Efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer

BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditional open surgery is the main treatment for ovarian cancer,but it has the disadvantages of big trauma and slow recovery.With the continuous development of minimally invasive technology,minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery.However,the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.AIM To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.METHODS The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively.According to the different surgical treatment methods,patients were divided into study group and control group(45 cases in each group).The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer,while the control group received traditional open surgery for ovarian cancer.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),clinical efficacy and safety of the two groups were compared.RESULTS The intraoperative blood loss,length of hospital stay,postoperative gas evacuation time,and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group(P<0.05).The incidence of postoperative complications in the study group was significantly lower than in the control group(P<0.05).The two groups had no significant differences in the preoperative adrenocorticotropic hormone(ACTH),androstenedione(AD),cortisol(Cor),cluster of differentiation 3 positive(CD3+),and cluster of differentiation 4 positive(CD4+)indexes(P>0.05).In contrast,postoperatively,the study group's ACTH,AD,and Cor indexes were lower,and the CD3+and CD4+indexes were higher than those in the control group(P<0.05).CONCLUSION Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety,improve the short-term prognosis and quality of life of patients,and is worth popularizing.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

LncRNA IDH1-AS1 sponges miR-518c-5p to suppress proliferation of epithelial ovarian cancer cell by targeting RMB47

Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.

Primary ovarian cancer combined with primary fallopian tube cancer:A case report

BACKGROUND Low grade serous carcinoma of the ovary(LGSOC)is a rare type of epithelial ovarian cancer with a low incidence rate.The origin of ovarian cancer has always been a hot topic in gynecological oncology research,and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes.Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system.There are only a few reports in the literature,but the mortality rate is very high.But in clinical practice,fallopian tube cancer is very common,but in most cases,it is classified as ovarian cancer.CASE SUMMARY We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment.The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube.No special treatment was performed after the surgery,and the patient was instructed to undergo regular follow-up without any signs of disease progression.CONCLUSION The prognosis of LGSOC is relatively good,over 80%of patients still experience disease recurrence.

Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor survival.it has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and development.However,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still unclear.Methods:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian carcinoma.Cytotoxicity assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer cells.RNA pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer cells.Results:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian cancer.Functional experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this function.Mechanistically,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

Exploring the molecular mechanisms and potential therapeutic strategies of ferroptosis in ovarian cancer

The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the modulation of ferroptosis.By targeting microRNA-587,lncRNA ADAMTS9 antisense RNA 1(ADAMTS9-AS1)can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis.Although ferroptosis holds promise in overcoming the resistance mechanism,there remain obstacles in utilizing it as a cancer treatment,including the potential harm of drugs to healthy cells.Hence,additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies.

Immune pathway through endometriosis to ovarian cancer

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women

BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.

Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

Ovarian Tumors in Senegalese Women: Impact of D-Loop Mutations between Healthy and Cancerous Tissues

In Senegal in particular, ovarian cancer, which is one of the most common gynecological cancers, accounts for 2.8% of deaths. The most important risk factor is genetic, with 10% of cases occurring in a context of genetic predisposition. The sequencing of the human genome, which has led to the discovery of millions of sequence variations, makes it possible to study variations within sequences. These variations are limited to Single Nucleotide Polymorphisms (SNPs) and this common form of polymorphism occurs approximately every 1000 bases in the human genome and 1.8 million SNPs are currently listed according to [1]. The aim of this study is to gain a better understanding of the impact of mutations in the D-loop region of mtDNA on ovarian cancer in Senegalese women. This study involved searching for mutations in our study population after DNA extraction and sequencing. Mutations were found after a comparison of our sequences with the Cambridge reference sequence (NC_012920). The mutations found in the DNA studied extend from position 7 to position 16568 and most of these mutations are located in the hypervariate zones (HV1 and HV2). Heteroplasmy with three mutant alleles was also found in certain variants. Common mutations were found in both healthy and cancerous tissues, with almost identical frequencies in both types of tissue. This enabled us to understand the spread of tumor cells throughout the ovary.

New Progress of CA125 Surveillance in Diagnosis and Treatment of Ovarian Cancer

The fatality rate of ovarian cancer (OC) is the highest, and the 5-year survival rate is only 50.8%. For more than 40 years, CA125 has been the most concerned and widely used biomarker of OC in clinical practice. In recent years, many researchers have proposed a reliable strategy of multiple markers combined with CA125 to screen OC to make up for the lack of accuracy of CA125, redefine the biochemical recurrence threshold of CA125, and use mathematical model scores to provide help for the feasibility of treatment and survival prognosis. To fully understand the role of CA125 in OC screening, initial treatment, and recurrence prediction, and summarize the limitations of CA125, this review has summarized the new progress of CA125 in the diagnosis and treatment of OC in recent years which can also provide a reference for clinicians.

Surgical resection and neoadjuvant therapy in patients with gastric cancer and ovarian metastasis: A real-world study

BACKGROUND Regarding when to treat gastric cancer and ovarian metastasis(GCOM)and whether to have metastatic resection surgery,there is presently debate on a global scale.The purpose of this research is to examine,in real-world patients with GCOM,the survival rates and efficacy of metastatic vs non-metastasized resection.AIM To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM.METHODS This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People’s Hospital from June 2009 to July 2023.The diagnosis of all patients was confirmed by pathology.The primary study endpoints included overall survival(OS),ovarian survival,OS after surgery(OSAS),disease-free survival(DFS),differences in efficacy.RESULTS This study had 41 patients in total.The surgical group(n=27)exhibited significantly longer median OS(mOS)and median overall months(mOM)compared to the nonoperative group(n=14)(mOS:23.0 vs 6.9 months,P=0.015;mOM:18.3 vs 3.8 months,P=0.001).However,there were no significant differences observed in mOS,mOM,median OSAS(mOSAS),and median DFS(mDFS)between patients in the surgical resection plus neoadjuvant therapy group(n=11)and those who surgical resection without neoadjuvant therapy group(n=16)(mOS:26.1 months vs 21.8 months,P=0.189;mOM:19.8 vs 15.2 months,P=0.424;mOSAS:13.9 vs 8.7 months,P=0.661,mDFS:5.1 vs 8.2 months,P=0.589).CONCLUSION Compared to the non-surgical group,the surgical group’s survival duration and efficacy are noticeably longer.The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.

Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer:a multicenter,open-label,non-inferiority,randomized controlled trial

Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.

TGF-β-regulated different iron metabolism processes in the development and cisplatin resistance of ovarian cancer

The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.

Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.

Multiple Potential Markers of Chemosensitivity of Ovarian Cancer, Among Which KELIM of CA125 Is Low Cost and Efficient

Aim: Ovarian cancer (OC) is a malignant cancer with the highest death rate among various kinds of gynecological tumors. The treatment pattern of HGSCs is mainly primary debulking surgery (PDS), followed by platinum-based adjuvant chemotherapy, which has been the preferred treatment plan in recent years. Treatment decision-making remains a problem that needs to be addressed. We write this article to summarize the relevant indicators reported and find better decision-making tools. Methods: We have extensively read and understood the literature in the research field involved. We searched for keywords in Pubmed: ovarian cancer;KELIM;chemosensitivity. Later we summarized and organized the current research status in the last two decades. Results: There are many predictors of chemotherapy sensitivity, including pathological chemotherapy response score (CRS), the level of tumor-infiltrating lymphocytes (TILs), BRCA mutations in germ lines or somatic cells, tumor homologous recombination deficiency (HRD), KELIM of CA125 and so on. Many clinical trials have testified that this marker of chemosensitivity all have their own advantages and disadvantages. KELIM of CA125 is low-cost and efficient, which is worth promoting and applying in clinical practice. Conclusions: Many studies have validated the predictive and guiding value of the KELIM of Ca125 in the diagnosis and therapy of ovarian cancer. Nowadays, KELIM of Ca125 is rarely known by clinical doctors and lacks clinical application. We advise that KELIM of CA125 is a potential prognostic factor of ovarian cancer. As a clinical doctor in the process of treating ovarian cancer, we can combine the patient’s situation with KELIM, to develop personalized treatment plans. Not only can it reduce the occurrence of complications, but it can also lower medical costs.

Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways

Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.

LncRNA CACNA1G-AS1 up-regulates FTH1 to inhibit ferroptosis and promote malignant phenotypes in ovarian cancer cells

Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.

Targeting endoplasmic reticulum stress signaling in ovarian cancer therapy

The endoplasmic reticulum(ER),an organelle present in various eukaryotic cells,is responsible for intracellular protein synthesis,post-translational modification,and folding and transport,as well as the regulation of lipid and steroid metabolism and Ca2+homeostasis.Hypoxia,nutrient deficiency,and a low pH tumor microenvironment lead to the accumulation of misfolded or unfolded proteins in the ER,thus activating ER stress(ERS)and the unfolded protein response,and resulting in either restoration of cellular homeostasis or cell death.ERS plays a crucial role in cancer oncogenesis,progression,and response to therapies.This article reviews current studies relating ERS to ovarian cancer,the most lethal gynecologic malignancy among women globally,and discusses pharmacological agents and possible targets for therapeutic intervention.

MiR-194-5p suppresses the warburg effect in ovarian cancer cells through the IGF1R/PI3K/AKT axis

Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor(IGF1R).In this study,we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells.Methods:The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection.ATP generation,glucose uptake,lactate production and extracellular acidification rate(ECAR)assay were used to analyze the effects of aerobic glycolysis in ovarian cancer cells.Gene expression was analyzed by quantitative polymerase chain reaction(qPCR)and western blot.Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancer tissues.Results:Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATP generation,glucose uptake,lactate production,and ECAR and inhibits both the mRNA and protein expression of PKM2,LDHA,GLUT1,and GLUT3.While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway,whose activation can sustain aerobic glycolysis in cancer cells,and the knockdown of miR-194-5p expression promoted the activation of the PI3K/AKT pathway.Conclusion:Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKT pathway,which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.