Medical Cell Biology Commons^™

Ewing’S Sarcoma, Chris Lucasti, Bs, Bruce A. Fenderson, Phd

Department of Pathology Honors Program Student Research Symposium

Ewing’s sarcoma is the second most common malignant tumor of the bone occurring in children and adolescents. Typically, patients present between the ages of 10 and 20, with the disease having a slight predilection for males.1 Tumors often arise in the mid-shaft with the femur being the most frequently affected bone. The most common chromosome translocation, t(11;22)(q24;q12), occurs between the EWS gene and the FLI-1 gene. This translocation has been implicated in these aggressive and malignant tumors.1–4 Oftentimes, patients present with pain and swelling in the area of the affected bone or joint.5 While there has been some improvement in …

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 …

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 …

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

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 …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

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 between 7-10 …

Metastatic Lobular Breast Carcinoma In A Meningioma: A Case Study, Sara Chapin, Msii, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Hormonal relationships between breast carcinoma and meningioma have long been reported in the literature. This association may be related to the widespread expression of progesterone receptors in meningiomas. Indeed, meningiomas are more common in women and may demonstrate increased growth during pregnancy. Women have an increased risk of meningioma following breast carcinoma diagnosis and vice versa. However, much more uncommon is a tumor to tumor metastases of breast carcinoma into a meningioma. We report a case of a 56 year old female with a past medical history of breast cancer, found to have a right sphenoorbital meningioma with metastatic lobular …

Role Of Smarce1 And Bhlhe40 In Breast Cancer Metastasis, Aarti Sethuraman

Theses and Dissertations (ETD)

No abstract provided.

Protein Trafficking Of Bk Channel Β1 Subunits In Cerebral Artery Myocytes, Xue Zhai

Theses and Dissertations (ETD)

Rationale: Large-conductance calcium (Ca²⁺)-activated potassium channels (BK) are expressed in arterial myocytes to control arterial contractility. It is composed of pore- forming BKα and auxiliary β1 subunits. Auxiliary β1 subunits associate with BKα which modulate Ca²⁺ sensitivity of BK channel. Previous data showed that BKα locates at cell membrane, whereas β1 subunits are primarily intracellular which regulated by Rab11A- positive recycling endosomes. Endothelin-1 (ET-1), a vasoconstrictor, induces contraction of myocytes. ET-1 inhibits BK channel but mechanisms are not fully understood. It is unclear that vasoconstrictors regulate the cellular distribution of BK channels. Furthermore, BK channels are involved …

Characterization Of The Hepatotoxicity Of Rifampicin And Isoniazid, Christopher T. Brewer

Theses and Dissertations (ETD)

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis …

Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, Minji Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich

University Scholar Projects

Chronic antigenic stimulation leads to T cell exhaustion, which drastically dampens T cell effector functions. Upon exhaustion, T cells progressively lose their proliferative capacity, cytokine production, and cytotoxic effector functions against tumors. T cell exhaustion involves programmed cell death-1 (PD-1), which is an inhibitory co-stimulation receptor. Limited scope of studies has been done regarding impact of PD-1 expression on the effector functions of γδ T cells. In this study, we investigated expression of PD-1 and its impact on effector functions of human γδ T cells. When γδ T cells were stimulated with phosphoantigens (HMBPP and POM₂-C-HMBP) and analyzed …

Puma Amplifies Necroptosis Signaling By Activating Cytosolic Dna Sensors., Dongshi Chen, Jingshan Tong, Liheng Yang, Liang Wei, Donna B. Stolz, Jian Yu, Jianke Zhang, Lin Zhang

Department of Microbiology and Immunology Faculty Papers

Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL …

Comparison Of Serum And Cervical Cytokine Levels Throughout Pregnancy Between Preterm And Term Births, Kristin Ashford, Niraj R. Chavan, Amanda T. Wiggins, Molly Malany Sayre, Andrea Mccubbin, Agatha S. Critchfield, John O'Brien

Nursing Faculty Publications

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births.

Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester).

Results For the CVF …

Comparative Cytotoxicity Study Of Nicotine And Cotinine On Mrc-5 Cell Line, Ana-Maria Vlasceanu, Daniela Luiza Baconi, Bianca Galateanu, Miriana Stan, Cristian Balalau

Journal of Mind and Medical Sciences

Nicotine has several health hazards regarding carcinogenic potential. It also imparts increased risk for respiratory, cardiovascular, and gastrointestinal disorders. Several mechanisms have been proposed for the carcinogenic potential, including effects on cell proliferation, inducing oxidative stress, DNA mutation, or inhibition of apoptosis. The cotinine metabolite is generally thought to have effects similar to nicotine in some experimental systems. The purpose of this study was to assess the nicotine and cotinine cytotoxicity on MRC-5 lung fibroblasts. The pulmonary fibroblasts were treated with various concentrations of nicotine or cotinine (in the range 1 µM – 2 mM) for 24 or 48 h …

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships In Healthy Humans, Matthew Sherwood, Richard A. Mckinley, Danielle Boeke, Jason G. Parrker, Lindsey K. Mcintire, Justin M. Nelson, Catherine Fletchall, Natasha Alexander, Amanda Mcconnell, Chuck Goodyear, Jeremy T. Nelson, Nathaniel R. Bridges

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects—primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a …

Expression Of Carbonic Anhydrase Iii, A Nucleus Pulposus Phenotypic Marker, Is Hypoxia-Responsive And Confers Protection From Oxidative Stress-Induced Cell Death., Elizabeth S. Silagi, Philip Batista, Irving Shapiro, Makarand V. Risbud

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis. NP, but not annulus fibrosus or end-plate cells, robustly expressed CAIII protein in skeletally mature animals. Although CAIII expression was hypoxia-inducible, …

Spsnet: Subpopulation-Sensitive Network-Based Analysis Of Heterogeneous Gene Expression Data., Abha Belorkar, Rajanikanth Vadigepalli, Limsoon Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Transcriptomic datasets often contain undeclared heterogeneity arising from biological variation such as diversity of disease subtypes, treatment subgroups, time-series gene expression, nested experimental conditions, as well as technical variation due to batch effects, platform differences in integrated meta-analyses, etc. However, current analysis approaches are primarily designed to handle comparisons between experimental conditions represented by homogeneous samples, thus precluding the discovery of underlying subphenotypes. Unsupervised methods for subtype identification are typically based on individual gene level analysis, which often result in irreproducible gene signatures for potential subtypes. Emerging methods to study heterogeneity have been largely developed in the context of …

Investigating Ampk Signalling Regulation Of Autophagy In A Model Of Ovarian Tumour Dormancy, Jeremi Laski

Western Research Forum

Investigating AMPK signalling regulation of autophagy in a model of ovarian tumour dormancy

Jeremi Laski and Trevor G. Shepherd

Background:

Ovarian cancer is the most deadly gynecologic malignancy in women. A particular subset of this disease, epithelial ovarian cancer (EOC), is responsible for over 70% of all diagnosed ovarian cancer cases, yet the mechanisms governing disease progression are poorly understood. One of the unique hallmarks of EOC metastasis lies in the process of spheroid formation, whereby tumour cells aggregate into larger 3D structures. These EOC spheroids have been shown to be metabolically dormant, while concurrently up-regulating autophagy (cellular waste …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …