Stage Ovarian Cancer Research Articles

The results of personificated ovarian cancer patients with peritoneal carcinomatosis treatment

The objective: to analyse of the experience of cytoreductive surgery using and hypenermic intraperitoneal chemperfusion (HIPEC) in patients with ovarian cancer IIIC stage, as well as overall and relapse-free survival in such patients. Materials and methods. 119 patients with ovarian cancer of the IIIC stage were involved into the study from 2013 to 2020 and they were treated at the University Clinic of Odessa National Medical University. Patients were divided into two groups: the clinical control group (n=53) included persons after suboptimal cytoreduction; the patients of the main group (n=66) had optimal or complete cytoreduction, and in some cases with subsequent intraoperative hyperthermic intraperitoneal chemotherapy. During the initial analysis of these groups, time (preoperative period, duration of surgery, number of postoperative bed-days), as well as the presence of complications in the postoperative period were determined. Results. In the main group there was an increase operation time due to large surgery volumes and the implementation of the HIPEC procedure with primary cytoreduction (p=0.001). In the postoperative period, an increase in the number of bed-days in the hospital in patients of the main group in relation to the control group was established, especially in those who had HIPEC (p=0.001). There was an increase in the number of surgical complications of class III-IV according to the Clavien-Dindo classification (from 5 % to 22.2 %) in patients after HIPEC. An increase in relapse-free survival from 10 months in the control group to 13-19 months in the main group was revealed. The recurrence median in the postoperative period in the control group was 10±1.3 months, and after interval cytoreduction and primary cytoreduction with HIPEC – 13±1.5 and 19±6.3 months, respectively. The index of relapse-free survival in the first 6 months in the control group was 63.2 %, in patients after optimal or complete cytoreduction – 88.0 %, in patients after optimal or complete cytoreduction and HIPEC – 90.4 %. One-year recurrence-free survival rate was 37.5 %, 63.2 % and 60.1 %, respectively, the average values of overall survival – 27.7±4.1 months versus 24.5±1.8 and 24.1±2.2 months, respectively. Conclusions. Cytoreductive surgery and methods of intraoperative hyperthermic intraperitoneal chemotherapy are perspective options of treatment of patients with peritoneal carcinomatosis by ovarian cancer regarding recurrence of the disease and survival, although they are accompanied by more postoperative complications and number of bed-days in hospital.

Nectin-4 as Blood-Based Biomarker Enables Detection of Early Ovarian Cancer Stages.

Ovarian cancer is the third most common gynecological malignancy and has the highest mortality rate. Owing to unspecific symptoms, ovarian cancer is not detected until an advanced stage in about two-thirds of cases. Therefore, it is crucial to establish reliable biomarkers for the early stages to improve the patients’ prognosis. The aim of this study is to investigate whether the ADAM17 substrates Nectin-4, Heparin-binding EGF-like growth factor (HB-EGF) and Amphiregulin (AREG) could function as potential tumor markers for ovarian cancer. In this study a set of 231 sera consisting of 131 ovarian cancer patients and 100 healthy age-matched controls were assembled. Nectin-4, HB-EGF and AREG levels of preoperatively collected sera were determined by enzyme-linked immunosorbent assay (ELISA). Our analysis revealed that Nectin-4 and HB-EGF were significantly increased compared to the age-matched control group (p < 0.0001, p = 0.016). Strikingly, significantly higher Nectin-4 and HB-EGF levels were detected in early-stage FIGO I/II (p <0.001; p = 0.025) compared to healthy controls. Eighty-four percent (16/19) of patients with low Ca-125 levels showed increased Nectin-4 levels. Our study proposes Nectin-4 and HB-EGF as promising blood-based biomarkers for the detection of early stages of ovarian cancer patients that would not have been detected by Ca-125.

Regulatory T Cells in Ovarian Carcinogenesis and Future Therapeutic Opportunities.

