The clinical efficacy and immune modulation of neoadjuvant immunochemotherapy for epithelial ovarian cancer (EOC) remain uncertain. To clarify these effects, the NAIVE trial (NCT04815408), a prospective phase II study, evaluated the efficacy of neoadjuvant platinum-based chemotherapy with tislelizumab (NACI) in comparison with chemotherapy alone (NAC) in patients with FIGO IIIC-IV EOC. The primary endpoint was the 1-year progression-free survival (PFS) rate; the secondary endpoints included PFS, R0 resection, clinical and pathological responses, and safety. Between April 2021 and July 2024, 25 patients were included in the final analysis. After a median follow-up period of 30.7 months, NACI was associated with numerically prolonged progression-free survival (27.2 vs. 21.8 months; HR = 0.44, 95% CI 0.15-1.26; P = 0.127), with higher 1-year (92.3% vs. 83.3%) and 2-year (62.3% vs. 31.8%) PFS rates than NAC. NACI also yielded superior tumor responses, including higher ORR (69.2% vs. 58.3%), more R0 resections, and increased CRS3 rates. No unexpected safety signals emerged, and immune-related adverse events were manageable. Immune profiling techniques, such as single-cell RNA sequencing and CyTOF, identified distinct signatures. NACI responders demonstrated heightened CD8+ T-cell-mediated toxicity and metabolic fitness, whereas nonresponders exhibited exhaustion phenotypes. Furthermore, the response correlated with enrichment of the CXCL13+Th1-GC B-cell-tertiary lymphoid structure (TLS) axis, accompanied by increased TLS activity and differentiation to IgG-producing plasma cells. Overall, NACI yielded PFS trends with acceptable safety, but without statistical significance. The mechanistic analyses highlight the role of the CXCL13+Th1-GC B-cell-TLS axis as a potential biomarker and driver of therapeutic response.

This study aims to characterize the expression pattern and biological functions of miR-433-3p in endometriosis. Eutopic and ectopic endometrial tissues were collected from endometriosis patients, and the expression level of miR-433-3p was detected by RT-qPCR. Serum samples were also collected from endometriosis patients and healthy female controls, and the diagnostic value of miR-433-3p for endometriosis was evaluated by receiver operating characteristic curve. In cell experiments, CCK-8 and Transwell assays were performed to assess the effects of miR-433-3p on the proliferation, migration and invasion of endometrial stromal cells (ESCs). RT-qPCR was used to detect the expression levels of epithelial-mesenchymal transition (EMT) markers. A dual-luciferase reporter assay was conducted to verify the targeted binding relationship between miR-433-3p and CHL1. The results showed that the level of miR-433-3p in ectopic endometrium was significantly lower than that in eutopic endometrium. Moreover, circulating miR-433-3p levels in the serum of endometriosis patients were significantly lower than those in healthy controls. Serum miR-433-3p demonstrated excellent diagnostic efficacy for endometriosis, with an AUC of 0.8777, a sensitivity of 93.90%, and a specificity of 76.25%. In cells, overexpression of miR-433-3p significantly suppressed the proliferation, migration, invasion and EMT. Mechanistically, CHL1 was identified as a direct downstream target of miR-433-3p, and rescue experiments confirmed that restored CHL1 expression could partially reverse the inhibitory effect of miR-433-3p on the aggressive biological phenotype of ESCs. Based on the above research results, we propose the following hypothesis: In endometriosis, miR-433-3p may inhibit the proliferation and invasion of ESCs by targeting CHL1. Moreover, circulating miR-433-3p is expected to become a non-invasive candidate biomarker for endometriosis.

