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Yusoff N.H.,Basic science and Oral Biology Unit | Alshehadat S.A.,Basic science and Oral Biology Unit | Azlina A.,Basic science and Oral Biology Unit | Azlina A.,Human Genome Center | And 3 more authors.
Tropical Life Sciences Research | Year: 2015

In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells. © Penerbit Universiti Sains Malaysia, 2015.

Nizam Z.M.,Human Genome Center | Aziz A.A.A.,Human Genome Center | Kaur G.,Institute for Research in Molecular Medicine INFORMM | Hassan M.R.A.,Hospital Sultanah Bahiyah | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2013

Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease.

Sheikh S.A.,Universiti Sains Malaysia | Roshan T.M.,Lady Davis Institute for Medical Research | Khattak M.N.,Singapore Clinical Research Institute | Baig A.A.,Human Genome Center | And 2 more authors.
Menopause International | Year: 2011

Objectives. In healthy postmenopausal women (PMW) increased platelet activation has been associated with adverse cardiovascular events. There is much debate about the relationship between platelet function and serum estradiol level in PMW. This study assessed the effect of short-term oral estrogen replacement therapy (ERT) on platelet activation markers (CD62P and PAC-1) and its correlation with age and body mass index (BMI) among healthy PMW. Methods. A prospective intervention study was conducted at Hospital University Sains Malaysia, involving 48 healthy PMW who were evaluated for platelet activation marker levels as determined by flow cytometry, before and after two weeks of oral ERT with 0.625 mg of conjugated equine estrogen once daily. The pre- and post-ERT platelets activation markers difference was analysed by paired t-test. Results. The pre-ERT, mean ± SD percentage levels of CD62P and PAC-1 were significantly reduced from 7.00 ± 5.91 and 41.75 ± 26.85 to 3.05 ± 2.47 and 20.86 ± 19.02, respectively, after two weeks of ERT (P value < 0.001). The correlation of platelet activation markers was significant with estradiol but not with age and BMI. Conclusion. Short-term ERT leads to reduction in platelet activity, which might contribute to protection against cardiovascular diseases in healthy PMW.

Shahpudin S.N.M.,Human Genome Center | Shahpudin S.N.M.,Universiti Sains Malaysia | Mustapha M.A.,Human Genome Center | Aziz A.A.A.,Human Genome Center | And 7 more authors.
International Medical Journal | Year: 2011

Background: Colorectal cancer (CRC) is a multifactorial disease with factors including dietary and lifestyle habits and genetic predisposition contributing to its etiopathogenesis. Even though the genetic predisposing factors are still unclear, genetic polymorphisms of genes encoding enzymes involved in xenobiotic metabolic pathways that activate or inactivate dietary carcinogens have been proposed as candidate genes. Three members of the Gluthathione S-Transferase (GSTs) family GSTP1, GSTT1 and GSTM1 have been analyzed in Malaysian population for polymorphic variants, and to elucidate their role in colorectal carcinogenesis. Objective: To determine the frequencies of GSTPI, GSTTI and GSTMI genotypes in 111 histopathologically confirmed CRC patients and 128 healthy controls and to evaluate the association risk of GSTPI, GSTTI and GSTMI genotypes on CRC predisposition. Material and Methods: Peripheral blood from the study subjects were collected in EDTA tubes and genomic DNA extracted using QIAGEN kit. The GSTPI Ile105Val polymorphism was analyzed by PCR-RFLP technique using BsmA1 restriction enzyme. The presence or absence of GSTM1 and GSTT1, genes were determined using a multiplex PCR protocol with albumin as the housekeeping gene. The resulting PCR fragments were separated on 2.0% agarose gel for GSTP1 and 3.0% agarose gel electrophoresis for the GSTT1 and GSTM1. Results and Conclusion: On evaluating the CRC risk association with variant genotypes singly, GSTTI null genotype was associated significantly with an elevated risk (OR 1.804, 95%CI: 1.065-3.361, p=0.027). When the polymorphic genotypes were analyzed in combination, the combination genotypes of GSTPI Val/Val/GSTM+/GSTTI+ (OR 4.000), Val/Val/GSTMI-/GSTTI- (OR 3.000), and GSTPI Ile/Ile/GSTMI+/GSTTI- (OR 2.833) showed higher associated risk for CRC susceptibility, however the risk values were not statistically significant. Further studies involving larger sample size may help to identify the more specific risk groups and to determine factors of importance in CRC development. © 2011 Japan International Cultural Exchange Foundation & Japan Health Sciences University.

Fang H.,University of Chicago | Yamaguchi R.,Human Genome Center | Liu X.,Section of Hematology Oncology | Daigo Y.,Shiga University of Medical Science | And 6 more authors.
OncoImmunology | Year: 2014

Immune responses play a critical role in various disease conditions including cancer and autoimmune diseases. However, to date, there has not been a rapid, sensitive, comprehensive, and quantitative analysis method to examine T-cell or B-cell immune responses. Here, we report a new approach to characterize T cell receptor (TCR) repertoire by sequencing millions of cDNA of TCR α and β chains in combination with a newly-developed algorithm. Using samples from lung cancer patients treated with cancer peptide vaccines as a model, we demonstrate that detailed information of the V-(D)-J combination along with complementary determining region 3 (CDR3) sequences can be determined. We identified extensive abnormal splicing of TCR transcripts in lung cancer samples, indicating the dysfunctional splicing machinery in T lymphocytes by prior chemotherapy. In addition, we found three potentially novel TCR exons that have not been described previously in the reference genome. This newly developed TCR NGS platform can be applied to better understand immune responses in many disease areas including immune disorders, allergies, and organ transplantations. © 2014 Taylor & Francis Group, LLC.

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