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23 results on '"Amin, Kunjlata M"'

4. Differential sensitivity of thoracic malignant tumors to adenovirus-mediated drug sensitization gene therapy

Author

Smythe, W.Roy, Hwang, Harry C., Elshami, Ashraf A., Amin, Kunjlata M., Albelda, Steven M., and Kaiser, Larry R.

Subjects
Cancer -- Drug therapy, Cancer -- Health aspects, Gene therapy -- Health aspects, Genetic research -- Health aspects, Ganciclovir -- Health aspects, Integrins -- Health aspects, Lung cancer, Non-small cell -- Drug therapy, Lung cancer, Non-small cell -- Health aspects, Health
Abstract

Byline: W.Roy Smythe, Harry C. Hwang, Ashraf A. Elshami, Kunjlata M. Amin, Steven M. Albelda, Larry R. Kaiser Abstract: Malignant mesothelioma may prove to be an attractive candidate for somatic gene therapy with replication-deficient recombinant adenovirus transfer of a toxic, or drug sensitization gene. Transfer of the herpes simplex thymidine kinase type I gene (HSV tk), followed by exposure to the acyclic nucleoside drug ganciclovir, has been shown to be an effective tumor cell killing system. To study generalized applicability, we tested a number of thoracic malignant cell lines for their sensitivity to gancyclovir after infection with an adenoviral vector containing the HSV tk gene (Ad.RSVtk). Using the concentration of gancyclovir required to kill 50% of the cells (IC50) as a measure of sensitivity, we detected variable sensitivity among cell lines, with mesothelioma most sensitive (IC50 = 0.075 to 2.8 [mu]mol/L gancyclovir), and non-small-cell carcinoma lines having an intermediate sensitivity (IC50 = 1.5 to 100 [mu]mol/L). In contrast, an ovarian carcinoma line was extremely resistant (IC50 > 2000 [mu]mol/L). To study the possible mechanisms for these differences, we studied cell lines with regard to their ability to be infected with an adenoviral vector containing a marker gene (Ad.CMVlacZ) and expression of the vitronectin receptor [alpha].sub.v (an integrin cell adhesion molecule shown to be required for adenovirus internalization after initial binding). We found that the degree of lacZ transduction correlated with HSV tk sensitivity, whereas vitronectin receptor expression did not, suggesting that differences in initial viral binding ability, rather than internalization, may explain the sensitivity differences seen in vitro. (J THORAC CARDIOVASC SURG 1995;109:626-31) Author Affiliation: Philadelphia, Pa Article Note: (footnote) [star] From the Department of Surgery, Section of General Thoracic Surgerya, and the Department of Medicine, Section of Pulmonary and Critical Careb, The Thoracic Oncology Research Laboratory, University of Pennsylvania Medical Center, Philadelphia, Pa., [star][star] Read at the Seventy-fourth Annual Meeting of The American Association for Thoracic Surgery, New York, N.Y., April 24-27, 1994., a Address for reprints: Larry R. Kaiser, MD, The Thoracic Oncology Research Laboratory, Hospital of the University of Pennsylvania, 809 Maloney Bldg., 3600 Spruce St., Philadelphia, PA 19104., aa 0022-5223/95 $3.00 + 0, acents 12/6/62042

Published
1995

6. Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy

Author

Sterman, Daniel H., primary, Recio, Adriana, additional, Vachani, Anil, additional, Sun, Jing, additional, Cheung, Lumei, additional, DeLong, Peter, additional, Amin, Kunjlata M., additional, Litzky, Leslie A., additional, Wilson, James M., additional, Kaiser, Larry R., additional, and Albelda, Steven M., additional

Published
2005
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14. Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy in Patients with Localized Malignancy: Results of a Phase I Clinical Trial in Malignant Mesothelioma

Author

Sterman, Daniel H., primary, Treat, Joseph, additional, Litzky, Leslie A., additional, Amin, Kunjlata M., additional, Coonrod, Laura, additional, Molnar-Kimber, Katherine, additional, Recio, Adri, additional, Knox, Linda, additional, Wilson, James M., additional, Albelda, Steven M., additional, and Kaiser, Larry R., additional

Published
1998
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15. Safety of Intrapleurally Administered Recombinant Adenovirus Carrying Herpes Simplex Thymidine Kinase DNA Followed by Ganciclovir Therapy in Nonhuman Primates

Author

KUCHARCZUK, JOHN C., primary, RAPER, STEVEN, additional, ELSHAMI, ASHRAF A., additional, AMIN, KUNJLATA M., additional, STERMAN, DANIEL H., additional, WHEELDON, ERIC B., additional, WILSON, JAMES M., additional, LITZKY, LESLIE A., additional, KAISER, LARRY R., additional, and ALBELDA, STEVEN M., additional

Published
1996
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22. Gene expression profiling of malignant mesothelioma.

Author

Singhal S, Wiewrodt R, Malden LD, Amin KM, Matzie K, Friedberg J, Kucharczuk JC, Litzky LA, Johnson SW, Kaiser LR, and Albelda SM

Subjects
Aged, Anions, Biomarkers, Tumor, Carrier Proteins biosynthesis, Cytoskeleton metabolism, DNA, Complementary metabolism, Down-Regulation, Female, Galectin 3 biosynthesis, Glucose metabolism, Humans, Immunohistochemistry, Lung Neoplasms diagnosis, Male, Mesothelioma diagnosis, Middle Aged, Models, Biological, Oligonucleotide Array Sequence Analysis, Peroxidases metabolism, RNA metabolism, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Up-Regulation, Vault Ribonucleoprotein Particles biosynthesis, Gene Expression Regulation, Neoplastic, Lung Neoplasms genetics, Lung Neoplasms metabolism, Mesothelioma genetics, Mesothelioma metabolism
Abstract

Purpose: Malignant mesothelioma is a uniformly fatal cancer of the pleural and peritoneal spaces. Several challenging clinical problems include poor understanding of the pathophysiology, inaccurate diagnosis from tissue samples, and unsuccessful treatment strategies. The purpose of this study was to use microarray analysis to identify specific gene expression changes in mesothelioma compared with normal mesothelium., Experimental Design: We performed gene expression analysis on mesothelioma tissue specimens from 16 patients and compared these to 4 control pleural tissue samples using cDNA microarray filters with 4132 clones. Multiple normalization and analysis approaches were used. Quantitative reverse transcription-PCR and immunohistochemistry were used to validate results., Results: Genes (166) were significantly up-regulated, and 26 were down-regulated. Validation of 18 genes using real-time PCR confirmed array predictions in every case. Analysis revealed activation of several key pathways including genes involved in glucose metabolism, mRNA translation, and cytoskeletal remodeling. Expression profiling identified processes likely responsible for 18-fluoro-2-deoxy-glucose uptake and tumor localization by positron emission tomography, and a role for hypoxia-inducible factor-1 was suggested. Potentially important up-regulated genes included gp96, lung resistance-related protein, galectin-3 binding protein, the M(r) 67,000 laminin receptor (on tumor vessels), and voltage-dependent anion channels. Prospective testing using reverse transcription-PCR confirmed up-regulation of these novel markers., Conclusions: Expression profiling revealed marked up-regulation of energy, protein translation, and cytoskeletal remodeling pathways in mesothelioma. Additional genes that could be important in our understanding of the pathogenesis of mesothelioma, aiding in diagnosis, or improving targets for therapy were also identified.

Published
2003

23. Alterations in cell cycle genes in early stage lung adenocarcinoma identified by expression profiling.

Author

Singhal S, Amin KM, Kruklitis R, DeLong P, Friscia ME, Litzky LA, Putt ME, Kaiser LR, and Albelda SM

Subjects
Adenocarcinoma metabolism, Aged, Cell Cycle genetics, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Staging, Oligonucleotide Array Sequence Analysis methods, RNA, Messenger metabolism, Transcription, Genetic, Adenocarcinoma genetics, Gene Expression Profiling, Genes, cdc physiology, Lung Neoplasms genetics, Lung Neoplasms metabolism, Neoplasm Proteins metabolism
Abstract

In normal lung epithelial cells, cellular division is an ordered, tightly regulated process involving multiple checkpoints that assess extracellular growth signals, cell size, and DNA integrity. In contrast, neoplastic lung cells develop the ability to bypass several of these checkpoints, particularly at the G1/S and G2/M boundaries. We used genomic profiling to compare gene expression levels in early stage lung adenocarcinomas and non-neoplastic pulmonary tissue in order to comprehensively identify alterations in the process of cell cycling. RNA extracted from node negative, poorly differentiated lung adenocarcinomas (15 patients) and non-neoplastic pulmonary tissue (5 patients) was hybridized to oligonu-cleotide microarray filters containing 44,363 genes. Ontological classification was used to extract genes involved with cell cycle progression. Further analysis discovered a subset of differentially expressed genes for further study. Of the 624 cell cycle genes on the microarray filters, 40 genes were predicted to be differentially expressed in lung adeno-carcinomas. Alterations in several genes (i.e., cyclin B1, cyclin D1, p21, MDM2) are consistent with published data in the literature. We also identified 19 novel genes that have neither been described in non-small cell lung cancer (i.e., cdc2, cullin 4A, ZAC, p57, DP-1, GADD45, PISSLRE, cdc20) nor in any other tumors (i.e., cyclin F, cullin 5, p34). These results identified several potential cell cycle genes altered in lung cancer.

Published
2003
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