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Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics

Wu YS, Lee ZY, Chuah LH, Mai CW, Ngai SC

Curr Cancer Drug Targets, 2019;19(2):82-100.
PMID: 29714144 DOI: 10.2174/1568009618666180430130248

Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC are discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future.

Matched MeSH terms: Biomarkers
Plasma miR-146a and miR-365 expression and inflammatory factors in patients with osteoarthritis

Wu W, Xuan Y, Ge Y, Mu S, Hu C, Fan R

Malays J Pathol, 2021 Aug;43(2):311-317.
PMID: 34448795

OBJECTIVE: To investigate the expression levels of micro-ribonucleic acid (miR)-146a and miR-365 in the plasma of osteoarthritis (OA) patients, to study their expression with the inflammatory factors and the severity of disease in patients and to analyse their diagnostic significance.
MATERIALS AND METHODS: A total of 42 OA patients diagnosed with OA and treated in our hospital from January 2017 to January 2018 were selected as the subjects, and 28 healthy people were enrolled as controls. The expressions of interleukin-1 beta (IL-1β) and IL-6 in the plasma of OA patients were detected via immunohistochemical staining. Moreover, the knee joint function of OA patients was evaluated by Lysholm score, Western Ontario and McMaster Universities (WOMAC) score and Visual Analogue Scale (VAS) score. The expression levels of plasma miR-146a and miR-365 in OA patients were measured through RT-PCR. Besides, the significance of the expression levels of miR-146a and miR-365 for the diagnosis of OA was analysed by ROC curves.
RESULTS: As compared with healthy people, OA patients had elevated expression levels of plasma IL-1β and IL-6, decreased Lysholm score, increased WOMAC and VAS scores as well as significantly up-regulated levels of plasma miR-146a and miR-365, which were of important significance for diagnosis.
CONCLUSION: The expression levels of plasma miR-146a, miR-365 and inflammatory factors are notably higher, the disease is more severe, and the function of knee joint movement is weaker in OA patients than those in healthy controls. It can be concluded that the levels of both miR-146a and miR-365 can serve as biomarkers of OA diagnosis.

Matched MeSH terms: Biomarkers
Combined detection of urinary biomarkers noninvasively predicts extent of renal injury in patients with early diabetic kidney disease with kidney qi deficiency syndrome: A retrospective investigation

Wu W, Meng XJ, Wan BY, Fang QJ, Liu YL, Wang J, et al.

Anat Rec (Hoboken), 2023 Dec;306(12):2945-2957.
PMID: 34910381 DOI: 10.1002/ar.24835

Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-β-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.

Matched MeSH terms: Biomarkers
Fulltext Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region

Wu CH, Chang YF, Chen CH, Lewiecki EM, Wüster C, Reid I, et al.

J Clin Densitom, 2021;24(1):3-13.
PMID: 31010789 DOI: 10.1016/j.jocd.2019.03.004

Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low adherence rates of medical treatment of osteoporosis, the experts reached consensus on the use of BTMs for both raising awareness and short-term monitoring of osteoporosis treatment in the AP region. The experts endorse the use of BTMs, especially serum C-terminal telopeptide of type 1 collagen (CTX) and serum procollagen type 1 N propeptide (P1NP), as short-term monitoring tools to help clinicians assess the responses to osteoporosis therapies and appropriately adjust treatment regimens earlier than BMD. Either the absolute values or the degree of change from baseline in BTMs can be used to monitor the potential efficacy of osteoporosis therapies. The use of BTMs can be incorporated in osteoporosis care programs, such as fracture liaison service (FLS), to improve patient adherence and treatment outcomes. Encouraging sufficient reimbursement from health care systems may facilitate widespread use of BTMs in clinical practice in the AP region.

Matched MeSH terms: Biomarkers
The immunohistochemistry signature of mismatch repair (MMR) proteins in a multiethnic Asian cohort with endometrial carcinoma

Woo YL, Cheah PL, Shahruddin SI, Omar SZ, Arends M

Int J Gynecol Pathol, 2014 Nov;33(6):554-9.
PMID: 25272293 DOI: 10.1097/PGP.0000000000000099

Endometrial cancer is the most common gynecologic cancer in developed countries and is rising in incidence globally. Although the 5-year survival rates are >80%, factors beyond conventional pathologic features that predict clinical outcomes are still being elucidated. The aims of this study were to define the prevalence and associations of deficient mismatch repair (dMMR) protein expression (MLH1, MSH2, MSH6, PMS2) by immunohistochemistry in a multiethnic Southeast Asian cohort with endometrioid endometrial cancer. A total of 77 patients with adequate formalin-fixed paraffin-embedded specimens were identified. The sections were stained in 2 centers for 4 MMR proteins and examined by 2 independent specialist histopathologists. The mean age for the cohort was 58.6 yr, with 19.4% (15/77) of patients' cancers showing loss of 2 MMR proteins. All 13 cancers with absent MLH1 showed PMS2 loss (13/15), whereas absent MSH2 correlated with MHS6 loss (2/15). There were no significant differences for dMMR cases in age, body mass index, histopathologic characteristics, and clinical outcomes. In dMMR cases, an overrepresentation of patients of Indian ethnic origin was observed compared with Chinese and Malays. These findings suggest that dMMR protein expression in a Southeast Asian endometrial cancer cohort does not correlate with disease outcomes.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Ratiometric Detection of microRNA Using Hybridization Chain Reaction and Fluorogenic Silver Nanoclusters

Wong ZW, Ng JF, New SY

Chem Asian J, 2021 Dec 13;16(24):4081-4086.
PMID: 34668337 DOI: 10.1002/asia.202101145

miRNA (miR)-155 is a potential biomarker for breast cancers. We aimed at developing a nanosensor for miR-155 detection by integrating hybridization chain reaction (HCR) and silver nanoclusters (AgNCs). HCR serves as an enzyme-free and isothermal amplification method, whereas AgNCs provide a built-in fluorogenic detection probe that could simplify the downstream analysis. The two components were integrated by adding a nucleation sequence of AgNCs to the hairpin of HCR. The working principle was based on the influence of microenvironment towards the hosted AgNCs, whereby unfolding of hairpin upon HCR has manipulated the distance between the hosted AgNCs and cytosine-rich toehold region of hairpin. As such, the dominant emission of AgNCs changed from red to yellow in the absence and presence of miR-155, enabling a ratiometric measurement of miR with high sensitivity. The limit of detection (LOD) of our HCR-AgNCs nanosensor is 1.13 fM in buffered solution. We have also tested the assay in diluted serum samples, with comparable LOD of 1.58 fM obtained. This shows the great promise of our HCR-AgNCs nanosensor for clinical application.

Matched MeSH terms: Biomarkers, Tumor/blood*; Biomarkers, Tumor/genetics
Dendritic fibromyxolipoma: a variant of spindle cell lipoma with extensive myxoid change, with cytogenetic evidence

Wong YP, Chia WK, Low SF, Mohamed-Haflah NH, Sharifah NA

Pathol. Int., 2014 Jul;64(7):346-51.
PMID: 25047505 DOI: 10.1111/pin.12176

Dendritic fibromyxolipoma (DFML), a rare, recently described distinct benign soft tissue tumor, has many clinicopathological features reminiscent of spindle cell lipoma and solitary fibrous tumor with myxoid change. It is distinguished histologically from both entities by the presence of spindle and stellate cells with dendritic cytoplasmic prolongations, prominent myxoid stroma with abundant keloidal collagen and occasional small plexiform vascular proliferation. We describe a case of histologically confirmed DFML of the left shoulder in a 67-year-old male, in which subsequent cytogenetic analysis revealed deletion involving 13q14.3 region in all the tumor cells, typically detected in spindle cell lipoma. In the presence of many clinicopathological similarities between DFML and spindle cell lipoma including chromosomal abnormalities, we postulate that DFML is merely a rare variant of spindle cell lipoma with extensive myxoid degeneration, and may not be considered as a separate entity. The possible differential diagnosis and their distinguishing features are briefly discussed.

