Predicting Prognosis and Platinum Resistance in Ovarian Cancer: Role of Immunohistochemistry Biomarkers.

Ovarian cancer is a lethal reproductive tumour affecting women worldwide. The advancement in presentation and occurrence of chemoresistance are the key factors for poor survival among ovarian cancer women. Surgical debulking was the mainstay of systemic treatment for ovarian cancer, which was followed by a successful start to platinum-based chemotherapy. However, most women develop platinum resistance and relapse within six months of receiving first-line treatment. Thus, there is a great need to identify biomarkers to predict platinum resistance before enrolment into chemotherapy, which would facilitate individualized targeted therapy for these subgroups of patients to ensure better survival and an improved quality of life and overall outcome. Harnessing the immune response through immunotherapy approaches has changed the treatment way for patients with cancer. The immune outline has emerged as a beneficial tool for recognizing predictive and prognostic biomarkers clinically. Studying the tumour microenvironment (TME) of ovarian cancer tissue may provide awareness of actionable targets for enhancing chemotherapy outcomes and quality of life. This review analyses the relevance of immunohistochemistry biomarkers as prognostic biomarkers in predicting chemotherapy resistance and improving the quality of life in ovarian cancer.

The Effect of Surgical Intervention of Endometriosis to CA-125 and Pain.

Endometriosis is an inflammatory condition characterised by the presence of endometrial growth beyond the uterine cavity. It is a debilitating disease requiring multiple modalities of treatment. In considering surgery as the option of treatment, the benefits should outweigh the risk. Besides direct surgical risk, intervention may lead to a reduction of ovarian reserve, in addition to premature menopause and low fecundity. To date, there is an inconclusive evidence to support any specific parameters in monitoring disease progression following surgical intervention. Serum cancer antigen (CA)-125 is expressed by coelomic epithelium and has been extensively studied as a biomarker for endometriosis. Elevated expression of CA-125 has been shown in endometrial tissues and the marker increased indirectly from peritoneal irritation that accompanies an extensive form of endometriosis. Additionally, the visual analogue scale (VAS) scores have been used as an objective measurement for measuring pain, especially in a complex disease such as endometriosis. This review aims to consolidate a series of clinical trials that utilised CA-125 level and VAS score as tools for monitoring patients undergoing surgery for endometriosis.

Reviewing the role of progesterone therapy in endometriosis.

Endometriosis is a benign, chronic inflammatory condition characterized by the presence and growth of endometrial implants outside the uterine cavity. The cause of endometriosis is multifactorial. It is due to the diversity of hypothesis and plausibility of hormonal alterations which could play a major role. Evidence has shown that progesterone resistance is a key factor for endometriosis sufferers. Medical therapy can avoid surgical intervention, which may lead to a reduced in ovarian reserve, and its effects of earlier menopause and reduced fecundity. Progesterone receptor isoform has provided new insight as the potential treatment. Progestin, anti-progestin and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating. Numerous types of these medications have been used on and off labeled to treat endometriosis with varying success. This review aims to consolidate series of clinical trials using progestins in endometriosis.

Unlocking ovarian cancer heterogeneity: advancing immunotherapy through single-cell transcriptomics.

Ovarian cancer, a highly fatal gynecological cancer, warrants the need for understanding its heterogeneity. The disease's prevalence and impact are underscored with statistics on mortality rates. Ovarian cancer is categorized into distinct morphological groups, each with its characteristics and prognosis. Despite standard treatments, survival rates remain low due to relapses and chemoresistance. Immune system involvement is evident in ovarian cancer's progression, although the tumor employs immune evasion mechanisms. Immunotherapy, particularly immune checkpoint blockade therapy, is promising, but ovarian cancer's heterogeneity limits its efficacy. Single-cell sequencing technology could be explored as a solution to dissect the heterogeneity within tumor-associated immune cell populations and tumor microenvironments. This cutting-edge technology has the potential to enhance diagnosis, prognosis, and personalized immunotherapy in ovarian cancer, reflecting its broader application in cancer research. The present review focuses on recent advancements and the challenges in applying single-cell transcriptomics to ovarian cancer.

Autologous Human Mesenchymal Stem Cell-Based Therapy in Infertility: New Strategies and Future Perspectives.

