Displaying publications 1 - 20 of 25 in total

Abstract:
Sort:
  1. Fulltext Prevalence and risk factors of Japanese encephalitis virus (JEV) in livestock and companion animal in high-risk areas in Malaysia
    Kumar K, Arshad SS, Selvarajah GT, Abu J, Toung OP, Abba Y, et al.
    Trop Anim Health Prod, 2018 Apr;50(4):741-752.
    PMID: 29243139 DOI: 10.1007/s11250-017-1490-6
    Japanese encephalitis (JE) is vector-borne zoonotic disease which causes encephalitis in humans and horses. Clinical signs for Japanese encephalitis virus (JEV) infection are not clearly evident in the majority of affected animals. In Malaysia, information on the prevalence of JEV infection has not been established. Thus, a cross-sectional study was conducted during two periods, December 2015 to January 2016 and March to August in 2016, to determine the prevalence and risk factors in JEV infections among animals and birds in Peninsular Malaysia. Serum samples were harvested from the 416 samples which were collected from the dogs, cats, water birds, village chicken, jungle fowls, long-tailed macaques, domestic pigs, and cattle in the states of Selangor, Perak, Perlis, Kelantan, and Pahang. The serum samples were screened for JEV antibodies by commercial IgG ELISA kits. A questionnaire was also distributed to obtain information on the animals, birds, and the environmental factors of sampling areas. The results showed that dogs had the highest seropositive rate of 80% (95% CI: ± 11.69) followed by pigs at 44.4% (95% CI: ± 1.715), cattle at 32.2% (95% CI: ± 1.058), birds at 28.9% (95% CI: ± 5.757), cats at 15.6% (95% CI: ± 7.38), and monkeys at 14.3% (95% CI: ± 1.882). The study also showed that JEV seropositivity was high in young animals and in areas where mosquito vectors and migrating birds were prevalent.
  2. Fulltext Transcriptional profiling of feline infectious peritonitis virus infection in CRFK cells and in PBMCs from FIP diagnosed cats
    Harun MS, Kuan CO, Selvarajah GT, Wei TS, Arshad SS, Hair Bejo M, et al.
    Virol J, 2013;10:329.
    PMID: 24209771 DOI: 10.1186/1743-422X-10-329
    BACKGROUND:
    Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV). Currently, the viruses virulence determinants and host gene expressions during FIPV infection are not fully understood.

    METHODS:
    RNA sequencing of Crandell Rees Feline Kidney (CRFK) cells, infected with FIPV strain 79-1146 at 3 hours post infection (h.p.i), were sequenced using the Illumina next generation sequencing approach. Bioinformatic's analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench mapped both control and infected cell reads to 18899 genes out of 19046 annotated genes. Kal's Z test statistical analysis was used to analyse the differentially expressed genes from the infected CRFK cells. Real time RT-qPCR was developed for further transcriptional profiling of three genes (PD-1, PD-L1 and A3H) in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diseased cats.

    RESULTS:
    Based on Kal's Z-test, with False Discovery Rate (FDR) <0.05 and >1.99 fold change on gene expressions, a total of 61 genes were differentially expressed by both samples, where 44 genes were up-regulated and the remainder were down-regulated. Most genes were closely clustered together, suggesting a homogeneous expression. The majority of the genes that were significantly regulated, were those associated with monocytes-macrophage and Th1 cell functions, and the regulation of apoptosis. Real time RT-qPCR developed focusing on 2 up-regulated genes (PD-L1 and A3H) together with an apoptosis associated gene PD-1 expressions in FIPV infected CRFK cells and in PBMCs from healthy and FIP diagnosed cats produced concordant results with transcriptome data.

    CONCLUSION:
    The possible roles of these genes, and their importance in feline coronaviruses infection, are discussed.
  3. Fulltext Molecular detection and characterisation of feline morbillivirus in domestic cats in Malaysia
    Mohd Isa NH, Selvarajah GT, Khor KH, Tan SW, Manoraj H, Omar NH, et al.
    Vet Microbiol, 2019 Sep;236:108382.
    PMID: 31500720 DOI: 10.1016/j.vetmic.2019.08.005
    Feline morbillivirus (FeMV), a novel virus from the family of Paramyxoviridae, was first identified in stray cat populations. The objectives of the current study were to (i) determine the molecular prevalence of FeMV in Malaysia; (ii) identify risk factors associated with FeMV infection; and (iii) characterise any FeMV isolates by phylogenetic analyses. Molecular analysis utilising nested RT-PCR assay targeting the L gene of FeMV performed on either urine, blood and/or kidney samples collected from 208 cats in this study revealed 82 (39.4%) positive cats. FeMV-positive samples were obtained from 63/124 (50.8%) urine and 20/25 (80.0%) kidneys while all blood samples were negative for FeMV. In addition, from the 35 cats that had more than one type of samples collected (blood and urine; blood and kidney; blood, urine and kidney), only one cat had FeMV RNA in the urine and kidney samples. Risk factors such as gender, presence of kidney-associated symptoms and cat source were also investigated. Male cats had a higher risk (p = 0.031) of FeMV infection than females. In addition, no significant association (p = 0.083) was observed between the presence of kidney-associated symptoms with FeMV status. From the 82 positive samples, FeMV RNA was detected from 48/82 (58.5%) pet cats and 34/126 (27.0%) shelter cats (p 
  4. The distribution of important sero-complexes of flaviviruses in Malaysia
    Kumar K, Arshad SS, Toung OP, Abba Y, Selvarajah GT, Abu J, et al.
    Trop Anim Health Prod, 2019 Mar;51(3):495-506.
    PMID: 30604332 DOI: 10.1007/s11250-018-01786-x
    Flaviviruses (FVs) are arthropod-borne viruses of medical and veterinary importance. Numerous species of FVs have been isolated from various host; mainly humans, animals, ticks, and mosquitoes. Certain FVs are extremely host-specific; at the same time, some FVs can infect an extensive range of species. Based on published literatures, 11 species of FVs have been detected from diverse host species in Malaysia. In humans, dengue virus and Japanese encephalitis virus have been reported since 1901 and 1942. In animals, the Batu Cave virus, Sitiawan virus, Carey Island, Tembusu virus, Duck Tembusu virus, and Japanese encephalitis viruses were isolated from various species. In mosquitoes, Japanese encephalitis virus and Kunjin virus were isolated from Culex spp., while Zika virus and Jugra virus were isolated from Aedes spp. In ticks, the Langat virus was isolated from Ixodes spp. One of the major challenges in the diagnosis of FVs is the presence of sero-complexes as a result of cross-reactivity with one or more FV species. Subsequently, the distribution of specific FVs among humans and animals in a specific population is problematic to assess and often require comprehensive and thorough analyses. Molecular assays such as quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and digital droplet RT-PCR (ddRT-PCR) have been used for the differentiation of flavivirus infections to increase the accuracy of epidemiological data for disease surveillance, monitoring, and control. In situations where sero-complexes are common in FVs, even sensitive assays such as qRT-pCR can produce false positive results. In this write up, an overview of the various FV sero-complexes reported in Malaysia to date and the challenges faced in diagnosis of FV infections are presented.
  5. Fulltext Enhanced anti-mammary gland cancer activities of tamoxifen-loaded erythropoietin-coated drug delivery system
    Beh CY, Rasedee A, Selvarajah GT, Yazan LS, Omar AR, Foong JN, et al.
    PLoS One, 2019;14(7):e0219285.
    PMID: 31291309 DOI: 10.1371/journal.pone.0219285
    Nanomedicine is an emerging area in the medical field, particularly in the treatment of cancers. Nanostructured lipid carrier (NLC) was shown to be a good nanoparticulated carrier for the delivery of tamoxifen (TAM). In this study, the tamoxifen-loaded erythropoietin-coated nanostructured lipid carriers (EPO-TAMNLC) were developed to enhance the anti-cancer properties and targetability of TAM, using EPO as the homing ligand for EPO receptors (EpoRs) on breast cancer tissue cells. Tamoxifen-loaded NLC (TAMNLC) was used for comparison. The LA7 cells and LA7 cell-induced rat mammary gland tumor were used as models in the study. Immunocytochemistry staining showed that LA7 cells express estrogen receptors (ERs) and EpoRs. EPO-TAMNLC and TAMNLC significantly (p<0.05) inhibited proliferation of LA7 in dose- and time-dependent manner. EPO-TAMNLC induced apoptosis and G0/G1 cell cycle arrest of LA7 cells. Both drug delivery systems showed anti-mammary gland tumor properties. At an intravenous dose of 5 mg kg-1 body weight, EPO-TAMNLC and TAMNLC were not toxic to rats, suggesting that both are safe therapeutic compounds. In conclusion, EPO-TAMNLC is not only a unique drug delivery system because of the dual drug-loading feature, but also potentially highly specific in the targeting of breast cancer tissues positive for ERs and EpoRs. The incorporation of TAM into NLC with and without EPO coat had significantly (p<0.05) improved specificity and safety of the drug carriers in the treatment of mammary gland tumors.
  6. Fulltext Japanese encephalitis in Malaysia: An overview and timeline
    Kumar K, Arshad SS, Selvarajah GT, Abu J, Toung OP, Abba Y, et al.
    Acta Trop, 2018 Sep;185:219-229.
    PMID: 29856986 DOI: 10.1016/j.actatropica.2018.05.017
    Japanese encephalitis (JE) is a vector-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). It causes encephalitis in human and horses, and may lead to reproductive failure in sows. The first human encephalitis case in Malaya (now Malaysia) was reported during World War II in a British prison in 1942. Later, encephalitis was observed among race horses in Singapore. In 1951, the first JEV was isolated from the brain of an encephalitis patient. The true storyline of JE exposure among humans and animals has not been documented in Malaysia. In some places such as Sarawak, JEV has been isolated from mosquitoes before an outbreak in 1992. JE is an epidemic in Malaysia except Sarawak. There are four major outbreaks reported in Pulau Langkawi (1974), Penang (1988), Perak and Negeri Sembilan (1998-1999), and Sarawak (1992). JE is considered endemic only in Sarawak. Initially, both adults and children were victims of JE in Malaysia, however, according to the current reports; JE infection is only lethal to children in Malaysia. This paper describes a timeline of JE cases (background of each case) from first detection to current status, vaccination programs against JE, diagnostic methods used in hospitals and factors which may contribute to the transmission of JE among humans and animals in Malaysia.
  7. Fulltext Zerumbone-Loaded Nanostructured Lipid Carrier Induces Apoptosis of Canine Mammary Adenocarcinoma Cells
    Foong JN, Selvarajah GT, Rasedee A, Rahman HS, How CW, Beh CY, et al.
    Biomed Res Int, 2018;2018:8691569.
    PMID: 30410940 DOI: 10.1155/2018/8691569
    Canine mammary gland tumor (CMT) is the most common tumor in intact female dog. Zerumbone (ZER) has promising anticancer properties, but plagued with poor water solubility, poor absorption, bioavailability, and delivery to target tissues. To solubilize, ZER was loaded into nanostructured lipid carrier (NLC) to produce ZER-loaded NLC (ZER-NLC). The objectives of this study were to determine the antiproliferative effect and the mode of cell death induced by ZER-NLC and ZER on a canine mammary gland tumor (CMT) adenocarcinoma primary cell line. There was no significant difference (p>0.05) between ZER-NLC and ZER treatments in the inhibition of CMT cell proliferation; thus, the loading of ZER into NLC did not compromise the cytotoxic effect of ZER. Microscopically, ZER-NLC- and ZER-treated CMT cells showed apoptotic cell morphology. ZER-NLC and ZER treatments significantly downregulated the antiapoptotic Bcl-2 and upregulated the proapoptotic Bax gene expressions in CMT cells. Both ZER-NLC and ZER-treated CMT cells showed significant (p<0.0001) increases in caspase-8, -9, and -3/7 protein activities. In conclusion, ZER-NLC induced CMT cell death via regulation of Bcl-2 and Bax gene expressions and caspase activations, indicating the involvement of both the intrinsic and extrinsic pathways of apoptosis. This study provided evidences for the potential of ZER-NLC as an anticanine mammary gland adenocarcinoma chemotherapy.
  8. Molecular epidemiology of Sporothrix schenkii isolates in Malaysia
    Kamal Azam NK, Selvarajah GT, Santhanam J, Abdul Razak MF, Ginsapu SJ, James JE, et al.
    Med Mycol, 2020 Jul 01;58(5):617-625.
    PMID: 31642485 DOI: 10.1093/mmy/myz106
    Sporothrix schenkii is a dimorphic fungus that causes infections in both humans and animals. We report on 25 S. schenkii isolates collected in 2017 from humans and cats clinically diagnosed with sporotrichosis, in Malaysia. These isolates were phenotypically identified as S. schenkii sensu lato and further defined as S. schenckii sensu stricto based on partial calmodulin gene sequence. Isolates from both humans and cats were genotypically identical but displayed phenotypic variation. Phylogenetic analyses based on partial calmodulin sequence showed that the Malaysian isolates clustered with global S. schenkii sensu stricto strains, in particular, of the AFLP type E. This analysis also revealed that partial calmodulin sequence alone was sufficient for classifying global S. schenckii sensu stricto strains into their respective AFLP types, from A to E. The genetically conserved S. schenkii sensu stricto species isolated from humans and cats is suggestive of a clonal strain present in Malaysia. To the best of our knowledge, this is the first report on molecular identification of Sporothrix schenkii strains from human infections in Malaysia. Further studies are required in order to elucidate the clonal nature of Malaysian S. schenkii isolates. Our findings indicate the presence of a predominant S. schenkii genotype in the environment, causing infections in both cats and humans in Malaysia.
  9. Fulltext Molecular detection and characterisation of Domestic Cat Hepadnavirus (DCH) from blood and liver tissues of cats in Malaysia
    Anpuanandam K, Selvarajah GT, Choy MMK, Ng SW, Kumar K, Ali RM, et al.
    BMC Vet Res, 2021 Jan 06;17(1):9.
    PMID: 33407487 DOI: 10.1186/s12917-020-02700-0
    BACKGROUND: A new domestic cat hepadnavirus (DCH, family Hepadnaviridae) was first reported from whole blood samples of domestic cats in Australia in 2018, and from cat serum samples in Italy in 2019. The pathogenesis of DCH is unknown, but it was reported in cats with viraemia (6.5-10.8%), chronic hepatitis (43%) and hepatocellular carcinoma (28%). Recent reports suggest that DCH resembles the human hepatitis B virus (HBV) and its related hepatopathies. This study aims to detect and characterize DCH among domestic cats in Malaysia. A cross-sectional study was performed on 253 cats, of which 87 had paired blood and liver samples, entailing whole-genome sequencing and phylogenetic analysis of DCH from a liver tissue sample.

