Displaying all 16 publications

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  1. Wong KK, Hussain FA
    PLoS One, 2020;15(6):e0233884.
    PMID: 32484822 DOI: 10.1371/journal.pone.0233884
    Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4+; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4+; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p<0.01 and false discovery rate<0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.
  2. Hasenan N, Mohd Isa SA, Hussain FA
    Asian Pac J Cancer Prev, 2021 Dec 01;22(12):4011-4016.
    PMID: 34967583 DOI: 10.31557/APJCP.2021.22.12.4011
    BACKGROUND: c-Myc has become significantly involved in aggressive B-cell non Hodgkin lymphoma (NHL), but little is known about its importance in T and NK cell NHL (TNKcNHLs) in association with prognostic factors. The study is to investigate the significance of c-Myc expression with clinicopathological features of TNKcNHLs patients.

    METHODOLOGY: A cross-sectional study of 32 archived tissue blocks of TNKcNHLs were immunohistochemically stained with c-Myc. The results were microscopically evaluated and statistically analysed to examine the association between the clinicopathological data with the c-Myc expression.

    RESULTS: c-Myc protein expressions were detected in 25/32 (78.1%) cases. The median age was 38-years.  Malay ethnicity (92.0%) with 21 males and 11 females. c-Myc expressions were seen in T lymphoblastic lymphoma (20%), ALK-positive ALCL (16%) ,PTCL,NOS (16%), extra nodal NK/T-cell lymphoma, nasal type (12%), extra-nodal involvement (78.1%), elevated serum LDH (83.3%) and high ECOG performance status (82.4%). However, no statistical significant of c-Myc in association with the clinicopathological parameters (p > 0.05).

    CONCLUSION: There was no statistically significant association of clinicopathological parameters and histological subtypes of TNKcNHLs contributed by small samples tested. However, the attribution of c-Myc in this disease should be further explored.

  3. Jaafar NA, Hussain FA, Mat Lazim N
    Indian J Otolaryngol Head Neck Surg, 2024 Feb;76(1):1220-1223.
    PMID: 38440494 DOI: 10.1007/s12070-023-04228-9
    Extraosseous plasmacytoma, a rare plasma cell neoplasm, was observed in a 52-year-old male with uncommon presentation in the oropharynx with cervical lymph node involvement. The patient presented with dysphonia and left neck swelling. This case report primarily focuses on the management, resulting in a successful treatment through radiotherapy.
  4. Shahidatul-Adha M, Saizul Z, Hussain FA, Abdullah B
    Cureus, 2021 Oct;13(10):e18548.
    PMID: 34754692 DOI: 10.7759/cureus.18548
    Rhabdomyosarcoma (RMS) is the most common soft-tissue tumor in children, frequently affecting the nose, nasopharynx, and paranasal sinuses. RMS of this sinonasal region manifests with non-specific nasal symptoms of allergic rhinitis, sinusitis, or upper airway infection. Associated ocular symptoms are rare. We describe a young girl who presented with acute onset squint secondary to sinonasal RMS. Imaging showed an aggressive sinonasal tumor with oropharyngeal, intraorbital, and intracranial extension. Histopathological findings were consistent with a diagnosis of rhabdomyosarcoma, embryonal type. The patient deteriorated rapidly due to disease complications. We provide a literature review of pediatric sinonasal RMS with various manifestations.
  5. Hasny NS, Amiruddin FM, Hussain FA, Abdullah B
    Medeni Med J, 2021 Dec 19;36(4):343-347.
    PMID: 34939401 DOI: 10.4274/MMJ.galenos.2021.40404
    Oncocytic papillary cystadenoma (OPC) is a relatively rare benign tumor of the salivary glands, frequently seen in minor salivary glands, and occasionally in major salivary glands, such as the parotid gland. Patients only become symptomatic upon progression of the swelling, causing obstructive symptoms depending on its location. To our knowledge, there are no reports of presentation with bleeding tumor. Herein, we report a case of an OPC of the right torus tubarius in a 54-year-old man who presented with recurrent epistaxis.
  6. 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.
  7. Bakrin IH, Hussain FA, Tuan Sharif SE
    Malays J Pathol, 2016 Aug;38(2):117-22.
    PMID: 27568668 MyJurnal
    Synovial sarcoma (SS) is a malignant soft tissue tumour of uncertain histogenesis which is defined by the translocation t(X;18) that produces the fusion oncogenes SYT-SSX. The emergence of transducer-like enhancer of split 1 (TLE1) as a new immunohistochemical (IHC) marker for SS has offered an alternative to pathologists in differentiating SS from other histological mimics, especially in the setting of limited molecular facilities. We investigated the utility of IHC TLE1 expression against histomorphological features and other IHC markers in SS and non-SS tumours. Twenty-six cases of histologically diagnosed SS and 7 non-SS (for which SS was in the differential diagnosis) were subjected to TLE1 IHC staining, which was graded from 0 to 3+. Of the 26 SS cases, 12 each were biphasic and monophasic types and 2 were poorly-differentiated. TLE1 was expressed in 22/26 (84.6%) SS cases, of which 11/12 (91.7%) were biphasic, 10/12 (83.3%) monophasic and 1/2 (50%) poorly-differentiated tumours. Two of 7 (28.6%) non-SS cases were positive for TLE1. Immunopositivity of SS and non-SS cases for EMA were 20/26 (76.9%) and 2/7 (28.6%) respectively and for CK7 were 7/26 (26.9%) and 0/7 (0%) respectively. All cases were negative for CD34. Consistent histomorphological features for SS included mild nuclear pleomorphism, alternating tumour cellularity, fascicular growth pattern and thick ropy stromal collagen. In conclusion, TLE1 is not a stand-alone diagnostic IHC marker for SS. However, in the absence of molecular studies, it can contribute added diagnostic value in combination with morphological evaluation and other IHC markers such as EMA and CD34.
  8. Lo R, Mohamad S, Krishnamoorthy M, Mohamad I, Zulkarnain S, Hussain FA
    Medeni Med J, 2020;35(1):67-70.
    PMID: 32733752 DOI: 10.5222/MMJ.2020.22208
    Vallecular lymphoma is an extremely rare tumour of oropharynx. We report a case of 61-year-old gentleman presented with severe dysphagia and globus sensation for two months. Patient underwent endoscopic transoral tumour debulking for diagnostic and therapeutic purpose. Histopathologically, patient was diagnosed as mantle cell lymphoma (MCL). In this case report, atypical presentation of the disease, histopathological features and its current treatments are discussed.
  9. Mohd Ridah LJ, A Talib N, Muhammad N, Hussain FA, Zainuddin N
    Asian Pac J Cancer Prev, 2017 10 26;18(10):2781-2785.
    PMID: 29072413
    Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.
  10. Muhd Besari A, Lim JA, Vellaichamy PT, Hussain FA, Kamaludin Z, Nor M
    Postgrad Med J, 2022 Mar 01;98(e2):e70.
    PMID: 37066525 DOI: 10.1136/postgradmedj-2021-140778
  11. Amri MF, Azizan N, Hussain FA, Hayati F, Syed Abdul Rahim SS, Azhar ZI
    Ann Med Surg (Lond), 2021 Apr;64:102242.
    PMID: 33815787 DOI: 10.1016/j.amsu.2021.102242
    The Coronavirus Disease 2019 (COVID-19) pandemic has taken the world into turmoil by surprise. The rapid spreading of this virus has led to an exponential increase in the number of cases. It has created a public health disaster, causing a collapse of the health system in every part of the world. Many sectors in the health area are affected, including histopathology services. The challenges and risk of viral transmission can come from various aspects and levels. For COVID-19 tests, there are even cases of no direct contact with the specimens; the specimens received infection from individuals of unknown status. The fixatives used for histopathology specimens are believed to be inactivated viruses, which can be an inactivate coronavirus. Even so, precautions have to be put in place to prevent the spread of infection to laboratory personnel, especially to those handling underfixed and fresh frozen cytology samples. Precautions must also be taken when dealing with histopathology services, by wearing full personal protective equipment and by executing other standard safety measures. The purpose of this review is to highlight the challenges faced in managing histopathology services in our centre during the COVID-19 pandemic.
  12. Asmaa MJS, Al-Jamal HA, Hussein AR, Yahaya BH, Hassan R, Hussain FA, et al.
    Int J Hematol Oncol Stem Cell Res, 2020 Jan 01;14(1):72-92.
    PMID: 32337016
    Background: Acute myeloid leukemia (AML) is the most common form of acute leukemias in adults which is clinically and molecularly heterogeneous. Several risk and genetic factors have been widely investigated to characterize AML. However, the concomitant epigenetic factors in controlling the gene expression lead to AML transformation was not fully understood. This study was aimed to identify epigenetically regulated genes in AML cell lines induced by epigenetic modulating agents, Trichostatin A (TSA) and 5-Azacytidine (5-Aza). Materials and Methods: MV4-11 and Kasumi 1 were treated with TSA and/or 5-Aza at IC50 concentration. Gene expression profiling by microarray was utilized using SurePrint G3 Human Gene Expression v3. Gene ontology and KEGG pathway annotations were analyzed by DAVID bioinformatics software using EASE enrichment score. mRNA expression of the differentially expressed genes were verified by quantitative real time PCR. Results: Gene expression analysis revealed a significant changes in the expression of 24,822, 15,720, 15,654 genes in MV4-11 and 12,598, 8828, 18,026 genes in Kasumi 1, in response to TSA, 5-Aza and combination treatments, respectively, compared to non-treated (p<0.05). 7 genes (SOCS3, TUBA1C, CCNA1, MAP3K6, PTPRC, STAT6 and RUNX1) and 4 genes (ANGPTL4, TUBB2A, ADAM12 and PTPN6) shown to be predominantly expressed in MV4-11 and Kasumi 1, respectively (EASE<0.1). The analysis also revealed phagosome pathway commonly activated in both cell lines. Conclusion: Our data showed a distinct optimal biological characteristic and pathway in different types of leukemic cell lines. These finding may help in the identification of cell-specific epigenetic biomarker in the pathogenesis of AML.
  13. Johnathan M, Muhamad SA, Gan SH, Stanslas J, Mohd Fuad WE, Hussain FA, et al.
    PLoS One, 2021;16(3):e0249091.
    PMID: 33784348 DOI: 10.1371/journal.pone.0249091
    Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.
  14. Al-Khreisat MJ, Ismail NH, Tabnjh A, Hussain FA, Mohamed Yusoff AA, Johan MF, et al.
    Diagnostics (Basel), 2023 Jun 15;13(12).
    PMID: 37370963 DOI: 10.3390/diagnostics13122068
    Burkitt lymphoma (BL) is a form of B-cell malignancy that progresses aggressively and is most often seen in children. While Epstein-Barr virus (EBV) is a double-stranded DNA virus that has been linked to a variety of cancers, it can transform B lymphocytes into immortalized cells, as shown in BL. Therefore, the estimated prevalence of EBV in a population may assist in the prediction of whether this population has a high risk of increased BL cases. This systematic review and meta-analysis aimed to estimate the prevalence of Epstein-Barr virus in patients with Burkitt lymphoma. Using the appropriate keywords, four electronic databases were searched. The quality of the included studies was assessed using the Joanna Briggs Institute's critical appraisal tool. The results were reported as percentages with a 95% confidence interval using a random-effects model (CI). PROSPERO was used to register the protocol (CRD42022372293), and 135 studies were included. The prevalence of Epstein-Barr virus in patients with Burkitt lymphoma was 57.5% (95% CI: 51.5 to 63.4, n = 4837). The sensitivity analyses demonstrated consistent results, and 65.2% of studies were of high quality. Egger's test revealed that there was a significant publication bias. EBV was found in a significantly high proportion of BL patients (more than 50% of BL patients). This study recommends EBV testing as an alternative for predictions and the assessment of the clinical disease status of BL.
  15. Salleh MN, Ahmad Kailani AAA, Nik Min NFA, Mohamad I, Hussain FA, Mat Zin AA
    Iran J Otorhinolaryngol, 2022 Mar;34(121):131-134.
    PMID: 35655769 DOI: 10.22038/IJORL.2021.58329.3007
    INTRODUCTION: Basal cell adenoma (BCA) is a rare benign epithelial tumour of the salivary gland majorly involving the parotid gland, and rarely the submandibular gland.

    CASE REPORT: We describe a rare case of BCA of the submandibular gland diagnosed preoperatively using fine needle aspiration cytology in a 60-year-old woman presenting with painless submandibular swelling. The surgery went uneventfully, and the histopathological examination confirmed the diagnosis.

    CONCLUSIONS: BCA can be accurately diagnosed only through histological observations due to its resemblance to various benign and malignant salivary and non-salivary gland tumours, which are difficult to biopsy.

  16. Langhorne P, O'Donnell MJ, Chin SL, Zhang H, Xavier D, Avezum A, et al.
    Lancet, 2018 05 19;391(10134):2019-2027.
    PMID: 29864018 DOI: 10.1016/S0140-6736(18)30802-X
    BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels.

    METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month.

    FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics.

    INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes.

    FUNDING: Chest, Heart and Stroke Scotland.

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