Medicine and Health Sciences Commons^™

Phosphorylation Of Vasodilator-Stimulated Phosphoprotein Ser239 Suppresses Filopodia And Invadopodia In Colon Cancer., David S Zuzga, Joshua Pelta-Heller, Peng Li, Alessandro Bombonati, Scott A Waldman, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

In colorectal cancer, the antitumorigenic guanylyl cyclase C (GCC) signalome is defective reflecting ligand deprivation from downregulation of endogenous hormone expression. Although the proximal intracellular mediators of that signal transduction system, including cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG), are well characterized, the functional significance of its distal effectors remain vague. Dysregulation of ligand-dependent GCC signaling through vasodilator-stimulated phosphoprotein (VASP), an actin-binding protein implicated in membrane protrusion dynamics, drastically reduced cGMP-dependent VASP phosphorylation levels in colorectal tumors from patients. Restoration of cGMP-dependent VASP phosphorylation by GCC agonists suppressed the number and length of locomotory (filopodia) and invasive (invadopodia) …

Aberrant Expression Of Cd56 On Granulocytes And Monocytes In Myeloproliferative Neoplasm And Myelodysplastic Syndrome, Ping Gong, Md, Fernanco Metrebian, Md, Alina Dulau-Florea, Md, Zi-Xuan Wang, Phd, Renu Bajaj, Phd, Stephen C Peiper, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Aberrant CD56 expression on granulocytes is seen in all aubtypes MPN and high grade MDS. CD56 expression in MPN correlated with bone marrow morphology, BCR/ABL transcript, and bone marrow engraftment study following treatment. Identification of abnormal CD56+ granulocytes and monocytes is helpful in both the initial diagnosis and long-term follow up of patients with MPN and MDS.

Loss Of Retinoblastoma (Rb) Tumor Suppressor Expression In Breast Cancer Correlates With Better Response To Neoadjuvant Chemotherapy, Jeanne Mcfalls, Md, Jessica Kline, Ba, Gordon Schwartz, Md, Mba, Facs, Angieszka Witkiewicz, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Loss of RB tumor suppressor staining in pre-treatment breast cancer biopsies can be used prior to initiation of neoadjuvant chemotherapy to predict good tumor response. This association between RB loss and good neoadjuvant response holds regardless of ER status and across various chemotherapy regimens. Assessment of RB status in the pre-treatment biopsy could be useful clinical tool to define patients who are most likely to benefit from neoadjuvant chemotherapy.

Expression Of Stem Cell Marker Aldh1 In Cervical Intraepithelial Neoplasia, Ping Gong, Juan Palazzo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Conclusions:

Cervical dysplasia show positive staining for ALDH1 compared to normal cervical mucosa.

ALDH1 positive cells distribution parallels the dysplastic cells in cervical dysplasia.

CSC, as detected by ALDH1 expression, may play a role in the progression of cervical intraepithelial neoplasia and carcinogenesis.

P53 Expression In Oropharyngeal Squamous Cell Carcinoma In Increased In Hpv Positive Smokers, Madalina Tuluc, Voichita Bar-Ad, Zi-Xuan Wang, Joseph Curry

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background and Objectives

High risk HPV is associated with oropharyngeal SCC (OSCC) and is responsible for the increasing incidence of this cancer type among younger patients.

Patients with HPV positive oropharyngeal SCC have a better prognosis when compared with HPV negative, tobacco induced SCC.

HPV E6 inactivates p53 leading to low expression of p53; tobacco induced oropharyngeal SCC is characterized by p53 overexpression, resistance to treatment and poor prognosis. However, in many cases of HPV OSCC, there is a history of current or remote smoking, making this disease a multifactorial process. We expect that smoking will influence the level of …

P16/Rb Correlations In Oropharyngeal Squamous Cell Carcinoma (Oscc), Madalina Tuluc, Voichita Bar-Ad, David Cognetti

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The objective of this study is to explore the patterns of Rb expression in p16 positive and negative OSCC, in relation to patient's smoking history.

Mutant Tdp-43 In Motor Neurons Promotes The Onset And Progression Of Als In Rats, Cao Huang, Jianbin Tong, Fangfang Bi, Hongxia Zhou, Xu-Gang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron degeneration, which ultimately leads to paralysis and death. Mutation of TAR DNA binding protein 43 (TDP-43) has been linked to the development of an inherited form of ALS. Existing TDP-43 transgenic animals develop a limited loss of motor neurons and therefore do not faithfully reproduce the core phenotype of ALS. Here, we report the creation of multiple lines of transgenic rats in which expression of ALS-associated mutant human TDP-43 is restricted to either motor neurons or other types of neurons and skeletal muscle and can be switched on and off. …

Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and …

Clinical Care Plan: Interdisciplinary Course (Ccpic), Marcia Levinson, Pt, Phd, Mft, Amy M Egras, Pharm.D, Bcps, E. Adel Herge, Otd, Otr/L, Kathryn Shaffer, Rn, Msn

Department of Physical Therapy Faculty Papers

Background/Rationale:

Interprofessional collaborative practice significantly improves patient outcomes, reduces mortality and enhances quality-of-life.

Person-focused care demands collaboration among professions in a team approach to address multiple issues including illness, prevention, and health promotion activities.

Key elements of successful implementation of interprofessional education supported by Clinical Care Plan, Interprofessional Course (CCPIC):

-Increasing knowledge of the roles, responsibilities, and competencies of multiple health professions.

-Collaborating in teams

-Recognizing the patient as the expert

-Communicating effectively

Course Statistics:

-176 students from various disciplines completed course (2008-2011).

Disciplines include:

-Medicine, Nursing, Occupational Therapy, Physical Therapy, Pharmacy

The Characteristics Of Borrelia Hermsii Infection In Human Hematopoeitic Stem Cell-Engrafted Mice Mirror Those Of Human Relapsing Fever, Raja Vuyyuru, Hongqi Liu, Tim Manser, Kishore Alugupalli

Department of Microbiology and Immunology Faculty Papers

Rodents are natural reservoirs for a variety of species of Borrelia that cause relapsing fevers in humans. The murine model of this disease recapitulates many of the clinical manifestations of the human disease and has revealed that T cell-independent antibody responses are required to resolve the bacteremic episodes. However, it is not clear whether such protective humoral responses are mounted in humans.

Macrophages And Neutrophils From Humans And Mice Kill Larval Strongyloides Stercoralis During Innate Immunity, Sandra Bonne-Annee, Laura A. Kerepesi, Jessica A. Hess Ligas, David Abraham, Phd

Department of Microbiology and Immunology Faculty Papers

The parasitic nematode Strongyloides stercoralis (Ss) infects 30-100 million people worldwide, yet little is known about the immune response in humans. Previous studies on innate immunity to Ss in mice have demonstrated a role for eosinophils, neutrophils (PMN) and complement activation in the protective immune response.

Expression Of Cancer Stem Cell Biomarkers In Male Breast Cancer, Ping Gong, Md, Juan P. Palazzo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Male breast cancer is an uncommon disease, representing <1% of all breast cancer diagnoses. The prognostic factors and expression of molecular markers in male breast carcinomas are similar to female cancer. Cancer stem cell (CSC)s have been associated with tumor aggressiveness and drug resistance. CSCs are characterized by CD44 and/or ALDH1 expression. We investigated their expression in male breast cancer.

The Role Of Mer In Apoptotic Cell Clearance In The Germinal Center, Tahsin N. Khan, Eric B. Wong, Ziaur S.M. Rahman, Phd

Department of Microbiology and Immunology Faculty Papers

Germinal centers (GCs) are specialized micro-environments that generate high affinity Ab-forming cells (AFCs) and memory B cells. Many B cells undergo apoptosis during clonal selection in GCs. The TAM (Tyro-3, Axl, and Mer) family receptor tyrosine kinases, including Mer, facilitate macrophage clearance of apoptotic cells. We previously showed that tingible body macrophages (TBMφs) in GCs express Mer. We observed that apoptotic cells (ACs) accumulated in GCs of mice deficient in Mer (Mer-/-), after immunization with T-dependent Ag. Accumulation of ACs in GCs of Mer-/- mice resulted in significantly increased AFCs, GCs, and Th1-skewed IgG2c Ab responses. We report here that …

A Compact Guide To The Diagnosis And Management Of Neurofibromatosis Type 1, Timothy Beer, David Strayer, Md, Phd

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

Brief Introduction

Neurofibromatosis type 1 (NF-1) is a multisystem neurocutaneous disorder resulting from mutations in the NF-1 gene on chromosome 17 (q11.2). Mutations in NF-1 result in deficient activity of the tumor suppresor protein neurofibromin, allowing for uncontrolled constitutive activity of the proliferative Raspathway in several neural cell types, including neurons, oligodendrocytes, astrocytes and Schawnn cells. Half of NF-1 cases are inherited in autosomal dominant fashion, while half develop sporadically. The syndrome has 100% penetrance but highly variable expressivity. The prevalence of this syndrome is 1/3,000, making it common enough to warrant YOU, the physician, taking a moment to learn …