Cancer Biology Commons^™

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

The Use Of Fecal Microbiota Transplant In Overcoming And Modulating Resistance To Anti-Pd-1 Therapy In Patients With Skin Cancer, Tahne Vongsavath, Rodd Rohmani, Kyaw Min Tun, Vignan Manne

Department of Internal Medicine Faculty Research

While immune checkpoint inhibitors have evolved into the standard of care for advanced melanoma, 40–50% of melanoma cases progress while on therapies. The relationship between bacterium and carcinogenesis is well founded, such as in H. pylori in gastric cancers, and Fusobacterium in colorectal cancers. This interplay between dysbiosis and carcinogenesis questions whether changes in the microbiome could affect treatment. Thus, FMT may find utility in modifying the efficacy of anti-PD-1. This review aims to examine the use of FMT in treatment-resistant melanoma. A literature search was performed using the keywords “fecal microbiota transplant” and “skin cancer”. Studies were reviewed for …

Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam

Physical Therapy Faculty Articles and Research

Introduction:

Cancer is one of the most prevalent diseases from children to elderly adults. This will be deadly if not detected at an earlier stage of the cancerous cell formation, thereby increasing the mortality rate. One such cancer is colorectal cancer, caused due to abnormal growth in the rectum or colon. Early screening of colorectal cancer helps to identify these abnormal growth and can exterminate them before they turn into cancerous cells.

Aim:

Therefore, this study aims to develop a robust and efficient classification system for colorectal cancer through Convolutional Neural Networks (CNNs) on histological images.

Methods:

Despite challenges in …

A Cyclin D1 Intrinsically Disordered Domain Accesses Modified Histone Motifs To Govern Gene Transcription, Xuanmao Jiao, Gabriele Di Sante, Mathew Casimiro, Agnes Tantos, Anthony Ashton, Zhiping Li, Yen Quach, Dharmendra Bhargava, Agnese Di Rocco, Claudia Pupo, Marco Crosariol, Tamas Lazar, Peter Tompa, Chenguang Wang, Zuoren Yu, Zhao Zhang, Kawthar Aldaaysi, Ratna Vadlamudi, Monica Mann, Emmanuel Skordalakes, Andrew Kossenkov, Yanming Du, Richard Pestell

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The essential G₁-cyclin, CCND1, is frequently overexpressed in cancer, contributing to tumorigenesis by driving cell-cycle progression. D-type cyclins are rate-limiting regulators of G₁-S progression in mammalian cells via their ability to bind and activate CDK4 and CDK6. In addition, cyclin D1 conveys kinase-independent transcriptional functions of cyclin D1. Here we report that cyclin D1 associates with H2B^S14 via an intrinsically disordered domain (IDD). The same region of cyclin D1 was necessary for the induction of aneuploidy, induction of the DNA damage response, cyclin D1-mediated recruitment into chromatin, and CIN gene transcription. In response to …

Role Of Cyp3a5 In Prostate Cancer Growth, Ranjana Mitra, Jake Mclean, Ajay P. Singh, Edwin C. Oh

COM Scholarship

No abstract provided.

Assessing The Role Of Kmt2b Knockdown In Rhabdoid Tumorigenesis Utilizing Crispri, Karah Edmonds, Andrea Florian Phd

Science University Research Symposium (SURS)

An aggressive blood cancer commonly observed in pediatric patients, Mixed Lineage Leukemia (MLL), has a regulatory MLL complex that promotes histone methyltransferation. Modifying histones utilizing histone methyltransferases like KMT2B (MLL2), is essential for gene expression by regulating transcription. Loss of function and inhibition of KMT2B leads to dysregulation of transcription and therefore promotes MLL tumorigenesis. To improve cancer-targeted therapies, we will use CRISPR interference (CRISPRi) to knock down the expression of KMT2B and measure levels of Rhabdoid tumor cell proliferation and apoptosis. Previous research surrounding the MLL complex suggests that decreased expression of KMT2B will lead to increased levels of …

Studying The Role Of Novel Carbon Nano Tubes As A Therapeutic Agent To Treat Triple Negative Breast Cancer (Tnbc) - An In Vitro And In Vivo Study, Kamal Asadipour, Narendra Banerjee, Jazmine Cuffee, Karrington Perry, Shennel Brown, Anasua Banerjee, Erik Armstrong, Stephen Beebe, Hirendra Banerjee

