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DIRECTED ENZYME PRODRUG THERAPY: THE SYNTHESIS OF A Β-GLUCURONIDE LINKER AND ITS COUPLING WITH Z-IODOCOMBSTATIN

Description
The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a…

The purpose of this project is to explore the benefit of using prodrugs in chemotherapy, as well as to explain the concept of angiogenesis and the importance of this process to tumor development. Angiogenesis is the formation of new blood capillaries that are necessary for the survival of a tumor, as a tumor cannot grow larger than 1-2 mm3 without developing its own blood supply. Vascular disrupting agents, such as iodocombstatin, a derivative of combretastatin, can be used to effectively cut off the blood supply to a growing neoplasm, effectively inhibiting the supply of oxygen and nutrients needed for cell division Thus, VDAs have a very important implication in terms of the future of chemotherapy. A prodrug, defined as an agent that is inactive in the body until metabolized to yield the drug itself, was synthesized by combining iodocombstatin with a β-glucuronide linker. The prodrug is theoretically hydrolyzed in the body to afford the active drug by β-glucuronidase, an enzyme that is produced five times as much by cancer cells as by normal cells. This effectively creates a “magic-bullet” form of chemotherapy, known as Direct Enzyme Prodrug Therapy (DEPT).
ContributorsClark, Caroline Marie (Author) / Pettit, George Robert (Thesis director) / Melody, Noeleen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
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Use of the Multiple Myeloma Immunosignature for the Synthesis of Synbody Therapeutic Treatment

Description
Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating…

Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating antigen-specific antibodies, but in MM the B cells express mutated, non-specific monoclonal antibodies. Therefore, it is hypothesized that antibody-based assay and therapy may be feasible for detecting and treating the disease. In this project, 330k peptide microarrays were used to ascertain the binding affinity of sera antibodies for MM patients with random sequence peptides; these results were then contrasted with normal donor assays to determine the "immunosignatures" for MM. From this data, high-binding peptides with target-specificity (high fluorescent intensity for one patient, low in all other patients and normal donors) were selected for two MM patients. These peptides were narrowed down to two lists of five (10 total peptides) to analyze in a synthetic antibody study. The rationale behind this originates from the idea that antibodies present specific binding sites on either of their branches, thus relating high binding peptides from the arrays to potential binding targets of the monoclonal antibodies. Furthermore, these peptides may be synthesized on a synthetic antibody scaffold with the potential to induce targeted delivery of radioactive or chemotherapeutic molecular tags to only myelomic B cells. If successful, this would provide a novel alternative to current treatments that is less invasive, has fewer side effects, more specifically targets the cause of MM, and reliably diagnoses the cancer in the presymptomatic stage.
ContributorsBerry, Jameson (Co-author) / Buelt, Allison (Co-author) / Johnston, Stephen (Thesis director) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Bailey v. Blue Cross Blue Shield of Virginia (1994)

Description

In 1994, the Eastern Virginia District court case Bailey v. Blue Cross Blue Shield of Virginia established that insurance companies could not deny coverage for experimental stem cell therapy treatments. The plaintiff, Mary Bailey, was diagnosed with advanced stage breast cancer and sought treatment involving high-dose chemotherapy and an advanced…

In 1994, the Eastern Virginia District court case Bailey v. Blue Cross Blue Shield of Virginia established that insurance companies could not deny coverage for experimental stem cell therapy treatments. The plaintiff, Mary Bailey, was diagnosed with advanced stage breast cancer and sought treatment involving high-dose chemotherapy and an advanced stem cell treatment, which was a novelty at the time. Stem cells are cells that have the potential to develop into several different types of cells in the body. The defendant was the health insurance company Blue Cross Blue Shield, which denied coverage for Bailey’s treatment. The district court sided with Bailey and ordered that BCBS could not deny coverage for her specific treatment. While Bailey v. Blue Cross Blue Shield of Virginia resulted in Bailey receiving compensation for her treatment, it also increased national awareness of stem cell therapy with chemotherapy.
ContributorsBains, Ajeet (Author) / Darby, Alexis (Editor) / Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia. (Publisher) / Arizona Board of Regents (Publisher)
Created2021-04-18
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“Improved Treatment for Cervical Cancer – Concurrent Chemotherapy and Radiotherapy” (1999), by Gillian Thomas

Description

On 15 April 1999, physician Gillian Thomas published the editorial “Improved Treatment for Cervical Cancer – Concurrent Chemotherapy and Radiotherapy,” henceforth “Improved Treatment,” in The New England Journal of Medicine. In that editorial, she discusses the potential benefits of combining chemotherapy drugs with radiation to treat women with cervical cancer.…

On 15 April 1999, physician Gillian Thomas published the editorial “Improved Treatment for Cervical Cancer – Concurrent Chemotherapy and Radiotherapy,” henceforth “Improved Treatment,” in The New England Journal of Medicine. In that editorial, she discusses the potential benefits of combining chemotherapy drugs with radiation to treat women with cervical cancer. At the time, healthcare professionals rarely treated cervical cancer by combining chemotherapy or radiation. Two months prior to Thomas’s publication, the US National Cancer Institute, headquartered in Bethesda, Maryland, released an announcement advocating for combining chemotherapy with radiation based on clinical trial results. In “Improved Treatment,” Thomas summarized the results of those clinical trials that had led to the announcement and communicated a new way to treat invasive cervical cancers, which persists as of 2019.
ContributorsDarby, Alexis (Author) / Guerrero, Anna Clemencia (Editor) / Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo Project Encyclopedia. (Publisher) / Arizona Board of Regents (Publisher)
Created2020-09-09