Infertility could be associated with a few factors including problems with physical and mental health, hormonal imbalances, lifestyles, and genetic factors. Given that there is a concern about the rise of infertility globally, increased focus has been given to its treatment for the last several decades. Traditional assisted reproductive technology (ART) has been the prime option for many years in solving various cases of infertility; however, it contains significant risks and does not solve the fundamental problem of infertility such as genetic disorders. Attention toward the utilization of MSCs has been widely regarded as a promising option in the development of stem-cell-based infertility treatments. This narrative review briefly presents the challenges in the current ART treatment of infertility and the various potential applications of autologous MSCs in the treatment of these reproductive diseases.

Recent Advances in Surface Plasmon Resonance (SPR) Technology for Detecting Ovarian Cancer Biomarkers.

Epithelial Ovarian Cancer (EOC) is a leading cause of cancer-related deaths among women, mainly due to a lack of early detection and screening methods. Advanced immunoassay techniques, such as Luminex and proximity extension assay (PEA) technology, show promise in improving EOC detection by utilizing highly sensitive and specific multiplex panels to detect multiple combinations of biomarkers. However, these advanced immunoassay techniques have certain limitations, especially in validating the performance characteristics such as specificity, sensitivity, limit of detection (LOD), and dynamic range for each EOC biomarker within the panel. Implementing multiplexing in point-of-care (POC) biosensors can enhance EOC biomarker detection, with Surface Plasmon Resonance (SPR) being a versatile option among optical biosensors. There is no study on multiplex SPR biosensors specifically tailored for diagnosing EOC. Recent studies have shown promising results in the single detection of EOC biomarkers using SPR, with LOD for cancer antigen 125 (CA125) at 0.01 U/mL-1 and human epididymis protein 4 (HE4) at 1pM. This study proposes a potential roadmap for scientists and engineers in academia and industry to develop a cost effective yet highly efficient SPR biosensor platform for detecting EOC.

Dysregulated Exosomes Result in Suppression of the Immune Response of Pregnant COVID-19 Convalescent Women.

A successful pregnancy outcome is dependent on a delicate balance between inflammatory and anti-inflammatory processes throughout the different trimesters. Interruption in this balance can lead to an adverse outcome resulting in pregnancy loss. Since late 2019, the emergence of the new SARS-CoV-2 virus has affected lives worldwide, including pregnant women; therefore, there is an urgent need to address different approaches in relation to prevention, diagnostics, and therapeutics. Early pregnancy is affected by SARS-CoV-2 infection leading to fetal demise. Available evidence also suggests that 90% of pregnant women infected with the SARS-CoV-2 virus seem to be asymptomatic. Nonetheless, it is still unclear how COVID-19 affects exosome production in pregnant women recovered from COVID-19 and how these exosomes regulate the adaptive immune response. In this study, we found several exosomes including CD9, CD31, CD40, CD45, CD41b, CD42a, CD62P, CD69, CD81, CD105, and HLA-DRDPDQ in the plasma of COVID-19-recovered pregnant women were significantly less abundant than the control group. Furthermore, to understand how these exosomes affect the adaptive immune response, we co-cultured the peripheral blood mononuclear cells (PBMCs) from healthy control (HC) pregnant women with exosomes of either Preg-HC or Preg-recovered COVID-19 women. We identified that Preg-recovered COVID-19 women have reduced capacity for the inflammatory cytokine TNF-α from cytotoxic CD8+ T cells. In summary, our study highlights that pregnant recovered COVID-19 women have reduced production of several exosomes and possess fewer immunogenic properties. Our study implicates that exosomes can control inflammation and antigen presentation capacity of immune cells, thus limiting the infection in pregnant women.

PD-L1 Expression in Endometrial Cancer and Its Association with Clinicopathological Features: A Systematic Review and Meta-Analysis.

Endometrial cancer (EC) is one of the most common malignancies of the female genital tract and its current treatment mainly relies on surgical removal of the tumour bulk, followed by adjuvant radiotherapy with or without chemotherapy/hormonal therapy. However, the outcomes of these approaches are often unsatisfactory and are associated with severe toxicity and a higher recurrence rate of the disease. Thus, more clinical research exploring novel medical intervention is needed. Involvement of the immune pathway in cancer has become important and the finding of a high positive expression of programmed cell death-ligand 1 (PD-L1) in EC may offer a better targeted therapeutic approach. Numerous studies on the PD-L1 role in EC have been conducted, but the results remained inconclusive. Hence, this systematic review was conducted to provide an update and robust analysis in order to determine the pooled prevalence of PD-L1 expression in EC and evaluate its association with clinicopathological features in different focuses of tumour cells (TC) and immune cells (IC). A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases. Twelve articles between 2016 and 2021 with 3023 EC cases met the inclusion criteria. The effect of PD-L1 expression on the outcome parameters was estimated by the odds ratios (ORs) with 95% confidence intervals (CIs) for each study. The pooled prevalence of PD-L1 was 34.26% and 51.39% in the tumour cell and immune cell, respectively, among women with EC. The PD-L1 expression was significantly associated with Stage III/IV disease (in both TC and IC) and correlated to the presence of lympho-vascular invasion in IC. However, the PD-L1 expression in TC was not associated with the age groups, histology types, myometrial invasion, and lympho-vascular invasion. In IC, PD-L1 expression was not associated with age group, histology type, and myometrial invasion. The meta-analysis survival outcomes of PD-L1 high expression had a significant association with worse OS in IC but not in TC.

