Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds,
2023
Chapman University
Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari
Pharmacy Faculty Articles and Research
The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a–d …
Identifying The Temporal N-Linked Glycosylation Changes During Liver Disease Progression: From Liver Injury To End-Stage Liver Disease,
2023
Medical University of South Carolina
Identifying The Temporal N-Linked Glycosylation Changes During Liver Disease Progression: From Liver Injury To End-Stage Liver Disease, Shaaron Ochoa-Rios
MUSC Theses and Dissertations
The high mortality rates of liver diseases and primary liver cancers can be attributed to the lack of screening and diagnostic strategies currently available for early detection. Non-alcoholic fatty liver disease (NAFLD) is an early stage of liver disease known to progress to a variety of pre-malignant and malignant conditions, like advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA). Based on the wide variety of diseases that NAFLD can progress to, strategies to understand and detect the progression of NAFLD are of great value. Core fucosylation of N-linked glycans has been demonstrated to be useful for the clinical diagnosis …
Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo,
2023
Thomas Jefferson University
Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …
Parkin Ubiquitination Of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression,
2023
Thomas Jefferson University
Parkin Ubiquitination Of Kindlin-2 Enables Mitochondria-Associated Metastasis Suppression, Minjeong Yeon, Irene Bertolini, Ekta Agarwal, Jagadish C Ghosh, Hsin-Yao Tang, David W. Speicher, Frederick Keeney, Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Edward F. Plow, Lucia R. Languino, Emmanuel Skordalakes, M Cecilia Caino, Dario C. Altieri
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
Mitochondria are signaling organelles implicated in cancer, but the mechanisms are elusive. Here, we show that Parkin, an E3 ubiquitination (Ub) ligase altered in Parkinson's disease, forms a complex with the regulator of cell motility, Kindlin-2 (K2), at mitochondria of tumor cells. In turn, Parkin ubiquitinates Lys581 and Lys582 using Lys48 linkages, resulting in proteasomal degradation of K2 and shortened half-life from ∼5 h to ∼1.5 h. Loss of K2 inhibits focal adhesion turnover and β1 integrin activation, impairs membrane lamellipodia size and frequency, and inhibits mitochondrial dynamics, altogether suppressing tumor cell-extracellular matrix interactions, migration, and invasion. Conversely, Parkin does …
Regulation Of De Novo And Maintenance Dna Methylation By Dnmt3a And Dnmt3b,
2023
The Texas Medical Center Library
Regulation Of De Novo And Maintenance Dna Methylation By Dnmt3a And Dnmt3b, Yang Zeng
Dissertations & Theses (Open Access)
DNA methylation (5-methylcytosine, 5mC) is essential for the regulation of gene expression and integrity of the mammalian genome. It occurs predominantly in the context of CpG dinucleotides to form a symmetrical pattern on both DNA strands, which allows DNA methylation patterns to be semi-conservatively maintained during DNA replication. There are two classes of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B function primarily as de novo methyltransferases that establish DNA methylation patterns, whereas DNMT1 is the major enzyme responsible for maintaining DNA methylation patterns by converting hemi-methylated CpGs to fully methylated CpGs during DNA replication. Two accessory factors also play critical regulatory …
Oncolytic Virus Immunotherapy: Development And Potential For Cancer Treatment,
2023
University of Connecticut
Oncolytic Virus Immunotherapy: Development And Potential For Cancer Treatment, Olivia Guinness
Honors Scholar Theses
The American Cancer Society estimates that in 2023, 1,958,310 new cancer cases and 609,820 cancer deaths will occur in the United States [16]. A promising therapeutic option that has been supported by recent clinical trials is the use of oncolytic viruses to treat malignant tumors. The mechanism of action of existing treatments, such as chemotherapy, radiotherapy, and surgery, differs from that of oncolytic virus therapy because oncolytic viruses are able to affect cancer cells with specificity, minimizing side effects. When infecting a normal, non-cancerous cell, oncolytic viruses do not replicate, leaving healthy cells unaffected. In tumor cells, oncolytic viruses will …
Investigating The Phenotypic Effects Of Ring1- And Yy1-Binding Protein (Rybp) In Glioblastoma Multiforme,
2023
Winthrop University
Investigating The Phenotypic Effects Of Ring1- And Yy1-Binding Protein (Rybp) In Glioblastoma Multiforme, Ronald W. Bucher
Graduate Theses
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer that has horrendous survival outcomes with the use of current therapies. Further study into its molecular mechanisms will inform development of new, more effective treatments. The Polycomb protein RING1- and YY1- Binding Protein (RYBP) has emerged as an important gene in multiple cancers. In complex with other Polycomb proteins, RYBP acts to repress regions of chromatin, though it also performs other functions independent of these complexes. RYBP has a tumor suppressive role in various cancers, but may act as an oncogene in others, demonstrating its context-specific effects. The role of …
Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape,
2023
The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences
Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li
Dissertations & Theses (Open Access)
Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NKTROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …
Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans,
2023
University of Arkansas, Fayetteville
Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans, Hannah Smith
Chemistry & Biochemistry Undergraduate Honors Theses
Isocitrate dehydrogenase is an important enzyme in the citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. While there are three isoforms of isocitrate dehydrogenase (IDH1, IDH2, and IDH3), this research will focus on IDH1. The phosphorylation of isocitrate dehydrogenase is a process that has been linked to the formation of both luminal-like and basal-like breast cancer. Despite these correlations, the mechanisms that cause breast cancer development are unknown. To examine this, an enzyme activity assay for each phosphorylation variant and crystallization were conducted. The results of these indicate that phosphorylation at each site (IDH1-T77, IDH1-S188, …
Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers,
2023
The Texas Medical Center Library
Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha
Dissertations & Theses (Open Access)
Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …
Investigation Of The Role Of Dax-1 In The Hpa Axis In Human Adrenal Cells,
2023
University of San Francisco
Investigation Of The Role Of Dax-1 In The Hpa Axis In Human Adrenal Cells, Katerina N. Fargas
Undergraduate Honors Theses
DAX-1 is a nuclear hormone orphan receptor that plays a key role in the development of reproductive tissues and steroid hormone production. The hypothalamic-pituitary-adrenal axis is the pathway for steroid hormone production, primarily glucocorticoids, mineralocorticoids, and adrenal androgens, in the human body. The mechanisms of DAX-1 in hormone production in the adrenal cortex of the HPA axis are not completely understood and, therefore, were the focus of this honors thesis research project. Due to the high level of DAX-1 expression, SW13 adrenal carcinoma cells were conducted for these experiments. We investigated whether glucocorticoids, specifically the synthetic glucocorticoid dexamethasone, had any …
P53 Dimers Elicit Unique Tumor Suppressive Activities Through An Altered Metabolic Program,
2023
The Texas Medical Center Library
P53 Dimers Elicit Unique Tumor Suppressive Activities Through An Altered Metabolic Program, Jovanka Gencel-Augusto
Dissertations & Theses (Open Access)
p53 is the most frequently mutated tumor suppressor in human cancer. As a tetrameric transcription factor, mutation of the p53 Tetramerization Domain (TD) is a mechanism by which cancers abrogate wild-type (WT) p53 function. p53 TD mutations result in a protein that preferentially forms monomers or dimers. These are also normal p53 states under basal cellular conditions. Although it is accepted that tetrameric p53 is required for full tumor suppressive activities, the physiological relevance of monomeric and dimeric states of p53 is not well understood. We have established in vivo models for monomeric and dimeric p53 which model Li-Fraumeni Syndrome …
Functional Analysis Of Daxx In Tumorigenesis Of Pancreatic Neuroendocrine Tumors And Embryonic Development,
2023
The Texas Medical Center Library
Functional Analysis Of Daxx In Tumorigenesis Of Pancreatic Neuroendocrine Tumors And Embryonic Development, Chang Sun
Dissertations & Theses (Open Access)
Death domain-associated protein 6 (Daxx) is a histone chaperone specific to Histone 3.3 (H3.3). DAXX interacts with ATRX forming a chromatin remodeling complex, which deposits H3.3 into telomeric and pericentric region of the genome. The importance of Daxx was manifested in embryonic development. The loss of Daxx leads to early lethality in mouse embryos around E6.5. Moreover, sequencing studies have revealed the importance of DAXX in human tumors. Mutually exclusive mutations in DAXX and ATRX occur in about 30% of pancreatic neuroendocrine tumors (PanNETs). Although lots of progress has been made in studying functions of DAXX, we still do not …
Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance,
2023
The Texas Medical Center Library
Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel
Dissertations & Theses (Open Access)
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …
Regulation And Function Of Zeb1 Acetylation In Lung Adenocarcinoma Progression And Metastasis,
2023
The Texas Medical Center Library
Regulation And Function Of Zeb1 Acetylation In Lung Adenocarcinoma Progression And Metastasis, Mabel Perez-Oquendo
Dissertations & Theses (Open Access)
Lung cancer metastasis is leading the causes of cancer-related mortality in the United States and worldwide. Epithelial-to-mesenchymal transition (EMT) is a model for metastasis that results in loss of specialized epithelial cell contacts and acquisition of mesenchymal invasive capacity. Zinc finger E-box-binding homeobox 1 (ZEB1) recognizes and binds to E-boxes of epithelial gene promoters to repress its transcription. ZEB1 has inconsistent molecular weights, which have been attributed to post-translational modifications (PTMs). In the presented dissertation, I specifically addressed the gap in the molecular mechanisms by which PTMs of ZEB1 regulate its ability to induce EMT and how its activity might …
A Dna-Peptide Crosslink (Dpc) Increases Mutagenicity In Sos-Induced Escherichia Coli,
2023
University of Connecticut
A Dna-Peptide Crosslink (Dpc) Increases Mutagenicity In Sos-Induced Escherichia Coli, Alessandra Bassani
Honors Scholar Theses
Bacteria, such as Escherichia coli, have an inducible system in response to DNA damage termed the SOS response. This system is activated when the replicative DNA polymerase (Pol) III encounters a lesion, uncouples from DNA helicase, and single-stranded DNA (ssDNA) accumulates at the replication fork. In this study, we investigated DNA-peptide crosslink (DpC), a common lesion that results from cross-linking of proteins or peptides, UV irradiation, and alkylating agents. To increase survival following formation of a lesion, the SOS response can utilize homologous recombination, translesion synthesis (TLS), or excision repair. With TLS, the levels of DNA Pol II, IV, …
Y Chromosome Gene Kdm5d Epigenetically Drives Sex Differences In Colorectal Cancer,
2023
The Texas Medical Center Library
Y Chromosome Gene Kdm5d Epigenetically Drives Sex Differences In Colorectal Cancer, Jiexi Li
Dissertations & Theses (Open Access)
Sex exerts a profound impact on cancer incidence, spectrum and outcomes, yet the molecular genetic bases of such sex differences are ill-defined and presumptively ascribed to X-chromosome genes and sex hormones. Such sex differences are particularly prominent in colorectal cancer (CRC) where men experience higher metastases and mortality. A murine CRC model, engineered with an inducible transgene encoding oncogenic mutant KRASG12D and conditional null alleles of Apc and Trp53 tumor suppressors (designated iKAP), revealed higher metastases and worse outcomes specifically in males with oncogenic mutant KRAS (KRAS*) CRC. Integrated cross-species molecular and transcriptomic analyses identified Y-chromosome gene histone demethylase …
Elucidating Mechanisms Involved In Host Microbial-Tumor Interactions,
2023
The Texas Medical Center Library
Elucidating Mechanisms Involved In Host Microbial-Tumor Interactions, Vidhi Chandra
Dissertations & Theses (Open Access)
Cancer is a rising cause of mortality worldwide. Microbiota is the collection of micro-organisms that live inside our bodies and can impact the host health and disease by interacting with the immune and metabolic systems. The relationship between the microbiota and cancer is complex. Gut and intratumoral microbiota can affect cancer development and progression by influencing patient outcomes and therapy responsiveness in several cancer types. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer surrounded by a highly immuno-suppressive tumor microenvironment (TME) which limits efficacy of most available therapies. The tumoral niche provides a privileged microenvironment for microbial colonization that can …
Computational Modeling Of The Fanconi Anemia Gene Network And Its Connection To Cancer,
2023
University of Arkansas, Fayetteville
Computational Modeling Of The Fanconi Anemia Gene Network And Its Connection To Cancer, Alyssa Warren-Belford
Biological Sciences Undergraduate Honors Theses
Fanconi anemia (FA) is a rare genetic condition in which the cell’s DNA repair machinery is dysregulated, significantly increasing the chances of tumorigenesis. Further research is being done in order to improve patient outcomes and incidences of cancer. Our group created a computational model of the FA DNA repair gene network, which removes interstrand crosslinks found in damaged DNA and repairs it so DNA synthesis can continue. Computer simulations show the number of DNA damage indicators decreased as the pathway continued. This was expected as the FA pathway repairs DNA damage. The goal of this project was to provide further …
Investigating The Role Of Spatial Compartmentalization And Genomic Translocations In Metastatic Cancer: A Multi-Omic Analysis,
2023
University of Tennessee, Knoxville
Investigating The Role Of Spatial Compartmentalization And Genomic Translocations In Metastatic Cancer: A Multi-Omic Analysis, Joshua Harris Garretson
Chancellor’s Honors Program Projects
No abstract provided.
