Biology Commons^™

A Novel Algorithm For The Virtual Screening Of Extensive Small Molecule Libraries Against Ercc1/Xpf Protein-Protein Interaction For The Identification Of Therapeutic Resistance-Bypassing Small Anticancer Molecules, Salma Ghazy, Lalehan Oktay, Serdar Durdagi

Turkish Journal of Biology

Background and aim:Cancer cell’s innate chemotherapeutic resistance continues to be an obstacle in molecular oncology. This theory is firmly tied to the cancer cells’ integral DNA repair mechanisms continuously neutralizing the effects of chemotherapy. Amidst these mechanisms, the nuclear excision repair pathway is crucial in renovating DNA lesions prompted by agents like Cisplatin. The ERCC1/XPF complex stands center-stage as a structure specific endonuclease in this repair pathway. Targeting the ERCC1/XPF dimerization brings forth a strategy to augment chemotherapy by eschewing the resistance mechanism integral to cancer cells. This study tracks and identifies small anticancer molecules, with ERCC1/XPF inhibiting potential, within …

Viral Epitope Scanning Reveals Correlation Between Seasonal Hcovs And Sars-Cov-2 Antibody Responses Among Cancer And Non-Cancer Patients, Salum J. Lidenge, Dicle Yalcin, Sydney J. Bennett, Owen Ngalamika, Brenda B. Kweyamba, Chacha J. Mwita, For Yue Tso, Julius Mwaiselage, John T. West, Charles Wood

School of Biological Sciences: Faculty Publications

Seasonal coronaviruses (HCoVs) are known to contribute to cross-reactive antibody (Ab) responses against SARS-CoV-2. While these responses are predictable due to the high homology between SARS-CoV-2 and other CoVs, the impact of these responses on susceptibility to SARS-CoV-2 infection in cancer patients is unclear. To investigate the influence of prior HCoV infection on anti- SARS-CoV-2 Ab responses among COVID-19 asymptomatic individuals with cancer and controls without cancers, we utilized the VirScan technology in which phage immunoprecipitation and sequencing (PhIP-seq) of longitudinal plasma samples was performed to investigate high-resolution (i.e., epitope level) humoral CoV responses. Despite testing positive for anti-SARS-CoV-2 Ab …

Expression Patterns Of M6a Rna Methylation Regulators Under Apoptotic Conditions In Various Human Cancer Cell Lines, Azime Akçaöz Alasar, Buket Sağlam, İpek Erdoğan Vatansever, Bünyamin Akgül

Turkish Journal of Biology

Background/aim: Cancer is a complex disease that involves both genetic and epigenetic factors. While emerging evidence clearly suggests that changes in epitranscriptomics play a crucial role in cancer pathogenesis, a comprehensive understanding of the writers, erasers, and readers of epitranscriptomic processes, particularly under apoptotic conditions remains lacking. The aim of this study was to uncover the changes in the expression of m6A RNA modifiers under apoptotic conditions across various cancer cell lines. Materials and methods: Initially, we quantified the abundance of m6A RNA modifiers in cervix (HeLa and ME180), breast (MCF7 and MDA-MB-231), lung (A549 and H1299), and colon (CaCo2 …

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

Locus-Specific Differential Expression Of Human Satellite Sequences In The Nuclei Of Cancer Cells And Heat-Shocked Cells, Christina Rabeler, N. Paterna, Rajiv Potluri , '20, Lia R. D’Alessandro , '21, Anusha Bhatia , '24, Shu Yi Chen , '24, Johanna Lee , '23, Bereketab Abeje , '23, Benjamin Lipchin , '25, B. R. Carone, Dawn M. Carone

Biology Faculty Works

Human satellites (HSats) are pericentric, tandemly repeating satellite DNA sequences in the human genome. While silent in normal cells, a subset of HSat2 noncoding RNA is expressed and accumulates in the nucleus of cancer cells. We developed a FISH-based approach for identification of the distribution of three subfamilies of HSat2 (A1, A2, B) sequences on individual human chromosomes. Further, using the HSat subfamily annotations in the T2T completed centromere satellite (CenSat) sequence, we isolated, defined and mapped differentially expressed sequence variants of nuclear-restricted HSat2 and HSat3 RNA from cancer cell lines and heat-shocked cells. We identified chromosome-specific and subfamily-specific expression …

Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch

Graduate Student Theses, Dissertations, & Professional Papers

The COP9 signalosome is a highly conserved eukaryotic complex regulating protein degradation via deneddylation of Cullin-RING E3 ligases. CSN5, the COP9’s fifth component, contains the catalytically active domain for CSN deneddylation. The complex is inactive without CSN5; however, CSN5 engages in COP9-independent binding with several other proteins, typically promoting either destruction or stabilization of its partners. Many of its confirmed interaction partners are also implicated in tumorigenesis (prominent examples being p27 and p53) and a complex cancer interactome has been established for CSN5. Additionally, CSN5 overexpression has been documented in a staggering array of cancers of diverse origins. This discovery …

Svm-Do: Identification Of Tumor-Discriminating Mrna Signatures Via Support Vectormachines Supported By Disease Ontology, Mustafa Erhan Özer, Pemra Özbek Sarica, Kazim Yalçin Arğa

Turkish Journal of Biology

Background/aim: The complicated nature of tumor formation makes it difficult to identify discriminatory genes. Recently, transcriptome-based supervised classification methods using support vector machines (SVMs) have become popular in this field. However, the inclusion of less significant variables in the construction of classification models can lead to misclassification. To improve model performance, feature selection methods such as enrichment analysis can be used to extract useful variable sets. The detection of genes that can discriminate between normal and tumor samples in the association of cancer and disease remains an area of limited information. We therefore aimed to discover novel and practical sets …

Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty

Theses & Dissertations

Ewing sarcoma (EWS) is the second most common bone malignancy in children and adolescents. Despite improvement in survival due to advances in multimodality treatment strategies, patients with metastatic or recurrent disease have very poor outcomes. Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown.

Studies presented in this dissertation establish that EHD1 overexpression is a feature of nearly 90% EWS patient tumors with high EHD1 expression specifying shorter patient survival. ShRNA-knockdown and …

Doxorubicin-Induced Modulation Of Tgf-Β Signaling Cascade In Mouse Fibroblasts: Insights Into Cardiotoxicity Mechanisms, Conner Patricelli, Parker Lehmann, Julia Thom Oxford, Xinzhu Pu

Biology Faculty Publications and Presentations

Doxorubicin (DOX)-induced cardiotoxicity has been widely observed, yet the specific impact on cardiac fibroblasts is not fully understood. Additionally, the modulation of the transforming growth factor beta (TGF-β) signaling pathway by DOX remains to be fully elucidated. This study investigated DOX’s ability to modulate the expression of genes and proteins involved in the TGF-β signaling cascade in mouse fibroblasts from two sources by assessing the impact of DOX treatment on TGF-β inducible expression of pivotal genes and proteins within fibroblasts. Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX in the presence of TGF-β1 to …

Ribosomal Protein L8 Regulates The Expression And Splicing Pattern Of Genes Associated With Cancer-Related Pathways, Leilei Xu, Gui Yang, Bin Song, Dong Chen, Akbar. Yunus, Jiangtao Chen, Xiaogang Yang, Zheng Tian

Turkish Journal of Biology

Background/aim: Ribosomal proteins have been shown to perform unique extraribosomal functions in cell apoptosis and other biological processes. Ribosomal protein L8 (RPL8) not only has important nonribosomal regulatory functions but also participates in the oncogenesis and development of tumors. However, the specific biological functions and pathways involved in this process are still unknown. Materials and methods: RPL8 was overexpressed (RPL8-OE) in HeLa cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transcriptome sequencing was performed to analyze the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs) by RPL8-OE, both of which were …

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …

Characterizing The Effects Of Benzyl-Amino Alcohol On Cell Growth, Viability, And Migration, Ryan Miller, Jeff Hansen, Sarah Mordan-Mccombs

Annual Student Research Poster Session

The research we are performing investigates a new compound classified as benzyl-amino alcohol and begins a new endeavor into the effects of this class of compound. This compound would work well in chemotherapies because affecting healthy cells can lead to a patient’s health decline.

