Cancer Biology Commons^™

Charge Modulation Of Peptide/Nucleic Acid Complexes: An Anionic Additive Enhances Gene Silencing And Crispr/Cas9 Editing By Promoting Intracellular Nucleic Acid Release, Abdulelah Alhazza, Sorour Khayyatnejad Shoushtari, Hasan Uludag, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Introduction: Small interfering RNA (siRNA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated Protein 9 (Cas9) complexes are effective approaches to temporarily downregulate protein expression via post-transcription RNA interference or permanently altering protein expression via editing genomic DNA, respectively. However, the efficient delivery of these mediators to targeted cells has been challenging, largely due to their anionic and hydrophilic nature, which hinders their interaction with the cell membrane and cellular internalization. Cell-penetrating peptides (CPPs) exhibit dual characteristics as a carrier for nucleic acid delivery, where positively charged components bind to the negatively charged nucleic acid, and the hydrophobic components …

P300/Cbp Inhibition With Inobrodib In Combination With Gilteritinib And Venetoclax Targets Leukemia Stem Cells In Epigenetic Mutant Aml, Melanie L. Goetz, Jennifer S. Romer-Seibert, Amanda M. Versace, Scott Kogan, Chetan Jeurkar, Robert L. Bowman, Nigel Brooks, Kris Frese, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Acute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult patients with AML and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and …

Inosine Accelerates Cancer Cell Killing By The Experimental Antifolate Ucp1162: Implications For Novel Combination Treatments, Reshma Ramesh, Charles Giardina, Alan Kuo

Honors Scholar Theses

Antifolates disrupt one-carbon metabolism (OCM), which stops nucleotide synthesis and therefore slows down cell proliferation. Our experimental antifolate, UCP1162, stops de novo purine synthesis and thymidine synthesis by targeting the OCM pathway. We investigated whether the downstream metabolites of OCM pathway: methionine, thymidine, and inosine, affect the cell death caused by UCP1162 using MV4-11 leukemia cells. Thymidine was found to partially rescue MV4-11 cells from UCP1162, in contrast, inosine was found to accelerate the cell death caused by UCP1162. These cytotoxic effects of UCP1162 alone and in combination with inosine were irreversible, as removal of treatment did not restore cell …

The Development Of A Crispr-Based Calibrated Functional Assay For Classifying Pathogenicity Of Msh2 And Msh6 Variants In Lynch Syndrome, Olivia N. Amodeo

Honors Scholar Theses

Lynch syndrome is a hereditary disease caused by the inheritance of a mismatch repair gene variant. Individuals with this condition are predisposed to cancer development, most commonly colorectal cancer. Current guidelines for variant classification are based on numerous evidence categories, including functional evidence. However, many novel clinical variants are not well characterized, and evidence is difficult to obtain if functional assays are not calibrated.

To address this, our lab created a calibrated functional assay that calculates an odds of pathogenicity score for MSH2 and MSH6 gene variants that can be used as evidence for classifying variants of uncertain significance. This …

Diacylglycerol Kinase Eta As A Novel Target In Nras Mutant Melanoma, Haley P. Wilson, Casey D. Stefanski, Signe Caksa, Glenn L. Mersky, Scott D. Varney, Jelan I. Haj, Dan A. Erkes, Timothy J. Purwin, Vivian Chua, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

NRAS mutations occur in 10%-30% of cutaneous melanomas and are associated with high tumor mutational burden. Mutant NRAS signaling drives aberrant cell growth and proliferation, in part, through activation of the RAF-MEK-ERK1/2 kinase pathway; however, targeted therapies to this pathway have limited effectiveness in patients with NRAS mutant melanoma. The role of other targetable signaling pathways in NRAS mutant melanoma is poorly characterized. Here, we demonstrated that one isoform of diacylglycerol kinase, diacylglycerol kinase eta (DGKη), a lipid signaling regulator, was highly expressed in NRAS mutant melanoma patient samples. Knockdown of DGKH in NRAS mutant melanoma cell lines resulted in …

Synthetic Lethality Between Rb-Loss And E2f3 Inhibition In Small Cell Cancers Targeted By Pyrimidine Synthesis Blockade, Evan R. Abt, Liang Wang, Grigor Varuzhanyan, Jack Freeland, Tian He, Guadalupe M. Peña-Garcia, Lauryn Ruegg, Jami Mclaughlin, Donghui Cheng, Nikolas G. Balanis, Chia-Chun Chen, Yang Xu, Yi Xing, Sanaz Memarzadeh, Caius G. Radu, Thomas G. Graeber, Owen N. Witte

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Small cell carcinoma is a highly lethal cancer variant often found with neuroendocrine (NE) features, as exemplified by small cell lung cancer and small cell NE prostate cancer (SCPC). A genome-wide CRISPR dependency screen using SCPC models generated through human prostate cell transformation identifies a requirement for the transcription factor E2F3. E2F3 dependency is linked to RB inactivation, a near universal occurrence across small cell cancers. The requirement for E2F3 is shared by RB-deficient cells originating from the prostate, lung, and adnexa. In RB-deficient cancer cells, E2F3 inhibition restrains cell cycle progression, proliferation, and tumor growth in vivo. Inhibition of …

