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  1. Fulltext Identification of Predictive DNA Methylation Biomarkers for Chemotherapy Response in Colorectal Cancer
    Baharudin R, Ab Mutalib NS, Othman SN, Sagap I, Rose IM, Mohd Mokhtar N, et al.
    Front Pharmacol, 2017;8:47.
    PMID: 28243201 DOI: 10.3389/fphar.2017.00047
    Resistance to 5-Fluorouracil (5-FU) is a major obstacle to the successful treatment of colorectal cancer (CRC) and posed an increased risk of recurrence. DNA methylation has been suggested as one of the underlying mechanisms for recurrent disease and its contribution to the development of drug resistance remains to be clarified. This study aimed to determine the methylation phenotype in CRC for identification of predictive markers for chemotherapy response. We performed DNA methylation profiling on 43 non-recurrent and five recurrent CRC patients using the Illumina Infinium HumanMethylation450 Beadchip assay. In addition, CRC cells with different genetic backgrounds, response to 5-FU and global methylation levels (HT29 and SW48) were treated with 5-FU and DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC). The singular and combined effects of these two drug classes on cell viability and global methylation profiles were investigated. Our genome-wide methylation study on the clinical specimens showed that recurrent CRCs exhibited higher methylation levels compared to non-recurrent CRCs. We identified 4787 significantly differentially methylated genes (P < 0.05); 3112 genes were hyper- while 1675 genes were hypomethylated in the recurrent group compared to the non-recurrent. Fifty eight and 47 of the significantly hypermethylated and hypomethylated genes have an absolute recurrent/non-recurrent methylation difference of ≥20%. Most of the hypermethylated genes were involved in the MAPK signaling pathway which is a key regulator for apoptosis while the hypomethylated genes were involved in the PI3K-AKT signaling pathway and proliferation process. We also demonstrate that 5-azadC treatment enhanced response to 5-FU which resulted in significant growth inhibition compared to 5-FU alone in hypermethylated cell lines SW48. In conclusion, we found the evidence of five potentially biologically important genes in recurrent CRCs that could possibly serve as a new potential therapeutic targets for patients with chemoresistance. We postulate that aberrant methylation of CCNEI, CCNDBP1, PON3, DDX43, and CHL1 in CRC might be associated with the recurrence of CRC and 5-azadC-mediated restoration of 5-FU sensitivity is mediated at least in part by MAPK signaling pathway.
    Matched MeSH terms: Cell Survival
  2. Fulltext Predictors of survival among end stage renal failure patients undergoing dialysis treatment in Pahang from 2000 to 2004
    Hamid, A.J., Azmi, M.T.
    Malaysian Journal of Community Health, 2009;15(1):75-84.
    MyJurnal
    Introduction : A retrospective cohort study was conducted among ESRD who received dialysis treatment (Haemodialysis and CAPD) in all government hospitals in the State of Pahang from 1st January 2000 to 31st December 2004.
    Objective : The aim of the study was to identify factors affecting the survival of patients undergoing dialysis in the state of Pahang.
    Methods : Survival time was measured from the date of dialysis until the subjects died, lost to follow up or until the end of the study period at 31st December 2004.
    Results : Diabetes mellitus was the major cause for ESRD (33%) out of 132 subjects eligible for the study. Seven (7.1%) and five (15.2%) deaths occurred among haemodialysis and CAPD patients respectively, but statistically of no difference between the two treatments (log-rank, p=0.093). Factors influencing the survival of haemodialysis patients were diabetes mellitus (p=0.014), albumin (p=0.0005), creatinine (p=0.020) and hemoglobin level (p=0.002), while age of treatment and diabetes mellitus affecting the survival of CAPD patient. Cox Proportional Hazard Regression showed that haemodialysis subjects with low albumin (HR 0.669 df 95% 0.513 - 0.873) and hemoglobin (HR 0.403 df 95% 0.225 - 0.720) level had lower survival rate but none for CAPD.
    Conclusion : Good nutritional status, higher hemoglobin level and prevention of diabetes mellitus are important for the survival of haemodialysis patient.
    Matched MeSH terms: Survival Rate
  3. Fulltext Biodynamics of hepatitis C virus in haemodialysis patients in Pahang
    Mohammed Saad, A.M., Mohammed Imad, A.M., Aini, H.H., Seman, M.R.
    International Medical Journal Malaysia, 2012;11(1):23-30.
    MyJurnal
    Introduction: HCV infection is frequent in patients undergoing maintenance haemodialysis, with prevalence between 8 and 10%. Hepatitis C has an adverse effect on both patient and graft survival in those who get renal transplants. There are relatively scarce reports on the natural fluctuation in viral load level in patients on chronic haemodialysis. Materials and Methods: This is a longitudinal short-term three months study, where 27 chronic haemodialysis patients infected with known HCV genotypes were recruited from seven haemodialysis centres in Pahang. Serum samples were collected monthly, both pre- and post-haemodialysis sessions, over a period of three months. Viral RNA was extracted from serum using QIAamp Viral RNA Extraction kit (Qiagen). The HCV viral load was measured using one-step reverse transcriptase qPCR (Applied Biosystems) targeting the 5`HCV non-coding region (5’UTR). The serum α-IFN level was measured using commercial ELISA kit (Amersham, UK). Six biochemical liver function tests (AST, ALP, TP, albumin, ALT and TB) were also done for all pre-haemodialysis samples. Results: All patients showed persistent low level viral load that varied significantly over the study period (p = 0.001). HCV genotype 1 viral load was significantly higher than that of genotype 3. Conclusion: No apparent correlation could be recognized between the viral loads and the corresponding interferon-alpha levels which were detectable in only a few patients during the period of study.
    Matched MeSH terms: Graft Survival
  4. Fulltext Aloe emodin enhances tamoxifen cytotoxicity effect on ER a-positive breast cancer cells, MCF-7, through downregulation of MEK1 and MEK2
    Amin, I.M., Sheikh Abdul Kadir, S.H., Isa, M.R., Rosdy. N.M.M.N.M., Hasani NAH
    JUMMEC, 2016;19(1):1-10.
    MyJurnal
    The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as many
    of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from
    the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breast
    cancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-
    10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of
    MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone
    or a combination of emodin and tamoxifen, at their respective IC50 concentrations and at different time points
    of 24 hours, 48 hours and 72 hours. The respective IC50s were the concentrations of aloe emodin and tamoxifen
    required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using
    trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes
    of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was
    evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of
    tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a
    rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen
    on the viability of ERa-positive-breast cancer cells.
    Matched MeSH terms: Cell Survival
  5. Surfactant replacement therapy: effect on hospital resource utilization for preterm infants with respiratory distress syndrome
    Lim, W.L., Lim, C.T., Chye, J.K., Ho, M.M.
    Malaysian Journal of Paediatrics and Child Health, 1998;10(2):8-13.
    MyJurnal
    The objective of this study was to examine the effect of surfactant replacement therapy on hospital resource uti-lization in a well defined cohort of preterm infants with respiratory distress syndrome (RDS). Thirty preterm infants 800g with RDS requiring mechanical ventila-tion with Fi02 of 0.4 given modified bovine surfactant (Survanta) were compared with an equal number of his-torical controls. The total cost of neonatal care was cal-culated in a detailed survey covering all aspects of resource use. Surfactant-treated infants had an improved survival rate (90.0% vs 66.7%, p=0.03) and a trend towards shorter ventilator days (11.8 vs 19.0 days, p=0.17). There were no significant differences in the number of laboratory and radiological investiga-tions, use of disposable items, equipment, medications and other therapies. The total hospital cost per livebirth for surfactant-treated and control infants were R/V120,281 and R1V121,785 respectively. Personnel salaries represented the largest sector of resource uti-lization. When analysed by birthweight categories, the cost per livebirth for surfactant-treated and control infants in the 800-999g category were RM37,315 and RM14,760 respectively. As for the surfactant-treated and control infants in the 1000-1499g category, the cost per livebirth were RM21,426 and RM32,327 respectively. We concluded that surfactant replacement therapy did not increase overall hospital resource uti-lization and may decrease the cost for infants weighing 1000g.
    Matched MeSH terms: Survival Rate
  6. Prevention of respiratory distress syndrome
    Yu, Victor Y.H.
    Malaysian Journal of Child Health, 1993;5(1):3-8.
    MyJurnal
    ANTENATAL CORTICOSTEROID THERAPY. Benefits. In 1969, the first study was published which showed that prematurely delivered lambs exposed prenatally to corticosteroids survived longer than placebo-treated control animals.' A randomised clinical trial (RCT) followed which demonstrated that antenatal corticosteroid therapy significantly reduced the incidence of respiratory distress syndrome (RDS) in infants born before 2 weeks gestation and reduced mortality in those born before 37 weeks.2 A meta-analysis has been published on 12 RCTs involving over 3000 women in preterm labour, using primarily 24mg of betamethasone or dexamethasone given in 2-6 divided doses over a 48-hour period.' It showed that antenatal corticosteroid therapy is associated with a significant reduction in the risk of RDS (a) if the infant is born > 24 hours or < 7 days of the treatment, (b) in both male and female infants and (c) even in infants < 31 weeks gestation. It also significantly reduces mortality rate and morbidity such as intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC), shortens the duration of hospitalisation and reduces treatment costs. The improvement in survival rate in infants born
    Matched MeSH terms: Survival Rate
  7. Gastroenterological problems in the neonates
    Lee, W.S.
    Malaysian Journal of Paediatrics and Child Health, 2001;13(1):45-49.
    MyJurnal
    Significant advances in perinatology and neonatology in the last decade have resulted in increased survival of extremely premature infants.' Survival rates at 25 and 26 weeks of gestation age ranging from 60% to 82% and from 75% to 93%, respectively, have been reported.' In Malaysia, the survival rates among premature very low birth weight infants (< 1500 g) were reported to be between 69% and 78%.2,3 Such improvements of survival have been attributed to the advances in the management of respiratory disease and intra-ventricular haemorrahge in the premature infants.',2 Thus, attention have recently been focused on the need to secure adequate nutrient intake of these premature infants. Parenteral nutrition has often been used to manage the transition between transplacental nutrition in-utero and post-natal enteral nutrition, but is associated with cholestasis and sepsis.4 However, the ability to deliver nutrition is limited not only by immature absorptive or digestive function but by inadequate motor activity. Gastroesophageal efflux (GER) and feeding intolerance are the major gastro-enterological problems of the premature neonates.
    Matched MeSH terms: Survival Rate
  8. Survival and Associated Risk Factors for Mortality Among Infants with Critical Congenital Heart Disease in a Developing Country
    Mat Bah MN, Sapian MH, Jamil MT, Alias A, Zahari N
    Pediatr Cardiol, 2018 Oct;39(7):1389-1396.
    PMID: 29756159 DOI: 10.1007/s00246-018-1908-6
    Critical congenital heart disease (CCHD) is associated with significant morbidity and mortality. However, data on survival of CCHD and the risk factors associated with its mortality are limited. This study examined CCHD survival and the risk factors for CCHD mortality. Using a retrospective cohort study of infants born with CCHD from 2006 to 2015, survival over 10 years was estimated using Kaplan-Meier analysis, and the risk factors for mortality were analyzed using multivariate Cox proportional hazards regression. A total of 491 CCHD cases were included in the study, with an overall mortality rate of 34.8% (95% confidence interval [CI] 30.6-39.2). The intervention/surgical mortality rate was 9.8% ≤ 30 days and 11.5% > 30 days after surgery, and 17% died before surgery or intervention. The median age at death was 2.7 months [first quartile: 1 month, third quartile: 7.3 months]. The CCHD survival rate was 90.4% (95% CI 89-91.8%) at 1 month, 69.3% (95% CI 67.2-71.4%) at 1 year, 63.4% (95% CI 61.1-65.7%) at 5 years, and 61.4% (95% CI 58.9-63.9%) at 10 years. Weight of
    Matched MeSH terms: Survival Rate
  9. Fulltext Palmitic acid induces neurotoxicity and gliatoxicity in SH-SY5Y human neuroblastoma and T98G human glioblastoma cells
    Ng YW, Say YH
    PeerJ, 2018;6:e4696.
    PMID: 29713567 DOI: 10.7717/peerj.4696
    Background: Obesity-related central nervous system (CNS) pathologies like neuroinflammation and reactive gliosis are associated with high-fat diet (HFD) related elevation of saturated fatty acids like palmitic acid (PA) in neurons and astrocytes of the brain.

    Methods: Human neuroblastoma cells SH-SY5Y (as a neuronal model) and human glioblastoma cells T98G (as an astrocytic model), were treated with 100-500 µM PA, oleic acid (OA) or lauric acid (LA) for 24 h or 48 h, and their cell viability was assessed by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of stable overexpression of γ-synuclein (γ-syn), a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson's disease (PD) α-synuclein [α-syn; wild-type (wt) and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated. The effects of co-treatment of PA with paraquat (PQ), a Parkinsonian pesticide, and leptin, a hormone involved in the brain-adipose axis, were also assessed. Cell death mode and cell cycle were analyzed by Annexin V/PI flow cytometry. Reactive oxygen species (ROS) level was determined using 2',7'-dichlorofluorescien diacetate (DCFH-DA) assay and lipid peroxidation level was determined using thiobarbituric acid reactive substances (TBARS) assay.

    Results: MTT assay revealed dose- and time-dependent PA cytotoxicity on SH-SY5Y and T98G cells, but not OA and LA. The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T) modestly (but still significantly) rescued the cytotoxicity of PA in SH-SY5Y and T98G cells. Co-treatment of increasing concentrations of PQ exacerbated PA's neurotoxicity. Pre-treatment of leptin, an anti-apoptotic adipokine, did not successfully rescue SH-SY5Y cells from PA-induced cytotoxicity-suggesting a mechanism of PA-induced leptin resistance. Annexin V/PI flow cytometry analysis revealed PA-induced increase in percentages of cells in annexin V-positive/PI-negative quadrant (early apoptosis) and subG0-G1 fraction, accompanied by a decrease in G2-M phase cells. The PA-induced ROS production and lipid peroxidation was at greater extent in T98G as compared to that in SH-SY5Y.

    Discussion: In conclusion, PA induces apoptosis by increasing oxidative stress in neurons and astrocytes. Taken together, the results suggest that HFD may cause neuronal and astrocytic damage, which indirectly proposes that CNS pathologies involving neuroinflammation and reactive gliosis could be prevented via the diet regimen.

    Matched MeSH terms: Cell Survival
  10. Fulltext Prediction of mortality in severe dengue cases
    Md-Sani SS, Md-Noor J, Han WH, Gan SP, Rani NS, Tan HL, et al.
    BMC Infect Dis, 2018 05 21;18(1):232.
    PMID: 29783955 DOI: 10.1186/s12879-018-3141-6
    BACKGROUND: Increasing incidence of dengue cases in Malaysia over the last few years has been paralleled by increased deaths. Mortality prediction models will therefore be useful in clinical management. The aim of this study is to identify factors at diagnosis of severe dengue that predicts mortality and assess predictive models based on these identified factors.

    METHOD: This is a retrospective cohort study of confirmed severe dengue patients that were admitted in 2014 to Hospital Kuala Lumpur. Data on baseline characteristics, clinical parameters, and laboratory findings at diagnosis of severe dengue were collected. The outcome of interest is death among patients diagnosed with severe dengue.

    RESULTS: There were 199 patients with severe dengue included in the study. Multivariate analysis found lethargy, OR 3.84 (95% CI 1.23-12.03); bleeding, OR 8.88 (95% CI 2.91-27.15); pulse rate, OR 1.04 (95% CI 1.01-1.07); serum bicarbonate, OR 0.79 (95% CI 0.70-0.89) and serum lactate OR 1.27 (95% CI 1.09-1.47), to be statistically significant predictors of death. The regression equation to our model with the highest AUROC, 83.5 (95% CI 72.4-94.6), is: Log odds of death amongst severe dengue cases = - 1.021 - 0.220(Serum bicarbonate) + 0.001(ALT) + 0.067(Age) - 0.190(Gender).

    CONCLUSION: This study showed that a large proportion of severe dengue occurred early, whilst patients were still febrile. The best prediction model to predict death at recognition of severe dengue is a model that incorporates serum bicarbonate and ALT levels.

    Matched MeSH terms: Survival Rate
  11. Flavonoids and its Neuroprotective Effects on Brain Ischemia and Neurodegenerative Diseases
    Putteeraj M, Lim WL, Teoh SL, Yahaya MF
    Curr Drug Targets, 2018;19(14):1710-1720.
    PMID: 29577854 DOI: 10.2174/1389450119666180326125252
    Brain ischemia is among the leading cause of death with majority of the cases are associated with ischemic strokes. It can occur in two forms of either focal or global ischemia. Neurodegenerative disorder such as Alzheimer and Parkinson diseases is also on the rise worldwide. These disorders have common similarities; i.e. they all affecting the central nervous system with debilitating effect to the patient. In this review, we look into the promising role of flavonoids, a natural bioactive compound found abundant in vegetables, fruits and traditional herbs. Treatment with flavonoids such as curcumin, lycopene, ginsenoside, vitexin and baicalin have shown promising neuroprotective effects against ischemic-induced injury. Besides anticancer, antioxidant and immunomodulation properties, flavonoid also exerts neuroprotective effects by increases neuronal viability, increases tissue perfusion and cerebral blood flow and reduce ischemic-related apoptosis. In addition, flavonoid also exerts anti-amyloidogenic effect and reduces loss of dopaminergic neurons in the brain. These results suggesting flavonoids might be able to serve as a potential therapeutic agent in brain disorders.
    Matched MeSH terms: Cell Survival
  12. The association between the behavior rating inventory of executive functioning and cognitive testing in children diagnosed with a brain tumor
    de Vries M, de Ruiter MA, Oostrom KJ, Schouten-Van Meeteren AYN, Maurice-Stam H, Oosterlaan J, et al.
    Child Neuropsychol, 2018 08;24(6):844-858.
    PMID: 28693404 DOI: 10.1080/09297049.2017.1350262
    Pediatric brain tumor survivors (PBTS) suffer from cognitive late effects, such as deteriorating executive functioning (EF). We explored the suitability of the Behavior Rating Inventory of Executive Function (BRIEF) to screen for these late effects. We assessed the relationship between the BRIEF and EF tasks, and between the BRIEF-Parent and BRIEF-Teacher, and we explored the clinical utility. Eighty-two PBTS (8-18 years) were assessed with EF tasks measuring attention, cognitive flexibility, inhibition, visual-, and working memory (WM), and with the BRIEF-Parent and BRIEF-Teacher. Pearson's correlations between the BRIEF and EF tasks, and between the BRIEF-Parent and BRIEF-Teacher were calculated. The BRIEF-Parent related poorly to EF tasks (rs < .26, ps > .01), but of the BRIEF-Teacher the WM-scale, Monitor-scale, Behavioral-Regulation-Index, and Meta-cognition-Index, and Total-score (rs > .31, ps < .01) related significantly to some EF tasks. When controlling for age, only the WM scale and Total score related significantly to the attention task (ps < .01). The inhibit scales of the BRIEF-Parent and BRIEF-Teacher correlated significantly (r = .33, p < .01). Children with clinically elevated scores on BRIEF scales that correlated with EF tasks performed worse on all EF tasks (ds 0.56-1.23, ps < .05). The BRIEF-Teacher Total and Index scores might better screen general EF in PBTS than the BRIEF-Parent. However, the BRIEF-Teacher is also not specific enough to capture separate EFs. Solely relying on the BRIEF as a screening measure of EFs in BPTS is insufficient. Questionnaires and tasks give distinctive, valuable information.
    Matched MeSH terms: Survival Rate
  13. Extensive peritoneal lavage after curative gastrectomy for gastric cancer (EXPEL): study protocol of an international multicentre randomised controlled trial
    Kim G, Chen E, Tay AY, Lee JS, Phua JN, Shabbir A, et al.
    Jpn J Clin Oncol, 2017 02 26;47(2):179-184.
    PMID: 28173154 DOI: 10.1093/jjco/hyw153
    Peritoneal recurrence after gastrectomy for gastric cancer is common and the prognosis is dismal. Recent evidence suggests that extensive peritoneal lavage with large volume of normal saline after surgery before abdominal closure can reduce the risk of peritoneal recurrence and improve overall survival. This study aims to evaluate the benefit of extensive intraoperative peritoneal lavage. This is a prospective, open-label, multicentre randomised controlled trial involving 15 international centres in China, Korea, Japan, Malaysia and Singapore. Patients with cT3/4 stomach cancer undergoing curative resection are randomised to either extensive peritoneal lavage (10 l of saline) or standard lavage (≤2 l of saline). The primary outcome is overall survival and secondary outcomes include disease-free survival and peritoneal recurrence. The minimum sample size is 600 subjects with 300 per arm completing 3 years follow-up. The data will be analysed on an intention-to-treat basis, assuming a two-sided test with a 5% level of significance.
    Matched MeSH terms: Disease-Free Survival
  14. HAART induces cell death in a cervical cancer cell line, HCS-2: A Scanning Electron Microscopy study
    Xulu KR, Hosie MJ
    J Microsc Ultrastruct, 2016 06 17;5(1):39-48.
    PMID: 30023236 DOI: 10.1016/j.jmau.2016.06.001
    Apoptosis is a tightly programmed cell suicide which occurs in multiple physiologic and pathological conditions where it plays an important role in tissue development and homeostasis by eliminating unwanted and damaged cells. Appropriate apoptosis signalling is crucial in maintaining the fine balance between cell death and cell survival in cancer. In response to death stimuli the morphology of the cell undergoes unique changes. The aim of this study was to examine and compare the changes in the cell surface morphology using scanning electron microscopy in HCS-2 cells, following 24 hour treatment with components of highly active antiretroviral therapy (HAART) at their clinical plasma concentrations. The cells were fixed in 2.5% Glutaraldehyde and post-fixed in 1% osmium tetroxide. The cells were then dehydrated through a graded series of alcohol and treated with hexamethyl-disilazane, then coated with a double layer of carbon. The cells were viewed under a Zeiss Ultra FEG Scanning Electron Microscope and a one way ANOVA and Tukey Kramer Post Hoc test was conducted based on the scoring of surface morphology of the cells using JMP 11 statistical software. The drugs used in this study induced morphological features which are known to be characteristic of apoptotic cell death. The drug combinations (ATP and LPV/r) were seemingly more effective than individual treatments in inducing cell death because morphological features observed were more advanced than those observed in individual treatments. However, LPV/r was more potent than ATP. In conclusion, HAART showed anticancer properties by inducing cell death through apoptosis.
    Matched MeSH terms: Cell Survival
  15. Fulltext Hepatocellular Carcinoma in Malaysia and Its Changing Trend
    Raihan R, Azzeri A, H Shabaruddin F, Mohamed R
    Euroasian J Hepatogastroenterol, 2018 05 01;8(1):54-56.
    PMID: 29963463 DOI: 10.5005/jp-journals-10018-1259
    Hepatocellular carcinoma (HCC) is one of the leading causes of death globally. In Malaysia liver cancer is the eighth most common cause of cancer for both gender and fifth most common cause of cancer for males. Liver cancer is a cause of premature death in Malaysia: The trend from 1990 to 2010 was observed upward. Since 1990, the annual years of life lost (YLLs) from liver cancer have increased by 31.5%. Older persons are at higher risk and there is male predominance observed. Curative surgical resection, liver transplantation, and supportive symptomatic care, including percutaneous ethanol injection and radiofrequency ablation (RFA), and noncurative transarterial chemoembolization (TACE) are among available treatment facilities. Yet the survival rate is very poor as majority of patients present at very advanced stage. Hepatitis B virus (HBV) remained the leading cause of HCC in Malaysia. Several studies showed cryptogenic causes, which are mainly nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) among the predominant causes of HCC in Malaysia than hepatitis C virus (HCV), alcohol, or any other reason. This mainly correlates with the increasing incidence of diabetes and obesity in Malaysia. How to cite this article: Raihan R, Azzeri A, Shabaruddin FH, Mohamed R. Hepatocellular Carcinoma in Malaysia and Its Changing Trend. Euroasian J Hepato-Gastroenterol 2018;8(1):54-56.
    Matched MeSH terms: Survival Rate
  16. Polydopamine-assisted chlorhexidine immobilization on medical grade stainless steel 316L: Apatite formation and in vitro osteoblastic evaluation
    Mohd Daud N, Hussein Al-Ashwal R, Abdul Kadir MR, Saidin S
    Ann. Anat., 2018 Nov;220:29-37.
    PMID: 30048761 DOI: 10.1016/j.aanat.2018.06.009
    Immobilization of chlorhexidine (CHX) on stainless steel 316L (SS316L), assisted by a polydopamine film as an intermediate layer is projected as an approach in combating infection while aiding bone regeneration for coating development on orthopedic and dental implants. This study aimed to investigate the ability of CHX coating to promote apatite layer, osteoblast cells viability, adhesion, osteogenic differentiation and mineralization. Stainless steel 316L disks were pre-treated, grafted with a polydopamine film and immobilized with different concentrations of CHX (10-30mM). The apatite layer formation was determined through an in vitro simulated body fluid (SBF) test by ATR-FTIR and SEM-EDX analyses. The osteoblastic evaluations including cells viability, cells adhesion, osteogenic differentiation and mineralization were assessed with human fetal osteoblast cells through MTT assay, morphology evaluation under FESEM, ALP enzyme activity and Alizarin Red S assay. The apatite layer was successfully formed on the CHX coated disks, demonstrating potential excellent bioactivity property. The CHX coatings were biocompatible with the osteoblast cells at low CHX concentration (<20mM) with good adhesion on the metal surfaces. The increment of ALP activity and calcium deposition testified that the CHX coated disks able to support osteoblastic maturation and mineralization. These capabilities give a promising value to the CHX coating to be implied in bone regeneration area.
    Matched MeSH terms: Cell Survival
  17. Risk factors for high death and loss-to-follow-up rates among patients with multidrug-resistant tuberculosis at a programmatic management unit
    Javaid A, Shaheen Z, Shafqat M, Khan AH, Ahmad N
    Am J Infect Control, 2017 Feb 01;45(2):190-193.
    PMID: 27769706 DOI: 10.1016/j.ajic.2016.07.026
    Among 186 retrospectively evaluated patients with multidrug-resistant tuberculosis, 33.9% were cured, 6.6% completed treatment, 25% died, 18.3% were lost to follow-up, 2.2% failed treatment, and 13.8% were still undergoing treatment by the end of the study period. Rural residence was a risk factor for loss to follow-up (odds ratio [OR], 3.315; P = .016), whereas baseline body weight <40 kg (OR, 2.175; P = .042) and resistance to ofloxacin (OR, 2.889; P = .025) were risk factors for death. Despite programmatic management, treatment outcomes of the current cohort were distressing.
    Matched MeSH terms: Survival Analysis
  18. Fulltext Subtractive hybridization identifies stem cell-associated genes in an acute myeloid leukemia with poor prognosis
    Ngiow Shin Foong, Maha Abdullah, Jasmine Lim, Cheong Soon-Keng, Seow Heng-Fong
    Malaysian Journal of Medicine and Health Sciences, 2016;12(1):19-31.
    MyJurnal
    Introduction: Current prognostic markers have improved survival prediction, however, it has not
    advanced treatment strategies. Gene expression profiling may identify biological markers suitable as
    therapeutic targets. Leukaemia stem cell is associated with adverse outcome, however, its biological
    characteristics are still being investigated. We observed higher in vitro cell viability in acute myeloid
    leukaemia (AML) samples with poor prognosis, which may be stem cell related. Objective: The
    objective of this study was to profile highly expressed genes in an AML sample of poor prognosis/high
    viability and compare with a sample of good prognosis/low viability. Method: Subtractive hybridization
    was performed on two AML samples with high blast counts (>80%), a poor prognosis, PP (disease free
    survival, DFS12 months) sample. The PP sample had
    higher CD34+ counts (73% vs 46%) and higher cell viability than the GP sample. cDNA libraries were
    subsequently cloned and sequenced. Results: cDNA subtracted from the PP samples was identified
    as genes active during fetal/embryonic development (LCOR, CNOT1, ORMDL1), HOX- related genes
    (HOXA3, PBX3, SF3B1), hematopoiesis (SELL, IL-3RA) and aerobic glycolysis/hypoxia (PGK1,
    HIGD1A) -associated genes. Majority of GP clones isolated contained genes involved in oxidative
    phosphorylation, OXPHOS (COXs, ATPs, MTND4 and MTRNR2), protein synthesis (including
    ribosomal proteins, initiating and elongation factors), chromatin remodeling (H2AFZ, PTMA), cell
    motility (MALAT1, CALM2, TMSB4X), and mitochondria (HSPA9, MPO) genes. Conclusion: Thus,
    the PP sample exhibited stem cell-like features while the GP sample showed cells at a high level of cell
    activity. These genes are potential prognostic markers and targets for therapy.
    Matched MeSH terms: Cell Survival
  19. Novel metabolites from Trichoderma atroviride against human prostate cancer cells and their inhibitory effect on Helicobacter pylori and Shigella toxin producing Escherichia coli
    Saravanakumar K, Mandava S, Chellia R, Jeevithan E, Babu Yelamanchi RS, Mandava D, et al.
    Microb Pathog, 2018 Oct 10;126:19-26.
    PMID: 30316006 DOI: 10.1016/j.micpath.2018.10.011
    The present study aimed to purify and identify the metabolites from T. atroviride using high-performance liquid chromatography (HPLC) and 1H and 13C nuclear magnetic resonance spectrometer (NMR) followed by analyzing their toxicological, antibacterial and anticancer properties. This work identified two metabolites - TM1 and TM2. TM1 was in two forms: (i) 1, 3-dione-5, 5-dimethylcyclohexane; and, (ii) 2-enone-3hydroxy -5,5-dimethylcylohex, while TM2 was 4H-1,3-dioxin-4-one-2,3,6-trimethyl. These metabolites did not exhibit any irritant or allergic reaction as revealed by HET- CAM test. TM2 significantly inhibited the growth of H. pylori and Shigella toxin producing Escherichia coli (STEC) as evident by in vitro and microscopic observations of bacterial cell death. TM2 also induced the cell death and cytotoxicity, as revealed by cell viability test and western blot analysis. According to microscopic, flow cytometer and western blot analysis, TM2 treated cells displayed higher ROS, cell death, and apoptosis-related protein expression than TM1 and control. This study concluded that TM2 derived from T. atroviride was a potential therapeutic agent for anti-prostate cancer and antibiotic agent against MDR- H. pylori and STEC and it is also recommended to carry out further in vivo animal model experiments with improved stability of the metabolites for future pharmaceutical trails.
    Matched MeSH terms: Cell Survival
  20. Expression of clusterin in colorectal carcinoma in relation to clinicopathological criteria
    Gomaa W, Al-Ahwal M, Al-Maghrabi H, Buhmeida A, Al-Qahtani M, Al-Maghrabi B, et al.
    Malays J Pathol, 2017 Dec;39(3):243-250.
    PMID: 29279586
    BACKGROUND/AIM: Colorectal carcinoma (CRC) carries a high incidence of morbidity and mortality. Prognosis is related to nodal metastasis and stage. Clusterin is a widely distributed glycoprotein with not yet fully understood functions. Clusterin may be overexpressed in some tumours or under expressed in other tumours. The aim behind this study is to examine the relation of clusterin cytoplasmic immunostaining to tumour characteristics, disease relapse, and survival in CRC.

    MATERIALS AND METHODS: Paraffin blocks of 133 CRCs were retrieved from the Department of Pathology, King Abdulaziz University, Jeddah, Saudi Arabia. Immunostaining was done using antibody to clusterin. Staining expression in 10% of malignant cells was used as a cut-off to determine low immunostaining and high immunostaining. Statistical tests were used to evaluate the association of clusterin immunostaining with clinicopathological parameters.

    RESULTS: Immunohistochemical results showed clusterin low immunostaining in CRC and nodal metastases. No association was found between clusterin immunostaining and tumour grade, age, tumour invasiveness, distant metastases, vascular invasion, nodal metastases, relapse, and survival.

    CONCLUSION: Our study showed low clusterin immunostaining in CRC with lack of association with prognostic indicators in CRC. These results raise the controversy of understanding the role of clusterin in CRC. Further molecular studies are required to explore more about possible mechanisms of clusterin association with tumorigenicity, apoptosis, tumour growth progression, local and vascular invasion, and metastasis of CRC.

    Matched MeSH terms: Disease-Free Survival
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