Chemicals and Drugs Commons^™

Evaluating The Therapeutic Efficacy Of Grb2 Inhibition In Ovarian Malignancies, Olivia Lara

Dissertations & Theses (Open Access)

Purpose: Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in ovarian cancer models.

Experimental Design: Murine orthotopic models of ovarian cancer (OVCAR5 and SKOV3ip1) were used to study the biological effects of L-Grb2 on tumor growth. In vitro experiments (cell viability assay, Western blot analysis, siRNA transfection, and reverse phase protein array) were carried out to elucidate the mechanism and potential predictors of tumor response to L-Grb2.

Results: Treatment with L-Grb2 decreased tumor growth …

An Automated Syringe Pump System For Improving The Reproducibility Of Dynamic Hyperpolarized Mri Phantoms, Harlee G. Harrison

Dissertations & Theses (Open Access)

AN AUTOMATED SYRINGE PUMP SYSTEM FOR IMPROVING THE REPRODUCIBILITY OF DYNAMIC HYPERPOLARIZED MRI PHANTOMS

Harlee Grace Harrison, B.S.

Advisory Professor: James Bankson, Ph.D.

Magnetic Resonance Imaging (MRI) is a powerful tool in the diagnosis of cancer due to its ability to provide good soft tissue contrast and image resolution without the use of ionizing radiation. The use of hyperpolarized pyruvate as a contrast agent for tumor metabolism during MR scans has the potential to provide information about tumor metabolism in vivo that is not available from traditional imaging measurements or any other method. Hyperpolarization is achieved through dynamic nuclear polarization. …

Circumventing Cisplatin Resistance In Ovarian Cancers Through Reactivation Of P53 By Non-Cross-Resistant Platinum Analogs, Michelle Martinez-Rivera

Dissertations & Theses (Open Access)

Abstract

CIRCUMVENTING CISPLATIN RESISTANCE IN OVARIAN CANCERS THROUGH REACTIVATION OF P53 BY NON-CROSS-RESISTANT PLATINUM ANALOGS

Michelle Martinez-Rivera, B.S.

Advisory Professor: Zahid H. Siddik, Ph.D.

Cisplatin (cis-Pt), an anticancer platinum (Pt) drug, is used widely in the treatment of several malignancies, such as ovarian cancer. This Pt compound induces DNA damage, which results in p53 activation through post-translational modifications, mainly phosphorylation, culminating in execution of programmed cell-death. However, despite initial therapeutic response to cis-Pt, clinical resistance to this drug emerges leading to disease progression. Pt-resistance phenotypes have been associated with dysfunction in the p53 signaling pathway. Therefore, an effort to understand …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations & Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Phage Display Library Screening For Psa-/Lo Prostate Cancer Cell-Binding Peptides, John R. Moore

Dissertations & Theses (Open Access)

Prostate cancer (PCa) is one of the leading malignancies affecting men worldwide. Our lab focuses on understanding the molecular mechanisms underlying prostate carcinogenesis and developing therapeutics that target the cells responsible for driving PCa and mediating therapy resistance. My master thesis research employs a phage display library screening technology aiming to identify peptides that preferentially home in to undifferentiated PCa cells, which our lab has previously demonstrated to be intrinsically resistant to castration.

There is now evidence that a population of cells in PCa possesses characteristics associated with stem cells; these cells are referred to as cancer stem cells (CSCs). …

Anti-Gd2 Etoposide-Loaded Immunoliposomes For The Treatment Of Gd2 Positive Tumors, Brandon S. Brown

Dissertations & Theses (Open Access)

Systemic chemotherapeutics remain the standard of care for most malignancies even though they frequently suffer from narrow therapeutic index, poor serum solubility, and off-target effects. Monoclonal antibodies that specifically bind antigens overexpressed on many tumors such as the ganglioside, GD2, can be conjugated to drug-loaded liposomes to create a targeted drug delivery system. In this study, we have encapsulated etoposide, a topoisomerase inhibitor effective against a wide range of cancers, in surface modified liposomes decorated with anti-GD2 antibodies. We characterized the properties of the liposomes using a variety of methods including dynamic light scattering, electron microscopy, and Fourier transformed infrared …

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations & Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …

Characterization And Optimization Of Antigen-Specific T Cell Responses During Ex Vivo Expansion Of Melanoma Tumor-Infiltrating Lymphocytes, Yufeng Li

Dissertations & Theses (Open Access)

Treatment of metastatic melanoma with tumor reactive T cells (adoptive T cell therapy, ACT) is a promising approach associated with a high clinical response rate. However, further optimization of this treatment modality is required to increase the clinical response after this therapy. ACT in melanoma involves an initial phase (pre-REP) of tumor-infiltrating lymphocyte (TIL) expansion ex vivo from tumor isolates followed by a second phase, “rapid expansion protocol” (REP) generating the billions of cells used as the TIL infusion product. The main question addressed in this thesis was how the currently used REP affected the responsiveness of the CD8+ T …