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Faizule_Hassan_Thesis.pdf (101.87 MB)

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Adenovirus Mediated Delivery of Decoy Hyper Binding Sites for Sequestration of an Oncogenic Transcription Factor HMGA as a Potential Novel Cancer Therapy and Antibacterial Activity of Local Mushrooms

Hassan, Faizule
http://rave.ohiolink.edu/etdc/view?acc_num=miami1511449587326648

Abstract Details

2017, Doctor of Philosophy, Miami University, Cell, Molecular and Structural Biology (CMSB).
The first section of this dissertation describes the development of strategies for the treatment of pancreatic cancer using a novel synthetic DNA sequence that functions as decoy binding site for an oncogenic protein called high mobility group A (HMGA) and adenovirus mediated gene therapy. The second part of this dissertation describes a survey study for evaluating the antibacterial activity of mushroom samples collected from local areas. The Chapter 1 provides background information about the HMGA and its role in tumor development and cancer progression. The Chapter 1 also provides background information about the adenovirus and its use in cancer treatment. In addition, Chapter 1 discusses about the medicinal use and antibacterial potential of mushrooms. In Chapter 2, we have devised a strategy of using engineered replication-defective adenovirus (Ad) to deliver decoy hyper binding sites for HMGA to the nucleus of cancer cells with the goal of sequestering excess HMGA at the decoy hyper binding sites due to binding competition. Sequestration of excess HMGA at the decoy binding sites is intended to reduce HMGA binding at the naturally occurring genomic HMGA binding sites, which should result in normalized gene expression and restored sensitivity to chemotherapy. Infection of five different pancreatic and liver cancer cell lines with the Ad containing the HMGA decoy hyper binding sites resulted in significant reduction in cell viability and increased sensitivity to chemotherapy. The Chapter 3 discusses toxicity and biodistribution following injection of the Ad containing the HMGA decoy hyper binding sites into mice liver or pancreas. This study provides essential preclinical information regarding toxicity and biodistribution needed to determine the potential of our engineered virus for future treatment of cancer in humans. The Cahpter 4 demonstrated a strategy to develop a conditionally replicating Ad virus which will selectively replicate in cancer cells while being unable to replicate in normal cells. We have shown that the deletion of two genes, E1ACR2 and E1B19K, increased cancer selective replication of the Ad and decrease chemotherapy resistance of pancreatic cacner cells. In Chapter 5, we have described a survey study where we showed antibacterial activity in 25 mushroom samples out of the 75 samples tested. Finally the Chapter 6 summarizes the present research and shows future direction.
Michael Kennedy, Dr. (Advisor)
Carole Dabney-Smith, Dr. (Committee Chair)
Rachael Morgan-Kiss, Dr. (Committee Member)
Gary Lorigan, Dr. (Committee Member)
David Tierney, Dr. (Committee Member)
183 p.
Biochemistry; Molecular Biology
High Mobility Group A; HMGA; Adenovirus; Replication-competent adenovirus; Replication-defective adenovirus; Cancer; Chemotherapy; Gene delivery; Mushroom; Antibiotic resistance;

Recommended Citations

Citations

  • Hassan, F. (2017). Adenovirus Mediated Delivery of Decoy Hyper Binding Sites for Sequestration of an Oncogenic Transcription Factor HMGA as a Potential Novel Cancer Therapy and Antibacterial Activity of Local Mushrooms [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1511449587326648

    APA Style (7th edition)

  • Hassan, Faizule. Adenovirus Mediated Delivery of Decoy Hyper Binding Sites for Sequestration of an Oncogenic Transcription Factor HMGA as a Potential Novel Cancer Therapy and Antibacterial Activity of Local Mushrooms . 2017. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1511449587326648.

    MLA Style (8th edition)

  • Hassan, Faizule. "Adenovirus Mediated Delivery of Decoy Hyper Binding Sites for Sequestration of an Oncogenic Transcription Factor HMGA as a Potential Novel Cancer Therapy and Antibacterial Activity of Local Mushrooms ." Doctoral dissertation, Miami University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1511449587326648

    Chicago Manual of Style (17th edition)

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© 2017, some rights reserved.Creative Commons License Adenovirus Mediated Delivery of Decoy Hyper Binding Sites for Sequestration of an Oncogenic Transcription Factor HMGA as a Potential Novel Cancer Therapy and Antibacterial Activity of Local Mushrooms by Faizule Hassan is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Miami University and OhioLINK.