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Full-Text Articles in Medicine and Health Sciences

Plant Based Polyphenols Decrease Cell Migration And Inhibit Proliferation Of Human Pancreatic Cancer Cells, Mary Gathoni May 2022

Plant Based Polyphenols Decrease Cell Migration And Inhibit Proliferation Of Human Pancreatic Cancer Cells, Mary Gathoni

Electronic Theses & Dissertations

Pancreatic cancer is one of the most highly malignant tumors of the digestive tract. Both the incidence and death rate of pancreatic cancer have increased since 2000. The disease has a poor prognosis with a relative 5-year survival rate of 10%. Pancreatic cancer-related mortality can be mainly attributed to lack of early diagnosis, tumor metastasis, lack of effective treatment strategies and drug resistance. There has been a mounting interest on the use of plant-based compounds such as polyphenols in cancer treatment therapies. This is mainly due to their low toxicity and fewer side effects compared to the conventional chemotherapeutic options …


A Bayesian Group Sequential Design For Randomized Biosimilar Clinical Trials With Adaptive Information Borrowing From Historical Data, Wen Zhang, Zhiying Pan, Ying Yuan May 2022

A Bayesian Group Sequential Design For Randomized Biosimilar Clinical Trials With Adaptive Information Borrowing From Historical Data, Wen Zhang, Zhiying Pan, Ying Yuan

Faculty, Staff and Student Publications

At the time of developing a biosimilar, the reference product has been on market for years and thus ample data are available on its efficacy and characteristics. We develop a Bayesian adaptive design for randomized biosimilar clinical trials to leverage the rich historical data on the reference product. This design takes a group sequential approach. At each interim, we employ the elastic meta-analytic-predictive (EMAP) prior methodology to adaptively borrow information from the historical data of the reference product to make go/no-go decision based on Bayesian posterior probabilities. In addition, the randomization ratio between the test and reference arms is adaptively …


Improvement In Post-Autologous Stem Cell Transplant Survival Of Multiple Myeloma Patients: A Long-Term Institutional Experience., Jordan Nunnelee, Francesca Cottini, Qiuhong Zhao, Muhammad Salman Faisal, Patrick Elder, Ashley Rosko, Naresh Bumma, Abdullah Khan, Srinivas Devarakonda, Don M Benson, Yvonne Efebera, Nidhi Sharma May 2022

Improvement In Post-Autologous Stem Cell Transplant Survival Of Multiple Myeloma Patients: A Long-Term Institutional Experience., Jordan Nunnelee, Francesca Cottini, Qiuhong Zhao, Muhammad Salman Faisal, Patrick Elder, Ashley Rosko, Naresh Bumma, Abdullah Khan, Srinivas Devarakonda, Don M Benson, Yvonne Efebera, Nidhi Sharma

Oncology Articles

Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression-free survival (PFS) and overall survival (OS). We performed a retrospective survival analysis on newly diagnosed MM (NDMM) patients receiving ASCT from 1992−2016 at the Ohio State University. A total of 1001 consecutive NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for the treatment of MM. Across the years (1992−2016), there was a statistically significant improvement in both PFS (p …


Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin May 2022

Bhlhe40 Regulates The T-Cell Effector Function Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery J Salmon, Alexander S Shavkunov, Qi Miao, Nicholas N Jarjour, Sunita Keshari, Ekaterina Esaulova, Charmelle D Williams, Jeffrey P Ward, Anna M Highsmith, Josué E Pineda, Reshma Taneja, Ken Chen, Brian T Edelson, Matthew M Gubin

Faculty, Staff and Student Publications

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell-dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti-PD-1 and anti-CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen-specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential …


The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin May 2022

The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin

Department of Cancer Biology Faculty Papers

Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mutant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with …


Dietary Supplement Use Among Brca1/2 Mutation Carriers, Ryan Rogers, Tara Ramgarajan, Virginia Uhley, Kristina Ivan, Dana Zakalik May 2022

Dietary Supplement Use Among Brca1/2 Mutation Carriers, Ryan Rogers, Tara Ramgarajan, Virginia Uhley, Kristina Ivan, Dana Zakalik

Posters

INTRODUCTION
Women who carry BRCA1/2 mutations are at significantly increased risk of breast, ovarian, pancreatic and other cancer. Little is known regarding the use of dietary supplements among women harboring BRCA1/2 mutations. This study aims to characterize the utilization of and attitudes toward dietary supplement use in women who carry BRCA1/2 mutations.


Fluoroscopic Demonstration Of Thoracic Tumor Immobilization With High Frequency Percussive Ventilation, Cristian Solano, Ina M. Sala, Beverly Maurer, Ronald Levitin, Thomas M. Guerrero May 2022

Fluoroscopic Demonstration Of Thoracic Tumor Immobilization With High Frequency Percussive Ventilation, Cristian Solano, Ina M. Sala, Beverly Maurer, Ronald Levitin, Thomas M. Guerrero

Posters

INTRODUCTION
High frequency percussive ventilation (HFPV) is a novel immobilization technique that utilizes high frequency low tidal volume ventilation to produce endotracheal percussion. In a previous departmental study of chest wall motion immobilization, it was found that volunteers were able to tolerate HFPV for varying lengths of time – from a few to tens of minutes. By investigating a novel process to immobilize the chest wall, and thus thoracic tumors, it can allow for more localized radiation delivery and reduction of healthy tissue irradiation.


Diminished Immune Surveillance During Histologic Progression Of Intraductal Papillary Mucinous Neoplasms Offers A Therapeutic Opportunity For Cancer Interception, Sharia Hernandez, Edwin Roger Parra, Naohiro Uraoka, Ximing Tang, Yu Shen, Wei Qiao, Mei Jiang, Shanyu Zhang, Barbara Mino, Wei Lu, Renganayaki Pandurengan, Cara Haymaker, Kajsa Affolter, Courtney L Scaife, Michele Yip-Schneider, C Max Schmidt, Matthew A Firpo, Sean J Mulvihill, Eugene J Koay, Huamin Wang, Ignacio I Wistuba, Anirban Maitra, Luisa M Solis, Subrata Sen May 2022

Diminished Immune Surveillance During Histologic Progression Of Intraductal Papillary Mucinous Neoplasms Offers A Therapeutic Opportunity For Cancer Interception, Sharia Hernandez, Edwin Roger Parra, Naohiro Uraoka, Ximing Tang, Yu Shen, Wei Qiao, Mei Jiang, Shanyu Zhang, Barbara Mino, Wei Lu, Renganayaki Pandurengan, Cara Haymaker, Kajsa Affolter, Courtney L Scaife, Michele Yip-Schneider, C Max Schmidt, Matthew A Firpo, Sean J Mulvihill, Eugene J Koay, Huamin Wang, Ignacio I Wistuba, Anirban Maitra, Luisa M Solis, Subrata Sen

Faculty, Staff and Student Publications

Purpose: Intraductal papillary mucinous neoplasms (IPMN) are bona fide precursors to pancreatic ductal adenocarcinoma (PDAC). While genomic alterations during multistep IPMN progression have been well cataloged, the accompanying changes within the tumor immune microenvironment (TIME) have not been comprehensively studied. Herein, we investigated TIME-related alterations during IPMN progression, using multiplex immunofluorescence (mIF) coupled with high-resolution image analyses.

Experimental design: Two sets of formalin-fixed, paraffin-embedded tissue samples from surgically resected IPMNs were analyzed. The training set of 30 samples consisted of 11 low-grade IPMN (LG-IPMN), 17 high-grade IPMN (HG-IPMN), and 2 IPMN with PDAC, while a validation set of 93 samples …


Overall Survival In Phase 3 Clinical Trials And The Surveillance, Epidemiology, And End Results Database In Patients With Metastatic Colorectal Cancer, 1986-2016: A Systematic Review, Chan Shen, Daniel Tannenbaum, Robert Horn, Jane Rogers, Cathy Eng, Shouhao Zhou, Benny Johnson, Scott Kopetz, Van Morris, Michael Overman, Christine Parseghian, George J Chang, Maria A Lopez-Olivo, Raghav Kanwal, Lee M Ellis, Arvind Dasari May 2022

Overall Survival In Phase 3 Clinical Trials And The Surveillance, Epidemiology, And End Results Database In Patients With Metastatic Colorectal Cancer, 1986-2016: A Systematic Review, Chan Shen, Daniel Tannenbaum, Robert Horn, Jane Rogers, Cathy Eng, Shouhao Zhou, Benny Johnson, Scott Kopetz, Van Morris, Michael Overman, Christine Parseghian, George J Chang, Maria A Lopez-Olivo, Raghav Kanwal, Lee M Ellis, Arvind Dasari

Faculty, Staff and Student Publications

Importance: Phase 3 trials for patients with metastatic colorectal cancer (mCRC) have been conducted with varying designs and often with surrogate end points for overall survival (OS).

