Life Sciences Commons^™

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

Investigating The Synergistic Effects Of Two Curcuminoids And Cisplatin On Cancer Cell Migration, Blaine Patty

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is a common chemotherapy drug used to treat various cancers; however, it is relatively ineffective against many cancers, including several types of lung cancer. One approach that could improve cisplatin’s effect is to combine it with another drug that produces a synergistic response greater than either drug alone. Curcumin, a naturally occurring plant compound, has been investigated for synergisms in conjunction with cisplatin chemotherapy, but curcumin use is hampered by its low bioavailability. This project investigated whether two synthetic curcumin analogs, EF-24 and CLEFMA (curcuminoids), which have greater solubility than curcumin, could, when combined with cisplatin, decrease the migration …

Investigating The Synergistic Effects Of Two Curcuminoids And Cisplatin On Cancer Cell Reactive Oxygen Species, Matthew Millay

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an anticancer drug which can cause the production of reactive oxygen species (ROS) that kill cancer cells. Curcumin is a naturally occurring plant compound that can increase ROS levels in cancer cells and enhance the activity of cisplatin against cancer, but it exhibits poor bioavailability. We investigated whether two synthetic curcumin analogs (curcuminoids), EF-24 and CLEFMA, with anti-cancer activity and improved bioavailability, increased cisplatin’s effect against cancer. A spectrophotometric fluorescent ROS assay was used to determine if cisplatin, the curcuminoids or combinations of cisplatin with a curcuminoid affected the level of ROS in the A549 non-small cell lung …

Microtubule-Actin Crosslinking Factor 1 And Plakins As Therapeutic Drug Targets, Quincy A. Quick

Biology Faculty Research

Plakins are a family of seven cytoskeletal cross-linker proteins (microtubule-actin crosslinking factor 1 (MACF), bullous pemphigoid antigen (BPAG1) desmoplakin, envoplakin, periplakin, plectin, epiplakin) that network the three major filaments that comprise the cytoskeleton. Plakins have been found to be involved in disorders and diseases of the skin, heart, nervous system, and cancer that are attributed to autoimmune responses and genetic alterations of these macromolecules. Despite their role and involvement across a spectrum of several diseases, there are no current drugs or pharmacological agents that specifically target the members of this protein family. On the contrary, microtubules have traditionally been targeted …

Study Of The Mechanism Of Action For Ru(Ii) Polypyridyl Complexes As Potential Anticancer Agents, Yang Sun

Theses and Dissertations--Chemistry

Application of chemotherapeutic agents in current cancer treatment has been limited by adverse effects as poor selectivity results in systemic toxicity; most chemotherapy approaches also experience inherited or acquired drug resistance which lead to reduced treatment outcome. Research efforts have focused on the discovery of novel chemotherapies that overcome the limitations mentioned above. Ru(II) polypyridyl complexes with anti-cancer properties have been extensively studied as traditional cytotoxic agents and photodynamic therapy agents due to their photophysical and photochemical characteristics.

Most research has focused on the design of Ru(II) polypyridyl complexes that have affinities to nucleic acids as inspired by the classic …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

Nonsurgical Approaches To Glioblastoma, Moshe Baitelman

The Science Journal of the Lander College of Arts and Sciences

Due to the sensitivity of location, brain cancer is one of the most difficult and deadly known cancers. There are various forms of cancer in the brain with many shared characteristics as well as unique manifestations in each. While cancers originating in the central nervous system present in several ways, the most common forms are high grade gliomas generally, and glioblastoma or anaplastic astrocytomas specifically. With the advent of technology, researchers have been able to propose and refine extensive profiles of these relentless tumors, enabling greater and more successful treatment profiles to be developed. Where treatments used to consist primarily …