Cancer Biology Commons^™

Role Of Mir-4732-3p In Breast Cancer Brain Metastasis And Brain Metastatic Tumor Microenvironment, Munazza Samar Khan

Dissertations and Theses (Open Access)

In this study, we aimed to identify microRNAs (miRNAs) that may play important roles in breast cancer brain metastasis (BCBM). To this end, we conducted miRNA-sequencing of extracellular vesicles isolated from the serum samples of 6 BCBM patients and 8 Stage I/II/III breast cancer patients, and identified 49 circulating miRNAs that were upregulated in BCBM patients compared to Stage I/II/III breast cancer. Upon further analysis, we identified miR-4732-3p to be upregulated in brain-tropic triple-negative breast cancer (TNBC) cell lines, compared to parental lines. MiR-4732-3p overexpression increased metastatic properties of TNBC cells, including proliferation, migration, invasion, and maintenance of a mesenchymal …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Stat3, Nf-Κb, And Estrogen Receptor Beta: The Balance Of Inflammation In K-Ras Mutant Lung Adenocarcinoma, Michael J. Clowers

Dissertations and Theses (Open Access)

K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. This network is underpinned by interaction and coordination of two inflammatory pathways: signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NF-κB). The balance of these transcription factors determines the degree of anti- vs. pro-tumor immunity, and a skewing towards STAT3 is known to promote tumor development and a pro-tumor TIME. It is also …

Mcf-7 Dense Breast Cancer Cells Modulate Stress Through Senescence, Lara Donadio, Moses Alfonso, Josiah Philip, Tyler Zatarain

Molloy Multidisciplinary Undergraduate Research Conference

Breast cancer remains a leading cause of cancer-related mortality among women worldwide, with dense breast tissue being recognized as a significant risk factor for its development. This dense breast tissue, characterized by a higher concentration of mammary glandular tissue, represents additional sites for tumor development. The following study explores how the MCF-7 immortal cell line, representing dense breast cancer, modulates stress responses through cellular senescence. Cellular senescence is a defense mechanism that halts the cell cycle and acts as a tumor suppression mechanism, preventing out-of-control cell proliferation triggered by cytological stress. To simulate these stress conditions, we applied two agents: …

Enhancing Skin Cancer Literacy Amongst Young Adults: A Digital Design, Katherine Stoll

Honors Projects

The skin plays a vital role in protection, regulation, and homeostasis of the human body. Skin cancer, despite being mostly preventable, is one of the most common cancers. Young adults, ages 18 to 25, are vulnerable targets due to risky behaviors and misinformation regarding skin cancer. This project was designed by using digital media and website design to enhance skin cancer health literacy among young adults. Using a systematic literature review and research methods, an interactive website was designed to improve skin cancer health literacy and eliminate common misconceptions. The topics addressed throughout the website were the biological factors of …

Leveraging Attention Mechanism To Unlock Gene And Protein Attributes, Ala Jararweh

Computer Science ETDs

Advancing personalized medicine depends on effectively integrating and interpreting the vast, heterogeneous landscape of biological data, from genomic sequences and transcriptomics to the insights embedded in scientific literature. Current machine learning models often focus on single data modalities, limiting their capacity to capture the multifaceted nature of biological systems. We address this gap by developing three attention-based machine-learning models integrating diverse data modalities. Firstly, DeepVul is a multi-task model that leverages cancer transcriptome data to predict genes critical for cancer survival and their corresponding drugs. Subsequently, LitGene refines gene representations by integrating textual information from the scientific literature. Finally, Protein2Text …

Understanding Challenges To Breast Cancer Screening For African American Women In Detroit: A Study Of Social And Healthcare Inequities, Miranda Goodson, Whitney Bowyer, Erika Lopez, Anna Lundh

Medical Student Research Symposium

African American (AA) women have lower adherence to breast cancer screening guidelines, which may contribute to delayed diagnoses and reduced survival rates. These disparities are often influenced by limited access to quality healthcare and persistent inequities faced within Michigan. With Detroit's population being 77% AA, examining studies focused on the experiences of Black women within urban healthcare networks is essential to understanding the connections between demographic, socioeconomic factors, and breast cancer outcomes. To assess these studies, a literature search was conducted using Ovid Medline yielding 24 associated articles.

Mammogram rates among AA women in Detroit remain low, reflecting a complex …

Characterizing Kmt2d In Endometrial Cancer, Katherine R. Davanzo

Medical Student Research Symposium

Endometrial cancer is rising in incidence in the United States, notably among premenopausal women. This increase and the trend of delayed childbearing warrant the need for further advancement in fertility-sparing treatment for endometrial cancer. A gene left widely unexplored in its possible clinical utility as a target for fertility-sparing treatment is KMT2D, a lysine-specific methyltransferase and tumor suppressor. Preliminary gene set enrichment analysis on a 12Z endometriotic epithelial cell line identified TIMP3 as a gene that is possibly regulated by KMT2D expression. TIMP3 encodes an irreversible inhibitor of matrix metalloproteinases (MMPs), a well-recognized class of proteins as contributing to the …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …

The Present And Future Of Robotic Surgery In Breast Cancer And Breast Reconstruction, Brett Allen, Alexis Knutson, Noama Iftekhar, Casey Giles, Jarrell Patterson, Joshua Macdavid, Richard Baynosa

Department of Plastic Surgery Faculty Research

Background: Breast cancer is the second most common cancer in women with an improving mortality rate and a growing need for reconstruction following oncologic resection. Advancements in robotic surgery and minimally invasive techniques have offered refinement to traditional open techniques of flap harvest for reconstruction, particularly regarding improved donor site morbidity. Methods: The literature review was based on a PubMed database search using the keyword “Robotic breast reconstruction” in conjunction with the Boolean operators “Flap”, “Latissimus”, and “DIEP” to specify the search. In total, 106 results were generated, which were then manually reviewed and condensed for a comprehensive stance on …

Dysregulation Of Cholesterol Metabolism And Sorafenib Drug Resistance In Hepatocellular Carcinoma, Veerababu Nagati, Dennis Kwabiah, Yamile Abuchard Anaya, Ana Ayala Pazzi, Manish K. Tripathi

Research Symposium

Background: Hepatocellular carcinoma (HCC) is among the most prevalent cancers and a leading cause of cancer-related deaths worldwide. Sorafenib, a multikinase inhibitor, serves as a key first-line treatment for HCC when surgical intervention is not an option. However, primary and acquired resistance to sorafenib has significantly limited its effectiveness, reducing the disease control rate. Dysregulation of numerous genes that influence cancer cell proliferation, survival, and drug resistance contributes to this challenge. Identifying the molecular drivers of sorafenib resistance remains critical to improving treatment outcomes. Several factors, including activation of oncogenic pathways (e.g., Akt/mTOR), hypoxia, cholesterol metabolism, EMT, multidrug resistance, and …

Investigating The Ability Of Foxo1 To Maintain Stem Cells, Stella A. Rios, Megan E. Keniry

Research Symposium

Background: Our group discovered that FOXO transcription factors drive stem gene expression in cancer to promote aggressiveness. Work by our group and others demonstrated that FOXO factors universally maintain stem cells including in cancer, embryonic, hematogenic and neuronal contents. Our current efforts are delineating the molecular underpinnings by which FOXO factors halt differentiation to maintain stem cells.

In this project, we are employing myoblasts as a valuable model to examine how Foxo1 maintains stem cells. Foxo1-regulated genes in myoblasts closely parallel its targets in glioblastoma and basal breast cancer stem cells, including targets such as Leukemia Inhibitory Factor, …

Uca1 As A Key Regulator Of The Warburg Effect During Anoikis Resistance In Colorectal Cancer Metastasis, Ricardo Pequeno Bracho, Salique Hassan Shaham, Yamile Abuchard Anaya, Sophia Leslie, Kyle Doxtater, Subhash Chauhan, Bilal Hafeez, Tamer Oraby, Manish K. Tripathi

Research Symposium

Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality in the United States. While localized CRC has a 90% five-year survival rate, this drops sharply to 14% upon metastasis. Metastasis occurs in approximately 40–50% of CRC cases and requires cancer cells to acquire anoikis resistance—a critical adaptation allowing survival after detachment from the extracellular matrix, enabling migration and colonization of secondary sites. Understanding the molecular mechanisms driving anoikis resistance, particularly those linked to altered glucose metabolism, is essential for developing targeted therapies for metastatic CRC.

Cancer cells frequently exhibit the Warburg Effect, a metabolic adaptation favoring glycolysis over …

5-Hydroxymethylcytosine Sequencing Of Plasma Cell-Free Dna Identifies Epigenomic Features In Prostate Cancer Patients Receiving Androgen Deprivation Therapies, Qianxia Li, Chiang-Ching Huang, Shane Huang, Yijun Tian, Jinyong Huang, Amirreza Bitaraf, Xiaowei Dong, Marja T. Nevalainen, Manishkumar Patel, Jodie Wong, Jingsong Zhang, Brandon J Manley, Jong Y. Park, Manish Kohli, Elizabeth M. Gore, Deepak Kilari, Liang Wang

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: We evaluated whether 5hmC signatures in cell-free DNA (cfDNA) are associated with treatment failure to androgen-deprivation therapies (ADT) among men with hormone-naive prostate cancer.

METHODS: We collected a total of 139 serial plasma samples from 55 prostate cancer patients receiving ADT at 3 time points including baseline (before initiating ADT, n = 55); 3 months (after initiating ADT, n = 55); and disease progression (n = 15) within 24 months or 24 months if no progression was detected (n = 14). We used selective chemical labeling sequencing to quantify 5hmC abundance across the genome and Kaplan-Meier analysis to assess …

Uncovering The Mechanisms Of Glioblastoma Relapse Prevention With Niclosamide And Camptothecin Treatment, Xiaoqian Fang, Araely Ruiz, Eunseo Yang, Brianna Morin, Kimberly Herrera-Toscano, Megan Szobody, Josue Fonseca, John-Beloved Osho, Raquel Lara

Research Symposium

Background: Glioblastoma multiforme (GBM) is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. In our previous studies, we demonstrated that niclosamide and camptothecin (CPT) synergistically suppressed the proliferation in human glioblastoma U87 MG cells. Recently, we observed that U87 MG cells failed to resume growth after the combined treatment was removed, a phenomenon not seen with either agent alone. We aimed to explore the sustained anti-tumor effects of niclosamide and CPT in GBM.

Methods: Human glioblastoma U87 MG cells were treated with 5 mM niclosamide, 5 mM …

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Crosstalk Between Nnos/No And Cox-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression, Anika Patel, Shirley Tong, Moom R. Roosan, Basir Syed, Amardeep Awasthi, Richard B. Silverman, Sun Yang

Pharmacy Faculty Articles and Research

Background/Objectives: Interferon gamma (IFN-γ) in the melanoma tumor microenvironment plays opposing roles, orchestrating both pro-tumorigenic activity and anticancer immune responses. Our previous studies demonstrated the role of neuronal nitric oxide synthase (nNOS) in IFN-γ-stimulated melanoma progression. However, the underlying mechanism has not been well defined. This study determined whether the nNOS/NO and COX-2/PGE2 signaling pathways crosstalk and augment the pro-tumorigenic effects of IFN-γ in melanoma. Methods: Bioinformatic analysis of patient and cellular proteomic data was conducted to identify proteins of interest associated with IFN-γ treatment in melanoma. Changes in protein expression were determined using various analytical techniques including …

Sigma1 Inhibitor Suppression Of Adaptive Immune Resistance Mechanisms Mediated By Cancer Cell Derived Extracellular Vesicles, Paola A. Castagnino, Derick A. Haas, Luca Musante, Nathalia A. Tancler, Bach V. Tran, Rhonda Kean, Alexandra R. Steck, Luis A. Martinez, Elahe A. Mostaghel, D. Craig Hooper, Felix J. Kim

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER. Sigma1 is a unique ligand-regulated integral membrane scaffolding protein enriched in the ER of cancer cells. PD-L1 is an integral membrane glycoprotein that is translated into the ER and processed through the cellular secretory pathway. At the cell surface, PD-L1 is an immune …

An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic …