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Biomedical subjects

Javed Khan

Publications and source records attributed to Javed Khan.

7 recordsLinked to original sources
PubMed2003

Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease.

Multiple sclerosis (MS) and other T cell-mediated autoimmune diseases develop in individuals carrying a complex susceptibility trait, probably following exposure to various environmental triggers. Owing to the presumed weak influence of single genes on disease predisposition and the recognized genetic heterogeneity of autoimmune disorders in humans, candidate gene searches in MS have been difficult. In an attempt to identify molecular markers indicative of disease status rather than susceptibility genes for MS, we show that gene expression profiling of peripheral blood mononuclear cells by cDNA microarrays can distinguish MS patients from healthy controls. Our findings support the concept that the activation of autoreactive T cells is of primary importance for this complex organ-specific disorder and prompt further investigations on gene expression in peripheral blood cells aimed at characterizing disease phenotypes.

Adult↗
PubMed2002

Cyclooxygenase-2 expression in pediatric sarcomas.

Therapies for metastatic pediatric sarcomas have reached maximum tolerated doses, but continue to provide suboptimal cure rates. Additionally, these treatments are associated with numerous short- and long-term side effects. Therefore, the search for newer, less toxic therapeutic agents is warranted. Overexpression of the inducible enzyme, cyclooxygenase-2 (COX-2), has been discovered in a variety of adult solid tumors and numerous studies have shown COX-2 inhibitors to have significant antiproliferative effects. Therefore, we sought to determine the expression of COX-2 in pediatric sarcomas. We evaluated rhabdomyosarcoma (RMS), osteosarcoma (OS), and Ewing sarcoma (EWS) samples for COX-2 expression by immunohistochemical analysis as well as by cDNA microarray analysis. COX-2 expression was detected in 48/58 (82.8%) tumors by immunohistochemistry and in an additional 52/59 (88.1%) tumors tested by microarray gene analysis. There was a trend toward increased COX-2 expression in metastatic rhabdomyosarcoma and osteosarcoma, though it did not reach clinical significance. The degree of COX-2 immunoreactivity did not vary significantly with other clinicopathologic features such as age, gender, or histologic classification. We conclude that the majority of these pediatric sarcoma samples express COX-2 to varying degrees. Therefore, studies testing the efficacy of COX-2 inhibitors in the treatment of pediatric sarcomas are warranted.

Adolescent↗
PubMed2002

Ewing sarcoma family of tumors express adenovirus receptors and are susceptible to adenovirus-mediated oncolysis.

PURPOSE: Attenuated viruses derived from adenoviruses (Ad) that kill tumor cells (oncolysis) are currently in clinical trials for selected cancers. Some cancers have proven resistant to Ad infection due to low expression of viral receptors. The authors sought to determine whether members of the Ewing sarcoma family of tumors (ESFTs) express Ad receptors and are sensitive to Ad-mediated oncolysis. METHODS: Using flow cytometry, the authors tested a panel of cell lines derived from ESFTs for expression of both the Ad receptor, coxsackie-adenovirus receptor (CAR), and the cellular mediator of Ad uptake, alpha(v)-integrins, as well as for Ad-mediated gene transduction. Cell survival assays were used to assess the sensitivity to Ad-mediated oncolysis. Immunohistochemistry was used to assess CAR expression in primary tumors. mRNA levels of CAR in cell lines and tumor samples were also queried from a cDNA expression database. RESULTS: The ESFT cell lines expressed CAR and alpha(v)-integrins, showed high levels of gene transduction, and were highly sensitive to viral oncolysis. Primary tumor samples were positive for CAR expression by immunohistochemistry. Microarray analysis confirmed CAR expression in ESFT cell lines and tumors. CONCLUSIONS: Ewing sarcoma cells express the Ad receptors and are sensitive to Ad oncolysis. Treatment of Ewing sarcoma using conditionally replicative adenoviruses should be explored.

Adenoviridae↗
PubMed2002

Analyzing array data using supervised methods.

Pharmacogenomics is the application of genomic technologies to drug discovery and development, as well as for the elucidation of the mechanisms of drug action on cells and organisms. DNA microarrays measure genome-wide gene expression patterns and are an important tool for pharmacogenomic applications, such as the identification of molecular targets for drugs, toxicological studies and molecular diagnostics. Genome-wide investigations generate vast amounts of data and there is a need for computational methods to manage and analyze this information. Recently, several supervised methods, in which other information is utilized together with gene expression data, have been used to characterize genes and samples. The choice of analysis methods will influence the results and their interpretation, therefore it is important to be familiar with each method, its scope and limitations. Here, methods with special reference to applications for pharmacogenomics are reviewed.

Artificial Intelligence↗