Stage Ovarian Cancer Research Articles

Bioinformatics analysis of the clinicopathological and prognostic significance of BAG3 mRNA in gynecological cancers

BAG3 is a co-chaperone BAG family protein that plays important roles in protein homeostasis, cell survival, cell motility, and tumour metastasis. This study aimed to clarify the clinicopathological and prognostic implications of BAG3 mRNA expression in tumours. We performed bioinformatics analysis on BAG3 mRNA expression using TCGA, XIANTAO, UALCAN, and Kaplan-Meier plotter databases. BAG3 mRNA expression was downregulated in breast and endometrial cancers and positively correlated with favourable PAM50 subtyping in breast cancer，clinical stage and short overall survival in ovarian cancer and negatively correlated with T stage, clinical stage, and histological grade in cervical and endometrial cancers. The top BAG3-related pathways included ligand-receptor interactions and activity, DNA packaging and nucleosomes, hormonal responses, membrane regions, microdomains and rafts, and endosomes in breast cancer; ligand-receptor interactions, transmembrane transporters and channels, cell adhesion, and keratinisation in cervical cancer; ligand-receptor interactions, anion transmembrane transporters, lipoproteins, keratinisation, cell adhesion, and protein processing in endometrial cancer; metabolism of porphyrin, chlorophyll, pentose, uronic acid, ascorbate, and alternate and cell adhesion in ovarian cancer. BAG3 expression could represent a potential marker for carcinogenesis, histogenesis, aggressive behaviours, and prognosis in gynecological cancers. IMPACT STATEMENT What is already known on this subject? BAG3 regulates cell activity, autophagy, and resistance to apoptosis through multiple domains and plays an important role in tumour development. BAG3 positively regulates tumour cell invasion and migration in cervical and ovarian cancers. What do the results of this study add? BAG3 expression is closely associated with histogenesis, clinicopathology, and prognosis in gynecological cancers and is involved in signalling pathways associated with the control of cell proliferation, migration, invasion, and drug resistance in tumours. What are the implications of these findings for clinical practice and/or further research? Abnormal BAG3 expression can be employed as a possible marker of tumour development, invasion, and prognosis, providing new ideas for treating cancer.

Molecular cloning and characterization of STC1 gene and its functional analyses in yak (Bos grunniens) cumulus granulosa cells

Cumulus granulosa cells (CGCs), an important type of ovarian somatic cells, carries out various functions related to oogenesis, follicular development, and steroidogenesis. Studying the biological mechanisms involved in the development and function of CGCs makes a great contribution to understanding the reproductive regulation in female animals. Stanniocalcin-1 (STC1) is an important Ca2+-regulated glycoprotein hormone that exhibits high expression levels in ovaries. In this study, we cloned the coding sequence of the yak STC1, predicted the structure of STC1 protein, detected the expression and localization of STC1 in yak ovaries, and analyzed the functions of STC1 in yak CGCs. The CDS (coding sequence) region of yak STC1 gene was found to be 744 bp and encoded 247 amino acids. Homology comparison revealed that STC1 protein was highly conserved among mammals. The STC1 mRNA displayed dynamic expression profiles in different stages of yak ovaries, and the highest expression was found in the follicular phase. Regarding localization, STC1 protein was widely distributed in various kinds of yak ovarian cells, including oocytes, mural granulosa cells, CGCs, and thecal cells. Repressing the expression of STC1 resulted in defective proliferation and survival of yak CGCs. In addition, knockdown the expression of STC1 repressed the secretion of progesterone and promoted the secretion of estrogen. Overexpression of STC1 partially rescued the proliferation of CGCs and resulted in opposite effects on the secretion of progesterone and estrogen. Several apoptosis and steroidogenesis-related genes, including BAX, BCL2, HSD3B1, HSD17B1, CYP11A1 and CYP17A1 showed altered expressions after repressing or increasing the expression of STC1 in yak CGCs. To the best of our knowledge, this study is the first to focus on the role of STC1 in yak CGCs, and the outcomes offer fresh insights into the mechanism governing yak reproduction.

