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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Mechanism of lipopolyamine-induced immunotozin sensitization in cancer cells

Haynes, Elizabeth M. 01 January 2010 (has links)
Immunotoxins (ITx) represent a new, alternate class of therapeutic agent. ITx is made when the active part of a toxin is conjugated with the binding portion of an antibody that recognizes a cancer-specific antigen. The antibody component makes ITx highly specific, as it will only bind to cells displaying the correct surface antigen. This characteristic lowers the chance of nonspecific cell damage, which causes many of the severe side effects of other chemotherapeutics. The ITx we use is a conjugate of saporin toxin. Saporin is a ribosomal inhibiting protein derived from the plant Saponaria officinales, which kills the cell by inhibiting protein synthesis. ITx enters the cancer cell by binding to the cellular marker it is specific for on the cell surface. From there, it is endocytosed, compartmentalized in an endosome, and eventually escapes to the cytosol where its ribosomal target is located. Increasing the rate of escape to the cytosol is the key to increasing cell death. The mechanism by which saporin escapes the endosome and enters the cytosol is poorly understood. Two potential mechanisms involving the rupture of the endocytic vesicle were examined. Through experiments using large unilamellar vesicles as endosomal mimics, we have been able to characterize the mechanism by which saporin works to burst the endosomal membrane through RET and calcein release. Understanding this process is the key to producing more effective immunotoxin sensitizing drugs.

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