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Full-Text Articles in Life Sciences

The Multilayered Control Of Acetylation During Adenovirus-Based Immunotherapy Of Cancer, Akhila Parthasarathy, Maria Frost, Andrew G Gillard, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo Jun 2025

The Multilayered Control Of Acetylation During Adenovirus-Based Immunotherapy Of Cancer, Akhila Parthasarathy, Maria Frost, Andrew G Gillard, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Adenoviruses are highly immunogenic agents that have shown promise first as gene delivery vectors and later as oncolytic viruses. Currently, oncolytic adenoviruses are featured in over 30% of cancer virotherapy clinical trials. Due to their effective cellular uptake and hijack of cellular machinery, replication-competent adenoviruses are promising therapeutic agents for treating a wide range of tumors. Adenoviral influence on host cell acetylome regulation has regained attention, as these viruses redirect or suppress acetylation during replication, making them potentially desirable therapeutic agents for cancers driven by epigenetic modifications. In this review, we aim to cover the viral processes influencing the acetylome …


Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed Jun 2025

Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed

Maaen Journal for Medical Sciences

Acromegaly is a rare endocrine clinical syndrome characterized by long-term elevated production of growth hormone (GH) due to a pituitary adenoma tumor. The main problem of acromegaly patients (AC-PTs) is prolonged elevated GH concentration, which leads to increased insulin-like growth factor 1 (IGF-1) production, causing the characteristic tissue and bone overgrowth. The appearance of diabetes in AC-PTs was linked with the high risks of cardiovascular morbidity, indicating that individuals with both conditions face heightened health challenges. Acromegaly typically has a higher cancer incidence rather than the general population. Without early diagnosis and effective treatment, excess GH can have widespread systemic …


Egfr Controls Transcriptional And Metabolic Rewiring In Krasg12d Colorectal Cancer, Dana Krauß, Veronica Moreno-Viedma, Emi Adachi-Fernandez, Cristiano De Sá Fernandes, Jakob-Wendelin Genger, Ourania Fari, Bernadette Blauensteiner, Dominik Kirchhofer, Nikolina Bradaric, Valeriya Gushchina, Georgios Fotakis, Thomas Mohr, Ifat Abramovich, Inbal Mor, Martin Holcmann, Andreas Bergthaler, Arvand Haschemi, Zlatko Trajanoski, Juliane Winkler, Eyal Gottlieb, Maria Sibilia Jun 2025

Egfr Controls Transcriptional And Metabolic Rewiring In Krasg12d Colorectal Cancer, Dana Krauß, Veronica Moreno-Viedma, Emi Adachi-Fernandez, Cristiano De Sá Fernandes, Jakob-Wendelin Genger, Ourania Fari, Bernadette Blauensteiner, Dominik Kirchhofer, Nikolina Bradaric, Valeriya Gushchina, Georgios Fotakis, Thomas Mohr, Ifat Abramovich, Inbal Mor, Martin Holcmann, Andreas Bergthaler, Arvand Haschemi, Zlatko Trajanoski, Juliane Winkler, Eyal Gottlieb, Maria Sibilia

Faculty, Staff and Student Publications

Inhibition of the epidermal growth factor receptor (EGFR) shows clinical benefit in metastatic colorectal cancer (CRC) patients, but KRAS-mutations are known to confer resistance. However, recent reports highlight EGFR as a crucial target to be co-inhibited with RAS inhibitors for effective treatment of KRAS mutant CRC. Here, we investigated the tumor cell-intrinsic contribution of EGFR in KRASG12D tumors by establishing murine CRC organoids with key CRC mutations (KRAS, APC, TP53) and inducible EGFR deletion. Metabolomic, transcriptomic, and scRNA-analyses revealed that EGFR deletion in KRAS-mutant organoids reduced their phenotypic heterogeneity and activated a distinct cancer-stem-cell/WNT signature associated with reduced cell size …


Fibroblast Dynamics During Mammary Oncogenesis: Senescence, Wnt9a And Beyond, Viktoria Boeker, Raghu Kalluri Jun 2025

Fibroblast Dynamics During Mammary Oncogenesis: Senescence, Wnt9a And Beyond, Viktoria Boeker, Raghu Kalluri

Faculty, Staff and Student Publications

Mammary gland fibroblasts are highly plastic and transition through distinct states during development and disease. A new study by Pascual et al (2025) provides a comprehensive single-cell atlas of murine mammary stromal cell hierarchies, revealing dysregulation of progenitor-driven fibroblast lineages in breast cancer and a senescence role of Wnt9a in cancer-associated myofibroblasts.


The Tweak/Fn14 Signaling Mediates Skeletal Muscle Wasting During Cancer Cachexia, Meiricris Tomaz Da Silva, Anirban Roy, Anh Tuan Vuong, Aniket S Joshi, Cristeena Josphien, Meghana V Trivedi, Sajedah M Hindi, Vihang A Narkar, Ashok Kumar May 2025

The Tweak/Fn14 Signaling Mediates Skeletal Muscle Wasting During Cancer Cachexia, Meiricris Tomaz Da Silva, Anirban Roy, Anh Tuan Vuong, Aniket S Joshi, Cristeena Josphien, Meghana V Trivedi, Sajedah M Hindi, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Cancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle wasting. The TWEAK-Fn14 system regulates muscle mass in diverse conditions. However, its role in the regulation of muscle mass during cancer cachexia remains less understood. Here, we demonstrate that the levels of Fn14 are induced in skeletal muscle of multiple mouse models of cancer cachexia. Muscle-specific deletion of Fn14 reduces myofiber atrophy in mouse models of pancreatic and lung cancer cachexia. Silencing of Fn14 in KPC pancreatic cancer cells prior to their implantation in mice attenuates tumor growth without affecting myofiber size. Muscle-specific deletion of Fn14 reduces the gene …


Histodx: Revolutionizing Breast Cancer Diagnosis Through Advanced Imaging Techniques, Wishal Arshad, Tehreem Masood, H. M. Shahzad, Hassan A. Ahmed, Syed Hamza Ahmed, Hafiz Muhammad Tayyab Khushi May 2025

Histodx: Revolutionizing Breast Cancer Diagnosis Through Advanced Imaging Techniques, Wishal Arshad, Tehreem Masood, H. M. Shahzad, Hassan A. Ahmed, Syed Hamza Ahmed, Hafiz Muhammad Tayyab Khushi

Business Faculty Publications

Breast cancer is the second leading cause of mortality among women worldwide, highlighting the need for efficient histopathology-based screening methods for early diagnosis. This study introduces HistoDX, a deep learning framework to classify Invasive Ductal Carcinoma (IDC) using 277,524 histopathology image patches (50x50 pixels) from Paul Mooney’s IDC dataset on Kaggle, comprising No Cancer and IDC(+) classes. HistoDX employs a preprocessing pipeline with normalization, data augmentation, and class balancing via oversampling and weighted loss to address the class imbalance. A customized convolutional neural network, built on EfficientNetV2-B3 with additional layers, achieves 97% accuracy and a 0.91 ROC-AUC score on the …


Thsd1 Is A Multifaceted Regulator In Health And Disease, Mengjun Dai, Kuizhi Qu, Sophie Liu, Zhen Xu, Yan-Ning Rui May 2025

Thsd1 Is A Multifaceted Regulator In Health And Disease, Mengjun Dai, Kuizhi Qu, Sophie Liu, Zhen Xu, Yan-Ning Rui

Faculty, Staff and Student Publications

Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) is a transmembrane protein increasingly recognized for its critical roles in vascular biology and disease pathogenesis. Initially identified as a marker of hematopoietic stem and endothelial cells during embryogenesis, THSD1 has since been implicated in a wide spectrum of physiological and pathological processes. This paper consolidates current knowledge on THSD1, with a focus on its roles in vascular integrity, perinatal disorders, and tumorigenesis. In vascular systems, THSD1 promotes focal adhesion assembly and suppresses autophagy-mediated adhesion turnover, thereby stabilizing endothelial attachment and maintaining barrier function. Genetic and functional studies support its protective role against …


A Bitter Brew For Cancer: Egcg’S Impact On Ewing Sarcoma Cells, Lizzeth Holguin, Mary-Esther Leblanc, Mariana Reyes, Terry Jo Shackleford May 2025

A Bitter Brew For Cancer: Egcg’S Impact On Ewing Sarcoma Cells, Lizzeth Holguin, Mary-Esther Leblanc, Mariana Reyes, Terry Jo Shackleford

Cell and Molecular Methods

Epigallocatechin Gallate (EGCG), a powerful antioxidant found in green tea, is an abundant treatment to treat Ewing Sarcoma cells, a pediatric cancer affecting the skeletal system. Given EGCG’s known role in other cancer treatments, these tests aim to investigate its effects as a standalone natural compound on Ewing Sarcoma cells. Focusing on the PI3K/AKT pathway, if the PI3K/AKT pathway is inhibited by EGCG, then it will lead to reduced cell survival and proliferation of EW8 cells. Using cell culture techniques, IncuCyte-based IC50 analysis, caspase 3/7, RNA purification, cDNA synthesis, and qRT-PCR, EGCG’s impact was assessed on cell apoptosis and gene …


The Effect Of Epigallocatechin Gallate (Egcg) And Alpha L-Mangostin On Tp53, Bax, And Vim Gene Expression And Apoptosis In Ewing Sarcoma Cells, Victoria Valdez, Terry Jo Shackleford May 2025

The Effect Of Epigallocatechin Gallate (Egcg) And Alpha L-Mangostin On Tp53, Bax, And Vim Gene Expression And Apoptosis In Ewing Sarcoma Cells, Victoria Valdez, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcoma (ES) is a malignant pediatric bone tumor driven by chromosomal translocations and fusion oncogenes with limited targeted treatment options. This study investigated the chemopreventive potential of two natural compounds, Epigallocatechin Gallate (EGCG) found in green tea, and Alpha L-Mangostin from mangosteen, on apoptosis and gene expression in ES cells. We hypothesized that EGCG and Alpha L-Mangostin treatment would induce apoptosis and downregulate cancer-promoting genes. To test this, we performed tissue culture, IC50 assays, caspase-based apoptosis detection, RNA purification, cDNA synthesis, and qRT-PCR on ES cell lines treated with a high and low concentration of the two compounds. Our …


Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy May 2025

Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy

Master's Theses

The DAX-1 gene (Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1) encodes for an orphan nuclear hormone receptor and its mutation is implicated in multiple diseases including congenital adrenal hypoplasia, adrenal cancer, and breast cancer. Previous research has linked DAX-1 downregulation to tumor initiation in breast tissue, suggesting the gene acts as a tumor suppressor with respect to breast cancer. Additional studies completed by the Tzagarakis-Foster laboratory have shown that methylation of the DAX-1 promoter region is heavily influential in breast cancer development, with release of epigenetic repression resulting in slowing of cellular proliferation …


Minimal Anti-Cancer Effects Of Mushroom-Derived Compounds Hispidin And Chaga Extract On Ewing Sarcoma Cells, Jordan Cosgrove, Fiona Coulbourne, Iris Reyna, Giselle Serna-Flores, Terry Jo Shackleford May 2025

Minimal Anti-Cancer Effects Of Mushroom-Derived Compounds Hispidin And Chaga Extract On Ewing Sarcoma Cells, Jordan Cosgrove, Fiona Coulbourne, Iris Reyna, Giselle Serna-Flores, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a rare and aggressive cancer of adolescents and young adults driven by the EWSR1–FLI1 gene fusion. Standard treatments include chemotherapy, surgery, and radiation, though survival rates remain low. Natural compounds such as hispidin, derived from fungi, and Chaga mushroom extract have shown potential anti-cancer effects by disrupting cell cycle progression and promoting apoptosis in other cancer models. In this study, we tested the effects of hispidin and Chaga extract on Ewing sarcoma cells to evaluate their ability to suppress cell growth and identify potential therapeutic benefits.


The Effects Of Panobinostat On Cellular Signaling Pathways And How It Relates To Antitumor Activities In Ewing Sarcoma Cancer Cells, Crystal Valenzuela, Andrew Martini, Hannah Navarro, Mario Flores, Terry Jo Shackleford May 2025

The Effects Of Panobinostat On Cellular Signaling Pathways And How It Relates To Antitumor Activities In Ewing Sarcoma Cancer Cells, Crystal Valenzuela, Andrew Martini, Hannah Navarro, Mario Flores, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a rare and aggressive cancer that primarily affects the bones and surrounding soft tissues, most commonly in children and young adults. Although the exact etiology remains unclear, a well-documented cause involves a chromosomal translocation resulting in the fusion of the EWSR1 and FLI1 genes. This fusion produces abnormal proteins that disrupt normal gene expression, cell signaling, and RNA processing, contributing to tumorigenesis. Prognosis varies significantly depending on the extent of metastasis, with 5-year survival rates ranging from 82% in localized cases to 39% in metastatic cases. Standard treatments include chemotherapy typically involving vincristine, doxorubicin, etoposide, and cyclophosphamide—surgical …