Matched MeSH terms: Biomarkers, Tumor/genetics
Primary extragonadal vaginal yolk sac tumour: A case report

Wong YP, Yahaya A, Che Abdul Aziz R, Chia PY, Loh CK, Tan GC

Malays J Pathol, 2020 Aug;42(2):301-305.
PMID: 32860387

INTRODUCTION: Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads.
CASE REPORT: We described a case of extragonadal vaginal YST in a one year and seven months old girl who presented with vaginal discharge and bleeding, and discuss its differential diagnosis and potential pitfalls in immunohistochemistry. She was found to have a suprapubic mass on examination. The serum alpha fetoprotein was 11919.4 ng/mL. Computed tomography of the pelvis revealed a large 6.4 cm heterogenous pelvic mass. Colposcopic examination of the pelvis showed a fungating vaginal mass that was subsequently confirmed as a yolk sac tumour. Immunohistochemically, the malignant cells were positive toward CKAE1/AE3, AFP and glypican-3, as well as CD117.
DISCUSSION: Solid pattern extragonadal vaginal YST may morphologically resemble dysgerminoma that is also CD117 positive, while the glandular pattern YST may have clear cytoplasm and is positive for cytokeratin; hence, may resemble clear cell carcinoma. Being mindful of these potential diagnostic caveats is necessary to prevent misdiagnosis.

Matched MeSH terms: Biomarkers, Tumor/metabolism
CD3-positive plasmablastic lymphoma reported in two cases: A potential diagnostic caveat

Wong YP, Masir N, Chew MX

Indian J Pathol Microbiol, 2021 8 4;64(3):579-583.
PMID: 34341278 DOI: 10.4103/IJPM.IJPM_616_20

Plasmablastic lymphoma (PBL) is a rare aggressive subtype of mature large B cell lymphoma involving almost exclusively the extranodal regions particularly the oral cavity, frequently described in immunocompromised patients. PBL is characterized histologically by diffuse proliferation of large neoplastic cells resembling B immunoblasts or plasmablasts. The diagnosis of PBL can be difficult due to its ambiguous histopathological features mimicking most large cell lymphomas and lacking a distinctive immunophenotypic pattern. They typically lack expression of CD20 and CD79a but may express plasma cell marker, CD138. Aberrant immunoexpression of CD3, a T-cell marker in PBL in the absence of other B-cell markers is exceptionally rare, may potentially lead to incorrect interpretation. Herein, we report a case series of CD3-positive PBL of oral cavity in two individuals, which were initially misdiagnosed as high-grade T-cell lymphomas including extranodal NK/T-cell lymphoma, nasal type. Useful distinguishing clinical settings, histomorphological features, immunohistochemistry and molecular expression profiles of PBL are discussed.

Matched MeSH terms: Biomarkers, Tumor
Fulltext Metastasis within a metastasis to the thyroid: A rare phenomenon

Wong YP, Affandi KA, Tan GC, Muhammad R

Indian J Pathol Microbiol, 2017 9 25;60(3):430-432.
PMID: 28937391 DOI: 10.4103/IJPM.IJPM_287_16

Metastatic disease involving the thyroid gland is uncommon. Solitary thyroid metastases from various primary sites particularly kidney, lung, and breast had been previously described. To the best of our knowledge, metastases from two topographically separate primary malignancies to the thyroid have never been documented hitherto. This is the first reported case of cancer-to-cancer metastasis involving an invasive breast carcinoma metastasized within a metastatic renal cell carcinoma in the nonneoplastic thyroid in a 58-year-old woman. Distinguishing a secondary thyroid metastases from a primary thyroid malignancy is utmost crucial as treatment differs. The possibility of tumor metastases from two separated primaries should always be considered in a tumor exhibiting malignant cell populations with two distinctive histomorphological appearances. The role of immunohistochemistry stains in equivocal cases cannot be overemphasized.

