Medicine and Health Sciences Commons^™

Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to …

Beginner's Guide To Colorectal Cancer Research, Kayla M. Walker

Summer Training Program in Cancer Immunotherapy

Introduction

For a while now obesity has been a health care concern for people all over the world. In the many years that obesity research has been conducted, various things have been taken into consideration including diet, exercise and medical history. In relatively recent years, researchers have expanded their definition of physical activity levels to include both the amounts of occupational physical activity and leisure time activity that a person partakes in.

The 2002 census occupation system assigned a 4 digit Metabolic equivalent (MET) to 509 separate occupations. These codes are particularly helpful for statistics agencies that need to collect …

Prophylactic Vs. Therapeutic: Dna Vaccine To Metastatic Colorectal Cancer Using Molecular Marker Guanylyl Cyclase-C, Anmol Khurana, Msii

Summer Training Program in Cancer Immunotherapy

The role of heat-stable enterotoxin receptor guanylyl cyclase C (GCC) is well known for its aberrant chloride conductance in the intestinal epithelium in response to bacterial infection. Recently, its use as a molecular marker to detect metastatic colon cancer has grown, as has its use as oral hormone therapy for tumor suppression. This study investigates the preliminary stages of a DNA dendritic cell-based vaccine development specific to targeting guanylyl cyclase in systemic tissues. Construction of the plasmid as well as its transduction to Class I MHC molecules in antigen-presenting dendritic cells is examined. Future exploration includes a comparative assessment of …

Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo

Summer Training Program in Cancer Immunotherapy

The mechanism by which the hapten 2,4-dinitrophenyl (DNP) mediates cell death is unclear according to current literature. To determine how DNP mediates death in the B16F10 murine melanoma cell line in vitro, cells were modified with 2,4-dinitro-1-fluorobenzene (DNFB). Following modification, cell lysates were collected and analyzed via Western blottings with known apoptotic or necrotic markers. Our results indicated that DNFB treated cells do not express the apoptotic marker Cleaved Caspase-3 and have no change in levels of the necrotic marker Cyclophilin A. We conclude that DNFB is not inducing apoptosis in B16F10 cells. Future research will further examine the …

Poor Positive Predictive Value Of Mcconnell’S Sign On Transthoracic Echocardiography For The Diagnosis Of Acute Pulmonary Embolism, Urvashi Vaid, Md, Ms, Esme Singer, Md, Gregary D. Marhefka, Md, Walter K. Kraft, Md, Michael Baram, Md, Fccm

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Abstract: Background: Acute pulmonary embolism (PE) is a life-threatening condition. Making a definitive diagnosis with radiologic studies may delay therapy or be unsafe for the patient. Echocardiography is readily available and can suggest PE by demonstrating right ventricular (RV) dysfunction. McConnell’s sign on echocardiogram (ECHO-CG) (RV dysfunction with characteristic sparing of the apex) has been reported to have high sensitivity and specificity for the diagnosis of acute PE. It is hypothesized that McConnell’s sign on ECHO-CG in patients hospitalized with suspected acute PE would have a high positive predictive value (PPV).

Methods: Data, from 2005 to 2010, were retrospectively collected …

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …

Molecular Staging Of Node Negative Patients With Colorectal Cancer., Terry Hyslop, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Metastatic disease is the principle cause of death from colorectal cancer. In that context, the most significant indicator of overall survival and therapeutic response to adjuvant chemotherapy is the presence of metastatic tumor cells in regional lymph nodes. Although histopathologic analysis of lymph nodes is central to all colorectal cancer staging paradigms, its prognostic and predictive value is limited. Indeed, about 30% of patients with histopathology-negative lymph nodes (pN0) die from metastatic disease, reflected by microscopic lymph node metastases that are overlooked by standard techniques. These unrecognized tumor cells are especially important when considering racial disparities in outcomes in colorectal …