A5051566309- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Histone Deacetylase Inhibitors Research
- Pharmacogenetics and Drug Metabolism
- Cancer-related molecular mechanisms research
- PARP inhibition in cancer therapy
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Estrogen and related hormone effects
- Lung Cancer Research Studies
- RNA modifications and cancer
- Drug Transport and Resistance Mechanisms
- Cancer therapeutics and mechanisms
- Hormonal Regulation and Hypertension
- Brain Metastases and Treatment
- Cancer Cells and Metastasis
- Neonatal Health and Biochemistry
- Ferroptosis and cancer prognosis
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Cancer, Lipids, and Metabolism
- Inflammatory mediators and NSAID effects
- Cancer Research and Treatments
- Breast Cancer Treatment Studies
Singapore Institute for Clinical Sciences
2012-2021
National Neuroscience Institute
2012-2021
Agency for Science, Technology and Research
2012-2021
Nanyang Technological University
2015-2018
National Cancer Centre Singapore
2007-2015
National University of Singapore
2007-2015
Institute of Molecular and Cell Biology
2015
Kyoto University
2012
Duke-NUS Medical School
2012
National Cancer Centre Japan
2012
In the human brain, microRNAs (miRNAs) from microRNA-376 (miR-376) cluster undergo programmed “seed” sequence modifications by adenosine-to-inosine (A-to-I) editing. Emerging evidence suggests a link between impaired A-to-I editing and cancer, particularly in high-grade gliomas. We hypothesized that disruption of alters expression genes regulating glioma tumor phenotypes. By sequencing miR-376 cluster, we show overall miRNA frequencies were reduced Specifically gliomas, miR-376a* accumulated...
Significance Glioblastoma (GBM) cells develop intrinsic or acquired insensitiveness to BET bromodomain inhibitors (BBIs) yet persistent protein dependency. Selective degradation of proteins by a next-generation chemical compound undermines the dependency and exerts superior antineoplastic effects over inhibition bromodomain. Given significant difference between in GBM cells, chemically induced serves as promising strategy overcome anticipated clinical BBIs resistance.
Abstract Intratumoral heterogeneity is a hallmark of glioblastoma (GBM) tumors, thought to negatively influence therapeutic outcome. Previous studies showed that mesenchymal tumors have worse outcome than the proneural subtype. Here we focus on STAT3 as its activation precedes proneural-mesenchymal transition. We first establish gene signature stratifies GBM patients into -high and -low cohorts. inhibitor treatment selectively mitigates cell viability tumorigenicity in orthotopic mouse...
The influence of three high frequency ABCB1 polymorphisms (c. 1236C>T , c. 2677G>A/T and 3435C>T ) the ABCG2 421C>A polymorphism on disposition doxorubicin in Asian breast cancer patients receiving adjuvant chemotherapy was investigated present study. allelic 1236T 2677T 2677A 3435T variants were 60%, 38%, 7%, 22%, respectively, 421A allele 23%. Pairwise analysis showed increased exposure levels to harboring at least one ( P = 0.03). Patients homozygous for CC‐GG‐CC genotype had...
Mutations in the parkin gene, which encodes a ubiquitin ligase, are major genetic cause of parkinsonism. Interestingly, also plays role cancer as putative tumor suppressor, and gene is frequently targeted by deletion inactivation human malignant tumors. Here, we investigated potential suppressor for gliomas. We found that expression was dramatically reduced glioma cells. Restoration promoted G(1) phase cell-cycle arrest mitigated proliferation rate cells vitro vivo. Notably,...
Background:Cell surface sialylation is associated with tumor cell invasiveness in many cancers. Glioblastoma the most malignant primary brain and highly infiltrative. ST3GAL1 sialyltransferase gene amplified a subclass of glioblastomas, its role self-renewal remains unexplored.
The present study aimed to identify polymorphic genes encoding carbonyl reductases ( CBR1 , CBR3 ) and investigate their influence on doxorubicin disposition in Asian breast cancer patients n = 62). Doxorubicin (60 mg/m 2 was administered every 3 weeks for four six cycles the pharmacokinetic parameters were estimated using non‐compartmental analysis (WinNonlin). Mann–Whitney U ‐test used assess genotypic–phenotypic correlations. Five (– 48G>A c. 219G>C 627C>T c.693G>A, +...
Abstract Purpose: To characterize pregnane X receptor (PXR) polymorphic variants in healthy Asian populations [Chinese, Malay and Indian (n = 100 each)], to investigate the association between PXR haplotypes hepatic mRNA expression of its downstream target genes, CYP3A4 ABCB1, as well their influence on clearance doxorubicin breast cancer patients. Experimental Design: genotyping was done by direct DNA sequencing, haplotype clusters were derived expectation-maximization algorithm....
