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

Swaminathan A, Abd Aziz NH, Ayub NA, Wong KK, Cheah FC

BMC Res Notes, 2021 Nov 22;14(1):420.
PMID: 34809696 DOI: 10.1186/s13104-021-05842-y

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

Kumar VR, Kampan NC, Abd Aziz NH, Teik CK, Shafiee MN, Menon PS

Cancers (Basel), 2023 Nov 27;15(23).
PMID: 38067311 DOI: 10.3390/cancers15235607

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

Abdul Karim AK, Abd Aziz NH, Md Zin RR, Mohd Mokhtar N, Shafiee MN

Malays J Med Sci, 2020 Dec;27(6):7-14.
PMID: 33447130 DOI: 10.21315/mjms2020.27.6.2

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

Abd Aziz NH, Yazid NA, Abd Rahman R, Abd Rashid N, Wong SK, Mohamad NV, et al.

Int J Environ Res Public Health, 2020 05 08;17(9).
PMID: 32397276 DOI: 10.3390/ijerph17093291

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.
Reviewing the role of progesterone therapy in endometriosis

Abdul Karim AK, Shafiee MN, Abd Aziz NH, Omar MH, Abdul Ghani NA, Lim PS, et al.

Gynecol Endocrinol, 2019 Jan;35(1):10-16.
PMID: 30044157 DOI: 10.1080/09513590.2018.1490404

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

Mamat Yusof MN, Chew KT, Kampan N, Abd Aziz NH, Md Zin RR, Tan GC, et al.

Cancers (Basel), 2022 Aug 13;14(16).
PMID: 36010904 DOI: 10.3390/cancers14163911

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

Wong YP, Tan GC, Omar SZ, Mustangin M, Singh Y, Salker MS, et al.

Int J Environ Res Public Health, 2022 Aug 03;19(15).
PMID: 35954874 DOI: 10.3390/ijerph19159517

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

Silva Raju J, Abd Aziz NH, Atallah GA, Teik CK, Shafiee MN, Mohd Saleh MF, et al.

Diagnostics (Basel), 2021 Mar 16;11(3).
PMID: 33809542 DOI: 10.3390/diagnostics11030526

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

Shafiee MN, Lim WK, Poh Shwen Shi C, Mohamed Yasin IA, Azemi AF, Zakaria ML, et al.

Horm Mol Biol Clin Investig, 2021 Aug 09;42(4):403-410.
PMID: 34364315 DOI: 10.1515/hmbci-2021-0017

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.