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All Subjects: Chemotherapy
Creators: Barbosa, Jennifer
Creators: Clark, Caroline Marie

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 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

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 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

Controlling Chemotherapy-Induced Nausea and Vomiting Through Guideline Adherence

Description

Background:
Thirty to fifty percent of cancer patients undergoing chemotherapy will experience
chemotherapy induced nausea and or vomiting (CINV) despite the use of antiemetic prophylaxis Uncontrollable CINV can lead to complications that add extra stress to patients, increase in healthcare costs, and utilization of resources. CINV can lead to chemotherapy dose reductions, treatment delays, chemotherapy changes, or discontinuation of treatment. Guidelines exist to better prevent and treat CINV. Evidence supports the use of guidelines to prevent CINV, however patients still suffer from CINV often due to a lack of guideline adherence.

Objectives:
The purpose of this project was to increase CINV guideline adherence by increasing knowledge of antiemetic guidelines utilizing an educational intervention for providers and nurses at an outpatient oncology office.

Methods:
A brief educational intervention on CINV and recommended NCCN guidelines was
conducted with providers and nurse (n=6) at an oncology practice in Southwestern United States. An evaluation to assess change in knowledge was performed using a pre and post test format. Statistical analysis was performed using descriptive statistics, McNemar tests and Wicoxan Signed Rank Test.

Findings:
There was a significant effect on knowledge of NCCN antiemetic guidelines (Z=-1.89, p=0.059, mean 2.5) post intervention. There also was a significant impact on likelihood to use guidelines in practice (Z=-1.89, p=0.059, mean 2.5). Increasing awareness and likelihood to CHEMOTHERAPY INDUCED NAUSEA AND VOMITING 3 follow recommended guidelines may improve CINV symptoms in patients undergoing chemotherapy and improve the treatment outcomes for these patients.

ContributorsBarbosa, Jennifer (Author) / Baker, Laurie (Thesis advisor)

Created2018-04-29