Chemistry Commons^™

Elucidating The Mechanism Of Bone Morphogenetic Protein (Bmp) -Mediated Sox2 Downregulation In Ovarian Cancer, Zainab Motolani Shonibare

Theses and Dissertations

Sex determining region Y-box 2 (Sox2) is a transcription factor essential for maintaining self-renewal and pluripotency of undifferentiated embryonic stem cells. Sox2 is involved in multiple processes of cancer cells, however, regulation of Sox2 expression and the consequences of that regulation in cancer remains elusive. Previously, we demonstrated that BMP9/GDF2 is significantly reduced in expression in ovarian cancer (OVCA) cells, methylated in patient tumors and, promoted anoikis resistance in both breast and OVCA cell lines. In an attempt to identify genes downstream of BMP9 that may provide anoikis resistance, transcriptomics was performed leading to the identification of Sox2, a developmental …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw

Electronic Theses & Dissertations

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal to be …

Synthesis Of Novel Reiii And Rev Metallointercalator Complexes For Use As Dna Damage Probes, Eli Schwartz

Honors Program Theses and Projects

Cancer is a disease that affects millions around the globe. Treatments such as radiation and chemotherapy are often used to treat cancerous tumors, but are not 100% effective in curing the patient. Alternatively, some research groups have proposed the use of metallointercalators, metal complexes consisting of a rhodium, ruthenium, or iridium metal center with bidentate supporting ligands such as bipyridine and phenanthroline, or tridentate ligands such as terpyridine. The complexes also contain a bidentate intercalating group such as dipyridophenazine. These complexes possess the ability to directly bind to DNA through intercalation between the stacks of DNA base pairs, giving them …

Caspases And Cancer: Connections Through Circular Dichroism Spectroscopy, Sarah M. Hethcox

Honors College Theses

While excessive cell death inevitably leads to negative effects, the endurance of damaged cells in the presence of death signals can be equally detrimental to health. Apoptosis, or programmed cell death, is a highly regulated process in which cues from within or from outside a cell can trigger an irreversible sequence of signals that carry out cell destruction known as the apoptotic cascade. A group of enzymes called caspases play a vital role in this cascade with some participating as initiators and others acting as effectors of protein cleavage and intracellular breakdown. Although it is normal for the activity of …

Application Of Nanomaterials In The Detection Of Volatile Organic Compounds In Exhaled Breath For Cancer Diagnosis, Wan-Qiao Bai, Xue-Zhi Qiao, Tie Wang

Journal of Electrochemistry

Volatile organic compounds (VOCs) generated in human body can reflect one’s health state, and numerous diseases are identified by some VOCs biomarkers. More recently, analyses of VOCs biomarkers from exhaled breath have turned into a research frontier worldwide because it offers a noninvasive way for diseases diagnosis. Various kinds of nanomaterials are used to enhance the performance of sensing techniques, and play an essential role in miniaturization detection. In this review, several kinds of nanomaterials (metallic, metal oxide, carbon-based, composites and MOFs-based materials) used in various VOCs detection methods, especially in VOCs sensors are summarized. Learning from the successful utilization …

Antitumor Properties Of Imidazolium Salts, Jenna Frantz

Williams Honors College, Honors Research Projects

This is the final write-up for an honors research project for the University of Akron Williams Honors College. Synthesis of novel imidazolium salts was conducted. Following synthesis of imidazolium salts, the stability of the compound was tested at 37°C over a 72-hour period to give preliminary information about drug stability in vivo. 2D NMR was also conducted to confirm the structure of TPP-1. The student wrote an experimental protocol for the use of C57BL/6 mice and performed the online CITI training by the IRB to prepare to work with animals in a study of the antitumor properties of imidazolium salts …

Design, Synthesis, Characterization And Anti-Cancer Effects Evaluation Of Interchain Cysteine Linked Antibody Drug Conjugates, Ke Li

Doctoral Dissertations

"Antibody drug conjugates (ADCs) are emerging therapeutic products specially designed for the treatment of cancers. Potent cytotoxic agents are linked to antibodies via linkers. Antibody drug conjugates, which take advantage of both antibodies and cytotoxic agents, showed high selectivity towards cancer cells. Cytotoxic agents are delivered to the cancer cells selectively and kill them from inside while leaving low or non-toxicity towards normal cells. Antibody drug conjugates are actually heterogeneous mixtures. The major heterogeneities mainly lie in the drug to antibody ratio (DAR) and drug linking positions, both of which potentially affect the therapeutic index of ADCs. In this research, …

Vitamin D: Controversy Cancer And Beyond, Cristian J. Rosales, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Vitamins are an essential part to wellbeing. This was not something always known however, as the Germ theory was the accepted thesis of the 18th century. It was found that certain accessory factors helped mitigate and even cure these diseases such as beriberi, scurvy, and rickets. Accessory factors, later coined vitamins by Casimir Funk, are an essential constituent of the human diet. Vitamin D is technically not a vitamin but functions as a steroid hormone whose most well-known purpose is calcification of the human skeleton. This helps prevent osteomalacia in adults and rickets, a serious problem in children due to …

Synthesis And Evaluation Of 4-Cycloheptylphenols As Selective Estrogen Receptor-Β Agonists (Serbas), K. L. Iresha Sampathi Perera, Alicia M. Hanson, Sergey V. Lindeman, Andrea Imhoff, Xingyun Lu, Daniel S. Sem, William A. Donaldson

Chemistry Faculty Research and Publications

A short and efficient route to 4-(4-hydroxyphenyl)cycloheptanemethanol was developed, which resulted in the preparation of a mixture of 4 stereoisomers. The stereoisomers were separated by preparative HPLC, and two of the stereoisomers identified by X-ray crystallography. The stereoisomers, as well as a small family of 4-cycloheptylphenol derivatives, were evaluated as estrogen receptor-beta agonists. The lead compound, 4-(4-hydroxyphenyl)cycloheptanemethanol was selective for activating ER relative to seven other nuclear hormone receptors, with 300-fold selectivity for the β over α isoform and with EC₅₀ of 30–50 nM in cell-based and direct binding assays.

14-3-3zeta Role In Promoting Survival Of Cells To Facilitate Progression Of Cancer, Katie Pennington, Eranga Roshan, Joshua Andersen, Katherine K. Mccormack

Student Works

The regulatory protein 14-3-3z promotes cellular growth and survival, and high expression levels of 14-3-3z are associated with mortality in multiple cancer types. 14-3-3z binds cellular proteins in a phosphorylation-dependent manner to modulate their functions. We have been characterizing the interactome of 14-3-3z which will likely lead to candidates for novel therapies for chemoresistant cancers. Tumor cells must be able to survive in a variety of stresses within the tumor microenvironment, including hypoxia, which occurs when tumors lack adequate blood supply. Previous data from our lab suggested that 14-3-3z promotes the adaptation of tumor cells to hypoxic stress. Our hypothesis …

Chemotherapeutic Applications Of Rhodamine Based Nanogumbos, Nimisha Bhattarai

LSU Doctoral Dissertations

The work presented in this dissertation employs nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS) for selective chemotherapeutic applications. GUMBOS, similar to ionic liquids, are organic salts consisting of a bulky cationic and anionic moiety. In contrast to ionic liquids, these materials have melting points ranging from 25–250 °C, making them solid phase at room temperature. Similar to ionic liquids, GUMBOS display tunable properties, such as hydrophobicity and solubility, through counter ion variation. These tunable properties provide a variety of applications for these GUMBOS, including selective chemotherapeutics applications. The …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

Application Of Synthetic Organic And Medicinal Chemistry Toward Medical Advances In Cancer, Antibiotics, And Drug Delivery, Marlon Lutz

Dissertations

Cancer and bacterial infections are a great concern in our society and have affected populations worldwide. The objective of this research was to discover new therapies for treating bacterial infections and cancer, and for promoting drug delivery.

DapE is an essential component in succinylase biosynthetic pathway, which is critical to production of lysine and m-DAP which both are essential in protein synthesis and bacterial peptidoglycan cell wall construction. Synthetic approaches were developed to prepare a new substrate for the N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) enzyme enabling the discovery of new antibiotics that inhibit DapE.

MMPs are over expressed in cancer, in …

Role Of Non-Muscle Myosin Ii In Hs578t/Hs578ts(I)8 Triple Negative Breast Cancer Progression, Shimara Gunawardana

Electronic Theses and Dissertations

Loss of cell-cell adhesion and migration are prerequisites for the formation of metastases. These events are mediated by changes in the actomyosin cytoskeleton. Nonmuscle myosin II (NMII) belongs to the myosin superfamily of motor proteins which binds to actin and controls actin cross-linking and contraction, however its role and regulation in cell-adhesion and migration remains poorly understood. In this study, we report that associations of α5β1integrin receptors and Ncadherins with NMII isoforms NM-IIA and NMII-B correlate with increased cell-cell adhesion and reduced migratory behavior of the parental Hs578T cells of the Hs578T/Hs578Ts(i)8 triple-negative breast cancer progression model. Using blebbistatin, a …

Chemically And Biologically Responsive Nanoparticle Systems For Biomarker Detection And Combination Cancer Therapy, Neil M. Robertson

Legacy Theses & Dissertations (2009 - 2024)

The uniqueness and expression of miRNAs as biomarkers in certain cancers has the potential to radically alter the detection, and therefore the treatment, of the disease. Not only are current detection methods time consuming, and not sensitive enough for biomedical applications, but these small RNAs have yet to be fully utilized in treatment. By utilizing different nanomaterials we aimed to create novel nanodevices for the early, sensitive and specific detection of these biomarkers in a minimally invasive way and develop dual drug releasing nanoparticles, which are entirely controllable, to aid in the treatment of resistant cancer phenotypes.

Dually Modified Transmembrane Proteoglycan Tβriii/Betaglycan In Cell Signaling And Cancer, Laura M. Jenkins

Theses and Dissertations

During tumor progression, cancer cells undergo a number of alterations to evade tumor inhibitory mechanisms, proliferate, invade surrounding tissues and metastasize to distant sites. These properties reflect changes in their cell signaling pathways that, in normal cells, control aberrant cell proliferation, motility, and survival. Over the past few decades, hyperactive Wnt/β-catenin signaling has been linked to the formation of multiple cancers, including malignant ovarian cancer, making identification of molecules regulating Wnt/β-catenin signaling crucial to the development of early detection methods and cancer treatment strategies. Proteoglycans, which regulate transmission of cellular signals, are implicated in the pathophysiology of diseases, including cancer, …

The Great Potential Of Redox Active Ligands: Applications In Cancer Research And Redox Active Catalysis, Meredith Miles

Browse all Theses and Dissertations

Metal N-heterocyclic carbene (NHC) complexes have recently gained much popularity due to their tunable, steric, and electronic properties. Applications for such versatile molecules include organocatalysis, olefin metathesis, sundry cyclization reactions, and materials chemistry. Redox active NHCs are of special interest due to their ability to alter the electronic properties of the metal centers they are ligated to. In the first chapter, Au(I)-NHC complexes were synthesized and tested for biological activity in human cancer cell lines. Increasing reactive oxygen species (ROS) in cellular systems has proven to be a successful pathway for treating cancer. The redox active group in this case …

Key Enzymes In Cancer: Mechanism Of Action And Inhibition With Anticancer Agents, Debasish Bandyopadhyay, Gabriel Lopez, Stephanie Cantu, Samantha Balboa, Annabel Garcia, Christina Silva, Diandra Valdes

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Several enzymes play significant role in different stages of cancer including proliferation, invasion, metastasis and angiogenesis. Mechanism of actions of a few key enzymes along with their inhibitors have been discussed with particular attentation to riboneucleotide reductase, thymidylate synthease, topoisomerase II, interleukins, cell survival proteins and aminopeptidase N.

Cytidine Deaminase As A Molecular Target In Cancer: An Insight, Claudia A. Almaraz, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Cancer is one of the leading causes of death globally. Although more than 400 varieties of cancer have been reported, based on cell lines, still the actual reason of all types of cancer is not very clear. Several internal and external factors have been identified and the study is ongoing. Up to now about 73 proteins have been identified that are capable to influence directly various phases of cancer including mutation, cell proliferation, invasion, angiogenesis, and metastasis. Cytidine deaminase is one of the important proteins that is responsible for various types of cancer that includes gastric, liver, biliary tract, bladder, …

Mri In Cancer: Improving Methodology For Measuring Vascular Properties And Assessing Radiation Treatment Effects In Brain, Chong Duan

Arts & Sciences Graduate Student Theses and Dissertations

Tumors cannot survive, progress and metastasize without recruiting new blood vessels. Vascular properties, including perfusion and permeability, provide valuable information for characterizing cancers and assessing therapeutic outcomes. Dynamic contrast-enhanced (DCE) MRI is a non-invasive imaging technique that affords quantitative parameters describing the underlying vascular structure of tissue. To date, the clinical application of DCE-MRI has been hampered by the lack of standardized and validated quantitative modeling approaches for data analysis.From a therapeutic perspective, radiation therapy is a central component of the standard treatment for patients with cancer. Besides killing cancer cells, radiation also induces parenchymal and stromal changes in normal …

Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie

Mahurin Honors College Capstone Experience/Thesis Projects

With the invention of advanced technology, focus has been put on understanding and looking for potential cures for many diseases, one of which is cancer. The difference in the leaving and non-leaving ligands of the FDA approved cancer drugs contributes to the differential cell specific cytotoxic effects. These drugs such as oxaliplatin approved for colorectal cancer, cisplatin approved for testicular cancer, and their analogs were used to treat different cancer cell lines in an MTT assay. This project aims to determine how changing the molecular shape of these compounds affects their uptake and toxicity into different cell lines. The assay …

One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii

Electronic Theses & Dissertations

In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer …

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 …

Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett

Undergraduate Honors Theses

Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no …

The Anticancer Effects Of The Different Analogs Of Cysteine Deleted Tachyplesin On A549 Lung Cancer Cells, Nathan Riley Hendrickson

Master's Theses and Doctoral Dissertations

It has been previously shown that cysteine-deleted tachyplesin (CDT) and its many analogs display antibacterial effects. However, little has been said about its possible anticancer effects and which analogs serve as the best inhibitors of the growing cancer cells. This research focused on CDT and four of its analogs: All D-CDT, Reverse DCDT, Reverse CDT, and Serine-Control CDT. MTT assays against the A549 adenocarcinoma lung cancer cell line showed All D-CDT to be the most effective analog in preventing cancer cell growth. Hyaluronidase and apoptosis assays were performed to better understand the mechanism by which the All D-CDT is preventing …

Synthesis Of Vorinostat And Cholesterol Conjugate To Enhance The Cancer Cell Uptake Selectivity, Nethrie D. Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su Ph.D.

Chemistry Faculty Publications

Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells. Herein, we designed and synthesized a SAHA cholesterol conjugate, and further formed …

Ligands Of Therapeutic Utility For The Liver X Receptors., Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar

Faculty and Staff Publications

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. …

Improving Binding Affinity Through Cyclization, Kaylee M. Newcomb, Nicolas Abrigo

Undergraduate Research Posters

Cancer chemotherapy results in systematic damage as the drugs used are also toxic to benign tissue. Sensitizing a cancer cell to therapy by interfering with the DNA repair mechanisms would decrease overall toxicity, as the necessary dosage of chemotherapy drugs would be lowered. The Hartman lab developed a peptide (8.6) that binds with a KD of 1 μM to the C-terminal domain of breast cancer associated protein (BRCA1), blocking homologous recombination. The crystal structure of the peptide shows the tyrosine and threonine residues are close together, suggesting that by cyclizing these positions, the peptide may already be constrained into its …

Functional And Mechanistic Insight Into The Role Of Atg9a In Autophagy, Vajira Kaushalya Weerasekara

Theses and Dissertations

The bulk degradative process of macroautophagy requires the dynamic growth of autophagosomes, which carry cellular contents to the lysosome for recycling. Atg9A, a multi-pass transmembrane protein, is an apical regulator of autophagosome growth, yet its regulatory mechanism remains unclear. Our work suggests that hypoxia (low glucose and oxygen) triggers a rearrangement of the small adapter protein 14-3-3ζ interactome. Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3z docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on …