Mortaparibplus- A Novel Anticancer Small Molecule Abrogating Mortalin-P53 Interaction In Cancer Cells, Anissa N. Sari, Ahmed Elwakeel, Jaspreet K. Dhanjal, Vipul Kumar, Durai Sundar, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug.

Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named Mortaparib^Plus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited …

Early Stage Or Curable Cancer Diagnoses In Minorities: A Journey Of Survivors, Lora Asberry

Master of Science in Integrative Biology Theses

Patients diagnosed with early-staged or curable forms of cancer experience physical, as well as, mental challenges associated with disease progression and treatment. Previous studies have demonstrated that minorities and underrepresented communities did not receive the same level of care in comparison to their non-minority counterparts. Previous studies have also demonstrated that health disparities among minorities affected their cancer journey. This study addressed: how medical disparities varied between minorities and non-minorities, the overall effects of the cancer diagnoses in minorities compared to non-minorities, whether these perspectives differed in male vs. female participants, and whether there were any possible communication barriers between …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

Cannabidiol As A Synergist In Chemotherapy, Liam Pontes

Honors Program Theses and Projects

Cannabidiol (CBD) is a non-psychoactive compound commonly found in hemp and non-hemp plants. It has a molecular effect on cells, but its effect in modifying cellular signaling pathways has not been thoroughly tested until recently. Experimentation was done to determine whether CBD could induce cell death in MCF7 breast cancer cells. Both normal MCF7 cells and Cisplatin resistant MCF7 cells were used for these experiments. The cells were dosed with 0, 0.5, and 1.0 g/ml CBD dissolved in methanol. Later micrographs of the treated cells were collected and Annexin staining to determine the effect of CBD on cell death was …

Characterization Of Neutrophil Extracellular Traps In Naked Mole-Rats: A Step Towards Cancer Resistance, Thomas Abraham Smith

Undergraduate Honors Capstone Projects

Cancer is the second leading cause of death in the United States, exceeded only by heart disease. One of every five deaths in the United States is due to cancer. A growing area of research involves the analysis of cancer resistant traits in other species to understand their biological mechanisms and eventually make translations to human cancer research and clinical treatment. Because of their remarkable cancer resistance, the naked mole-rat (NMR) is a prime subject for this research, and various studies have already suggested that the immune mechanisms of the NMR might be harnessed for human cancer therapies^1-4,7. …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

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 …

Transcriptional Silencing Of Cdk18 And Its Role In Lung Carcinogenesis Of Brg1-Mutant Lung Cancers, Loryn M. Phillips

Biology ETDs

BRG1 is mutated in 10% of lung cancers, making this mutation clinically relevant. The downstream effects of BRG1 included significantly affecting the cell cycle control and chromosomal replication pathway. CDK18, a cyclin-dependent kinase, was determined to be the gene with significantly decreased expression (p < 0.0001) in the cell cycle control and chromosomal replication pathway. CDK18 is active during the S-phase of the cell cycle and required for genomic stability. Studies were conducted to determine the epigenetic mechanisms that contributed to the repression of CDK18. Histone methylation contributes to the repression of CDK18, and histone deacetylation globally regulates expression of CDK18, while cytosine methylation was found to not contribute to CDK18 expression. Studies were performed to elucidate CDK18 functional role lung carcinogenesis and the genome-wide impact of CDK18 repression. Repression of CDK18 affects cell migration, proliferation, cell-cell signaling, and anchorage-independent growth that contribute to cancer initiation and progression.

Endothelial-To-Osteoblast Transition In Normal Mouse Bone Development, Song-Chang Lin, Guoyu Yu, Yu-Chen Lee, Jian H Song, Xingzhi Song, Jianhua Zhang, Theocharis Panaretakis, Christopher J Logothetis, Yoshihiro Komatsu, Li-Yuan Yu-Lee, Guocan Wang, Sue-Hwa Lin

Faculty, Staff and Student Publications

Metastatic prostate cancer (PCa) in bone induces bone-forming lesions. We have previously shown that PCa-induced bone originates from endothelial cells (ECs) that have undergone EC-to-osteoblast (OSB) transition. Here, we investigated whether EC-to-OSB transition also occurs during normal bone formation. We developed an EC and OSB dual-color reporter mouse (DRM) model that marks EC-OSB hybrid cells with red and green fluorescent proteins. We observed EC-to-OSB transition (RFP and GFP co-expression) in both endochondral and intramembranous bone formation during embryonic development and in adults. Co-expression was confirmed in cells isolated from DRM. Bone marrow– and lung-derived ECs underwent transition to OSBs and …

Movement As Medicine: Dance/Movement Therapy For Individuals With Autism, Parkinson’S Disease, And Cancer, Alessia Zanobini

CMC Senior Theses

Dance/movement therapy (D/MT) is the psychotherapeutic use of expressive, creative movement to support holistic well-being. D/MT views the human being as a single body-mind unit and movement as a manifestation of life experiences. While typically practiced as a mental health intervention, D/MT can be adapted for a variety of populations. This thesis evaluates scientific data for the non-traditional use of D/MT for three conditions: autism, Parkinson’s disease, and cancer. For individuals on the autism spectrum, D/MT can strengthen attunement skills, provide creative communication outlets, and relieve harmful physical manifestations of autism. For individuals with Parkinson’s disease, D/MT can simultaneously ease …

Hydroquinidine Displays A Significant Anti-Carcinogenic Activity In Breast And Ovarian Cancer Cells Via Inhibiting Cell-Cycle And Stimulating Apoptosis, Mervenur Yavuz, Betül Şahi̇n, Ahmet Tarik Baykal, Turan Demi̇rcan

Turkish Journal of Biology

Breast and ovarian cancers are women's most commonly diagnosed cancers. Seeking an efficient anticarcinogenic compound is still a top priority regarding the aggressiveness of these cancers and the limited benefit of current therapies. Hydroquinidine (HQ) is a natural alkaloid used in arrhythmia and Brugada syndrome. As an ion channel blocker, HQ exhibits its activity by altering ion gradient and membrane potential. Considering the growing evidence of ion channel blockers' antineoplastic potential, we were prompted to test HQ's effect on breast and ovarian cancers. MCF-7 and SKOV-3 cell lines were used to inspect how HQ acts on survival, clonogenicity, migration, tumorigenicity, …

Methionine Restriction And Cancer Treatment: A Systems Biology Study Of Yeast To Investigate The Possible Key Players, Esra Börklü

Turkish Journal of Biology

Background/aim: Dietary restriction, mainly carbon and/or methionine restriction are among the upcoming supporting interventions along with chemotherapy in various cancers. Although dietary restriction has been proven to be beneficial, the main cellular machineries affected by its administration lacks deeper information considerably, a notable pitfall in its use as a personalized nutritional approach. Materials and methods: In this study, cellular effects of methionine restriction on a yeast model are explored via systems biology approaches. The methionine biosynthesis network, constructed by integrating interaction data with gene ontology terms, was analysed topologically, and proved to be informative about the intertwined relationship of methionine …