Clinical residency training plays a crucial role in cultivating competent gynecologists capable of integrating theoretical knowledge with clinical practice. However, traditional lecture-based teaching in China often limits resident engagement and practical experience due to heavy clinical workloads and restricted patient access, particularly in gynecology. To address these challenges, we implemented a combined problem-based learning and case-based learning (PBL–CBL) model aimed at enhancing residents’ clinical reasoning, learning initiative, and satisfaction. A prospective quasi-experimental educational study was conducted among 50 gynecology residents at The Second Affiliated Hospital of Zhejiang University School of Medicine between September 2018 and July 2025. Participants were assigned to either a PBL–CBL group or a traditional lecture-based group. Both groups received instruction on abnormal uterine bleeding using identical materials, instructors, and class hours. Teaching effectiveness was evaluated through pre- and post-course theoretical and skills examinations, as well as an anonymous questionnaire assessing learning interest, initiative, and satisfaction. Statistical analyses were performed using SPSS 23.0, with P < 0.05 considered significant. Both groups showed significant improvement in theoretical and skills scores after the course. While there was no significant difference in overall theoretical or skills examination scores between groups, the PBL–CBL group achieved higher post-class case analysis scores (41.6 ± 3.44 vs. 38.08 ± 3.42, P = 0.001) and reported greater satisfaction (82.92 ± 4.9 vs. 79.67 ± 3.49, P = 0.01). Questionnaire results indicated that the PBL–CBL model significantly enhanced residents’ learning interest, initiative, and critical thinking ability compared with traditional teaching. The integrated PBL–CBL teaching model effectively improved gynecology residents’ reasoning ability, engagement, and satisfaction without compromising theoretical or procedural performance. This hybrid approach offers a feasible and scalable pedagogical innovation for residency programs, particularly in clinical settings where direct patient exposure is limited. Adoption of this model may contribute to cultivating reflective, competent, and patient-centered gynecologists.

BACKGROUND:Intratumoral angiogenesis is crucial for the proliferation and metastasis of ovarian cancer. This study aims to comprehensively analyze the impact of angiogenesis-related genes on clinical outcomes, the immune landscape, and immunotherapy response in ovarian cancer. RESULTS:Through integrated analysis of transcriptomic data from The Cancer Genome Atlas and Gene Expression Omnibus databases, we identified two novel angiogenesis subtypes that exhibited significant differences in clinicopathological features, prognostic outcomes, and tumor microenvironment characteristics. An angiogenesis-based risk score was developed, which effectively stratified patients into distinct risk groups. These groups demonstrated divergent clinical prognosis, immune cell infiltration patterns, expression levels of immune checkpoint genes, and sensitivity to chemotherapeutic agents. Furthermore, growth arrest-specific 1 was validated as a hub prognostic gene, showing abnormal expression in ovarian cancer tissues. Functional experiments confirmed that upregulation of growth arrest-specific 1 significantly suppressed the proliferative and migratory capacities of ovarian cancer cells. CONCLUSIONS:Our findings underscore the integral relationship between angiogenesis and the immune microenvironment in ovarian cancer. The angiogenesis-based risk score provides a promising prognostic tool, and growth arrest-specific 1 is implicated as a potential diagnostic and prognostic biomarker for ovarian cancer patients.

Introduction The prognosis for epithelial ovarian cancer (EOC) is exceedingly poor, with patients diagnosed with stage III/IV tumours typically offered cytoreductive surgery in conjunction with chemotherapy as a standard treatment option. This approach is intended to reduce the risk of surgery and address ovarian cancers that are not amenable to surgical intervention. A promising alternative and important treatment option is neoadjuvant chemotherapy (NACT) in conjunction with interstitial tumour cytoreductive surgery. The combination of neoadjuvant immunotherapy with chemotherapy has recently demonstrated remarkable efficacy, particularly in melanoma and lung cancer, with notable pathological responses and therapeutic benefits in tumour tissue. The NeoAdjuvant chemotherapy with or without tIslelizumab followed by debulking surgery for oVarian cancEr(NAIVE) study aims to assess the clinical efficacy and safety of NACT in combination with tislelizumab (a monoclonal antibody for programmed cell death protein 1) for advanced EOC.Methods and analysis The NAIVE study is an investigator-initiated, prospective, single-centre, open-label, randomised controlled trial for advanced EOC with the International Federation of Gynaecology and Obstetrics (FIGO) stage IIIc with a Suidan CT score of 3 or greater or a Fagotti laparoscopic score of 8 or greater; or FIGO stage IV. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate, measured as the percentage of patients who are free of tumour progression or death for 1 year after receiving the first dose of study drug. The secondary endpoints encompassed the R0 resection rate, the clinical response rate and other relevant metrics. Enrolled patients will be randomly assigned in a 1:1 ratio to either the experimental arm, which will receive neoadjuvant platinum-based chemotherapy in combination with tislelizumab, or the control arm, which will receive neoadjuvant platinum-based chemotherapy. The study will enrol 40 patients, with enrolment scheduled to start in April 2021 and complete in April 2025, given a 1-year PFS rate of 60%. The study will provide new evidence regarding the clinical efficacy and safety of NACT in combination with tislelizumab for advanced ovarian cancer. The results will contribute to a deeper understanding of the clinical effects, safety profile and fundamental immunological processes. The findings will contribute to the growing body of evidence in support of the incorporation of immunotherapy into the treatment paradigm for ovarian cancer, thus facilitating the development of more personalised and efficacious therapeutic modalities.Ethics and dissemination This trial has received ethical approval from the Institutional Ethics Committee of the Second Affiliated Hospital of the Medical College of Zhejiang University. Presentations at scientific and professional meetings and publication in peer-reviewed journals will disseminate the results of the study.Trial registration number NCT04815408.

Leukemia is a type of malignant tumor affecting hematopoietic system. Cervical cancer is a malignant tumor of female reproductive tract. The relationship between Calmodulin 3 (CALM3) and leukemia, cervical cancer remains unclear. Leukemia dataset GSE26294 and cervical cancer dataset GSE173097 profiles were downloaded from gene expression omnibus. Principal component analysis, differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis, protein-protein interaction network construction and analysis, survival analysis were performed. Gene expression heatmaps were plotted. Comparative Toxicogenomics Database (CTD) was used to find diseases most related to core genes. 77 DEGs were identified. According to gene ontology, in biological process category, they were mainly enriched in cell proliferation, immune response, and apoptotic process. In cellular component category, they were mainly enriched in nucleus and Golgi apparatus. In molecular function category, they were mainly enriched in DNA binding, protein binding, transcription factor activity. In Kyoto encyclopedia of gene and genome analysis, they were mainly enriched in cell adhesion molecules, Wnt signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, and basal cell carcinoma. The soft-threshold power in WGCNA was set to 1, generating 6 modules. Finally identifying 3 core genes (CALM3, secreted frizzled-related protein 4, plasminogen). CTD analysis revealed that core genes were related to leukemia, coagulation disorders, vaginal tumors, cervical tumors, autoimmune diseases, and inflammation. CALM3 is lowly expressed in leukemia samples and highly expressed in cervical cancer samples.

Referring all women who tested positive for human papillomavirus (HPV) 16/18 to colposcopy may lead to potential over-referral issues. Triage tests based on cytology results face challenges in achieving accurate diagnoses. Our study aims to assess the clinical effectiveness of PAX1/JAM3 methylation (CISCER) test as a triage method for HPV 16/18-positive women. From November 2021 to December 2022, a total of 334 women who tested positive for HPV 16/18 and were referred to colposcopy at The Second Affiliated Hospital of Zhejiang University School of Medicine were studied. The clinical utility of the CISCER test, cytology, and the combination of CISCER with cytology as potential triage tests was compared. We observed a significant increase in the methylation levels of PAX1 gene and JAM3 gene in women with cervical intraepithelial neoplasia (CIN) grade 2 or severe (CIN2+). The CISCER test demonstrated superior triage performance over cytology, even when used in combination with cytology, showing a high sensitivity of 89.0

Immunotherapy is less efficient for epithelial ovarian cancer and lacks ideal biomarkers to select the best beneficiaries for immunotherapy. CX3CR1 as chemokine receptor mainly expressed on immune cell membranes, and combined with its unique ligand CX3CL1, mediates tissue chemotaxis and adhesion of immune cells. However, the immune functional and prognostic value of CX3CR1 in epithelial ovarian cancer has not been clarified. A comprehensive retrospective analysis was performed by using the online database to identify the underlying immunological mechanisms and prognostic value of CX3CR1. The Human Protein Atlas, gene expression profiling interactive analysis, and TISIDB (an integrated repository portal for tumor-immune system interactions) database showed that CX3CR1 expressed higher in epithelial ovarian cancer than that in normal ovarian tissue. Four hundred twenty-two cases from Gene Expression Profiling Interactive Analysis and 1656 cases from Kaplan-Meier plotter database showed higher expression of CX3CR1 (above median) was associated with unfavorable overall survival. TIMER, UALCAN, and TISIDB database were applied to validate CX3CR1 negative impact on overall survival. In addition, correlation analysis showed that the expression level of CX3CR1 was positive association with infiltrating levels of B cells (R = 0.31, P = 3.10e-12), CD8(+) T cells (R = 0.26, P = 7.93e-09), CD4(+) T cells (R = 0.11, P = 1.41e-02), macrophages (R = 0.32, P = 4.29e-13), dendritic cells (R = 0.27, P = 2.98e-09), and neutrophil (R = 0.25, P = 3.25e-08) in epithelial ovarian cancer. Therefore, CX3CR1 involved in reshaping the immune microenvironment for epithelial ovarian cancer and maybe a potential immunotherapy target and prognostic marker for ovarian cancer.

Introduction: Myocardial fibrosis and cardiac dysfunction are the main characteristics of diabetic heart disease. However, the molecular mechanisms underlying diabetic myocardial fibrosis remain unclear. Objectives: This study aimed to investigate the heterogeneity of cardiac fibroblasts in diabetic mice and its possible mechanism in the development of diabetic myocardial fibrosis. Methods: We established a diabetic mouse model by injecting mice with streptozotocin. The overall cell profiles in diabetic hearts were analyzed using single-cell RNA transcriptomic techniques. Cardiac function was evaluated by echocardiography. Cardiac fibrosis was assessed by Masson’s trichrome and Sirius red staining. Protein expression was analyzed using Western blotting and immunofluorescence staining. Results: A total of 11,585 cells were captured in control (Ctrl) and diabetic (DM) hearts. Twelve cell types were identified in this study. The number of fibroblasts was significantly higher in the DM hearts than in the Ctrl group. The fibroblasts were further re-clustered into nine subsets. Interestingly, cluster 4 fibroblasts were significantly increased in diabetic hearts compared with other fibroblast clusters. Lysyl oxidase (Lox) was highly expressed in DM fibroblasts (especially in cluster 4). Beta-aminopropionitrile, a Lox inhibitor, inhibited collagen expression and alleviated cardiac dysfunction in the diabetic group. Lysyl oxidase inhibition also reduced high glucose-induced collagen protein upregulation in primary fibroblasts. Moreover, a TGF-β receptor inhibitor not only prevented an increase in Lox and Col I but also inhibited the phosphorylation of Smad2/3 in fibroblasts. Conclusions: This study revealed the heterogeneity of cardiac fibroblasts in diabetic mice for the first time. Fibroblasts with high expression of Lox (cluster 4 fibroblasts) were identified to play a crucial role in fibrosis in diabetic heart disease. The findings of this study may provide a possible therapeutic target for interstitial fibrosis.

Background: We recently reported a novel IgG4-centered immune evasion mechanism in cancer, and this was achieved mostly through the Fc-Fc reaction of increased IgG4 to cancer-bound IgG in cancer microenvironment. The mechanism was suggested to be related to cancer hyperprogressive disease (HPD) which is a side-effect often associated to IgG4 subtype PD-1 antibody immunotherapy. HPD was reported to occur in cancers with certain mutated genes including KRAS and such mutations are often associated to glutathione (GSH) synthesis. Therefore, we hypothesize that IgG4 and GSH may play a synergistic role in local immunosuppression of cancer. Methods: Quantitatively analyzed the distribution and abundance of GSH and IgG4 in human cancer samples with ELISA and immunohistochemistry. The interactions between GSH and IgG4 were examined with Electrophoresis and Western Blot. The synergistic effects of the two on classic immune responses were investigated in vitro. The combined effects were also tested in a lung cancer model and a skin graft model in mice. Results: We detected significant increases of both GSH and IgG4 in the microenvironment of lung cancer, esophageal cancer, and colon cancer tissues. GSH disrupted the disulfide bond of IgG4 heavy chain and enhanced IgG4’s ability of Fc-Fc reaction to immobilized IgG subtypes. Combined administration of IgG4 and GSH augmented the inhibitory effect of IgG4 on the classic ADCC, ADCP, and CDC reactions. Local administration of IgG4/GSH achieved the most obvious effect of accelerating cancer growth in the mouse lung cancer model. The same combination prolonged the survival of skin grafts between two different strains of mouse. In both models, immune cells and several cytokines were found to shift to the state of immune tolerance. Conclusion: Combined application of GSH and IgG4 can promote tumor growth and protect skin graft. The mechanism may be achieved through the effect of the Fc-Fc reaction between IgG4 and other tissue-bound IgG subtypes resulting in local immunosuppression. This reaction was facilitated by increased GSH to dissociate the two heavy chains of IgG4 Fc fragment at its disulfide bonds. Our findings unveiled the interaction between the redox system and the immune systems in cancer microenvironment. It offers a sensible explanation for HPD and provides new possibilities for manipulating this mechanism for cancer immunotherapy.

N-Acylethanolamine Acid Amidase ( NAAA ) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of NAAA in tumor immunity are still unclear. By using a series of bioinformatics approaches, we study combined data from different databases, including the Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Human Protein Atlas, TIMER, and ImmuCellAI to investigate the role of NAAA expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between NAAA expression and gene alterations, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that NAAA displayed abnormal expression within most malignant tumors, and overexpression of NAAA was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that NAAA was significantly associated with cell cycle and immune regulation-related signaling pathways, such as in innate immune system, adaptive immune system, neutrophil degranulation, and Toll-like receptor signaling pathways (TLRs). Further, the expression of NAAA was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophage (TAM). In addition to this, we found that NAAA is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that NAAA expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that NAAA plays an important role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.

Background: Although various effective compounds for the second- and third-line treatment of advanced or recurrent cervical cancer improved the overall survival, the optimal regimen remains controversial. Previous studies revealed that apatinib had extensive anti-tumor activities. However, almost all studies on apatinib in recurrent cervical cancer are non-randomized controlled trials with small sample sizes, different first-line treatments, and uncontrolled statistical analysis, which may result in a lack of effective metrics to evaluate the efficacy and safety of apatinib. Here, this meta-analysis aims to evaluate the efficacy and safety of apatinib in patients with advanced or recurrent cervical cancer.Methods: PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for relevant studies. Outcomes including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for further analysis.Results: Seven studies involving 243 patients were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 22.9% and 68.6%, respectively. With regard to survival analysis, the pooled PFS and OS were 5.19 months and 10.63 months, respectively. The most common treatment-related adverse events of apatinib were hand–foot syndrome (all grade: 39.6%, ≥grade III: 7.5%), hypertension (all grade: 34.5%, ≥grade III: 9.2%), and fatigue (all grade: 28.0%, ≥grade III: 5.1%).Conclusions: In summary, this meta-analysis demonstrated that apatinib has promising efficacy and safety for patients with advanced or recurrent cervical cancer.Systematic Review Registration:https://inplasy.com/inplasy-2022-7-0049/, identifier INPLASY202270049

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OBJECTIVES:To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer.MATERIALS AND METHODS:MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers.RESULTS:MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063).CONCLUSIONS:MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker.

Background Recent impressive advances in cancer immunotherapy have been largely derived from cellular immunity. The role of humoral immunity in carcinogenesis has been less understood. Based on our previous observations we hypothesize that an immunoglobulin subtype IgG4 plays an essential role in cancer immune evasion. Methods The distribution, abundance, actions, properties and possible mechanisms of IgG4 were investigated with human cancer samples and animal tumor models with an extensive array of techniques both in vitro and in vivo. Results In a cohort of patients with esophageal cancer we found that IgG4-containing B lymphocytes and IgG4 concentration were significantly increased in cancer tissue and IgG4 concentrations increased in serum of patients with cancer. Both were positively related to increased cancer malignancy and poor prognoses, that is, more IgG4 appeared to associate with more aggressive cancer growth. We further found that IgG4, regardless of its antigen specificity, inhibited the classic immune reactions of antibody-dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis and complement-dependent cytotoxicity against cancer cells in vitro, and these effects were obtained through its Fc fragment reacting to the Fc fragments of cancer-specific IgG1 that has been bound to cancer antigens. We also found that IgG4 competed with IgG1 in reacting to Fc receptors of immune effector cells. Therefore, locally increased IgG4 in cancer microenvironment should inhibit antibody-mediated anticancer responses and help cancer to evade local immune attack and indirectly promote cancer growth. This hypothesis was verified in three different immune potent mouse models. We found that local application of IgG4 significantly accelerated growth of inoculated breast and colorectal cancers and carcinogen-induced skin papilloma. We also tested the antibody drug for cancer immunotherapy nivolumab, which was IgG4 in nature with a stabilizing S228P mutation, and found that it significantly promoted cancer growth in mice. This may provide an explanation to the newly appeared hyperprogressive disease sometimes associated with cancer immunotherapy. Conclusion There appears to be a previously unrecognized immune evasion mechanism with IgG4 playing an essential role in cancer microenvironment with implications in cancer diagnosis and immunotherapy.

BACKGROUND:Few screening markers for malignant transformation in borderline ovarian tumors (BOT) have been clearly established. The kinase noncatalytic C-lobe domain containing 1 (KNDC1), a brain-specific Ras guanine nucleotide exchange factor, negatively regulates dendrite growth. However, the biological role and underlying mechanism of KNDC1 in human cancers, including ovarian cancer (OC), remain unknown. METHODS:Gene chip screening was used to detect the expression of KNDC1 mRNA in normal ovarian tissues, BOT tissues, and OC tissues. And results were further validated by RT-qPCR, Western blotting and immunohistochemistry. KNDC1 overexpression and knockdown ovarian cancer cells were established to study the possible pathways that KNDC1 was involved. The effects of KNDC1 on the malignant behaviors of ovarian tumors were also investigated both in vitro and in vivo. RESULTS:We observed that the expression of KNDC1 mRNA and KNDC1 protein in OC was significantly downregulated compared with BOT. Subsequent investigation revealed that knockdown of KNDC1 enhanced the proliferation of ovarian cancer cells in vitro via induction of ERK1/2 phosphorylation, whereas reinforcing the expression of KNDC1 attenuated the ERK1/2 activity. Similarly, knockdown of KNDC1 also promoted cell proliferation in vivo. Survival analysis showed that lower KNDC1 predicted a poor progression-free survival (PFS) for patients. CONCLUSION:Collectively, we conclude that KNDC1 might function as a tumor suppressor in ovarian tumors, inhibiting the proliferation of ovarian cells by suppressing ERK1/2 activity and hindering the malignant transformation of BOT.

Department of Gynecology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China Abstract: Tumor-associated macrophages (TAMs) that appear in every stage of cancer progression are usually tumor-promoting cells and are present abundantly in the tumorassociated microenvironment. In ovarian cancer, the overall and intratumoral M1/M2 ratio is a relatively efficient TAM parameter for predicting the prognosis of patients, especially for serous tissue type cancer. TAMs exhibit immunological checkpoint modulators, such as the B7 family and programmed death-ligand 1 (PD-L1), and play a key role in the development, metastasis and invasion of ovarian cancer, but the underlying mechanism is barely understood. Ovarian cancer is a severe gynecological malignancy with high mortality. Ovarian cancer-associated death can primarily be attributed to cancer metastasis. The majority of patients are diagnosed with wide dissemination in the peritoneum and omentum, limiting the effectiveness of surgery and chemotherapy. In addition, unlike other well-documented cancers, metastasis through vasculature is not a usual dissemination pathway in ovarian cancer. This review sheds light on TAMs and the main process and mechanism of ovarian cancer metastasis.

