Ovarian cancer continues to carry a poor prognosis, particularly in resource-limited settings. Using estimates from the International Agency for Research on Cancer, we conducted a secondary analysis of ovarian cancer burden across 47 Asian countries in 2022 and projected the burden through 2050. Age-standardized incidence and mortality rates (ASIR, ASMR) were obtained from GLOBOCAN 2022, using the Segi–Doll standard population. Associations with the Human Development Index (HDI) were assessed using Spearman’s correlation. Age–period–cohort (APC) modeling was applied to explore generational risk patterns based on mortality data from 1993 to 2022. In 2022, Asia accounted for 178.2 thousand new cases and 109.5 thousand deaths. ASIR and ASMR were 6.2 and 3.7 per 100,000, respectively. Brunei Darussalam exhibited the highest incidence (13.2 per 100,000), and the Philippines had the highest mortality (7.5 per 100,000). APC analysis revealed higher cohort-specific risks among women born in more recent birth cohorts relative to those born in 1949–1957 (reference cohort). ASIR (r = 0.425, P < 0.05) and ASMR (r = 0.309, P < 0.05) were positively correlated with HDI among women aged ≥ 50 years. High body-mass index emerged as the leading modifiable risk factor contributing to mortality, with the highest contributions in Kuwait (22.3

Objective Resistance to platinum-based chemotherapy remains a key obstacle in ovarian cancer treatment. This study aims to investigate the role of Uncoordinated 51-like kinase 2 (ULK2) in chemoresistance of ovarian cancer and elucidate its underlying mechanisms using 3D patient-derived organoids. Methods Survival analysis was first performed using the Kaplan‒Meier plotter database. Immunohistochemical profiling delineated differential ULK2 expression patterns between chemoresistant and chemosensitive ovarian cancer tissue samples and organoids. ULK2 overexpression was achieved in cisplatin-resistant ovarian cancer organoids via lentiviral vector transduction. Then, we conducted an in-depth examination of the alterations in phosphorylated proteins induced by ULK2 overexpression using phosphoproteomics technology. To investigate the influence of ULK2 on chemosensitivity in ovarian cancer, Cell Counting Kit-8 (CCK-8) and in vivo experiments were conducted. Glycolysis was quantitatively assessed, and the underlying molecular mechanism was systematically investigated. Results ULK2 high-expression ovarian cancer exhibited enhanced chemosensitivity and conferred survival advantage. CCK-8 and mouse experiments demonstrated that ULK2 overexpression decreased cisplatin resistance in patient-derived organoids. Gene Ontology (GO) analysis of phosphoproteomics profiling highlighted the predominant role of ULK2 in metabolic processes with experimental validation demonstrating its suppression of glycolysis. Mechanistically, ULK2 attenuated c-Jun expression by phosphorylation of c-Jun at Ser243. Moreover, c-Jun overexpression counteracted the chemosensitivity and glycolytic suppression induced by the ectopic ULK2 expression in ovarian cancer. Conclusions ULK2 overcomes cisplatin resistance in ovarian cancer by downregulating glycolysis, a process mediated by phosphorylation-induced c-Jun degradation. These findings emphasized the role of ULK2 as a tumor suppressor, offering novel insights for chemotherapy in ovarian cancer.