Objectives: To critically examine the factors associated with clinically relevant improvement in OS (defined as ≥2 months) in these trials and to evaluate their association with outcomes reflected in Surveillance, Epidemiology, and End Results (SEER) registry data.

Evidence review: Medline, EMBASE, Cochrane, Web of Science, ClinicalTrials.gov, EU Clinical Trials Register, and the International Clinical Trials Registry Platform were searched for phase 3 trials of systemic therapy for patients with mCRC by decade (1986-1996, …


Tumor Immune Microenvironment Of Brain Metastases: Toward Unlocking Antitumor Immunity, Matthew R Strickland, Christopher Alvarez-Breckenridge, Justin F Gainor, Priscilla K Brastianos May 2022

Tumor Immune Microenvironment Of Brain Metastases: Toward Unlocking Antitumor Immunity, Matthew R Strickland, Christopher Alvarez-Breckenridge, Justin F Gainor, Priscilla K Brastianos

Faculty, Staff and Student Publications

UNLABELLED: Brain metastasis (BrM) is a devastating complication of solid tumors associated with poor outcomes. Immune-checkpoint inhibitors (ICI) have revolutionized the treatment of cancer, but determinants of response are incompletely understood. Given the rising incidence of BrM, improved understanding of immunobiologic principles unique to the central nervous system (CNS) and dissection of those that govern the activity of ICIs are paramount toward unlocking BrM-specific antitumor immunity. In this review, we seek to discuss the current clinical landscape of ICI activity in the CNS and CNS immunobiology, and we focus, in particular, on the role of glial cells in the CNS …


Hypomethylating Agent And Venetoclax With Flt3 Inhibitor “Triplet” Therapy In Older/Unfit Patients With Flt3 Mutated Aml, Musa Yilmaz, Hagop Kantarjian, Nicholas J Short, Patrick Reville, Marina Konopleva, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Abhishek Maiti, Elias Jabbour, Nitin Jain, Ghayas Issa, Koichi Takahashi, Koji Sasaki, Maro Ohanian, Sherry Pierce, Guillin Tang, Sanam Loghavi, Keyur Patel, Sa A Wang, Guillermo Garcia-Manero, Michael Andreeff, Farhad Ravandi, Naval Daver May 2022

Hypomethylating Agent And Venetoclax With Flt3 Inhibitor “Triplet” Therapy In Older/Unfit Patients With Flt3 Mutated Aml, Musa Yilmaz, Hagop Kantarjian, Nicholas J Short, Patrick Reville, Marina Konopleva, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Abhishek Maiti, Elias Jabbour, Nitin Jain, Ghayas Issa, Koichi Takahashi, Koji Sasaki, Maro Ohanian, Sherry Pierce, Guillin Tang, Sanam Loghavi, Keyur Patel, Sa A Wang, Guillermo Garcia-Manero, Michael Andreeff, Farhad Ravandi, Naval Daver

Faculty, Staff and Student Publications

In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a …


Genomic Correlates Of Outcome In Tumor-Infiltrating Lymphocyte Therapy For Metastatic Melanoma, Caitlin A Creasy, Yuzhong Jeff Meng, Marie-Andrée Forget, Tatiana Karpinets, Katarzyna Tomczak, Chip Stewart, Carlos A Torres-Cabala, Shari Pilon-Thomas, Amod A Sarnaik, James J Mulé, Levi Garraway, Matias Bustos, Jianhua Zhang, Sapna P Patel, Adi Diab, Isabella C Glitza, Cassian Yee, Hussein Tawbi, Michael K Wong, Jennifer Mcquade, Dave S B Hoon, Michael A Davies, Patrick Hwu, Rodabe N Amaria, Cara Haymaker, Rameen Beroukhim, Chantale Bernatchez May 2022

Genomic Correlates Of Outcome In Tumor-Infiltrating Lymphocyte Therapy For Metastatic Melanoma, Caitlin A Creasy, Yuzhong Jeff Meng, Marie-Andrée Forget, Tatiana Karpinets, Katarzyna Tomczak, Chip Stewart, Carlos A Torres-Cabala, Shari Pilon-Thomas, Amod A Sarnaik, James J Mulé, Levi Garraway, Matias Bustos, Jianhua Zhang, Sapna P Patel, Adi Diab, Isabella C Glitza, Cassian Yee, Hussein Tawbi, Michael K Wong, Jennifer Mcquade, Dave S B Hoon, Michael A Davies, Patrick Hwu, Rodabe N Amaria, Cara Haymaker, Rameen Beroukhim, Chantale Bernatchez

Faculty, Staff and Student Publications

Purpose: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL) historically yields a 40%-50% response rate in metastatic melanoma. However, the determinants of outcome are largely unknown.

