Medical Cell Biology Commons^™

Peripheral T-Cell Lymphoma Arising From Age-Related Ebv-Associated Lymphoproliferative Disorder (Ar-Ebvlpd), Alaina Chodoff, Msii, Guldeep Uppal, Md, Jerald Z. Gong, Md

Department of Pathology Honors Program Student Research Symposium

In the setting of underlying immune suppression, Epstein Barr Virus (EBV) is a well-recognized oncogenic agent that induces the malignant proliferation of B-cells. EBV-lymphoproliferative disorders (LPDs) have recently been linked to immunosenescence. We present a unique case of Age-Related EBV-Lymphoproliferative Disorder (AR-EBVLPD) in a 70 year old female that deviates from the characteristic progression of this disease. Over the course of 18 months, the patient’s clinical condition worsened without a definitive diagnosis to explain the severe, atypical widespread chronic inflammation spanning her gastrointestinal tract, from esophagus to small bowel. The diagnosis of AR-EBVLPD, polymorphic extranodal subtype, was delayed until the …

Hiv Associated Neurocognitive Disorders In An Antiretroviral Therapy Era, Molly Halloran, David S. Strayer, Md, Phd

Department of Pathology Honors Program Student Research Symposium

HIV emerged as a major threat to world health over 30 years ago, and while its effects on the immune system are widely known, HIV also has broad and devastating effects on the nervous system. Despite our potent antiretroviral therapies (ART), these HIV-associated neurocognitive disorders (HAND) continue to afflict HIV infected individuals. With over 33 million people infected worldwide and evidence that neurological damage can accrue in virologically well controlled individuals, HAND is a pressing challenge. Nevertheless, many questions remain unanswered about this spectrum of disorders.

Molecular Profiling Of Patients With Non Small Cell Lung Cancer At Jefferson University Hospital, Erin Bange, Renu Bajaj, Ms, Phd, Cg (Ascp), Cm, Facmg

Department of Pathology Honors Program Student Research Symposium

Companion diagnostics is the use of specific tests whose results are linked to a particular drug. It allows clinicians the ability to better target the mechanism of pathology in the patient and follow it up with a therapy specifically designed to treat the disease process at hand. This approach to medicine has particularly been championed in the field of oncology with the development of such drugs as Zelboraf for the treatment of metastatic melanoma with the BRAFV600 mutation or Xalkori for late stage lung cancer expressing an abnormal ALK protein. In the case of non-small cell lung cancer (NSCLC) Jefferson …

Plasmapheresis And Hiv-Associated Thrombotic Microangiopathy: An Institutional Review, Megan Fisher, Ms2, Nancy Edger Hall, Rn, Mba, Jennifer Webb, Md, Julie Karp, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a systemic disorder that classically results from a deficiency in the von Willebrand factor-cleaving enzyme, ADAMTS13. The human immunodeficiency virus (HIV) is a secondary cause of TTP. It has been recognized that some patients with HIV-associated TTP do not have a deficiency in ADAMTS13 activity. The role of plasmapheresis (PLEX) in these patients is unclear. This study reviewed 8 cases of HIV-associated TTP at Thomas Jefferson University Hospital. All patients responded to treatment; however, we were unable to make any conclusions regarding the use of PLEX in patients with normal ADAMTS13 activity. HAART initiation is …

Her-2 Heterogeneity In Breast Cancer: A Case Study, Kinnari Patel, Theodore Parsons

Department of Pathology Honors Program Student Research Symposium

CASE

The patient is a 75 year-old female with a history of stage 1 invasive ductal carcinoma of the left breast measuring 1.2 cm. Core biopsy of the mass demonstrated Nottingham grade 3 invasive ductal carcinoma; ER negative, PR negative, HER-2 negative (1+). The patient underwent mastectomy in April 2013. Mastectomy confirmed Nottingham grade 3 invasive ductal carcinoma pT1c/pN0/pMX with peritumoral lymphovascular invasion and invasive tumor less than 1 mm from the superoanterior margin. Due to comorbidities the patient was not considered a candidate for adjuvant chemotherapy.

In January 2014 the patient presented with a mastectomy site recurrence. Needle core …

Personalized Immune Therapy For Cancer A Potential Game-Changing Treatment, Emily Evron, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

T-CELL RECEPTOR, NORMALLY

T-cell receptors reside on the surface of T-cells, and recognize a specific antigen presented by an MHC molecule

Next, the T-cells become either CD4 or CD8 cells

Co-stimulation is a key step in activating the T-cell; B7 proteins on the surface of antigen-presenting cells interact with CD28/CTLA-4 receptors on the T-cell.

