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Family development: a classic example

Bul Keluarga, 1979 Jul-Aug;97:4-5, 8.
PMID: 12261448

PIP: On August 15, 1978, the integrated parasite control/family planning program was launched by the National Family Planning Board in the Tanjong Malim Estate in Kuala Lumpur (the estate is a rubber oil palm plantation) to enhance the health status of the estate workers and their families. Personal hygiene, good toilet habits, and washing fruits and vegetables before eating were emphasized. Pre- and post-surveys of worm infestation of the estate population revealed that treatment with drugs dramatically reduced the rate of intestinal helminthiasis infection among the population. To sustain the prevention or total eradication of the disease, an ongoing educational program was initiated and included the following features: 1) increasing knowledge of the community as to how intestinal helminthiasis is transmitted, and ways of limiting transmission; 2) providing safe and sanitary toilet facilities for young children, and; 3) periodic deworming of susceptible population every 3 months. The estate members are also encouraged to plant vegetables in their backyard. The National Family Planning Board also helped the estate members organize different functional groups, such as Mothers' Group. This multifaceted approach to family planning appears to have an encouraging future, particularly in family development.

Matched MeSH terms: Disease; Parasitic Diseases*
The place of Bactrim and Vibramycin in acute salpingitis

Ng A

Med J Malaysia, 1975 Dec;30(2):133-4.
PMID: 1241709
Matched MeSH terms: Acute Disease
Letter: An acute attack of quartan malaria in a leprosy patient being treated with diaminodiphenylsulphone

Laing AB, Gooi HC, Gelber RH

Trans R Soc Trop Med Hyg, 1974;68(2):165-6.
PMID: 4617939
Matched MeSH terms: Acute Disease
Therapeutic effects of sub-mucous diathermy of inferior turbinates, with special reference to ethnic groups in Malaya

Gnanapragasam A

Med J Malaya, 1972 Jun;26(4):266-71.
PMID: 5069416
Matched MeSH terms: Chronic Disease
Respiratory function among Malaysian aboriginals

Dugdale AE, Bolton JM, Ganendran A

Thorax, 1971 Nov;26(6):740-3.
PMID: 5144653
Matched MeSH terms: Chronic Disease
Filariasis in Sabah, East Malaysia

Barclay R

Ann Trop Med Parasitol, 1969 Dec;63(4):473-88.
PMID: 4393668
Matched MeSH terms: Disease Vectors
Fulltext Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, et al.

Nat Genet, 2018 07;50(7):928-936.
PMID: 29892016 DOI: 10.1038/s41588-018-0142-8

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.

Matched MeSH terms: Genetic Predisposition to Disease
Fulltext Association of MMP-9 gene polymorphisms with nephrolithiasis patients

Mehde AA, Mehdi WA, Yusof F, Raus RA, Zainal Abidin ZA, Ghazali H, et al.

J Clin Lab Anal, 2018 Jan;32(1).
PMID: 28205286 DOI: 10.1002/jcla.22173

BACKGROUND: Nephrolithiasis is one of the causes which lead to chronic kidney disease (CKD). Matrix metalloproteinases (MMPs) are endopeptidases degrading extracellular matrix which correlate with the pathogenesis of atherosclerosis. The current study was designed to analyze the association of (R279Q, C1562T) polymorphism of MMP-9 with nephrolithiasis patients.
METHODS: Genotyping of MMP-9/R279Q and of MMP-9/C1562T polymorphism were carried out by PCR-based restriction digestion method. Serum level of MMP-9, oxidative stress marker, MDA, and uric acid were measured in patients and control.
RESULTS: Allele frequencies of the MMP-9/C1562T polymorphism for C and T allele were 71.25% and 28.75% in patients, 87.08% and 12.92% in control respectively. The homozygote TT was more frequent in the nephrolithiasis patients group, while T allele frequency was significantly higher in the nephrolithiasis patients group than in the control group. The patients with CT and TT genotype showed a significant increase in serum MMP-9, Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Malondialdehyde (MDA), and uric acid when compared to CC genotype in patients with nephrolithiasis. The R279Q polymorphism site with regard to the relationship with nephrolithiasis was not significant.
CONCLUSION: The result indicates that patients with TT genotype had an increased risk of stones. Also, the results demonstrate that TT allele of the C1562T polymorphism in the MMP-9gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with TT genotype of MMP-9.

Matched MeSH terms: Genetic Predisposition to Disease
Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease

Wadhwa R, Aggarwal T, Malyla V, Kumar N, Gupta G, Chellappan DK, et al.

J Cell Physiol, 2019 08;234(10):16703-16723.
PMID: 30912142 DOI: 10.1002/jcp.28482

Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome-wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9).

Matched MeSH terms: Pulmonary Disease, Chronic Obstructive
Fulltext Prevalence and risk factors of hypertension in myanmar: a systematic review and meta-analysis

Naing C, Aung K

Medicine (Baltimore), 2014 Nov;93(21):e100.
PMID: 25380081 DOI: 10.1097/MD.0000000000000100

Hypertension (HPT) is the most common condition seen in primary care that can lead to health consequences and death if not detected early and treated appropriately.This study aimed to synthesize the prevalence, awareness, and control of HPT, and investigate the risk factors for HPT in Myanmar.We performed a meta-analysis of observational studies. Relevant studies were searched in electronic databases. The methodological quality of the included studies was assessed in 3 domains: selection bias, measurement bias, and bias related to data analysis. The overall prevalence and proportions was calculated using random-effect model of DerSimonian-Laird method. To identify the risk factors for HPT in Myanmar, we entered the ratio measures of the (adjusted) effect as a log odds ratio (OR) and the standard error of the log OR using generic inverse-variance weighting method. For stability of results, we performed leave-one-study-out sensitivity analysis by omitting individual studies one at a time from the meta-analysis.Seven studies (n = 20,901) were included in this analysis. Overall prevalence of HPT in Myanmar was 22% (95% confidence interval (CI): 14%-31.7%, I: 99.6%), stratified as 21.5% (95% CI: 14.1%-29.9%, I: 98.7%) in men and 22.7% (95% CI: 10.8%-34.6%, I: 99.5%) in women. Overall, prevalence of HPT increased with an advancing age of the participants. The proportions of awareness and controlled HPT were 55% (95% CI: 43%-67%, I: 97.7%) and 11% (95% CI: 6%-15%, I: 93.8%), respectively. A weak but significant association was observed between HPT and alcohol drinking (summary OR: 1.38, 95% CI: 1.14%-1.65, I: 0%) and smoking (summary OR: 1.32, 95% CI: 1.0%-1.74, I: 50%). In sensitivity analysis, when a study that made confirmation of HPT by the former World Health Organization criteria was dropped, the prevalence increased to 26% (95% CI: 20.8%-32.1%, I: 98.1%).HPT was considerably prevalent in Myanmar, while the levels of awareness and controlled HPT were low. Health promotion strategy tailored to the education on modifiable risk factors and establishment of blood pressure screening in primary health care context would be of immense value. Upcoming well-powered studies, using the standardized research design and covering more regions of the country are recommended.

Matched MeSH terms: Disease Management
Fulltext Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Silvestri V, Barrowdale D, Mulligan AM, Neuhausen SL, Fox S, Karlan BY, et al.

Breast Cancer Res, 2016 Feb 09;18(1):15.
PMID: 26857456 DOI: 10.1186/s13058-016-0671-y

BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).
METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.
RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).
CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Matched MeSH terms: Genetic Predisposition to Disease
Fulltext Docking based screening and molecular dynamics simulations to identify potential selective PDE4B inhibitor

Al-Nema M, Gaurav A, Lee VS

Heliyon, 2020 Sep;6(9):e04856.
PMID: 32984588 DOI: 10.1016/j.heliyon.2020.e04856

Inhibition of phosphodiesterase 4 (PDE4) is a promising therapeutic approach for the treatment of inflammatory pulmonary disorders, i.e. asthma and chronic obstructive pulmonary disease. However, the treatment with non-selective PDE4 inhibitors is associated with side effects such as nausea and vomiting. Among the subtypes of PDE4 inhibited by these inhibitors, PDE4B is expressed in immune, inflammatory and airway smooth muscle cells, whereas, PDE4D is expressed in the area postrema and nucleus of the solitary tract. Thus, PDE4D inhibition is responsible for the emetic response. In this regard, a selective PDE4B inhibitor is expected to be a potential drug candidate for the treatment of inflammatory pulmonary disorders. Therefore, a shared feature pharmacophore model was developed and used as a query for the virtual screening of Maybridge and SPECS databases. A number of filters were applied to ensure only compounds with drug-like properties were selected. Accordingly, nine compounds have been identified as final hits, where HTS04529 showed the highest affinity and selectivity for PDE4B over PDE4D in molecular docking. The docked complexes of HTS04529 with PDE4B and PDE4D were subjected to molecular dynamics simulations for 100ns to assess their binding stability. The results showed that HTS04529 was bound tightly to PDE4B and formed a more stable complex with it than with PDE4D.

Matched MeSH terms: Pulmonary Disease, Chronic Obstructive
Fulltext Echovirus serotypes circulating in Malaysia from 2014 to 2019

Manisya Zauri Abdul Wahid, Tengku Rogayah T. Abd. Rashid, Hariyati Md. Ali, Hamadah Mohd Shafiff, Mohd. Shamsul Samsuddin, Syarifah Nur Aisyatun Syed Mohd Salleh, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):91-91.
MyJurnal

Introduction:Echoviruses are Enteroviruses (HEVs) that infect millions of people annually worldwide, primarily paediatrics. These viruses are frequently associated with outbreaks and sporadic cases of viral meningitis, enceph-alitis, paralysis, myocarditis, severe systemic infections; and hand-foot-mouth disease. This study is a retrospective study to identify Echovirus serotypes circulating in Malaysia from January 2014 to June 2019, and their roles in outbreak prediction. This study investigated the Echovirus serotypes circulating in Malaysia from January 2014 to June 2019. Methods: A total of 13,855 inpatient samples consisting respiratory secretion, stool, tissue and body fluid from around the country were received by the Virology Unit, Institute for Medical Research between January 2014 and June 2019. The presence of HEV’s RNA was detected by qPCR. The identified positive sample was further isolated by cell culture and identified by Immunofluorescence Assay (IFA). The IFA positive samples were subjected to amplification of partial VP4 gene by RT-PCR, and proceeded to Sanger sequencing for phylogenetic analysis by using ChromasPro and MEGA Software. The sequence generated were analysed by BLAST to confirm the sequence serotypes generated. Results: Echovirus genome was detected in 0.35% (37/10,681) of the patients. The circulating Echovirus subtypes in Malaysia between January 2014 and June 2019 were Echo-11 (43.2%; 16/37), followed by Echo-6 (16.2%; 6/37); 8.1% (3/37) of Echo-7 and Echo-13, respectively. Meanwhile, other types of Echoviruses (24.3%; 9/37) such as Echo 3-5, Echo-14, Echo-16, Echo-18, Echo-25 and Echo-30 were also detected in this study. Conclusion: In this study, it has been found that Echovirus 11 serotype is the most predominant Echovirus serotype circulating in Malaysia between January 2014 and June 2019. It has been reported to cause severe diseases, such as aseptic meningitis. Therefore, the identification of circulating serotypes of Echovirus is critical to predict the Echovi-rus outbreak and to reduce the risk of developing severe disease in Malaysia.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext Is it safe to prescribe triple drugs therapy for lymphatic filariasis infection in Epidermolysis Bullosa patient? a case report

S. Izuddin, Nur Dalila Zakaria, Nur L. A., Omar K. K.

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):85-85.
MyJurnal

Introduction:Filariasis is an endemic infection in tropical and subtropical countries. The disease is caused by para-sites from the group filarodidae. Epidermolysis Bullosa, on the other hand is a group of rare genetic skin diseases that characterize by skin blister and erode facilely. Due to rarity of Epidermolysis Bullosa and uncommon occurrence of Filariasis, there is extremely limited case or paper reporting on safety profile of medication that are used to treat Filariasis patient with underlying Epidermolysis Bullosa.Serious adverse event that is anticipated in this cohort of patient are Stevens-Johnson syndrome and Mazotti reaction. Case description: Surveillance activity is necessary in high endemic localities in Sabah in order to control the spread of this mosquitoes-borne disease. The available tool is Brugia RapidTM kit, a test kit that detects filarial antibodies.A 13 year-old boy with underlying Epidemolysis Bullosa Simplex was detected during surveillance activities. It was further confirmed with night blood on microscopic slide that depicted high density of parasite (microfilaria count: 31). The WHO specifically exempted the following groups from the treatment - children under 5 years of age; pregnant women; and seriously ill individuals i.e. those who are having acute or chronic illness that makes them too sick or weak to get out of bed; and those with an illness who are life-dependent on medical intervention. This is because ingestion of the medications can result in adverse events due to the destruction of killed parasites. No guideline is available for treatment of lymphatic filariasis in rare genetic disorders. Conclusion: The recommended dosage for IDA is Ivermectin 3mcg/kg, Diethylcarbamazine 6mg/kg and Albendazole 400mg for positive patient yearly. Patient was admitted in hospital for observation treatment with the suggested dose. From the case study it shows it is safe to treat this cohort patient. However, it is advisable to treat such rare cases by case basis and in comparison to others where treatment is given in the community this patients should be treat in more control environment such in the hospital.

Matched MeSH terms: Chronic Disease
Fulltext Knowledge on life-style related Non-Communicable Disease (NCDs) among indigenous people (Orang Asli) in Negeri Sembilan, Malaysia

Muslimah Ithnin, Mohd Dzulkhairi Mohd Rani, Norsham Juliana Nordin, Mohd Azmani Sahar, Nadia Mohd Effendy, Khadijah Hasanah Abang Abdullah, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(104):52-52.
MyJurnal

Introduction:Orang Asli (OA) in Malaysia is considered vulnerable to social, economic and legal abuse. The in-crease in prevalence of Non-Communicable Diseases (NCDs) among OA was reported due to their lifestyle changes. Our study aimed to determine the level of knowledge on NCDs among OA community and its’ association with demographic factors. Methods: A cross-sectional study by face-to-face interview was conducted among consented adult OA in Jelebu, Negeri Sembilan using a validated questionnaire. Their knowledge on risk factors, complica-tions and treatment of cardiovascular diseases, diabetes mellitus, and chronic obstructive pulmonary diseases was asked. Respective thresholds and ranges for poor, moderate and good categories were set as 0-15, 15–21 and 21-28. Mann-Whitney and Kruskal-Wallis test was used to test the association between the demographic profile and knowledge score since the data was not normally distributed. Results: A total of 325 respondents with mean age 39.94 (±13.196) ranged from 18 to 83-year-old participated in this study. Majority were females (71.1%) with pri-mary education (39.1%) and mean household income of RM 615.47 (± 446.79). Their mean knowledge score was 12.82 (±9.671). Majority of them had poor knowledge (51.7%). The respondents with higher education background had significantly better knowledge score compared to lower education background (p

Matched MeSH terms: Pulmonary Disease, Chronic Obstructive
Fulltext Islamic perspective on elective abortion of Zika virus infected pregnant women

Syazwani Hamdan, Mohd Rahman Omar, Mohammad Naqib Hamdan, Ummu Aiman Faisal

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):60-60.
MyJurnal

Introduction: Zika virus infection is caused by flavivirus virus and spread by Aedes mosquitoes. Since first report-ed in 1947, it spread to various countries especially in the equatorial region including Malaysia. The infection is non-fatal to an adult. However, the major risk of its infection is towards unborn baby when the mother is infected. The vertical transmission to the foetus possess various risks include the teratogenic effect that may lead to elective abortion. Thus, the objectives of this review are to discover about Zika virus and its effect on pregnant women and to evaluate Islamic perspective about elective abortion of Zika virus-infected women. Methods: This review was done through reviewing evidence from the journals, books and reports. The data were reviewed thematically according to the objectives. Results: Studies shown that Zika virus may cause miscarriage, preterm birth, microcephaly and other malformation known as Congenital Zika syndrome. This leads to a demand for elective abortion which raised Islamic ethical issue if it is permissible. In Islam, abortion is extremely prohibited once the foetus reached 120-day of con-ception unless it causes harm to the mother’s life. But, if the foetus age is less than 120-day, abortion is permissible when the pregnancy affects the mother’s health. Abortion due to foetal microcephaly and congenital malformation is prohibited. Conclusion: Effort must be taken to prevent the spread of Zika virus to reduce the need for an elective abortion through an education Muslim community regarding elective abortion.

Matched MeSH terms: Infectious Disease Transmission, Vertical
Fulltext Malaysia’s success in eliminating mother-to-child transmission of HIV and syphilis

Mohd Nasir Abd Aziz

Malaysian Journal of Medicine and Health Sciences, 2019;15(104):24-24.
MyJurnal

Introduction: HIV and syphilis testing has been part of Malaysia’s comprehensive maternal & child health pro-gramme for more than 2 decades. Part of this antenatal package include lifelong antiretroviral (ARV) treatment to HIV+ pregnant women, free antiretroviral therapy (ART) prophylaxis/ infant formula for all HIV-exposed infants and appropriate management for syphilis positive antenatal mothers. The objective of this paper is to present the analysis of Malaysia’s achievement in obtaining the elimination of mother-to-child transmission of HIV (eMTCT) and syphilis status from the World Health Organisation (WHO). Methods: This survey is based on our surveillance and analysis of data on HIV and syphilis testing on pregnant women over a three-year period, beginning from 2015. Results: Malaysia’s national health survey revealed 97.4% of pregnant women in Malaysia had a minimum of four antenatal visits. The MOH’s surveillance system also showed 95.1% and 95.8% of pregnant women received HIV/ syphilis screening in 2015 and 2016 respectively, whilst the HIV vertical transmission rate declined from 16.12% in 2000 to 2.46% and 1.99% in 2015 and 2016 respectively. Congenital syphilis rates declined from 6.0 / 100,000 live births in 2012 to 5.0 and 4.0/ 100,000 live births in 2015 and 2016 respectively. In addition, more than 95% of antenatal mothers living with HIV received ARV and almost 100% of TPHA positive (Treponema pallidum haemagglutination) of expectant mothers received appropriate treatment. Conclusion: Based on such impressive findings, Malaysia was recognised by WHO in May 2018 as the first country in the Western Pacific Region to have successfully “eliminated” a significant public health problem.

Matched MeSH terms: Infectious Disease Transmission, Vertical
Fulltext Microencapsulated frankincense essential oil: a potential remedy and prevention of mouth diseases

Mohamed Soleiman Barre, Fathilah Ali, Mohamed Elwathig Saeed Mirghani, Noor Faizul Hadri Nordin

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):22-22.
MyJurnal

The global burden of disease studies estimated that oral diseases affected half of the world’s population (3.58 billion people) with dental caries (tooth decay) in permanent teeth being the most prevalent condition assessed. On the other hand, the increasing resistance of dental caries towards the available antimicrobials and extensive use of the controversial synthetic chemicals to overcome these problems have attracted the scientific community’s attention to the search for new cost-effective remedies of natural products. Frankincense or Boswellia species are highly import-ant aromatic plants belonging to the Burseraceae family. The present study will focus on an in-vitro anti-inflamma-tion and anti-bacterial activity of Boswellia carterii (BC) Essential oil (EO) encapsulated into the Gum Arabic (GA) polymer. Thus, certain mouth pathogenic bacteria, which are the main contributors to dental caries and gingivitis, namely (Streptococcus mutans and Lactobacillus species), and their in-vitro responses to the defined micro-particles, will pave the way to introduce a new potential remedy to the forth mentioned problems.

Matched MeSH terms: Global Burden of Disease
Fulltext Protein and gene expression of leukemia stem cells markers in acute myeloid leukemia

Amrina Mohamad Amin, Maha Abdullah, Sabariah Md Noor, Raudhawati Osman, Wan Hayati Mohd Yaacob, Cheong Soon Keng

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):23-23.
MyJurnal

Introduction: Acute myeloid leukaemia (AML) is a clonal haematological neoplasm characterised by proliferation of immature myeloid cells in the bone marrow resulting in impairment normal cell development in bone marrow. This leads to anaemia, thrombocytopenia and neutropenia. AML primarily affects older adults, with a median age at diagnosis of 69 years but is also seen in all other age groups. AML is recognized as a kind of cancer with marked heterogeneity in both biology of the cells and reactions to treatment. Treatment with intensive chemotherapy regi-mens of adult AML patients who are ≤ 60 years old results in hematologic remission in about 35% of patients, but at least 30% of these patients will experience a relapse. Mechanism leading to early relapse is still unclear. Leukaemia stem cell (LSC) is shown to correlate with poor prognosis. Biomarkers such as aldehyde dehydrogenase (ALDH) and CD34+CD38- have been identified as potential LSC biomarkers in previous studies. The objective of this study is to examine the expression of such markers for LSC and determine the association. Methods: Peripheral blood or bone marrow samples from untreated, newly diagnosed acute myeloid leukemias of all age, gender and race were collect-ed from Hospital Melaka and Kelang. Diagnosis of AML is based on WHO classification which include morphology, cytochemistry, immunophenotyping and cytogenetics. Mononuclear cells were isolated from bone marrow aspirate samples by gradient density centrifugation on Ficoll-Hypaque. Immunophenotyping using CD13, CD14, CD33, CD34, CD38 and ALDH were carried out to identify the presence and proportion of the various populations of inter-est. Results: There was a strong, positive correlation between ALDH and CD34+CD38- cell population, which was statistically significant (rs = 0.5989, p< 0.05). Conclusion: The strong correlation of ALDH activity and CD34+CD38- expression supported the potential of these biomarkers to identify LSCs cell in AML patients. However, due to the heterogeneity of AML, further studies using more markers and larger sample size are needed to determine the validity and to correlate with disease-free survival rate of AML patients.

Matched MeSH terms: Disease-Free Survival
Fulltext Targeting bladder cancer stem cells using Newcastle disease virus

Arcana Thirumorthy, De-Ming Chau, Khatijah Yusoff, Abhi Veerakumarasivam

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):24-24.
MyJurnal

Introduction: Bladder cancer is associated with high risk of tumour recurrence and therapeutic resistance. Cancer stem cells (CSC) within a particular tumour are postulated to drive tumorigenesis and influence tumour behaviour. Recent studies have shown that Newcastle disease virus (NDV) is able to selectively kill and exert a strong oncolytic effect against various cancer types. However little is known about the oncolytic effect of NDV against CSC. In this study, the oncolytic effect of NDV against putative bladder CSC was examined. Methods: Putative bladder CSC was selectively grown in the form of 3D-spheroids from six different bladder cancer cell lines. The spheroid cells were characterised for their stemness properties to ensure that these cells truly represent CSC. This was conducted via the analysis of CSC associated genes and cell surface markers expression. Subsequently, the oncolytic effect of the wild-type NDV-AF2240 strain against the bladder cancer spheroids was investigated. Results: All the spheroids expressed significantly high levels of CSC-associated genes. Flow-cytometry analysis revealed that the expression pattern of the CSC-associated surface markers was different in the spheroid cells; suggesting heterogeneity in the expression signatures of these cells. The infection of spheroids with NDV showed that the NDV was able to target bladder cancer spheroids but there was a spectrum of response across the different spheroids. Intriguingly, NDV was able to persistently infect bladder cancer spheroids that were not sensitive towards NDV infection as the presence of NDV viral genes were detected in the spheroid cells. The NDV persistently infected bladder cancer spheroids were resistant to superinfection and developed an antiviral state by expressing low levels of interferon-beta (IFN-b). NDV persistency of infection affects the process of epithelial to mesenchymal transition (EMT) of cancer cells as the spheroid forming ability of an established NDV persistently infected bladder cancer cell line, EJ28-PI was shown to be impaired. The EJ28-PI cells expressed significantly high levels of the EN2 gene. Knockdown of the EN2 expression reduced the viability of EJ28-PI cells; suggesting a role for EN2 in mediating NDV persistency of infection in cancer cells. Conclusion: Bladder CSC gene expression signatures influence the efficacy of NDV-mediated oncolysis. Our current work is focused on identifying genes and signalling pathways that influence NDV-mediated oncolysis us-ing whole-transcriptomic sequencing. The findings of this study can potentially be used to enhance the efficacy of NDV-mediated oncolysis and accelerate the translation of NDV as an oncotherapeutic agent in the clinic.

Matched MeSH terms: Newcastle disease virus

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