Regulatory T cells (Tregs) have been shown to play a role in the development of solid tumors. A better understanding of the biology of Tregs, immune suppression by Tregs, and how cancer developed with the activity of Tregs has facilitated the development of strategies used to improve immune-based therapy. In ovarian cancer, Tregs have been shown to promote cancer development and resistance at different cancer stages. Understanding the various Treg-mediated immune escape mechanisms provides opportunities to establish specific, efficient, long-lasting anti-tumor immunity. Here, we review the evidence of Treg involvement in various stages of ovarian cancer. We further provide an overview of the current and prospective therapeutic approaches that arise from the modulation of Treg-related tumor immunity at those specific stages. Finally, we propose combination strategies of Treg-related therapies with other anti-tumor therapies to improve clinical efficacy and overcome tumor resistance in ovarian cancer.

Cumulative burden of symptomatology in patients with gynecologic malignancies undergoing chemotherapy.

Patients with gynecologic malignancies commonly experience distressing symptoms during chemotherapy. This study sought to evaluate whether symptoms accumulated over the course of several chemotherapy cycles, which could provide essential information for planning supportive interventions. Patients with gynecologic malignancies completed questionnaires about fatigue, depressive symptoms, sleep, and physical activity 1 week before and after chemotherapy cycles 1, 3, and 6. Multilevel models examined the effects of time (pre- and postchemotherapy), treatment cycle (1, 3, 6), and their interaction on symptoms. Logistic regression models examined the effects of time, treatment cycle, and their interaction on the proportion of participants exceeding thresholds for clinically meaningful symptomatology. Most participants (N = 140; Mage = 60.8 years, SD = 10.4) had ovarian cancer (49%) and Stage III disease (55%). Participants reported worse fatigue, depressive symptoms, sleep disturbance, and sleep efficiency from pre- to posttreatment at each cycle (ps < .001). With each successive cycle, participants reported worse pretreatment fatigue (p < .001) and depressive symptoms (p < .01) but better sleep efficiency (p = .02). Fatigue increases attenuated across cycles (p = .04). There were no changes in physical activity. Across time points, at least half of participants met clinical thresholds for fatigue, sleep disturbance, and low sleep efficiency and were minimally physically active. Postchemotherapy cycle 6, 23% of participants reported clinically meaningful depressive symptoms. Patients with gynecologic malignancies have high rates of clinically meaningful symptomatology during chemotherapy. Patients may experience a cumulative burden of symptomatology as treatment progresses, which could have therapeutic implications. Early implementation of supportive interventions should be considered to prevent or mitigate cumulative treatment burden. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Clinical Characteristics of Patients Underwent Frozen Section Biopsy of Ovarian Masses in BSMMU, Dhaka, Bangladesh

Background: Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. Frozen section is an important and helpful adjunct in the intraoperative diagnosis of ovarian tumors. The aim of the study was to evaluate the clinical characteristics of patients undergoing frozen section biopsy in the diagnosis of ovarian malignancies.&#x0D; Materials and methods: This prospective observational study included 30 cases of ovarian masses from the Department of Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2014 to August 2014. Clinical feature, sonographic evaluation, CA-125, CA-19-9 and frozen section biopsy report were collected.&#x0D; Results: The mean age was 35.6±12.4 years with range from 14 to 70 years. Frozen section biopsy was true positive in 6 cases and no false positive, 1 false negative and true negative in 23 cases compared to histopathology. Frozen section biopsy has sensitivity, specificity, accuracy, positive predictive and negative predictive values were respectively, 85.7%, 100.0%, 96.7%, 100.0% and 95.8% in evaluation of ovarian masses.&#x0D; Conclusion: The histopathological diagnosis of the present study significantly correlated well with frozen section biopsy findings and the validity tests are almost identical as observed by many investigators.&#x0D; IAHS Medical Journal Vol 4(2), December 2021; 32-35

Expression of scp3 and dazl reveals the meiotic characteristics of the olive flounder Paralichthys olivaceus†.

Olive flounder Paralichthys olivaceus is an important cultured marine fish. We found that the meiosis marker scp3 and its intrinsic regulator dazl were mainly expressed in the gonads. During the ovarian differentiation, scp3 signal was detected first in pre-meiotic oogonia at 60-mm total length (TL) and then in primary oocytes at 80- and 100-mm TL, with a sharp increase in scp3 expression level observed at 80- and 100-mm TL. Dazl signal was detected in primordial germ cells at 30-mm TL and oogonia at 60-mm TL, but no significant change of expression was observed. During the testicular differentiation period, scp3 and dazl expression remained at low levels, and scp3 signal was weakly detected in spermatogonia at 80-mm TL, whereas dazl signal was not found. During the ovarian developmental stages, the highest expression levels of scp3 and dazl were detected at stages I and II, respectively, and strong signals of scp3 and dazl were detected in primary oocytes and oocytes at phases I and II. In the testis, the high expression of scp3 and dazl was detected at stages II-IV and II-III, respectively. Scp3 signal was weakly observed in pre-meiotic spermatogonia at stages I and II and strongly detected in primary spermatocytes at stages III-V. Dazl was detected in the nuclei of spermatogonia and spermatids at stages II-IV. Furthermore, scp3 expression in the ovary could be promoted by 17α-ethynylestradiol and tamoxifen, whereas dazl expression could be downregulated by tamoxifen.

BDP1 as a biomarker in serous ovarian cancer.

TFIIIB, an RNA polymerase III specific transcription factor has been found to be deregulated in human cancers with much of the research focused on the TBP, BRF1, and BRF2 subunits. To date, the TFIIIB specific subunit BDP1 has not been investigated in ovarian cancer but has previously been shown to be deregulated in neuroblastoma, breast cancer, and Non-Hodgkins lymphoma. Using in silico analysis of clinically derived platforms, we report a decreased BDP1 expression as a result of deletion in serous ovarian cancer and a correlation with higher and advanced ovarian stages. Further analysis in the context of TP53 mutations, a major contributor to ovarian tumorigenesis, suggests that high BDP1 expression is unfavorable for overall survival and high BDP1 expression occurs in stages 2, 3 and 4 serous ovarian cancer. Additionally, high BDP1 expression is disadvantageous and unfavorable for progression-free survival. Lastly, BDP1 expression significantly decreased in patients treated with first-line chemotherapy, platin and taxane, at twelve-month relapse-free survival. Taken together with a ROC analysis, the data suggest BDP1 could be of clinical relevance as a predictive biomarker in serous ovarian cancer. Lastly, this study further demonstrates that both the over- and under expression of BDP1 warrants further investigation and suggests BDP1 may exhibit dual function in the context of tumorigenesis.

Insulin-like Peptide Receptor (ILPR) in the Cuttlefish Sepiella japonica: Characterization, Expression, and Regulation of Reproduction.

Insulin-like peptide receptor (ILPR) can effectively regulate ovarian development in invertebrates, but its effect in cuttlefish has not been reported. We isolated and characterized a ILPR gene from Sepiella japonica, referred to as SjILPR. This gene displayed significant homologies to Octopus bimaculoides ILPR, and contained all typical features of insulin receptors and tyrosine kinase domain structure. SjILPR is expressed in all detected tissues, with the highest expression in the ovary. During ovarian development stages, its expression levels in the ovary, pancreas, and liver were correlated to the female reproductive cycle. After the silencing of SjILPR in vivo, comparative transcriptome analysis identified 4314 differentially expressed genes (DEGs) in the injected group, including 2586 down-regulated genes and 1728 up-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that 832 DEGs were assigned to 222 pathways, many pathways of which were related to gonadal development. Four down-regulated genes relevant to ovarian development (Vitellogenin 1, Vitellogenin 2, Cathepsin L1-like, and Follistatin) were selected to confirm the accuracy of RNA-seq data by qRT-PCR. These results showed that SjILPR might regulate ovarian development to control reproduction by affecting the expression of the relevant genes in female S. japonica.

Comparative transcriptome analysis of early sexual differentiation in the male and female gonads of common carp (Cyprinus carpio)