    RESULTS: Among the 253 cats included in this study, 12.3% of the whole blood samples tested positive for DCH. The detection rate was significantly higher in pet cats (16.6%, n = 24/145) compared to shelter cats (6.5%, n = 7/108). Liver tissues showed higher a DCH detection rate (14.9%, n = 13/87) compared to blood; 5 out of these 13 cats tested positive for DCH in their paired liver and blood samples. Serum alanine transaminase (ALT) was elevated (> 95 units/L) in 12 out of the 23 DCH-positive cats (52.2%, p = 0.012). Whole-genome sequence analysis revealed that the Malaysian DCH strain, with a genome size of 3184 bp, had 98.3% and 97.5% nucleotide identities to the Australian and Italian strains, respectively. The phylogenetic analysis demonstrated that the Malaysian DCH genome was clustered closely to the Australian strain, suggesting that they belong to the same geographically-determined genetic pool (Australasia).

    CONCLUSIONS: This study provided insights into a Malaysian DCH strain that was detected from a liver tissue. Interestingly, pet cats or cats with elevated ALT were significantly more likely to be DCH positive. Cats with positive DCH detection from liver tissues may not necessarily have viraemia. The impact of this virus on inducing liver diseases in felines warrants further investigation.

  10. Fulltext Screening of Streptococcus suis in swine workers of selected states in Peninsular Malaysia
    Lee CY, Zakaria Z, Selvarajah GT, Mustaffa-Kamal F, Voon KGL, Fong MWC, et al.
    Vet World, 2024 Jan;17(1):1-7.
    PMID: 38406356 DOI: 10.14202/vetworld.2024.1-7
    BACKGROUND AND AIM: Streptococcus suis is a zoonotic pathogen that is highly associated with contact between live pigs and raw pig material. In view of the recent reports of human infections in Malaysia, epidemiological data on the status of S. suis in the human population, especially among people working closely with pigs and/or raw pork, should be provided. The aim of this study was to detect S. suis among individuals working in the swine industry in several major pig production areas in Peninsular Malaysia.

    MATERIALS AND METHODS: Demographic information, exposure determinants, and oral swabs were collected from swine personnel, including farmers, butchers, and veterinarians. Oral swabs were subjected to bacterial isolation and conventional polymerase chain reaction (PCR) assays for S. suis detection.

    RESULTS: The study included 40 participants working in the swine industry, with a predominant representation of males (62.5%) and Malaysian Chinese individuals (60.0%) who consumed pork (92.5%). Notably, none of the participants reported consuming raw or partially cooked pork. In spite of their occupational exposure risk, none of the oral swabs showed positive results for S. suis infection.

    CONCLUSION: To the best of our knowledge, this is the first report and detection study of S. suis using oral swabs obtained from swine personnel in Peninsular Malaysia.

  11. Fulltext In Vitro Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles against Feline Infectious Peritonitis Virus and Pharmacokinetics Study in Cats
    Ng SW, Selvarajah GT, Hussein MZ, Yeap SK, Omar AR
    Biomed Res Int, 2020;2020:3012198.
    PMID: 32596292 DOI: 10.1155/2020/3012198
    Feline infectious peritonitis (FIP) is an important feline viral disease, causing an overridden inflammatory response that results in a high mortality rate, primarily in young cats. Curcumin is notable for its biological activities against various viral diseases; however, its poor bioavailability has hindered its potential in therapeutic application. In this study, curcumin was encapsulated in chitosan nanoparticles to improve its bioavailability. Curcumin-encapsulated chitosan (Cur-CS) nanoparticles were synthesised based on the ionic gelation technique and were spherical and cuboidal in shape, with an average particle size of 330 nm and +42 mV in zeta potential. The nanoparticles exerted lower toxicity in Crandell-Rees feline kidney (CrFK) cells and enhanced antiviral activities with a selective index (SI) value three times higher than that of curcumin. Feline-specific bead-based multiplex immunoassay and qPCR were used to examine their modulatory effects on proinflammatory cytokines, including tumour necrosis factor (TNF)α, interleukin- (IL-) 6, and IL-1β. There were significant decrements in IL-1β, IL-6, and TNFα expression in both curcumin and Cur-CS nanoparticles. Based on the multiplex immunoassay, curcumin and the Cur-CS nanoparticles could lower the immune-related proteins in FIP virus (FIPV) infection. The single- and multiple-dose pharmacokinetics profiles of curcumin and the Cur-CS nanoparticles were determined by high-performance liquid chromatography (HPLC). Oral delivery of the Cur-CS nanoparticles to cats showed enhanced bioavailability with a maximum plasma concentration (Cmax) value of 621.5 ng/mL. Incorporating chitosan nanoparticles to deliver curcumin improved the oral bioavailability and antiviral effects of curcumin against FIPV infection. This study provides evidence for the potential of Cur-CS nanoparticles as a supplementary treatment of FIP.
  12. Fulltext The Role of Breast Cancer Stem Cell-Related Biomarkers as Prognostic Factors
    Ko CCH, Chia WK, Selvarajah GT, Cheah YK, Wong YP, Tan GC
    Diagnostics (Basel), 2020 Sep 19;10(9).
    PMID: 32961774 DOI: 10.3390/diagnostics10090721
    Breast cancer is one of the leading causes of cancer-related deaths in women worldwide, and its incidence is on the rise. A small fraction of cancer stem cells was identified within the tumour bulk, which are regarded as cancer-initiating cells, possess self-renewal and propagation potential, and a key driver for tumour heterogeneity and disease progression. Cancer heterogeneity reduces the overall efficacy of chemotherapy and contributes to treatment failure and relapse. The cell-surface and subcellular biomarkers related to breast cancer stem cell (BCSC) phenotypes are increasingly being recognised. These biomarkers are useful for the isolation of BCSCs and can serve as potential therapeutic targets and prognostic tools to monitor treatment responses. Recently, the role of noncoding microRNAs (miRNAs) has extensively been explored as novel biomarker molecules for breast cancer diagnosis and prognosis with high specificity and sensitivity. An in-depth understanding of the biological roles of miRNA in breast carcinogenesis provides insights into the pathways of cancer development and its utility for disease prognostication. This review gives an overview of stem cells, highlights the biomarkers expressed in BCSCs and describes their potential role as prognostic indicators.
  13. The Roles of Tissue Rigidity and Its Underlying Mechanisms in Promoting Tumor Growth
    Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF
    Cancer Invest, 2020 Sep;38(8-9):445-462.
    PMID: 32713210 DOI: 10.1080/07357907.2020.1802474
    Tissues become more rigid during tumorigenesis and have been identified as a driving factor for tumor growth. Here, we highlight the concept of tissue rigidity, contributing factors that increase tissue rigidity, and mechanisms that promote tumor growth initiated by increased tissue rigidity. Various factors lead to increased tissue rigidity, promoting tumor growth by activating focal adhesion kinase (FAK) and Rho-associated kinase (ROCK). Consequently, result in recruitment of cancer-associated fibroblasts (CAFs), epithelial-mesenchymal transition (EMT) and tumor protection from immunosurveillance. We also discussed the rationale for targeting tumor tissue rigidity and its potential for cancer treatment.
  14. Fulltext Expression profiles of immune mediators in feline Coronavirus-infected cells and clinical samples of feline Coronavirus-positive cats
    Safi N, Haghani A, Ng SW, Selvarajah GT, Mustaffa-Kamal F, Omar AR
    BMC Vet Res, 2017 Apr 07;13(1):92.
    PMID: 28388950 DOI: 10.1186/s12917-017-1019-2
    BACKGROUND: There are two biotypes of feline coronavirus (FCoV): the self-limiting feline enteric coronavirus (FECV) and the feline infectious peritonitis virus (FIPV), which causes feline infectious peritonitis (FIP), a fatal disease associated with cats living in multi-cat environments. This study provides an insight on the various immune mediators detected in FCoV-positive cats which may be responsible for the development of FIP.

    RESULTS: In this study, using real-time PCR and multiplex bead-based immunoassay, the expression profiles of several immune mediators were examined in Crandell-Reese feline kidney (CRFK) cells infected with the feline coronavirus (FCoV) strain FIPV 79-1146 and in samples obtained from FCoV-positive cats. CRFK cells infected with FIPV 79-1146 showed an increase in the expression of interferon-related genes and pro-inflammatory cytokines such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, and IL8. In addition, an increase in the expression of the above cytokines as well as GM-CSF and IFNγ was also detected in the PBMC, serum, and peritoneal effusions of FCoV-positive cats. Although the expression of MX1 and viperin genes was variable between cats, the expression of these two genes was relatively higher in cats having peritoneal effusion compared to cats without clinically obvious effusion. Higher viral load was also detected in the supernatant of peritoneal effusions compared to in the plasma of FCoV-positive cats. As expected, the secretion of IL1β, IL6 and TNFα was readily detected in the supernatant of peritoneal effusions of the FCoV-positive cats.

    CONCLUSIONS: This study has identified various pro-inflammatory cytokines and interferon-related genes such as MX1, viperin, CXCL10, CCL8, RANTES, KC, MCP1, IL8, GM-CSF and IFNγ in FCoV-positive cats. With the exception of MX1 and viperin, no distinct pattern of immune mediators was observed that distinguished between FCoV-positive cats with and without peritoneal effusion. Further studies based on definitive diagnosis of FIP need to be performed to confirm the clinical importance of this study.

