Medicine and Health Sciences Commons^™

Investigating Pinch-1 In Glioblastoma Multiforme: A Potential Adjuvant Therapy Target To Improve Treatment Outcomes, Saikrishna Gaddam, Dianne Langford

Rowan-Virtua Research Day

Gliomas account for approximately 80% of all brain cancers and 30% of central nervous system tumors. Glioblastoma multiforme (GBM), the most common, is unfortunately, the most aggressive glioma cancer type. Despite treatment efforts such as surgery, radiation, and chemotherapy, nearly all low-grade astrocytoma progress to GBM without complete surgical resection. Achieving full surgical removal is typically impossible, leading to an almost 100% recurrence rate of GBM after 9 months with a median survival of approximately 15 months. This poor prognosis is due to its high invasiveness and resistance to therapy. Therefore, improved therapeutic approaches are needed to reduce recurrence and …

Machine Learning And Protein Engineering Approaches To Understanding Kinesin-5 Activity, Jason Eden Sanchez

Open Access Theses & Dissertations

Cancer is a term describing a collection of diseases that result in uncontrolled cell growth. Cancer has manifold etiologies and underlying cancers are rouge biochemical pathways involving many different proteins. In the current work, two approaches are used to enhance knowledge of kinesin-5, a potential cancer target involved in cell division. Kinesin-5 promotes cell division by cross-linking and separating microtubules in dividing cells. The first approach uses machine learning (ML) to identify small molecule inhibitors for kinesin-5. Though decades of research have uncovered classes of small-molecules which inhibit kinesin-5 in vitro and in vivo, no candidates have reached phase III …

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 …

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 …

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 …

Utilization Of Genomic Prostate Score With Prostate Specific Antigen Density In Patients On Active Surveillance For Low-Risk Prostate Cancer, William Nguyen, Young Son, Benjamin Fink, Shawon Akanda, Vaishnavi Patel, Virgil Demario, Mark Quiring, Ronald Clearie, Donna Mehdiyar, Thao-Mi Ha, Kimberly Toumazos, Gordon Brown

Research Day

Introduction and objectives: Prostate cancer is prevalent in men and the second leading cause of cancer related death. However, not all prostate cancer is lethal. and active surveillance is an accepted treatment approach in appropriately risk stratified patients. Nonetheless, there is a subset of patients on active surveillance (AS) that escalates to treatment and a paucity of data to identify patients requiring treatment intensification Biomarkers such as Oncotype DX have been utilized in multiple malignancies including prostate cancer and aid in shared decision-making regarding treatment. In this study, we present real world data on the use of Oncotype DX Genomic …

Protein Kinase C Delta Peptide Activator Provides Protection During Hypoxia/Reoxygenation And Elicits Significant Anti-Cancer Effects In Vitro, Juliet M. Melnik, Qian Chen, Robert J. Barsotti, Lindon H. Young

Research Day

Introduction

Protein kinase C delta (PKCδ) activation is known to inhibit NOX-2/superoxide (SO) release in polymorphonuclear leukocytes (PMNs) and elicit cardioprotective effects in ischemia-reperfusion (I/R) injury. Augmenting PKCδ activity also promotes tumor suppressive effects via apoptosis. This study examined the cardioprotective and anticancer effects of PKCδ peptide activator (PKCδ+) in endothelial cells and cardiomyocytes, cardiovascular cells particularly susceptible to oxidative damage due to their high concentration of mitochondria.

Methods

Hypoxia/Reoxygenation: Human umbilical vein endothelial cells (HUVECs) and rat cardiomyocytes (H9C2 cells), were cultured at 37°C in EBM-2 medium and DMEM, respectively and pretreated with PKCδ+ (Myr+MRAAEDPM) (0.25-5μM) or untreated …

Contrasting Patients' And Healthcare Professionals' Experience In Hematological Cancer Care Pathway: A Narrative Study, Karine Bilodeau, Cynthia Henriksen, Camilia Aloisio Alves, Charlotte Gélinas-Gagné, Lynda Piché, Jacinthe Pepin, Virginia Lee, Marie-France Vachon, Nathalie Folch, Marie-Pascale Pomey, Nicolas Fernandez

Patient Experience Journal

Hematological cancers represent 10% of cancers diagnosed in Canada. Treatments involve complex care pathways and various modalities as well as the management and monitoring of multiple side effects. There is limited understanding of these pathways from the perspectives of the people living with cancer (PLC) and the healthcare professional (HCP). The aim of this article is to contrast the experiences of PLCs and HCPs in the context of hematological cancer care pathway. Narrative study approach was chosen for this exploratory study. Twenty-one narratives were co-created with PLCs (n = 12) and HCPs (n = 9). A structural and comparative analysis …

Daily Routine Redesign To Optimize Occupational Performance For Individuals With Cancer During And Post-Treatment, Summer M. Mazade, Cassandra Nelson

Spring 2025 OTD Capstone Symposium

Cancer and cancer treatment impacts individual's ability to participate in daily activities due to the symptoms or side effects that they experience. With advancements in cancer screenings and treatments, there is a growing population of those living with long term side effects that lower their quality of life. A program was developed to redesign cancer survivors' daily routine based on their symptoms and priorities to increase occupational performance in activities of daily living. The program showed a positive impact on the lives of cancer survivors' daily lives.

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 …

Intervention To Increase Uptake Of Cervical Screening In Norfolk City, Frederick Kankam Adu

Graduate Student Government Association Research Conference

The Objective is to determine the impact free screening and education to females between the ages 21 to 64 years, or under 21 years who are sexually active and unvaccinated against HPV virus have on uptake of cervical screening. In this study we use Before and After study design. The Outcomes for cervical screening are categorized as negative, atypical squamous cells undetermined significance( ASCUS), low-grade squamous intraepithelial lesion( LGSIL), high-grade squamous intraepithelial lesion(HGSIL), unsatisfactory samples, and HPV positive. Colposcopy will be performed if abnormal pap-smear is found. And outcomes of colposcopies, after abnormal Pap tests will be classified as negative( …

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,

Vision For The Future Of Oncology Physical Therapy: Apta Oncology’S Strategic Plan, Christopher M. Wilson, Emily Compagner

Oncology Rehabilitation in Practice

This article summarizes the 2024-27 strategic plan of the Academy of Oncologic Physical Therapy. The strategic plan consists of five strategic pillars — advocacy, engagement, education, collaboration, and research. Although the strategic plan is slated for another review in 2027, the 2024-27 strategic plan sets forth the key initiatives to advance the field of cancer physical therapy and oncology rehabilitation. This piece summarizes some key initiatives and how the academy and the profession will aim to achieve the APTA and APTA Oncology visions. For the full 2024-27 strategic plan of APTA Oncology, visit www.oncologypt.org.

Editorial: Adverse And Toxic Effects Of Childhood Cancer Treatments, Volume Ii, Antonio Ruggiero, Roderick Skinner, Pinki Prasad

School of Medicine Faculty Publications

No abstract provided.

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 …

Do Patients Want Their Spirituality Addressed During Their Hospital Journey; A Cross-Sectional Study At A Tertiary Care Center In Lebanon, Mohammad Assaf, Ali Ahmad, Hanine Atwi, Joseph Habib, Magda Haj, Reham Yehia, Amal C Rahi, Marianne Majdalani

Faculty, Staff and Student Publications

Background: Spirituality (including religiosity) is a powerful concept in Middle Eastern populations for members of all religious affiliations. This study aims to assess the desire of cancer and critically ill adult inpatients to be asked about their spiritual history, the impact their religious and spiritual beliefs have on their medical decisions, and if such beliefs help them cope with their illnesses.

Methods: A questionnaire consisting of demographics and spirituality questions was developed and administered to 100 patients in a cross-sectional study. We performed psychometric analysis of the questionnaire through reliability and validity testing including construct validity using PCA with a …

Occupational Therapy For Participation In Spirituality For Individuals With Cancer: A Scoping Review, Natalie Fernandez, Lesley Khan-Farooqi, Steven Gerardi

Spring 2025 OTD Capstone Symposium

The incidence of cancer continues to rise. For many individuals with cancer, spirituality is an important part of life. Spirituality impacts the individual’s meaning, purpose, self-identity, occupational engagement, occupational performance, and quality of life. However, there are sometimes barriers to participation in religions activities. Occupational therapy (OT) is indicated when people have barriers to participation. However, spirituality is not consistently addressed in OT practice and OT practitioners may not feel comfortable in addressing barriers to participation in spiritual activities among their clients with cancer. Objective: Scoping review methodology was used to answer the research question, how are OT practitioners addressing …

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 …

The Role Of Churches In Enhancing Cancer Screening Adherence: A Focus On Faith-Based Health Literacy Among African American Women, Miranda I. Goodson, Genevieve Murray

Medical Student Research Symposium

Background: It is estimated that cancer is the second leading cause of death for African American women in the United States. One study revealed that Black women have a 1 in 3 chance of developing cancer with a 1 in 6 chance of mortality. Research has shown a lower breast cancer screening adherence among women in cultural minorities and faith-based communities. The importance of spirituality and religion as an influential factor on Black community members’ beliefs about health and medicine must be considered as churches are pillars of social support within Black American communities.

Methods: A search for studies about …

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. …

The Hidden Scars Of Healing, Amanda Almeida

be Still

A photograph collection of Mark's unique road to healing, and a medical narrative.

A Cellular And Molecular Dissection Of The Breast: Identification Of Pericytes As A Driver Of Tumor Cell Proliferation, Katelyn M. Del Toro

Biomedical Sciences ETDs

Tissues are composed of many different types of cells. Each has a specific function and exists within a unique context—all of which define the landscape of the tissue. The cellular and molecular interactions within a tissue are critical to its form and function. Defining these interactions is an important step in understanding the aberrant nature of diseases like cancer, where tissue homeostasis has been abandoned. This requires reliable models of each cell type. Yet, in many tissues, including the breast, comprehensive methods to identify, purify, and study each tissue cell type have not been defined. This is a critical deficiency …

Pericardial Effusion Associated With Direct Oral Anticoagulant Use In A Single Center Experience, Jessica Song, Mark Jaradeh, William Xu, Andres Deluna, Rajkumar J. Sevak, Clifford Wang, Susan X. Zhao

Pacific Faculty Work

Background: Pericardial effusion (PEff) has been described to occur in association with direct oral anticoagulant (DOAC). Objectives: The purpose of this study was to assess the incidence, characteristics, and predisposing factors of PEff associated with DOACs. Methods: In this retrospective single center study, multivariable logistic regression analysis was used to identify factors associated with PEff in adult patients (age ≥18 years) in the Santa Clara Health System between 2013 and 2023. Results: Of the 456 patients with at least small to moderate PEff, 50 were on DOACs (DOAC PEff), 16 on warfarin (warfarin PEff), and 390 with no anticoagulation (NA …

Steroid Receptors And Coregulators: Dissemination Of Sex Differences And Emerging Technologies, Sally Pauss, Evelyn A. Bates, Genesee J. Martinez, Zane T. Bates, Zachary A. Kipp, Cassandra D. Gipson, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Steroid receptors are ligand-induced transcription factors that have broad functions among all living animal species, ranging from control of sex differences, body weight, stress responses, and many others. Their binding to coregulator proteins is regulated by corepressors and coactivators that interchange upon stimulation with a ligand. Coregulator proteins are an imperative and understudied aspect of steroid receptor signaling. Here, we discuss steroid receptor basics from protein domain structures that allow them to interact with coregulators and other proteins, their essential functions as transcription factors, and other elemental protein–protein interactions. We deliberate about the mechanisms that coregulators control in steroid receptor …

Developing And Validating Brain Tumor Organoid Models To Evaluate Novel Therapeutics In Vitro, Dev P. Patel

Senior Theses

Glioblastoma (GBM), a World Health Organization Grade IV brain tumor, remains one of the most aggressive and treatment-resistant malignancies. It is characterized by rapid proliferation, deep infiltration, and a high level of genotypic and phenotypic heterogeneity. Despite advancements in medical technology and neuro-oncology, GBM remains one of the most treatment-resistant cancers with a median survival rate of only nine months post-diagnosis and less than 5% of patients surviving beyond 5 years of diagnosis. The standard treatment constitutes maximum surgical resection followed by chemotherapy and radiation. These therapeutic strategies are blocked by significant challenges like the blood-brain barrier (BBB), and intratumoral …

Symptom Documentation In Unstructured Palliative Care Notes Of Children And Adolescents With Cancer., Katherine Bernier Carney, Jacob Wilkes, Tumilara Aderibigbe, Kristin Stegenga, Holly Spraker-Perlman, Lauri A. Linder

Manuscripts, Articles, Book Chapters and Other Papers

CONTEXT: Children and adolescents with cancer experiencing complex symptoms can benefit from subspeciality palliative care. However, standardized methods of symptom documentation by pediatric palliative care teams are lacking. Understanding current approaches to symptom documentation will inform next steps to optimize symptom support.

OBJECTIVE: To explore the documentation of symptom prevalence and characteristics in unstructured clinical notes by pediatric palliative care clinicians caring for children and adolescents with cancer.

METHODS: We reviewed unstructured clinical notes documented by the pediatric palliative care team for 115 children and adolescents with cancer. Symptom-related data were abstracted and evaluated using content analysis based on the …

Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia And Cancer And Prolongs Lifespan In A Pten Loss-Of-Function-Induced Cancer Model, Nicole C Kelp, Cindy A Pru, Sandeep Paudel, John P Lydon, J Julie Kim, John J Peluso, James K Pru

Faculty, Staff and Students Publications

The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that PGRMC1 enhances tumor growth and chemoresistance, the exact role of members of the PGRMC family in cancer development in vivo remains unclear. In this study, we examined the effect of deleting Pgrmc2 on the development of endometrial hyperplasia and cancer using a murine phosphatase and tensin homologue (Pten) conditional loss-of-function model. We previously established that …

Poor Cancer Prevention And Detection In Zimbabwe, Kenyon C. Chipman

Journal of Nonprofit Innovation

Abstract

In the aftermath of the HIV/AIDS epidemic, Sub-Saharan Africa, particularly Zimbabwe, has witnessed a surge in noncommunicable diseases such as cancer. Despite the decline in HIV/AIDS and other cancer-associated illnesses like HPV, these diseases have set the stage for a growing cancer epidemic. Key contributing factors to this rise include a lack of knowledge about cancer among both patients and health professionals, the prevalence of cancer-associated communicable diseases, and limited accessibility to early detection and prevention services and resources. These factors have led to late diagnoses, increased burden on the healthcare system, and adverse effects on individuals and families. …

Differences In Covid-19 Deaths Amongst Cancer Patients And Possible Mediators For This Relationship, Leah Vaidya, Nubaira Rizvi, Xiao Cheng Wu, Lauren S. Maniscalco, Yong Yi, Augusto Ochoa, Qingzhao Yu

School of Public Health Faculty Publications

Previous research demonstrated Non-Hispanic Black populations experience higher COVID-19 mortality rates than Non-Hispanic White individuals. Additionally, cancer status is a known risk factor for COVID-19 death. While prior studies investigated comorbidities as exploratory variables in differences in COVID-19 hospitalization, none have explored their role in COVID-19-related deaths. This study aimed to evaluate whether Charlson Comorbidity Index (CCI) and subsequently, individual diseases are potential explanatory variables for this relationship. The analysis focused on Non-Hispanic Black and Non-Hispanic White cancer patients aged 20 or older, diagnosed between 2011 and 2019, who tested positive for COVID-19 from the start of pandemic through June …

Breast Cancer Diagnoses Are Increasing Among Racial And Ethnic Minority Women In The U.S., Esther Oshaji

Population Health Research Brief Series

Breast cancer is the second most common cancer and a leading cause of cancer deaths among women in the United States. This data slice uses data from the Surveillance, Epidemiology and End Results Program (SEER) Incidence Database to examine trends in breast cancer incidence rates among women by race and ethnicity in the U.S. from 2000 to 2021. The author finds that, while incidence rates remain highest among non-Hispanic White women, the largest increases in diagnoses have been among American Indian/Alaska Native Asian/Pacific Islander women.