Matched MeSH terms: Biomarkers, Tumor/analysis
P16INK4a: a potential diagnostic adjunct for prediction of high-grade cervical lesions in liquid-based cytology: with HPV testing and histological correlation

Wong YP, Abdul Raub SH, Mohd Dali AZ, Kassim F, Visvalingam V, Zakaria Z, et al.

Malays J Pathol, 2016 Aug;38(2):93-101.
PMID: 27568665

Human papillomavirus (HPV) is a necessary cause of cervical cancer and its precursors. Increased expression of high-risk hrHPV viral oncogenes in abnormal cells might increase the expression of p16INK4a. We aimed to determine the role of p16INK4a in detecting hrHPV-transformed epithelial cells in liquid-based cervical cytology, and compared the results with hrHPV DNA testing by realtime polymerase chain reaction (RT-PCR). Fifty-seven cytological samples were tested for p16INK4a immunomarker and hrHPV DNA. Test performance of both tests was determined by comparing sensitivity, specificity and predictive values using available histological follow-up data as gold standard. Of 57 samples, 36 (63.2%) showed immunoreactivity for p16INK4a and 43 (75.4%) were hrHPV-infected. A fairly low concordance rate (k = 0.504) between p16INK4a immunolabelling and hrHPV DNA status was noted. For prediction of cervical intraepithelial neoplasia (CIN) II and worse lesions, p16INK4a had a sensitivity and specificity of 93.5% and 60%; whereas hrHPV DNA testing had a sensitivity and specificity of 100% and 20%. Dual testing by combining p16INK4a and hrHPV showed sensitivity and specificity of 100% and 33.3%. In conclusion, p16INK4a is useful in predicting severity of the cytological abnormalities. Although p16INK4a is more specific but less sensitive than hrHPV in detecting high-grade cervical lesions, a combination of both tests failed to demonstrate significant improvement in diagnostic sensitivity, specificity and predictive value. Larger-scale prospective studies are required to assess further whether this biomarker should be routinely used as primary screening tool independently or in combination with hrHPV testing to improve diagnostic accuracy in cervical cytology.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Identification of potential glycoprotein biomarkers in oral squamous cell carcinoma using sweet strategies

Wong YL, Anand R, Yuen KM, Mustafa WMW, Abraham MT, Tay KK, et al.

Glycoconj J, 2021 02;38(1):1-11.
PMID: 33547992 DOI: 10.1007/s10719-021-09973-z

The prevalence of oral squamous cell carcinoma (OSCC) is high in South and Southeast Asia regions. Most OSCC patients are detected at advanced stages low 5-year survival rates. Aberrant expression of glycosylated proteins was found to be associated with malignant transformation and cancer progression. Hence, identification of cancer-associated glycoproteins could be used as potential biomarkers that are beneficial for diagnosis or clinical management of patients. This study aims to identify the differentially expressed glycoproteins using lectin-based glycoproteomics approaches. Serum samples of 40 patients with OSCC, 10 patients with oral potentially malignant disorder (OPMD), and 10 healthy individuals as control group were subjected to two-dimensional gel electrophoresis (2-DE) coupled with lectin Concanavalin A and Jacalin that specifically bind to N- and O-glycosylated proteins, respectively. Five differentially expressed N- and O-glycoproteins with various potential glycosylation sites were identified, namely N-glycosylated α1-antitrypsin (AAT), α2-HS-glycoprotein (AHSG), apolipoprotein A-I (APOA1), and haptoglobin (HP); as well as O-glycosylated AHSG and clusterin (CLU). Among them, AAT and APOA1 were further validated using enzyme-linked immunosorbent assay (ELISA) (n = 120). It was found that AAT and APOA1 are significantly upregulated in OSCC and these glycoproteins are independent risk factors of OSCC. The clinical utility of AAT and APOA1 as potential biomarkers of OSCC is needed for further evaluation.

Matched MeSH terms: Biomarkers, Tumor/blood*
Fulltext A case of t(14; 18)-negative follicular lymphoma with atypical immunophenotype: usefulness of immunoarchitecture of Ki67, CD79a and follicular dendritic cell meshwork in making the diagnosis

Wong Y, Abdul-Rahman F, Samsudin AT, Masir N

Malays J Pathol, 2014 Aug;36(2):125-9.
PMID: 25194535 MyJurnal

Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy. Histopathological examination of the lymph node showed complete architectural effacement by neoplastic follicles containing expanded CD21-positive follicular dendritic cell meshwork. The neoplastic cells expressed pan-B cell markers (CD20, CD79a) and germinal centre marker (BCL6) but not BCL2 and CD10. Of interest are the staining patterns of Ki67 and CD79a. We observed that the Ki67- positive proliferating cells were evenly distributed within the neoplastic follicles without zonation. In addition, CD79a was homogeneously strong within the neoplastic follicles. These staining patterns were distinctly different from that observed in reactive lymphoid follicles. Fluorescent insitu hybridisation (FISH) analysis however showed absence of BCL2 gene rearrangement. Despite the atypical immunophenotype and lack of BCL2 gene rearrangement, the diagnosis of follicular lymphoma was made based on careful observation of the morphology as well as immunoarchitecture of the Ki67, CD79a and CD21 markers.

Matched MeSH terms: Biomarkers, Tumor/metabolism*
Fulltext Analysis of Entamoeba histolytica excretory-secretory antigen and identification of a new potential diagnostic marker

Wong WK, Tan ZN, Othman N, Lim BH, Mohamed Z, Olivos Garcia A, et al.

Clin Vaccine Immunol, 2011 Nov;18(11):1913-7.
PMID: 21918120 DOI: 10.1128/CVI.05356-11

Serodiagnosis of amoebiasis remains the preferred method for diagnosis of amoebic liver abscess (ALA). However, the commercially available kits are problematic in areas of endemicity due to the persistently high background antibody titers. Human serum samples (n = 38) from patients with ALA who live in areas of endemicity were collected from Hospital Universiti Sains Malaysia during the period of 2008 to 2010. Western blots using excretory-secretory antigen (ESA) collected from axenically grown Entamoeba histolytica were probed with the above serum samples. Seven antigenic proteins of ESA with various reactivities were identified, i.e., 152 kDa, 131 kDa, 123 kDa, 110 kDa, 100 kDa, 82 kDa, and 76 kDa. However, only the 152-kDa and 110-kDa proteins showed sensitivities above 80% in the Western blot analysis. All the antigenic proteins showed undetectable cross-reactivity when probed with healthy human serum samples (n = 30) and serum samples from other infections (n = 33). From the matrix-assisted laser desorption ionization-two-stage time of flight (MALDI-TOF/TOF) analysis, the proteins were identified as heavy subunits of E. histolytica lectin and E. histolytica pyruvate phosphate dikinase, respectively. Use of the E. histolytica lectin for diagnosis of ALA has been well reported by researchers and is being used in commercialized kits. However, this is the first report on the potential use of pyruvate phosphate dikinase for diagnosis of ALA; thus, this molecule merits further evaluation on its diagnostic value using a larger panel of serum samples.

Matched MeSH terms: Biomarkers/blood
Effects of 25-hydroxyvitamin D and vitamin D-binding protein on bone mineral density and disease activity in Malaysian patients with rheumatoid arthritis

Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, Yeap SS

Int J Rheum Dis, 2018 May;21(5):992-1000.
PMID: 28217867 DOI: 10.1111/1756-185X.13048

AIM: Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate 'bioavailable' levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls.

METHODS: A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys® Vitamin D total assay. Serum VDBP was measured using a Quantikine® enzyme-linked immunosorbent assay kit. BMD was assessed using dual-energy X-ray absorptiometry (DXA).

RESULTS: Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.

