Cancer Biology Commons^™

Sigrescuer: A Pan-System Framework For Noise Correction And Mutational Signature Identification Across Sequencing Platforms, Peter T. Nguyen, Maria Zhivagui

Nevada Institute of Personalized Medicine Faculty Research

Introduction: Mutational signatures serve as molecular fingerprints of the biological processes and exposures that shape cancer genomes. However, accurate signal recovery remains challenging due to pervasive background variants, sequencing artifacts, technical noise, and platform-specific biases that obscure true mutagenic patterns, hampering biomarker discovery, and mechanistic interpretation. Methods: Here we introduce SigRescueR, a rigorous, pan-system, computational framework based on Bayesian inference designed for noise correction and mutational signature identification. SigRescueR applies statistically robust baseline correction to effectively disentangle true mutational signals from confounding noise and artifacts. Results: When applied to extensive datasets spanning experimental models and human cancers, SigRescueR reliably identified …

Fiber Optic Polarimetric Stress Sensor Improvements, Maxwell R. Richter, Max Randall, Mark C. Harrison

Engineering Faculty Articles and Research

The progression of diseases such as cancer has been correlated with tissue stiffness. For example, breast cancer tissue has been found to be stiffer than healthy mammary tissue. At present, stiffness measurement devices are not suitable for nondestructive, high-resolution measurements on small, delicate samples. We report a compact, portable, and sensitive fiber optic stress sensor that overcomes many of these limitations and is suitable for soft materials such as tissue. We demonstrate several improvements to a previous fiber stress sensor in physical hardware, software, and data analysis. We have designed and fabricated a custom enclosure to shield the sensitive setup …

Nanoencapsulation Of Tomentosin-Rich Pulicaria Crispa Fraction In Mil-53(Fe) Improves The Release Profile And In Vitro Anti-Colorectal Cancer Activity, Hamies Baher

Dentistry

No abstract provided.

Comparison Of Surgical Treatment Patterns And Temporal Trends For Stage I-Iii Invasive Rectal Adenocarcinoma Among Regions In The United States, Whitney Elks, Declan Feery, Celina Cosme, Kavita Batra, Lance Horner, Charles St Hill, Ovunc Bardakcioglu

School of Medicine Faculty Research

Background: Practice patterns of surgical management of rectal adenocarcinoma vary among US regions. Nationwide, there has been an overall trend toward the performance of anterior resection (AR) over abdominoperineal resection (APR) in the surgical management of invasive rectal adenocarcinoma when feasible. It is suspected that this trend is adopted at a slower rate in underserved regions of the United States. Methods: Data from the NCDB for 2004–2019 was queried for patients with stage I-III rectal adenocarcinoma who underwent anterior resection (AR) or abdominoperineal resection (APR). Comparisons of AR versus APR were made among year, region, approach, and stage. Results: Of …

New Inhibitors Of Neuronal Nitric Oxide Synthase For The Treatment Of Melanoma, Amardeep Awasthi, Anika Patel, Huiying Li, Koon Mook Kang, Christine D. Hardy, Anas Ansari, Raghad Nowar, Hasan Alhaddad, Md. Emtiaz Hasan, Sun Yang, Thomas L. Poulos, Richard B. Silverman

Pharmacy Faculty Articles and Research

In 2024, an estimated 100,640 new cases of invasive melanoma were diagnosed in the U.S., with 9290 deaths. Our previous studies revealed that neuronal nitric oxide synthase (nNOS) derived nitric oxide plays a critical role in melanoma progression, making nNOS inhibition a promising strategy. High structural similarity among NOS isoforms requires careful design of nNOS inhibitors to avoid off-target effects. Our previous lead, HH044, demonstrated potent antimelanoma activity but exhibited only moderate nNOS selectivity. Here, we utilized a structure-based approach to design nNOS inhibitors that promote interactions with human nNOS-specific residue His342. Compound 9 exhibited inhibition of both human ( …

Updating Misev: When, What, How, And Why?, Naveed Akbar, Dylan Burger, Benedetta Bussolati, Edit Buzás, Randy Carney, Young-Eun Cho, Tom Driedonks, Juan Manuel Falcon-Perez, Yu Fujita, Deborah Goberdhan, An Hendrix, Yiyao Huang, Suresh Mathivanan, Mỹ Mahoney, Sujata Mohanty, Andreas Möller, Nicole Noren Hooten, Stefano Pluchino, Carlos Salomon, Ana Claudia Torrecilhas, Sara Veiga, Kenneth Witwer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

No abstract provided.

Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …

An Antioxidant Cocktail Of Tert-Butylhydroquinone And A Manganese Porphyrin Induces Toxic Levels Of Oxidative Stress In Cancer Cells, Sandra Tamarin, Hannah Jung, Joseph Lamorte, Laura Biesterveld, Gabriel Piñero, Grace Turchetta, Molly Myers, Rebecca Oberley-Deegan, Aimee Eggler

Student Papers, Posters & Projects

Despite significant advancement in cancer treatments, therapies with minimal toxicity to healthy cells are still limited. One targetable weakness of cancer cells is their sensitivity to oxidative stress. We find that the combination of two antioxidants—the common food additive tert-butylhydroquinone (tBHQ) and a manganese porphyrin in clinical trials, MnTnBuOE-2-PyP5+ (MnBuOE)—increases oxidative stress and causes apoptotic death in several cancer cell lines, but not in mouse primary fibroblasts. Investigating the mechanism of cell death, MnBuOE is observed to catalyze the oxidation of tBHQ, producing the electrophilic quinone tert-butylquinone (tBQ). A critical role for tBQ and its electrophilic character was revealed with …

Antiestrogens As Bone Protective Therapeutics For Estrogen Receptor-Positive Breast Cancer In The Presence Of Osteoporosis, Faith E. Parker, Emily K. Zboril, David C. Boyd, Rachel Myrick, J. Chuck Harrell

UROP Posters

Breast cancer (BC) is one of the most significant causes of mortality among women and the second leading cause of cancer death in women. The estrogen receptor (ER) is a key oncogenic driver in the majority of breast cancer. ER+ BC is the most common molecular subtype of BC. Management of ER+ breast cancer varies depending on menopausal status. For premenopausal women, the goal is to suppress estradiol production from the ovaries with surgical oophorectomy and/or aromatase inhibitors. In postmenopausal women, endocrine therapy (ET) serves to suppress estradiol production from sources other than the ovaries. During the menopausal transition, estradiol …

Evaluation Of Peptides And Peptide–Doxorubicin Conjugates Designed And Synthesized For Targeting Triple-Negative Breast Cancer Via Cell-Surface Receptors, Shih-Jing (Jane) Yao

Pharmaceutical Sciences (PhD) Dissertations

A significant problem faced in oncology is the lack of chemotherapeutic agents that are tumor site-specific, resulting in reduced therapeutic efficacy and unintended infliction of harm to surrounding healthy tissues and cells that often lead to serious side effects. Current strategies being explored to circumvent this issue aim to refine delivery of  chemotherapeutic agents specifically to tumor sites, which may be achieved via conjugation of these agents to biomarker-specific ligands. This forms the foundation of ligand-targeted drug delivery. Among different breast cancers, treatment of the triple-negative breast cancer (TNBC) subtype has been particularly challenging, largely due to the absence of …

Investigation Of Genx Exposure To Pathways Associated With Colorectal Cancer Risk, Emily J. Ferguson

Theses and Dissertations--Toxicology and Cancer Biology

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants widely detected in drinking water and food sources, resulting in chronic human exposure. Among these compounds, hexafluoropropylene oxide dimer acid (HFPO-DA), commonly known as GenX, has been introduced as a short-chain replacement for legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Although GenX is believed to be a safer alternative, emerging research suggests it can still affect human health.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related death in the United States, highlighting the need to better understand environmental …

Uncovering The Mechanism Of Reep2-Mediated Emt-Driven Membrane Trafficking In Lung Adenocarcinoma, Kevin Fulp

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking is frequently disrupted during cancer progression, and the underlying mechanisms remain largely unknown. Currently, no effective drugs target dysregulated membrane trafficking for cancer treatment. Recent evidence has demonstrated that epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma (LUAD) employs a membrane trafficking program to coordinate cancer cell invasion and immunosuppression. To further dissect the pro-tumorigenic membrane trafficking program, we initiated an in vivo CRISPRi screen to assess more than 2,000 membrane trafficking-related genes in a syngeneic mouse LUAD model. We identified REEP2, an endoplasmic reticulum (ER) shaping protein, as a novel regulator of EMT-driven membrane trafficking. High REEP2 expression is …

Reep2-Driven Pro-Metastatic Secretion Promotes Lung Cancer Progression, Oluwafunminiyi E. Obaleye

Theses and Dissertations--Toxicology and Cancer Biology

Membrane trafficking plays a critical role in cellular function and is frequently dysregulated in cancer to promote metastasis. In lung adenocarcinoma (LUAD), the epithelial-to-mesenchymal transition (EMT) activating transcription factor, ZEB1, drives a pro-metastatic membrane trafficking program; however, the underlying molecular mechanisms remain poorly understood. Using a CRISPR interference (CRISPRi) in vivo screen of 2,099 membrane trafficking regulators in a syngeneic mouse model of EMT-driven LUAD, we identified REEP2 — an endoplasmic reticulum (ER) shaping protein — as a critical regulator of tumor progression. REEP2 mRNA expression correlates with poor prognosis, EMT signatures, and an immunosuppressive tumor microenvironment in LUAD patients. …

Exploring The Synergistic Effects Of Cisplatin And Curcumin In Osteosarcoma Cells, Ellis Stafford, Alexa Cabral, Andrea Florian Ph.D., Reese Nagy

SPARK Symposium Presentations

Osteosarcoma (OS) is a highly aggressive bone cancer characterized by rapid metastasis, which drastically reduces patient survival rates from 70% in localized cases to 30% upon metastasis. Current treatments combining chemotherapy with cisplatin and surgical intervention are often ineffective against metastatic OS and are associated with significant side effects. Cisplatin targets cancer cells by binding to DNA, disrupting transcription and replication, and inducing apoptosis. To address the challenges associated with current treatments, this study investigates the potential of combining cisplatin with curcumin, the bioactive compound derived from turmeric, as a novel therapeutic approach. Curcumin has shown anticancer properties by inducing …

Proteome-Based Identification And Validation Of Nxpe3 In Childhood Acute Lymphoblastic Leukaemia, Najia Tabassum, Yamna Khurshid, Basir Syed, Aftab Ahmad, Sadia Muhammad, Rehan Imad, Talat Mirza

Pharmacy Faculty Articles and Research

Background: Childhood acute lymphoblastic leukaemia (cALL) tends to metastasize to central nervous system. Treatment with antileukemic agents against CNS leukaemia is an essential component for cure in ALL. Hence, it is essential to identify biomarkers for CNS infiltration. Proteomics, supported by mass spectrometry, is the platform for exploring biomarkers in various biological samples, contributing to translational research. Objectives: This study aimed to identify the plasma proteome profile of children across different risk groups of cALL. Neurexophilin and PC-esterase family, member 3 (NXPE3), was validated. The protein-protein interactions (PPI) of NXPE3 were evaluated with bioinformatics analyses. Methods: Plasma …

Crispr Transgenic Clytia Hemisphaerica As A Vector For Toxin Delivery In A Zebrafish Melanoma Model, Theodore G. Paz

Theses, Dissertations and Culminating Projects

The jellyfish Clytia hemisphaerica has the potential to be used in cancer therapies with the discovery of potential active toxin target regions to be modified for use. The program Venomix is a Uniprot-based database that was utilized in this experiment to generate likely flagged hit regions using Clytia hemisphaerica CDS files run against its database of terrestrial toxins (Furuno et al., 2003; Macrander et al., 2018). By themselves they are indeterminate as to whether they are active toxin region hits (Macrander et al., 2018). With further analysis such as toxin homology in closely related, annotated marine taxa and accounting for …

Forecasting Lung Cancer Burden Using Multicenter Real-World Data, Omer Aydin, Levent Korkmaz, Aybeyan Selim, Murat Kuzlu, Ferhat Ozgur Catak, Huseyin Kusetogullari, Umit Cali

Engineering Technology Faculty Publications

Background – Lung cancer continues to place a significant clinical and operational burden on healthcare infrastructure and systems. While essential epidemiological data can be obtained from population-based registries, these systems often fail to provide information on long-term follow-up and healthcare utilization dynamics. Real-world data collected from healthcare institutions offer valuable insights; however, in-depth and careful analysis is necessary to distinguish true diagnostic trends from changes in service utilization and access.

Objectives – The primary objective of this study is to characterize and forecast the prevalence of lung cancer diagnoses at the specified hospitals for future years. The study aims to …

A Sweet Spot For Chemotherapy: The Influence Of Insulin And Glucagon On Oxaliplatin Sensitivity In Colorectal Cancer Cells, Daniella Cohen, Andrea Florian

SPARK Symposium Presentations

There is a well-established relationship between cellular metabolism, cancer progression, and treatment response. Metabolic hormones such as insulin and glucagon regulate pathways involved in cell growth, survival, and stress responses and have been linked to tumor development and chemotherapy sensitivity. Understanding how metabolic signaling influences cancer treatment may provide insight into factors that affect therapeutic outcomes. This study aims to investigate how insulin and glucagon affect the susceptibility of colorectal cancer cells (CRC) to the chemotherapeutic agent oxaliplatin. CRC cells were treated with insulin or glucagon and exposed to varying concentrations of oxaliplatin. Cell viability was measured to evaluate treatment …

Comparing The Differences Of Hsp90Α And Hsp90Β In Native Protein Complex Incorporation, Daryna Serediuk

Honors Theses and Capstones

Epichaperomes are long-lasting, stable assemblies of chaperones, co-chaperones, and associated factors that facilitate cell survival in maladaptive cellular states. Their inhibition has emerged as an attractive therapeutic strategy for the treatment of cancer and neurodegenerative diseases (Rodina et al., 2016). Epichaperomes are hallmarks of robust proliferation in cancer cell populations across many cancer types and are abundantly present in several stem cell varieties, including induced pluripotent stem cells, human embryonic kidney cells, and cancer stem cells (Kishinevsky et al., 2018).

The core protein of the eukaryotic heat shock protein machinery, Heat Shock Protein 90 (Hsp90), is a central chaperone that …

Brain-Derived Extracellular Vesicles Potentially Mediate Crosstalk With Peripheral Organs In Neurodegenerative Diseases, Ramzi H. Hamdalla, Vibha B. Bhaskar, Changhai Tian

Toxicology and Cancer Biology Faculty Publications

Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of …