Experimental design: We investigated tumor-based genomic correlates of overall survival (OS), progression-free survival (PFS), and response to therapy by interrogating tumor samples initially collected to generate TIL infusion products.

Results: Whole-exome sequencing (WES) data from 64 samples indicated a positive correlation between neoantigen load and OS, but not PFS or response to therapy. RNA sequencing analysis of 34 samples showed that expression of PDE1C, RTKN2, and NGFR was enriched in responders who had improved …


Development Of A Deep Neural Network For Synthesis Of Non-Contrast Cranial T1-Weighted Magnetic Resonance Imaging, Agueda M. Taylor, Evan Porter, Thomas Guerrero May 2022

Development Of A Deep Neural Network For Synthesis Of Non-Contrast Cranial T1-Weighted Magnetic Resonance Imaging, Agueda M. Taylor, Evan Porter, Thomas Guerrero

Posters

INTRODUCTION
Although 122 out of 1000 people in the US have MRI’s done each year, there are over 4 million with contraindications that subsequently forgo the diagnostic benefits. Studies in recent years have implemented artificial intelligence (AI) algorithms such as deep neural networks (DNN) for production of synthetic medical imaging. The goals of this project are to develop a DNN, specifically a Generative Adversarial Network (GAN) that will predict synthetic Cranial T1 Weighted MRI from non-contrast CT, and to evaluate the model quality.


Functional Lung Segmentation From Computed Tomography Images Using Deep Learning, Duyen M. Quach, Evan Porter, Thomas M. Guerrero May 2022

Functional Lung Segmentation From Computed Tomography Images Using Deep Learning, Duyen M. Quach, Evan Porter, Thomas M. Guerrero

Posters

INTRODUCTION
Functional avoidance treatment planning allows radiation oncologists to intentionally minimize radiation dose to higher-functioning lung areas while favoring radiation dose towards lower-functioning regions. This treatment planning method has been shown to reduce pulmonary toxicity for patients receiving radiation therapy. Functional lung information, traditionally ventilation or perfusion SPECT scans, is required to plan for functional avoidance.


Evaluating The Impact Of Software Distortion Correction On Target Doses In Cranial Stereotactic Radiosurgery, Sharjil Shamim, Zachary Seymour May 2022

Evaluating The Impact Of Software Distortion Correction On Target Doses In Cranial Stereotactic Radiosurgery, Sharjil Shamim, Zachary Seymour

Posters

INTRODUCTION
Brainlab’s Elements suite proposed a novel MR distortion correction method based on CT imaging. This involves registration of sub-volumes from MR imaging to generate single continuous deformation field maps, creating a corrected MR image set. No literature currently exists studying the impact of software correction on target dose for cranial stereotactic radiosurgery. In this study, we aim to evaluate the impact of Brainlab distortion correction on radiation target dose compared to original treatment plans without distortion correction.


The Prognostic Significance Of Glucose-6-Phosphate Dehydrogenase As A Biomarker In Head And Neck Squamous Cell Carcinomas Treated With Conventional Chemoradiation, Kenneth H. Barker, Barbara L. Pruetz, Jessica D. Arden, Thomas J. Quinn, George D. Wilson May 2022

The Prognostic Significance Of Glucose-6-Phosphate Dehydrogenase As A Biomarker In Head And Neck Squamous Cell Carcinomas Treated With Conventional Chemoradiation, Kenneth H. Barker, Barbara L. Pruetz, Jessica D. Arden, Thomas J. Quinn, George D. Wilson

Posters

INTRODUCTION
The prognosis of patients with head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation can be predicted using p16 as a surrogate biomarker of Human Papilloma Virus (HPV) status, but a subset of patients continues to do poorly despite a positive or negative p16 status. This project attempted to identify another biomarker, glucose-6-phosphate dehydrogenase (G6PD) as a marker for prognosis in HNSCC patients. Radiation induces oxidative damage to destroy tumor cells, and G6PD is a key enzyme involved in protecting cells from oxidative damage. The goal of this project was to identify a prognostic biomarker that would aid …


Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong May 2022

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system 12-14. Our …


Treatment Of Recurrent Wilms Tumor With Irinotecan/Temozolomide, Meagan Vacek, Terrie Flatt May 2022

Treatment Of Recurrent Wilms Tumor With Irinotecan/Temozolomide, Meagan Vacek, Terrie Flatt

Posters

Background: Despite improvement in relapse free survival (RFS) in recurrent Wilms tumor, the 4-year RFS rate for patients treated with vincristine/dactinomycin/doxorubicin is approximately 40%. Ifosfamide, carboplatin and etoposide are commonly used in relapsed solid tumors, but have significant toxicities and require hospital admission for administration. Our patient focused on quality of life, and this led to exploration of other treatment options. Objective: Describe a case of multiply relapsed Wilms tumor with management on oral irinotecan/temozolomide for improved quality of life and remission for almost 1 year. Design/Method: Case Report Results: The patient is an 11-year-old female diagnosed with Wilms tumor …


Memory T Cell Populations In Human Leukemia, Sara Mcelroy, Fang Tao, John Szarejko, John M. Perry May 2022

Memory T Cell Populations In Human Leukemia, Sara Mcelroy, Fang Tao, John Szarejko, John M. Perry

Posters

Background Incorporating the immune system into cancer management is an area of robust research. Treatment modalities aimed at activating cytotoxic T cells against malignancies include immune checkpoint inhibitors, bispecific T-cell engagers, and chimeric antigen receptor (CAR) tumor-specific T cells. Most anti-cancer T cell research is narrowly focused, but knowledge about the nature of diverse sub-populations of T cells in cancer, particularly memory T cells, is vital prior to potential incorporation into therapies. T memory stem cells (Tscm) are of interest due to their longevity and powerful abilities of self-renewal and creating the full spectrum of memory CD8+ T cells, including …


Inducing Alternative Forms Of Cell Death In Multidrug Resistant Ovarian Cancer, Chloe Reese Kotrba May 2022

Inducing Alternative Forms Of Cell Death In Multidrug Resistant Ovarian Cancer, Chloe Reese Kotrba

Undergraduate Honors Thesis Collection

Ovarian cancer remains the deadliest gynecological cancer for women today. In 2021, an estimated 21,410 new cases of ovarian cancer were diagnosed in the US, and approximately 13,770 of these women will not survive the disease[2]. This malignancy’s low survival rate is attributed to late diagnoses, as well as the cancer’s tendency to recur after chemotherapy treatment due to acquired drug resistance. The standard of care for this disease includes surgery and chemotherapy. One of the commonly used chemotherapeutic drugs is cisplatin, which works by inducing a programmed form of cell death known as apoptosis. However, many ovarian cancer tumors …


Implementation Of A Nurse Driven Palliative Care Consult: A Quality Improvement Project, Socnite Sebourne-Francis May 2022

Implementation Of A Nurse Driven Palliative Care Consult: A Quality Improvement Project, Socnite Sebourne-Francis

DNP Projects

Background: Palliative care consult (PCC) is an approach that can improve the quality of life and symptom management of patients facing life-threatening illnesses. At a 20-bed medical oncology unit in Connecticut, patients with poor prognosis and worsening symptoms have high re-admission rates within 30 days of post-hospital discharge; yet healthcare providers fail to initiate PCC.

Purpose: This project hypothesizes how implementing a nurse-driven PCC on admission or hospital stays compared to the timing of a physician to a physician PCC improves a plan of care for oncology patients? Will it result in a decrease in 30-day re-admission rates? The …


Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu May 2022

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer, Richard Fu

Honors Theses

RAS is a prevalent oncogene that is mutated in 27% of human cancers. Gain-of-function RAS mutations activate multiple downstream pathways, including the RAS-RAF-MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. RAS proteins such as KRAS, a member of the RAS protein family, and their downstream effectors are attractive targets for cancer therapy since their mutations act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named MCI-062 was …


The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz May 2022

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …


The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen May 2022

The Role Of Obesity In Macrophage-Mediated Mechanisms Promoting Early-Onset Colon Cancer., Katharina Marietta Scheurlen

Electronic Theses and Dissertations

Early-onset colon cancer (EOCC) is a leading cause of cancer death among people younger than 50 years of age in the United States and is associated with metabolic dysfunction and obesity. Anti-inflammatory tumor-associated macrophages (TAM) and low Peroxisome Proliferator Activated Receptor Gamma (PPARγ) gene expression in colon cancer (CC) tissue promote tumor progression and decreased patient survival. Obesity-related hormones, such as leptin and adiponectin, have the potential to affect gene expression in TAM to promote CC progression and thereby link obesity and EOCC. The aim of this project was to identify target genes in human CC and to investigate the …


The Experience Of Scanxiety In Survivors Of Pancreatic Cancer: A Phenomenological Study., Susan Winebrenner May 2022

The Experience Of Scanxiety In Survivors Of Pancreatic Cancer: A Phenomenological Study., Susan Winebrenner

Electronic Theses and Dissertations

Surveillance scans can signify a crisis point in a cancer patient’s life, provoking fear and anxiety that negatively impact quality of life. Scan-related anxiety or scanxiety has been briefly discussed in the literature among lung cancer and lymphoma populations, but relatively few investigations have studied the psychological impact of routine surveillance scans during cancer survivorship. The purpose of this study was to illuminate the lived experience of scanxiety in survivors of pancreatic cancer who have undergone curative surgical resection. Hermeneutic phenomenology as applied by Heidegger provided the philosophical underpinnings for this study and van Manen’s methodological approach was used to …


Decreasing Time To Antibiotic Administration In Febrile Neutropenic Adult Oncology Patients In The Emergency Department: An Evidence-Based Quality Improvement Project, Kristin Murray May 2022

Decreasing Time To Antibiotic Administration In Febrile Neutropenic Adult Oncology Patients In The Emergency Department: An Evidence-Based Quality Improvement Project, Kristin Murray

DNP Projects

Introduction—Significance and Background: Febrile Neutropenia (FN) is the most common and serious complication of hematopoietic cancers and in patients receiving chemotherapy. Patients in this immunocompromised state have weakened immunity to fight off infection and a mortality rate of almost 10%. Thus, Infectious Diseases Society of America has identified the single most important determining factor of outcomes is the timing of antibiotic (TTA) administration and has identified the gold standard to be 60 minutes. Current practice does not follow guidelines and the current policy does not address the urgency of antibiotic administration.

Purpose: The purpose of this project is to improve …


Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer., Richard Fu May 2022

Applying Mci-062, A Novel Pan-Ras Inhibitor, To Treat Kras-Mutant Lung Cancer., Richard Fu

Poster Presentations

Honors thesis poster presentation.

RAS, one of the most prevalent oncogenes, is mutated in 27% of human cancers. Gainof- function RAS mutations activate multiple downstream pathways, including the RASRAF- MEK-ERK and PI3K/AKT/mTOR pathways, which are critical in tumorigenesis and cancer cell proliferation. The RAS proteins KRAS, HRAS, and NRAS along with their downstream effectors are attractive targets for cancer therapy since they act as frequent drivers in lung, colorectal, and pancreatic cancers. However, RAS proteins have relatively smooth surfaces that lack traditional binding pockets, making inhibitors specific to RAS difficult to create. Recently, a novel small molecule pan-RAS inhibitor named …


Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi May 2022

Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi

Electrical & Computer Engineering Faculty Publications

Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids …


Outstanding Outcomes In Infants With Kmt2a-Germline Acute Lymphoblastic Leukemia Treated With Chemotherapy Alone: Results Of The Children's Oncology Group Aall0631 Trial, Erin M. Guest, John A. Kairalla, Joanne M. Hilden, Zoann E. Dreyer, Andrew J. Carroll, Nyla A. Heerema, Cindy Y. Wang, Meenakshi Devidas, Lia Gore, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Michael Borowitz, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown May 2022

Outstanding Outcomes In Infants With Kmt2a-Germline Acute Lymphoblastic Leukemia Treated With Chemotherapy Alone: Results Of The Children's Oncology Group Aall0631 Trial, Erin M. Guest, John A. Kairalla, Joanne M. Hilden, Zoann E. Dreyer, Andrew J. Carroll, Nyla A. Heerema, Cindy Y. Wang, Meenakshi Devidas, Lia Gore, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Michael Borowitz, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh May 2022

Atr-Mediated Cd47 And Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming And Abscopal Responses In Colorectal Cancer, Cheng-En Hsieh, Cheng-En Hsieh

Dissertations and Theses (Open Access)

Radiotherapy of colorectal cancer (CRC) can prime adaptive immunity against tumor-associated antigen (TAA)-expressing CRC cells systemically. However, incidences of abscopal tumor remission are extremely rare, and the post-irradiation immune escape mechanisms in CRC remain elusive. We report that CRC cells utilize a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate immune activation. This post-irradiation CD47 and PD-L1 upregulation can be observed across various human solid tumor cells. Concordantly, …