Advantages and Limitations of Ultrasound as a Screening Test for Ovarian Cancer.

Ovarian cancer (OC) is the seventh most common malignancy diagnosed among women, the eighth leading cause of cancer mortality globally, and the most common cause of death among all gynecological cancers. Even though recent advances in technology have allowed for more accurate radiological and laboratory diagnostic tests, approximately 60% of OC cases are diagnosed at an advanced stage. Given the high mortality rate of advanced stages of OC, early diagnosis remains the main prognostic factor. Our aim is to focus on the sonographic challenges in ovarian cancer screening and to highlight the importance of sonographic evaluation, the crucial role of the operator΄s experience, possible limitations in visibility, emphasizing the importance and the necessity of quality assurance protocols that health workers have to follow and finally increasing the positive predictive value. We also analyzed how ultrasound can be combined with biomarkers (ex. CA-125) so as to increase the sensitivity of early-stage OC detection or, in addition to the gold standard examination, the CT (Computed tomography) scan in OC follow-up. Improvements in the performance and consistency of ultrasound screening could reduce the need for repeated examinations and, mainly, ensure diagnostic accuracy. Finally, we refer to new very promising techniques such as liquid biopsies. Future attempts in order to improve screening should focus on the identification of features that are unique to OC and that are present in early-stage tumors.

Minimally Invasive Staging of Early-Stage Epithelial Ovarian Cancer versus Open Surgery in Terms of Feasibility and Safety: A Systematic Review and Meta-Analysis.

Epithelial ovarian cancer is women's fourth most common oncological cause of death. One of the main prognostic factors in ovarian cancer is the tumor stage. For instance, surgical staging of the disease is focal when choosing the best therapeutic option for each case. Although open surgery is the prevalent approach for staging and treating ovarian cancer, the use of minimally invasive surgery (MIS) has found recent application in staging or restaging cases of early disease. Our work compares oncological outcomes after MIS staging for FIGO I epithelial ovarian cancer with the laparotomic approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations, we systematically searched the Pub Med and Scopus databases in February 2023. No temporal nor geographical limitation was made. We included the articles containing data about Disease-Free Survival (DFS) and Overall Survival (OS), Recurrence Rates (RR), and Upstaging Rates (UpR). We used comparative studies for the meta-analysis. After the database search and article selection, 19 works matched the inclusion criteria for the systematic review. Eleven of these were comparative studies between MIS and Open Surgical Staging (OSS) approaches for ovarian cancer staging and were included in the meta-analysis. The meta-analysis did not show a statistically significant difference between the MIS and the OSS group concerning DFS, OS, and RR. Only Upstaging Rate ≥ FIGO Stage II was statistically significative higher in the OSS group. Likewise, MIS is confirmed to be an approach with a lower profile of surgical complications. In conclusion, our study did not show one approach to be safer than the other. However, the lack of dedicated studies limits the evidence of our study. For instance, we recommend adequately selecting the specimen, minimizing the risk of spillage, and optimizing surgical staging.

The importance of the regularity of preventive examinations in the early diagnosis of ovarian cancer

Objective. To show the importance of regularity of preventive examinations in early diagnostics of ovarian cancer. Malignant ovarian tumors occupy the third place in the frequency of occurrence among the gynecological tumors after cancer of the uterine body and cervix but they leave them behind with regard to the mortality rate. Detection of the disease at late stages leads to only 17 % five-year survival rate in Europe and Russia.
 Materials and methods. A prospective study was conducted on the basis of the Gynecological Unit of Perm Regional Oncological Dispensary. It enclosed 50 patients aged 45 to 77 years, operated for ovarian cancer with various stages of the disease. The following methods were used: collection of complaints and anamnesis, study of outpatient cards and medical histories, assessment of morphological conclusions.
 Results. According to the anamnesis, all patients represented a risk group for ovarian cancer. The annual gynecological preventive examination was carried out in 40 % of patients, ultrasound examination of the pelvic organs was performed in 28 % of cases. The smallest group,10 % of patients, was a group of patients with stage I of the disease and asymptomatic course of pathology, who underwent preventive examinations and ultrasound in 100 % of cases. The largest number of patients had stage III 40 %, annual preventive examinations were carried out in 20 % of women of this group without ultrasound examination of the pelvic organs. In 64 % of cases, a late examination by a doctor was detected a year or more after the symptoms of the disease occurred. Patients with stages III and IV of the disease were postmenopausal, were unemployed and lived in rural areas.
 Conclusions. The absence of symptoms at an early stage of ovarian cancer and late onset of treatment with the complaints available actualizes the need for annual preventive gynecological examinations with mandatory ultrasound verification of the diagnosis to identify the disease in time.

GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of ovarian cancer.

e17604 Background: Ovarian cancer (OC) is the deadliest gynecological cancer, often diagnosed at advanced stages. A fast and accurate diagnostic method for early-stage OC is needed. The tumor marker gangliosides, GD2 and GD3, exhibit properties that make them ideal potential diagnostic biomarkers but they have never before been quantified in OC. We investigated the diagnostic utility GD2 and GD3 for diagnosis of all subtypes and stages of OC. Methods: This retrospective study evaluated GD2 and GD3 expression in biobanked tissue and serum samples from patients with invasive epithelial OC, healthy donors, non-malignant gynecological conditions, and other cancers. GD2 and GD3 levels were evaluated in tissue samples by immunohistochemistry (n=299), and in two cohorts of serum samples by quantitative ELISA. A Discovery Cohort (n=379) showed feasibility of GD2 and GD3 quantitative ELISA for diagnosing OC, and a subsequent Model Cohort (n=200) was used to train and cross-validate a diagnostic model. Results: GD2 and GD3 were expressed in tissues of all OC subtypes and FIGO stages but not in surrounding healthy tissue or other controls. In serum, GD2 and GD3 were elevated in patients with OC. A novel diagnostic model that included serum levels of GD2 and GD3 was superior to the standard of care (CA125, p<0.001) at detecting OC, as well as, in early-stage (I/II) OC samples. Conclusions: GD2 and GD3 are high value candidates for building a novel diagnostic panel. A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early-stage. Further research exploring the utility GD2 and GD3 for diagnosis of OC is warranted. Future work will aim to validate these biomarkers in independent prospective studies. [Table: see text]

Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage ovarian cancer: A prospective multicentre study (SELLY).

e17579 Background: Comprehensive surgical staging of early epithelial ovarian cancer includes systematic paraaortic and bilateral pelvic lymphadenectomy but its therapeutic role is controversial and it is associated with potential severe morbidity. The feasibility of sentinel lymph-node (SLN) identification in early stage ovarian cancer has been shown only. We did a prospective multicenter study to assess the feasibility, detection rate and diagnostic accuracy of the SLN procedure in predicting the pathological pelvic-node status in patients with early stage ovarian cancer. Methods: This is a phase II single arm study (EUDRACT 2019-001088-58) including patients with presumed stage I-II epithelial ovarian cancer planned for immediate or delayed minimally-invasive comprehensive staging. The ovarian pedicle is injected with 2 mL of a 1.25 mg/mL indocyanine green (ICG) solution. The pelvic and lumbo-aortic retroperitoneum is then accessed and inspected to identify and remove SLNs. Staging is then completed including systematic pelvic and para-aortic lymphadenectomy and an histopathological examination of all nodes is performed. The primary endpoint was estimation of the sensitivity and sensibility of SLN in predicting nodal status. Assuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (i.e. the maximum marginal error) d=5%, a type I error α = 0.05, a sample size of 141 patients is needed to test the general hypothesis (i.e. to answer whether SLN(s) identified with ICG can accurately predict nodal status at histology of patients with apparently early EOC). Assuming a drop-out rate of 20%, a total of 176 patients will be enrolled in the study. Results: One-hundred and seventy-six patients were included with a drop-out rate of 22%. Sentinel node was identified in 102 patients (detection rate, 58%, [95% CI: 51-65]). There were no clinical differences between patients with successful or unsuccessful mapping. Both the infundibolopelvic ligament and the legamentum ovarii proprium were injected in 29.0% of cases. Twenty-one patients had positive nodes and 71% of them showed successful mapping. Among the latter, a negative sentinel node was identified in 3 patients (Sensitivity 78.6% [95% CI: 57-100]; Specificity 100%; Accuracy 97% [95% CI: 94-100]; PPV 100%; NPV 96,6% [95% CI: 93-100]). Twenty-two (12.5%) intra- and 25 (14.2%) postoperative complications occurred (12 G1; 9 G2; 2 G3, 2 G4). Clinical trial information: EUCTR2019-001088-58 .

Trends in ovarian cancer incidence and incidence-based mortality: A 15-year population-based analysis.

5570 Background: The predicted incidence and incidence-based mortality (IBM) of ovarian cancer (OC) in 2023 is lower than prior years. OC encompasses a range of heterogeneous cancers with subtypes categorized on histology and site of origin. Given differences in survival and treatment paradigms, we aim to characterize trends in OC incidence and IBM based on histology and site of origin to determine what factors are responsible for the decline. Methods: Patients with OC from 2000-2019 were identified from the US Surveillance, Epidemiology, and End Results 17 registry database. Using ICD-O-3 codes, patients with epithelial, stromal, and germ cell cancers of the ovary, fallopian tube, and peritoneum were included. Incidence and IBM were reported as age-adjusted rates and stratified by cancer subtype. Using Joinpoint 4.9.1.0, we characterized piecewise log-linear time trends to identify inflection points in the rates’ annual percentage change (APC). Results: The incidence of epithelial OC decreased significantly from 2004-2019 (APC -1.24%). When stratified by disease stage, this trend was seen in distant disease (APC -2.11%) and unknown/unstaged disease (APC -3.40%); however, there was a significant increase in incidence of local disease (APC +0.83%). There was no significant change in the incidence of germ cell and stromal OC from 2004-2019 in all stages. (APC -0.30% and +0.33%). Among all OC subtypes, there was a significant decline in incidence from 2000-2019 (APC -1.57%) with a sharper decline from 2015-2019 (APC -3.41%). Among all cancer subtypes, the incidence trended down from 2000-2019, with a significant decline from 2015-2019 (APC -2.37%). Similar trends are observed in IBM. Among all stages of epithelial OC, there was a significant decrease in IBM from 2006-2019 (APC -2.02%). When stratified by disease stage, there was a decline in IBM in local disease (APC -7.19%, 2014-2019) and distant disease (APC -2.44%, 2010-2019). There were no changes in IBM of germ cell and stromal OC from 2004-2019 (APC +0.78% and -0.20%). Among all cancers, IBM significantly decreased from 2006-2019 (APC -2.28%). When stratified by disease stage, there was no change among local disease and an increase in regional disease from 2006-2019 with the increase from 2006-2010 (APC +14.35%) compared to 2010-2019 (APC +1.45%). Conversely, there was a significant decrease in IBM for distant disease (APC -2.51% from 2010-2019) and unknown/unstaged disease (APC -3.27% from 2006-2019). Conclusions: There has been an overall decline in incidence and IBM of OC over a 15-year period, primarily driven by the epithelial histology. Over the past 20 years, OC has been increasingly diagnosed at earlier stages with a corresponding improvement in survival. While stage migration and improved survival may contribute to these trends, they do not entirely explain them. As new treatments become available, the incidence and IBM of OC may further decline.