Role Of Na⁺/K⁺-Atpase And Sodium–Calcium Exchanger In Digitoxin-Induced Cytotoxicity In Triple Negative Breast Cancer Cells, Alyson Sotomayor Quispe, Marilyn Odom Phd

SPARK Symposium Presentations

Triple Negative Breast Cancer (TNBC) is characterized by the absence of estrogen, progesterone, and HER2 receptors, limiting targeted treatment options. Digitoxin, a drug used to treat heart failure and atrial fibrillation through Na⁺/K⁺-ATPase inhibition, has demonstrated anticancer effects in TNBC cells, including apoptosis via the NF-κB pathway. This study investigates whether the Na⁺/K⁺-ATPase and sodium–calcium exchanger contribute to the mechanism of action of digitoxin in TNBC cells. We hypothesize that these transporters mediate digitoxin-induced cytotoxic effects. To test this, MDA-MB-468 cells were treated with digitoxin, and protein localization and expression were analyzed using immunofluorescence and Western blot. Digitoxin treatment resulted …

Advancements In Extracellular Vesicle Research, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The AAEV (American Association of Extracellular Vesicles) Annual Meeting at the John P. McGovern Commons in Houston, TX convened over 300 leading re- searchers, clinicians, and industry experts from around the world to advance the rapidly evolving field of extracellular vesicle (EV) science. EVs, nanoscale lipid- bound particles released by all prokaryotic and eukaryotic cells, have emerged as crucial mediators of intercellular communication, trans- porting proteins, nucleic acids, and lipids that influence a wide spectrum of physiological and pathological processes. Their involvement in immune modulation, tissue regeneration, cancer progression, metabolic regulation, and other complex biological functions positions EVs as promising …

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.

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 …

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 …

Synergistic Sensitization Of Pancreatic Cancer Cells By Nanosecond Pulsed Electric Fields And Cold Atmospheric Plasma Via Amplifying Ros And Apoptotic Signaling, Zobia Minhas, Edwin A. Oshin, Lifang Yang, Chunqi Jiang, Siqi Guo

Bioelectrics Publications

Pancreatic cancer remains a highly lethal malignancy, with standard therapies offering limited benefits in advanced stages; thus, novel strategies that exploit specific cancer cell vulnerabilities are urgently needed. Building on our previous findings that nanosecond pulsed electric fields (nsPEF) combined with cold atmospheric plasma (CAP) produce enhanced cytotoxicity, this study investigates the molecular mechanisms underlying this synergy. Pan02 pancreatic cancer cells were subjected to nsPEF, CAP, or a combination of both. We assessed cell viability, reactive oxygen species (ROS) production, and mitochondrial integrity using metabolic assays, flow cytometry, and fluorescence microscopy. Apoptotic markers were evaluated via Western blotting and caspase …

Nanosecond Electric Pulses As A Novel In Situ Vaccination Strategy For Cancer Treatment: Mechanisms, Challenges And Prospects, Siqi Guo

Bioelectrics Publications

Nanosecond electric pulses (nsEPs) are an emerging pulsed-power technology with unique bioelectric characteristics distinct from conventional long-pulse electroporation. As a tunable physical modality, nsEPs can modulate intracellular structures, membrane dynamics, and signaling pathways. Increasing evidence supports nsEPs as a promising non-thermal tumor ablation approach due to their high spatial precision, preservation of critical tissue structures, and minimal adverse effects. One of the most significant discoveries associated with nsEP tumor ablation is the induction of potent systemic antitumor immunity, particularly in situ vaccination (ISV) effects and, in some cases, abscopal effects against distant untreated tumors. Substantial evidence demonstrates that nsEPs can …

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 …

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 …

Ovarian Cancer Immunology And Immunotherapy: Editorial Note, Chris D. Platsoucas

Biological Sciences Faculty Publications

[Introduction] As the guest editor of the Special Issue on Ovarian Cancer Immunology Immunotherapy, I would like to include certain brief comments on the current state of the field and to introduce the Special Issue. Ovarian carcinoma and malignant melanoma are the first human tumors where immune responses, primarily restricted to autologous tumor cells, were first demonstrated. T-cell lines and clones developed in recombinant interleukin-2 (rIL-2) from tumor-infiltrating lymphocytes (TIL) from these tumors exhibited cytotoxicity and/or cytokine production, primarily restricted to autologous tumor cells. The T-cell receptor (TCR) and the CD3 differentiation antigen on effector T cells and HLA on …

Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry

Department of Biomedical and Translational Sciences Faculty Publications

Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling …

An Analysis Of Heart Failure Among Cancer Patients In The United States Between 1999 And 2020, Abes A. Bautista Neughebauer, Deepak Talreja, Apostolos Gaitanidis

Department of Medicine Faculty Publications

Background: Cancer and heart failure (HF) are highly prevalent in the population and can co-exist, due to shared risk factors and an aging population. The HF-related mortality burden in cancer patients across in the United States (US) remains poorly understood. The goal of this study is to evaluate the patterns of HF-related deaths among cancer patients in the United States.

Methods: A retrospective analysis was performed using the Centers for Disease Control and Prevention (CDC) WONDER Multiple Cause of Death database between years 1999 and 2020. HF-related deaths were defined as death certificates listing HF as a contributing cause of …

Serum Protein Signatures For Breast Cancer Detection In Treatment-Naïve African American Women Using Integrated Proteomics And Pattern Analysis, Padma Tadi Uppala, Elmer Rivera, Hyun J. Kwon, Sharon S. Lum

Faculty Publications

Breast cancer is the leading cause of cancer-related mortality in African American (AA) women. In this study we evaluated the serum proteomic profile of AA women with breast cancer using an integrated proteomic framework with multivariate pattern analysis. Using 2D-DIGE, thousands of serum protein spots were detected across 33 gels; 46 spots met criteria for presence, statistical significance, and differential expression. Proteins from the spots were identified by MALDI-TOF/TOF and matched in curated databases, highlighting serum biomarkers including ceruloplasmin, alpha-2-macroglobulin, complement component C3 and C6, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein and haptoglobin-related protein. LC-MS/MS analysis revealed 163 differentiating peptides after imputing and …

Immunological Surveillance Against Cancer Across Mammals, Orsolya Vincze, Piotr Minias, Alexandre Corthay, Fernando Colchero, Jean-François Lemaître, Louise Maille, Tamás Malkócs, Justus Hagemann, Dalia A. Conde, Samuel Pavard, Antoine M. Dujon, Beata Ujvari, Frédéric Thomas, Amy M. Boddy, Carlo C. Maley, Damien Chevallier, Tuul Sepp, Thomas Pradeu, Mathieu Giraudeau

Presidential Fellows Articles and Research

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class …

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …

Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a decreased expression of genes related to replication and cell cycle. Moreover, deficiency in CDC6, an essential regulator of DNA replication, phenocopies SETDB1 inhibition. Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs …

Molecular Determinants Of Neoadjuvant Chemotherapy Resistance In Breast Cancer: An Analysis Of Gene Expression And Tumor Microenvironment, Hedda Michelle Guevara-Nieto, Carlos A. Orozco-Castaño, Rafael Parra-Medina, Jenny Nathaly Poveda-Garavito, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba Lucia Combita

School of Graduate Studies Faculty Publications

Neoadjuvant chemotherapy (NAC) is a critical component of breast cancer treatment, but the molecular mechanisms underlying resistance remain poorly understood. This study aimed to identify transcriptomic changes associated with NAC resistance across four breast cancer subtypes: Luminal A, Luminal B/HER2-positive, Luminal B/HER2-negative, and Triple-Negative Breast Cancer (TNBC). RNA-seq analysis was performed on paired pre- and post-NAC breast cancer samples from 32 nonresponders. Differentially expressed genes (DEGs) were identified, and functional enrichment analyses were conducted. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Tumor microenvironment (TME) infiltration was estimated using deconvolution algorithms. The results revealed distinct gene expression profiles …

Htlv-1 And Atll: Epidemiology, Oncogenesis, And Opportunities For Community-Informed Research In The United States, Adrian D. Altieri, Sean P. Reilly, Abu Mansalay, Alan Khoo, Nettie Johnson, Zafar K. Khan, Amy Leader, Pooja Jain, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Human T-cell leukemia virus type 1 (HTLV-1), the first oncogenic human retrovirus, causes adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-cells that is incurable in most patients and is associated with a median survival of less than 1 year. HTLV-1 also causes inflammatory disorders, including HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uveitis. The estimated lifetime risks of ATLL and HAM/TSP in HTLV-1 carriers are 3-5% and 0.25-1.8%, respectively. Although there is uncertainty about other health effects of HTLV-1, a recent meta-analysis showed an association between HTLV-1 and cardiovascular, cerebrovascular, and metabolic diseases and a 57% increased risk …

Swollen Lymph Node Metastasis In Gastric Cancer: A Forgotten Prognostic Signal In Need Of Clinical Action, Keykavous Parang, Amir Nasrolahi Shirazi

Pharmacy Faculty Articles and Research

Gastric cancer (GC) remains a leading cause of cancer mortality. While the extent of nodal involvement is a well-known prognostic factor, the specific entity of swollen lymph node metastasis (SLNM), bulky nodal tumor deposits detectable radiologically or pathologically, has received little attention in staging. Recent data from a study by Cui et al demonstrated that SLNM is an independent predictor of very poor survival in GC. Through robust data and rigorous propensity-matched analyses, SLNM emerged not merely as an anatomical finding but as an independent predictor of poor prognosis, even among patients undergoing curative resection. As precision oncology advances, the …