Haploidentical Hematopoietic Stem Cell Transplantation: Rationale, Development, And Jefferson’S Method, Susan Mcilvaine, Dolores Grosso, Rn, Crnp, Dnp, Beth Colombe

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

There are many indications for hematopoietic stem cell transplantation. In addition to hematologic malignancies, transplants are performed in certain non-hematologic malignancies, for marrow disorders such as Sickle Cell Anemia, and for various inherited disorders such as SCID. Traditionally, transplants have been performed between donors and recipients that are a complete HLA match (typically matched siblings). That is, patients have identical HLA alleles on both copies of chromosome 6. HLA alleles code for major histocompatibility complex molecules, which are the proteins that cause transplant rejection when a mismatch between donor and recipient is present. Thus, matched transplants have been historically …

Small Cell Carcinoma Of The Bladder: A Rare Entity, Andrew H. Matthews, Ruth Birbe, Md

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Primary small cell carcinoma of the urinary bladder is a rare tumor, accounting for less than 1% of the annual 70,000 cases of urinary bladder cancer.¹ Accordingly, little data is available beyond case series to guide diagnosis or treatment. Overall prognosis remains poor with five year survival often markedly below 50%. Current staging and treatment remains largely based on extrapolation from small cell carcinoma of the lung. We review two recent cases of bladder small cell carcinoma with a focus on comparing and contrasting with lung small carcinoma.

Giant Cell Tumor Of Soft Tissue: A Case Study, Rachel Schneider, Brian J. O'Hara

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Giant cell tumors of soft tissue are relatively uncommon tumors. They are considered to be the soft tissue counterpart to giant cell tumors of bone. Both tumors consist of multi-nucleated giant cells evenly distributed throughout a background of epithelioid mononuclear cells, and are usually benign, but can be locally invasive. Giant cell tumors of soft tissue typically occur in patients over age 40, and show no gender or racial predilection. They present as firm, well demarcated masses, which are not connected to the underlying muscle, tendon, or bone. Giant cell tumors of soft tissue are generally small, and tend …

Small Cell Carcinoma Of The Breast, Victor Carlson, Paolo Cotzia, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

Small cell carcinoma of the breast (SCCB) is a rare, highly aggressive neoplasm first reported in 1983. With striking histologic similarity to small cell carcinoma of the lung, it is comprised of small cells with relatively large, hyperchromatic nuclei and scanty cytoplasm. While capable of hormone secretion, this is a rare occurrence in this variant of small cell carcinoma. Patients typically present with a suspicious breast mass confirmed on imaging, with variable lymph node invasion.

Fibrosing Cholestatic Hepatitis C Post-Liver Transplantation: A Case Study, Layla Hatem, Wei Jiang, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Introduction:

Liver Transplantation:

• Hepatitis C infection is the most common indication for liver transplantation in the US
• HCV infection of the liver allograft occurs within hours from circulating virions.

-Serum RNA levels are observed in the first several weeks.

-Acute hepatitis occurs in 2-6 months

-Chronic hepatitis occurs in 3-9 months

***Persistence of HCV infection is the rule after transplantation due to immune suppression

Chronic recurrent HCV infection post transplantation

• There are four distinct patterns of recurrent chronic HCV in the liver allograft.

-Usual chronic HCV (>70%)

-Fibrosing Cholestatic Hepatitis C (5-10%)

-Plasma cell-rich HCV

-HCV overlapping with rejection …

Motor Axon Synapses On Renshaw Cells Contain Higher Levels Of Aspartate Than Glutamate, Dannette Shanon Richards, Ronald W. Griffith, Shannon H. Romer, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw …

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes Within Heterochromatin To Suppress Transcription, Kevin M. Creamer

Theses and Dissertations (ETD)

Eukaryotic DNA is packaged into the nucleus in complex with proteins that regulate access and utilization of the genetic material. These DNA and protein complexes form a dynamic structure known as chromatin. Nucleosomes are the repeating unit of chromatin, and consist of DNA wrapped around an octamer of histone proteins. Nucleosomes can then be modified and spatially arranged to facilitate processes such as transcription, DNA replication, and repair. A special transcriptionally repressive chromatin structure assembles onto gene-poor, repetitive regions of the genome known as constitutive heterochromatin. Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/HDAC repressor complex …

Molecular Characterization Of Glioblastoma Cancer Stem Cells, Jo Meagan Garner

Theses and Dissertations (ETD)

Malignant gliomas are locally aggressive, highly vascular tumors that have an overall survival time less than 14 months, and current therapies provide little improvement in the disease course and outcome. While glioblastoma multiforme (GBM) patients present uniform histological phenotypes, the molecular determinants of the disease vary considerably between individual cases resulting in complicated prognosis. The heterogeneity, aggressiveness and rapid tumor relapse of GBM is believed to be sustained by cancer stem-like cell populations that are able to initiate and maintain tumors. Although CSCs represent only a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance …

Differential Regulation Of Iress In The Aurora A Mrna By Bfgf Through The Mtor Complex To Rc2 Modulates Aurora A Kinase Expression, Roy L. Voice Iii

Dissertations and Theses (Open Access)

Identifying the mechanisms that contribute to tumorigenesis is a major area of focus in our fight against cancer. Epithelial malignant tumors, such as breast, colon, ovarian and pancreatic cancers have been shown to overexpress proteins that control cell mitosis, growth, and proliferation. One of those proteins is the Aurora A kinase. Aurora A kinase is a member of a small family of kinases that contribute to mitotic events such as centrosome duplication, separation, and maturation. Aurora A overexpression leads to genomic instability, which can contribute to tumorigenesis, on the other hand, inhibiting Aurora A expression leads to apoptosis, making it …

Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu

Electronic Theses and Dissertations

Innate immune and inflammatory responses contribute to myocardial and cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLRs) play a critical role in the induction of innate immune and inflammatory responses via activation of nuclear factor kappa B (NF-κB). We have shown that activation of NF-κB contributes to myocardial and cerebral I/R injury. Indeed, inhibition of TLR4-mediated NF-κB activation significantly decreased myocardial and cerebral I/R injury via activation of PI3K/Akt signaling. PI3K/Akt signaling is an important pathway in regulating cellular survival and inflammatory responses. Therefore, an important question is how to differentially modulate PI3K/Akt signaling and TLR/NF-κB-mediated signaling pathway during I/R injury? …

Photobiostimulation In C. Elegans As A Model For Low Level Light Therapy, Michael J. Spoto, Daryl D. Hurd

Science Scholars

Low-Level Laser Therapy (LLLT) is a developing therapeutic technique that has been gaining recognition in the scientific community in recent years. Previous experiments performed in LLLT research projects have been primarily mammalian and cell culture based. These experiments have produced results showing accelerated tissue repair. In this experiment, we introduce a new model, Caenorhabitidis elegans, a free-living soil nematode, to be used in LLLT research by testing the effects of exposure of the organism to various wavelengths and intensities of light commonly used in LLLT. C. elegans was shown to respond to photobiostimulation when exposed to specific wavelengths of …

Bcl2 Expression And Bcl2/Myc Dual Expression Predicts Inferior Survival In Primary Central Nervous System Lymphoma, Guldeep Uppal, Md, Zi-Xuan (Zoe) Wang, Phd, Renu Bajaj, Phd, Mark T. Curtis, Md, Phd, Charalambos C. Solomides, Md, Jon Glass, Md, Peter M. Banks, Stephen C. Peiper, Md, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background

Primary CNS lymphoma (PCNSL) is a rare type of diffuse large B-cell lymphoma (DLBCL) arising from and usually confined to CNS. Understating of the pathogenesis and prognostic markers is a challenge due to rarity of this neoplasm and paucity of the material available to study. Recent studies have shown that dual expression of MYC and BCL2 in DLBCL contributes to inferior overall survival. The prognostic value of MYC and BCL2 in PCNSL is not well studied.

Mir-17/20 Sensitization Of Breast Cancer Cells To Chemotherapy-Induced Apoptosis Requires Akt1., Zuoren Yu, Zengguang Xu, Gabriele Disante, Jennifer Wright, Min Wang, Yuan Li, Qian Zhao, Tao Ren, Xiaoming Ju, Ellen Gutman, Guangxue Wang, Sankar Addya, Tieyan Li, Zhendong Xiang, Chenguang Wang, Xiongfei Yang, Xiaolai Yang, Richard Pestell

Department of Cancer Biology Faculty Papers

The serine threonine kinase Akt1 has been implicated in the control of cellular metabolism, survival and growth. Herein, disruption of the ubiquitously expressed member of the Akt family of genes, Akt1, in the mouse, demonstrates a requirement for Akt1 in miRNA-mediated cellular apoptosis. The miR-17/20 cluster is known to inhibit breast cancer cellular proliferation through G1/S cell cycle arrest via binding to the cyclin D1 3'UTR. Here we show that miR-17/20 overexpression sensitizes cells to apoptosis induced by either Doxorubicin or UV irradiation in MCF-7 cells via Akt1. miR-17/20 mediates apoptosis via increased p53 expression which promotes Akt degradation. Akt1-/- …

Adult Spinal Motoneurones Are Not Hyperexcitable In A Mouse Model Of Inherited Amyotrophic Lateral Sclerosis, Nicolas Delestrée, Marin Manuel, Caroline Iglesias, Sherif M. Elbasiouny, C. J. Heckman, Daniel Zytnicki

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is progressive degeneration of motoneurones, it has been suggested that an intrinsic hyperexcitability of motoneurones (i.e. an increase in their firing rates), contributes to excitotoxicity and to disease onset. Here we show that there is no such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1 around the time of the first muscle fibre denervations. We showed that the recruitment current, the voltage threshold for spiking and the frequency–intensity gain in the …