BACKGROUND:Cisplatin-based chemotherapy serves as a fundamental approach in the treatment of cervical cancer; however, its effectiveness is often hindered by the development of drug resistance, which presents a significant obstacle in clinical practice. METHODS:Differentially expressed genes (DEGs) related to ferroptosis in cervical cancer were examined compared to healthy controls, using data from the Gene Expression Omnibus (GEO) database and the ferroptosis database (FerrDb V2). Lipid peroxidation, ferrous ion (Fe2+) concentration, and reactive oxygen species (ROS) were examined. In vitro and in vivo studies were carried out to explore the influence of Ribonucleotide reductase M2 (RRM2) on the effectiveness of cisplatin chemotherapy. RESULTS:We identified an aggregate of 4,385 statistically significant DEGs, among which 122 genes were related to ferroptosis. Moreover, the ferroptosis-related gene RRM2 was notably overexpressed in cervical cancer and demonstrated remarkable sensitivity and specificity for diagnosing cervical cancer. Additionally, the expression levels were inversely correlated with the outcomes of patients with cervical cancer. Furthermore, RRM2 silencing increased cervical cancer cell ferroptosis and enhanced the efficacy of cisplatin treatment in vitro and in vivo. Finally, our experiments established a positive association between RRM2 and the classical ferroptosis inhibition factor GTP cyclohydrolase 1 (GCH1) by immunofluorescence and immunoblotting. CONCLUSION:RRM2 plays roles in the evaluation and outcome prediction of cervical cancer, potentially impacting cisplatin sensitivity through regulation of ferroptosis. This investigation provides novel insights into the tumorigenic functions of RRM2, highlighting its potential use as a prognostic biomarker in cervical carcinoma.

Ovarian cancer is known for its high recurrence rates and poor prognosis, primarily due to chemoresistance, which significantly limits treatment options. Grasping the processes that contribute to chemoresistance is essential for the advancement of more efficient therapy methods. Firstly, we discovered that nuclear receptor subfamily 1 group D member 2 (NR1D2) was significantly elevated in cisplatin-resistant ovarian cancer cells, as revealed by RNA sequencing. Subsequent study indicated that NR1D2 was highly expressed in chemo-resistant ovarian cancer samples than the chemo-sensitive group, and negatively correlated with ovarian cancer patients' survival. Moreover, NR1D2 silencing markedly contributed to cisplatin susceptibility of ovarian cancer cells. Additionally, the analysis of untargeted metabolomics mass spectrometry demonstrated a significant correlation between NR1D2 and the process of ferroptosis. Following this, we observed that NR1D2 silencing considerably increased the concentration of lipid peroxidation malondialdehyde (MDA) and ferrous ion, concomitant with downregulation of ferroptosis suppressor protein 1 (FSP1). Finally, the study revealed that NR1D2 influences immune infiltration in ovarian cancer. In summary, NR1D2 served as a prognostic biomarker in ovarian cancer and induced cisplatin-resistance. Furthermore, its expression was linked to ferroptosis and immune regulation within the tumor microenvironment. Targeting NR1D2 may provide a potential therapeutic strategy to enhance treatment efficacy in ovarian cancer.

ObjectiveTo establish a predictive model for distinguishing testicular benign or yolk sac tumors in children.MethodsWe retrospectively analyzed data for 119 consecutive patients with unilateral testicular tumors treated at a single institution from June 2014 to July 2020. The patients were divided into the benign (n = 90) and yolk sac (n = 29) tumor groups based on the pathological diagnosis. We recorded patient age, serum markers [serum alpha-fetoprotein (AFP), human chorionic gonadotropin], and tumor ultrasonic findings (maximum diameter, ultrasonic echo, blood flow signal). Predictive factors were identified using descriptive statistical methods. A nomogram was established for preoperative prediction. An additional 46 patients were used as a validation cohort to verify the model.ResultsPatients with testicular yolk sac tumors were younger (median age: 14.0 vs. 34.0 months, P = 0.001) and had a higher incidence of elevated AFP levels (93.1% vs. 2.2%, P < 0.001). Ultrasonography indicated that testicular yolk sac tumors tended to have larger maximum diameters (26.5 ± 11.3 vs. 16.6 ± 9.2 cm, P < 0.001), a higher proportion of hypoechoic masses (44.8% vs. 8.9%, P < 0.001), and a higher incidence of masses with strong blood flow signals (93.1% vs. 5.6%, P < 0.001). A nomogram based on age, AFP levels, and ultrasound blood flow signals effectively predicted the probability of yolk sac tumor in children, with an accuracy of 0.98 (95% confidence interval: 0.984–1.003). The Brier score of the nomogram was 0.0002.ConclusionA nomogram based on age, AFP levels, and ultrasound blood flow signals can effectively predict the probability of testicular yolk sac tumor preoperatively, aiding in clinical decision-making and patient counseling.