SARS-CoV-2 Infection in Pregnancy: Placental Histomorphological Patterns, Disease Severity and Perinatal Outcomes.

The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p < 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p < 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.

Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials.

Polycystic ovary syndrome (PCOS) and endometriosis are reproductive disorders that may cause infertility. The pathology of both diseases has been suggested to be associated with sex steroid hormone receptors, including oestrogen receptors (ER), progesterone receptors (PRs) and androgen receptors (ARs). Therefore, with this review, we aim to provide an update on the available knowledge of these receptors and how their interactions contribute to the pathogenesis of PCOS and endometriosis. One of the main PCOS-related medical conditions is abnormal folliculogenesis, which is associated with the downregulation of ER and AR expression in the ovaries. In addition, metabolic disorders in PCOS are caused by dysregulation of sex steroid hormone receptor expression. Furthermore, endometriosis is related to the upregulation of ER and the downregulation of PR expression. These receptors may serve as therapeutic targets for the treatment of PCOS-related disorders and endometriosis, considering their pathophysiological roles. Receptor agonists may be applied to increase the expression of a specific receptor and treat endometriosis or metabolic disorders. In contrast, receptor antagonist functions to reduce receptor expression and can be used to treat endometriosis and induce ovulation. Understanding PCOS and the pathological roles of endometriosis sex steroid receptors is crucial for developing potential therapeutic strategies to treat infertility in both conditions. Therefore, research should be continued to fill the knowledge gap regarding the subject.

Maternal and umbilical cord blood polymorphonuclear leukocytes showed moderate oxidative burst at phagocytosis of Gardnerella vaginalis.

OBJECTIVE: Pregnant women with bacterial vaginosis due to Gardnerella vaginalis (GV) infection presents with a wide-ranging disease symptomatology. We speculate this may be due to interaction that varies between host immune response and the pathogen. We studied the oxidative burst in polymorphonuclear leukocytes (PMNL)s from maternal blood (MB) and cord blood (CB) upon phagocytosis of GV and compared against E. coli and Group B Streptococcus (GBS). RESULTS: The PHAGOBURST™ assay detects fluorescence from oxidized dihydrorhodamine during oxidative burst. The average percentage of PMNL showing oxidative burst was almost two-fold greater with GBS (99.5%) and E. coli (98.2%) than GV (56.9%) (p < 0.01) in MB, but a similar proportion of PMNL with burst activity was seen in CB (84.7%). The mean fluorescence intensity (MFI) of oxidative burst in MB PMNL with GV was lower compared to E. coli but comparable to GBS. The MFI of CB PMNL (1580 ± 245.8) was significantly higher than MB PMNL (1198 ± 262.1) with GV, p = 0.031. The live-cell imaging showed neutrophil oxidative burst upon phagocytosis of GV produces hypochlorous acid (HOCl). Overall, the HOCL-mediated microbicidal activity against GV is more variable and less robust than E. coli and GBS, especially in maternal than CB PMNL.

New Predictive Biomarkers for Ovarian Cancer.

Ovarian cancer is the eighth-most common cause of death among women worldwide. In the absence of distinctive symptoms in the early stages, the majority of women are diagnosed in advanced stages of the disease. Surgical debulking and systemic adjuvant chemotherapy remain the mainstays of treatment, with the development of chemoresistance in up to 75% of patients with subsequent poor treatment response and reduced survival. Therefore, there is a critical need to revisit existing, and identify potential biomarkers that could lead to the development of novel and more effective predictors for ovarian cancer diagnosis and prognosis. The capacity of these biomarkers to predict the existence, stages, and associated therapeutic efficacy of ovarian cancer would enable improvements in the early diagnosis and survival of ovarian cancer patients. This review not only highlights current evidence-based ovarian-cancer-specific prognostic and diagnostic biomarkers but also provides an update on various technologies and methods currently used to identify novel biomarkers of ovarian cancer.

