Cancer Biology Commons^™

Mitochondrial Transfer And Induced Ros As A Therapeutic Strategy In Idh2-Mutant Chondrosarcoma, Vegas R. Bedder, Caleb Wyckoff, Chris Osgood, Gavin A. Vasquez, Michael Stacey

Knowledge and Creativity Expo

Chondrosarcoma (CS) are common bone cancers that produce cartilaginous tumors and are extremely refractive to chemo-and-radiation therapies, leaving very limited treatment options. They contain mutations in the isocitrate dehydrogenase genes, IDH1 or IDH2. Either IDH1 or IDH2 mutations are present in individual tumors, but not both. They both convert alphaketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG). D2HG can be transported from the tumors to cells of the tumor microenvironment (TME) where it can alter metabolic and epigenetic profiles in recipient cells. The process of α-KG to D2HG conversion occurs in the cytoplasm of IDH1 mutant cells, and in the …

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 …

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 …

Mitochondria-Mediated Epigenetic Transfer Between Chondrosarcoma And Wild-Type Cells, Caleb C. J. Wyckoff

Biomedical Sciences Theses & Dissertations

Glioblastoma (GB), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), cholangiocarcinoma, and chondrosarcoma (CS) cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme exhibits transformation of alpha-ketoglutarate (αKG) into the oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers. Mitochondrial-mediated transfer between cancer cells and recipient cells is a significant event that impacts the physiology of the receiving cell, specifically the epigenetic landscape. Previous experiments indicating increased DNA methylation in mesenchymal stem cells exposed to IDH1 or IDH2 conditioned medium underscore the potential role of D2HG to alter methylation states. Additionally, the presence of …

Potentiation Of Gelonin Cytotoxicity By Pulsed Electric Fields, Olga N. Pakhomova, Eleni Zivla, Giedre Silkuniene, Mantas Silkunas, Andrei G. Pakhomov

Bioelectrics Publications

Gelonin is a ribosome-inactivating protein with extreme intracellular toxicity but poor permeation into cells. Targeted disruption of cell membranes to facilitate gelonin entry is explored for cancer and tissue ablation. We demonstrate a hundreds- to thousands-fold enhancement of gelonin cytotoxicity by pulsed electric fields in the T24, U-87, and CT26 cell lines. The effective gelonin concentration to kill 50% of cells (EC₅₀) after electroporation ranged from <1 nM to about 100 nM. For intact cells, the EC₅₀ was unattainable even at the highest gelonin concentration of 1000 nM, which reduced cell survival by only 5–15%. For isoeffective electroporation treatments using 300 ns, 9 µs, and 100 µs pulses, longer pulses were more efficient at lowering gelonin EC₅₀. Increasing the electric field strength of 8, 100 µs pulses from 0.65 to 1.25 kV/cm reduced gelonin EC₅₀ from 128 nM to 0.72 nM. Conversely, the presence of 100 nM gelonin enabled a more than 20-fold reduction in the number of pulses required for equivalent cell killing. Pulsed electric field-mediated delivery of gelonin shows promise for hyperplasia ablation at concentrations sufficiently low to minimize or avoid systemic toxicity.

Physical Ablative Methods And Cancer Cell Death: Implications For Immunity And Therapies, Alessandra Rossi, Claudia Muratori

Bioelectrics Publications

Surgery has traditionally been a cornerstone in cancer treatment, yet its feasibility can be limited by factors such as tumor location and patient health conditions. When surgery is not viable, thermal and pulsed electric field (PEF)-based ablation technologies offer valuable alternatives. Emerging evidence suggests that these approaches not only target tumors effectively but also stimulate antitumor immune responses. In this review, we begin by examining the distinctive features of hyperthermic treatments (radiofrequency and microwave ablation), cryoablation, and PEF-technologies. Subsequently, we discuss the mechanisms of cell death, stress responses, and release of danger signals triggered by these diverse ablation technologies. Finally, …

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Redirection Of Cancer Cell Fate, Julie Sofie Bjerring, Yara Khodour, Emilee Anne Peterson, Patrick Christian Sachs, Robert David Bruno

School of Medical Diagnostics & Translational Sciences Publications

The mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) by which this alteration occurs has yet to be defined. Here, we test the hypothesis that mitochondrial transfer from normal mammary epithelial cells to breast cancer cells plays a role in this redirection process. We evaluate mitochondrial transfer in 2D and 3D organoids using our unique 3D bioprinting system to produce chimeric organoids containing normal and cancer cells. We demonstrate that breast cancer tumoroid growth is hindered following interaction with mammary epithelial cells …

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …

Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai

Department of Medicine Faculty Publications

Purpose

ERBB2 (HER2) alterations (e.g., overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial.

