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42 - Evaluating Erk Inhibitor Sensitivity In Hras-Mutant Head And Neck Squamous Cell Carcinoma, Da'Jhnae Gambrell-Sanders 2018 Clark Atlanta University

42 - Evaluating Erk Inhibitor Sensitivity In Hras-Mutant Head And Neck Squamous Cell Carcinoma, Da'jhnae Gambrell-Sanders

Georgia Undergraduate Research Conference (GURC)

Head and neck squamous cell carcinoma (HNSCC) is a significant public health problem and the prognosis is very poor. There are limited treatments. RAS is a membrane-associated GTP binding protein that is a well-established driver for cancer progression. One approach to target RAS is to inhibit the activity of its downstream effectors. Of many pathways that is downstream of RAS, a critical pathway in other cancers is the MAPK pathway. Activated RAS binds to RAF which in turns activates MEK1 and MEK2 protein kinases. Ultimately, the MEK1/2 protein kinases phosphorylate ERK1/2 which control critical cell processes. SCH772984 is ...


Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay 2018 Selected Works

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

David Turay, MD

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It ...


Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli 2018 Thomas Jefferson University; University of Delaware

Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Recent results from single cell gene and protein regulation studies are starting to uncover the previously underappreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges. In this study, we focus on relating the dynamic changes in distributions of hepatic stellate ...


Reducing O Negative Blood Product Usage In A Tertiary Care Academic Medical Center, Wendy Weiler, Tracy Cook, MMC Blood Bank, Mark Parker, Stephen Tyzik, Suneela Nayak, Ruth Hanselman, Amy Sparks 2018 Maine Medical Center

Reducing O Negative Blood Product Usage In A Tertiary Care Academic Medical Center, Wendy Weiler, Tracy Cook, Mmc Blood Bank, Mark Parker, Stephen Tyzik, Suneela Nayak, Ruth Hanselman, Amy Sparks

Operational Excellence

MANAGEMENT OF O NEGATIVE BLOOD USE

O registered blood cells are the universal donor but it comprises only 7% of the blood supply. As a result, inappropriate use can result in shortages.

At an academic tertiary care medical center, a performance improvement goal was established that O negative blood cells would make up less than 12% of all blood type transfused by the end of their fiscal year.

A root cause analysis established reasons for the use of O negative blood cells. A number of countermeasures were initiated using the plan, do, study, act (PDSA) problem solving model. Using newly ...


Mir-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness With Therapeutic Potential., Sara E. Meyer, David E. Muench, Andrew M. Rogers, Tess J. Newkold, Emily Orr, Eric O'Brien, John P. Perentesis, John G. Doench, Ashish Lal, Patrick J. Morris, Craig J. Thomas, Judy Lieberman, Edwina McGlinn, Bruce J. Aronow, Nathan Salomonis, H. Leighton Grimes 2018 Thomas Jefferson University; Cincinnati Children’s Hospital Medical Center

Mir-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness With Therapeutic Potential., Sara E. Meyer, David E. Muench, Andrew M. Rogers, Tess J. Newkold, Emily Orr, Eric O'Brien, John P. Perentesis, John G. Doench, Ashish Lal, Patrick J. Morris, Craig J. Thomas, Judy Lieberman, Edwina Mcglinn, Bruce J. Aronow, Nathan Salomonis, H. Leighton Grimes

Department of Cancer Biology Faculty Papers

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation ...


The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant 2018 Rockdale Magnet School

The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant

The International Student Science Fair 2018

Hyperthermia is a treatment for liver cancer where the tumor is exposed to a relatively high heat temperature. This process is designed to make the tumor more susceptible to chemotherapy. My thought process was that if hyperthermia can kill cancerous cells, then there will be negative long term effects on the noncancerous cells surrounding the tumor. The project experimented on Kidney cells because the Kidney and Liver both go through the process of filtration. This means that the Kidney cells should give similar results that Liver cells would. Kidney cells were heated at 40 degrees Celsius for time amounts of ...


The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant 2018 Rockdale Magnet School

The Effect Of Hyperthermia On Liver Cell Viability, Jada Grant

The International Student Science Fair 2018

Hyperthermia is a treatment for liver cancer where the tumor is exposed to a relatively high heat temperature. This process is designed to make the tumor more susceptible to chemotherapy. My thought process was that if hyperthermia can kill cancerous cells, then there will be negative long term effects on the noncancerous cells surrounding the tumor. The project experimented on Kidney cells because the Kidney and Liver both go through the process of filtration. This means that the Kidney cells should give similar results that Liver cells would. Kidney cells were heated at 40 degrees Celsius for time amounts of ...


A Humanized Hypertrophic Cardiomyopathy Model To Elucidate Molecular Mechanism In Disease Pathology, Ragavi Vijayakumar, Maxine Hong 2018 NUS High School of Mathematics and Science

A Humanized Hypertrophic Cardiomyopathy Model To Elucidate Molecular Mechanism In Disease Pathology, Ragavi Vijayakumar, Maxine Hong

The International Student Science Fair 2018

Hypertrophic cardiomyopathy (HCM), that clinically manifests as an enlarged heart is a highly prevalent cardiac disorder with propensity towards arrhythmia-induced sudden cardiac death. The mechanism of HCM remains poorly defined, necessitating further understanding of the disease for improved therapeutic strategies. As it is challenging to obtain cardiac biopsies from human subjects, using induced pluripotent stem cells technology, we generated cardiomyocytes (CMs) in a dish from HCM patients. These HCM-CMs presented the clinical manifestation in that they were significantly larger in size in comparison to control (healthy)-CMs. Furthermore, gene expression profiling of cardiac ion channels revealed increased transcripts encoding for ...


Concurrent Regulation Of Lkb1 And Camkk2 In The Activation Of Ampk In Castrate-Resistant Prostate Cancer By A Well-Defined Polyherbal Mixture With Anticancer Properties., Amber F. MacDonald, Ahmed Bettaieb, Dallas R. Donohoe, Dina S. Alani, Anna Han, Yi Zhao, Jay Whelan 2018 University of Tennessee, Knoxville

Concurrent Regulation Of Lkb1 And Camkk2 In The Activation Of Ampk In Castrate-Resistant Prostate Cancer By A Well-Defined Polyherbal Mixture With Anticancer Properties., Amber F. Macdonald, Ahmed Bettaieb, Dallas R. Donohoe, Dina S. Alani, Anna Han, Yi Zhao, Jay Whelan

Department of Cancer Biology Faculty Papers

BACKGROUND: Zyflamend, a blend of herbal extracts, effectively inhibits tumor growth using preclinical models of castrate-resistant prostate cancer mediated in part by 5'-adenosine monophosphate-activated protein kinase (AMPK), a master energy sensor of the cell. Clinically, treatment with Zyflamend and/or metformin (activators of AMPK) had benefits in castrate-resistant prostate cancer patients who no longer responded to treatment. Two predominant upstream kinases are known to activate AMPK: liver kinase B1 (LKB1), a tumor suppressor, and calcium-calmodulin kinase kinase-2 (CaMKK2), a tumor promotor over-expressed in many cancers. The objective was to interrogate how Zyflamend activates AMPK by determining the roles of ...


Atrx Mutation In Pineal Parenchymal Tumor Of Intermediate Differentiation, Michelle Nagurney, MD, Christopher Farrell, MD, Zi-Xuan Wang, PhD, Mark T. Curtis, MD 2018 Thomas Jefferson University

Atrx Mutation In Pineal Parenchymal Tumor Of Intermediate Differentiation, Michelle Nagurney, Md, Christopher Farrell, Md, Zi-Xuan Wang, Phd, Mark T. Curtis, Md

Department of Pathology, Anatomy, and Cell Biology Posters

Objectives

Based on our identification of an ATRX mutation in a PPTID of a 22 year old female, we analyzed the frequency of ATRX loss in pineal parenchymal tumors using ATRX immunohistochemical staining.


Understanding Regenerative Medicine And Its Position In Healthcare, Tyler F. Ward 2018 Eastern Kentucky University

Understanding Regenerative Medicine And Its Position In Healthcare, Tyler F. Ward

Kentucky Journal of Undergraduate Scholarship

Abstract: Regenerative medicine is an emerging field of the healthcare industry that has the potential to treat a myriad of health conditions. Induced pluripotent stem cells, human embryonic stem cells, and tissue engineering are a few of the treatment methods that may be delivered by healthcare professionals in personalized medicine. Food and Drug Administration (FDA) approval is necessary within the United States before any of these treatment options are available. Specific cellular therapies are currently undergoing clinical trials and it may be years before approval is acquired. The National Institute of Health is proactively working to ensure that healthcare policies ...


Defining The Radioresponse Of Mossy Cells, Devon Ivy 2018 California State University, San Bernardino

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in ...


Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, MD 2018 Thomas Jefferson University

Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, Md

Department of Pathology Honors Program Student Research Symposium

Point-of-care hemoglobin (Hb) testing has not been evaluated in the resuscitation of acutely hemorrhaging patients to guide transfusion therapy. This study assessed the correlation of Hb values determined by point-of-care (EPOC) and traditional laboratory (CBC) methods in patients undergoing massive transfusion. All patients transfused per the massive transfusion protocol (MTP) between February 2013 and October 2017 were identified. The EPOC result was most often within 1 g/dL of the CBC result when EPOC resulted in a Hb between 7-10 g/dL and when drawn within 15 minutes of the CBC specimen. In patients on MTP with an EPOC Hb ...


The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, MD 2018 Thomas Jefferson University

The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md

Department of Pathology Honors Program Student Research Symposium

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has become a gold standard technique in ophthalmologic practice, and has revolutionized the diagnosis and treatment of retinal disease. As SD-OCT uses low interference interferometry and mathematical algorithms to produce detailed theoretical cross-sectional images of the retina, it is crucial to examine correlations between SD-OCT images and their corresponding histopathologic slides.

Methods: In the present study, careful correlative light microscopy was performed on the eye that was enucleated from an elderly patient who had a uveal melanoma and early agerelated macular degeneration evident clinically as soft drusen. SD-OCT was performed prior to enucleation ...


A New Frontier In Breast Cancer Management: Oncotype Dx, Gabriella Rollo, Jeremy Molligan, MD, Juan P. Palazzo, MD 2018 Thomas Jefferson University

A New Frontier In Breast Cancer Management: Oncotype Dx, Gabriella Rollo, Jeremy Molligan, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

Diagnosing and prognosticating breast cancer has traditionally relied upon histomorphologic analysis and immunohistochemistry. With the recent advent of multigene molecular assays, traditional methods are being augmented with molecular biomarkers. Implementation of the Oncotype DX assay has led to a change in treatment of patients with early stage, estrogen positive cancer. Oncotype DX uses the expression of 21 genes at the mRNA level to determine a 10 year recurrence risk in node negative and 5 year recurrence risk in node positive cancer. 16 malignancy markers related to estrogen, HER2, cell proliferation, and invasion potential are compared with 5 reference genes and ...


The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, MD 2018 Thomas Jefferson University

The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

In recent years, liquid biopsy has emerged as a potential alternative/adjunct to standard tissue biopsy in the diagnosis of malignancies. Current use of this technique, which tracks distinctive molecules released from neoplastic cells including circulating tumor cells (CTCs), exosomes, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA) and miRNA, has generally been limited to determining therapies in lung cancer based on detectable mutations (EFGR, EML4-ALK). However, recent studies have demonstrated the possibility for using these molecules as more efficient prognostic and diagnostic biomarkers in breast, colon, rectum, lung, liver, and pancreatic cancer. Due to the need for standardization in sampled ...


Clinico-Pathological Features And Pd-1/Pd-L1 Expression In Primary Mediastinal Large B Cell Lymphoma, Lydia Glick, Geetha Jagannathan, MD, Guldeep Uppal, MD 2018 Thomas Jefferson University

Clinico-Pathological Features And Pd-1/Pd-L1 Expression In Primary Mediastinal Large B Cell Lymphoma, Lydia Glick, Geetha Jagannathan, Md, Guldeep Uppal, Md

Department of Pathology Honors Program Student Research Symposium

Primary Mediastinal Large B Cell Lymphoma (PMBCL) is a distinct subtype of Diffuse Large B Cell Lymphoma (DLBCL) that has been historically reported to have a worse prognosis than DLBCL. Occasional studies have reported PD-L1 expression in PMBCL, which can emerge as an important target for immune-check point therapy. This study aimed to evaluate clinico-pathological features and characterize the expression of PD-1 and PD-L1 in a single cohort of 15 patients with PMBCL.

A total of 15 cases of PMBCL were retrieved from records of the department of Pathology; eleven of these had tissue available for additional immunohistochemistry, specifically, PD-L1 ...


Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, BA, Stacey K. Mardekian, MD 2018 Thomas Jefferson University

Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, Ba, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Anaplastic thyroid carcinoma (ATC) has the poorest prognosis of all thyroid cancers. Morphologically, it is characterized by pleomorphic undifferentiated cells. In some cases, a differentiated precursor lesion, either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma, can be identified adjacent to the anaplastic component. There are certain morphological variants of PTC that are known to be associated with more aggressive behavior, but a recently described, understudied variant is the hobnail variant. It is characterized histologically by micropapillary structures lined by cells with abundant eosinophilic cytoplasm and apically-placed bulging nuclei. The aim of this study was to evaluate the frequency of ...


Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, BS, David Strayer, MD, PhD, Douglas Drelich, MD 2018 Thomas Jefferson University

Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, Bs, David Strayer, Md, Phd, Douglas Drelich, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a rare coagulation disorder with a typical clinical presentation of low platelets and excessive clotting. Mortality for this disorder may be high if untreated and therefore necessitates a high clinical suspicion. Here we describe a 46-year-old African American woman with a past medical history of multiple cerebrovascular accidents presenting to hematology after a suspected diagnosis of TTP. Presumptive diagnosis of acquired TTP called for treatment with IVIg, but a diagnosis of congenital TTP (Upshaw Schulman syndrome) was made after testing showed a lack of ADAMTS13 antibodies. Treatment with fresh frozen plasma (FFP) showed increase in ...


Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, MD 2018 Thomas Jefferson University

Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Recent reclassification of a subset of non-invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) tumors as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has led to important changes in the clinical management of patients with these indolent lesions. Although there are established diagnostic criteria to differentiate NIFTP from EFVPTC, our objective was to determine further differences in histological characteristics between NIFTP and noninvasive EFVPTC. Additionally, we sought to identify histological differences between non-invasive and invasive EFVPTC lesions beyond the key finding of invasion. 68 encapsulated follicular lesions with papillary-like nuclear features from patients treated at Thomas Jefferson ...


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