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  1. Perumal K, Mun KS, Yap NY, Razack AHA, Gobe GC, Ong TA, et al.
    Biomed Res Int, 2020;2020:3682086.
    PMID: 32802842 DOI: 10.1155/2020/3682086
    Background: The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer.

    Objective: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant.

    Results: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC.

    Conclusion: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.

  2. Jayapalan RR, Bahuri NFA, Mun KS, Narayanan V
    SAGE Open Med Case Rep, 2019;7:2050313X19828539.
    PMID: 30783531 DOI: 10.1177/2050313X19828539
    Perivascular epithelioid cell tumour is a rare mesenchymal tumour with distinct immunohistochemical profile. While it is known to occur in various anatomical sites, the central nervous system had always been a protected site for primary or secondary perivascular epithelioid cell tumours. We describe a 61-year-old lady who presented with symptoms of raised intracranial pressure, 3 months after the resection of duodenal and thoracic tumours which were histologically consistent with perivascular epithelioid cell tumour. She was investigated and then subsequently subjected to resection of two metastatic intracranial lesions. The radiological, intraoperative as well as histopathological findings of the metastatic lesions are discussed. Metastatic perivascular epithelioid cell tumour of the brain is extremely rare. However, patients who are stratified as high risk for recurrence or metastases should undergo an early magnetic resonance imaging/computed tomography of the brain in addition to a whole-body positron emission tomography scan, to allow for early detection and management of these tumours.
  3. Abdalla YOA, Nyamathulla S, Shamsuddin N, Arshad NM, Mun KS, Awang K, et al.
    Toxicol Appl Pharmacol, 2018 10 01;356:204-213.
    PMID: 30138658 DOI: 10.1016/j.taap.2018.08.014
    1'-S-1'-acetoxychavicol acetate (ACA) has been previously reported to reduce tumor volume in nude mice, at an effective dose of 1.56 mg/kg body weight. However, the detailed toxicological profile for ACA has not yet been performed. Herein, we investigated the toxicity of intravenous administration of ACA in male and female Sprague-Dawley rats, both acutely (with single doses of 2.00, 4.00 and 6.66 mg/kg body weight, for 14 days), and sub-acutely (with weekly injections of 0.66, 1.33, and 2.22 mg/kg, for 28 days). In both toxicity studies, treatment with ACA did not affect behavior, food/water intake or body weight, nor did it induce any changes in clinically relevant hematological and biochemical parameters or mortality, suggesting that the LD50 of ACA was higher than 6.66 mg/kg body weight, regardless of sex. Sub-acutely, there was however, mild focal inflammation of kidneys and lobular hepatitis, but these were not associated with significant functional adverse effects. Therefore, the no-observed-adverse-effect level (NOAEL) for intravenous administration of ACA in the present 28-day sub-acute study was 2.22 mg/kg body weight, in both male and female rats. These findings provide useful information regarding the safety of ACA use in a healthy, non-tumor-bearing rat model.
  4. Teoh KH, Looi LM, Sabaratnam S, Cheah PL, Nazarina AR, Mun KS
    Malays J Pathol, 2011 Jun;33(1):35-42.
    PMID: 21874750 MyJurnal
    Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.
  5. Tang IP, Shashinder S, Loganathan A, Anura MM, Zakarya S, Mun KS
    Singapore Med J, 2009 Sep;50(9):e326-8.
    PMID: 19787162
    An aneurysmal bone cyst is a rare bone lesion. Its origin and precise nature remain unknown. It is seen as a locally-destructive, rapidly expandable, benign multicystic mass. We report a 17-year-old boy with an aneurysmal bone cyst of the maxilla, with extensive local involvement and bony destruction that was treated surgically. There was no recurrence noted after four years of follow-up.
  6. Subramaniam M, Arshad NM, Mun KS, Malagobadan S, Awang K, Nagoor NH
    Biomolecules, 2019 10 18;9(10).
    PMID: 31635311 DOI: 10.3390/biom9100626