Methods

HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association.

Results

Of the 653 cases, HER2 IHC scores were distributed as 3 + (3.1%), …

The Role Of Tgf-Beta Superfamily Members In Immune Homeostasis And Disease, Natalie Eva Nieuwenhuizen, Ioannis Eleftherianos, Piotr Jan Kraj, Maria Semitekolou

Biological Sciences Faculty Publications

[Introduction] The Transforming Growth Factor beta (TGF-beta) superfamily, encompassing molecules such as TGFs, activins, Bone Morphogenetic Proteins (BMPs), Growth/Differentiation Factor (GDFs) and Nodals, represents the largest family of growth and differentiation factors, playing crucial roles in developmental and physiological processes across animal species (1). These molecules are integral to tissue homeostasis and cell fate determination. Among them, TGF-beta is particularly noted for its regulatory influence on immune responses and tissue fibrosis (2, 3). Recent research has expanded our understanding of the immune functions of other superfamily members, including activin A and BMPs (4). These molecules signal through receptor complexes composed …

A Comparison Of In Vitro Studies Between Cobalt(Iii) And Copper(Ii) Complexes With Thiosemicarbazone Ligands To Treat Triple Negative Breast Cancer, Duaa R. Alajroush, Chloe B. Smith, Brittney F. Anderson, Ifeoluwa T. Oyeyemi, Stephen J. Beebe, Alvin A. Holder

Undergraduate Research Symposium

Triple negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, and disproportionately affects African American women. TNBC cells lack the common hormone receptors that many pre-existing cancer treatments target. Fortunately, metal-based complexes with thiosemicarbazone ligands have gained significant attention for their potential as anti-cancer agents. Cobalt(III) complex ([Co(phen)2(MeATSC)](NO3)3•1.5H2O•C2H5OH]) and Copper(II) complex ([Cu(acetylethTSC)Cl]Cl•0.25C2H5OH) specifically have properties of high toxicity, which can contribute to decreased cancer cell activity. The effects of these complexes are currently being investigated on cancerous and non-cancerous breast cell lines. The cytotoxic effect of the cobalt(lll) complex and the copper(ll) complex was analyzed …

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) …

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 …

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 …

Machine Learning As A Tool For Early Detection: A Focus On Late-Stage Colorectal Cancer Across Socioeconomic Spectrums, Hadiza Galadima, Rexford Anson-Dwamena, Ashley Johnson, Ghalib Bello, Georges Adunlin, James Blando

Community & Environmental Health Faculty Publications

Purpose: To assess the efficacy of various machine learning (ML) algorithms in predicting late-stage colorectal cancer (CRC) diagnoses against the backdrop of socio-economic and regional healthcare disparities. Methods: An innovative theoretical framework was developed to integrate individual- and census tract-level social determinants of health (SDOH) with sociodemographic factors. A comparative analysis of the ML models was conducted using key performance metrics such as AUC-ROC to evaluate their predictive accuracy. Spatio-temporal analysis was used to identify disparities in late-stage CRC diagnosis probabilities. Results: Gradient boosting emerged as the superior model, with the top predictors for late-stage CRC diagnosis being anatomic site, …

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Methylene Blue-Mediated Photodynamic Therapy In Combination With Doxorubicin: A Novel Approach In The Treatment Of Ht-29 Colon Cancer Cells, Nima Rastegar-Pouyani, Jaber Zafari, Alireza Nasirpour, Hossein Vazini, Nabbaa Najjar, Seyedeh Zohreh Azarshin, Fatemeh Javani Jouni

Electrical & Computer Engineering Faculty Publications

Introduction: With an alarmingly growing number of patients diagnosed with colorectal cancer, adopting innovative anti-cancer approaches has recently garnered great attention. One interesting concept is the co-administration of cytotoxic agents and safer modalities such as photodynamic therapy (PDT), which can subsequently improve therapeutic efficacy and potentially reduce the risks of severe adverse effects and drug resistance. In the course of PDT, a locally injected photosensitizer (PS) is irradiated with a light source, which subsequently generates reactive oxygen species (ROS) and induces programmed cell death in tumor cells.

