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1. Long-Term Patient-Reported Dyspareunia After Definitive Chemoradiation for Anal Cancer: Using the Anterior Vaginal Wall as an Organ-at-Risk to Define an Actionable Dosimetric Goal

Author

Michael K. Rooney, MD, Joshua S. Niedzielski, PhD, Ramon M. Salazar, PhD, Angelica Arzola, PA-C, Prajnan Das, MD, MS, MPH, Eugene J. Koay, MD, PhD, Albert Koong, MD, PhD, Ethan B. Ludmir, MD, Bruce D. Minsky, MD, Sonal Noticewala, MD, Grace L. Smith, MD, PhD, MPH, Cullen Taniguchi, MD, PhD, and Emma B. Holliday, MD

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: Chemoradiation therapy (CRT) is the standard treatment for squamous cell carcinoma of the anus (SCCA). This study aimed to investigate the relationship between vaginal dosimetry and long-term patient-reported dyspareunia after treatment. We further aimed to use the anterior vaginal wall (AVW) as an organ at risk to define an actionable dosimetric clinical goal to decrease the risk of patient-reported dyspareunia. Methods and Materials: Women with SCCA treated with intensity modulated radiation therapy–based CRT were surveyed at least 2 years after successfully completing therapy. A Female Sexual Function Index (FSFI) pain subscore ≤4 was used to define dyspareunia. Dosimetric parameters were calculated for both the full vaginal canal and AVW. Multivariable linear regression models were created to identify predictors of FSFI pain subscore using backward selection to identify final variables include in the models. An actionable dosimetric predictor for dyspareunia was established using the Youden index method for cutoff optimization. Results: Of 184 women who were contacted, 90 (49%) returned completed surveys. Of those who completed surveys, 51 (56.7%) reported being sexually active, and 47 had dosimetric data available for review. Of sexually active respondents, 32 (68%) had an FSFI pain subscore ≤4. Multiple regression models were generated using the full vaginal canal and AVW as organs at risk, and both models showed similar predictive relationships with volumetric dose parameters emerging as the best dosimetric predictors for dysparenuia. Age over 65 years was also associated with higher FSFI pain subscores (eg, less pain with intercourse) in both models. AVW V35 Gy < 60% was identified as the optimal cutoff to reduce the risk of patient-reported dyspareunia. Conclusions: Increased dose to the vaginal canal is significantly associated with worse patient-reported dyspareunia following CRT for SCCA. Minimizing dose to the AVW to V35 Gy < 60% may reduce the risk of this quality of life-limiting toxicity. Further prospective evaluation is needed to validate these findings.

Published
2024
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2. Effectively Conducting Oncology Clinical Trials During the COVID-19 Pandemic

Author

Debra Nana Yeboa, MD, Chidinma Anakwenze Akinfenwa, MD, MPH, Jonathan Nguyen, MS, Diana Amaya, RN, Beth de Gracia, RN, Matthew Ning, MD, MPH, Victoria Cox, Brian De, MD, Benjamin D. Smith, MD, Lili Lin, MD, Sam Beddar, PhD, Hanh Hoang, MS, Albert Koong, MD, PhD, and Zhongxing Liao, MD

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: Clinical trial enrollment has declined globally as a result of the coronavirus disease 2019 (COVID-19) pandemic. This underscores the importance of structured methods to continue critical medical research safely and efficiently. Methods and Materials: We report the effect of a phased trial reopening strategy, remote research staffing, and telemedicine on cancer trial enrollment at one of the largest radiation oncology academic cancer centers. In phase 1, trials investigating definitive therapeutic benefit were opened, followed by trials not increasing patient exposure or pulmonary toxicity risk in phase 2. During phase 2.5, multicenter trials reopened and limited research staff were allowed on site. Results: Despite initial enrollment declines during the early pandemic, the percentage of new patients enrolling in clinical trials from March to August 2020 was 8.8%, and represented a 10.5% relative increase from 2019. Monthly accrual enrollment from March to August 2019 ranged from 42 to 71, compared with enrollment during COVID-19 from 23 to 73 patients (P < .001). Conclusions: Through a phased approach to trial reopening and adaptive techniques, the division of radiation oncology maintained cancer trial accrual during the COVID-19 pandemic. The experience may help centers maintain accrual, preserve clinical trial integrity, and minimize risk to patients and staff.

Published
2021
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3. Hyperfractionated abdominal reirradiation for gastrointestinal malignancies

Author

Andrew Hunt, Prajnan Das, Bruce D. Minsky, Eugene J. Koay, Sunil Krishnan, Joseph M. Herman, Cullen Taniguchi, Albert Koong, Grace L. Smith, and Emma B. Holliday

Subjects
Reirradiation, External beam, Hyperfractionated, Abdominal, Gastrointestinal malignancies, Toxicity, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background We sought to determine the role of abdominal reirradiation for patients presenting with recurrent or new primary gastrointestinal (GI) malignancies. At our institution, we have established a hyperfractionated, accelerated reirradiation regimen consisting of 39 Gray (Gy) in 26 twice-daily fractions. Although this regimen is used frequently in the pelvis, we sought to determine its toxicity and efficacy for abdominal tumors. Methods Twenty-four patients who received abdominal reirradiation with a hyperfractionated, accelerated approach from 2000 to 2017 were identified. Overall survival (OS) and local progression-free survival (LPFS) were calculated using the Kaplan-Meier method. Several patient, tumor and treatment characteristics were evaluated on univariate analyses for association with OS and LPFS using a Cox proportional hazards model. Results Of the twenty-four patients identified, the majority (n = 11, 46%) had pancreatic adenocarcinoma as their primary disease but also included upper GI adenocarcinoma (n = 4), colon adenocarcinoma (n = 3), hepatobiliary cancers (n = 4) and other malignancies (n = 2). The majority of patients received 45–50.4Gy in 1.8Gy fractions as their initial abdominal radiation course. The median reirradiation dose was 39Gy in 26 twice-daily fractions with a minimum six hour interval. The median [interquartile range (IQR)] interval between the courses of radiotherapy was 28 [18.6–38.9] months. Only palliative reirradiation intent was associated with decreased OS. While colon adenocarcinoma primary was significantly associated with increased LPFS, the sample size was small (n = 3). The 1-yr rate of LPFS was 38%. The median [IQR] duration of freedom from local progression was 8 [3.8–19.2] months. The 1-year OS was 50% and the median (IQR) OS was 14 [6.3–19.6] months. Thirteen patients (54%) had acute side effects with one patient experiencing G3 nausea and one experiencing a G4 bleed; the remaining patients experienced G1-G2 symptoms. Conclusion Hyperfractionated, accelerated reirradiation to the abdomen was relatively well-tolerated but provided limited local control to recurrent or second primary abdominal malignancies. Reirradiation could play a role in treating these patients with palliative or curative intent, but alternative strategies for delivering increased biologically effective dose should be further explored.

Published
2018
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4. Oxygen consumption can regulate the growth of tumors, a new perspective on the Warburg effect.

Author

Yijun Chen, Rob Cairns, Ioanna Papandreou, Albert Koong, and Nicholas C Denko

Subjects
Medicine, Science
Abstract

The unique metabolism of tumors was described many years ago by Otto Warburg, who identified tumor cells with increased glycolysis and decreased mitochondrial activity. However, "aerobic glycolysis" generates fewer ATP per glucose molecule than mitochondrial oxidative phosphorylation, so in terms of energy production, it is unclear how increasing a less efficient process provides tumors with a growth advantage.We carried out a screen for loss of genetic elements in pancreatic tumor cells that accelerated their growth as tumors, and identified mitochondrial ribosomal protein L28 (MRPL28). Knockdown of MRPL28 in these cells decreased mitochondrial activity, and increased glycolysis, but paradoxically, decreased cellular growth in vitro. Following Warburg's observations, this mutation causes decreased mitochondrial function, compensatory increase in glycolysis and accelerated growth in vivo. Likewise, knockdown of either mitochondrial ribosomal protein L12 (MRPL12) or cytochrome oxidase had a similar effect. Conversely, expression of the mitochondrial uncoupling protein 1 (UCP1) increased oxygen consumption and decreased tumor growth. Finally, treatment of tumor bearing animals with dichloroacetate (DCA) increased pyruvate consumption in the mitochondria, increased total oxygen consumption, increased tumor hypoxia and slowed tumor growth.We interpret these findings to show that non-oncogenic genetic changes that alter mitochondrial metabolism can regulate tumor growth through modulation of the consumption of oxygen, which appears to be a rate limiting substrate for tumor proliferation.

Published
2009
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5. Patient-Reported Bowel and Urinary Function in Long-Term Survivors of Squamous Cell Carcinoma of the Anus Treated With Definitive Intensity Modulated Radiation Therapy And Concurrent Chemotherapy

Author

Brian De, Kelsey L. Corrigan, Michael K. Rooney, Ethan B. Ludmir, Prajnan Das, Grace L. Smith, Cullen M. Taniguchi, Bruce D. Minsky, Eugene J. Koay, Albert Koong, Van K. Morris, Craig A. Messick, Y. Nancy You, George J. Chang, O. Lenaine Westney, Graciela M. Nogueras Gonzalez, and Emma B. Holliday

Subjects
Male, Cancer Research, Radiation, Rectal Neoplasms, Anal Canal, Syndrome, Anus Neoplasms, Cross-Sectional Studies, Postoperative Complications, Oncology, Carcinoma, Squamous Cell, Quality of Life, Humans, Female, Radiology, Nuclear Medicine and imaging, Patient Reported Outcome Measures, Survivors, Fecal Incontinence
Abstract

Definitive radiation therapy with concurrent chemotherapy is curative for nonmetastatic squamous cell carcinoma of the anus (SCCA). However, the true effect of chemoradiation on long-term functional outcomes is poorly understood owing to limited follow-up and patient-reported outcomes (PROs).We conducted a cross-sectional survey of 248 patients with SCCA treated with definitive intensity modulated radiation and concurrent chemotherapy from 2010 to 2018 who were alive and without recurrence. PRO measures were collected, including Functional Assessment of Cancer Therapy-General (FACT-G7), Fecal Incontinence Quality of Life (FIQoL), Low Anterior Resection Syndrome (LARS), and International Consultation on Incontinence Questionnaires (ICIQ). Models were used to determine the association between demographic, tumor, treatment, and dosimetric data with PROs.One hundred twelve (45%) patients completed PROs. Median [interquartile range (IQR)] time from radiation completion to survey was 51 [37-85] months. The median scores [IQR] for FACT-G7, FIQoL, and LARS were 21 [15-24], 14 [11-16], and 32 [25-37], respectively. For men, median subscores [IQR] for ICIQ voiding and incontinence subscores were 5 [2-6] and 1 [1-3], respectively. For women, median subscores [IQR] for ICIQ voiding, incontinence, and filling were 1 [1-3], 5 [3-8], and 4 [2-5], respectively. Higher (better) FIQoL scores were associated with higher (better) FACT-G7 scores (β = 0.83; 95% confidence interval, 0.58-1.09; P.001), and higher (worse) LARS scores were associated with lower (worse) FACT-G7 scores (β = -0.22; 95% confidence interval, -0.31 to -0.13; P.001). A separate multivariable analysis revealed higher bowel bag D1% was associated with lower (worse) FIQoL (P = .001) and higher (worse) LARS (P = .003) scores. Higher bladder V40 Gy was associated with increased (worse) ICIQ voiding subscore (P = .001).Patients treated with modern chemoradiation for SCCA experience significant long-term bowel toxic effects with considerable effect on quality of life. Minimizing bowel hotspots and bladder V40 Gy may improve bowel and urinary function. Other interventions to reduce long-term toxic effects and improve quality of life are needed.

Published
2022
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7. Data from A Novel Aldehyde Dehydrogenase-3 Activator (Alda-89) Protects Submandibular Gland Function from Irradiation without Accelerating Tumor Growth

Author

Quynh-Thu Le, Daria Mochly-Rosen, Amato Giaccia, Albert Koong, Edward Graves, Davud Sirjani, Cato Chan, Rehan Ali, Christina S. Kong, Che-Hong Chen, Hongbin Cao, and Nan Xiao

Abstract

Purpose: To determine the effect of Alda-89 (an ALDH3 activitor) on (i) the function of irradiated (radiotherapy) submandibular gland (SMG) in mice, (ii) its toxicity profile, and (iii) its effect on the growth of head and neck cancer (HNC) in vitro and in vivo.Experimental Design: Adult mice were infused with Alda-89 or vehicle before, during, and after radiotherapy. Saliva secretion was monitored weekly. Hematology, metabolic profile, and postmortem evaluation for toxicity were examined at the time of sacrifice. Alda-89 or vehicle was applied to HNC cell lines in vitro, and severe combined immunodeficient (SCID) mice transplanted with HNC in vivo with or without radiation; HNC growth was monitored. The ALDH3A1 and ALDH3A2 protein expression was evaluated in 89 patients with HNC and correlated to freedom from relapse (FFR) and overall survival (OS).Results: Alda-89 infusion significantly resulted in more whole saliva production and a higher percentage of preserved acini after radiotherapy compared with vehicle control. There was no difference in the complete blood count, metabolic profile, and major organ morphology between the Alda-89 and vehicle groups. Compared with vehicle control, Alda-89 treatment neither accelerated HNC cell proliferation in vitro, nor did it affect tumor growth in vivo with or without radiotherapy. Higher expression of ALDH3A1 or ALDH3A2 was not significantly associated with worse FFR or OS in either human papillomavirus (HPV)-positive or HPV-negative group.Conclusion: Alda-89 preserves salivary function after radiotherapy without affecting HNC growth or causing measurable toxicity in mice. It is a promising candidate to mitigate radiotherapy-related xerostomia. Clin Cancer Res; 19(16); 4455–64. ©2013 AACR.

Published
2023
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9. Data from Cetuximab-Based Immunotherapy and Radioimmunotherapy of Head and Neck Squamous Cell Carcinoma

Author

Xiaoyuan Chen, Sanjiv Sam Gambhir, Quynh-Thu Le, Albert Koong, Donald Courter, Qizhen Cao, Xilin Sun, and Gang Niu

Abstract

Purpose: To show the relationship between antibody delivery and therapeutic efficacy in head and neck cancers, in this study we evaluated the pharmacokinetics and pharmacodynamics of epidermal growth factor receptor (EGFR)–targeted immunotherapy and radioimmunotherapy by quantitative positron emission tomography (PET) imaging.Experimental Design: EGFR expression on UM-SCC-22B and SCC1 human head and neck squamous cell cancer (HNSCC) cells were determined by flow cytometry and immunostaining. Tumor delivery and distribution of cetuximab in tumor-bearing nude mice were evaluated with small animal PET using 64Cu-DOTA-cetuximab. The in vitro toxicity of cetuximab to HNSCC cells was evaluated by MTT assay. The tumor-bearing mice were then treated with four doses of cetuximab at 10 mg/kg per dose, and tumor growth was evaluated by caliper measurement. FDG PET was done after the third dose of antibody administration to evaluate tumor response. Apoptosis and tumor cell proliferation after cetuximab treatment were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Ki-67 staining. Radioimmunotherapy was done with 90Y-DOTA-cetuximab.Results: EGFR expression on UM-SCC-22B cells is lower than that on SCC1 cells. However, the UM-SCC-22B tumors showed much higher 64Cu-DOTA-cetuximab accumulation than the SCC1 tumors. Cetuximab-induced apoptosis in SCC1 tumors and tumor growth was significantly inhibited, whereas an agonistic effect of cetuximab on UM-SCC-22B tumor growth was observed. After cetuximab treatment, the SCC1 tumors showed decreased FDG uptake, and the UM-SCC-22B tumors had increased FDG uptake. UM-SCC-22B tumors are more responsive to 90Y-DOTA-cetuximab treatment than SCC1 tumors, partially due to the high tumor accumulation of the injected antibody.Conclusion: Cetuximab has an agonistic effect on the growth of UM-SCC-22B tumors, indicating that tumor response to cetuximab treatment is not necessarily related to EGFR expression and antibody delivery efficiency, as determined by PET imaging. Although PET imaging with antibodies as tracers has limited function in patient screening, it can provide guidance for targeted therapy using antibodies as delivery vehicles. Clin Cancer Res; 16(7); 2095–105. ©2010 AACR.

Published
2023
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12. Robotic intrafractional US guidance for liver SABR: System design, beam avoidance, and clinical imaging

Author

Jeffrey, Schlosser, Ren Hui, Gong, Ralf, Bruder, Achim, Schweikard, Sungjune, Jang, John, Henrie, Aya, Kamaya, Albert, Koong, Daniel T, Chang, and Dimitre, Hristov

Subjects
EMERGING IMAGING AND THERAPY MODALITIES, Liver Neoplasms, Humans, Equipment Failure, Dose Fractionation, Radiation, Radiotherapy, Intensity-Modulated, Robotics, Radiosurgery, Radiotherapy, Image-Guided, Ultrasonography
Abstract

To present a system for robotic 4D ultrasound (US) imaging concurrent with radiotherapy beam delivery and estimate the proportion of liver stereotactic ablative body radiotherapy (SABR) cases in which robotic US image guidance can be deployed without interfering with clinically used VMAT beam configurations.The image guidance hardware comprises a 4D US machine, an optical tracking system for measuring US probe pose, and a custom-designed robot for acquiring hands-free US volumes. In software, a simulation environment incorporating the LINAC, couch, planning CT, and robotic US guidance hardware was developed. Placement of the robotic US hardware was guided by a target visibility map rendered on the CT surface by using the planning CT to simulate US propagation. The visibility map was validated in a prostate phantom and evaluated in patients by capturing live US from imaging positions suggested by the visibility map. In 20 liver SABR patients treated with VMAT, the simulation environment was used to virtually place the robotic hardware and US probe. Imaging targets were either planning target volumes (PTVs, range 5.9-679.5 ml) or gross tumor volumes (GTVs, range 0.9-343.4 ml). Presence or absence of mechanical interference with LINAC, couch, and patient body as well as interferences with treated beams was recorded.For PTV targets, robotic US guidance without mechanical interference was possible in 80% of the cases and guidance without beam interference was possible in 60% of the cases. For the smaller GTV targets, these proportions were 95% and 85%, respectively. GTV size (1/20), elongated shape (1/20), and depth (1/20) were the main factors limiting the availability of noninterfering imaging positions. The robotic US imaging system was deployed in two liver SABR patients during CT simulation with successful acquisition of 4D US sequences in different imaging positions.This study indicates that for VMAT liver SABR, robotic US imaging of a relevant internal target may be possible in 85% of the cases while using treatment plans currently deployed in the clinic. With beam replanning to account for the presence of robotic US guidance, intrafractional US may be an option for 95% of the liver SABR cases.

Published
2016

13. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin Jaiswal, Michael Curran, Tina C. Albershardt, Anshika Bajaj, Jacob F. Archer, Rebecca S. Reeves, Lisa Y. Ngo, Peter Berglund, Jan ter Meulen, Caroline Denis, Hormas Ghadially, Thomas Arnoux, Fabien Chanuc, Nicolas Fuseri, Robert W. Wilkinson, Nicolai Wagtmann, Yannis Morel, Pascale Andre, Michael B. Atkins, Matteo S. Carlino, Antoni Ribas, John A. Thompson, Toni K. Choueiri, F. Stephen Hodi, Wen-Jen Hwu, David F. McDermott, Victoria Atkinson, Jonathan S. Cebon, Bernie Fitzharris, Michael B. Jameson, Catriona McNeil, Andrew G. Hill, Eric Mangin, Malidi Ahamadi, Marianne van Vugt, Mariëlle van Zutphen, Nageatte Ibrahim, Georgina V. Long, Robyn Gartrell, Zoe Blake, Ines Simoes, Yichun Fu, Takuro Saito, Yingzhi Qian, Yan Lu, Yvonne M. Saenger, Sadna Budhu, Olivier De Henau, Roberta Zappasodi, Kyle Schlunegger, Bruce Freimark, Jeff Hutchins, Christopher A. Barker, Jedd D. Wolchok, Taha Merghoub, Elena Burova, Omaira Allbritton, Peter Hong, Jie Dai, Jerry Pei, Matt Liu, Joel Kantrowitz, Venus Lai, William Poueymirou, Douglas MacDonald, Ella Ioffe, Markus Mohrs, William Olson, Gavin Thurston, Cristian Capasso, Federica Frascaro, Sara Carpi, Siri Tähtinen, Sara Feola, Manlio Fusciello, Karita Peltonen, Beatriz Martins, Madeleine Sjöberg, Sari Pesonen, Tuuli Ranki, Lukasz Kyruk, Erkko Ylösmäki, Vincenzo Cerullo, Fabio Cerignoli, Biao Xi, Garret Guenther, Naichen Yu, Lincoln Muir, Leyna Zhao, Yama Abassi, Víctor Cervera-Carrascón, Mikko Siurala, João Santos, Riikka Havunen, Suvi Parviainen, Akseli Hemminki, Angus Dalgleish, Satvinder Mudan, Mark DeBenedette, Ana Plachco, Alicia Gamble, Elizabeth W. Grogan, John Krisko, Irina Tcherepanova, Charles Nicolette, Pooja Dhupkar, Ling Yu, Eugenie S. Kleinerman, Nancy Gordon, Italia Grenga, Lauren Lepone, Sofia Gameiro, Karin M. Knudson, Massimo Fantini, Kwong Tsang, James Hodge, Renee Donahue, Jeffrey Schlom, Elizabeth Evans, Holm Bussler, Crystal Mallow, Christine Reilly, Sebold Torno, Maria Scrivens, Cathie Foster, Alan Howell, Leslie Balch, Alyssa Knapp, John E. Leonard, Mark Paris, Terry Fisher, Siwen Hu-Lieskovan, Ernest Smith, Maurice Zauderer, William Fogler, Marilyn Franklin, Matt Thayer, Dan Saims, John L. Magnani, Jian Gong, Michael Gray, George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose, Taylor H. Schreiber, Sofia R. Gameiro, Paul E. Clavijo, Clint T. Allen, James W. Hodge, Kwong Y. Tsang, Jane Grogan, Nicholas Manieri, Eugene Chiang, Patrick Caplazi, Mahesh Yadav, Patrick Hagner, Hsiling Chiu, Michelle Waldman, Anke Klippel, Anjan Thakurta, Michael Pourdehnad, Anita Gandhi, Ian Henrich, Laura Quick, Rob Young, Margaret Chou, Andrew Hotson, Stephen Willingham, Po Ho, Carmen Choy, Ginna Laport, Ian McCaffery, Richard Miller, Kimberly A. Tipton, Kenneth R. Wong, Victoria Singson, Chihunt Wong, Chanty Chan, Yuanhiu Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, James West, Bryan A. Irving, Ritika Jaini, Matthew Loya, Charis Eng, Melissa L. Johnson, Alex A. Adjei, Mateusz Opyrchal, Suresh Ramalingam, Pasi A. Janne, George Dominguez, Dmitry Gabrilovich, Laura de Leon, Jeannette Hasapidis, Scott J. Diede, Peter Ordentlich, Scott Cruickshank, Michael L. Meyers, Matthew D. Hellmann, Pawel Kalinski, Amer Zureikat, Robert Edwards, Ravi Muthuswamy, Nataša Obermajer, Julie Urban, Lisa H. Butterfield, William Gooding, Herbert Zeh, David Bartlett, Olga Zubkova, Larissa Agapova, Marina Kapralova, Liudmila Krasovskaia, Armen Ovsepyan, Maxim Lykov, Artem Eremeev, Vladimir Bokovanov, Olga Grigoryeva, Andrey Karpov, Sergey Ruchko, Alexandr Shuster, Danny N. Khalil, Luis Felipe Campesato, Yanyun Li, Adam S. Lazorchak, Troy D. Patterson, Yueyun Ding, Pottayil Sasikumar, Naremaddepalli Sudarshan, Nagaraj Gowda, Raghuveer Ramachandra, Dodheri Samiulla, Sanjeev Giri, Rajesh Eswarappa, Murali Ramachandra, David Tuck, Timothy Wyant, Jasmin Leshem, Xiu-fen Liu, Tapan Bera, Masaki Terabe, Birgit Bossenmaier, Gerhard Niederfellner, Yoram Reiter, Ira Pastan, Leiming Xia, Yang Xia, Yangyang Hu, Yi Wang, Yangyi Bao, Fu Dai, Shiang Huang, Elaine Hurt, Robert E. Hollingsworth, Lawrence G. Lum, Alfred E. Chang, Max S. Wicha, Qiao Li, Thomas Mace, Neil Makhijani, Erin Talbert, Gregory Young, Denis Guttridge, Darwin Conwell, Gregory B. Lesinski, Rodney JM Macedo Gonzales, Austin P. Huffman, Ximi K. Wang, Ran Reshef, Andy MacKinnon, Jason Chen, Matt Gross, Gisele Marguier, Peter Shwonek, Natalija Sotirovska, Susanne Steggerda, Francesco Parlati, Amani Makkouk, Mark K. Bennett, Ethan Emberley, Tony Huang, Weiqun Li, Silinda Neou, Alison Pan, Jing Zhang, Winter Zhang, Netonia Marshall, Thomas U. Marron, Judith Agudo, Brian Brown, Joshua Brody, Christopher McQuinn, Matthew Farren, Hannah Komar, Reena Shakya, Thomas Ludwug, Y. Maurice Morillon, Scott A. Hammond, John W. Greiner, Pulak R. Nath, Anthony L. Schwartz, Dragan Maric, David D. Roberts, Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Deborah J. Wong, Manish Patel, Gerald Falchook, Shubham Pant, Patrick A. Ott, Melinda Whiteside, Amita Patnaik, John Mumm, Filip Janku, Ivan Chan, Todd Bauer, Rivka Colen, Peter VanVlasselaer, Gail L. Brown, Nizar M. Tannir, Martin Oft, Jeffrey Infante, Evan Lipson, Ajay Gopal, Sattva S. Neelapu, Philippe Armand, Stephen Spurgeon, John P. Leonard, Rachel E. Sanborn, Ignacio Melero, Thomas F. Gajewski, Matthew Maurer, Serena Perna, Andres A. Gutierrez, Raphael Clynes, Priyam Mitra, Satyendra Suryawanshi, Douglas Gladstone, Margaret K. Callahan, James Crooks, Sheila Brown, Audrey Gauthier, Marc Hillairet de Boisferon, Andrew MacDonald, Laura Rosa Brunet, William T. Rothwell, Peter Bell, James M. Wilson, Fumi Sato-Kaneko, Shiyin Yao, Shannon S. Zhang, Dennis A. Carson, Cristina Guiducci, Robert L. Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Tomoko Hayashi, Ezra E. W. Cohen, David Schaer, Yanxia Li, Julie Dobkin, Michael Amatulli, Gerald Hall, Thompson Doman, Jason Manro, Frank Charles Dorsey, Lillian Sams, Rikke Holmgaard, Krishnadatt Persaud, Dale Ludwig, David Surguladze, John S. Kauh, Ruslan Novosiadly, Michael Kalos, Kyla Driscoll, Hardev Pandha, Christy Ralph, Kevin Harrington, Brendan Curti, Wallace Akerley, Sumati Gupta, Alan Melcher, David Mansfield, David R. Kaufman, Emmett Schmidt, Mark Grose, Bronwyn Davies, Roberta Karpathy, Darren Shafren, Katerina Shamalov, Cyrille Cohen, Naveen Sharma, James Allison, Tala Shekarian, Sandrine Valsesia-Wittmann, Christophe Caux, Aurelien Marabelle, Brian M. Slomovitz, Kathleen M. Moore, Hagop Youssoufian, Marshall Posner, Poonam Tewary, Alan D. Brooks, Ya-Ming Xu, Kithsiri Wijeratne, Leslie A. A. Gunatilaka, Thomas J. Sayers, John P. Vasilakos, Tesha Alston, Simon Dovedi, James Elvecrog, Iwen Grigsby, Ronald Herbst, Karen Johnson, Craig Moeckly, Stefanie Mullins, Kristen Siebenaler, Julius SternJohn, Ashenafi Tilahun, Mark A. Tomai, Katharina Vogel, Eveline E. Vietsch, Anton Wellstein, Martin Wythes, Stefano Crosignani, Joseph Tumang, Shilpa Alekar, Patrick Bingham, Sandra Cauwenberghs, Jenny Chaplin, Deepak Dalvie, Sofie Denies, Coraline De Maeseneire, JunLi Feng, Kim Frederix, Samantha Greasley, Jie Guo, James Hardwick, Stephen Kaiser, Katti Jessen, Erick Kindt, Marie-Claire Letellier, Wenlin Li, Karen Maegley, Reece Marillier, Nichol Miller, Brion Murray, Romain Pirson, Julie Preillon, Virginie Rabolli, Chad Ray, Kevin Ryan, Stephanie Scales, Jay Srirangam, Jim Solowiej, Al Stewart, Nicole Streiner, Vince Torti, Konstantinos Tsaparikos, Xianxian Zheng, Gregory Driessens, Bruno Gomes, Manfred Kraus, Chunxiao Xu, Yanping Zhang, Giorgio Kradjian, Guozhong Qin, Jin Qi, Xiaomei Xu, Bo Marelli, Huakui Yu, Wilson Guzman, Rober Tighe, Rachel Salazar, Kin-Ming Lo, Jessie English, Laszlo Radvanyi, Yan Lan, Michael Postow, Yasin Senbabaoglu, Billel Gasmi, Hong Zhong, Cailian Liu, Daniel Hirschhorhn-Cymerman, Yuanyuan Zha, Gregory Malnassy, Noreen Fulton, Jae-Hyun Park, Wendy Stock, Yusuke Nakamura, Hongtao Liu, Xiaoming Ju, Rachelle Kosoff, Kimberly Ramos, Brandon Coder, Robert Petit, Michael Princiotta, Kyle Perry, Jun Zou, Ainhoa Arina, Christian Fernandez, Wenxin Zheng, Michael A. Beckett, Helena J. Mauceri, Yang-Xin Fu, Ralph R. Weichselbaum, Whitney Lewis, Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Dongyun Wu, Jin Li, Xiaoling Liang, Xiangjun Zhou, Jinlin Hou, Raffit Hassan, Thierry Jahan, Scott J. Antonia, Hedy L. Kindler, Evan W. Alley, Somayeh Honarmand, Weiqun Liu, Meredith L. Leong, Chan C. Whiting, Nitya Nair, Amanda Enstrom, Edward E. Lemmens, Takahiro Tsujikawa, Sushil Kumar, Lisa M. Coussens, Aimee L. Murphy, Dirk G. Brockstedt, Sven D. Koch, Martin Sebastian, Christian Weiss, Martin Früh, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geissler, Frank Griesinger, Jens Kollmeier, Alexandros Papachristofilou, Fatma Doener, Mariola Fotin-Mleczek, Madeleine Hipp, Henoch S. Hong, Karl-Josef Kallen, Ute Klinkhardt, Claudia Stosnach, Birgit Scheel, Andreas Schroeder, Tobias Seibel, Ulrike Gnad-Vogt, Alfred Zippelius, Ha-Ram Park, Yong-Oon Ahn, Tae Min Kim, Soyeon Kim, Seulki Kim, Yu Soo Lee, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Shari Pilon-Thomas, Amy Weber, Jennifer Morse, Krithika Kodumudi, Hao Liu, John Mullinax, Amod A. Sarnaik, Luke Pike, Andrew Bang, Tracy Balboni, Allison Taylor, Alexander Spektor, Tyler Wilhite, Monica Krishnan, Daniel Cagney, Brian Alexander, Ayal Aizer, Elizabeth Buchbinder, Mark Awad, Leena Ghandi, Jonathan Schoenfeld, Elizabeth Lessey-Morillon, Lisa Ridnour, Neil H. Segal, Manish Sharma, Dung T. Le, Robert L. Ferris, Andrew D. Zelenetz, Ronald Levy, Izidore S. Lossos, Caron Jacobson, Radhakrishnan Ramchandren, John Godwin, A. Dimitrios Colevas, Roland Meier, Suba Krishnan, Xuemin Gu, Jaclyn Neely, John Timmerman, Claire I. Vanpouille-Box, Silvia C. Formenti, Sandra Demaria, Erik Wennerberg, Aranzazu Mediero, Bruce N. Cronstein, Michael P. Gustafson, AriCeli DiCostanzo, Courtney Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A. Gastineau, Bruce D. Johnson, Allan B. Dietz, Cameron MacDonald, Mark Bucsek, Guanxi Qiao, Bonnie Hylander, Elizabeth Repasky, William J. Turbitt, Yitong Xu, Andrea Mastro, Connie J. Rogers, Sita Withers, Ziming Wang, Lam T. Khuat, Cordelia Dunai, Bruce R. Blazar, Dan Longo, Robert Rebhun, Steven K. Grossenbacher, Arta Monjazeb, William J. Murphy, Scott Rowlinson, Giulia Agnello, Susan Alters, David Lowe, Nicole Scharping, Ashley V. Menk, Ryan Whetstone, Xue Zeng, Greg M. Delgoffe, Patricia M. Santos, Jian Shi, Greg Delgoffe, Misako Nagasaka, Ammar Sukari, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Natalie Collins, Robert Manguso, Hans Pope, Yashaswi Shrestha, Jesse Boehm, W. Nicholas Haining, Kyle R. Cron, Ayelet Sivan, Keston Aquino-Michaels, Marco Orecchioni, Davide Bedognetti, Wouter Hendrickx, Claudia Fuoco, Filomena Spada, Francesco Sgarrella, Gianni Cesareni, Francesco Marincola, Kostas Kostarelos, Alberto Bianco, Lucia Delogu, Jessica Roelands, Sabri Boughorbel, Julie Decock, Scott Presnell, Ena Wang, Franco M. Marincola, Peter Kuppen, Michele Ceccarelli, Darawan Rinchai, Damien Chaussabel, Lance Miller, Andrew Nguyen, J. Zachary Sanborn, Charles Vaske, Shahrooz Rabizadeh, Kayvan Niazi, Steven Benz, Shashank Patel, Nicholas Restifo, James White, Sam Angiuoli, Mark Sausen, Sian Jones, Maria Sevdali, John Simmons, Victor Velculescu, Luis Diaz, Theresa Zhang, Jennifer S. Sims, Sunjay M. Barton, Angela Kadenhe-Chiweshe, Filemon Dela Cruz, Andrew T. Turk, Christopher F. Mazzeo, Andrew L. Kung, Jeffrey N. Bruce, Darrell J. Yamashiro, Eileen P. Connolly, Jason Baird, Marka Crittenden, David Friedman, Hong Xiao, Rom Leidner, Bryan Bell, Kristina Young, Michael Gough, Zhen Bian, Koby Kidder, Yuan Liu, Emily Curran, Xiufen Chen, Leticia P. Corrales, Justin Kline, Ethan G. Aguilar, Jennifer Guerriero, Alaba Sotayo, Holly Ponichtera, Alexandra Pourzia, Sara Schad, Ruben Carrasco, Suzan Lazo, Roderick Bronson, Anthony Letai, Richard S. Kornbluth, Sachin Gupta, James Termini, Elizabeth Guirado, Geoffrey W. Stone, Christina Meyer, Laura Helming, Nicholas Wilson, Robert Hofmeister, Natalie J. Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A. Fuertes Marraco, Daniel E. Speiser, Tara S. Abraham, Bo Xiang, Michael S. Magee, Scott A. Waldman, Adam E. Snook, Wojciech Blogowski, Ewa Zuba-Surma, Marta Budkowska, Daria Salata, Barbara Dolegowska, Teresa Starzynska, Leo Chan, Srinivas Somanchi, Kelsey McCulley, Dean Lee, Nico Buettner, Feng Shi, Paisley T. Myers, Stuart Curbishley, Sarah A. Penny, Lora Steadman, David Millar, Ellen Speers, Nicola Ruth, Gabriel Wong, Robert Thimme, David Adams, Mark Cobbold, Remy Thomas, Mariam Al-Muftah, Michael KK Wong, Michael Morse, Joseph I. Clark, Howard L. Kaufman, Gregory A. Daniels, Hong Hua, Tharak Rao, Janice P. Dutcher, Kai Kang, Yogen Saunthararajah, Vamsidhar Velcheti, Vikas Kumar, Firoz Anwar, Amita Verma, Zinal Chheda, Gary Kohanbash, John Sidney, Kaori Okada, Shruti Shrivastav, Diego A. Carrera, Shuming Liu, Naznin Jahan, Sabine Mueller, Ian F. Pollack, Angel M. Carcaboso, Alessandro Sette, Yafei Hou, Hideho Okada, Jessica J. Field, Weiping Zeng, Vincent FS Shih, Che-Leung Law, Peter D. Senter, Shyra J. Gardai, Nicole M. Okeley, Jennifer G. Abelin, Abu Z. Saeed, Stacy A. Malaker, Jeffrey Shabanowitz, Stephen T. Ward, Donald F. Hunt, Pam Profusek, Laura Wood, Dale Shepard, Petros Grivas, Kerstin Kapp, Barbara Volz, Detlef Oswald, Burghardt Wittig, Manuel Schmidt, Julian P. Sefrin, Lars Hillringhaus, Valeria Lifke, Alexander Lifke, Anna Skaletskaya, Jose Ponte, Thomas Chittenden, Yulius Setiady, Eva Sivado, Vincent Thomas, Meddy El Alaoui, Sébastien Papot, Charles Dumontet, Mike Dyson, John McCafferty, Said El Alaoui, Praveen K. Bommareddy, Andrew Zloza, Frederick Kohlhapp, Ann W. Silk, Sachin Jhawar, Tomas Paneque, Jenna Newman, Pedro Beltran, Felicia Cao, Bang-Xing Hong, Tania Rodriguez-Cruz, Xiao-Tong Song, Stephen Gottschalk, Hugo Calderon, Sam Illingworth, Alice Brown, Kerry Fisher, Len Seymour, Brian Champion, Emma Eriksson, Jessica Wenthe, Ann-Charlotte Hellström, Gabriella Paul-Wetterberg, Angelica Loskog, Ioanna Milenova, Magnus Ståhle, Justyna Jarblad-Leja, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Sharad Goyal, Ann Silk, Janice Mehnert, Nashat Gabrail, Jennifer Bryan, Daniel Medina, Leah Mitchell, Kader Yagiz, Fernando Lopez, Daniel Mendoza, Anthony Munday, Harry Gruber, Douglas Jolly, Steven Fuhrmann, Sasa Radoja, Wei Tan, Aldo Pourchet, Alan Frey, Ian Mohr, Matthew Mulvey, Robert H. I. Andtbacka, Merrick Ross, Sanjiv Agarwala, Kenneth Grossmann, Matthew Taylor, John Vetto, Rogerio Neves, Adil Daud, Hung Khong, Stephanie M. Meek, Richard Ungerleider, Scott Welden, Maki Tanaka, Matthew Williams, Sigrun Hallmeyer, Bernard Fox, Zipei Feng, Christopher Paustian, Carlo Bifulco, Sadia Zafar, Otto Hemminki, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Tameem Ansari, Srividya Sundararaman, Diana Roen, Paul Lehmann, Anja C. Bloom, Lewis H. Bender, Ian B. Walters, Jay A. Berzofsky, Fanny Chapelin, Eric T. Ahrens, Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Alexander Scholz, Danhui Zhang, Gilson Baia, Yann Chong Tan, Jeremy Sokolove, Dongkyoon Kim, Kevin Williamson, Xiaomu Chen, Jillian Colrain, Gregg Espiritu Santo, Ngan Nguyen, Wayne Volkmuth, Norman Greenberg, William Robinson, Daniel Emerling, Charles G. Drake, Daniel P. Petrylak, Emmanuel S. Antonarakis, Adam S. Kibel, Nancy N. Chang, Tuyen Vu, Dwayne Campogan, Heather Haynes, James B. Trager, Nadeem A. Sheikh, David I. Quinn, Peter Kirk, Murali Addepalli, Thomas Chang, Ping Zhang, Marina Konakova, Katsunobu Hagihara, Steven Pai, Laurie VanderVeen, Palakshi Obalapur, Peiwen Kuo, Phi Quach, Lawrence Fong, Deborah H. Charych, Jonathan Zalevsky, John L. Langowski, Yolanda Kirksey, Ravi Nutakki, Shalini Kolarkar, Rhoneil Pena, Ute Hoch, Stephen K. Doberstein, John Cha, Zach Mallon, Myra Perez, Amanda McDaniel, Snjezana Anand, Darrin Uecker, Richard Nuccitelli, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, Ariana N. Renrick, Menaka Thounaojam, Portia Thomas, Samuel Pellom, Anil Shanker, Duafalia Dudimah, Alan Brooks, Yu-Lin Su, Tomasz Adamus, Qifang Zhang, Sergey Nechaev, Marcin Kortylewski, Spencer Wei, Clark Anderson, Chad Tang, Jonathan Schoenhals, Efrosini Tsouko, John Heymach, Patricia de Groot, Joe Chang, Kenneth R. Hess, Adi Diab, Padmanee Sharma, David Hong, James Welsh, Andrea J. Parsons, Jardin Leleux, Stephane Ascarateil, Marie Eve Koziol, Dina Bai, Peihong Dai, Weiyi Wang, Ning Yang, Stewart Shuman, Liang Deng, Patrick Dillon, Gina Petroni, David Brenin, Kim Bullock, Walter Olson, Mark E. Smolkin, Kelly Smith, Carmel Nail, Craig L. Slingluff, Meenu Sharma, Faisal Fa’ak, Louise Janssen, Hiep Khong, Zhilan Xiao, Yared Hailemichael, Manisha Singh, Christina Vianden, Willem W. Overwijk, Andrea Facciabene, Pierini Stefano, Fang Chongyung, Stavros Rafail, Michael Nielsen, Peter Vanderslice, Darren G. Woodside, Robert V. Market, Ronald J. Biediger, Upendra K. Marathi, Kevin Hollevoet, Nick Geukens, Paul Declerck, Nathalie Joly, Laura McIntosh, Eustache Paramithiotis, Magnus Rizell, Malin Sternby, Bengt Andersson, Alex Karlsson-Parra, Rui Kuai, Lukasz Ochyl, Anna Schwendeman, James Moon, Weiwen Deng, Thomas E. Hudson, Bill Hanson, Chris S. Rae, Joel Burrill, Justin Skoble, George Katibah, Michele deVries, Peter Lauer, Thomas W. Dubensky, Xin Chen, Li Zhou, Xiubao Ren, Charu Aggarwal, Drishty Mangrolia, Roger Cohen, Gregory Weinstein, Matthew Morrow, Joshua Bauml, Kim Kraynyak, Jean Boyer, Jian Yan, Jessica Lee, Laurent Humeau, Sandra Oyola, Susan Duff, David Weiner, Zane Yang, Mark Bagarazzi, Douglas G. McNeel, Jens Eickhoff, Robert Jeraj, Mary Jane Staab, Jane Straus, Brian Rekoske, Glenn Liu, Marit Melssen, William Grosh, Nikole Varhegyi, Nadejda Galeassi, Donna H. Deacon, Elizabeth Gaughan, Maurizio Ghisoli, Minal Barve, Robert Mennel, Gladice Wallraven, Luisa Manning, Neil Senzer, John Nemunaitis, Masahiro Ogasawara, Shuichi Ota, Kaitlin M. Peace, Diane F. Hale, Timothy J. Vreeland, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Guy T. Clifton, Mark O. Hardin, Anne Toms, Na Qiao, Jennifer Litton, George E. Peoples, Elizabeth A. Mittendorf, Lila Ghamsari, Emilio Flano, Judy Jacques, Biao Liu, Jonathan Havel, Vladimir Makarov, Timothy A. Chan, Jessica B. Flechtner, John Facciponte, Stefano Ugel, Francesco De Sanctis, George Coukos, Sébastien Paris, Agnes Pottier, Laurent Levy, Bo Lu, Federica Cappuccini, Emily Pollock, Richard Bryant, Freddie Hamdy, Adrian Hill, Irina Redchenko, Hussein Sultan, Takumi Kumai, Valentyna Fesenkova, Esteban Celis, Ingrid Fernando, Claudia Palena, Justin M. David, Elizabeth Gabitzsch, Frank Jones, James L. Gulley, Mireia Uribe Herranz, Hiroshi Wada, Atsushi Shimizu, Toshihiro Osada, Satoshi Fukaya, Eiji Sasaki, Milad Abolhalaj, David Askmyr, Kristina Lundberg, Ann-Sofie Albrekt, Lennart Greiff, Malin Lindstedt, Dallas B. Flies, Tomoe Higuchi, Wojciech Ornatowski, Jaryse Harris, Sarah F. Adams, Todd Aguilera, Marjan Rafat, Laura Castellini, Hussein Shehade, Mihalis Kariolis, Dadi Jang, Rie vonEbyen, Edward Graves, Lesley Ellies, Erinn Rankin, Albert Koong, Amato Giaccia, Reham Ajina, Shangzi Wang, Jill Smith, Mariaelena Pierobon, Sandra Jablonski, Emanuel Petricoin, Louis M. Weiner, Lorcan Sherry, John Waller, Mark Anderson, Alison Bigley, Chantale Bernatchez, Cara Haymaker, Harriet Kluger, Michael Tetzlaff, Natalie Jackson, Ivan Gergel, Mary Tagliaferri, Patrick Hwu, Mario Snzol, Michael Hurwitz, Theresa Barberi, Allison Martin, Rahul Suresh, David Barakat, Sarah Harris-Bookman, Charles Drake, Alan Friedman, Sara Berkey, Stephanie Downs-Canner, Robert P. Edwards, Tyler Curiel, Kunle Odunsi, Tullia C. Bruno, Brandon Moore, Olivia Squalls, Peggy Ebner, Katherine Waugh, John Mitchell, Wilbur Franklin, Daniel Merrick, Martin McCarter, Brent Palmer, Jeffrey Kern, Dario Vignali, Jill Slansky, Anissa S. H. Chan, Xiaohong Qiu, Kathryn Fraser, Adria Jonas, Nadine Ottoson, Keith Gordon, Takashi O. Kangas, Steven Leonardo, Kathleen Ertelt, Richard Walsh, Mark Uhlik, Jeremy Graff, Nandita Bose, Ravi Gupta, Nitin Mandloi, Kiran Paul, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan, Amitabha Chaudhuri, Yu Chen, Jing Lin, Yun-bin Ye, Chun-wei Xu, Gang Chen, Zeng-qing Guo, Andrey Komarov, Alex Chenchik, Michael Makhanov, Costa Frangou, Yi Zheng, Carla Coltharp, Darryn Unfricht, Ryan Dilworth, Leticia Fridman, Linying Liu, Milind Rajopadhye, Peter Miller, Fernando Concha-Benavente, Julie Bauman, Sumita Trivedi, Raghvendra Srivastava, James Ohr, Dwight Heron, Uma Duvvuri, Seungwon Kim, Heather Torrey, Toshi Mera, Yoshiaki Okubo, Eva Vanamee, Rosemary Foster, Denise Faustman, Edward Stack, Daisuke Izaki, Kristen Beck, Dan Tong Jia, Paul Armenta, Ashley White-Stern, Douglas Marks, Bret Taback, Basil Horst, Laura Hix Glickman, David B. Kanne, Kelsey S. Gauthier, Anthony L. Desbien, Brian Francica, Justin L. Leong, Leonard Sung, Ken Metchette, Shailaja Kasibhatla, Anne Marie Pferdekamper, Lianxing Zheng, Charles Cho, Yan Feng, Jeffery M. McKenna, John Tallarico, Steven Bender, Chudi Ndubaku, Sarah M. McWhirter, Elena Gonzalez Gugel, Charles J. M. Bell, Adiel Munk, Luciana Muniz, Nina Bhardwaj, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nathalie Scholler, Catherine Yin, Pien Van der Meijs, Andrew M. Prantner, Cecile M. Krejsa, Leia Smith, Brian Johnson, Daniel Branstetter, Paul L. Stein, Juan C. Jaen, Joanne BL Tan, Ada Chen, Timothy Park, Jay P. Powers, Holly Sexton, Guifen Xu, Steve W. Young, Ulrike Schindler, Wentao Deng, David John Klinke, Hannah M. Komar, Gregory Serpa, Omar Elnaggar, Philip Hart, Carl Schmidt, Mary Dillhoff, Ming Jin, Michael C. Ostrowski, Madhuri Koti, Katrina Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Charles Graham, Andrew Craig, Julie-Ann Francis, Beatrix Kotlan, Timea Balatoni, Emil Farkas, Laszlo Toth, Mihaly Ujhelyi, Akos Savolt, Zoltan Doleschall, Szabolcs Horvath, Klara Eles, Judit Olasz, Orsolya Csuka, Miklos Kasler, Gabriella Liszkay, Eytan Barnea, Collin Blakely, Patrick Flynn, Reid Goodman, Raphael Bueno, David Sugarbaker, David Jablons, V. Courtney Broaddus, Brian West, Paul R. Kunk, Joseph M. Obeid, Kevin Winters, Patcharin Pramoonjago, Edward B. Stelow, Todd W. Bauer, Osama E. Rahma, Adam Lamble, Yoko Kosaka, Fei Huang, Kate A. Saser, Homer Adams, Christina E. Tognon, Ted Laderas, Shannon McWeeney, Marc Loriaux, Jeffery W. Tyner, Brian J. Druker, Evan F. Lind, Zhuqing Liu, Shanhong Lu, Lawrence P. Kane, Gulidanna Shayan, Julia Femel, Ryan Lane, Jamie Booth, Amanda W. Lund, Anthony Rodriguez, Victor H. Engelhard, Alessandra Metelli, Bill X. Wu, Caroline W. Fugle, Rachidi Saleh, Shaoli Sun, Jennifer Wu, Bei Liu, Zihai Li, Zachary S. Morris, Emily I. Guy, Clinton Heinze, Jasdeep Kler, Monica M. Gressett, Lauryn R. Werner, Stephen D. Gillies, Alan J. Korman, Hans Loibner, Jacquelyn A. Hank, Alexander L. Rakhmilevich, Paul M. Harari, Paul M. Sondel, Erica Huelsmann, Joseph Broucek, Dorothee Brech, Tobias Straub, Martin Irmler, Johannes Beckers, Florian Buettner, Elke Schaeffeler, Matthias Schwab, Elfriede Noessner, Alison Wolfreys, Andre Da Costa, John Silva, Andrea Crosby, Ludovicus Staelens, Graham Craggs, Annick Cauvin, Sean Mason, Alison M. Paterson, Andrew C. Lake, Caroline M. Armet, Rachel W. O’Connor, Jonathan A. Hill, Emmanuel Normant, Ammar Adam, Detlev M. Biniszkiewicz, Scott C. Chappel, Vito J. Palombella, Pamela M. Holland, Annette Becker, Manmohan R. Leleti, Eric Newcomb, Joanne B. L. Tan, Suthee Rapisuwon, Arash Radfar, Kellie Gardner, Geoffrey Gibney, Michael Atkins, Keith R. Rennier, Robert Crowder, Ping Wang, Russell K. Pachynski, Rosa M. Santana Carrero, Sarai Rivas, Figen Beceren-Braun, Scott Anthony, Kimberly S. Schluns, Deepali Sawant, Maria Chikina, Hiroshi Yano, Creg Workman, Elise Salerno, Ileana Mauldin, Donna Deacon, Sofia Shea, Joel Pinczewski, Thomas Gajewski, Stefani Spranger, Brendan Horton, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Raj K. Puri, Randy F. Sweis, Riyue Bao, Jason Luke, Marie-Nicole Theodoraki, Frances-Mary Mogundo, Haejung Won, Dayson Moreira, Chan Gao, Xingli Zhao, Priyanka Duttagupta, Jeremy Jones, Massimo D’Apuzzo, and Sumanta Pal

Subjects
0301 basic medicine, Pharmacology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Cancer, Immunotherapy, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, Molecular Medicine, Immunology and Allergy, Medicine, business
Abstract

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Published
2016
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14. Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines

Author

Margaret A, Tempero, Mokenge P, Malafa, Stephen W, Behrman, Al B, Benson, Ephraim S, Casper, E Gabriela, Chiorean, Vincent, Chung, Steven J, Cohen, Brian, Czito, Anitra, Engebretson, Mary, Feng, William G, Hawkins, Joseph, Herman, John P, Hoffman, Andrew, Ko, Srinadh, Komanduri, Albert, Koong, Andrew M, Lowy, Wen Wee, Ma, Nipun B, Merchant, Sean J, Mulvihill, Peter, Muscarella, Eric K, Nakakura, Jorge, Obando, Martha B, Pitman, Sushanth, Reddy, Aaron R, Sasson, Sarah P, Thayer, Colin D, Weekes, Robert A, Wolff, Brian M, Wolpin, Jennifer L, Burns, and Deborah A, Freedman-Cass

Subjects
Pancreatic Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, Guidelines as Topic, Adenocarcinoma, Neoadjuvant Therapy
Abstract

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.

Published
2014

15. First study of on-treatment volumetric imaging during respiratory gated VMAT

Author

Kihwan, Choi, Lei, Xing, Albert, Koong, and Ruijiang, Li

Subjects
Respiratory-Gated Imaging Techniques, Lung Neoplasms, Treatment Outcome, Phantoms, Imaging, Humans, Pilot Projects, Radiotherapy Dosage, Radiotherapy, Intensity-Modulated, Radionuclide Imaging, Tomography, X-Ray Computed, Radiotherapy, Image-Guided, Medical Physics Letter
Abstract

To obtain on-treatment volumetric patient anatomy during respiratory gated volumetric modulated arc therapy (VMAT).On-board imaging device integrated with Linacs offers a viable tool for obtaining patient anatomy during radiation treatment delivery. In this study, the authors acquired beam-level kV images during gated VMAT treatments using a Varian TrueBeam™STx Linac. These kV projection images are triggered by a respiratory gating signal and can be acquired immediately before treatment MV beam on at every breathing cycle during delivery. Because the kV images are acquired with an on-board imaging device during a rotational arc therapy, they provide the patient anatomical information from many different angles or projection views (typically 20-40). To reconstruct the volumetric image representing patient anatomy during the VMAT treatment, the authors used a compressed sensing method with a fast first-order optimization algorithm. The conventional FDK reconstruction was also used for comparison purposes. The method was tested on a dynamic anthropomorphic physical phantom as well as a lung patient.The reconstructed volumetric images for a dynamic anthropomorphic physical phantom and a lung patient showed clearly visible soft-tissue target as well as other anatomical structures, with the proposed compressed sensing-based image reconstruction method. Compared with FDK, the compressed sensing method leads to a ≈ two and threefold increase in contrast-to-noise ratio around the target area in the phantom and patient case, respectively.The proposed technique provides on-treatment volumetric patient anatomy, with only a fraction (10%) of the imaging dose used in conventional CBCT procedures. This anatomical information may be valuable for geometric verification and treatment guidance, and useful for verification of treatment dose delivery, accumulation, and adaptation in the future.

Published
2013

16. Contributors

Author

Andre Abitbol, David H. Abramson, Ranjana Advani, Mohammed Ahmed, Oguz Akin, Kaled M. Alektiar, Michael Alvarado, Howard I. Amols, John G. Armstrong, Barbara L. Asselin, Igor J. Barani, Christopher A. Barker, Luc Beaulieu, Joel S. Bedford, Adrian C. Begg, Søren M. Bentzen, Alison Bevan, Luc M. Bidaut, Eleanor A. Blakely, J. Martin Brown, Chandra M. Burman, Oren Cahlon, Matthew D. Callister, Peter Carroll, Joseph R. Castro, Daniel T. Chang, Susan M. Chang, Devron H. Char, Allen M. Chen, Andy Chen, Chien Peter Chen, Dennis S. Chi, Prakash Chinnaiyan, Robert W. Cho, Walter H. Choi, Lanceford M. Chong, Orlo H. Clark, Michael F. Clarke, Fergus V. Coakley, A. Dimitrios Colevas, Louis S. Constine, Steven Coutre, Bruce Culliney, Inder K. Daftari, