Pharmacology, Toxicology and Environmental Health 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 …

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 …

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 …

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 …

Advances In Tumor-Targeted Therapy Using Nanomedicine., Divya Karukonda

Electronic Theses and Dissertations

Despite continuous improvement and significant progress made in diagnostic and therapeutic approaches for cancer, it is still the leading cause of death worldwide. Although conventional chemotherapy has made significant advances in improving patient survival the indiscriminate destruction of normal cells leads to severe side effects and poor clinical outcomes. Thus, there is a need for effective delivery of drugs to the tumor site avoiding normal tissues to reduce toxicity in the rest of the body. For this reason, a novel multidisciplinary field called Nanotechnology has evolved in recent years and advances in this field have contributed to the development of …

Prevention And Treatment Of Familial Adenomatous Polyposis And Colorectal Cancer By Bilberry-Derived Anthocyanidins., Ashley M. Mudd

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. Familial adenomatous polyposis (FAP) is an inherited disorder which if left untreated will develop into colon cancer. The family of plant-derived compounds, anthocyanins, show significant therapeutic potential against a variety of diseases, however, they are limited by their instability and poor bioavailability. The goal of my Master’s research project was to determine whether anthocyanidins (non-glycosylated anthocyanins) are more effective than the native anthocyanins, and whether exosomal formulation of anthocyanidins (ExoAnthos) can enhance therapeutic potency compared with free Anthos against both FAP and CRC. The antiproliferative …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Development Of Neurotensin-Based Radiopharmaceuticals For Neurotensin-Receptor-1-Positive Tumors Targeting, Yinnong Jia

Theses & Dissertations

The neurotensin receptor 1 (NTR1) is overexpressed in many cancers, due to its role as a growth pathway. These NTR1-positive cancers include pancreatic, colon, prostate and breast cancers. In the radiopharmaceutical field, the overexpression of NTR1 in cancer has prompted the development of NTR1-targeted diagnostics and therapeutics. The neurotensin (NT) peptide exhibits low nanomolar affinity for NTR1 and has been the paradigm for NTR1-targeted agents. Since the 1980’s, radiolabeled NT analogs have been developed and evaluated for targeting NTR1-positive cancers. Since native NT is rapidly degraded in vivo by a variety of peptidases, a tremendous amount of effort has been …

Understanding The Genotoxicity Of Silver Nanoparticles And The Chemoprevention Of Pomegranate Extract, Sameera Nallanthighal

Legacy Theses & Dissertations (2009 - 2024)

The use of silver nanoparticles (AgNPs) in a wide variety of consumer products (i.e. toothpastes, food containers, dietary supplements and garments) for their antimicrobial properties can lead to potential oral exposure in humans. To enhance their stability, AgNPs are coated with capping agents such as citrate and polyvinylpyrrolidone (PVP). Despite the lack of significant general toxicity based on hematology, blood chemistry and histology evaluations, the potential genotoxic effects of AgNPs cannot be ruled out and have to be addressed. Studies examining the genotoxic risks of AgNPs are needed because genotoxicity is a strong indicator of cancer risk. Here we examined …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Transferrin Receptor Targeted Delivery Of Sirna For Gene Therapy, Yuran Xie

Wayne State University Dissertations

Gene therapy is thought to be a solution for various difficult to treat diseases such as cancer. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence disease related gene have been exploit in different diseases. However, lack of safe and efficient siRNA delivery systems limits the application of siRNA therapy in clinic. Transferrin receptor (TfR) is an essential transmembrane receptor involved in iron uptake. TfR universally express in most cells/ tissues but upregulated in certain cells, for example, many cancer cells and activated T cells (ATCs). To overcome the biological barriers and increase siRNA delivery efficiency, in …

Current And Emerging Uses Of Statins In Clinical Therapeutics: A Review, Jonathan T. Davies, Spencer F. Delfino, Chad E. Feinberg, Meghan F. Johnson, Veronica L. Nappi, Joshua T. Olinger, Anthony P. Schwab, Hollie I. Swanson

Pharmacology and Nutritional Sciences Faculty Publications

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin …

Stock Market Reactions To The Iarc Announcement Linking Red Meat And Processed Meat To Cancer, Scott B. Lehman

Journal of Environmental and Resource Economics at Colby

This study investigates how food companies were affected by the International Agency for Research on Cancer’s report that linked processed meat and red meat consumption to increased risk of cancer. The results indicate that neither fast food companies nor meat producers were greatly affected by the announcement in the days immediately following the release.

Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson

Wayne State University Dissertations

Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …

Ethnobotany Of Camptotheca Decaisne: New Discoveries Of Old Medicinal Uses, Shiyou Li, Wanli Zhang

NCPC Publications and Patents

Camptotheca trees had been used as fuelwood and an ornamental species in its native China. There were no reports on medicinal uses of Camptotheca in China and thus it was believed the trees had no medicinal before its antitumor activity discovered in 1957. We conducted national surveys of Camptotheca in China from 1994 to 1999. We found that Camptotheca acuminate is commonly known as happytree (xi shu) because the trees can be used as folk medicine to cure stubborn phlegm as well as other diseases, thus making patients “happy”. There are three local names to refer the uses of C. …

Curcumin-Free Turmeric Exhibits Anti-Inflammatory And Anticancer Activities: Identification Of Novel Components Of Turmeric (Abstract), Bharat Aggarwal, Wei Yuan, Shiyou Li, Subash C. Gupta

NCPC Publications and Patents

Abstract attached

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …

Biochemical Pathways In Cancer, Eun-Kyoung Yim Breuer, Mandi M. Murph, Rolf J. Craven

Pharmacology and Nutritional Sciences Faculty Publications

No abstract.

Solar Synthesis Of Acyl Hydroquinones And Their Bioactivity., Fernando De Leon, Shizue Mito

COURI Symposium Abstracts, Summer 2012

Without the Sun, we would not enjoy the benefits of life here on the Earth. This energy is essential and crucial for sustaining life: playing important roles in circadian rhythms and photosynthesis in plants. In our research, this endlessly renewable clean energy source is utilized for photo-Friedel-Crafts acylation of 1,4 - benzoquinones and 1,4 - naphthoquinones. Photo-Friedel-Crafts acylation was first discovered in 1891 and although there have been reported examples of acylated products, the substrates are still limited. In this project a variety of aldehydes having different substituents are examined, and bioassays were performed. While conventional methods for photochemistry use …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations and Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Compositional Determinants Of The Pharmacological Actions Of Heparins, Angel Lee Gray-Shah

Dissertations

This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).

In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Gynecomastia, ปารณีย์ มีแต้ม

The Thai Journal of Pharmaceutical Sciences

Gynecomastia เป็นภาวะปกติที่พบในทารก ชายวัยรุ่น และผู้สูงอายุ นอกจากนั้นยังเป็นพยาธิ สภาพเนื่องจ...