Methods: In this study, to evaluate the potential anti-cancer effects of chemotherapy combined …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D'Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well-studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: Von Hippel-Landau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). …

Paper-Based Dna Biosensor For Rapid And Selective Detection Of Mir-21, Alexander Hunt, Sri Ramulu Torati, Gymama Slaughter

Electrical & Computer Engineering Faculty Publications

Cancer is the second leading cause of death globally, with 9.7 million fatalities in 2022. While routine screenings are vital for early detection, healthcare disparities persist, highlighting the need for equitable solutions. Recent advancements in cancer biomarker identification, particularly microRNAs (miRs), have improved early detection. MiR-21 is notably overexpressed in various cancers and can be a valuable diagnostic tool. Traditional detection methods, though accurate, are costly and complex, limiting their use in resource-limited settings. Paper-based electrochemical biosensors offer a promising alternative, providing cost-effective, sensitive, and rapid diagnostics suitable for point-of-care use. This study introduces an innovative electrochemical paper-based biosensor that …

Identifying New Cancer Genes Based On The Integration Of Annotated Gene Sets Via Hypergraph Neural Networks, Chao Deng, Hong-Dong Li, Li-Shen Zhang, Yiwei Liu, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation

Identifying cancer genes remains a significant challenge in cancer genomics research. Annotated gene sets encode functional associations among multiple genes, and cancer genes have been shown to cluster in hallmark signaling pathways and biological processes. The knowledge of annotated gene sets is critical for discovering cancer genes but remains to be fully exploited.

Results

Here, we present the DIsease-Specific Hypergraph neural network (DISHyper), a hypergraph-based computational method that integrates the knowledge from multiple types of annotated gene sets to predict cancer genes. First, our benchmark results demonstrate that DISHyper outperforms the existing state-of-the-art methods and highlight the advantages of …

Sccad: Cluster Decomposition-Based Anomaly Detection For Rare Cell Identification In Single-Cell Expression Data, Yunpei Xu, Shaokai Wang, Qilong Feng, Jiazhi Xia, Yaohang Li, Hong-Dong Li, Jianxin Wang

Computer Science Faculty Publications

Single-cell RNA sequencing (scRNA-seq) technologies have become essential tools for characterizing cellular landscapes within complex tissues. Large-scale single-cell transcriptomics holds great potential for identifying rare cell types critical to the pathogenesis of diseases and biological processes. Existing methods for identifying rare cell types often rely on one-time clustering using partial or global gene expression. However, these rare cell types may be overlooked during the clustering phase, posing challenges for their accurate identification. In this paper, we propose a Cluster decomposition-based Anomaly Detection method (scCAD), which iteratively decomposes clusters based on the most differential signals in each cluster to effectively separate …

Triphlapan: Predicting Hla Molecules Binding Peptides Based On Triple Coding Matrix And Transfer Learning, Meng Wang, Chuqi Lei, Jianxin Wang, Yaohang Li, Min Li

Computer Science Faculty Publications

Human leukocyte antigen (HLA) recognizes foreign threats and triggers immune responses by presenting peptides to T cells. Computationally modeling the binding patterns between peptide and HLA is very important for the development of tumor vaccines. However, it is still a big challenge to accurately predict HLA molecules binding peptides. In this paper, we develop a new model TripHLApan for predicting HLA molecules binding peptides by integrating triple coding matrix, BiGRU + Attention models, and transfer learning strategy. We have found the main interaction site regions between HLA molecules and peptides, as well as the correlation between HLA encoding and binding …

Gene Expression Under Combined Hypoxia And Acidosis In Chondrosarcoma, Michael Stacey, Kostika Vangjeli, Christopher Osgood

Bioelectrics Publications

Chondrosarcomas are the second most common cause of bone cancer and are removed surgically with wide margins. On recurrence, they are resistant to chemo and radiation therapy and new treatment options are critically required. This tumor type produces hyaline cartilage, a cartilage normally formed under hypoxic and acidic environment due to lack of vasculature in cartilage. Paradoxically, chondrosarcomas arise in the well vascularized, oxygen rich environment of the bone. Hypoxia and acidosis are two stressors where the cellular effects are typically reported separately even though cells experience combined effects of hypoxia and acidosis. Given the mechanistic links between hypoxia and …

Enhancing The Conformational Stability Of The Cl-Par-4 Tumor Suppressor Via Site-Directed Mutagenesis, Samjhana Pandey, Krishna K. Raut, Antoine Baudin, Lamya Djemri, David S. Libich, Komala Ponniah, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Intrinsically disordered proteins play important roles in cell signaling, and dysregulation of these proteins is associated with several diseases. Prostate apoptosis response-4 (Par-4), an approximately 40 kilodalton proapoptotic tumor suppressor, is a predominantly intrinsically disordered protein whose downregulation has been observed in various cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) is active and plays a role in tumor suppression by inhibiting cell survival pathways. Here, we employed site-directed mutagenesis to create a cl-Par-4 point mutant (D313K). The expressed and purified D313K protein was characterized using biophysical techniques, and the results were compared to that of the wild-type (WT). We have …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …