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Full-Text Articles in Life Sciences

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 Jan 2024

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 …


Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch Jan 2024

Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch

Graduate Student Theses, Dissertations, & Professional Papers

The COP9 signalosome is a highly conserved eukaryotic complex regulating protein degradation via deneddylation of Cullin-RING E3 ligases. CSN5, the COP9’s fifth component, contains the catalytically active domain for CSN deneddylation. The complex is inactive without CSN5; however, CSN5 engages in COP9-independent binding with several other proteins, typically promoting either destruction or stabilization of its partners. Many of its confirmed interaction partners are also implicated in tumorigenesis (prominent examples being p27 and p53) and a complex cancer interactome has been established for CSN5. Additionally, CSN5 overexpression has been documented in a staggering array of cancers of diverse origins. This discovery …


Food Additive Evidence In Food Supplements Most Commonly Consumed By Cancer Patients, Safa Mazouzi, Samira Djekoun Bensoltane, Sabiha Bouzbid, Nesrine Adjabi Dec 2023

Food Additive Evidence In Food Supplements Most Commonly Consumed By Cancer Patients, Safa Mazouzi, Samira Djekoun Bensoltane, Sabiha Bouzbid, Nesrine Adjabi

Journal of Bioresource Management

The goal of this research is to highlight food additives in the formulations of food supplements consumed by cancer patients. It is a survey conducted at the Cancer treatment center in Annaba to collect a list of food supplements used by these patients. Following a screening of their ingredients for incorporated food additives, which we then classified according to the degree of toxicity, these supplements were classified according to their origin (local or imported). Our findings show that these various groups of dietary supplements contain a variety of food additives with varying degrees of toxicity, such as colorants (E422), acidity …


Svm-Do: Identification Of Tumor-Discriminating Mrna Signatures Via Support Vectormachines Supported By Disease Ontology, Mustafa Erhan Özer, Pemra Özbek Sarica, Kazim Yalçin Arğa Dec 2023

Svm-Do: Identification Of Tumor-Discriminating Mrna Signatures Via Support Vectormachines Supported By Disease Ontology, Mustafa Erhan Özer, Pemra Özbek Sarica, Kazim Yalçin Arğa

Turkish Journal of Biology

Background/aim: The complicated nature of tumor formation makes it difficult to identify discriminatory genes. Recently, transcriptome-based supervised classification methods using support vector machines (SVMs) have become popular in this field. However, the inclusion of less significant variables in the construction of classification models can lead to misclassification. To improve model performance, feature selection methods such as enrichment analysis can be used to extract useful variable sets. The detection of genes that can discriminate between normal and tumor samples in the association of cancer and disease remains an area of limited information. We therefore aimed to discover novel and practical sets …


Glp1 Receptor Agonists-Effects Beyond Obesity And Diabetes, Sydney S Wilbon, Mikhail G Kolonin Dec 2023

Glp1 Receptor Agonists-Effects Beyond Obesity And Diabetes, Sydney S Wilbon, Mikhail G Kolonin

Faculty, Staff and Student Publications

Glucagon-like peptide-1 receptor agonists (GLP1RA) have been transformative for patients and clinicians in treating type-2 diabetes and obesity. Drugs of this class, the bioavailability of which is continuously improving, enable weight loss and control blood glucose with minimal unwanted side effects. Since adopting GLP1RA for treating metabolic diseases, animal and clinical studies have revealed their beneficial effects on several other pathologies, including cardiovascular diseases, neurodegeneration, kidney disease, and cancer. A notable commonality between these diseases is their association with older age. Clinical trials and preclinical data suggest that GLP1RA may improve outcomes in these aging-related diseases. Some of the benefits …


Desmoglein-2 As A Cancer Modulator: Friend Or Foe?, Kay Myo Min, Charlie Ffrench, Barbara Mcclure, Michael Ortiz, Emma Dorward, Michael Samuel, Lisa Ebert, Mỹ Mahoney, Claudine Bonder Dec 2023

Desmoglein-2 As A Cancer Modulator: Friend Or Foe?, Kay Myo Min, Charlie Ffrench, Barbara Mcclure, Michael Ortiz, Emma Dorward, Michael Samuel, Lisa Ebert, Mỹ Mahoney, Claudine Bonder

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological …


Targeting Metabolic Switches And Dna Damage Repair For The Treatment Of Human Diseases, Rasangi Chathurika Kankanam Pathirage Dec 2023

Targeting Metabolic Switches And Dna Damage Repair For The Treatment Of Human Diseases, Rasangi Chathurika Kankanam Pathirage

Theses & Dissertations

Tuberculosis and Cancer treatments share common challenges due to prolonged therapy, the necessity of combination therapy and severe side effects. Characterization of novel drug targets and identification of new drugs modulating such targets within the context of multidrug treatments will contribute to overcoming current therapeutic challenges.

Tuberculosis (TB) is one of the challenging diseases to treat due to the persistence of Mycobacterium tuberculosis (Mtb) in the dormant phase. Current TB drugs are more effective toward actively dividing bacteria and less effective toward dormant bacteria. The metabolic transition between actively dividing bacteria and dormant bacteria is driven by pivotal metabolic enzymes …


Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang Dec 2023

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …


Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty Dec 2023

Characterization Of Trafficking And Metabolic Functions Of The Endocytic Regulator Ehd1 In Ewing Sarcoma, Sukanya Chakraborty

Theses & Dissertations

Ewing sarcoma (EWS) is the second most common bone malignancy in children and adolescents. Despite improvement in survival due to advances in multimodality treatment strategies, patients with metastatic or recurrent disease have very poor outcomes. Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown.

Studies presented in this dissertation establish that EHD1 overexpression is a feature of nearly 90% EWS patient tumors with high EHD1 expression specifying shorter patient survival. ShRNA-knockdown and …


Characterizing Stress Granule Regulation By Pas Kinase, Ataxin-2 And Ptc6 And Investigating The Lifespan Of Covid-19 Virus On Currency, Colleen R. Newey Dec 2023

Characterizing Stress Granule Regulation By Pas Kinase, Ataxin-2 And Ptc6 And Investigating The Lifespan Of Covid-19 Virus On Currency, Colleen R. Newey

Theses and Dissertations

The protein Ataxin-2 is a known positive regulator of stress granules in humans, mice and yeast (known as yeast PBP1). Due to the role that stress granules play in diseases including Amyotrophic Lateral Sclerosis (ALS) and cancer, this thesis investigates the role of Ataxin-2 and its protein binding partners in stress granule development and its effects on various metabolic phenotypes of the cell. PAS kinase is a sensory protein kinase, conserved from yeast to man, which regulates respiration and lipid biosynthesis. Our lab discovered that PAS kinase phosphorylates and activates Ataxin-2 in yeast, and that PAS kinase overexpression enhances localization …


Kinome Profiling Identifies Mark3 And Stk10 As Potential Therapeutic Targets In Uveal Melanoma, Usman Baqai, Alison M Kurimchak, Isabella V Trachtenberg, Timothy J Purwin, Jelan I Haj, Anna Han, Kristine Luo, Nikole Fandino Pachon, Angela Jeon, Vivian Chua, Michael A Davies, J Silvio Gutkind, Jeffrey L Benovic, James S Duncan, Andrew E Aplin Dec 2023

Kinome Profiling Identifies Mark3 And Stk10 As Potential Therapeutic Targets In Uveal Melanoma, Usman Baqai, Alison M Kurimchak, Isabella V Trachtenberg, Timothy J Purwin, Jelan I Haj, Anna Han, Kristine Luo, Nikole Fandino Pachon, Angela Jeon, Vivian Chua, Michael A Davies, J Silvio Gutkind, Jeffrey L Benovic, James S Duncan, Andrew E Aplin

Faculty, Staff and Student Publications

Most uveal melanoma cases harbor activating mutations in either GNAQ or GNA11. Despite activation of the mitogen-activated protein kinase (MAPK) signaling pathway downstream of Gαq/11, there are no effective targeted kinase therapies for metastatic uveal melanoma. The human genome encodes numerous understudied kinases, also called the "dark kinome". Identifying additional kinases regulated by Gαq/11 may uncover novel therapeutic targets for uveal melanoma. In this study, we treated GNAQ-mutant uveal melanoma cell lines with a Gαq/11 inhibitor, YM-254890, and conducted a kinase signaling proteomic screen using multiplexed-kinase inhibitors followed by mass spectrometry. We observed downregulated expression and/or activity of 22 kinases. …


Alpha Particle-Emitting Radiopharmaceuticals As Cancer Therapy: Biological Basis, Current Status, And Future Outlook For Therapeutics Discovery, Ryan P Coll, Scott J Bright, David K J Martinus, Dimitra K Georgiou, Gabriel O Sawakuchi, H Charles Manning Dec 2023

Alpha Particle-Emitting Radiopharmaceuticals As Cancer Therapy: Biological Basis, Current Status, And Future Outlook For Therapeutics Discovery, Ryan P Coll, Scott J Bright, David K J Martinus, Dimitra K Georgiou, Gabriel O Sawakuchi, H Charles Manning

Faculty, Staff and Student Publications

Critical advances in radionuclide therapy have led to encouraging new options for cancer treatment through the pairing of clinically useful radiation-emitting radionuclides and innovative pharmaceutical discovery. Of the various subatomic particles used in therapeutic radiopharmaceuticals, alpha (α) particles show great promise owing to their relatively large size, delivered energy, finite pathlength, and resulting ionization density. This review discusses the therapeutic benefits of α-emitting radiopharmaceuticals and their pairing with appropriate diagnostics, resulting in innovative "theranostic" platforms. Herein, the current landscape of α particle-emitting radionuclides is described with an emphasis on their use in theranostic development for cancer treatment. Commonly studied radionuclides …


Improving Radiotherapy In Immunosuppressive Microenvironments By Targeting Complement Receptor C5ar1, Callum Beach, David Maclean, Dominika Majorova, Stavros Melemenidis, Dhanya K Nambiar, Ryan K Kim, Gabriel N Valbuena, Silvia Guglietta, Carsten Krieg, Mahnaz Darvish-Damavandi, Tatsuya Suwa, Alistair Easton, Lily Vs Hillson, Ashley K Mcculloch, Ross K Mcmahon, Kathryn Pennel, Joanne Edwards, Sean M O'Cathail, Campbell S Roxburgh, Enric Domingo, Eui Jung Moon, Dadi Jiang, Yanyan Jiang, Qingyang Zhang, Albert C Koong, Trent M Woodruff, Edward E Graves, Tim Maughan, Simon Ja Buczacki, Manuel Stucki, Quynh-Thu Le, Simon J Leedham, Amato J Giaccia, Monica M Olcina Dec 2023

Improving Radiotherapy In Immunosuppressive Microenvironments By Targeting Complement Receptor C5ar1, Callum Beach, David Maclean, Dominika Majorova, Stavros Melemenidis, Dhanya K Nambiar, Ryan K Kim, Gabriel N Valbuena, Silvia Guglietta, Carsten Krieg, Mahnaz Darvish-Damavandi, Tatsuya Suwa, Alistair Easton, Lily Vs Hillson, Ashley K Mcculloch, Ross K Mcmahon, Kathryn Pennel, Joanne Edwards, Sean M O'Cathail, Campbell S Roxburgh, Enric Domingo, Eui Jung Moon, Dadi Jiang, Yanyan Jiang, Qingyang Zhang, Albert C Koong, Trent M Woodruff, Edward E Graves, Tim Maughan, Simon Ja Buczacki, Manuel Stucki, Quynh-Thu Le, Simon J Leedham, Amato J Giaccia, Monica M Olcina

Faculty, Staff and Student Publications

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell-specific functions. C5aR1 targeting resulted in increased …


Crispr-Cas9-Based Functional Interrogation Of Unconventional Translatome Reveals Human Cancer Dependency On Cryptic Non-Canonical Open Reading Frames, Caishang Zheng, Yanjun Wei, Peng Zhang, Kangyu Lin, Dandan He, Hongqi Teng, Ganiraju Manyam, Zhao Zhang, Wen Liu, Hye Rin Lindsay Lee, Ximing Tang, Wei He, Nelufa Islam, Antrix Jain, Yulun Chiu, Shaolong Cao, Yarui Diao, Sherita Meyer-Gauen, Magnus Höök, Anna Malovannaya, Wenbo Li, Ming Hu, Wenyi Wang, Han Xu, Scott Kopetz, Yiwen Chen Dec 2023

Crispr-Cas9-Based Functional Interrogation Of Unconventional Translatome Reveals Human Cancer Dependency On Cryptic Non-Canonical Open Reading Frames, Caishang Zheng, Yanjun Wei, Peng Zhang, Kangyu Lin, Dandan He, Hongqi Teng, Ganiraju Manyam, Zhao Zhang, Wen Liu, Hye Rin Lindsay Lee, Ximing Tang, Wei He, Nelufa Islam, Antrix Jain, Yulun Chiu, Shaolong Cao, Yarui Diao, Sherita Meyer-Gauen, Magnus Höök, Anna Malovannaya, Wenbo Li, Ming Hu, Wenyi Wang, Han Xu, Scott Kopetz, Yiwen Chen

Faculty, Staff and Student Publications

Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. To fill this gap and systematically identify colorectal cancer (CRC) dependency on non-canonical ORFs, we apply an integrative multiomic strategy, combining ribosome profiling and a CRISPR-Cas9 knockout screen with large-scale analysis of molecular and clinical data. Many such ORFs are upregulated in CRC compared to normal tissues and are associated with clinically relevant molecular subtypes. We confirm the in vivo tumor-promoting function of the microprotein SMIMP, encoded by a …


The Transcription Factor Irf4 Determines The Anti-Tumor Immunity Of Cd8+ T Cells, Hui Yan, Yulin Dai, Xiaolong Zhang, Hedong Zhang, Xiang Xiao, Jinfei Fu, Dawei Zou, Anze Yu, Tao Jiang, Xian C Li, Zhongming Zhao, Wenhao Chen Nov 2023

The Transcription Factor Irf4 Determines The Anti-Tumor Immunity Of Cd8+ T Cells, Hui Yan, Yulin Dai, Xiaolong Zhang, Hedong Zhang, Xiang Xiao, Jinfei Fu, Dawei Zou, Anze Yu, Tao Jiang, Xian C Li, Zhongming Zhao, Wenhao Chen

Faculty, Staff and Student Publications

Understanding the factors that regulate T cell infiltration and functional states in solid tumors is crucial for advancing cancer immunotherapies. Here, we discovered that the expression of interferon regulatory factor 4 (IRF4) was a critical T cell intrinsic requirement for effective anti-tumor immunity. Mice with T-cell-specific ablation of IRF4 showed significantly reduced T cell tumor infiltration and function, resulting in accelerated growth of subcutaneous syngeneic tumors and allowing the growth of allogeneic tumors. Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into …


An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo Nov 2023

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …


The Typical Trna Co-Expresses Multiple 5' Trna Halves Whose Sequences And Abundances Depend On Isodecoder And Isoacceptor And Change With Tissue Type, Cell Type, And Disease, Robert Akins, Kayleigh Ostberg, Tess Cherlin, Nikolas Tsiouplis, Phillipe Loher, Isidore Rigoutsos Nov 2023

The Typical Trna Co-Expresses Multiple 5' Trna Halves Whose Sequences And Abundances Depend On Isodecoder And Isoacceptor And Change With Tissue Type, Cell Type, And Disease, Robert Akins, Kayleigh Ostberg, Tess Cherlin, Nikolas Tsiouplis, Phillipe Loher, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

Transfer RNA-derived fragments (tRFs) are noncoding RNAs that arise from either mature transfer RNAs (tRNAs) or their precursors. One important category of tRFs comprises the tRNA halves, which are generated through cleavage at the anticodon. A given tRNA typically gives rise to several co-expressed 5'-tRNA halves (5'-tRHs) that differ in the location of their 3' ends. These 5'-tRHs, even though distinct, have traditionally been treated as indistinguishable from one another due to their near-identical sequences and lengths. We focused on co-expressed 5'-tRHs that arise from the same tRNA and systematically examined their exact sequences and abundances across 10 different human …


In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood Nov 2023

In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood

Faculty, Staff and Student Publications

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …


Doxorubicin-Induced Modulation Of Tgf-Β Signaling Cascade In Mouse Fibroblasts: Insights Into Cardiotoxicity Mechanisms, Conner Patricelli, Parker Lehmann, Julia Thom Oxford, Xinzhu Pu Nov 2023

Doxorubicin-Induced Modulation Of Tgf-Β Signaling Cascade In Mouse Fibroblasts: Insights Into Cardiotoxicity Mechanisms, Conner Patricelli, Parker Lehmann, Julia Thom Oxford, Xinzhu Pu

Biology Faculty Publications and Presentations

Doxorubicin (DOX)-induced cardiotoxicity has been widely observed, yet the specific impact on cardiac fibroblasts is not fully understood. Additionally, the modulation of the transforming growth factor beta (TGF-β) signaling pathway by DOX remains to be fully elucidated. This study investigated DOX’s ability to modulate the expression of genes and proteins involved in the TGF-β signaling cascade in mouse fibroblasts from two sources by assessing the impact of DOX treatment on TGF-β inducible expression of pivotal genes and proteins within fibroblasts. Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX in the presence of TGF-β1 to …


Focalizing Regions Of Biomarker Relevance Facilitates Biomarker Prediction On Histopathological Images, Jiefeng Gan, Hanchen Wang, Hui Yu, Zitong He, Wenjuan Zhang, Ke Ma, Lianghui Zhu, Yutong Bai, Zongwei Zhou, Alan Yullie, Xiang Bai, Mingwei Wang, Dehua Yang, Yanyan Chen, Guoan Chen, Joan Lasenby, Chao Cheng, Jia Wu, Jianjun Zhang, Xinggang Wang, Yaobing Chen, Guoping Wang, Tian Xia Oct 2023

Focalizing Regions Of Biomarker Relevance Facilitates Biomarker Prediction On Histopathological Images, Jiefeng Gan, Hanchen Wang, Hui Yu, Zitong He, Wenjuan Zhang, Ke Ma, Lianghui Zhu, Yutong Bai, Zongwei Zhou, Alan Yullie, Xiang Bai, Mingwei Wang, Dehua Yang, Yanyan Chen, Guoan Chen, Joan Lasenby, Chao Cheng, Jia Wu, Jianjun Zhang, Xinggang Wang, Yaobing Chen, Guoping Wang, Tian Xia

Faculty, Staff and Student Publications

Image-based AI has thrived as a potentially revolutionary tool for predicting molecular biomarker statuses, which aids in categorizing patients for appropriate medical treatments. However, many methods using hematoxylin and eosin-stained (H&E) whole-slide images (WSIs) have been found to be inefficient because of the presence of numerous uninformative or irrelevant image patches. In this study, we introduced the region of biomarker relevance (ROB) concept to identify the morphological areas most closely associated with biomarkers for accurate status prediction. We actualized this concept within a framework called saliency ROB search (SRS) to enable efficient and effective predictions. By evaluating various lung adenocarcinoma …