CONCLUSIONS: In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Semblance; Klinik Pakar Puchong, Puchong, Kuala Lumpur, Malaysia

Matched MeSH terms: Biomarkers/blood
Effectiveness of a colour coded HbA1c graphical record in improving diabetes control in people with type 2 diabetes: a randomized control trial

Wong SS, Ng CJ, Liew SM, Hussein N

Diabetes Res Clin Pract, 2012 Feb;95(2):e41-4.
PMID: 22119614 DOI: 10.1016/j.diabres.2011.11.001

We conducted a six-month randomized-controlled-trial to evaluate the effectiveness of a colour-coded HbA1c-graphical record in improving HbA1c level among type 2 diabetes patients. There was an improvement in the mean HbA1c knowledge score but the usage of the colour-coded HbA1c-graphical record did not produce reduction in the HbA1c level.
Study site: Primary care clinic, University Malaya Medical Centre, Kuala Lumpur, Malaysia

Matched MeSH terms: Biomarkers/blood
Fulltext The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence

Wong SK, Mohamad NV, Ibrahim N', Chin KY, Shuid AN, Ima-Nirwana S

Int J Mol Sci, 2019 Mar 22;20(6).
PMID: 30909398 DOI: 10.3390/ijms20061453

Bone remodelling is a tightly-coordinated and lifelong process of replacing old damaged bone with newly-synthesized healthy bone. In the bone remodelling cycle, bone resorption is coupled with bone formation to maintain the bone volume and microarchitecture. This process is a result of communication between bone cells (osteoclasts, osteoblasts, and osteocytes) with paracrine and endocrine regulators, such as cytokines, reactive oxygen species, growth factors, and hormones. The essential signalling pathways responsible for osteoclastic bone resorption and osteoblastic bone formation include the receptor activator of nuclear factor kappa-B (RANK)/receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG), Wnt/β-catenin, and oxidative stress signalling. The imbalance between bone formation and degradation, in favour of resorption, leads to the occurrence of osteoporosis. Intriguingly, vitamin E has been extensively reported for its anti-osteoporotic properties using various male and female animal models. Thus, understanding the underlying cellular and molecular mechanisms contributing to the skeletal action of vitamin E is vital to promote its use as a potential bone-protecting agent. This review aims to summarize the current evidence elucidating the molecular actions of vitamin E in regulating the bone remodelling cycle.

Matched MeSH terms: Biomarkers
Fulltext Effects of metabolic syndrome on bone mineral density, histomorphometry and remodelling markers in male rats

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

PLoS One, 2018;13(2):e0192416.
PMID: 29420594 DOI: 10.1371/journal.pone.0192416

This study aimed to evaluate the effects of metabolic syndrome (MetS) induced by high-carbohydrate high-fat (HCHF) diet on bone mineral density (BMD), histomorphometry and remodelling markers in male rats. Twelve male Wistar rats aged 12 weeks old were randomized into two groups. The normal group was given standard rat chow while the HCHF group was given HCHF diet to induce MetS. Abdominal circumference, blood glucose, blood pressure, and lipid profile were measured for the confirmation of MetS. Bone mineral density, histomorphometry and remodelling markers were evaluated for the confirmation of bone loss. The HCHF diet caused central obesity, hyperglycaemia, hypertension, and dyslipidaemia in male rats. No significant difference was observed in whole body bone mineral content and BMD between the normal and HCHF rats (p>0.05). For bone histomorphometric parameters, HCHF diet-fed animals had significantly lower osteoblast surface, osteoid surface, osteoid volume, and significantly higher eroded surface; resulting in a reduction in trabecular bone volume (p<0.05). Feeding on HCHF diet caused a significantly higher CTX-1 level (p<0.05), but did not cause any significant change in osteocalcin level compared to normal rats (p>0.05). In conclusion, HCHF diet-induced MetS causes imbalance in bone remodelling, leading to the deterioration of trabecular bone structure.

