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Kshv Susceptibility And Transmission Within Tonsillar Specimens, Farizeh Aalam

Pharmaceutical Sciences (PhD) Dissertations

Despite nearly three decades of research, not much is known regarding the early stages of development for KSHV lymphoproliferative disorders, hindering our ability to develop prophylactic measures or effective treatments. This dissertation will focus on the host and viral factors influencing the magnitude and dynamics of KSHV infection in the human tonsil to pave the way for future interventions directed at limiting person-to-person transmission of KSHV.

To understand the contribution of host factors to KSHV susceptibility in B lymphocytes, we generated a library of 40 tonsillar specimens. Our results indicate that the immunological composition of tonsillar lymphocytes varies across our …

Development Of Novel Peptide-Doxorubicin Conjugates For Targeting Triple-Negative Breast Cancer, Azam Saghaeidehkordi

Pharmaceutical Sciences (PhD) Dissertations

Triple-negative breast cancer (TNBC) is the most aggressive and difficult to treat subtype of breast cancer. Chemotherapy is an active treatment option in combination with other treatments; however, the side effects limit the effective therapeutic dose. To selectively target the cancer cells, I have synthesized three peptide-drug conjugates (PDCs) to specifically target the TNBC cells. The first PDC contains peptide 18-4 with an additional cysteine in the N-terminal (NH2- CWxEAAYQrFL-CONH2) linked to aldoxorubicin (Aldox), a modified version of a common chemotherapy drug doxorubicin (Dox). The cytotoxicity of the PDC and free Dox (positive control) were assessed against MDA-MB-231, MDA-MB-468, and …

Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei

Pharmaceutical Sciences (PhD) Dissertations

The aim of this thesis was to design, synthesize, and characterize a novel peptide-doxorubicin conjugate, evaluate in vitro stability and cytotoxicity properties of the conjugate and study its mechanism for uptake into the triple-negative breast cancer (TNBC) cells. For the synthesis of the conjugate, first, doxorubicin (Dox) was conjugated to a highly efficient established cross-linker, MCC, to give an intermediate product, MCC-Dox. MCC-Dox was characterized using NMR spectroscopy, mass spectrometry, and RP-HPLC and purified for subsequent reaction. Second, the 11-mer peptide 18-4 (NH₂-CWxEAAYQrFL-CONH₂) with high proteolytic stability and specificity for breast cancer cells was reacted with …

Viral Factors Influencing Early Infection Events During Ex-Vivo Kshv Infection, Ramina Nabiee

Pharmaceutical Sciences (PhD) Dissertations

The enigma of Kaposi Sarcoma Herpes Virus infection, and its persistence despite a quarter century of research on the virus, has given rise to an immediate need for addressing fundamental questions about basic immunology and virology knowledge regarding this virus. Kaposi Sarcoma Herpes Virus (KSHV), also known as Human Herpesvirus 8 (HHV8), is the etiological agent of Kaposi Sarcoma (KS) and other lymphoproliferative cancers, such as Multicentric Castleman’s Disease (MCD), Primary Effusion Lymphoma (PEL), and a newly discovered rare disease called KSHV Inflammatory Cytokines Syndrome (KICS). Epidemic KS, also known as AIDS-KS, is the most common cancer in untreated HIV …

Structural Characterization And In Vitro Antiproliferative Activity Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa

Pharmaceutical Sciences (PhD) Dissertations

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling, in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and in vitro antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds.

Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the …