The growth rate of allotetraploid common carp (Cyprinus carpio) is sex dimorphic. Thus, intervention for controlling sex is crucial for farming this fish. However, few studies have investigated the spatiotemporal interaction of interaction of various genes related to sex determination/early gonadal differentiation in carp. In this study, comparative gonadal transcriptomic analyses were conducted during 4 key sex differentiaton stages for common carp of both sexes including sex determination stage, pre-gonadal, gonadal differentiation, and maturation stages. Altogether, 305.66 Gb raw reads were obtained form 48 libraries. Differentially expressed genes (DEGs) associated with sex differentiation and gonadal development were identified at each time point. Male-specific DEGs including dmrt1, amh, hmga2, sox3, dmrt2, wnt2b, and wnt9b, and female-biased DEGs including foxl2, cyp19a1a, zp3, zp4, and gper1 were identified. The trend analysis of the key genes of sex determination and gonadal differentiation indicated that 35 dph or earlier is the male sex determination period, 90–100 dph is the key window period of male sex differentiation, and 90–100 dph may be the key window period of female sex differentiation. Functional enrichment analysis showed that DEGs at the testicular undifferentiated stages were mainly enriched in androgen receptor signaling, while DEGs from the onset of testicular differentiation to maturity were enriched in male sex differentiation, spermatogenesis, and male gonadal development. In genetic females, DEGs at the undifferentiated ovarian stage are mainly enriched in insulin-like growth factor (IGF) transport, whereas DEGs from the onset of ovarian differentiation to maturation are mainly enriched in ovarian steroidogenesis and oocyte meiosis. Protein-protein interaction (PPI) analysis revealed that 8 DEGs, including Foxl2, Src, Ncor1, and Smad4, were identified as hub proteins. Additionally, plasma 17β-estradiol and 11-Ketotestosterone levels were sexually dimorphic in C. carpo. The study provide insights into the genetic network of the underlying mechanisms of early sex determination and gonadal differentiation in C. carpo for intervening all-female production in better way.

Guideline adherence in ovarian cancer for surgical staging in the Netherlands

ObjectivePrevious studies have shown low adherence to surgical staging guidelines in patients with clinical early-stage ovarian carcinoma. The aim of this study was to identify guideline adherence for surgical staging...

The roles of BTG1 mRNA expression in cancers: A bioinformatics analysis.

BTG1 (B-cell translocation gene 1) may inhibit proliferation and cell cycle progression, induce differentiation, apoptosis, and anti-inflammatory activity. The goal of this study was to clarify the clinicopathological and prognostic significances of BTG1 mRNA expression and related signal pathways in cancers. Using the Oncomine, TCGA (the cancer genome atlas), xiantao, UALCAN (The University of ALabama at Birmingham Cancer data analysis Portal), and Kaplan-Meier plotter databases, we undertook a bioinformatics study of BTG1 mRNA expression in cancers. BTG1 expression was lower in gastric, lung, breast and ovarian cancer than normal tissue due to its promoter methylation, which was the opposite to BTG1 expression. BTG1 expression was positively correlated with dedifferentiation and histological grading of gastric cancer (p < 0.05), with squamous subtype and young age of lung cancer (p < 0.05), with infrequent lymph node metastasis, low TNM staging, young age, white race, infiltrative lobular subtype, Her2 negativity, favorable molecular subtyping, and no postmenopause status of breast cancer (p < 0.05), and with elder age, venous invasion, lymphatic invasion, and clinicopathological staging of ovarian cancer (p < 0.05). BTG1 expression was negatively correlated with favorable prognosis of gastric, lung or ovarian cancer patients, but the converse was true for breast cancer (p < 0.05). KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that the top signal pathways included cytokine-cytokine receptor interaction, cell adhesion molecules, chemokine, immune cell receptor and NF (nuclear factor)-κB signal pathways in gastric and breast cancer. The top hub genes mainly contained CD (cluster of differentiation) antigens in gastric cancer, FGF (fibroblast growth factor)-FGFR (FGF receptor) in lung cancer, NADH (nicotinamide adenine dinucleotide): ubiquinone oxidoreductase in breast cancer, and ribosomal proteins in ovarian cancer. BTG1 expression might be employed as a potential marker to indicate carcinogenesis and subsequent progression, even prognosis.

SURVIVAL RATES FOR STAGE 3 OVARIAN CANCER. PROGNOSTIC FACTORS

Introduction. At the present stage, the therapy of patients with stage 3 ovarian cancer remains insufficiently effective. Modern methods of treatment of patients are accompanied by low survival, which requires the study of additional prognostic factors to individualize treatment.&#x0D; Methods. The study is based on the results of treatment of 136 patients with stage 3 ovarian cancer. The three- and five-year overall and recurrence-free survival of ovarian cancer patients, in correlation with treatment and prognosis, namely, histological type of tumor, degree of tumor differentiation, and tumor resuscitation after surgery, was studied and evaluated.&#x0D; Results. In the structure of ovarian cancer stage 3 for 2014-2019 in Ivano-Frankivsk region a three-year overall survival is 34%, recurrence-free survival is 17%. It was found that no patient with R1-R2 lived without recurrence for 4 years. Patients without residual tumor have a four-year recurrence-free survival (29.4%). Adenocarcinoma G1 was observed in 73 patients, G2 was detected in 29 patients, G3 – respectively in 33 patients. Thus, most patients suffered from highly differentiated tumors (54.1%), 21.5% of patients had moderately differentiated carcinoma.&#x0D; Conclusions. The work was carried out according to the plan of scientific research of the Ivano-Frankivsk National Medical University (IFNMU) and is a part of the planned scientific theme of the Department of Oncology: state registration number: 0121U109033; 2021-2026 "Individualization of the treatment of cancer of the reproductive system and gastrointestinal tract by studying prognostic factors and improving diagnostic methods." The author is a direct executor of a fragment of research work. It was found that starting from the 4th year of follow-up, the overall survival was higher by 14.1% in patients who received surgery followed by adjuvant chemotherapy compared with patients who received additional neoadjuvant PCT treatment cycles (p˂0.05). Starting from the 24th month, a significantly higher recurrence-free survival was among the patients who did not receive additional neoadjuvant chemotherapy; in the 3rd year of follow-up the recurrence-free survival was 17.9% among patients who underwent surgery with subsequent adjuvant chemotherapy, which is 10.5% more than among patients who received additional neoadjuvant courses of chemotherapy. Clinical and morphological factors related to the survival of patients with stage 3 ovarian cancer have been identified. Negative prognostic factors include R2: 64.4% of patients with R0 have a three-year overall survival, which is 41% higher than in R2, respectively (p˂0.05). In case of R0, the three-year recurrence-free survival is 52.3%, while for R1 and R2 it is 23.2% and 4.4%, respectively, without disease progression (p˂0.05). The prognostic value of G for overall and recurrence-free survival in patients with ovarian cancer was assessed. Favorable prognostic factors include G1: five-year overall survival in case of G1 is 19.7%, which is 11.8% higher than in patients with G3. There were no patients with G2 (p˂0.05). The four-year recurrence-free survival of G1 is 11.2%, which is 3.5% higher than in case of G3. There were no patients with G2 (p˂0.05).&#x0D; The relapse-free survival of patients with low-differentiated tumors is significantly higher up to the 24th month of observation compared to highly differentiated tumors, from the 36th month of observation, no difference in the survival of patients of the research groups was found.

Estradiol-17 β levels as a tool for sex determination in Farmed Anguilla japonica

In this study, the levels of plasma estradiol-17β (E2) in farmed Anguilla japonica were measured to determine their sex. The analyses were performed for two different size groups (large group, Total length (TL): 61–69 cm; small group, TL: 53–60 cm). The anatomical and histological observations showed that the large group consisted of 29% males and 71% females; the small group, 54% males and 45% females. The gonad histology showed that in the large group, 88% of the eels had immature gonads with ongoing sexual differentiation, 12% were mature with completed sexual differentiation. In the small group, 87% of the eels had immature gonads. The plasma E2 hormone levels were higher in the females of both sizes. In the large group, the average plasma E2 in females was 415 pg/ml, which was significantly higher than the average of 109 pg/ml in males (P < 0.05). In the small group, the average plasma E2 hormone level was 618 pg/ml, which was much higher than the average of 108 pg/ml in males. Quantitative real-time PCR showed that zygote arrest 1 (zar 1) and zona pellucida glycoprotein 3 (zp3) were more highly expressed in females than male. In the H-E staining, an eel in the oil droplet containing ovary stage had a high level of plasma E2 (1500 pg/ml), while an eel with testis in the spermatocyte stage had a low (60 pg/ml). E2 is a potentially useful tool and could play an important role in sex determination in broodstocks.

Lower expression of NINJ1 (Ninjurin 1), a mediator of plasma membrane rupture, is associated with advanced disease and worse prognosis in serous ovarian cancer.

Gasdermin proteins (GSDMs) form pores in cell membranes upon various stimuli, leading to the release of certain proinflammatory molecules such as IL-1β and IL-18, and this ultimately results in pyroptotic cell death. NINJ1 (Ninjurin 1) has recently been identified as a cell membrane protein responsible for the final complete plasma membrane rupture following lytic cell death mechanisms including pyroptosis, causing the release of relatively larger molecules such as HMGB1 and LDH. In this study, we reported the presence of higher GSDMD and lower GSDME protein levels in ovarian tumors compared to surrounding non-malignant stromain the tumor microenvironment. GSDME protein levels are also lower in the tumorsof theomentum compared to adjacentstromal cells.We found that NINJ1 expression decreases from early to late stage in serous ovarian cancer, and the percentage of NINJ1 copy number loss events is the highest in ovarian cancer among other cancers. Moreover, we showed that low expression of NINJ1 is associated with shorter overall survival of patients with ovarian cancer. In support of the findings showing that low NINJ1 expression contributes to worse prognosis in this most lethal gynecological malignancy, NINJ1 expression was found to be lower in cisplatin-resistant ovarian cancer cells compared to cisplatin-sensitive counterparts in vitro. We suggest that the members of gasdermin family might have distinct functions in serous ovarian cancer, and low levels of NINJ1 might contribute, at least in part, to the progression and poorer prognosis of ovarian cancer. A complete picture of how pyroptosis and subsequent plasma membrane rupture are involved in ovarian cancer will be of high importance in order to identify actionable therapeutic vulnerabilities within this newly identified group of proteins.

103P The effect of carboplatin on sodium-dependent phosphate transporter NaPi2b expression in the OVCAR-4 ovarian cancer cell line

The platinum and taxane drugs as a neoadjuvant and adjuvant chemotherapy are the most used for treatment of ovarian cancer (OC). In later stages of ovarian cancer, targeted therapy with monoclonal antibodies may be included in the treatment regimen. Sodium-dependent phosphate transporter NaPi2b is a perspective target for the ovarian cancer treatment with monoclonal antibodies since the overexpression of NaPi2b was found in about 90% of the cases of OC. Currently NaPi2b-specific therapeutic monoclonal antibodies XMT-1536 (NCT03319628) and XMT-1592 (NCT04396340) are successfully undergoing clinical trials for the treatment of ovarian and lung cancers.

Neoadjuvant Chemotherapy Versus Primary Debulking Surgery in FIGO Stage III and IV Epithelial Ovarian, Tubal or Peritoneal Cancer: A Systematic Review and Meta-Analysis.

Objective: To investigate whether neoadjuvant chemotherapy (NACT) confers superior outcomes compared to primary debulking surgery (PDS) in patients with stage III and IV epithelial ovarian, tubal or peritoneal cancer as well as in patients with high tumour load. Methods: We searched the electronic databases PubMed, Cochrane Central Register of Controlled trials, and Scopus from inception to March 2021. We considered randomised controlled trials (RCTs) comparing NACT with PDS for women with epithelial ovarian cancer (EOC) stages III and IV. The primary outcomes were overall survival and progression-free survival. Secondary outcomes were optimal cytoreduction rates, peri-operative adverse events, and quality of life. Results: Six RCTs with a total of 1901 participants were included. Meta-analysis demonstrated similar overall survival (HR = 0.96, 95% CI [0.86-1.07]) and progression-free survival (HR = 0.98, 95% CI [0.89-1.08]) between NACT and PDS. Subgroup analyses did not demonstrate higher survival for stage IV patients (HR = 0.88, 95% CI [0.71-1.09]) nor for patients with metastatic lesions >5cm (HR = 0.86, 95% CI [0.69-1.08]) treated with NACT, albeit with some uncertainty due to imprecision. Similarly, no survival benefit was observed in the subgroup of patients with metastatic lesions >10cm (HR = 0.94, 95% CI [0.78-1.12]). NACT was associated with significantly higher rates of complete cytoreduction (RR = 2.34, 95% CI [1.48-3.71]). Severe peri-operative adverse events were less frequent in the NACT arm (RR = 0.34, 95% CI [0.16-0.72]. Conclusion: Patients with stage III and IV epithelial ovarian cancer undergoing NACT or PDS have similar overall survival. NACT is likely associated with higher rates of complete cytoreduction and lower risk of severe adverse events and peri-operative death.

