Pharmacological and Clinical Importance of Integrin Antagonists in Treatment of Cancer

Integrins are heterodimeric molecules that are composed of 18 α -subunits and 8 β -subunits. They exist in 24 distinctive shapes based on combination of these sub-units and are mainly responsible for the adhesion of extracellular matrix (ECM) and immunoglobulin family molecules. Integrins mediate adhesion of epithelial cells to the basement membrane and also help in the migration, proliferation and survival of tumor cells. Studies also reveal that certain integrins act as markers for tumor cells and they also assist in both tumor progression and apoptosis. Studies reveal that unligated integrins in association with caspase 8 result in inhibition of ECM adhesion might result and integrin mediated death (IMD) on the other hand integrins in association with oncogenes or receptor tyrosine kinases can result in enhanced tumorigenesis. Among several types of integrins, αvβ 3 and α 5 β 1 have gained importance in anti-angiogenesis studie

Pharmacological and Clinical Importance of Integrin Antagonists in Treatment of Cancer

Integrins are heterodimeric molecules that are composed of 18 \ud α\ud -subunits and 8 \ud β\ud -subunits. They exist in 24\ud distinctive shapes based on combination of these sub-units and are mainly responsible for the adhesion of\ud extracellular matrix (ECM) and immunoglobulin family molecules. Integrins mediate adhesion of epithelial cells to the\ud basement membrane and also help in the migration, proliferation and survival of tumor cells. Studies also reveal that\ud certain integrins act as markers for tumor cells and they also assist in both tumor progression and apoptosis. Studies\ud reveal that unligated integrins in association with caspase 8 result in inhibition of ECM adhesion might result and\ud integrin mediated death (IMD) on the other hand integrins in association with oncogenes or receptor tyrosine kinases\ud can result in enhanced tumorigenesis. Among several types of integrins, \ud αvβ\ud 3 and \ud α\ud 5\ud β\ud 1 \ud have gained importance in\ud anti-angiogenesis studie

Purification and characterization of cysteine protease from germinating cotyledons of horse gram

<p>Abstract</p> <p>Background</p> <p>Proteolytic enzymes play central role in the biochemical mechanism of germination and intricately involved in many aspects of plant physiology and development. To study the mechanism of protein mobilization, undertaken the task of purifying and characterizing proteases, which occur transiently in germinating seeds of horse gram.</p> <p>Results</p> <p>Cysteine protease (CPRHG) was purified to homogeneity with 118 fold by four step procedure comprising Crude extract, (NH4)2SO4 fractionation, DEAE-Cellulose and CM-sephacel chromatography from the 2 day germinating cotyledons of horse gram (<it>Macrotyloma uniflorum </it>(Lam.) Verdc.). CPRHG is a monomer with molecular mass of 30 k Da, was determined by SDS-PAGE and gel filtration. The purified enzyme on IEF showed two isoforms having pI values of 5.85 and 6.1. CPRHG composed of high content of aspartic acid, glutamic acid and serine. The enzyme activity was completely inhibited by pCMB, iodoacetate and DEPC indicating cysteine and histidine residues at the active site. However, on addition of sulfhydryl reagents (cysteine, dithiothreitol, glutathione and beta-ME) reverse the strong inhibition by pCMB. The enzyme is fairly stable toward pH and temperature. Immunoblot analysis shows that the enzyme synthesized as zymogen (preproenzyme with 81 kDa) and processed to a 40 kDa proenzyme which was further degraded to give 30 kDa active enzyme.</p> <p>Conclusion</p> <p>It appears that the newly synthesized protease is inactive, and activation takes place during germination. CPRHG has a broad substrate specificity and stability in pH, temperature, etc. therefore, this protease may turn out to be an efficient choice for the pharmaceutical, medicinal, food, and biotechnology industry.</p

Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

Cancer progression is a multistep process during which normal cells exhibit molecular changes that culminate into the highly malignant and metastatic phenotype, observed in cancerous tissues. The initiation of cell transformation is generally associated with genetic alterations in normal cells that lead to the loss of intercellular- and/or extracellular-matrix- (ECM-) mediated cell adhesion. Transformed cells undergo rapid multiplication and generate more modifications in adhesion and motility-related molecules which allow them to escape from the original site and acquire invasive characteristics. Integrins, which are multifunctional adhesion receptors, and are present, on normal as well as transformed cells, assist the cells undergoing tumor progression in creating the appropriate environment for their survival, growth, and invasion. In this paper, we have briefly discussed the role of ECM proteins and integrins during cancer progression and described some unique conditions where adhesion-related changes could induce genetic mutations in anchorage-independent tumor model systems

Review Article Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

Cancer progression is a multistep process during which normal cells exhibit molecular changes that culminate into the highly malignant and metastatic phenotype, observed in cancerous tissues. The initiation of cell transformation is generally associated with genetic alterations in normal cells that lead to the loss of intercellular-and/or extracellular-matrix-(ECM-) mediated cell adhesion. Transformed cells undergo rapid multiplication and generate more modifications in adhesion and motilityrelated molecules which allow them to escape from the original site and acquire invasive characteristics. Integrins, which are multifunctional adhesion receptors, and are present, on normal as well as transformed cells, assist the cells undergoing tumor progression in creating the appropriate environment for their survival, growth, and invasion. In this paper, we have briefly discussed the role of ECM proteins and integrins during cancer progression and described some unique conditions where adhesion-related changes could induce genetic mutations in anchorage-independent tumor model systems