Medicine and Health Sciences Commons^™

Surgical Approaches To Adenocarcinoma Of The Gastroesophageal Junction: The Siewert Ii Conundrum., Andrew M. Brown, Danica N. Giugliano, Adam C. Berger, Michael J. Pucci, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy.

PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. …

Posttranscriptional Regulation Of Parg Mrna By Hur Facilitates Dna Repair And Resistance To Parp Inhibitors, Saswati N. Chand, Mahsa Zarei, M. J. Schiewer, Akshay R. Sanan, Carmella Romeo, Shruti Lal, Joseph A. Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric R. Londin, Wei Jiang, Nicole Meisner-Kober, Michael J. Pishvaian, Karen E. Knudsen, Charles Yeo, John M Pascal, Jordan M. Winter, Jonathan R. Brody

Department of Surgery Faculty Papers

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3⁰ untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to …

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark B. Faries, John F. Thompson, Alistair J. Cochran, Robert H. Andtbacka, Nicola Mozzillo, Jonathan S. Zager, Tiina Jahkola, Tawnya L. Bowles, Alessandro Testori, Peter D. Beitsch, Harald J. Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W.J.M. Wouters, Michael S. Sabel, Edward A. Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R. Rossi, Rogerio I. Neves, Steven D. Trocha, Frances Wright, David R. Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B. Johnson, Patrick Terheyden, Adam C. Berger, Tara L. Huston, Jeffrey D. Wayne, B. Mark Smithers, Heather B. Neuman, Schlomo Schneebaum, Jeffrey E. Gershenwald, Charlotte E. Ariyan, Darius C. Desai, Lisa Jacobs, Kelly M. Mcmasters, Anja Gesierich, Peter Hersey, Steven D. Bines, John M. Kane, Richard J. Barth, Gregory Mckinnon, Jeffrey M. Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A. Hoefer, James M Lewis, Randall Scheri, Mark C. Kelley, Omgo E. Nieweg, R. Dirk Noyes, Dave S.B. Hoon, He-Jing Wang, David A. Elashoff, Robert M. Elashoff

Department of Surgery Faculty Papers

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Crispr Knockout Of The Hur Gene Causes A Xenograft Lethal Phenotype., Shruti Lal, Edwin C, Cheung, Mahsa Zarei, Ranjan Preet, Saswati N. Chand, Nicole C. Mambelli-Lisboa, Carmella Romeo, Matthew C. Stout, Eric Londin, Austin Goetz, Cinthya Y. Lowder, Avinoam Nevler, Charles Yeo, Paul M. Campbell, Jordan M. Winter, Dan A. Dixon, Jonathan Brody

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the United States, whereas colorectal cancer is the third most common cancer. The RNA-binding protein HuR (ELAVL1) supports a pro-oncogenic network in gastrointestinal (GI) cancer cells through enhanced HuR expression. Using a publically available database, HuR expression levels were determined to be increased in primary PDA and colorectal cancer tumor cohorts as compared with normal pancreas and colon tissues, respectively. CRISPR/Cas9 technology was successfully used to delete the HuR gene in both PDA (MIA PaCa-2 and Hs 766T) and colorectal cancer (HCT116) cell lines. HuR deficiency has …