The transient receptor potential melastatin 4 (TRPM4) channel has been suggested to play a key role in the treatment of ischemic stroke. However, vivo evaluation TRPM4 channel, particular by direct suppression, is lacking. In this study, we used multimodal imaging assess edema formation and quantify amount metabolically functional brain salvaged after rat model stroke reperfusion. upregulation endothelium emerges as early 2 h post-stroke induction. Expression was suppressed directly with...
Molecular profiling of the most aggressive brain tumor glioblastoma (GBM) on basis gene expression, DNA methylation, and genomic variations advances both cancer research clinical diagnosis. The enhancer architectures regulatory circuitries governing tumor-intrinsic transcriptional diversity subtype identity are still elusive. Here, by mapping H3K27ac deposition, we analyze active landscapes across 95 GBM biopsies, 12 normal tissues, 38 cell line counterparts. Analyses differentially...
SLCO1B3 is an influx transporter located at the hepatocyte basolateral membrane and it involved in uptake of a broad range drug substrates including docetaxel. The pharmacogenetics not well characterized previous vivo vitro studies reported conflicting results with regards to functional effects limited number polymorphisms that were studied. Docetaxel displays wide interindividual variability its pharmacokinetics pharmacodynamics understanding might provide clinical benefits guiding...
What is already known about this subject • Recent studies on pharmacogenetics of warfarin have implicated apolipoproteinE ( APOE ) polymorphisms to influence the vitamin K dependent coagulation cascade and hence efficacy warfarin. Studies among Caucasian African Americans showed a significant but conflicting role (APOE) isoforms in pharmacogenetics. The contribution influencing variations requirements Asian subjects remains be investigated. study adds This first report population Asians...
Aims: We explore the role of an elevated O2−:H2O2 ratio as a prosurvival signal in glioma-propagating cells (GPCs). hypothesize that depleting this sensitizes GPCs to apoptotic triggers. Results: observed conferred enhanced resistance GPCs, and depletion by pharmacological genetic methods sensitized established reactive oxygen species (ROS) Index quantitative measure normalized determined its utility predicting chemosensitivity. Importantly, mice implanted with reduced ROS demonstrated...
Patient-derived glioma-propagating cells (GPC) contain karyotypic and gene expression profiles that are found in the primary tumor. However, their clinical relevance is unclear. We ask whether GPCs contribute to disease progression survival outcome patients with glioma by analyzing profiles.We tapped into public sources of GPC data derived a signature distinguishing oligodendroglial from glioblastoma multiforme (GBM) GPCs. By adapting method biology, Connectivity Map, we interrogated its...
Gliomas are the most devastating of primary adult malignant brain tumors. These tumors highly infiltrative and can arise from cells with extensive self-renewal capability chemoresistance, frequently termed glioma-propagating (GPCs). GPCs thus plausible culprits tumor recurrence. Treatment strategies that eradicate will greatly improve disease outcome. Such findings support use as in vitro cellular systems for small-molecule screening. However, nuances using a screening platform not trivial....
Parkinson's disease (PD) is an age-dependent neurodegenerative condition. Leucine-rich repeat kinase 2 (LRRK2) mutations are the most frequent cause of sporadic and autosomal dominant PD. The exact role LRRK2 protective variants (R1398H, N551K) together with a pathogenic mutant (G2019S) in aging neurodegeneration unknown. We generated following myc-tagged UAS-LRRK2 transgenic Drosophila: (WT), N551K, R1398H, G2019S single allele, double-mutants (N551K/G2019S or R1398H/G2019S). alone were...
13501 Background: Doxorubicin, a topoisomerase II inhibitor, is widely used in the management of breast cancer. The aim present study was to characterize population pharmacokinetics doxorubicin among Asian cancer patients and explore influence patient covariates on its disposition characteristics. Methods: patients(N=51) receiving adjuvant chemotherapy with Adriamycin(A) Cyclophosphamide(C) were recruited for study. Patients received (range:56–61 mg/m2) as 20 minutes intravenous infusion...
Abstract Cell surface sialylation has been associated with tumor cell invasiveness in several cancers. Patients grade IV glioblastoma multiforme (GBM) often show a median survival period of fifteen months, even the current standard-of-care treatment. Among reasons for this poor prognosis lies cellular and molecular heterogeneity cells. The Cancer Genome Atlas efforts have shown that histologically identical GBM tumors can be divided into four subtypes based on gene expression, each subtype...