Ribosomal Protein L8 Regulates The Expression And Splicing Pattern Of Genes Associated With Cancer-Related Pathways, Leilei Xu, Gui Yang, Bin Song, Dong Chen, Akbar. Yunus, Jiangtao Chen, Xiaogang Yang, Zheng Tian Oct 2023

Ribosomal Protein L8 Regulates The Expression And Splicing Pattern Of Genes Associated With Cancer-Related Pathways, Leilei Xu, Gui Yang, Bin Song, Dong Chen, Akbar. Yunus, Jiangtao Chen, Xiaogang Yang, Zheng Tian

Turkish Journal of Biology

Background/aim: Ribosomal proteins have been shown to perform unique extraribosomal functions in cell apoptosis and other biological processes. Ribosomal protein L8 (RPL8) not only has important nonribosomal regulatory functions but also participates in the oncogenesis and development of tumors. However, the specific biological functions and pathways involved in this process are still unknown. Materials and methods: RPL8 was overexpressed (RPL8-OE) in HeLa cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transcriptome sequencing was performed to analyze the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs) by RPL8-OE, both of which were …


Sptan1/Numb Axis Senses Cell Density To Restrain Cell Growth And Oncogenesis Through Hippo Signaling, Dongxue Su, Yuxi Li, Weiji Zhang, Huan Gao, Yao Cheng, Yongqiang Hou, Junhong Li, Yi Ye, Zhangjian Lai, Zhe Li, Haitao Huang, Jiaxin Li, Jinhuan Li, Mengyu Cheng, Cheng Nian, Na Wu, Zhien Zhou, Yunzhi Xing, Yu Zhao, He Liu, Jiayu Tang, Qinghua Chen, Lixin Hong, Wengang Li, Zhihai Peng, Bin Zhao, Randy L Johnson, Pingguo Liu, Wanjin Hong, Lanfen Chen, Dawang Zhou Oct 2023

Sptan1/Numb Axis Senses Cell Density To Restrain Cell Growth And Oncogenesis Through Hippo Signaling, Dongxue Su, Yuxi Li, Weiji Zhang, Huan Gao, Yao Cheng, Yongqiang Hou, Junhong Li, Yi Ye, Zhangjian Lai, Zhe Li, Haitao Huang, Jiaxin Li, Jinhuan Li, Mengyu Cheng, Cheng Nian, Na Wu, Zhien Zhou, Yunzhi Xing, Yu Zhao, He Liu, Jiayu Tang, Qinghua Chen, Lixin Hong, Wengang Li, Zhihai Peng, Bin Zhao, Randy L Johnson, Pingguo Liu, Wanjin Hong, Lanfen Chen, Dawang Zhou

Faculty, Staff and Student Publications

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin α chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and …


Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi Oct 2023

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …


Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou Oct 2023

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Faculty, Staff and Student Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …


Characterizing The Effects Of Benzyl-Amino Alcohol On Cell Growth, Viability, And Migration, Ryan Miller, Jeff Hansen, Sarah Mordan-Mccombs Oct 2023

Characterizing The Effects Of Benzyl-Amino Alcohol On Cell Growth, Viability, And Migration, Ryan Miller, Jeff Hansen, Sarah Mordan-Mccombs

Annual Student Research Poster Session

The research we are performing investigates a new compound classified as benzyl-amino alcohol and begins a new endeavor into the effects of this class of compound. This compound would work well in chemotherapies because affecting healthy cells can lead to a patient’s health decline.


Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo Oct 2023

Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In this comprehensive review, we will dissect the impact of research on proteoglycans focusing on recent developments involved in their synthesis, degradation, and interactions, while critically assessing their usefulness in various biological processes. The emerging roles of proteoglycans in global infections, specifically the SARS-CoV-2 pandemic, and their rising functions in regenerative medicine and biomaterial science have significantly affected our current view of proteoglycans and related compounds. The roles of proteoglycans in cancer biology and their potential use as a next-generation protein-based adjuvant therapy to combat cancer is also emerging as a constructive and potentially beneficial therapeutic strategy. We will discuss …


Raman Spectral Cytopathology For Cancer Diagnostic Applications, Fiona Lyng, Damian Traynor, Isha Behl, Declan O'Dea, Hugh Byrne Oct 2023

Raman Spectral Cytopathology For Cancer Diagnostic Applications, Fiona Lyng, Damian Traynor, Isha Behl, Declan O'Dea, Hugh Byrne

Books/Book Chapters

Histopathology is currently regarded as the “gold standard” patient sampling technique for cancer diagnostics. It involves extraction of a tissue sample, or biopsy, which is then sectioned and stained for evaluation by a pathologist [1]. Cytopathology, on the other hand, is the field of disease diagnosis at the cellular level [2], necessitating only the microscopic evaluation of samples of cells which can be harvested by less invasive methods such as exfoliative brushing, needle probes or from biofluids. Based on the identification of abnormalities in cellular appearance, cytopathology is currently widely used to aid in the screening of cancer, as well …


Precise Method To Identify Kinase Drug Targets In Complex Diseases: The First Step Towards Sustainable And Effective Treatment, Hasbanny Irisson, Marzieh Ayati Sep 2023

Precise Method To Identify Kinase Drug Targets In Complex Diseases: The First Step Towards Sustainable And Effective Treatment, Hasbanny Irisson, Marzieh Ayati

Research Symposium

Background: Kinases are enzymes that have proven to be important drug targets due to their role in critical biological mechanisms such as phosphorylation. Phosphorylation happens when a kinase catalyzes the transfer of a phosphate group to a protein in a phosphorylated site, which then becomes known as the substrate of the kinase. Any dysregulation of protein phosphorylation causes a wide range of complex diseases including cancer. Thus, discovering the links between kinases and their substrates (i.e. predicting kinase-substrate associations (KSAs)) is crucial in developing effective and sustainable treatments. Presently, less than 5% of phosphorylated sites have an associated kinase, and …


Identification And Characterization Of Anticancer Potential Of A Novel Small Molecule, Mortaparibmild, Hazna Noor Meidinna, Anissa Nofita Sari, Sunil C. Kaul, Renu Wadhwa Sep 2023

Identification And Characterization Of Anticancer Potential Of A Novel Small Molecule, Mortaparibmild, Hazna Noor Meidinna, Anissa Nofita Sari, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background: The development of new anticancer drugs and treatment modalities form a priority research field. The tumor suppressor protein p53 is frequently mutated or functionally inactivated in a large variety of cancers. Its inactivation by mortalin, a member of the heat shock 70 protein family, has been shown to contribute to carcinogenesis. The small molecule inhibitors of mortalin-p53 interactions have been shown to reactivate p53 yielding apoptosis/growth arrest in cancer cells. Therefore, abrogators of mortalin-p53 interaction have emerged as possible new therapeutic anticancer reagents.

Methods: We performed chemical library screening based on the imaging of mortalin-p53 interaction, leading to the …


Engineered Exosomes For The Multimodal Imaging Directed Photo-Immunotherapy Of Colorectal Cancer, Deepak S. Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu Sep 2023

Engineered Exosomes For The Multimodal Imaging Directed Photo-Immunotherapy Of Colorectal Cancer, Deepak S. Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Rio Grande Valley experience severe cancer health disparity. A novel therapeutic modality may serve as better therapeutic option. Nanohybrids endowed with multifunctionality, longer circulation time, large surface area have emerged as an active preference for cancer research. However, rising concern of nanomaterials toxicity and scalability issues has slowed their translation to clinics. Exosomes (Exo) are endogenous endocytic origin 40-100 nm vesicles found in various body fluids, which in comparison to synthetic nanoparticles, are biodegradable, highly biocompatible as well as immunocompatible in nature. Although bulk isolation of exosomes from human body fluids is still a problem and engineering of exosomes …