Background Ovarian cancer is an aggressive malignancy with high mortality known for its considerable metastatic potential. This study aimed to explore the expression and functional role of Unc-51 like autophagy activating kinase 2 (ULK2) in the progression of ovarian cancer. Methods ULK2 expression patterns in ovarian cancer tissues as well as benign tumor control samples obtained from our institution were evaluated using immunohistochemistry. Cell counting kit 8 and Transwell assays were applied to assess the effects of ULK2 overexpression on cell proliferation, migration and invasion, respectively. RNA sequencing was performed to explore potential mechanisms of action of ULK2 beyond its classical autophagy modulation. Results Our experiments showed significant downregulation of ULK2 in ovarian cancer tissues. Importantly, low expression of ULK2 was markedly correlated with decreased overall survival. In vitro functional studies further demonstrated that overexpression of ULK2 significantly suppressed tumor cell proliferation, migration, and invasion. RNA sequencing analysis revealed a potential regulatory role of ULK2 in the insulin signaling pathway through upregulation of insulin-like growth factor binding protein-3 (IGFBP3) in ovarian cancer cells. Conclusions In summary, the collective data indicated that ULK2 acted as a tumor suppressor in ovarian cancer by upregulating the expression of IGFBP3. Our study underscores the potential utility of ULK2 as a valuable prognostic marker for ovarian cancer.

Ample evidence reveals that glycolysis is crucial to tumor progression; however, the underlying mechanism of its drug resistance is still worth being further explored. TRAF6, an E3 ubiquitin ligase, is well recognized to overexpress in various types of cancer, which predicts a poor prognosis. In our study, we discovered that TRAF6 was expressed more significantly in the case of triple-negative breast cancer (TNBC) than in other of breast cancers, promoting chemoresistance to paclitaxel; that inhibited TRAF6 expression in the chemoresistant TNBC (TNBC-CR) cells enhanced the sensitivity by decreasing glucose uptake and lactate production; that TRAF6 regulated glycolysis and facilitated chemoresistance via binding directly to PKM2; and that overexpressing PKM2 in the TNBC-CR cells with TRAF6 knocked down regained significantly TRAF6-dependent drug resistance and glycolysis. Additionally, we verified that TRAF6 could facilitate PKM2-mediated glycolysis and chemoresistance in animal models and clinical tumor tissues. Thus, we identified the novel function of TRAF6 to promote glycolysis and drug resistance in TNBC with the regulation of PKM2, which could provide a potential molecular target for TNBC treatment.

背景与目的 细胞程序性死亡配体1(programmed cell death-ligand 1,PD-L1)通过与细胞程序性死亡受体1(programmed cell death-1,PD-1)相互作用,在免疫检查点应答中发挥作用,但是,PD-L1在肿瘤细胞中的作用机制尚未阐明.本研究探讨了PD-L1在卵巢癌进展和转移过程中的分子调控机制.方法 对良性卵巢肿瘤组织和卵巢癌组织标本进行免疫组化分析,在PD-L1敲减的卵巢癌细胞中进行迁移、侵袭和血管生成实验.通过免疫沉淀、质谱、染色质免疫沉淀、斑马鱼和小鼠实验,探讨PD-L1在卵巢癌中的具体功能和作用的分子机制.结果 体内和体外实验结果表明,PD-L1通过促进血管生成促进卵巢癌的转移和侵袭.在机制上,PD-L1直接与血管内皮生长因子受体2(vascular endothelial growth factor receptor-2,VEGFR2)相互作用,并激活FAK/AKT通路,进而促进血管生成和肿瘤进展,并与卵巢癌患者预后不良相关.同时,研究发现PD-L1为致癌转录因子c-JUN的下游调控因子,从而使PD-L1在卵巢癌中高表达.此外,实验表明PD-L1抑制剂度伐利尤单抗(durvalumab)和抗血管生成药物阿帕替尼(apatinib)联合使用可以增强抗血管生成作用,抑制卵巢癌细胞转移和侵袭.结论 我们的研究结果表明,PD-L1通过激活c-JUN/VEGFR2信号轴促进卵巢癌的血管生成和转移,PD-L1抑制剂和抗血管生成药物联合使用可能是治疗卵巢癌患的潜在方法.

BACKGROUND:Rapid progression and early metastasis remain the main cause of high mortality in epithelial ovarian cancer (EOC) patients. The objective of this study was to explore the mechanisms of EOC progression and detect the function of leucine-rich alpha-2-glycoprotein 1 (LRG1) in modulating the pathologic process.METHODS:Ultracentrifugation was initially performed to extract exosomes from the urine samples of EOC patients and healthy female subjects. Mass spectrometry (MS) was employed to analyze differentially expressed proteins. Survival analysis was performed to examine the association between LRG1 levels and the prognosis of EOC patients. LRG1 silencing ovarian cancer cell lines were built and cell migration was further evaluated via wound healing and transwell assays. Immunoblot, immunofluorescence and immunohistochemistry analyses were performed. A subcutaneous tumor model was established to study the function of LRG1 in vivo.RESULTS:Exosomal LRG1 was specifically expressed in urine samples of EOC patients and high LRG1 levels were significantly associated with poor prognosis. Function analyses showed that LRG1 was associated with ovarian cancer migration and progression. Mechanistically, LRG1 was significantly related to the focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathway.CONCLUSIONS:LRG1 participated in progression and metastasis of ovarian cancer via activation of the FAK/AKT pathway probably.

BACKGROUND:Stanniocalcin 1 (STC1) plays an integral role in ovarian cancer (OC). However, the functional role of STC1 in metastasis, lipid metabolism and cisplatin (DDP) chemoresistance in OC is not fully understood.METHODS:Single-cell sequencing and IHC analysis were performed to reveal STC1 expression profiles in patient tissues. Metastasis, lipid metabolism and DDP chemoresistance were subsequently assessed. Cell-based in vitro and in vivo assays were subsequently conducted to gain insight into the underlying mechanism of STC1 in OC.RESULTS:Single-cell sequencing assays and IHC analysis verified that STC1 expression was significantly enhanced in OC tissues compared with para-carcinoma tissues, and it was further up-regulated in peritoneal metastasis tissues compared with OC tissues. In vitro and in vivo experiments demonstrated that STC1 promoted metastasis, lipid metabolism and DDP chemoresistance in OC. Simultaneously, STC1 promoted lipid metabolism by up-regulating lipid-related genes such as UCP1, TOM20 and perilipin1. Mechanistically, STC1 directly bound to integrin β6 (ITGB6) to activate the PI3K signaling pathway. Moreover, STC1 was directly regulated by Forkhead box C2 (FOXC2) in OC. Notably, targeting STC1 and the FOXC2/ITGB6 signaling axis was related to DDP chemoresistance in vitro.CONCLUSIONS:Overall, these findings revealed that STC1 promoted metastasis, lipid metabolism and DDP chemoresistance via the FOXC2/ITGB6 signaling axis in OC. Thus, STC1 may be used as a prognostic indicator in patients with metastatic OC. Meanwhile, STC1 could be a therapeutic target in OC patients, especially those who have developed chemoresistance to DDP.

To investigate the urodynamic study (UDS) result in pediatric patients suffering from spastic cerebral palsy (CP). Medical records of patients diagnosed CP having pre-operative UDS results underwent selective dorsal rhizotomy (SDR) from Jan. 2020 to May. 2021 were retrospectively reviewed. Fifty-seven cases diagnosed spastic CP were included in the study (mean age, 6.73 ± 2.84 years), among which, 46 were ambulatory and 11 non-ambulatory. Average gross motor function measure-66 (GMFM-66) score was 62.16 ± 11.39. Reduced bladder capacity was seen in 49.12% of these cases and cases with lower GMFM-66 score possessed a higher incidence rate of having low bladder capacity (p < 0.01). Detrusor overactivity (DO) was shown in 33.33% of the patients. Cases with younger age presented a higher prevalence of DO (p < 0.05). Meanwhile, more non-ambulant patients suffered from DO (p < 0.05). Increased post-voiding residual (PVR) was seen in 21.05% of the cases. Those with higher average threshold in sphincter-associated input spinal nerve roots (rootlets) witnessed a higher rate of having abnormal PVR (p < 0.05). Abnormal UDS results were prevalent in pediatric patients suffering from CP. Motor function, age and threshold of their sphincter-associated spinal nerve roots laid corresponding effect on the abnormal UDS results.

目的 探讨丝切蛋白1(CFL1)对卵巢癌生物学功能的影响,并初步探寻其机制.方法 检测CFL1在良恶性卵巢肿瘤中表达水平;结合GEO数据库以及上海交通大学医学院附属新华医院卵巢癌样本资料分析CFL1对卵巢癌患者预后的影响;划痕以及Transwell实验检测CFL1沉默对卵巢癌细胞迁移、侵袭能力的影响;Western blot探索相关分子机制.结果 卵巢癌组织中CFL1显著高表达,且其在转移灶组织中表达水平高于原发灶,在晚期卵巢癌组织中表达水平高于早期卵巢癌;CFL1高表达患者总生存期(OS)以及无进展生存期(PFS)明显缩短;CFL1沉默显著降低蛋白激酶B(AKT1)磷酸化激活,抑制卵巢癌细胞侵袭迁移.结论CFL1与卵巢癌患者预后呈显著负相关,并可通过激活AKT通路促进卵巢癌细胞侵袭转移,故靶向抑制CFL1或可成为卵巢癌治疗的新手段.

AbstractBackgroundChemotherapy resistance is a primary reason of ovarian cancer therapy failure; hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets.MethodsRNA sequencing of cisplatin‐resistant and ‐sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin‐1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1‐knockout cisplatin‐resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and Fӧrster resonance energy transfer‐fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish.ResultsFBN1 expression was significantly enhanced in cisplatin‐resistant ovarian cancer organoids and tissues, indicating that FBN1 might be a key factor in chemoresistance of ovarian cancer. We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo, which promoted the cisplatin‐resistance of ovarian cancer. Knockout of FBN1 combined with treatment of the antiangiogenic drug apatinib improved the cisplatin‐sensitivity of ovarian cancer cells. Mechanistically, FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) at the Tyr1054 residue, which activated its downstream focal adhesion kinase (FAK)/protein kinase B (PKB or AKT) pathway, induced the phosphorylation of signal transducer and activator of transcription 2 (STAT2) at the tyrosine residue 690 (Tyr690), promoted the nuclear translocation of STAT2, and ultimately altered the expression of genes associated with STAT2‐mediated angiogenesis and glycolysis.ConclusionsThe FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1‐targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.

BACKGROUND:Although programmed cell death-ligand 1 (PD-L1) plays a well-known function in immune checkpoint response by interacting with programmed cell death-1 (PD-1), the cell-intrinsic role of PD-L1 in tumors is still unclear. Here, we explored the molecular regulatory mechanism of PD-L1 in the progression and metastasis of ovarian cancer. METHODS:Immunohistochemistry of benign tissues and ovarian cancer samples was performed, followed by migration, invasion, and angiogenesis assays in PD-L1-knockdown ovarian cancer cells. Immunoprecipitation, mass spectrometry, and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD-L1 in ovarian cancer. RESULTS:Our results showed that PD-L1 induced angiogenesis, which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer. Mechanistically, PD-L1 was identified to directly interact with vascular endothelial growth factor receptor-2 (VEGFR2) and then activated the FAK/AKT pathway, which further induced angiogenesis and tumor progression, leading to poor prognosis of ovarian cancer patients. Meanwhile, PD-L1 was found to be regulated by the oncogenic transcription factor c-JUN at the transcriptional level, which enhanced the expression of PD-L1 in ovarian cancer. Furthermore, we demonstrated that PD-L1 inhibitor durvalumab, combined with the antiangiogenic drug, apatinib, could enhance the effect of anti-angiogenesis and the inhibition of cell migration and invasion. CONCLUSION:Our results demonstrated that PD-L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c-JUN/VEGFR2 signaling axis, suggesting that the combination of PD-L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.

Background: Due to its high ability of metastasis, ovarian cancer remains the most lethal gynecological malignancy, yet its underlying mechanism remains unconfirmed. Objectives : The main purpose is to probe into the role and regulation mechanism of octamer-binding transcription factor 4 (OCT4) in angiogenesis and metastasis in ovarian cancer. Methods : Immunohistochemistry (IHC) and immunofluorescence in epithelial ovarian cancer specimens and benign ovarian tumor samples were performed, followed by RNA-sequencing and examination of angiogenesis, cell migration and invasion in OCT4 knockdown cell lines and the controls. Co-Immunoprecipitation (Co-IP), mass spectrometry, immunoblotting, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses were conducted along with models of zebrafishes and nude mice of transplanted tumors to gain insights into the specific functions and mechanisms of action of OCT4 in ovarian cancer. Results : Firstly, we discovered that OCT4 expression was enhanced in ovarian cancer tissues significantly, especially in the metastatic lesions, indicating that OCT4 might be a key for the metastasis of ovarian cancer. Furtherly, we observed and verified that OCT4 promoted cell migration and invasion, and induced angiogenesis in vitro and in vivo. Mechanistically, OCT4 modulated the transcription of leucine‑rich PPR motif‑containing protein (LRPPRC)，and furtherly interacted with vascular endothelial growth factor receptor 2 (VEGFR2)/LRPPRC complex and ultimately triggered the downstream FAK/AKT signaling pathway . Conclusions: Together, through models of ovarian cancer cells, zebrafishes and tumor-transplanted mice, this study highlighted the importance of OCT4/LRPPRC/VEGFR2 signaling axis in metastasis of ovarian cancer and angiogenesis. Thus, our finding supplied a potential novel molecular-targeted approach for the treatment of ovarian cancer.

Ovarian cancer (OC) is one of the most common malignant tumors in women. OC is associated with the activation of oncogenes, the inactivation of tumor suppressor genes, and the activation of abnormal cell signaling pathways. Moreover, epigenetic processes have been found to play an important role in OC tumorigenesis. Epigenetic processes do not change DNA sequences but regulate gene expression through DNA methylation, histone modification, and non-coding RNA. This review comprehensively considers the importance of epigenetics in OC, with a focus on microRNA and long non-coding RNA. These types of RNA are promising molecular markers and therapeutic targets that may support precision medicine in OC. DNA methylation inhibitors and histone deacetylase inhibitors may be useful for such targeting, with a possible novel approach combining these two therapies. Currently, the clinical application of such epigenetic approaches is limited by multiple obstacles, including the heterogeneity of OC, insufficient sample sizes in reported studies, and non-optimized methods for detecting potential tumor markers. Nonetheless, the application of epigenetic approaches to OC patient diagnosis, treatment, and prognosis is a promising area for future clinical investigation.

Abstract Background Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet. Methods Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α. Results In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin. Conclusion In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.

BACKGROUND:Ovarian cancer is highly lethal and has a poor prognosis due to metastasis. Long non-coding RNAs (lncRNAs) are key regulators of tumor development, but their role in ovarian cancer metastasis remains unclear.METHODS:The expression of lnc-CTSLP8 in ovarian cancer was analyzed in public databases (TCGA and GEO) and validated via qRT-PCR. Lnc-CTSLP8 overexpression and knockout cell lines were constructed using a lentiviral vector and the CRISP/Cas9 system. Cell proliferation, colony formation, migration, and invasion were analyzed. An ovarian orthotopic tumor mouse model was used for the in vivo study. Changes in autophagosomes, autolysosomes, and mitochondria in ovarian cancer cells were observed via transmission electron microscopy. EMT markers were detected by immunoblotting and immunofluorescence assays. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assays were performed to confirm the interaction between lnc-CTSLP8 and miR-199a-5p.RESULTS:A novel pseudogene, lnc-CTSLP8, was identified in ovarian cancer, with significantly elevated expression in metastatic tumor tissues compared to primary ovarian tumors. When overexpressed, lnc-CTSLP8 promoted ovarian cancer in vitro and in vivo by acting as a sponge for miR-199a-5p. Autophagy and EMT in ovarian cancer were also enhanced by lnc-CTSLP8. Mechanistically, lnc-CTSLP8 upregulated CTSL1 as a competitive endogenous RNA and exhibited oncogenic effects. Moreover, CTSL1 inhibitor treatment and miR-199a-5p overexpression abrogated the effects of lnc-CTSLP8 overexpression.CONCLUSIONS:lnc-CTSLP8 acts as a ceRNA in ovarian cancer and represents a potential therapeutic target for metastatic ovarian cancer.

Abstract Objective To investigate the urodynamic study (UDS) result in pediatric patients with spastic cerebral palsy (CP). Material and methods Medical records of CP with pre-operative UDS results underwent selective dorsal rhizotomy (SDR) from Jan. 2020 to May. 2021 were retrospectively reviewed. Results Fifty-seven cases with spastic CP were included in the study. Among these cases, 46 were ambulatory and 11 were non-ambulatory. Average gross motor function measure - 66 (GMFM - 66) score was 62.16 ± 11.39. Reduced bladder capacity was seen in 49.12% of these cases and cases with lower GMFM - 66 score had a higher incidence rate of having low bladder capacity (p < 0.01). Detrusor overactivity (DO) was shown in 33.33% of patients. Cases with younger age had higher prevalence of DO (p < 0.05). Meanwhile, more non-ambulant patients had DO (p < 0.05). Increased post-voiding residual (PVR) was seen in 21.05% of cases. Those with higher average threshold in sphincter-associated input spinal nerve roots (rootlets) had higher rate of having abnormal PVR (p < 0.05). Conclusion Abnormal UDS results were prevalent in pediatric spastic CP. Motor function, age and threshold of their sphincter-associated spinal nerve rootlets were related to the abnormal UDS results.

Background: Ovarian cancer remains the most lethal gynecologic malignancy. In this study, we aimed to identify the specific risk factors affecting overall survival (OS) and develop a nomogram for prognostic prediction of ovarian cancer patients based on data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Information from the SEER database on ovarian cancer between 2004 and 2016 was screened and retrieved. Cases were randomly divided into the training cohort hand the validation cohort at a 7:3 ratio. The prognostic effects of individual variables on survival were evaluated via Kaplan-Meier method and Cox proportional hazards regression model using data from the training cohort. A nomogram was formulated to predict the 3- and 5-year OS rates of patients with ovarian cancer, and then validated both in the training cohort and the validation cohort. Results: A total of 28,375 patients were selected from 75,921 samples (19,862 in training cohort and 8,513 in validation cohort). Cox regression analysis identified race, age laterality, histology, stage, grade, surgery, chemotherapy, radiotherapy, and marital status as independent risk factors for ovarian cancer prognosis. A nomogram was developed based on the results of multivariate analysis and validated using an internal bootstrap resampling approach, which demonstrated a sufficient level of discrimination according to the C-index (0.752, 95% CI: 0.746-0.758 in the training cohort, 0.755, 95% CI: 0.746-0.764). Conclusions: We developed a nomogram valuable for accurate prediction of 3- and 5-year OS rates of ovarian cancer patients based on individual characteristics.