    Cancer development and progression are extremely complex due to the alteration of various genes and pathways. In most cases, multiple agents are required to control cancer progression. The purpose of this study is to investigate, using a mouse model, the synergistic interactions of anti-cancer agents, 1'-S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP), and cisplatin (CDDP) in double and triple combinations to treat chemo-sensitize and immune-sensitize breast cancer. Changes in tumor volume and body weight were monitored. Organs were harvested and stained using hematoxylin-eosin for histopathological assessment. Milliplex enzyme-linked immunosorbent assay (ELISA) was performed to determine cytokine levels, while immunohistochemistry (IHC) was conducted on tumor biopsies to verify systemic drug effects. In vivo mouse models showed tumor regression with maintenance of regular body weight for all the different treatment regimens. IHC results provided conclusive evidence indicating that combination regimens were able to down-regulate nuclear factor kappa-B activation and reduce the expression of its regulated pro-inflammatory proteins. Reduction of pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IFN-ɣ) levels were observed when using the triple combination, which indicated that the synergistic drug combination was able to significantly control cancer progression. In conclusion, ACA, MIP, and CDDP together serve as promising candidates for further development and for subsequent clinical trials against estrogen-sensitive breast cancer.
  7. Cheah PL, Looi LM, Nazarina AR, Mun KS, Goh KL
    Malays J Pathol, 2008 Dec;30(2):103-7.
    PMID: 19291919 MyJurnal
    Transaminase enzymes, alanine (ALT) and aspartate transaminase (AST), have been reported to be raised and implicated to have prognostic value in hepatocellular carcinoma (HCC). Ki67, a marker of cellular proliferative activity, has also been noted to be increased in HCC. A study was conducted at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur to determine the possible association of proliferative activity, as determined by Ki67, with the transaminase enzymes. 31 cases of histologically diagnosed HCC who underwent tumour resection were retrieved from departmental archives. The patients' ages ranged between 40 to 79 years with a mean of 58.3 years. There was a male preponderance with M:F = 2.9:1. Ethnic Chinese formed 83.9% of the cases. 4 microm sections, cut from the formalin-fixed, paraffin-embedded tumour tissue block of each case, were immunohistochemically stained with Ki67 (DAKO monoclonal MIB-1) using the commercial DakoCytomation EnVision+System-HRP kit. The latest ALT and AST levels, assayed within 7 days prior to tumour resection, were retrieved from the patients' case records. 24 (77.4%) HCC demonstrated elevation of either ALT and/or AST. 27 (87.1%) HCC were immunopositive for Ki67. Ki67 immunoexpression was significantly correlated with raised transaminases (p<0.05). Hypothetically, the mechanism by which this phenomenon may occur may simply be release of transaminases due to destruction of hepatocytes by the cancer. Thus rising levels of the transaminases could signal a more rapid growth of the tumour and these routinely performed tests can be of prognostic value in management of HCC patients.
  8. El-Ishaq A, Alshawsh MA, Mun KS, Chik Z
    PeerJ, 2020;8:e9138.
    PMID: 32607276 DOI: 10.7717/peerj.9138
    Asparagus africanus Lam. is a plant used traditionally to treat different ailments. Currently, scanty information is available on its safety. The aim of this study is to determine the acute toxicity of the methanolic extract on vital organs and its associated biochemical parameters. Fifteen female Sprague-Dawley rats were divided into five groups. Group I served as normal control, groups II, III, IV, and V were orally administered single dose of crude extract dissolved in distilled water at 5 mg/kg BW, 50 mg/kg BW, 300 mg/kg BW and 2,000 mg/kg BW. Rats were observed for 14 days and body weights were recorded. On day 15, the rats were sacrificed and blood samples were collected for biochemical and haematological analyses, while the liver and kidneys were sampled for histopathological examination. Body weight and haematology parameters results showed significance difference (p 
  9. Samberkar S, Rajandram R, Mun KS, Samberkar P, Danaee M, Zulkafli IS
    Malays J Pathol, 2019 Dec;41(3):233-242.
    PMID: 31901907
    INTRODUCTION: Tissue biomarker carbonic anhydrase IX (CAIX) is purported to have prognostic value for renal cell carcinoma (RCC) but contradicting findings from previous studies have also been documented. This study aims to perform a systematic review and meta-analysis on the role of CAIX in RCC disease progression.