Prognostic value of insulin-like growth factor receptor 1 (IGF1R) expression in high-grade serous ovarian cancer (HGSOC) treated with first line platinum derivative based chemotherapy.

e17577 Background: Insulin-like growth factor receptor 1 (IGF1R) expression is frequently observed in ovarian cancer patients. Based on data from the literature, the IGF1(IGF2)/IGF1R pathway may be associated with resistance to platinum derivative based chemotherapy. Methods: The study group included 64 Caucasian women with serous high-grade ovarian cancer (HSOC) stage III-IV TNM/FIGO classification, treated 1st line platinum derivative based chemotherapy between 2004-2014. The analysis of clinical data was carried out based on data from medical records. IGF1R expression was assessed by immunohistochemistry using the monoclonal antibody Roche Rabbit Monoclonal (G11) in tissues from paraffin-embedded blocks. Progression free survival (PFS) was analyzed as the time from the start of chemotherapy to progression. Overall survival (OS) was defined as the time from diagnosis to the patient's death, regardless of cause, or to the last contact with the patient. In all analyses, the significance level was p = 0.05. Statistical analysis was performed using the 3.4.3 version of R statistical environment. Results: The median follow-up was 1023 days (range 157 to 3420 days). The median PFS was 14.0 (95%CI: 11.9-18.0) months. Median OS was not reached. The average patients age was 62 years (range 37-83). Platinum-sensitivity, partial platinum-sensitivity, platinum resistance and platinum-insensitivity were found in 23 (37.1%), 17 (27.4%), 21 (33.9%) and 1 (1.6%) patients, respectively. Any IGF1R expression was noted in 57 patients with the median H-score of 220 (range: 0-300; IQR: 100-207). Median PFS for IGF1R H-score 220 and IGF1R > 220 was 15.4 (95% CI: 13.1-23.3) and 10.8 (95% CI: 9.6-NA) months, respectively. In multivariate analysis PFS was associated with the extent of surgery: cytoreduction secondary vs. primary (WR = 1.94; p = 0.03), suboptimal vs. optimal (WR = 2.16; p = 0.01), body mass index (WR = 0.44; p = 0.05) and IGF1R expression ( > 220) (WR = 2.84; p = 0.04). Conclusions: High expression of IGF1R (H-score > 220) in stage III/IV HGSOC patients treated in 1st line platinum derivative-based chemotherapy is a negative prognostic factor.

A study on the seasonal cyclicity of ovarian development in adult Himalayan snow trout, Schizothorax plagiostomus.

Schizothorax plagiostomus, commonly known as snow trout, is a popular food fish found in parts of Central Asia and the Indo-Himalayan region. Despite such a broad range of distribution and potential financial value, it is a highly neglected cold-water ichthyofauna. Furthermore, an alarming decline in Schizothoracine population has been reported in the recent past due to climate change and uncontrolled anthropogenic interference. In this study, the seasonal variations in ovarian architecture and development were examined in adult S. plagiostomus from Garhwal Himalayan region, Uttarakhand, India. Ovarian-somatic index ranged from 16.86 ± 0.29 to 0.31 ± 0.56, with a maximal value in September and a minimal value in April. Ovarian histology revealed the abundance of primary growth oocytes in resting and preparatory stages; primary/secondary vitellogenic oocytes with numerous cortical alveoli were predominant in the developing stage of pre-spawning ovaries; secondary/tertiary vitellogenic oocytes were conspicuous in actively spawning ovaries; and atretic follicles/oocytes were discernible during the regressing stage of spent ovaries. Scanning electron microscopy of mature ova (mean diameter 2.003 ± 0.01 mm) prominently showed the structure micropyle (mean diameter 12.93 ± 3.38 μm). Fecundity analyses suggested that September was the principal breeding season, whereas residual spawning occurred with fresh rain in late winter during February-March. Collectively, this is the first comprehensive qualitative and quantitative report of the seasonal variations in the ovarian development and function for S. plagiostomus. These data may provide valuable information towards the captive breeding programme as well as conservation and management for Schizothoracine fishes in normal and altered climatic conditions.

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

Characteristics of the receptor phenotype of tumor-associated immune cells of the epithelial-mesenchymal microenvironment of ovarian cancer

Among all histological types, serous carcinomas account for up to 85%. Due to pronounced heterogeneity (at the molecular and genetic level) and chemoresistance, difficulties arise in finding active targets for tumor elimination.
 Aim. To establish a link between the population composition of tumor-associated immune cells of the microenvironment and the stage of serous ovarian cancer.
 Materials and methods. The analysis of the pathologic and anatomical material in 74 patients with serous ovarian cancer was carried out. Monoclonal antibodies were used to determine antigens in the samples: CD3, CD4, CD8, CD11b, CD14 and CD16.
 Results. The obtained results of the immunohistochemical study showed that in the composition of the immune cells of the microenvironment, the largest number of cells, at all stages (IIV) of the oncological process, are represented by macrophages (CD11b+, CD14+), CD3+ lymphocytes are in second place in terms of the number of cells, followed by CD8+ and CD4+ and the smallest number of CD16+ cells.
 Conclusion. As a result of the immunohistochemical study, a multidirectional trend was found between the population composition of tumor-associated immune cells of the microenvironment and the stage of serous ovarian cancer. With an increase in the stage of the disease, the number of macrophages (CD11b+, CD14+) and lymphocytes (CD3+, CD16+) decreased regardless of the degree of differentiation of the tumor. With an increase in the tumor stage, the number of CD4+ and CD8+ populations decreased, but in this case, the degree of differentiation played a significant role, i.e. the higher the tumor stage and the lower the degree of differentiation, the fewer cells were detected.

LC-MS Based Metabolomic Profiling of Largehead Hairtail (Trichiurus japonicus) Ovary Reveals Metabolic Signatures of Ovarian Developmental Process (II–IV)

Trichiurus japonicus is an economically important fish that ranks 11th in global marine fish capture production. However, the reproductive characteristics of this fish have undergone notable changes in recent decades, potentially affecting the quality of offspring and sustainable utilization. To improve our understanding of the physiological regulation of maturation in T. japonicus, untargeted liquid chromatography mass spectrometry was utilized to identify the small molecules that characterize the comprehensive metabolic profiles of ovaries during ovary development from stage II to stage IV. According to the results of OPLS-DA, the ovarian metabolite profiles of the three developmental stages were separated. The concentrations of 124 and 100 metabolites were significantly altered between stage II vs. III and III vs. IV, respectively. Lipids and lipid-like molecules accounted for the largest proportion of the altered metabolites, followed by amino acids, peptides, and analogues. The significantly altered metabolites-enriched pathways differed slightly between stages II and III and stages III and IV. Steroid-related pathways were heavily affected during stages II to III, while significantly altered metabolites from stages III to IV were involved in oocyte-maturation-related pathways. Through metabonomics analysis, potentially important metabolic pathways and metabolites between different ovarian stages were detected, providing basic information for further investigation of maturation mechanisms in wild fish.

Prostaglandin E2 mediates chorion formation of the Asian tiger mosquito, Aedes albopictus, at late oogenesis.

Chorion-i.e., the eggshell-is formed during the late stage of oogenesis by follicular epithelium in the ovary. Although the endocrine signal(s) driving choriogenesis remain unclear in mosquitoes, this process in other insects has been suspected to involve the mediation of prostaglandins (PGs). This study tested the role of PG in the choriogenesis of the Asian tiger mosquito, Aedes albopictus, and its influence on controlling the expressions of genes associated with chorion formation by a transcriptome analysis. An immunofluorescence assay showed that PGE2 is localised in follicular epithelium. With the treatment of aspirin, an inhibitor of PG biosynthesis, at mid oogenesis, the PGE2 signal disappeared in the follicular epithelium led to significantly inhibited chorion formation along with a malformed eggshell. Ovary transcriptomes were assessed by RNASeq at the mid and late ovarian developmental stages. Differentially expressed genes (DEGs) exhibiting more than twofold changes in expression levels included 297 genes at mid stage and 500 genes at late stage. These DEGs at these two developmental stages commonly included genes associated with egg and chorion proteins of Ae. albopictus. Most chorion-associated genes were clustered in the 168 Mb region on a chromosome and exhibited significantly induced expressions at both ovarian developmental stages. The inhibition of PG biosynthesis significantly suppressed the expression of the chorion-associated genes while the addition of PGE2 rescued the gene expressions and led to recovery of choriogenesis. These results suggest that PGE2 mediates the choriogenesis of Ae. albopictus.