Bioelectrics Publications

Triple Negative Breast Cancer (TNBC) is a malignant cancer with a very high mortality rate around the world. African American(AA) women are 28% more likely to die from triple-negative breast cancer (TNBC) than white women with the same diagnosis. AA patients are also more likely to be diagnosed at a later stage of the disease and have the lowest survival rates for any stage of diagnosis; There are very few existing anti TNBC drugs with therapeutic efficacy hence newer anti TNBC drug design and investigation is needed. Carbon Nano Tubes(CNT) in recent years have shown effective anti-cancer properties in various …

Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) …

Plk1 Overexpression Drives Tumorigenesis In A Prostate Cancer Mouse Model, Emile Kachouh

Theses and Dissertations

Prostate cancer is the leading cause of cancer-related deaths among men worldwide, and the development of resistance to existing treatments necessitates the exploration of new therapeutic strategies, including combination therapies. This study investigates the role of Polo-like kinase 1 (PLK1), located on chromosome 16p12.2, as an oncogene in prostate cancer. We generated a transgenic mouse model with prostate-specific overexpression of PLK1 to closely mimic human prostate cancer progression. Quantitative PCR (qPCR) analysis was employed to characterize the molecular profile of PLK1, revealing its implication in multiple pathways. To further elucidate the functional consequences of PLK1 overexpression, we confirmed phenotypic progression …

Investigating The Regulation Of Epithelial-Mesenchymal Transition Through Fibronectin-Mediated Tgf-Β1 Mechanotransduction Using In Vitro Models Of Triple-Negative Breast Cancer, Michael M. Sofroniou

Theses and Dissertations

TGF-β1 is a potent regulator of epithelial-mesenchymal transtion (EMT), a cellular
transdifferentation process that promotes cellular motility and matrix remodeling, critical to tumorigenesis and metastasis. TGF-β1-induced EMT promotes the assembly of FN, which synergistically binds latent TGF-β1 to aid in its activation. The purpose of of this work is to further probe the effects of autocrine TGF-β1 signaling during EMT progression by utilizing CRISPR-Cas9 deletion of the TGFB1 gene in in vitro models of triple-negative breast cancer. The studies outlined in this work demonstrate that autocrine TGF-β1 maintains a baseline level of mesenchymal marker expression. It also functions to desensitize …

Elucidation Of Mismatch Repair Regulation By Abl1: Advantages/Disadvantages Of Tyrosine Kinase Inhibitor Treatment, Hannah Daniels

Theses and Dissertations--Toxicology and Cancer Biology

DNA mismatch repair (MMR) is a critical repair process necessary for not only repairing mispairs incorporated into the DNA during replication, but also for inducing apoptosis in response to certain types of DNA damage. MMR is required for maintaining genomic integrity and due to the importance of this pathway, any impairment of its function can lead to increased mutation frequency, which is well known to be a driving force of cancer development, progression, and resistance. Despite extensive studies involving the proteins involved in the MMR pathway, the regulation of those proteins remains relatively unknown. Regulation of MLH1, a protein necessary …

Acquired Treatment Resistance In Prostate Cancer Via The Production Of Radiation Derived Extracellular Vesicles Containing Mitochondrial Proteins, Caitlin Miller

Theses and Dissertations--Toxicology and Cancer Biology

Radiation treatment (RT) is one of the most commonly administered treatments for prostate cancer (PCa) patients, yet the recurrence of tumors after RT remains one of the significant challenges in the eradication of PCa. In addition to induction of DNA damage, ROS production, and cell death, we found that RT promotes Extracellular vesicle (EV) production in PCa cells, at least in part, through H₂O₂ production (Miller CE et al., Antioxidants 2022, PMID 36358489). Since we observed EV production upon RT, EVs and their contents could play a role(s) in cancer survival after RT. By using flow cytometry …

Porcupine’S Role In The Enhancement Of Enzalutamide Efficacy In Drug Resistant Prostate Cancer, Katelyn Jones

Theses and Dissertations--Toxicology and Cancer Biology

Androgen receptor (AR) signaling continues to participate as a vital component of castration-resistant prostate cancer (CRPC). Subsequently, this has led to the development of Androgen Signaling Inhibitors (ASI), specifically Enzalutamide (ENZ), which is a direct inhibitor of AR, to clinically manage CRPC. Inevitably, ENZ treatment only provides improvement for approximately two months before advancing to an incurable form, ENZ-resistant CRPC. With PCa ranking as the second leading cause of cancer-related deaths in USA males, there is an urgency and necessity for the discovery and development of novel therapeutic approaches for CRPC. Wnt signaling has been extensively documented in its involvement …

Therapeutic Approaches And Novel Mechansims In Cancer Progression, Kendall Simpson

Theses and Dissertations--Toxicology and Cancer Biology

Prostate cancer (PCa) remains the most diagnosed cancer among men in the United States. There are various therapeutic routes that are implored to combat this fatal disease, and our work aims to increase the options made available to PCa patients. A combination treatment of Enzalutamide (Enz), an FDA approved drug for castration-resistant PCa patients, and Metformin, an FDA approved drug for type 2 diabetes, was utilized to enhance the efficacy of Enz in Enz-resistant PCa, both in vitro and in vivo. Thymic Lymphoma is one of the most common malignancies that can occur in various tissues and organs. Genomic stability …

Delineating Contributions Of Genotype And Lineage To Lung Cancer Therapy Response, Kassandra Jo Naughton

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) heterogeneity is a major challenge for determining effective treatment strategies. Adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) are histologically and epigenetically distinct subtypes of NSCLC. Patients with ADC tumors harboring mutations in both KRAS and LKB1 (aka STK11) have lower survival rates than those with KRAS-only tumors. KRAS/LKB1 tumors are not only aggressive, but also respond poorly to immunotherapy. However, these data are limited to ADCs, and it is unclear if SCCs with this genotype are also resistant to immunotherapy. We developed a mouse model of Kras^mut/Lkb1^mut capable of producing …

Dynamics Of Cell Membrane Lesions And Adaptive Conductance Under The Electrical Stress, Mantas Silkunas, Olga N. Pakhomova, Giedre Silkuniene, Andrei G. Pakhomov

Bioelectrics Publications

Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reflection fluorescence (TIRF) imaging of Ca(2+) entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a …

Zebrafish Drug Screening Identifies Erlotinib As An Inhibitor Of Wnt/ Β-Catenin Signaling And Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd A. Al-Hamaly, Anna H. Cox, Meghan G. Haney, Wen Zhang, Emma C. Arvin, Shilpa Sampathi, Mary Wimsett, Chunming Liu, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The effi- cacy of the top hit, Erlotinib, extended to human cells, where it …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

A Rainy Day For Cancer: The Characterization And Utilization Of The Long Non-Coding Rna Lnc-Rainy In The Radiation Response Of Non-Small Cell Lung Cancer, Emily S. Rice

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung Cancer remains the leading cause of cancer-related deaths worldwide. While important improvements have been made to the treatment of non-small cell lung cancer (NSCLC), treatment resistance is a critical issue facing the majority of patients. Previously, our lab identified a group of long non-coding RNAs (lncRNAs) known as linc-SPRY3 RNAs, expressed on the Y-chromosome, that play a role in radiation sensitivity by decreasing tumor burden in vitro and in vivo after radiation. Through molecular cloning methods and further functional characterization, here we present evidence that the linc-SPRY3 RNAs were originally mischaracterized as individual linc-RNAs but are in fact parts …

Enhancement Of Antitumor Effects Of Berberine Chloride With A Copper(Ii) Complex Against Human Triple Negative Breast Cancer: In Vitro Studies, Duaa R. Alajroush, Brittney F. Anderson, Janae A. Bruce, Christian I. Lartey, Dazonte A. Mathurin, Sean T. Washington, Tanaya S. Washington, Sidy Diawara, Sakariyau A. Waheed, Kaylin L. Thomas, Stephen J. Beebe, Alvin A. Holder

Chemistry & Biochemistry Faculty Publications

In this study, the copper(II) complex [Cu(chromoneTSC)Cl₂]•0.5H₂O•0.0625C₂H₅OH (where chromoneTSC = (E)-N-Ethyl-2-((4-oxo-4H-chromen-3-yl)methylene)-hydrazinecarbothioamide) was synthesized and characterized; then used to carry out in vitro studies in combination with berberine chloride (BBC). The ligand and complex were characterized by elemental analysis, FTIR and NMR (¹H and ¹³C) spectroscopy, and conductivity measurements. The cytotoxic effect was analyzed by using the CCK-8 viability assay in cancer MDA-MB-231 VIM RFP and non-cancer MCF-10A cell lines. The IC₅₀ values for the complex and BBC were 21.2 ± 1.6 and 48.3 ± 2.4 μM, respectively at 24 h incubation, while the IC₅₀ value of the combination treatment …