    MATERIALS AND METHODS: Following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, online searches of multiple databases were performed to retrieve articles from their inception until December 2017. Inclusion criteria included all English-based original articles of immunohistochemistry (IHC) studies investigating CAIX expression in human RCC tissue. Four articles were finally selected for meta-analysis with a total of 1964 patients. Standard meta-analysis methods were applied to evaluate the role of CAIX in RCC prognosis. The relative risk (RR) and its 95% confidence interval (CI) were recorded for the association between biomarker and prognosis, and data were analysed using MedCalc statistical software.

    RESULTS: The meta-analysis showed that high CAIX expression was associated with low tumour stage (RR 0.90%, 95% CI 0.849-0.969, p= 0.004), low tumour grade (RR 0.835%, 95% CI 0.732-0.983, p= 0.028), absence of nodal involvement (RR 0.814%, 95% CI 0.712-0.931, p= 0.003) and better ECOS-PS index (RR 0.888%, 95% CI 0.818-0.969, p= 0.007). The high tissue CAIX expression in RCC is hence an indication of an early malignancy with a potential to predict favourable disease progression and outcome.

    CONCLUSION: The measurement of this marker may be beneficial to determine the course of the illness. It is hoped that CAIX can be developed as a specific tissue biomarker for RCC in the near future.

  10. Sulaiman H, Ponnampalavanar S, Mun KS, Italiano CM
    BMC Infect Dis, 2013 Nov 09;13:527.
    PMID: 24209898 DOI: 10.1186/1471-2334-13-527
    BACKGROUND: Infections due to Mycobacterium tuberculosis, Burkholderia pseudomallei and non-typhoidal Salmonella cause significant morbidity and mortality throughout the world. These intracellular pathogens share some common predisposing factors and clinical features. Co-infection with two of these organisms has been reported previously but, to our knowledge, this is the first time that infection with all three has been reported in one person.

    CASE PRESENTATION: In September 2010, a 58-year-old diabetic Malaysian male presented with fever and a fluctuant mass on the right side of his neck. B. pseudomallei was isolated from an aspirate of this lesion and there was radiological evidence of disseminated infection in the liver and spleen. The recurrence of clinical symptoms over ensuing months prompted further aspiration and biopsy of a cervical abscess and underlying lymph nodes. Salmonella enterica serovar Stanley and then M. tuberculosis were identified from these specimens by culture and molecular methods. The patient responded to targeted medical management of each of these infections.

    CONCLUSION: In endemic settings, a high index of suspicion and adequate tissue sampling are imperative in identifying these pathogenic organisms. Diabetes was identified as a predisposing factor in this case while our understanding of other potential risk factors is evolving.

  11. Rajagopal R, Leong SH, Jawin V, Foo JC, Ahmad Bahuri NF, Mun KS, et al.
    J Pediatr Hematol Oncol, 2021 Oct 01;43(7):e913-e923.
    PMID: 33633029 DOI: 10.1097/MPH.0000000000002116
    BACKGROUND: A higher incidence of pediatric intracranial germ cell tumors (iGCTs) in Asian countries compared with Western countries has been reported. In Malaysia, the literature regarding pediatric iGCTs have been nonexistent. The aim of this study was to review the management, survival, and long-term outcomes of pediatric iGCTs at a single tertiary center in Malaysia.

    PATIENTS AND METHODS: We retrospectively reviewed data from patients below 18 years of age with iGCTs treated at the University Malaya Medical Center (UMMC) from 1998 to 2017.

    RESULTS: Thirty-four patients were identified, with a median follow-up of 3.54 years. Sixteen (47%) patients had pure germinoma tumors (PGs), and the remaining patients had nongerminomatous germ cell tumors (NGGCTs). The median age was 12 years, with a male:female ratio of 4.7:1. Abnormal vision, headache with vomiting, and diabetes insipidus were the commonest presenting symptoms. Twenty-eight patients received initial surgical interventions, 24 were treated with chemotherapy, and 28 received radiotherapy. Eight patients experienced relapses. The 5- and 10-year event-free survival rates were similar at 61.1%±12.6% and 42.9%±12.1% for PG and NGGCT, respectively. The 5- and 10-year overall survival rates were the same at 75.5%±10.8% and 53.3%±12.3% for PG and NGGCT, respectively. Four patients died of treatment-related toxicity. Most of the survivors experienced good quality of life with satisfactory neurologic status.

