Biomedical subjects

Sher Singh

Publications and source records attributed to Sher Singh.

7 recordsLinked to original sources

PubMed2007

A five-gene signature and clinical outcome in non-small-cell lung cancer.

BACKGROUND: Current staging methods are inadequate for predicting the outcome of treatment of non-small-cell lung cancer (NSCLC). We developed a five-gene signature that is closely associated with survival of patients with NSCLC. METHODS: We used computer-generated random numbers to assign 185 frozen specimens for microarray analysis, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, or both. We studied gene expression in frozen specimens of lung-cancer tissue from 125 randomly selected patients who had undergone surgical resection of NSCLC and evaluated the association between the level of expression and survival. We used risk scores and decision-tree analysis to develop a gene-expression model for the prediction of the outcome of treatment of NSCLC. For validation, we used randomly assigned specimens from 60 other patients. RESULTS: Sixteen genes that correlated with survival among patients with NSCLC were identified by analyzing microarray data and risk scores. We selected five genes (DUSP6, MMD, STAT1, ERBB3, and LCK) for RT-PCR and decision-tree analysis. The five-gene signature was an independent predictor of relapse-free and overall survival. We validated the model with data from an independent cohort of 60 patients with NSCLC and with a set of published microarray data from 86 patients with NSCLC. CONCLUSIONS: Our five-gene signature is closely associated with relapse-free and overall survival among patients with NSCLC.

Aged↗

PubMed2006

A kinetic-dynamic model for regulatory RNA processing.

A kinetic-dynamic model was proposed to simulate RNA processing by determining four essential reaction rates, including the rates of transcription, pre-mRNA turnover, pre-mRNA splicing, and mRNA decay. A family competition evolutionary algorithm (FCEA) was adapted herein to approximate these rates. Several artificial datasets were used to verify the correctness and robustness of the FCEA. The model was finally applied on time series data of yeast prp4-l mutant cells for determination of rates of RNA processing. Based on the FCEA, the model indicated that the pre-mRNA splicing was decreased in the mutant cells as well as the possible effects on transcription, pre-mRNA turnover, and mRNA decay, which was consistent with surveyed literature.

Kinetics↗

PubMed2006

Characterization and gene expression profiling of five new human embryonic stem cell lines derived in Taiwan.

Many human embryonic stem cell (hESC) lines have been reported, but only a few of them have been fully characterized. In this report, five new hESC lines were derived from 32 discarded blastocysts in Taiwan, and these lines were continuously cultured on mitotically inactivated mouse embryonic fibroblast (MEF) feeder layer in the hESC medium for more than 44 passages and underwent freezing/thawing processes. All five hESC lines expressed characteristic undifferentiated hESC markers, such as SSEA-4, TRA-1-81, alkaline phosphatase, TERT, and the transcription factors POU5F1 (OCT4) and NANOG. hESC lines T1 and T3 possess normal female karyotypes, whereas lines T4 and T5 are normal male, but line T2 is male trisomy 12 (47XY,+12). hESC lines T1, T2, T3, and T5 were able to produce teratomas in severe combined immunodeficient (SCID) mice, and line T4 could only form embryoid bodies (EBs) in vitro. Global gene expression profiles of these five newly derived hESC lines were analyzed using the Affymetrix human genome U133 plus 2.0 GeneChip. The results showed that 4,145 transcripts, including 19% of unknown functions, were detected in all five hESC lines. Comparison of the 4,145 genes commonly expressed in the five hESC lines with those genes expressed in teratomas produced by the hESC line T1 and placenta revealed 40 genes exclusively expressed in all five hESC lines. These 40 genes include the previously reported stemness genes, such as POU5F1 (OCT4), NANOG, TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 responsible for self-renewal and pluripotent differentiation. The global gene expression analysis also indicated that the transforming growth factor-beta (TGF-beta)/activin branch components inhibin BC, ACVR2A, ACVR1 (ALK2), TGFBR1 (ALK5), and SMAD2 were found to be highly expressed in undifferentiated states of these five hESC lines and decreased upon differentiation. In short, the hESC nature of these five hESC lines is supported by the undifferentiated state, extensive renewal capacity, and pluripotency, including the ability to form teratomas and/or EBs. These cell lines will be useful for human embryonic stem cell biology and drug development.

Animals↗

PubMed2005

Analysis of gene expression in single human oocytes and preimplantation embryos.

Little is known about the gene expression in human oocytes and early embryo development because of the rare availability of the materials. The recent advancement of biotechnology has allowed one to analyze the gene expression in single human oocytes and preimplantation embryos. Gene expression of human lactate dehydrogenase isozymes (LDH-A, LDH-B, and LDH-C) and small ubiquitin-like modifier isoforms (SUMO-1, SUMO-2, and SUMO-3) in four oocytes, two 4-cell and three 8-cell embryos was studied using the reverse transcription-polymerase chain reaction. The mRNAs for SUMO-1, SUMO-2, SUMO-3, and LDH-B (heart) were detected in all of oocytes, 4- and 8-cell embryos. The mRNA for LDH-A (muscle) was detected in two of four oocytes and one of three 8-cell embryos. However, the mRNA for testis-specific LDH-C was not detected at all as expected. A cDNA microarray containing 9600 cDNA spots was used to investigate differential expression of human genes in oocyte, 4-cell and 8-cell embryos. The expression of 184, 29, and 65 genes was found to have a value more than twofold above the median value of all genes expressed in oocyte, 4- and 8-cell embryos, respectively, indicating that the expression of some zygotic genes had already occurred at 4-cell embryo.

Actins↗

PubMed2005

Dynamical coupling of PBPK/PD and AUC-based toxicity models for arsenic in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan.

A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models were developed for arsenic (As) in tilapia Oreochromis mossambicus from blackfoot disease area in Taiwan. The PBPK/PD model structure consisted of muscle, gill, gut wall, alimentary canal, and liver, which were interconnected by blood circulation. We integrate the target organ concentrations and dynamic response describing uptake, metabolism, and disposition of As and the associated area-under-curve (AUC)-based toxicological dynamics following an acute exposure. The model validations were compared against the field observations from real tilapia farms and previously published uptake/depuration experimental data, indicating that predicted and measured As concentrations in major organs of tilapia were in good agreement. The model was utilized to reasonably simulate and construct a dose-dependent dynamic response between mortality effect and equilibrium target organ concentrations. Model simulations suggest that tilapia gills may serve as a surrogate sensitive biomarker of short-term exposure to As. This integrated As PBPK/PD/AUC model quantitatively estimates target organ concentration and dynamic response in tilapia and is a strong framework for future waterborne metal model development and for refining a biologically-based risk assessment for exposure of aquatic species to waterborne metals under a variety of scenarios.

Animals↗

PubMed2005

Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system.

The atypical teratoid/rhabdoid tumor, primary to the central nervous system, is a highly malignant and aggressive neoplasm of infancy and childhood. Although having distinct biological features and clinical outcomes, it is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma. To further distinguish the underlying pathogenesis and to identify biological markers for clinical use, an atypical teratoid/rhabdoid tumor-derived cell line was established and its gene expression pattern analyzed in comparison to the human astrocyte SVG12 cell line and the human DAOY medulloblastoma cell line using a complementary DNA microarray method. The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients. Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.

Cell Line↗

PubMed2003

Acute toxicity and bioaccumulation of arsenic in tilapia (Oreochromis mossambicus) from a blackfoot disease area in Taiwan.

The general objective of our work was to determine the acute toxicity and bioaccumulation of arsenic (As) in tilapia (Oreochromis mossambicus) from the blackfoot disease (BFD) area in Taiwan. The average concentration of As in pond water ranged from 17.8 to 49 microg L(-1). Acute toxicity tests showed that the As concentration that caused toxicity to tilapia ranged from 69 060 microg As L(-1), in the 24-h toxicity test, to 28 680 microg As L(-1), in the 96-h toxicity test. We measured As concentrations in various tissues of tilapia to identify the affinities of tissues for As. Significant correlations were found among the As concentrations in all tissues. The highest bioconcentration factor (BCF) was found in the intestine (maximum value: 2270). The order of BCFs was: intestine > stomach > liver approximately gill > muscle. Arsenic concentrations in all tissues were allometric, negatively correlating with fish body weight [r(2) = 0.63 +/- 0.045 (mean +/- SE), p < 0.05]. Our results also revealed that As concentrations in muscle tissue were positively correlated with As accumulation in the viscera (r(2) = 0.85, p < 0.05). Significantly higher concentrations of As were obtained in the viscera of tilapia [12.65 +/- 10.17 microg g(-1) dry wt (mean +/- SD)] than in the muscle tissue (3.55 +/- 0.42 microg g(-1) dry wt). Our results suggest that a simple way of reducing the health risk associated with consuming tilapia is to trim and cook the fish properly, that is, removing the viscera of tilapia can greatly reduce the amount of As ingested and consequently reduce the health risks.

Animals↗