(R1980) Effect Of Climate Change On Brain Tumor, Pardeep Kumar, Sarita Jha, Rajiv Aggarwal, Govind Kumar Jha

Applications and Applied Mathematics: An International Journal (AAM)

In this paper, we introduce a new dynamical model addressing the variation in climate condition due the presence of microorganisms. We also introduce a new dynamical model of cancer growth which includes three interactive cell populations with drug free environment, namely tumor cells, healthy host cells, and immune effector cells. In this, we considered the super growth of tumor cells. For the choice of certain parameters, both of the systems exhibit chaotic behavior. The aim of this work is to design the controller to control the chaos and to provide sufficient conditions which achieve synchronization of two non-identical systems, which …

Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess

Open Access Theses & Dissertations

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …

Targeting Of The Hedgehog Signaling Pathway In Cancer Treatment, Andrew J. Hawes

The Cardinal Edge

The Hedgehog (Hh) signaling pathway is a developmental pathway that is highly conserved evolutionarily. While typically only displaying high activity during embryogenesis, overactivation of the Hh pathway in adults has been linked to multiple forms of cancer including acute myeloid leukemia, myelofibrosis, basal-cell carcinoma, pancreatic ductal adrenal carcinoma, and triple negative breast cancer. The prevalence of Hh activation in many different cancers has made it a prime target for inhibition of these cancers through novel therapies. This literature review sought to assess the current state of cancer treatment through inhibition of Hh signaling. Most current clinical trials involving the pathway …

Cyclase-Associated Protein 1 (Cap1) In Cyclic Adenosine Monophosphate (Camp) And Protein Kinase C (Pkc) Signals To Regulate Cancer Cell Functions, Lokesh Kalki Mani Sai Akana

Student Theses and Dissertations

Cyclase-Associated Protein 1 (CAP1) is an actin-regulating protein that promotes actin dynamics and is also involved in cell adhesion and proliferation as well as implicated in human cancers. We previously found that phosphorylation at the Ser307/Ser309 tandem regulatory site on CAP1 is critical for CAP1 functions in breast and pancreatic cancer cells. We silenced CAP1 through RNAi in HCT116 and SW480 colon cancer cells as confirmed in Western blotting. We have found that depletion of CAP1 led to reduced FAK (Focal Adhesion Kinase) activity and matrix adhesion in SW480 cells, while it stimulated FAK activity and cell adhesion in HCT116 …

Parallel Networks That Govern The Transcriptional Response To Stress, Serene Anne Durham

Legacy Theses & Dissertations (2009 - 2024)

The transcription factor, p53, plays a pivotal role in the oversight of many stimulus-dependent pathways. Its ability to respond to a wide variety of cellular stress stimuli by activating a broad range of target genes has led it to be characterized as a stress-dependent transcription factor. Our research focuses on deconvoluting the varied transcriptional response to distinct stress signals in an attempt to define the regulatory strategies leading to gene activation after cell stress. We have found that distinct stress response networks, some of which are p53-independent, are converging at activation of a common set of target genes. Our data …

Evidence That The Transcriptional Repressor Icer Is Regulated Via The N-End Rule For Ubiquitination, Angelo Cirinelli, Justin Wheelan, Christopher Grieg, Carlos A. Molina

Department of Biology Faculty Scholarship and Creative Works

ICER is a transcriptional repressor that is mono- or poly-ubiquitinated. This either causes ICER to be translocated from the nucleus, or degraded via the proteasome, respectively. In order to further studies the proteins involved in ICER regulation mass spectrometry analysis was performed to identify potential candidates. We identified twenty eight ICER-interacting proteins in human melanoma cells, Sk-Mel-24. In this study we focus on two proteins with potential roles in ICER proteasomal degradation in response to the N-end rule for ubiquitination: the N-alpha-acetyltransferase 15 (NAA15) and the E3 ubiquitin-protein ligase UBR4. Using an HA-tag on the N- or C-terminus of ICER …