    CONCLUSIONS: The survival rate of childhood iGCTs in UMMC was inferior to that reported in developed countries. Late diagnosis, poor adherence to treatment, and treatment-related complications were the contributing factors. Although these results highlight a single institution experience, they most likely reflect similar treatment patterns, outcomes, and challenges in other centers in Malaysia.

  12. Tan SH, Mun KS, Chandran PA, Manuel AM, Prepageran N, Waran V, et al.
    Childs Nerv Syst, 2015 Jul;31(7):1165-9.
    PMID: 25712744 DOI: 10.1007/s00381-015-2667-9
    This paper reports an unusual case of a transsphenoidal encephalocele and discusses our experience with a minimally invasive management. To the best of our knowledge, we present the first case of a combined endoscopic transnasal and transoral approach to a transsphenoidal encephalocele in an infant.
  13. Ng CH, Pathy NB, Taib NA, Teh YC, Mun KS, Amiruddin A, et al.
    Asian Pac J Cancer Prev, 2011;12(11):2943-6.
    PMID: 22393968
    INTRODUCTION: The age standardised incidence rate (ASR) of breast cancer in Malaysia which is a high middle- income country is similar to Indonesia, a low middle-income country. (Globocan 2008) It is however unknown whether the presentation of breast cancer differs between these two countries.

    OBJECTIVE: We compared the stage, age at presentation, and pathological characteristics of breast cancer between two tertiary hospitals in Indonesia and Malaysia; Dharmais Cancer Centre (DCC), which is the national cancer referral centre in Indonesia, and University Malaya Medical Centre (UMMC), which is an academic hospital with established breast oncology services in Kuala Lumpur. One thousand, one hundred and fourteen consecutive women (477 in UMMC: 637 in DCC) who were newly diagnosed with breast cancer between January and December, 2010 were included. Patient's age, TNM stage at presentation, and pathological characteristics were compared. Estrogen receptor (ER) and progesterone receptor (PR) were considered positive if 10% or greater of invasive cell nuclei were stained while HER2 was considered positive with an immunohistochemistry staining intensity of 3+ . Logistic regression analyses were performed to identify differences.
    RESULTS: Median age at diagnosis was 52 years in UMMC and 47 years in DCC, whereby patients in DCC were more likely to be very young at diagnosis (aged < 35 years) compared to their counterparts in UMMC (Odds ratio (OR): 2.09; 95%CI: 1.32-3.31). Approximately one third of patients in UMMC presented with TNM stage III or IV, compared to 63% in DCC. Patients in DCC were three times more likely to present with metastatic breast cancer compared to patients in UMMC (OR: 3.01; 95% CI: 2.02-4.48). The percentage of low grade tumours in DCC was higher than in UMMC (28% vs 11% respectively), and the difference persisted even after multivariate adjustment. Although the frequency of ER and PR positivity appeared to be higher in UMMC (65% and 55% respectively) compared to DCC (48% and 40% respectively), these differences were not statistically significant following adjustment for age, stage, HER2 status and grade. The frequency of HER2 positivity was 45% in DCC compared to 26% in UMMC, and remained significantly higher even after multivariate adjustment (multivariate OR:1.76; 95%CI:1.25-2.47, in DCC compared to UMMC). The proportion of triple negative breast cancer was however similar in the two centres (19% in UMMC vs 21% in DCC).
    CONCLUSION: Indonesian women with breast cancer seem to present at a younger age and at later stages compared to Malaysian women. Their tumors were more likely to be of low grade and HER2 positive, even after adjustment for other factors, while hormone receptor positivity proved similar in the two groups. The higher HER2 positivity rate in Indonesian patients warrants further study.
  14. Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA
    Asian Pac J Cancer Prev, 2010;11(3):713-6.
    PMID: 21039041
    A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.
  15. Foo JC, Jawin V, Yap TY, Ahmad Bahuri NF, Ganesan D, Mun KS, et al.
    Childs Nerv Syst, 2021 05;37(5):1573-1580.
    PMID: 33580355 DOI: 10.1007/s00381-021-05080-4
    PURPOSE: Multidisciplinary team meetings (MDTMs) are essential in the clinical management of pediatric central nervous system (CNS) tumors. Evaluations of the impact of MDTMs on childhood CNS tumors and clinicians' perspectives on their effectiveness are scarce.

