Outcome In Ovarian Cancer Patients Research Articles

Cytoreductive HIPEC-Combined Surgery in Treatment of Advanced Ovarian Cancer

Background. Ovarian cancer ranks 5th in the structure of female oncological mortality in the Russian Federation, with a first-year post-diagnosis rate of almost 35%. In 75% cases, ovarian cancer is diagnosed at stages III—IV. The disease usually represents as peritoneal carcinomatosis regarded as an advanced form that demands attention, which renders the issue highly relevant. We present a literature review and analysis of combined treatment outcomes in ovarian cancer patients hospitalised at the Kuvatov Republican Clinical Hospital within period 2020—2021.Materials and methods. The article reviews foreign and national scientific literature, as well as reports the case data on 18 patients diagnosed with ovarian cancer and treated at the Department of Oncology of the Kuvatov Republican Clinical Hospital within period 2020—2021.Results and discussion. A complete cytoreductive surgery was performed in 100% cases. In cohort I, mean operation time was 256 vs. 364 min, mean intraoperative blood loss — 1200 vs. 1050 mL, mean hospital stay — 14.6 vs. 18.7 bed-days. Postoperative complications were 16.7 vs. 50% in cohort I vs. II. A 30-day mortality rate was 0 vs. 16.6% in cohort I vs. II. The monitoring and enrolment of patients currently continues.Conclusion. A HIPEC procedure is not a radical measure and can only achieve a maximum efficacy if coupled with a complete cytoreduction. The treatment of stage III—IV ovarian cancer patients in a concurrent combined approach is promising and requires further in-depth research and a more robust statistics.

HLA-DR Presentation of the Tumor Antigen MSLN Associates with Clinical Outcome of Ovarian Cancer Patients.

Simple SummaryThe immunopeptidome represents the entirety of peptides that are presented on the surface of cells on human leukocyte antigen (HLA) molecules and are recognized by the T-cell receptors of CD4+ and CD8+ T-cells. Malignant cells present tumor-associated antigens essential for tumor immune surveillance, which can be targeted by T-cell-based immunotherapy approaches. For ovarian carcinomas, various tumor-associated antigens, such as Mucin-16 and Mesothelin, have been described. The aim of our study is to analyze immunopeptidome-defined tumor antigen presentation in ovarian carcinoma patients in relation to clinical characteristics and disease outcomes to define potential biomarkers. Our work demonstrates the central role of HLA-DR-restricted peptide presentation of the tumor antigen Mesothelin and of CD4+ T-cell responses for tumor immune surveillance, and underlines Mesothelin as a prime target antigen for novel immunotherapeutic approaches for ovarian carcinoma patients.T-cell recognition of HLA-presented antigens is central for the immunological surveillance of malignant disease and key for the development of novel T-cell-based immunotherapy approaches. In recent years, large-scale immunopeptidome studies identified naturally presented tumor-associated antigens for several malignancies. Regarding ovarian carcinoma (OvCa), Mucin-16 (MUC16) and Mesothelin (MSLN) were recently described as the top HLA class I- and HLA class II-presented tumor antigens, respectively. Here, we investigate the role and impact of immunopeptidome-presented tumor antigens on the clinical outcomes of 39 OvCa patients with a follow-up time of up to 50 months after surgery. Patients with a HLA-restricted presentation of high numbers of different MSLN-derived peptides on their tumors exhibited significantly prolonged progression-free (PFS) and overall survival (OS), whereas the presentation of MUC16-derived HLA class I-restricted peptides had no impact. Furthermore, a high HLA-DRB gene expression was associated with increased PFS and OS. In line, in silico prediction revealed that MSLN-derived HLA class II-presented peptides are predominantly presented on HLA-DR allotypes. In conclusion, the correlation of MSLN tumor antigen presentation and HLA-DRB gene expression with prolonged survival indicates a central role of CD4+ T-cell responses for tumor immune surveillance in OvCa, and highlights the importance of immunopeptidome-guided tumor antigen discovery.

Postoperative pulmonary complications and outcomes in cytoreductive surgery for ovarian cancer: a propensity-matched analysis

ObjectivesTo assess the prevalence of postoperative pulmonary complications (PPCs), the perioperative factors associated with PPCs, and the association of PPCs with postoperative outcomes in ovarian cancer patients undergoing cytoreductive surgery.MethodsA retrospective analysis was conducted on patients who underwent cytoreductive surgery in our hospital, between September 2017 and January 2021, and patient medical records were reviewed to collect relevant clinical information. Univariable and multivariable analyses were used to identify significant risk factors for PPCs. Analysis of the association of PPCs with postoperative outcomes, mortality and 30-day readmission, was undertaken utilizing propensity score-matched controls and multivariable logistic regression model.ResultsFinal analysis was performed with 268 ovarian cancer patients after cytoreductive surgery, among whom the incidence of PPCs was 26.9%, and the most frequent pulmonary complication was pleural effusion. According to the multivariate analysis, the intraoperative fluid infusion volume (L) (odds ratio (OR) 1.34; 95% confidence intervals (CI) 1.01–1.77; P = 0.040), diameter size of diaphragmatic resection (cm) (OR 1.16; 95% CI 1.06–1.28; P = 0.002), and surgical complexity scores (OR 1.26; 95% CI 1.13–1.42; P < 0.001) were significantly associated with the development of PPCs. The multivariable logistic regression analyses with propensity-matched controls demonstrated that the occurrence of PPCs significantly increased the risk of 30-day readmission (OR 6.01; 95% CI 1.12–32.40; P = 0.037) and did not significantly affect inpatient mortality.ConclusionOvarian cancer patients undergoing cytoreductive surgery, especially those with diaphragmatic resection or higher surgical complexity scores, represent a high-risk population for PPCs. In addition, goal-directed fluid therapy is vital to reducing the occurrence of PPCs in patients at risk. PPCs were not associated with in-hospital mortality but were significantly associated with an increased risk of 30-day readmission after cytoreductive surgery.

Adenosine Receptor A2B Negatively Regulates Cell Migration in Ovarian Carcinoma Cells.

The purinergic system is fundamental in the tumor microenvironment, since it regulates tumor cell interactions with the immune system, as well as growth and differentiation in autocrine-paracrine responses. Here, we investigated the role of the adenosine A2B receptor (A2BR) in ovarian carcinoma-derived cells’ (OCDC) properties. From public databases, we documented that high A2BR expression is associated with a better prognostic outcome in ovarian cancer patients. In vitro experiments were performed on SKOV-3 cell line to understand how A2BR regulates the carcinoma cell phenotype associated with cell migration. RT-PCR and Western blotting revealed that the ADORA2B transcript (coding for A2BR) and A2BR were expressed in SKOV-3 cells. Stimulation with BAY-606583, an A2BR agonist, induced ERK1/2 phosphorylation, which was abolished by the antagonist PSB-603. Pharmacological activation of A2BR reduced cell migration and actin stress fibers; in agreement, A2BR knockdown increased migration and enhanced actin stress fiber expression. Furthermore, the expression of E-cadherin, an epithelial marker, increased in BAY-606583-treated cells. Finally, cDNA microarrays revealed the pathways mediating the effects of A2BR activation on SKOV-3 cells. Our results showed that A2BR contributed to maintaining an epithelial-like phenotype in OCDC and highlighted this purinergic receptor as a potential biomarker.

The use of biomarkers to stratify surgical care in women with ovarian cancer: Scientific Impact Paper No. 69 May 2022.

Biomarkers may offer unforeseen insights into clinical diagnosis, as well as the likely course and outcome of a condition. In this paper, the focus is on the use of biological molecules found in body fluids or tissues for diagnosis and prediction of outcome in ovarian cancer patients. In cancer care, biomarkers are being used to develop personalised treatment plans for patients based on the unique characteristics of their tumour. This tailoring of care can be used to pursue specific targets identified by biomarkers, or treat the patient according to specific tumour characteristics. Surgery is one of the core treatments for ovarian cancer, whether it is offered in primary surgery or following chemotherapy in delayed surgery. Biomarkers already exist to guide the treatment of tumours with chemotherapy, but very little research has determined the value of biomarkers in tailoring surgical care for ovarian cancer. Such research is required to identify new biomarkers and assess their effectiveness in a clinical setting as well as to help identify specific tumour types to guide surgery. Biomarkers could help to determine the success of removing the disease surgically, or help to identify tumour deposits that persist after chemotherapy. All of these aspects would improve current practice. This Scientific Impact Paper highlights research that may pave the way towards bespoke surgery according to the biological characteristics of a tumour and aid gynaecological oncologists to provide surgical treatment according to individual need, rather than a blanket approach for all.

Pheophorbide A and SN38 conjugated hyaluronan nanoparticles for photodynamic- and cascadic chemotherapy of cancer stem-like ovarian cancer

In this study, we designed photo-triggered reactive oxygen species (ROS)-generating pheophorbide A and ROS-cleavable thioketal-SN38 conjugated hyaluronan-cholesterol nanoparticles (PheoA-SN38-HC NPs). And we observed the combined therapeutic effects of PheoA-SN38-HC NPs against HEY-T30 human ovarian cancer (OC) model. Clinical Proteomic Tumor Analysis Consortium (CPTAC) data showed that the expression of cancer stem cell (CSC) markers (CD44, ALDH1A1, and CD117) is highly associated with poor clinical outcomes in OC patients. We proved that HEY-T30 cells overexpress CSC markers and much more invasive than other cancer cells. Flow cytometry (FACS) and microscopic analysis revealed the active targeting property of PheoA-SN38-HC NPs to CD44+ HEY-T30 cells. Moreover, the combination therapeutic effect of PheoA-SN38-HC NPs was clearly demonstrated against in vitro HEY-T30 cells and an in vivo xenograft mouse model. In particular, the paracrine cytotoxic effect of SN38 probably compensates the locoregional therapeutic limitation of photodynamic therapy.

NAP1L1 promotes tumor proliferation through HDGF/C-JUN signaling in ovarian cancer

BackgroundNucleosome assembly protein 1-like 1 (NAP1L1) is highly expressed in various types of cancer and plays an important role in carcinogenesis, but its specific role in tumor development and progression remains largely unknown. In this study, we suggest the potential of NAP1L1 as a prognostic biomarker and therapeutic target for the treatment of ovarian cancer (OC).MethodsIn our study, a tissue microarray (TMA) slide containing specimens from 149 patients with OC and 11 normal ovarian tissues underwent immunohistochemistry (IHC) to analyze the correlation between NAP1L1 expression and clinicopathological features. Loss-of- function experiments were performed by transfecting siRNA and following lentiviral gene transduction into SKOV3 and OVCAR3 cells. Cell proliferation and the cell cycle were assessed by the Cell Counting Kit-8, EDU assay, flow cytometry, colony formation assay, and Western blot analysis. In addition, co-immunoprecipitation (Co-IP) and immunofluorescence assays were performed to confirm the relationship between NAP1L1 and its potential targets in SKOV3/OVCAR3 cells.ResultsHigh expression of NAP1L1 was closely related to poor clinical outcomes in OC patients. After knocking down NAP1L1 by siRNA or shRNA, both SKOV3 and OVCAR3 cells showed inhibition of cell proliferation, blocking of the G1/S phase, and increased apoptosis in vitro. Mechanism analysis indicated that NAP1L1 interacted with hepatoma-derived growth factor (HDGF) and they were co-localized in the cytoplasm. Furthermore, HDGF can interact with jun proto-oncogene (C-JUN), an oncogenic transformation factor that induces the expression of cyclin D1 (CCND1). Overexpressed HDGF in NAP1L1 knockdown OC cells not only increased the expression of C-JUN and CCND1, but it also reversed the suppressive effects of si-NAP1L1 on cell proliferation.ConclusionsOur data demonstrated that NAP1L1 could act as a prognostic biomarker in OC and can interact with HDGF to mediate the proliferation of OC, and this process of triggered proliferation may contribute to the activation of HDGF/C-JUN signaling in OC cells.

An update on the safety of olaparib for treating ovarian cancer

ABSTRACT Introduction PARP inhibitors have dramatically improved outcomes for ovarian cancer patients, transforming oncologists’ armamentarium and fueling hope for more cures and longer survival. Areas covered The recent PARP inhibitor randomized trials of FDA approved PARP inhibitors for ovarian cancer, olaparib, rucaparib and niraparib, and implications for clinical care are discussed with a focus on toxicity and risks. PARP adds NAD polymers to DNA-binding proteins, improving survival of cells after DNA damage, and acting as a scaffold for important DNA Damage Response (DDR) enzymes. If this system is inhibited, PARP activation cannot support DNA repair when there is synthetic lethality from BRCA mutations or homologous repair dysfunction (HRD), and the accumulation of DNA damage can kill cancer and lead to the catastrophic complications of MDS/AML. Although the risk of AML can be a < 1% risk, the incidence of MDS/AML presently approaches 10% in patients with BRCA mutations, multiple prior lines of platinum therapy, and protracted exposure to PARP inhibitors. Expert opinion PARP inhibitors are a well-tolerated and exciting new class of agents that improve survival despite the risk of AML. Understanding of the biology has led to optimal use and potential new strategies for overcoming PARP resistance.

KLF8 is activated by TGF-β1 via Smad2 and contributes to ovarian cancer progression.

Krüppel-like factor 8 (KLF8) is a transcription factor expressed abnormally in various cancer types and promotes oncogenic transformation. However, the role of KLF8 in ovarian cancer (OC) progression remains unclear. This study reports that transforming growth factor-β1(TGF-β1)/Smad2/KLF8 axis regulates epithelial-mesenchymal transition (EMT) and contributes to OC progression. We analyzed the KLF8 expression in OC cells and tissues, wherein a significant overexpression of KLF8 was observed. Increased KLF8 expressions were correlated with higher cell proliferation, EMT, migration, and invasion and conferred poor clinical outcomes in OC patients. Overexpressed KLF8 increases F-actin polymerization and induces cytoskeleton remodeling of OC cells. Furthermore, a dissection of the molecular mechanism defined that TGF-β1 triggers KLF8 through the Smad2 pathway and regulates EMT. Pharmacological and genetic inhibition of Smad2 followed by TGF-β1 treatment failed to activate KLF8 expression and induction of EMT. Using promoter-luciferase reporter assays, we defined that upon TGF-β1 activation, phosphorylated Smad2 binds and promotes the KLF8 promoter activity, and knockdown of Smad2 inhibits KLF8 promoter activation. Together, these results demonstrate that TGF-β1 activates KLF8 expression by the Smad2 pathway, and KLF8 contributes to OC progression and may serve as a potential therapeutic strategy for treating OC patients.

Retrospective analysis of bevacizumab-induced arthralgia and clinical outcomes in ovarian cancer patients. Single center experience

BackgroundJoint manifestations are ill-defined adverse events that were frequently reported of bevacizumab in ovarian cancer patients. The aim of this study is to describe the incidence and severity of joint manifestations among bevacizumab treated patients as well as their relation to clinical outcomes. MethodsMedical charts of all ovarian cancer patients that received bevacizumab from 2012 through 2017 were reviewed. Joint manifestations were staged. Kaplan-Meier Survival curves were generated; survival differences were estimated. Results76 Patients diagnosed with stage III or IV ovarian cancer were included. 23 patients (30.3%) developed joint manifestations, 12 of them had Grade I, 4 Grade II and 7 Grade III. Only 3 patients developed arthritis. In 8 cases (34.8%) one joint was affected and in the remaining 15, multiple sites. Median number of bevacizumab cycles to arthralgia development was 7. 3 patients were managed with corticosteroids or methotrexate, all had grade 3 AEs. The remaining received common analgesics. Median duration of the AE was 4.8 months. 7 patients discontinued bevacizumab due to AE. In all but 3 patients AE was finally resolved. Median number of bevacizumab cycles received, frequency of treatment completion or treatment discontinuation due to disease progression did not differ significantly among patients that developed joint manifestations or not. Median PFS and median OS did not differ statistical significantly. ConclusionJoint manifestations are common AEs in bevacizumab treated ovarian cancer patients and led to treatment discontinuation in 9% of the patients. However, this has not adversely affected the clinical outcome of the patients. Further research is needed for the appropriate management of these patients.

Ascites in ovarian cancer: MicroRNA deregulations and their potential roles in ovarian carcinogenesis.

Ovarian cancer comprises the most lethal gynecologic malignancy and is accompanied by the high potential for the incidence of metastasis, recurrence and chemotherapy resistance, often associated with a formation of ascitic fluid. The differentially expressed ascites-derived microRNAs may be linked to ovarian carcinogenesis. The article focuses on a number of miRNAs that share a common expression pattern as determined by independent studies using ascites samples and with regard to their functions and outcomes in experimental and clinical investigations.Let-7b and miR-143 have featured as tumor suppressors in ovarian cancer, which is in line with data on other types of cancer. Although two miRNAs, i.e. miR-26a-5p and miR-145-5p, act principally as tumor suppressor miRNAs, they occasionally exhibit oncogenic roles. The performance of miR-95-3p, upregulated in ascites, is open to debate given the current lack of supportive data on ovarian cancer; however, data on other cancers indicates its probable oncogenic role. Different findings have been reported for miR-182-5p and miR-200c-3p; in addition to their presumed oncogenic roles, contrasting findings have indicated their ambivalent functions. Further research is required for the identification and evaluation of the potential of specific miRNAs in the diagnosis, prediction, treatment and outcomes of ovarian cancer patients.

Association Between Risk of Malnutrition and Surgical Outcome in Ovarian Cancer Patients

Ovarian cancer is the fourth most cancer in Indonesia. Treatment of ovarian cancer is surgery. Malnutrition may complicate healing, so studying the association between malnutrition and surgical outcome in ovarian cancer patients is necessary. A cross-sectional study was conducted in Dr. Cipto Mangunkusumo General Hospital from July 2018 - March 2019. fromo 63 patients underwent surgery, four were excluded due to non-malignant ovarian pathology results. Parameters assessed were characteristic subjects and risk factors of malnutrition in ovarian cancer patients. Malnutrition was assessed using the Patient-Generated Subjective Global Assessment (PGSGA) and surgery factors assessed were the length of surgery, size of the tumor, and blood loss during surgery. The nutritional status was classified as well-nourished and malnourished. The receiver operating characteristic (ROC) curve is used to assess malnutrition, length of stay, size of the tumor, and blood loss during surgery. The result shows that the prevalence of malnutrition in ovarian cancer was 78% (moderate was 42.4% and severe was 35.6%), and the median length of stay was eight days. There is an association (chi-square test, p&lt;0.05) between malnutrition and surgical outcome in ovarian cancer patients. Malnutrition is associated (chi-square test, p&lt;0.05) with a length of stay and increased blood loss during surgery.

UCP1 modulates immune infiltration level and survival outcome in ovarian cancer patients

BackgroundThe uncoupling proteins (UCPs) are critical genes associated with tumorigenesis and chemoresistance. However, little is known about the molecular mechanism of the UCPs in ovarian cancer (OV).Material and methodsUCPs expression analysis was conducted using Gene Expression Profiling Interactive Analysis (GEPIA), and its potential in clinical prognosis was analyzed using Kaplan- Meier analyses. The influence of UCPs on immune infiltration was analyzed by TIMER. In addition, the correlation between UCPs expression and molecular mechanisms was investigated by TIMER and Cancer Single-cell State Atlas (CancerSEA).ResultsUCP1, UCP2, UCP3 and UCP5 expression levels correlated with a favorable prognosis and tumor progression. Moreover, UCP1 expression correlated to several immune cell markers and regulated tumorigenesis, such as tumor invasion, EMT, metastasis and DNA repair. In addition, UCP1 potentially involved in genes expression of SNAI2, MMP2, BRCA1 and PARP1.ConclusionsThese results implied a critical role of UCP1 in the prognosis and immune infiltration of ovarian cancer. In addition, UCP1 expression participated in regulating multiple oncogenes and tumorigenesis.

Ovarian cancer and KiSS-1 gene expression: A consideration of the use of Kisspeptin plus Kisspeptin aptamers in diagnostics and therapy

Gynaecological cancers continue to present a significant health burden upon the health of the global female population. This deficit is most prominent with ovarian cancer which possesses the lowest survival rate compared to all other cancers occurring within this anatomical region, with an annual UK-mortality of 7,300. The poor tolerability and selectively of the treatment options that are currently available is likely to have contributed to this high mortality rate thus, demonstrating the need for the development of enhanced therapeutic approaches. Aptamer technology would involve the engineering of specifically sequenced oligonucleotide chains, which bind to macromolecular targets with a high degree of affinity and selectively. Recent in-vitro studies conducted upon the clinical utility of this technique have supported its superiority in targeting individual therapeutic drug targets compared to various other targeting moieties currently within therapeutic use such as, monoclonal antibodies. For this reason, the employment of this technique is likely to be favourable in reducing the incidence of non-specific, chemotherapy-associated adverse effects. Kisspeptin is a naturally expressed polypeptide with an established role in the development of the reproductive system and other proposed roles in influencing the ability of ovarian cancer growths to exhibit the metastasis hallmark. This distinctive feature would indicate the potential for the manipulation of this pathway through the application of aptamer structures in developing a novel prophylactic strategy and improve the long-term outcome for ovarian cancer patients.

Integrative analysis deciphers the heterogeneity of cancer-associated fibroblast and implications on clinical outcomes in ovarian cancers

Accumulating evidence has recognized that cancer-associated fibroblasts (CAFs) are major players in the desmoplastic stroma of ovarian cancer, modulating tumor progression and therapeutic response. However, it is unclear regarding the signatures of CAFs could be utilized to predict the clinical outcomes of ovarian cancer patients. To fill in this gap, we explored the intratumoral compartment of ovarian cancer by analyzing the single-cell RNA-sequencing (scRNA-seq) datasets of ovarian carcinoma samples, and identified two distinct CAFs (tumor-promoting CAF_c1 subtype and myofibroblasts-like CAF_c2 subtype). The clinical significance of CAF subtypes was further validated in The Cancer Genomics Atlas (TCGA) database and other independent immunotherapy response datasets, and the results revealed that the patients with a higher expression of CAF_c1 signatures had a worse prognosis and showed a tendency of resistance to immunotherapy. This work uncovered the signatures of the CAF_c1 subtype that could serve as a novel prognostic indicator and predictive marker for immunotherapy.

Prevalence of BRCA1 and BRCA2 pathogenic sequence variants in ovarian cancer patients in the Gulf region: the PREDICT study

BackgroundPatients with pathogenic sequence variants (PSVs) in BRCA1/BRCA2 are at high risk of developing ovarian cancer (OC). However, genetic testing for BRCA1/BRCA2 PSVs is still not a routine practice in the Middle East. With the lack of epidemiological studies in the region, we aim to describe the prevalence of BRCA1/BRCA2 PSVs in patients with OC across different countries in the Gulf region.MethodsThe PREDICT study was an observational, prospective, epidemiological study, which consecutively recruited women with ovarian, primary peritoneal, and fallopian tube cancers from the following Gulf countries over the period from July 2017 to July 2019; United Arab Emirates (UAE), Kuwait, and Oman. The study was approved by the local ethics committee of participating centers. The BRCA1/BRCA2 PSVs were assessed by tissue genetic testing using next-generation sequencing (NGS).ResultsA total of 105 women were included with a median age at diagnosis of 52 years (IQR 44.5 – 61.0). Nearly 11.4% of patients reported a family history of ovarian or breast cancer, while 4.7% of patients reported a family history of other cancers. Most of the patients (70.3%) had advanced disease (FIGO stage III/IV) at presentation. Eighty-eight patients (84%) were successfully tested for somatic BRCA1/BRCA2 PSVs. Fifteen patients (17%) were found to have PSVs in either BRCA1, BRCA2, or both genes; of them, 10 patients (11.2%) had BRCA1 somatic PSVs alone, eight patients (9.1%) had BRCA2 somatic PSVs, while three patients (2.9%) had both PSVs. Five patients with BRCA1/BRCA2 somatic PSVs had germline PSVs tests, and three of them tested positive. Concerning treatment, 87.6% of patients received perioperative chemotherapy and 6.6% as first-line palliative chemotherapy. Eighty-seven (82.9%) patients underwent debulking surgery, with no residual disease in 42.5% of patients.ConclusionOur study showed that the prevalence of BRCA1/BRCA2 somatic PSVs in patients with OC is higher than the reported global figures (2-8%). However, more studies are warranted to further elucidate the prevalence of BRCA1/BRCA2 somatic and germline PSVs, as well as other relevant genetic alterations, to better understand their impact on OC patient outcomes in Gulf countries.Trial registrationNCT03082976.

The Platelet-Activating Factor Receptor's Association with the Outcome of Ovarian Cancer Patients and Its Experimental Inhibition by Rupatadine.

The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic effect on ovarian cancer cells. The clinically approved PAFR antagonist rupatadine effectively inhibited in vitro cell proliferation and migration of ovarian cancer cells. PAFR is a prognostic marker in ovarian cancer patients and its inhibition through rupatadine may have important therapeutic implications in the therapy of ovarian cancer patients.

Non-Surgical Management of Malignant Bowel Obstruction in Advanced Ovarian Cancer patients: A Systematic Review and Meta-Analysis.

Background:Malignant bowel obstruction is a common cause of morbidity and mortality in patients with advanced ovarian cancer. Many patients aren’t suitable for, or decline, surgical decompression. The outcomes for this frail group of patients are not well characterized.Aim:To evaluate survival outcomes of ovarian cancer patients who undergo non-surgical management of malignant bowel obstruction.Design:Systematic review and meta-analysis.Data Sources:Online literature search of Pubmed, Embase and Medline libraries up until December 2020. Searching abstracts of scientific meetings, reference lists of included studies and contacting experts in the field.Selection Criteria:Studies that investigated non-surgical management of confirmed bowel obstruction in advanced ovarian cancer patients were included. All levels of evidence including RCTs, cohort studies and case-series if they included greater than 5 patients.Data Collection and Analysis:The studies were independently chosen by two reviewers who extracted and analyzed the data separately through OpenMeta Analyst software. Study quality was assessed using the JADAD score and the Newcastle Ottawa Score.Results:24 studies met the eligibility criteria for the systematic review and 9 for the meta-analysis. Median survival of patients managed non-surgically for bowel obstruction was 44 days (95% CI 38-49 days, I 2 = 0%, P = 0.128).Conclusion:The quality of studies was relatively low, however the evidence shows that non-surgical management of bowel obstruction results in a short life expectancy but with controlled symptoms. Where quality of life is the main concern, this may be a feasible and effective strategy.

The Emerging Role of Non-coding RNAs in Drug Resistance of Ovarian Cancer.

Ovarian cancer is one of the most common gynecological malignancies with highest mortality rate among all gynecological malignant tumors. Advanced ovarian cancer patients can obtain a survival benefit from chemotherapy, including platinum drugs and paclitaxel. In more recent years, the administration of poly-ADP ribose polymerase inhibitor to patients with BRCA mutations has significantly improved the progression-free survival of ovarian cancer patients. Nevertheless, primary drug resistance or the acquisition of drug resistance eventually leads to treatment failure and poor outcomes for ovarian cancer patients. The mechanism underlying drug resistance in ovarian cancer is complex and has not been fully elucidated. Interestingly, different non-coding RNAs (ncRNAs), such as circular RNAs, long non-coding RNAs and microRNAs, play a critical role in the development of ovarian cancer. Accumulating evidence has indicated that ncRNAs have important regulatory roles in ovarian cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically highlight the emerging roles and the regulatory mechanisms by which ncRNAs affect ovarian cancer chemoresistance. Additionally, we suggest that ncRNAs can be considered as potential diagnostic and prognostic biomarkers as well as novel therapeutic targets for ovarian cancer.

Timing of intervention and complications of tunneled peritoneal catheter placement for recurrent malignant ascites in ovarian cancer patients

Objectives: In ovarian cancer patients, recurrent malignant ascites reduces quality of life and is associated with a poor prognosis. There is a lack of guidance in the literature regarding the placement of a tunneled peritoneal catheter in this patient population. We evaluated the outcomes of ovarian cancer patients who underwent tunneled peritoneal catheter placement for recurrent malignant ascites. Methods: We queried the institutional interventional radiology records from 5/2009 to 5/2020 for female patients with ovarian cancer who had a tunneled peritoneal catheter placed for malignant ascites. We evaluated patient characteristics, number of paracentesis procedures recorded prior to placement, complications, and the time between placement and death. Descriptive statistics were performed. Results: 30 patients were identified. The mean age was 68 (range, 42-88). 77% of patients were White and the average BMI was 26. 56.7% of patients had stage IIIC ovarian cancer and the 83.3% had papillary serous adenocarcinoma. Patients had a mean of four lines (range, 0-11) of chemotherapy before undergoing tunneled peritoneal catheter placement. The mean number of paracentesis performed prior to peritoneal catheter placement was two (range, 0-6). There were six minor complications (20%), including two catheter-related infections requiring removal and four instances of catheter dysfunction requiring revision. The median time of catheter placement to death was 44 days (range, 3-151). Conclusions: The complication rate of tunneled peritoneal catheter placement is low, as evidenced by no major complications found in this patient population. The short period from catheter placement until patient death suggests that tunneled peritoneal catheters should be pursued earlier in the disease course if patients have symptomatic, recurrent ascites.