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RNase A and DNase I inhibit metastasis by catalyzing metastasis pathomorphosis which is apoptosis, necrosis and destruction of oncocytes (epithelial cells with large amounts of mitochondira). This capability retards the primary tumor growth by 30-40%. The tumor bearing mice received doses of RNase A, DNase I or a mixture of the two and the most significant effect observed was in the mice treated with both enzymes simultaneously. Thus the simultaneous administration of RNase A and DNase I lead to an anti-metastatic effect and results in an almost complete absence in the metastases of the tumor. Further observations suggest that RNase A and DNase I are toxic at high levels. So for effective treatment ultra low doses are required to stay below the level of toxicity. | RNase A and DNase I inhibit metastasis by catalyzing metastasis pathomorphosis which is apoptosis, necrosis and destruction of oncocytes (epithelial cells with large amounts of mitochondira). This capability retards the primary tumor growth by 30-40%. The tumor bearing mice received doses of RNase A, DNase I or a mixture of the two and the most significant effect observed was in the mice treated with both enzymes simultaneously. Thus the simultaneous administration of RNase A and DNase I lead to an anti-metastatic effect and results in an almost complete absence in the metastases of the tumor. Further observations suggest that RNase A and DNase I are toxic at high levels. So for effective treatment ultra low doses are required to stay below the level of toxicity. | ||
Another member in the ribonuclease family and structural homologue to bovine pancreatic ribonuclease A is frog onconase or ONC. ONC is found in oocytes and early embryos of northern leopard frogs. The frog ribonuclease variant shows both cytostatic (cell growth suppression) and cytotoxic (prevents cell divisions) characteristics when it interacts with tumor cells. But it can also degrade tRNA’s selectively and is in a higher levels of clinical trials for treatment for asbestos-related lung cancer. | |||
This studies aim was to determine the intramolecular interactions that control the oxidative folding of the proteins in order to be able to predict the structures of proteins and then make more effective mimics of the ONC. In order to determine the interactions the regeneration of RNase A was studied in depth. The results show that although RNase A and ONC are structurally very similar there are significant differences in their oxidative folding pathways. The first step of regeneration, which is rate limiting, is the formation of an unstructured disulfide containing intermediate. The oxidative folding in RNase A has no stable disulfide intermediate whereas in INC there the presence of a stable disulfide intermediate is clearly evident. This finding indicates that the intramolecular interactions that stabilize the intermediates during the folding process differ but are able to give rise to very similar three-dimensional final stage. It was also found that ONC lacks the 65-72 disulfide bond that is key to the folding process but the folding of ONC is faster than that of RNase A. In the case of both enzymes, entropy is lost in the formation of the disulfide bonds, but it may be driven by enthalpically favorable interactions of the side chains. Further experiments are being done to identify the intramolecular interactions that account of the increased rate and formation of the structured intermediates. | |||
<Structure load='7RSA' size='300' frame='true' align='left' caption='Insert caption here' scene='Insert optional scene name here' /> | <Structure load='7RSA' size='300' frame='true' align='left' caption='Insert caption here' scene='Insert optional scene name here' /> | ||