  15. Fulltext Development of erythropoietin receptor-targeted drug delivery system against breast cancer using tamoxifen-loaded nanostructured lipid carriers
    Beh CY, How CW, Foo JB, Foong JN, Selvarajah GT, Rasedee A
    Drug Des Devel Ther, 2017;11:771-782.
    PMID: 28352153 DOI: 10.2147/DDDT.S123939
    Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds.
  16. Fulltext Cellular Metabolic Profiling of CrFK Cells Infected with Feline Infectious Peritonitis Virus Using Phenotype Microarrays
    Ng SW, Selvarajah GT, Cheah YK, Mustaffa Kamal F, Omar AR
    Pathogens, 2020 May 25;9(5).
    PMID: 32466289 DOI: 10.3390/pathogens9050412
    Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis.

    METHODS: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray™ plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells.

    RESULTS: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells.

    CONCLUSION: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection.

  17. Roles of Rho‑associated kinase in lung cancer (Review)
    Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF
    Int J Oncol, 2021 02;58(2):185-198.
    PMID: 33491756 DOI: 10.3892/ijo.2020.5164
    Lung cancer is one of the most lethal forms of cancer known to man, affecting millions of individuals worldwide. Despite advancements being made in lung cancer treatments, the prognosis of patients with the disease remains poor, particularly among patients with late‑stage lung cancer. The elucidation of the signaling pathways involved in lung cancer is a critical approach for the treatment of the disease. Over the past decades, accumulating evidence has revealed that Rho‑associated kinase (ROCK) is overexpressed in lung cancer and is associated with tumor growth. The present review discusses recent findings of ROCK signaling in the pathogenesis of lung cancer that were conducted in pre‑clinical studies. The significant role of ROCK in cancer cell apoptosis, proliferation, migration, invasion and angiogenesis is discussed. The present review also suggests the use of ROCK as a potential target for the development of lung cancer therapies, as ROCK inhibition can reduce multiple hallmarks of cancer, particularly by decreasing cancer cell migration, which is an initial step of metastasis.
  18. Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma
    Mauchle U, Selvarajah GT, Mol JA, Kirpensteijn J, Verheije MH
    Vet J, 2015 Aug;205(2):281-7.
    PMID: 25190293 DOI: 10.1016/j.tvjl.2014.08.006
    Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs.
  19. Fulltext Comparative aspects of microRNA expression in canine and human cancers
    Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC
    J Vet Sci, 2018 Mar 31;19(2):162-171.
    PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162
    MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.
  20. First molecular detection of porcine bocavirus in Malaysia
    Mohan Jacob D, Lee CY, Arshad SS, Selvarajah GT, Bande F, Ong BL, et al.
    Trop Anim Health Prod, 2018 Apr;50(4):733-739.
    PMID: 29243138 DOI: 10.1007/s11250-017-1489-z
    Several strains of porcine bocaviruses have been reported worldwide since their first detection in Sweden in 2009. Subsequently, the virus has been reported to be associated with gastrointestinal and respiratory signs in weaner and grower pigs. Although Malaysia is host to a self-sufficient swine livestock industry, there is no study that describes porcine bocavirus in the country. This report is the first to describe porcine bocavirus (PBoV) in Malaysian swine herds. PBoV was identified in various tissues from sick and runt pigs using the conventional PCR method with primers targeting conserved regions encoding for the nonstructural protein (NS1) gene. Out of 103 samples tested from 17 pigs, 32 samples from 15 pigs were positive for porcine bocavirus. In addition, a higher detection rate was identified from mesenteric lymph nodes (52.9%), followed by tonsil (37.0%), and lungs (33.3%). Pairwise comparison and phylogenetic analyses based on a 658-bp fragment of NS1 gene revealed that the Malaysian PBoV strains are highly similar to PBoV3 isolated in Minnesota, USA. The presence of porcine bocavirus in Malaysia and their phylogenetic bond was marked for the first time by this study. Further studies will establish the molecular epidemiology of PBoV in Malaysia and clarify pathogenicity of the local isolates.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links