The Effects Of Hispidin And Eribulin Mesylate On Cell Proliferation Of Ewing Sarcoma Cell Lines, Elena Mares, Angelina Juarrita, Sierra Munoz, Terry Jo Shackleford May 2025

The Effects Of Hispidin And Eribulin Mesylate On Cell Proliferation Of Ewing Sarcoma Cell Lines, Elena Mares, Angelina Juarrita, Sierra Munoz, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a type of cancer that targets the cells within bones and soft tissue and is most prevalent in younger populations. It is important to look at this specific cancer because there is no cure yet, and the risks increase, even after a patient has completed their treatment. We hypothesize that if we treat Ewing sarcoma cell lines with natural compounds, specifically Hispidin and Eribulin Mesylate, then the cell lines will decrease in cell viability and there will be an increase in apoptosis of the cancerous cell lines. We performed a series of experiments, which included IC50 analysis, …


Validating The Ability Of Iag933 To Block The Interaction Of Yap1 And Tead In Ovarian Cancer Cells, Alex Sage May 2025

Validating The Ability Of Iag933 To Block The Interaction Of Yap1 And Tead In Ovarian Cancer Cells, Alex Sage

Theses & Dissertations

Ovarian cancer is the most common and deadliest gynecologic malignancy. Approximately 40% of ovarian cancer patients exhibit chemoresistance after receiving initial treatment in the form of neoadjuvant chemotherapy or interval debulking surgery, of which YAP1 (Yes-associated protein 1) has been implicated in enhancing the resistance of ovarian cancer to Cisplatin and Taxol.1,2. This highlights the need to develop new therapeutic strategies that target the Hippo pathway to overcome resistance to traditional therapies.

YAP1 is a protein that acts as a transcription coregulator, promoting the transcription of genes involved in cellular proliferation and suppressing apoptotic genes. It is a …


Pan-Cancer Universal Targets For Immunotherapy Resulted From Transposable Elements Activation, Yonghao Liang May 2025

Pan-Cancer Universal Targets For Immunotherapy Resulted From Transposable Elements Activation, Yonghao Liang

Arts & Sciences Graduate Student Theses and Dissertations

Transposable elements (TEs) contribute to nearly half of the human genome yet have been overlooked in genomic medicines due to the stereotypic impression as “junk DNA” and technical challenges. However, studies in the last two decades demonstrated that dysregulation of the epigenome in cancer cells resurrects the cis-regulatory functions of TEs, including the promoter activities. The tumor-specific TE activation events along with the resulting tumor-specific RNA and protein molecules, provide a potential “gold mine” for identifying tumor-specific therapeutic targets for cancer treatments, including immunotherapy. Here, I present a series of works to investigate the potential of providing actionable, pan-cancer, and …


Computational Design Of Potent Sirna For Braf Oncogene Silencing For Enhancing Cancer Therapy, Muhammad Hermawan Widyananda, Ricadonna Raissa May 2025

Computational Design Of Potent Sirna For Braf Oncogene Silencing For Enhancing Cancer Therapy, Muhammad Hermawan Widyananda, Ricadonna Raissa

Karbala International Journal of Modern Science

The discovery of oncogenic BRAF mutations has prompted the development of inhibitors, yet resistance remains widespread. A more effective strategy involves targeting BRAF mRNA with siRNA to overcome resistance to BRAF inhibitors. This study aims to design potent siRNA for BRAF oncogene silencing using a computational approach. The full coding sequence of BRAF was retrieved from the NCBI database and potential siRNAs were predicted using the Ui-Tei, Reynolds, and Amarzguioui rules. Identified siRNAs were further analyzed using various prediction systems and parameters, including their interaction with the hAgo2 protein. The results identified that seven siRNAs (siRNA 23, siRNA 24, siRNA …


Disulfide-Cleavable Linkers In Antibody-Drug Conjugates For Targeted Cancer Therapy, Emily Hwang May 2025

Disulfide-Cleavable Linkers In Antibody-Drug Conjugates For Targeted Cancer Therapy, Emily Hwang

Undergraduate Honors Thesis Collection

This project aims to discover a way to improve the safety of and reduce adverse side effects of disulfide-linked antibody-drug conjugates. Disulfide-cleavable linkers for antibody-drug conjugates function by exploiting the differential concentrations of dominant thiol species in the blood plasma and in the cytosol of malignant cells. This project aimed to identify a relationship between the stability of disulfide cleavable linkers in the blood plasma and disulfide linker structure, to prevent premature release of the cytotoxic drug. Three disulfide linker analogs with varying carbon chain lengths were synthesized through reaction with 2,2’-dipyridyl disulfide. Each analog was conjugated to a fluorescent …


Examining The Molecular Mechanisms Of Glucagon-Like Peptide-1 Receptor Agonists In Cancer Cell Biology, Oliver G. Sabet May 2025

Examining The Molecular Mechanisms Of Glucagon-Like Peptide-1 Receptor Agonists In Cancer Cell Biology, Oliver G. Sabet

Honors Scholar Theses

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are synthetic analogs of glucagon-like peptide-1 (GLP-1) used to treat obesity and diabetes by reducing blood glucose levels and appetite. While early rodent studies suggested a link between GLP-1RAs and thyroid cancer pathogenesis, evidence in humans remains inconclusive, with randomized controlled trials not supporting that link. Due to the rapid, widespread use of these drugs, concerns have expanded to other obesity-associated cancers, with conflicting findings on their role in cancer progression. With this contradictory evidence in a novel intersection of obesity medicine and oncology, this literature review aims to summarize current understandings between GLP-1-RAs and …


Which Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce Cytokine Responses That Are Linked To A More Toxic Car T Cell Therapy In Acute Lymphocytic Leukemia?, Elisabeth Cohen May 2025

Which Costimulatory Domains In Chimeric Antigen Receptor T Cells Induce Cytokine Responses That Are Linked To A More Toxic Car T Cell Therapy In Acute Lymphocytic Leukemia?, Elisabeth Cohen

Longwood Senior Thesis Proposal

No abstract provided.


A Stakeholder-Informed Conceptual Framework For Evaluating Genomics In Precision Oncology, Julie A. Wiedower May 2025

A Stakeholder-Informed Conceptual Framework For Evaluating Genomics In Precision Oncology, Julie A. Wiedower

All Dissertations

This dissertation explores the value of genomic testing in precision oncology with an emphasis on how US payers conceptualize and prioritize elements of value. This research aims to address gaps in understanding payer perspectives and proposes a stakeholder-informed framework for evaluating genomic testing in oncology. To achieve this aim, the presented research investigates payer perspectives, value-based cancer care priorities, and the conceptual understanding of the value of a genetic diagnosis to establish a framework for value with the payer audience in mind. Chapter 1 outlines relevant background information relating to the genomic revolution and challenges in translating genomic testing technologies …


Pembrolizumab In Patients With Advanced Miscellaneous Rare Cancers: Results From A Phase 2 Basket Trial, Mirella Nardo, Camila Braganca Xavier, Bettzy Stephen, Jeffrey A How, Justin Moyers, Vivek Subbiah, David S Hong, Aung Naing May 2025

Pembrolizumab In Patients With Advanced Miscellaneous Rare Cancers: Results From A Phase 2 Basket Trial, Mirella Nardo, Camila Braganca Xavier, Bettzy Stephen, Jeffrey A How, Justin Moyers, Vivek Subbiah, David S Hong, Aung Naing

Faculty, Staff and Student Publications

Introduction: Rare solid tumors account for one-quarter of cancers among adults in the United States, but few resources have been devoted to their treatment. We evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with rare solid tumors.

Methods: We conducted a phase 2 basket trial that included patients with rare, advanced tumors. Patients were enrolled in the study in nine tumor-specific and a 10th cohort of miscellaneous rare histologies. Patients received pembrolizumab 200 mg intravenously every 21 days. The primary endpoint was the non-progression rate at 27 weeks per immune-related Response Evaluation Criteria in Solid Tumors …


Multiscale Integration Of Receptor-Ligand Dynamics Into Discrete And Continuous Tumor Growth Models With Application To Tyrosine Kinase Inhibitor Treatment, Romasa Qasim May 2025

Multiscale Integration Of Receptor-Ligand Dynamics Into Discrete And Continuous Tumor Growth Models With Application To Tyrosine Kinase Inhibitor Treatment, Romasa Qasim

Open Access Theses & Dissertations

The epidermal growth factor (EGF) receptor cascade plays a crucial role in the survival and proliferation of tumor cells. Tyrosine kinase inhibitors (TKIs) are a class of drugs that inhibit epidermal growth factor receptors (EGFRs), thereby preventing the downstream signal transduction. Despite their importance, models that link spatial receptor dynamics to tumor growth remain scarce. Further, TKIs act through selective mechanisms, inhibiting active, inactive, or all receptor states, which poses a challenge to traditional modeling approaches.

We propose to numerically study two mathematical models incorporating receptor-dynamics into cancer models to describe the impact of EGFR overexpression and TKIs. The first …


Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley May 2025

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …


Studies To Understand The Stability And Liabilities Of Legumain-Cleavable Antibody-Drug Conjugates, Michele Yi Apr 2025

Studies To Understand The Stability And Liabilities Of Legumain-Cleavable Antibody-Drug Conjugates, Michele Yi

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) offer targeted drug delivery of potent cytotoxic payloads, minimizing systemic toxicity. However, the stability of the linker is integral to ensure that there is minimal off-target payload release and little systemic toxicity. This study analyzes the physical and biological stability of our new legumain-cleavable vs traditional cathepsin-cleavable antibody-drug conjugates (ADCs), with a focus on hydrophobicity, thermal stability, aggregation, and biological payload release. Our findings indicate that decreased hydrophobicity of the legumain-cleavable ADCs compared to cathepsin-cleavable ADCs is correlated with decreased aggregation (predicting lower uptake by liver macrophages and therefore slower clearance and less systemic toxicity) and lower …


Exploring Ddr2’S Role In Caf Extracellular Matrix Production And Tumor Progression, Favour Ayomide Akinjiyan Apr 2025

Exploring Ddr2’S Role In Caf Extracellular Matrix Production And Tumor Progression, Favour Ayomide Akinjiyan

Arts & Sciences Graduate Student Theses and Dissertations

Ovarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, …


Enriched Pathways In Gut Microbiome Predict Response To Immune Checkpoint Inhibitor Treatment Across Demographic Regions And Various Cancer Types, Xunhui Cai, Jennifer Y Cho, Lijun Chen, Yufeng Liu, Fenghu Ji, Katia Salgado, Siyi Ge, Dehua Yang, Hui Yu, Jianbo Shao, P Andrew Futreal, Boris Sepesi, Don Gibbons, Yaobing Chen, Guoping Wang, Chao Cheng, Meng Wu, Jianjun Zhang, Ansel Hsiao, Tian Xia Apr 2025

Enriched Pathways In Gut Microbiome Predict Response To Immune Checkpoint Inhibitor Treatment Across Demographic Regions And Various Cancer Types, Xunhui Cai, Jennifer Y Cho, Lijun Chen, Yufeng Liu, Fenghu Ji, Katia Salgado, Siyi Ge, Dehua Yang, Hui Yu, Jianbo Shao, P Andrew Futreal, Boris Sepesi, Don Gibbons, Yaobing Chen, Guoping Wang, Chao Cheng, Meng Wu, Jianjun Zhang, Ansel Hsiao, Tian Xia

Faculty, Staff and Student Publications

Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore,


Natural Killer Cells’ Functional Impairment Drives The Immune Escape Of Pre-Malignant Clones In Early-Stage Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Bijender Kumar, Natthakan Thongon, Feiyang Ma, Kelly S Chien, Yi J Kim, Hui Yang, Sanam Loghavi, Roselyn Tan, Vera Adema, Zongrui Li, Tomoyuki Tanaka, Hidetaka Uryu, Rashmi Kanagal-Shamanna, Gheath Al-Atrash, Rafael Bejar, Pinaki Prosad Banerjee, Sophia Lynn Cha, Guillermo Montalban-Bravo, Max Dougherty, Maria Claudina Fernandez Laurita, Noelle Wheeler, Baosen Jia, Eirini P Papapetrou, Franco Izzo, Daniela E Dueñas, Salome Mcallen, Yiqian Gu, Gabriele Todisco, Francesca Ficara, Matteo Giovanni Della Porta, Abhinav Jain, Koichi Takahashi, Karen Clise-Dwyer, Stephanie Halene, Maria Teresa Sabrina Bertilaccio, Guillermo Garcia-Manero, May Daher, Simona Colla Apr 2025

Natural Killer Cells’ Functional Impairment Drives The Immune Escape Of Pre-Malignant Clones In Early-Stage Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Bijender Kumar, Natthakan Thongon, Feiyang Ma, Kelly S Chien, Yi J Kim, Hui Yang, Sanam Loghavi, Roselyn Tan, Vera Adema, Zongrui Li, Tomoyuki Tanaka, Hidetaka Uryu, Rashmi Kanagal-Shamanna, Gheath Al-Atrash, Rafael Bejar, Pinaki Prosad Banerjee, Sophia Lynn Cha, Guillermo Montalban-Bravo, Max Dougherty, Maria Claudina Fernandez Laurita, Noelle Wheeler, Baosen Jia, Eirini P Papapetrou, Franco Izzo, Daniela E Dueñas, Salome Mcallen, Yiqian Gu, Gabriele Todisco, Francesca Ficara, Matteo Giovanni Della Porta, Abhinav Jain, Koichi Takahashi, Karen Clise-Dwyer, Stephanie Halene, Maria Teresa Sabrina Bertilaccio, Guillermo Garcia-Manero, May Daher, Simona Colla

Faculty, Staff and Student Publications

Dissecting the preneoplastic disease states' biological mechanisms that precede tumorigenesis can lead to interventions that can slow down disease progression and/or mitigate disease-related comorbidities. Myelodysplastic syndromes (MDS) cannot be cured by currently available pharmacological therapies, which fail to eradicate aberrant hematopoietic stem cells (HSCs), most of which are mutated by the time of diagnosis. Here, we sought to elucidate how MDS HSCs evade immune surveillance and expand in patients with clonal cytopenias of undetermined significance (CCUS), the pre-malignant stage of MDS. We used multi-omic single-cell approaches and functional in vitro studies to show that immune escape at disease initiation is …


A Scoping Review Of Omop Cdm Adoption For Cancer Research Using Real World Data, Liwei Wang, Andrew Wen, Sunyang Fu, Xiaoyang Ruan, Ming Huang, Rui Li, Qiuhao Lu, Heather Lyu, Andrew E Williams, Hongfang Liu Apr 2025

A Scoping Review Of Omop Cdm Adoption For Cancer Research Using Real World Data, Liwei Wang, Andrew Wen, Sunyang Fu, Xiaoyang Ruan, Ming Huang, Rui Li, Qiuhao Lu, Heather Lyu, Andrew E Williams, Hongfang Liu

Faculty, Staff and Student Publications

The Observational Medical Outcomes Partnership (OMOP) common data model (CDM) supports large-scale research by enabling distributed network analyses. However, the breadth of its adoption in cancer research is not well understood. We conducted a scoping review to describe the adoption of the OMOP CDM in cancer research. A total of 49 unique articles were included in the review, with 30 on the data analysis theme, and 20 on the infrastructure theme. This review highlighted that while the OMOP CDM ecosystem has enabled successful data support for cancer research, particularly for collaborative studies, ongoing model development and iterative improvement remain needed …


Anticancer Activity Of Allium Cepa Through The Inactivation Of Nf-Κb Pathway: A Literature-Based Study, Sharmita Ghosh Situ, Md. Sakib Al Hasan, Emon Mia, Md. Nasimul Haque Shipon, Md. Faisal Amin, Asmaul Husna Bristy, Yasin Emon Apr 2025

Anticancer Activity Of Allium Cepa Through The Inactivation Of Nf-Κb Pathway: A Literature-Based Study, Sharmita Ghosh Situ, Md. Sakib Al Hasan, Emon Mia, Md. Nasimul Haque Shipon, Md. Faisal Amin, Asmaul Husna Bristy, Yasin Emon

School of Integrative Biological & Chemical Sciences Faculty Publications

Allium cepa (onion) is a bulbous herb renowned for its diverse health benefits. This study aims to summarize the anticancer potential of A. cepa through the inactivation of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reviewing experimental findings across various cancer models. A thorough examination of the literature was carried out using databases like Google Scholar, PubMed, Web of Science, and ScienceDirect. The findings revealed that phytochemicals such as stigmasterol, fisetin, quercetin, isorhamnetin, morin, kaempferol, luteolin, β-carotene, and β-sitosterol exhibit strong anticancer properties against various cancers, including breast, bladder, colon, colorectal, cervical, lung, liver, oral, pancreatic, …


Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden Apr 2025

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

Longwood Senior Thesis Proposal

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