BioNanoMedicine: a nanotechnology platform for the 21st century.
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Biomedical subjects
Publications and source records attributed to Krishnarao Appasani.
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RNA interference (RNAi) is a newly discovered and popular technology platform among researchers not only in the fields of RNA biology and molecular cell biology. It has created excitement in clinical sciences such as oncology, neurology, endocrinology, infectious diseases and drug discovery. There is an urgent need to educate and connect academic and industry researchers for the purpose of knowledge transfer. Thus, GeneExpression Systems of Waltham organized its Second International Conference in Waltham City (May 2-4, 2004, MA, USA) on the theme of 'RNA interference: From Biology to Drugs & Therapeutics.' About 200 participants and 32 speakers attended this two and half-day event which was arranged in six scientific and three technology sessions and ended with a panel discussion. This report covers a few representative talks from academia, biotech and the drug industry.
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Malignant pleural mesothelioma (MPM) is a highly lethal pleural neoplasm that is often resistant to chemotherapeutic drugs, including cisplatin, and for which little is known regarding carcinogenic pathways. We used differential display to compare gene expression patterns in mesothelioma, normal pleura and normal lung, in order to better understand MPM pathobiology, and to search for genes that may facilitate drug resistance in this cancer. The human inhibitor of apoptosis protein-1 gene (IAP-1/MIHC/cIAP2) was discovered to be highly expressed in MPM. We confirmed overexpression of IAP-1 mRNA and protein in 39 additional human MPM tumor specimens and 3/5 (60%) MPM cell lines by multiple methods, including real time quantitative reverse transcription-PCR and western blot analysis. Using an antisense targeting approach, we found that attenuation of IAP-1 mRNA levels decreases baseline cell viability and increases the sensitivity of MPM cell lines to cisplatin by nearly 20-fold. Reduced IAP-1 gene expression also results in a concordant increase of the pro-apoptotic cleavage product of caspase 9 and a reduction in the number of viable tumor cells. Our observations strongly suggest that IAP-1 is at least partly responsible for promoting carcinogenesis and mediating resistance to cisplatin in many MPM tumors and that further study of this apoptotic pathway is warranted.