Neo-vascularization-based therapeutic perspectives in advanced ovarian cancer.

The process of angiogenesis is well described for its potential role in the development of normal ovaries, and physiological functions as well as in the initiation, progression, and metastasis of ovarian cancer (OC). In advanced stages of OC, cancer cells spread outside the ovary to the pelvic, abdomen, lung, or multiple secondary sites. This seriously limits the efficacy of therapeutic options contributing to fatal clinical outcomes. Notably, a variety of angiogenic effectors are produced by the tumor cells to initiate angiogenic processes leading to the development of new blood vessels, which provide essential resources for tumor survival, dissemination, and dormant micro-metastasis of tumor cells. Multiple proangiogenic effectors and their signaling axis have been discovered and functionally characterized for potential clinical utility in OC. In this review, we have provided the current updates on classical and emerging proangiogenic effectors, their signaling axis, and the immune microenvironment contributing to the pathogenesis of OC. Moreover, we have comprehensively reviewed and discussed the significance of the preclinical strategies, drug repurposing, and clinical trials targeting the angiogenic processes that hold promising perspectives for the better management of patients with OC.

Quantitative Analysis of Ovarian Dynamics of European Sardine Sardina pilchardus (Walbaum, 1792) during Its Spawning Period

Fish with indeterminate fecundity spawn multiple times throughout a protracted reproductive period. During that period several ovulation events succeed one another, and different oocyte developmental stages co-occur in the ovaries with new oocytes consistently recruiting from one growth phase to the next to form the sequential batches. In this study, we examined in detail the oocyte recruitment and development pattern of the sequential batches in a commercially important fish with indeterminate fecundity, the European sardine. The numbers and sizes of oocytes at different developmental stages were estimated for four phases of the ovulatory cycle (ovarian stages) and during the main spawning season (November–March) by applying the oocyte packing density theory in combination with stereological techniques. General linear models (GLMs) were used to test for changes in oocyte sizes as well as relative oocyte numbers per developmental stage within the different ovarian stages in the successive spawning months. A temporal association between several transition events of the oocyte development process was revealed. Specifically, the final maturation of the advanced batch triggered (a) the recruitment of oocytes from primary to secondary growth phase, (b) de novo vitellogenesis and (c) a surge of yolk deposition in primary vitellogenic oocytes. Oocyte recruitment was completed two days after the ovulation of the advanced batch and relative numbers of primary and secondary growth oocytes were thereafter stable until the next final maturation event. This pattern of oocyte recruitment and growth remained unchanged during the course of the spawning season. This study advances our knowledge on oocyte recruitment and development in fish with indeterminate fecundity, which is key to understanding reproduction and its drivers at the individual and population level.

MiR‑4732‑5p promotes ovarian cancer mobility by targeting MCUR1.

MicroRNAs (miRNAs/miRs) play critical roles in tumor progression. However, the role of miR-4732 and its underlying molecular mechanism in ovarian cancer (OC) remain unclear. In the present study, the high expression of miR-4732 was confirmed to be associated with the mortality of patients with OC following surgery, according to The Cancer Genome Atlas Ovarian Cancer database (TCGA-OV). Additionally, the expression of miR-4732 was positively associated with an increased tendency to exhibit an early TNM stage (IIA, IIB and IIC) of OC, indicating its promotional role in the early stages of tumorigenesis. By performing in vitro gain-of-function experiments, the transient transfection of IGROV1 cells with miR-4732-5p mimics enhanced cell viability according to Cell Counting Kit-8 assay, and cell migration and invasion in Transwell assays. However, though the application of loss-of-function experiments, the transient transfection of IGROV1 cells with miR-4732-5p inhibitors hindered cell viability, cell migration and invasion in vitro. Mitochondrial calcium uniporter regulator 1 (MCUR1) was validated as a downstream direct target of miR-4732-5p through bioinformatics analysis, western blotting and luciferase assays. Therefore, the results of the present study provide evidence that miR-4732-5p may promote OC cell mobility through the direct targeting of the tumor suppressor, MCUR1.