A 49-year-old woman, gravida 5, para 1, with a diagnosis of congenital uterine arteriovenous malformation (AVM), presented to our hospital for a further hysterectomy. The patient underwent uterine artery embolization (UAE) to treat profuse vaginal bleeding on October 9, 2017. During the process of UAE, a tortuous and dilated uterine artery with focal aneurysm were seen. And there were also aboudant arteriovenous shunting (Fig. 1). At 1 week after UAE, magnetic resonance imaging (MRI) revealed an enlarged uterus and thickened myometrium (Fig. 2A), with malformed vessels involving almost the entire myometrium (Fig. 2B and C) and some ectatic feeding vessels around the uterus (Fig. 2D). On October 23, 2017, the patient underwent computed tomography (CT) angiography at the Women's Hospital School of Medicine, Zhejiang University, which showed extremely tortuous and dilated right ovarian vessels (Fig. 3). Fig. 2Magnetic resonance imaging findings. (A) Enlarged uterus and thickened myometrium in a T2-weighted image. (B) Multiple long T2 mottling signals representing the malformed vessels in a T1-weighted image. (C) Multiple long T1 and short T2 signals representing the malformed vessels involving almost the whole myometrium in a coronal T2-weighted image. (D) Tortuous and dilated feeding vessels in an enhanced MRI image. The uterus had inhomogeneous enhancement. View Large Image Figure Viewer Download Hi-res image Fig. 3Computed tomography angiography showing tortuous and dilated vessels, with more obvious dilation of the right ovarian vessel (red arrow). View Large Image Figure Viewer Download Hi-res image

Tumor-associated macrophages (TAMs) that appear in every stage of cancer progression are usually tumor-promoting cells and are present abundantly in the tumor-associated microenvironment. In ovarian cancer, the overall and intratumoral M1/M2 ratio is a relatively efficient TAM parameter for predicting the prognosis of patients, especially for serous tissue type cancer. TAMs exhibit immunological checkpoint modulators, such as the B7 family and programmed death-ligand 1 (PD-L1), and play a key role in the development, metastasis and invasion of ovarian cancer, but the underlying mechanism is barely understood. Ovarian cancer is a severe gynecological malignancy with high mortality. Ovarian cancer-associated death can primarily be attributed to cancer metastasis. The majority of patients are diagnosed with wide dissemination in the peritoneum and omentum, limiting the effectiveness of surgery and chemotherapy. In addition, unlike other well-documented cancers, metastasis through vasculature is not a usual dissemination pathway in ovarian cancer. This review sheds light on TAMs and the main process and mechanism of ovarian cancer metastasis.

The roles of long non-coding RNAs (lncRNAs), a class of long non-protein-coding RNAs, in the tumorigenesis of ovarian epithelial cells remain unknown. In this study, we discovered that the expression of long intergenic non-coding RNA 1088 (LINC01088) was clearly reduced in benign epithelial ovarian tumor tissues compared to matched normal ovarian tissues. This was shown by global cDNA gene chip scanning and real-time qPCR, and validated in 42 clinical specimens. Furthermore, we found that LINC01088 inhibited the growth of ovarian cancer xenografts in nude mice. Correlation analysis between LINC01088 and mircoRNAs (miRNAs) conducted using primary clinical samples and RNA co-precipitation experiments revealed that miR-24-1-5p was one of the targets of LINC01088. Overexpression of miR-24-1-5p facilitated cell proliferation both in vitro and in vivo, however, LINC01088 could partially reverse the cell proliferation induced by miR-24-1-5p. Finally, we demonstrated that p21 activated kinase 4 (PAK4) was one of the downstream key targets of miR-24-1-5p by luciferase reporter assay and Western blotting; and our results showed a remarkable decrease in cell proliferation after overexpression of PAK4. We conclude that LINC01088 might function as a tumor suppressor, inhibiting the tumorigenesis of ovarian epithelial cells through LINC01088/ miR-24-1-5p/ PAK4 axis.