NR2F1 Regulates TGF-β1-Mediated Epithelial-Mesenchymal Transition Affecting Platinum Sensitivity and Immune Response in Ovarian Cancer.

Simple SummaryIn ovarian cancer (OC), platinum-based therapy remains the front-line therapy, but drug resistance is common. In the current study, we analyzed two Gene Expression Omnibus (GEO) datasets to identify the responsible genes involved in the mechanism of platinum resistance. Thirteen co-upregulated genes and one co-downregulated gene were obtained. Among them, NR2F1 revealed the highest correlation with a poor prognosis. Mechanism research revealed that NR2F1 promotes epithelial-mesenchymal transition (EMT) through TGFβ-1 signaling, participating in platinum resistance. We also found that NR2F1 was positively correlated with the infiltration of immunosuppressive cancer-associated fibroblasts (CAFs). Higher expression of NR2F1 was correlated with a poorer response to immune check blockades including anti-PD-L1. In the future, by analyzing the expression status of NR2F1 and the effect of platinum and immunotherapy in the clinical setting, it is expected that NR2F1 will be established as an effective drug selection marker, guiding treatment selection in OC patients.The mechanism underlying platinum resistance in ovarian cancer (OC) remains unclear. We used bioinformatic analyses to screen differentially expressed genes responsible for platinum resistance and explore NR2F1′s correlation with prognostic implication and OC staging. Moreover, Gene-set enrichment analysis (GSEA) and Gene Ontology (GO) analyses were used for pathway analysis. Epithelial-mesenchymal transition (EMT) properties, invasion, and migration capacities were analyzed by biochemical methods. The association between NR2F1 and cancer-associated fibroblast (CAF) infiltration and immunotherapeutic responses were also researched. A total of 13 co-upregulated genes and one co-downregulated gene were obtained. Among them, NR2F1 revealed the highest correlation with a poor prognosis and positively correlated with OC staging. GSEA and GO analysis suggested the induction of EMT via TGFβ-1 might be a possible mechanism that NR2F1 participates in resistance. In vitro experiments showed that NR2F1 knockdown did not affect cell proliferation, but suppressed cell invasion and migration with or without cisplatin treatment through the EMT pathway. We also found that NR2F1 could regulate TGF-β1 signaling, and treating with TGF-β1 could reverse these effects. Additionally, NR2F1 was predominantly associated with immunosuppressive CAF infiltration, which might cause a poor response to immune check blockades. In conclusion, NR2F1 regulates TGF-β1-mediated EMT affecting platinum sensitivity and immune response in OC patients.

Ovarian development, spawning season, size at maturity and fecundity of Acentrogobius viridipunctatus (Valenciennes, 1837) in the Vietnamese Mekong Delta.

This present study provides an overview of the reproductive traits, including ovarian development, spawning season, size at maturity (Lm), and fecundity of Acentrogobius viridipunctatus – a high economic value fish in the Vietnamese Mekong Delta (VMD). A total of 432 females were collected using trawl nets from January to December 2020 at four sites, including Long Huu-Tra Vinh (LHTV), Trung Binh-Soc Trang (TBST), Dien Hai-Bac Lieu (DHBL), and Tan Thuan-Ca Mau (TTCM). The ovarian diameter was seen to increase from 2.09 (stage I) to 6.57 mm (stage V). Histological analysis showed that the goby was a multi-spawner due to the different oocyte stages found in stages IV and V of ovaries. It can release eggs all year-round due to the monthly appearance of ovarian stages IV and V during the study period, with the main peak in the 2–4 months of the wet season noted with the highest value of gonadosomatic index at that time. The Lm increased from 6.6 cm at TBST to 9.4 cm at TTCM. This species displayed relatively high fecundity, ranging from 5,481 to 130,683 eggs/female. The average fecundity of this fish was 27,698 ± 7,983 eggs/female at LHTV, 46,592 ± 7,264 eggs/female at TBST, 23,271 ± 4,985 eggs/female at DHBL, and 31,408 ± 2,515 eggs/female at TTCM. Egg diameter ranged from 0.45 ± 0.01 at DHBL to 0.50 ± 0.01 at TBST. For sustainable exploitation, local governments should ask the fishers to avoid catching fish during the main spawning period, and the fish length at first capture should be >Lm.

Eyestalk neuropeptide identification in the female red deep-sea crab, Chaceon quinquedens

Eyestalk-derived neuropeptides, primarily the crustacean hyperglycemic hormone (CHH) neuropeptide family, regulate vitellogenesis in decapod crustaceans. The red deep-sea crab, Chaceon quinquedens, a cold-water species inhabiting depths between 200 and 1800 m, has supported a small fishery, mainly harvesting adult males in the eastern US for over 40 years. This study aimed to understand the role of eyestalk-neuropeptides in vitellogenesis in C. quinquedens with an extended intermolt stage. Chromatography shows two CHH and one MIH peak in the sinus gland, with a CHH2 peak area four times larger than CHH1. The cDNA sequence of MIH and CHH of C. quinquedens is isolated from the eyestalk ganglia, and the qPCR assay shows MIH is significantly higher only at ovarian stages 3 than 4 and 5. However, MIH transcript and its neuropeptides do differ between stages 1 and 3. While CHH transcripts remain constant, its neuropeptide levels are higher at stages 3 than 1. Additionally, transcriptomic analysis of the de novo eyestalk ganglia assembly at ovarian stages 1 and 3 found 28 eyestalk neuropeptides. A GIH/VIH or GSH/VSH belonging to the CHH family is absent in the transcriptome. Transcripts per million (TPM) values of ten neuropeptides increase by 1.3 to 2.0-fold at stage 3 compared to stage 1: twofold for Bursicon α, followed by CHH, AKH/corazonin-like, Pyrokinin, CCAP, Glycoprotein B, PDH1, and IDLSRF-like peptide, and 1.3-fold of allatostatin A and short NP-F. WXXXRamide, the only downregulated neuropeptide, decreases TPM by ∼ 2-fold at stage 3, compared to stage 1. Interestingly, neuroparsin with the highest TPM values remains the same in stages 1 and 3. The mandibular organ-inhibiting hormone is not found in de novo assembly. We report that CHH, MIH, and eight other neuropeptides may play a role in vitellogenesis in this species.

Changes in subcellular localization of Lysyl-tRNA synthetase and the 67-kDa laminin receptor in epithelial ovarian cancer metastases.

Although lysyl-tRNA synthetase (KARS1) is predominantly located in the cytosol, it is also present in the plasma membrane where it stabilizes the 67-kDa laminin receptor (67LR). This physical interaction is strongly increased under metastatic conditions. However, the dynamic interaction of these two proteins and the turnover of KARS1 in the plasma membrane has not previously been investigated. Our objective in this study was to identify the membranous location of KARS1 and 67LR and investigate if this changes with the developmental stage of epithelial ovarian cancer (EOC) and treatment with the inhibitor BC-K01. In addition, we evaluated the therapeutic efficacy of BC-K01 in combination with paclitaxel, as the latter is frequently used to treat patients with EOC. Overall survival and prognostic significance were determined in EOC patients according to KARS1 and 67LR expression levels as determined by immunohistochemistry. Changes in the location and expression of KARS1 and 67LR were investigated in vitro after BC-K01 treatment. The effects of this compound on tumor growth and apoptosis were evaluated both in vitro and in vivo. EOC patients with high KARS1 and high 67LR expression had lower progression-free survival rates than those with low expression levels of these two markers. BC-K01 reduced cell viability and increased apoptosis in combination with paclitaxel in EOC cell xenograft mouse models. BC-K01 decreased membranous KARS1 expression, causing a reduction in 67LR membrane expression in EOC cell lines. BC-K01 significantly decreased in vivo tumor weight and number of nodules, especially when used in combination with paclitaxel. Co-localization of KARS1 and 67LR in the plasma membrane contributes to EOC progression. Inhibition of the KARS1-67LR interaction by BC-K01 suppresses metastasis in EOC.