Prognostic Value of TNFR2 and STAT3 among High-Grade Serous Ovarian Cancer Survivors According to Platinum Sensitivity.

This study's goal was to determine the protein expression level of tumour necrosis factor receptor 2 (TNFR2) and signal transducer and activator of transcription 3 (STAT3) in high-grade serous ovarian cancer (HGSC) tissues in relation to the platinum-based chemotherapy response and the prognosis outcome. A total of 25 HGSC patients underwent primary surgical debulking followed by first-line adjuvant platinum-based chemotherapy. Tissue microarray (TMA) slides were constructed utilising archived formalin fixed paraffin embedded (FFPE). The protein expression of TNFR2 and STAT3 were analysed using immunohistochemistry (IHC) staining and subsequently were correlated to the clinicopathological characteristics, platinum sensitivity as well as the duration of progression-free survival. About 14 out of 25 patients (56.0%) were platinum-sensitive. The progression free survival was significantly longer in the platinum-sensitive (PS) group when compared to those with the platinum-resistant group (PR), p = 0.0001. Among patients with TNFR2 strong expression on ovarian tissue, there was a significantly longer progression-free survival interval of 540 days in the PS group compared to PR, p = 0.0001. Patients with STAT3 expression also showed significantly better progression-free survival of 660 days in the PS group when compared to the PR group, p = 0.0001. In conclusion, patients with strong TNFR2 and STAT3 expression in the ovarian tissue had significantly longer progression-free survival interval in the PS group. Nevertheless, further research with a larger number of tissues may be required to demonstrate further significant differences.

PTEN protein expression has role in predicting disease-free-interval in endometrioid endometrial carcinoma.

OBJECTIVES: To determine the significance of tumour PTEN protein expression in endometrioid endometrial carcinoma (EEC) and it is correlation with tumour characteristics. METHODS: A total of 30 eligible archived paraffin-embedded tissue blocks from 61 EEC cases (January 2015-December 2017) were retrieved from the Histopathology Laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) following institutional ethic approval. For PTEN protein detection, immunohistochemistry (IHC) staining was performed and the data was correlated with clinicopathologic parameters. RESULTS: Fourteen samples (46.7%) showed positive PTEN protein expression, while 16 (53.3%) were negative. The mean age was 62.00 ± 9.51 years old, while the mean Body Mass Index (BMI) was 27.28 ± 7.16 kg/m2. There was no significant difference between age (p=0.27, 95% CI: -10.98 to 3.21) and BMI (p=0.67, 95% CI: -4.30 to 6.58) with PTEN protein expression. There were significant correlation between PTEN protein expression with myometrial invasion (p=0.010), but not with lymphovascular space invasion (p=0.743), grade (p=0.532), stage (p=0.733) and CA-125 level (p=0.47). The higher stage correlates with the presence of LVSI (p=0.002). PTEN positive associated with longer disease-free-interval (p=0.025), but not improving the overall survival (p=0.38). CONCLUSIONS: Positive PTEN protein expression correlates with less myometrial invasion.

Is First Trimester Maternal 25-Hydroxyvitamin D Level Related to Adverse Maternal and Neonatal Pregnancy Outcomes? A Prospective Cohort Study among Malaysian Women.

Information on the role of 25-hydroxyvitamin D (25(OH)D) in preventing adverse pregnancy/neonatal outcomes is limited in Malaysia. This study aims to determine the relationship between the level of maternal 25(OH)D in the first trimester of pregnant women and their pregnancy/neonatal outcomes. A total of 60 pregnant women in the first trimester were recruited and followed until the end of their pregnancy. The occurrence of any antenatal, delivery, and neonatal complications was recorded. Their blood was collected in the first trimester for total serum 25(OH)D determination using enzyme-linked immunosorbent assay. Overall, 10% of the women had vitamin D deficiency, while 57% had vitamin D insufficiency in their first trimester. No statistically significant difference in 25(OH)D level/status was observed between women with or without antenatal and delivery complications (p > 0.05). No difference in maternal serum 25(OH)D level and vitamin D status was observed between neonates with or without complications (p > 0.05). In conclusion, there is a high prevalence of vitamin D insufficiency among Malaysian pregnant women, but it is not associated with adverse maternal and neonatal outcomes. More comprehensive studies should be planned to verify this relationship.