    METHODS: We retrospectively reviewed the clinical data of pediatric patients (aged <18 years) with CNS tumors diagnosed and treated in the Pediatric Hematology-Oncology Division at the University Malaya Medical Center from 2008 to 2019. We also conducted a web-based survey of the core members of the multidisciplinary team to evaluate the impact of the MDTMs.

    RESULTS: During the pre-MDTM era (2008-2012), 29 CNS tumors were diagnosed and treated, and during the MDTM era (2014-2019), 49 CNS tumors were diagnosed and treated. The interval for histologic diagnosis was significantly shorter during the MDTM era (p=0.04), but the interval from diagnosis to chemotherapy or radiotherapy and the 5-year overall survival of the 78 patients did not improve (62.1% ± 9.0% vs. 68.8% ± 9.1%; p=0.184). However, the 5-year overall survival of patients with medulloblastoma or rare tumors significantly improved in the MDTM era (p=0.01). Key factors that contributed to delayed treatment and poor outcomes were postoperative complications, the facility's lack of infrastructure, poor parental education about early treatment, cultural beliefs in alternative medicine, and infection during chemotherapy. Eighteen clinicians responded to the survey; they felt that the MDTMs were beneficial in decision-making and enhanced the continuity of coordinated care.

    CONCLUSION: MDTMs significantly reduced the diagnostic interval and improved the overall outcomes. However, delayed treatment remains a major challenge that requires further attention.

  16. Pailoor J, Mun KS, Leow M
    Malays J Pathol, 2012 Dec;34(2):97-101.
    PMID: 23424771 MyJurnal
    Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.
  17. Wang C, Zainal NS, Chai SJ, Dickie J, Gan CP, Zulaziz N, et al.
    Front Immunol, 2021;12:763086.
    PMID: 34733290 DOI: 10.3389/fimmu.2021.763086
    HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The vaccines inhibited tumor growth and improved the outcome alone and upon combination with anti-PD1 and resulted in tumor clearance in approximately 75% of mice. Pre-existence of MAGED4B and FJX1-reactive T cells in HNSCC patients suggests that these widely expressed antigens are highly immunogenic and could be further expanded by vaccination. The DNA vaccines targeting these antigens induced robust T cell responses and with the anti-PD1 antibody conferring excellent tumor control. This opens up an opportunity for combination immunotherapy that might benefit a wider population of HNSCC patients in an antigen-specific manner.
  18. Anthony R, Rajandram R, Yap NY, Mun KS, Samberkar PN, Kuppusamy S
    Malays J Pathol, 2023 Aug;45(2):261-269.
    PMID: 37658535
    BACKGROUND: Ubiquitously Transcribed Tetracopeptide Repeat on X Chromosome (UTX) and Jumonji Domain-Containing Protein 3 (JMJD3) are histone H3 lysine 27 (H3K27) demethylases that are found to play tumour suppressor or oncogenic roles in many cancers. However, their roles in urothelial carcinoma (UC) have not been well studied.

    OBJECTIVE: This study investigated UTX and JMJD3 protein expression patterns in UC and assess their clinical significance.

    PATIENTS AND METHODS: Immunohistochemistry (IHC) method was performed on formalin-fixed paraffin-embedded (FFPE) of UC tissues and compared to the normal bladder tissues from the autopsy specimen. The staining intensity of FFPE tissues were captured with the nuclear and overall positive pixels quantified using Aperio ImageScope software.