Matched MeSH terms: Biomarkers/metabolism*
Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28

Wong PF, Cheong WF, Shu MH, Teh CH, Chan KL, AbuBakar S

Phytomedicine, 2012 Jan 15;19(2):138-44.
PMID: 21903368 DOI: 10.1016/j.phymed.2011.07.001

Bioactive compounds from the medicinal plant, Eurycoma longifolia Jack have been shown to promote anti-proliferative effects on various cancer cell lines. Here we examined the effects of purified eurycomanone, a quassinoid found in Eurycoma longifolia Jack extract, on the expression of selected genes of the A549 lung cancer cells. Eurycomanone inhibited A549 lung cancer cell proliferation in a dose-dependent manner at concentrations ranging from 5 to 20 μg/ml. The concentration that inhibited 50% of cell growth (GI(50)) was 5.1 μg/ml. The anti-proliferative effects were not fully reversible following the removal of eurycomanone, in which 30% of cell inhibition still remained (p<0.0001, T-test). At 8 μg/ml (GI(70)), eurycomanone suppressed anchorage-independent growth of A549 cells by >25% (p<0.05, T-test, n=8) as determined using soft agar colony formation assay. Cisplatin, a chemotherapy drug used for the treatment of non small cell lung cancer on the other hand, inhibited A549 cells proliferation at concentrations ranging from 0.2 μg/ml to 15 μg/ml with a GI(50) of 0.58 μg/ml. The treatment with eurycomanone reduced the abundance expression of the lung cancer markers, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, p53 tumor suppressor protein and other cancer-associated genes including prohibitin (PHB), annexin 1 (ANX1) and endoplasmic reticulum protein 28 (ERp28) but not the house keeping genes. The mRNA expressions of all genes with the exception of PHB were significantly downregulated, 72 h after treatment (p<0.05, T-test, n=9). These findings suggest that eurycomanone at viable therapeutic concentrations of 5-20 μg/ml exhibited significant anti-proliferative and anti-clonogenic cell growth effects on A549 lung cancer cells. The treatment also resulted in suppression of the lung cancer cell tumor markers and several known cancer cell growth-associated genes.

Matched MeSH terms: Biomarkers, Tumor/chemistry*
Comparative transcriptional study of the effects of high intracellular zinc on prostate carcinoma cells

Wong PF, Abubakar S

Oncol Rep, 2010 Jun;23(6):1501-16.
PMID: 20428803

The normally high concentration of zinc in normal prostate gland is significantly reduced in malignant prostate tissues, but its precise role in prostate tumorigenesis remains unclear. The present study investigates the growth and transcriptional responses of LNCaP prostate cancer cells to prolonged high Zn2+ treatment. Restoration of high intracellular Zn2+ to LNCaP cells significantly reduced the cell proliferation rate by 42.2+/-7.4% at the exponential growth phase and the efficiency of colony formation on soft agar by 87.2+/-2.5% at week 5 post-treatment. At least 161 LNCaP cell genes responded to the high intracellular Zn2+, including approximately 10.6% genes that negatively regulate cell growth and approximately 16.1% genes that promote cancer cell proliferation. Inhibition of cell growth was transient as normal proliferation rate and colony formation efficiency were restored later even in the continuous presence of high intracellular Zn2+. RT-qPCR showed constitutively higher expression levels of FBL, CD164 and STEAP1 in LNCaP cells. FBL and CD164 were responsive to the treatment with Zn2+ in PNT2 prostate normal cells and were further overexpressed in the prolonged Zn2+-treated LNCaP cells. These observations suggest that in general high Zn2+ has suppressive effects on prostate cancer cell growth but continuous exposure to an environment of high Zn2+ can lead to the overexpression of cancer promoting genes such as FBL and CD164. This could be the antagonistic mechanism used to overcome the initial cell growth inhibitory effects of high Zn2+. These findings support a potential detrimental role of Zn2+ in prostate cancer.

Matched MeSH terms: Biomarkers, Tumor/genetics*; Biomarkers, Tumor/metabolism

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