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The Immunomodulatory Potential of Selected Bioactive Plant-Based Compounds in Breast Cancer: A Review

Baraya YS, Wong KK, Yaacob NS

Anticancer Agents Med Chem, 2017;17(6):770-783.
PMID: 27539316 DOI: 10.2174/1871520616666160817111242

Breast cancer has continued to cause high cancer death rates among women worldwide. The use of plants' natural products in breast cancer treatment has received more attention in recent years due to their potentially wider safety margin and the potential to complement conventional chemotherapeutic drugs. Plantbased products have demonstrated anticancer potential through different biological pathways including modulation of the immune system. Immunomodulatory properties of medicinal plants have been shown to mitigate breast cancer cell growth. Different immune cell types participate in this process especially cytotoxic T cells and natural killer cells, and cytokines including chemokines and tumor necrosis factor-α. Medicinal plants such as Glycyrrhiza glabra, Uncaria tomentosa, Camellia sinensis, Panax ginseng, Prunus armenaica (apricot), Allium sativum, Arctium lappa and Curcuma longa were reported to hold strong potential in breast cancer treatment in various parts of the world. Interestingly, research findings have shown that these plants possess bioactive immunomodulators as their main constituents producing the anticancer effects. These immunomodulatory compounds include ajoene, arctigenin, β-carotene, curcumin, epigallocatechin-3-gallate, ginsan, glabridin and quinic acid. In this review, we discussed the ability of these eight immunomodulators in regulating the immune system potentially applicable in breast cancer treatment via anti-inflammatory (curcumin, arctigenin, glabridin and ajoene) and lymphocytes activation (β-carotene, epigallocatechin-3-gallate, quinic acid and ginsan) properties, as well as future research direction in their use for breast cancer treatment.
Fulltext Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia

Wong KK, Lawrie CH, Green TM

Biomark Insights, 2019;14:1177271919846454.
PMID: 31105426 DOI: 10.1177/1177271919846454

Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hypomethylating agents (azacitidine and decitabine) in AML patients are presented. Novel hypomethylating agent (guadecitabine) and experimental DNMT inhibitors in AML are also discussed. In summary, hypermethylation of tumour suppressors mediated by DNMT1 or DNMT3B contributes to the progression and severity of AML (except MLL-AF9 and inv(16)(p13;q22) AML for DNMT3B), while mutation affecting DNMT3A represents an early genetic lesion in the pathogenesis of AML. In clinical trials of AML patients, expression of DNMTs is downregulated by hypomethylating agents while the clinical response predictive roles of DNMT biomarkers remain unresolved. Finally, nucleoside hypomethylating agents have continued to show enhanced responses in clinical trials of AML patients, and novel non-nucleoside DNMT inhibitors have demonstrated cytotoxicity against AML cells in pre-clinical settings.
Comorbid association of antiphospholipid antibodies and migraine: A systematic review and meta-analysis

Islam MA, Alam F, Wong KK

Autoimmun Rev, 2017 May;16(5):512-522.
PMID: 28279839 DOI: 10.1016/j.autrev.2017.03.005

BACKGROUND: Antiphospholipid antibodies (aPLs) namely anticardiolipin (aCL) antibody, anti-β2-glycoprotein I (β2GPI) antibody and lupus anticoagulant (LA) are autoantibodies produced against anionic phospholipids and proteins on plasma membranes. Migraine is a primary headache disorder which has growing evidences of autoimmune-mediated pathogenesis and previous studies suggested the presence of aPLs in migraine patients.

AIMS: The aim of this study was to evaluate the comorbid association between aPLs (aCL, anti-β2GPI and LA) and migraine compared to healthy controls.

METHODS: Studies were searched through PubMed, ISI Web of Science and Google Scholar databases without restricting the languages and year (up to October 2016) and were selected based on the inclusion criteria. Two authors independently extracted data from the included studies. All analyses were conducted by using random effects model to calculate the odds ratio (OR) and 95% confidence interval (CI). Quality assessment was carried out by using the modified Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualization of funnel plots, Begg's and Egger's tests.

RESULTS: The database searches produced 1995 articles, 13 of which were selected (912 migraineurs and 822 healthy controls). 8.59%, 15.21% and 4.11% of the migraineurs exhibited aCL, anti-β2GPI and LA which was 4.83, 1.63 and 3.03 times higher, respectively, than healthy controls. A significant presence of aCL (OR: 3.55, 95% CI: 1.59-7.95; p=0.002) or anti-β2GPI antibodies (OR: 2.02, 95% CI: 1.20-3.42; p=0.008) was observed in migraine patients, however, LA was not significantly associated (OR: 2.02, 95% CI: 0.50-8.37; p=0.320). Majority of the studies (n=10 of 13) demonstrated NOS score of 7 or above and no significant publication bias was observed.

CONCLUSION: Migraine might be an autoimmune-associated neurologic disorder. The presence of aCL or anti-β2GPI antibodies was significant in migraine patients compared to healthy controls, suggesting an involvement of these autoantibodies in migraine attack.
Margetuximab and trastuzumab deruxtecan: New generation of anti-HER2 immunotherapeutic agents for breast cancer

Nur Husna SM, Wong KK

Mol Immunol, 2022 Dec;152:45-54.
PMID: 36272249 DOI: 10.1016/j.molimm.2022.10.005

Advances in the development of anti-HER2 monoclonal antibodies (mAbs) represent one of the most significant milestones in the treatment of HER2+ breast cancer patients. However, HER2+ metastatic breast cancer (MBC) patients display resistance towards first-generation anti-HER2 mAbs or antibody-drug conjugate (ADC) treatment. In recent years, new generation of anti-HER2 mAb and ADC including margetuximab and trastuzumab deruxtecan (T-DXd), respectively, have been approved for the treatment of previously treated HER2+ MBC patients. The successes of margetuximab and T-DXd have renewed the interest in the research and development of anti-HER2 immunotherapies for both HER2+ and HER2-low breast cancer patients. In this review, we focus on these two immunotherapeutics in terms of their mechanisms of action, preclinical findings and clinical trials leading to their approval, as well as the mechanisms of resistance to conventional anti-HER2 immunotherapies (i.e. trastuzumab, pertuzumab and T-DM1). In the future, combination of either margetuximab or T-DXd with small molecule inhibitors such as tyrosine kinase inhibitors that elicit anticancer immunogenicity may further enhance the efficacy of margetuximab or T-DXd in the treatment of HER2+ MBC patients.
Fulltext Evaluation of delivery of enteral nutrition in mechanically ventilated Malaysian ICU patients

Yip KF, Rai V, Wong KK

BMC Anesthesiol, 2014;14:127.
PMID: 25587238 DOI: 10.1186/1471-2253-14-127

There are numerous challenges in providing nutrition to the mechanically ventilated critically ill ICU patient. Understanding the level of nutritional support and the barriers to enteral feeding interruption in mechanically ventilated patients are important to maximise the nutritional benefits to the critically ill patients. Thus, this study aims to evaluate enteral nutrition delivery and identify the reasons for interruptions in mechanically ventilated Malaysian patients receiving enteral feeding.
Fulltext Editorial: A new frontier for traditional medicine research-Multi-omics approaches

Fu X, Wong KK, Tseng Y

Front Pharmacol, 2023;14:1203097.
PMID: 37229267 DOI: 10.3389/fphar.2023.1203097
Fulltext Multiomics in silico analysis identifies TM4SF4 as a cell surface target in hepatocellular carcinoma

Wong KK, Ab Hamid SS

PLoS One, 2025;20(2):e0307048.
PMID: 39999090 DOI: 10.1371/journal.pone.0307048

The clinical application of cellular immunotherapy in hepatocellular carcinoma (HCC) is impeded by the lack of a cell surface target frequently expressed in HCC cells and with minimal presence in normal tissues to reduce on-target, off-tumor toxicity. To address this, an in silico multomics analysis was conducted to identify an optimal therapeutic target in HCC. A longlist of genes (n = 12,948) expressed in HCCs according to The Human Protein Atlas database were examined. Eight genes were shortlisted to identify one with the highest expression in HCCs, without being shed into circulation, and with restrictive expression profile in other normal human tissues. A total of eight genes were shortlisted and subsequently ranked according to the combination of their transcript and protein expression levels in HCC cases (n = 791) derived from four independent datasets. TM4SF4 was the top-ranked target with the highest expression in HCCs. TM4SF4 showed more favorable expression profile with significantly lower expression in normal human tissues but more highly expressed in HCC compared with seven other common HCC therapeutic targets. Furthermore, scRNA-seq and immunohistochemistry datasets showed that TM4SF4 was absent in immune cell populations but highly expressed in the bile duct canaliculi of hepatocytes, regions inaccessible to immune cells. In scRNA-seq dataset of HCCs, TM4SF4 expression was positively associated with mitochondrial components and oxidative phosphorylation Gene Ontologies in HCC cells (n = 15,787 cells), suggesting its potential roles in mitochondrial-mediated oncogenic effects in HCC. Taken together, TM4SF4 is proposed as a promising cell surface target in HCC due to its high expression in HCC cells with restricted expression profile in non-cancerous tissues, and association with HCC oncogenic pathways.
Oil droplets and solid particles removal using circular separator with inclined coalescence mediums: comparison between co-current and counter-current flow

Ngu LH, Law PL, Wong KK, Yusof AA

Water Sci Technol, 2010;62(5):1129-35.
PMID: 20818055 DOI: 10.2166/wst.2010.407

This research investigated the effects of co- and counter-current flow patterns on oil-water-solid separation efficiencies of a circular separator with inclined coalescence mediums. Oil-water-solid separations were tested at different influent concentrations and flowrates. Removal efficiencies increased as influent flowrate decreased, and their correlationship can be represented by power equations. These equations were used to predict the required flowrate, Q(ss50), for a given influent suspended solids concentration C(iss) to achieve the desired effluent suspended solids concentration, C(ess) of 50 mg/L, to meet environmental discharge requirements. The circular separator with counter-current flow was found to attend removal efficiencies relatively higher as compared to the co-current flow. As compared with co-current flow, counter-current flow Q(ss50) was approximately 1.65 times higher than co-current flow. It also recorded 13.16% higher oil removal at influent oil concentration, C(io) of 100 mg/L, and approximately 5.89% higher TSS removal at all influent flowrates. Counter-current flow's better removal performances were due to its higher coalescing area and constant interval between coalescence plate layers.
Fulltext Influenza and respiratory syncytial viruses: Efficacy of different diagnostic assays

Rahman MM, Wong KK, Alfizah H, Hussin S, Isahak I

Pak J Med Sci, 2015 Jul-Aug;31(4):791-4.
PMID: 26430404 DOI: 10.12669/pjms.314.7003

To determine the efficacy of cell culture, immunoflourescence Assay (IFA) and real time polymerase chain reaction (rRT-PCR) in relation to diagnosis of influenza and Respiratory Syncytial Virus (RSV).
Removal of Cu and Pb by tartaric acid modified rice husk from aqueous solutions

Wong KK, Lee CK, Low KS, Haron MJ

Chemosphere, 2003 Jan;50(1):23-8.
PMID: 12656225

A study on the modification of rice husk by various carboxylic acids showed that tartaric acid modified rice husk (TARH) had the highest binding capacities for Cu and Pb. The carboxyl groups on the surface of the modified rice husk were primarily responsible for the sorption of metal ions. A series of batch experiments using TARH as the sorbent for the removal of Cu and Pb showed that the sorption process was pH dependent, rapid and exothermic. The sorption process conformed to the Langmuir isotherm with maximum sorption capacities of 29 and 108 mg/g at 27 +/- 2 degrees C for Cu and Pb, respectively. The uptake increased with agitation rate. Decrease in sorbent particle size led to an increase in the sorption of metal ions and this could be explained by an increase in surface area and hence binding sites. Metal uptake was reduced in the presence of competitive cations and chelators. The affinity of TARH for Pb is greater than Cu.
Bilateral ovarian cysts in a newborn: a case report

Lim CT, Wong KK, Yap YF, Sivanesaratnam V

Asia Oceania J Obstet Gynaecol, 1992 Mar;18(1):19-22.
PMID: 1627057

Large ovarian cysts in the fetus are uncommon. Ultrasonography has helped in the detection of these cysts antenatally and in the newborn female infant. A case of bilateral ovarian cysts in a newborn is presented. The choice of management between conservative measures and surgical approaches remains controversial.
Development and evaluation of a computer expert system for the management of fetal distress

Wong KK, Ng KH, Nah SH, Yusof K, Rajeswari K

Asia Oceania J Obstet Gynaecol, 1994 Mar;20(1):19-23.
PMID: 8172522

The general lack of specialist obstetricians in a developing country such as Malaysia prompted us to develop a computer expert system for the management of fetal distress in rural hospitals. It was based on accepted production rules and implemented on a microcomputer. The clinical prototype was evaluated by 8 specialist obstetricians and 21 non-specialist doctors involved in obstetric care. The initial impression was that this type of expert system may help in diagnosis, decision-making and teaching.
Fulltext Slicc damage index score in systemic lupus erythematosus patients and its associated factors

Ghazali WSW, Daud SMM, Mohammad N, Wong KK

Medicine (Baltimore), 2018 Oct;97(42):e12787.
PMID: 30334968 DOI: 10.1097/MD.0000000000012787

The aims of this study were to determine damage index in systemic lupus erythematosus (SLE) patients based on Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) and to determine the laboratory and clinico-demographic factors affecting SDI.This is a retrospective cohort study of 94 SLE patients attending rheumatology clinics in 2 local hospitals in Kelantan, Malaysia. The patients were divided into 2 groups based on SDI score assigned by the attending physician, 0 (without damage) or ≥1 (with damage). Newly diagnosed SLE patients with disease duration less than 6 months were excluded.A total of 45 (47.9%) SLE patients showed damage by SDI score. Majority of the subjects had neuropsychiatric damages (21/94; 22.3%) followed by skin (12/94; 12.8%) and musculoskeletal (6/94; 6.4%) damage. SDI score was significantly associated with higher disease duration (6.2 ± 6.57 years vs 4.5 ± 3.7 years; P = .018), lower prednisolone dose (8.74 ± 10.89 mg vs 4.89 ± 3.81 mg; P
Fulltext Anti-cyclic citrullinated peptide antibody is highly associated with rheumatoid factor and radiological defects in rheumatoid arthritis patients

Sulaiman FN, Wong KK, Ahmad WAW, Ghazali WSW

Medicine (Baltimore), 2019 Mar;98(12):e14945.
PMID: 30896663 DOI: 10.1097/MD.0000000000014945

Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body. RA can lead to destruction of bone and cartilage which may cause severe disability and it is characterized by the presence of serum rheumatoid factor (RF). The anti-cyclic citrullinate peptide (anti-CCP) antibody is another serum biomarker used in RA diagnosis with higher sensitivity and specificity.In this cross-sectional study with retrospective record review, 159 established RA patients from Hospital Universiti Sains Malaysia (HUSM) were recruited. Enzyme-linked immunosorbent assays (ELISAs) for serum RF and anti-CCP were performed. Our goal was to evaluate the significance of anti-CCP antibody in predicting the disease activity and progression in terms of radiological and extra-articular manifestations upon diagnosis.Of the 159 RA patients included in this study, mean age was 48.3 years old and majority (n = 134; 84.3%) were female. A total of 83 (52.2%) and 99 (62.3%) patients had anti-CCP antibody and RF, respectively. Mean Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (ESR) (DAS28-ESR) score for all patients was 4.74 (medium and high disease activity). Fifty-eight (36.5%) patients had radiological defects and 49 (30.8%) patients had extra-articular involvement manifested by rheumatoid nodule, pulmonary involvement, and anemia.In terms of anti-CCP antibody association with clinical and laboratory parameters, a significant co-occurrence of RF and anti-CCP antibody (P = .002) was observed. Anti-CCP antibody was significantly associated with radiological defects in which majority of patients with such defects (n = 40/58; 68.9%) were positive for anti-CCP antibody (P = .001). However, there was no significant difference between mean and classes of disease activity score and extra-articular manifestations between different anti-CCP antibody groups. In addition, extra-articular manifestations were not associated with high disease activity upon RA diagnosisThere was a significant association between anti-CCP antibody positivity and positive RF. Radiological defects were the sole clinical parameter significantly associated with anti-CCP antibody positivity, indicating that patients positive for anti-CCP antibody should be routinely monitored for radiological defects and their onset.
Gardnerella vaginalis in perinatology: An overview of the clinicopathological correlation

Wong YP, Tan GC, Wong KK, Anushia S, Cheah FC

Malays J Pathol, 2018 Dec;40(3):267-286.
PMID: 30580358

Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1β and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes.
Molecular detection of Enterobacteriaceae isolates producing blaOXA-48 and blaOXA-181 genes: A single centre study

Heng PY, Sulong A, Ali UKS, Wong KK

Malays J Pathol, 2019 Aug;41(2):139-148.
PMID: 31427549

INTRODUCTION: OXA-48, a carbapenem-hydrolysing class D β-lactamase, and its variant, OXA-181, are increasingly reported worldwide. This study aimed to describe the prevalence and distribution of OXA-48 and OXA-181 carbapenem-resistant Enterobacteriaceae (CRE) in a tertiary medical centre in Malaysia.
MATERIALS & METHODS: A total of 13,098 Enterobacteriaceae isolates from various clinical samples were sent to our laboratory between January 2011 and December 2012. Of these, 90 demonstrated reduced susceptibility to at least one carbapenem and were included in this study. Only 88 isolates were successfully subcultured on blood agar (BA). Another 2 isolates failed to grow and were excluded. Of the 88, 2 isolates had the same identification number (repetitive isolates); therefore, 1 isolate was excluded from further analyses. Only 87 isolates were subjected to molecular detection of the blaOXA-48 and blaOXA-181 genes by polymerase chain reaction.
RESULTS: Eighty-seven non-repetitive isolates grew following subculture on BA. Of these, 9 (10.34%) were positive for OXA-48 (7 Klebsiella pneumoniae, 2 Escherichia coli). Each isolate originated from different patients. All patients had a history of treatment with at least one cephalosporin and/or carbapenem prior to the isolation of OXA-48 CRE. OXA-181 was detected in one (1.15%) out of the 87 isolates; CONCLUSIONS: The prevalence of OXA-48 and OXA-181 CRE among all Enterobacteriaceae isolates in our institution is 0.069% and 0.008%, respectively. Nevertheless, our findings suggest that OXA-48 and OXA-181 carbapenemases appear to be important and possibly under-recognised causes of carbapenem resistance in Malaysia.
DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma

Loo SK, Ab Hamid SS, Musa M, Wong KK

Pathol Res Pract, 2018 Jan;214(1):134-143.
PMID: 29137822 DOI: 10.1016/j.prp.2017.10.005

Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) <0.05]. Cell cycle progression and DNA replication were among the significantly enriched biological processes (FDR <0.05). Expression of genes involved in the activation of cell cycle and DNA replication (e.g. CDK1, CCNA2, E2F2, PCNA, RFC5 and POLD3) were highly correlated (r>0.8) with DNMT1 expression and significantly downregulated (log fold-change
Fulltext N-Acetylcysteine as Adjuvant Therapy for COVID-19 - A Perspective on the Current State of the Evidence

Wong KK, Lee SWH, Kua KP

J Inflamm Res, 2021;14:2993-3013.
PMID: 34262324 DOI: 10.2147/JIR.S306849

The looming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a long-lasting pandemic of coronavirus disease 2019 (COVID-19) around the globe with substantial morbidity and mortality. N-acetylcysteine, being a nutraceutical precursor of an important antioxidant glutathione, can perform several biological functions in mammals and microbes. It has consequently garnered a growing interest as a potential adjunctive therapy for coronavirus disease. Here, we review evidence concerning the effects of N-acetylcysteine in respiratory viral infections based on currently available in vitro, in vivo, and human clinical investigations. The repurposing of a known drug such as N-acetylcysteine may significantly hasten the deployment of a novel approach for COVID-19. Since the drug candidate has already been translated into the clinic for several decades, its established pharmacological properties and safety and side-effect profiles expedite preclinical and clinical assessment for the treatment of COVID-19. In vitro data have depicted that N-acetylcysteine increases antioxidant capacity, interferes with virus replication, and suppresses expression of pro-inflammatory cytokines in cells infected with influenza viruses or respiratory syncytial virus. Furthermore, findings from in vivo studies have displayed that, by virtue of immune modulation and anti-inflammatory mechanism, N-acetylcysteine reduces the mortality rate in influenza-infected mice animal models. The promising in vitro and in vivo results have prompted the initiation of human subject research for the treatment of COVID-19, including severe pneumonia and acute respiratory distress syndrome. Albeit some evidence of benefits has been observed in clinical outcomes of patients, precision nanoparticle design of N-acetylcysteine may allow for greater therapeutic efficacy.
Th1, Th2, and Th17 cytokines in systemic lupus erythematosus

Muhammad Yusoff F, Wong KK, Mohd Redzwan N

Autoimmunity, 2020 02;53(1):8-20.
PMID: 31771364 DOI: 10.1080/08916934.2019.1693545

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the breakdown of immune tolerance leading to excessive inflammation and tissue damage. Imbalance in the levels of cytokines represents one of the multifactorial causes of SLE pathogenesis and it contributes to disease severity. Deregulated levels of T helper type 1 (Th1), type 2 (Th2), and type 17 (Th17) cytokines have been associated with autoimmune inflammation. Growing evidence has shown deregulated levels of Th1, Th2, and Th17 cytokines in SLE patients compared to healthy controls associated with disease activity and severity. In this review, we describe and discuss the levels of Th1, Th2, and Th17 cytokines in SLE patients, and clinical trials involving Th1, Th2, and Th17 cytokines in SLE patients. In particular, with the exception of IL-2, IL-4, and TGF-β1, the levels of Th1, Th2, and Th17 cytokines are increased in SLE patients associated with disease severity. Current phase II or III studies involve therapeutic antibodies targeting IFN-α and type I IFN receptor, while low-dose IL-2 therapy is assessed in phase II clinical trials.
Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer

Wong KK, Hussain FA, Loo SK, López JI

APMIS, 2017 Dec;125(12):1092-1101.
PMID: 28972294 DOI: 10.1111/apm.12775

Spermatogenesis-associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non-malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non-malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non-malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty-nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H-score) was not associated with overall survival or disease-specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease.

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