    RESULTS: JMJD3 protein uptake was present in both nucleus and cytoplasm but UTX protein was predominantly seen in the cytoplasm of UC tissue. UTX was under expressed whereas JMJD3 was over expressed in UC compared to normal bladder. UTX and JMJD3 were not related to clinical stage and grade. However, significant association between JMJD3 expression and invasiveness of tumour (p<0.05) was noted, especially in MIBC group (88.9%). UTX and JMJD3 did not yield any significance as prognostic factors for diseasespecific survival.

    CONCLUSIONS: Low expression of UTX protein in UC may indicate possible loss of its tumour suppressor activity and higher JMJD3 protein expression may indicate oncogenic activity. Hence, JMJD3 protein could be a potential diagnostic biomarker in detecting bladder UC of higher stages. Further investigation needed to study the dysregulation of this protein expression with associated gene expression.

  19. Subramaniam B, Arshad NM, Malagobadan S, Misran M, Nyamathulla S, Mun KS, et al.
    Pharmaceutics, 2021 Mar 24;13(4).
    PMID: 33804975 DOI: 10.3390/pharmaceutics13040439
    1'-acetoxychavicol acetate (ACA) extracted from the rhizomes of Alpinia conchigera Griff (Zingiberaceae) has been shown to deregulate the NF-ĸB signaling pathway and induce apoptosis-mediated cell death in many cancer types. However, ACA is a hydrophobic ester, with poor solubility in an aqueous medium, limited bioavailability, and nonspecific targeting in vivo. To address these problems, ACA was encapsulated in a nanostructured lipid carrier (NLC) anchored with plerixafor octahydrochloride (AMD3100) to promote targeted delivery towards C-X-C chemokine receptor type 4 (CXCR4)-expressing prostate cancer cells. The NLC was prepared using the melt and high sheer homogenization method, and it exhibited ideal physico-chemical properties, successful encapsulation and modification, and sustained rate of drug release. Furthermore, it demonstrated time-based and improved cellular uptake, and improved cytotoxic and anti-metastatic properties on PC-3 cells in vitro. Additionally, the in vivo animal tumor model revealed significant anti-tumor efficacy and reduction in pro-tumorigenic markers in comparison to the placebo, without affecting the weight and physiological states of the nude mice. Overall, ACA-loaded NLC with AMD3100 surface modification was successfully prepared with evidence of substantial anti-cancer efficacy. These results suggest the potential use of AMD3100-modified NLCs as a targeting carrier for cytotoxic drugs towards CXCR4-expressing cancer cells.
  20. Zhu CZ, Ting HN, Ng KH, Mun KS, Ong TA
    Phys Eng Sci Med, 2024 Mar;47(1):61-71.
    PMID: 37843766 DOI: 10.1007/s13246-023-01341-5
    Many studies have investigated the dielectric properties of human and animal tissues, particularly to differentiate between normal cells and tumors. However, these studies are invasive as tissue samples have to be excised to measure the properties. This study aims to investigate the dielectric properties of urine in relation to bladder cancer, which is safe and non-invasive to patients. 30 healthy subjects and 30 bladder cancer patients were recruited. Their urine samples were subjected to urinalysis and cytology assessment. A vector network analyzer was used to measure the dielectric constant (Ɛ') and loss factor (Ɛ″) at microwave frequencies of between 0.2 and 50 GHz at 25 °C, 30 °C and 37 °C. Significant differences in Ɛ' and Ɛ″ were observed between healthy subjects and patients, especially at frequencies of between 25 and 40 GHz at 25 °C. Bladder cancer patients had significant lower Ɛ' and higher Ɛ″ compared with healthy subjects. The Ɛ' was negatively correlated with urinary exfoliated urothelial cell number, and Ɛ″ was positively correlated. The study achieved a receiver operating characteristic area under curve (ROC-AUC) score of 0.69099 and an optimum accuracy of 75% with a sensitivity of 80% and a specificity of 70%. The number of exfoliated urothelial cell had significant effect on the dielectric properties, especially in bladder cancer patients. Urinary dielectric properties could potentially be used as a tool to detect bladder cancer.
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