this issue, we focused on chimeric mice with humanized livers (PXB‐mice), which have been increasingly reported to accurately predict human CL in recent years. The predictive accuracy for nine low‐CLint compounds with no significant turnover in a human hepatocyte assay was investigated using PXB‐mouse methods, such as single‐species allometric scaling (PXB‐SSS) approach and a novel physiologically based scaling (PXB‐PBS) approach that assumes that the CLint per hepatocyte is equal between humans and PXB‐mice. The percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CLint compounds were 89% and 100%, respectively, for both PXB‐SSS and PXB‐PBS approaches. Moreover, the predicted CL was mostly consistent among the methods. Conversely, the percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CLint compounds were 50% and 63%, respectively, for multispecies allometric (MA) scaling. Overall, these PXB‐mouse methods were much more accurate than conventional MA scaling approaches, suggesting that PXB‐mice are useful tools for predicting the human CL of low‐CLint compounds that are slowly metabolized. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: Malignant transformation of mature cystic teratoma (MTMCT) of the ovary is a rare gynecological malignancy and commonly arises in women older than 50 years of age. The most common histological type of MTMCT is squamous cell carcinoma (SCC), and the prognosis is extremely poor. Patient‐derived xenograft (PDX) models are promising animal models for preclinical drug screening. Here, we report the generation of a new PDX model of MTMCT, and a new cell line established from the tumors of PDX model animals. Methods: Tumor tissue was obtained from a 32‐year‐old patient with MTMCT. To generate PDX, NSG (NOD.Cg‐PrkdcscidIl2rgtm1Wjl/SzJ) mice, a strain of super‐immunodeficient mice, were used. Tumor‐bearing mice were sacrificed, followed by the collection of these tumors and re‐transplantation into new NSG mice (in vivo passage). Tumor samples were also cultured in vitro. Adherent cells were continuously cultured and passaged, a cell line was established. Results: In the primary PDX mouse, tumor engraftment was confirmed 30 days after tumor implantation. After three times in vivo passage, we confirmed that the cryopreserved tumors could be engrafted even when transplanted into BALB/c nude mice. Using the tumor tissue at the time of the first in vivo passage, a new cell line NOSCC1 was established. PDX tumors and cell‐line derived xenograft tumors exhibited similar morphology of SCC. Conclusion: We established a new PDX model of MTMCT and a new cell line of it, which may be important tools for the development of new therapies and the elucidation of the carcinogenic mechanisms of MTMCT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The authors propose a new non‐destructive inspection method for underground fiberglass‐reinforced plastic mortar pipelines utilizing the periodic patterns of microwave guided‐modes on a hollow cylindrical dielectric waveguide. By the spatial synthesis of the microwaves utilizing the periodicity in the circumferential direction of a pipe, the authors found that a periodic pattern of the microwaves such as the Talbot effect with producing self‐images at the Talbot distance, was observed over the pipe‐wall. Further, adjusting the phase relationship between adjoining antenna elements changed the positions of the peak and null in the periodic pattern on the pipe‐wall. Additionally, when an unwanted foreign object was attached to the pipe, the periodic pattern of the microwaves can be disturbed according to the size and position of the object, and it is possible to inspect the pipeline using narrow‐band microwave signals. This paper experimentally demonstrated the successful detection of a foreign object on the pipe‐wall by scanning Talbot‐like patterns with a sensor along the pipe‐wall. This technique enables the non‐destructive inspection of pipelines using only narrow‐band, licence‐free microwave signals. [ABSTRACT FROM AUTHOR]

Aim: Accumulation of ascites fluid is a major obstacle in the late phase of epithelial ovarian cancer. However, there is no consensus on a specific treatment for malignant ascites. The present study evaluated the clinical benefit of half‐dose bevacizumab therapy (7.5 mg/kg every 3–4 weeks). Methods: This was a single‐arm interventional study performed at Aichi Cancer Center Hospital. Four patients with platinum‐resistant epithelial ovarian cancer and symptomatic malignant ascites were no longer considered candidates for standard chemotherapy. As a palliative approach, half‐dose bevacizumab therapy (7.5 mg/kg every 3–4 weeks) was used with informed consent. The clinical data of these patients were retrospectively reviewed. Results: All patients had been heavily pretreated and showed progressive disease. Thus, standard chemotherapy was no longer feasible, and palliative paracentesis for malignant ascites was clinically needed. Among the four patients, three did not require additional paracentesis after bevacizumab therapy, and there were no adverse events. One patient needed paracentesis owing to lymphorrhea. Conclusion: The use of bevacizumab therapy as a palliative approach for malignant ascites might be an option in patients with terminal‐stage ovarian cancer. However, further evaluation is needed with regard to the possibility of severe side effects and medical expenses. [ABSTRACT FROM AUTHOR]

We report a case of a male patient with a 19‐year history of monoclonal and later polyclonal gammopathy who subsequently developed tetraparesis, bulbar palsy, and respiratory failure. Autopsy findings showed degeneration of the hypoglossal nuclei, prominent neuronal loss and atrophy in the anterior horn of the whole spinal cord despite the presence of mild astrocytosis, degeneration of the gracilis on one side, and infiltration of inflammatory cells, which included B cells and plasma cells in the anterior and posterior roots of the lumbar spinal cord, iliopsoas muscle, and perivascular area of the cervical cord. On immunostaining, cytoplasmic inclusions of phosphorylated transactivation response DNA‐binding protein of 43 kDa were observed in the motor neurons and astrocytes of the hypoglossal nuclei and whole spinal cord. The final diagnosis was paraneoplastic lower motor neuron disease with sensorimotor neuropathy due to Waldenström's macroglobulinemia. [ABSTRACT FROM AUTHOR]

Malignant transformations of mature cystic teratomas (MCT) are extremely rare and most of them are squamous cell carcinomas (SCC). Therefore no effective postoperative treatment has been established. In this article, we report two cases in which radiotherapy was effective for SCC arising from MCT. Case 1 was a 64-year-old woman with stage IIA of this tumor. After primary surgery, chemotherapy and interval debulking surgery were performed. She received radiotherapy for relapsed tumors, and has been well for 36 months since the initial diagnosis. Case 2 was a 37-year-old woman with stage IIB of this tumor. After primary debulking surgery, she received chemoradiotherapy for a residual tumor and has been well for 27 months since the surgery. Although there is no established therapy, radiotherapy or concurrent chemoradiotherapy might have beneficial effects on this tumor, similarly to those on SCC from other tissue. [ABSTRACT FROM AUTHOR]