Ovarian Cancer in Iran: National Based Study.

Ovarian cancer (OC) is the 7th most common cancer, with 239,000 new cases per year. In Iran, it is the 8th most common cancer, with an ASIR of 3.9/100,000 women. The 5-year overall survival in Iran based on previous studies is about 61% which in comparison with eastern countries has better survival. The study included patients from the Iran National Cancer Registry from 2009-2014. Several steps were taken to control data quality. This study used a Kaplan-Meier survival curve to compare OC survival rates across geographical, pathological, and other variables. All analyses were done in R (4.02) and SPSS (26), with a 0.05 P-value considered statistically significant. The study enrolled 7977 cases of OC. OC's ASIR was 4.10/100,000. In epithelial and non-specific OC, ASIR was >0.5. Five-year survival was 55% and 10-year survival was 45%. OC is the 8th most common cancer in Iran, with lower age-specific incidence and better overall survival than East Asia and North America. In Iran, as in Eastern Europe, OC incidence correlated with reduced total fertility rate and population aging. Five and 10-year overall survival rates were 55% and 44%, respectively, higher than the West. This may be because late stage OC patients are excluded from pathology and classified as "undiagnosed" in death certificates or hospitalization files.

MALIGNANT STRUMA OVARII (KASUS LANGKA)

Struma ovarii (SO) are rare and accur in 2-3% of mature ovarian teratomas, most SO cases are benign. Malignant struma ovarii (MSO) is even more rare and occurs in 0,5- 5% of all cases, with the most common histologies identified are papillary and follicular carcinoma, most commonly affect patients in their 4th to 6th decade of life. Due to the rarity of malignant transformation, data about its management are lacking. A 49-years-old woman P2A0 with abdominal pain and pelvic mass, admitted for a hysterectomy and bilateral salpingo-oophorectomy. The left ovary was measured 13x11x5 cm, cystic and partly solid, filled with gelatinous fluid, composed of thyroid follicles with the appearance of "ground glass", "nuclear inclusion" and "nuclear groove", forming a papillifer structure. The diagnostic of MSO is based on histological features include cellular atypia, increased hyperplasia, nuclear pleomorphism, mitotic activity, vascular and/or capsular invasion. To be classified as a MSO, teratoma containing 50% or more thyroid tissue. MSO necessitates surgical staging for ovarian cancer with pelvic washings, total abdominal hysterectomy, bilateral salpingo- oophorectomy, lymph node sampling, total thyroidectomy, and radioactive I-131 ablation. Based on the clinical examination and histopatological examination the patient was diagnosed with MSO (ICD O: 9090/3).

Function Analysis of Cholesterol 7-Desaturase in Ovarian Maturation and Molting in Macrobrachium nipponense: Providing Evidence for Reproductive Molting Progress.

The Cholesterol 7-desaturase gene plays an important role in insect ecdysone synthesis, but its role in ovarian development has not been reported. In this study, characteristics and the phylogenetic relationship of Cholesterol 7-desaturase were identified by bioinformatics. qPCR showed that the Mn-CH7D gene was highly expressed in the ovary, which was much higher than that in other tissues, and the expression level of Mn-CH7D reached the highest level at the third stage of the ovarian development stage (O-III). During embryonic development, the Mn-CH7D gene expression was highest in the zoea stage. The function of the Mn-CH7D gene was explored by RNA interference. The experimental group was injected with Mn-CH7D dsRNA through the pericardial cavity of M. nipponense, while the control group was injected with the same volume of dsGFP. Statistical analysis of gonadal development and GSI calculation showed that the silencing of Mn-CH7D resulted in the suppression of gonadal development. In addition, the molting frequency of the experimental group was significantly lower than that of the control group during the second molting cycle after silencing Mn-CH7D. On the seventh day after silencing, ecdysone content in the experimental group was significantly reduced. These results demonstrated that the Mn-CH7D gene played a dual role in ovarian maturation and molting of M. nipponense.