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Phase Iib, Randomized, Double-Blind Trial Of Gc4419 Versus Placebo To Reduce Severe Oral Mucositis Due To Concurrent Radiotherapy And Cisplatin For Head And Neck Cancer., Carryn M. Anderson, Christopher M Lee, Deborah P. Saunders, Amarinthia Curtis, Neal Dunlap, Chaitali Nangia, Arielle S. Lee, Sharon M. Gordon, Philip Kovoor, Roberto Arevalo-Araujo, Voichita Bar-Ad, Abhinand Peddada, Kyle Colvett, Douglas Miller, Anshu K. Jain, James Wheeler, Dukagjin Blakaj, Marcelo Bonomi, Sanjiv S. Agarwala, Madhur Garg, Francis Worden, Jon Holmlund, Jeffrey M. Brill, Matt Downs, Stephen T. Sonis, Sanford Katz, John M. Buatti

Department of Radiation Oncology Faculty Papers

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM).

PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly …

Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl

Department of Cancer Biology Faculty Papers

The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X …

Minimal Information For Studies Of Extracellular Vesicles 2018 (Misev2018): A Position Statement Of The International Society For Extracellular Vesicles And Update Of The Misev2014 Guidelines, Clotilde Théry, Kenneth W. Witwer, Elena Aikawa, Maria Jose Alcaraz, Johnathon D. Anderson, Ramaroson Andriantsitohaina, Anna Antoniou, Tanina Arab, Fabienne Archer, Georgia K. Atkiin-Smith, D. Craig Ayre, Jean-Marie Bach, Daniel Bachurski, Hossein Baharvand, Leonora Balaj, Shawn Baldacchino, Natalie N. Bauer, Amy A. Baxter, Mary Bebawy, Carla Beckham, Apolonija Bedina Zavec, Abderrahim Benmoussa, Anna C. Berardi, Paolo Bergese, Ewa Bielska, Cherie Blenkiron, Sylwia Bobis-Wozowicz, Eric Boilard, Wilfrid Boireau, Antonella Bongiovanni, Francesc E. Borràs, Steffi Bosch, Chantal M. Boulanger, Xandra Breakefield, Andrew M. Breglio, Meadhbh Á. Brennan, David R. Brigstock, Alain Brisson, Marike L.D. Broekman, Jacqueline F. Bromberg, Paulina Bryl-Górecka, Shilpa Buch, Amy H. Buck, Dylan Burger, Sara Busatto, Dominik Buschmann, Benedetta Bussolati, Edit I. Buzás, James Bryan Byrd, Giovanni Camussi, David R.F. Carter, Sarah Caruso, Lawrence W. Chamley, Yu-Ting Chang, Chichen Chen, Shuai Chen, Lesley Cheng, Andrew R. Chin, Aled Clayton, Stefano P. Clerici, Alex Cocks, Emanuele Cocucci, Robert J. Coffey, Anabela Cordeiro-Da-Silva, Yvonne Couch, Frank A.W. Coumans, Beth Coyle, Rossella Crescitelli, Miria Ferreira Criado, Crislyn D’ Souza-Schorey, Saumya Das, Amrita Datta Chaudhuri, Paola De Candia, Eliezer F. De Santana Junior, Olivier De Wever, Hernando A. Del Portillo, Tanguy Demaret, Sarah Deville, Andrew Devitt, Bert Dhondt, Dolores Di Vizio, Lothar C. Dieterich, Vincenza Dolo, Ana Paula Dominguez Rubio, Massimo Dominici, Mauricio R. Dourado, Tom A.P Driedonks, Filipe V. Duarte, Heather M. Duncan, Ramon M. Eichenberger, Karin Ekström, Samir El Andaloussi, Celine Elie-Caille, Uta Erdbrügger, Juan M. Falcón-Pérez, Farah Fatima, Jason E. Fish, Miguel Flores-Bellver, András Försönits, Annie Frelet-Barrand, Fabia Fricke, Gregor Fuhrmann, Susanne Gabrielsson, Ana Gámez-Valero, Chris Gardiner, Kathrin Gärtner, Raphael Gaudin, Yong Song Gho, Bernd Giebel, Caroline Gilbert, Mario Gimona, Ilaria Giusti, Deborah C.I. Goberdhan, André Görgens, Sharon M. Gorski, David W. Greening, Julia Christina Gross, Alice Gualerzi, Gopal N. Gupta, Dakota Gustafson, Aase Handberg, Reka A. Haraszti, Paul Harrison, Hargita Hegyesi, An Hendrix, Andrew F. Hill, Fred H. Hochberg, Karl F. Hoffmann, Beth Holder, Harry Holthofer, Baharak Hosseinkhani, Guoku Hu, Yiyao Huang, Veronica Huber, Stuart Hunt, Ahmed Gamal-Eldin Ibrahim, Tsuneya Ikezu, Jameel M. Inal, Mustafa Isin, Alena Ivanova, Hannah K. Jackson, Soren Jacobsen, Steven M. Jay, Muthuvel Jayachandran, Guido Jenster, Lanzhou Jiang, Suzanne M. Johnson, Jennifer C. Jones, Ambrose Jong, Tijana Jovanovic-Talisman, Stephanie Jung, Raghu Kalluri, Shin-Ichi Kano, Sukhbir Kaur, Yumi Kawamura, Evan T. Keller, Delaram Khamari, Elena Khomyakova, Anastasia Khvorova, Peter Kierulf, Kwang Pyo Kim, Thomas Kislinger, Mikael Klingeborn, David J. Klinke Ii, Miroslaw Kornek, Maja M. Kosanović, Árpád Ferenc Kovács, Eva-Maria Krämer-Albers, Susanne Krasemann, Mirja Krause, Igor V. Kurochkin, Gina D. Kusuma, Sören Kuypers, Saara Laitinen, Scott M. Langevin, Lucia R. Languino, Joanne Lannigan, Cecilia Lässer, Louise C. Laurent, Gregory Lavieu, Elisa Lázaro-Ibáñez, Soazig Le Lay, Myung-Shin Lee, Yi Xin Fiona Lee, Debora S. Lemos, Metka Lenassi, Aleksandra Leszczynska, Isaac T.S. Li, Ke Liao, Sten F. Libregts, Erzsebet Ligeti, Rebecca Lim, Sai Kiang Lim, Aija Linē, Karen Linnemannstöns, Alicia Llorente, Catherine A. Lombard, Magdalena J. Lorenowicz, Ákos M. Lörincz, Jan Lötvall, Jason Lovett, Michelle C. Lowry, Xavier Loyer, Quan Lu, Barbara Lukomska, Taral R. Lunavat, Sybren L.N. Maas, Harmeet Malhi, Antonio Marcilla, Jacopo Mariani, Javier Mariscal, Elena S. Martens-Uzunova, Lorena Martin-Jaular, M. Carmen Martinez, Vilma Regina Martins, Mathilde Mathieu, Suresh Mathivanan, Marco Maugeri, Lynda K. Mcginnis, Mark J. Mcvey, David G. Meckes, Jr., Katie L. Meehan, Inge Mertens, Valentina R. Minciacchi, Andreas Möller, Malene Møller Jørgensen, Aizea Morales-Kastresana, Jess Morhayim, François Mullier, Maurizio Muraca, Luca Musante, Veronika Mussack, Dillon C. Muth, Kathryn H. Myburgh, Tanbir Najrana, Muhammad Nawaz, Irina Nazarenko, Peter Nejsum, Christian Neri, Tommaso Neri, Rienk Nieuwland, Leonardo Nimrichter, John P. Nolan, Esther N.M. Nolte-’ T Hoen, Nicole Noren Hooten, Lorraine O’Driscoll, Tina O’Grady, Ana O’Loghlen, Takahiro Ochiya, Martin Olivier, Alberto Ortiz, Luis A. Ortiz, Xabier Osteikoetxea, Ole Ostegaard, Matias Ostrowski, Jaesung Park, D. Michiel Pegtel, Hector Peinado, Francesca Perut, Michael W. Pfaffl, Donald G. Phinney, Bartijn C.H. Pieters, Ryan C. Pink, David S. Pisetsky, Elke Pogge Von Strandmann, Iva Polakovicova, Ivan K.H. Poon, Bonita H. Powell, Ilaria Prada, Lynn Pulliam, Peter Quesenberry, Annalisa Radeghieri, Robert L. Raffai, Stefania Raimondo, Janusz Rak, Marcel I. Ramirez, Graça Raposo, Morsi S. Rayyan, Neta Regev-Rudzki, Fran L. Ricklefs, Paul D. Robbins, David D. Roberts, Silvia C. Rodrigues, Eva Rohde, Sophie Rome, Kasper M.A. Rouschop, Aurelia Rughetti, Ashley E. Russell, Paula Saá, Susmita Sahoo, Edison Salas-Huenuleo, Catherine Sánchez, Julie A. Saugstad, Meike J. Saul, Raymond M. Schiffelers, Raphael Schneider, Tine Hiorth Schøyen, Aaron Scott, Eriomina Shahaj, Shivani Sharma, Olga Shatnyeva, Faezeh Shekari, Ganesh Vilas Shelke, Ashok K. Shetty, Kiyotaka Shiba, Pia R-M Siljander, Andreia M. Silva, Agata Skowronek, Orman L. Snyder Ii, Rodrigo Pedro Soares, Barbara W. Sódar, Carolina Soekmadji, Javier Sotillo, Philip D. Stahl, Willem Stoorvogel, Shannon L. Stott, Erwin F. Strasser, Simon Swift, Hidetoshi Tahara, Muneesh Tewari, Kate Timms, Swasti Tiwari, Rochelle Tixeira, Mercedes Tkach, Wei Seong Toh, Richard Tomasini, Ana Claudia Torrecilhas, Juan Pablo Tosar, Vasilis Toxavidis, Lorena Urbanelli, Pieter Vader, Bas W.M. Van Balkom, Susanne G. Van Der Grein, Jan Van Deun, Martijn J.C. Van Herwijnen, Kendall Van Keuren-Jensen, Guillaume Van Niel, Martin E. Van Royen, Andre J. Van Wijnen, M. Helena Vasconcelos, Ivan J. Vechetti Jr., Tiago D. Veit, Laura J. Vella, Émilie Velot, Frederik J. Verweij, Beate Vestad, Jose L. Viñas, Tamás Visnovitz, Krisztina V. Vukman, Jessica Wahlgren, Dionysios C. Watson, Marca H.M. Wauben, Alissa Weaver, Jason P. Webber, Viktoria Weber, Ann M. Wehman, Daniel J. Weiss, Joshua A. Welsh, Sebastian Wendt, Asa M. Wheelock, Zoltán Wiener, Leonie Witte, Joy Wolfram, Angeliki Xagorari, Patricia Xander, Jing Xu, Xiaomei Yan, María Yáñez-Mó, Hang Yin, Yuana Yuana, Valentina Zappulli, Jana Zarubova, Vytautas Žėkas, Jian-Ye Zhang, Zezhou Zhao, Lei Zheng, Alexander R. Zheutlin, Antje M. Zickler, Pascale Zimmermann, Angela M. Zivkovic, Davide Zocco, Ewa K. Zuba-Surma

Department of Cancer Biology Faculty Papers

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines …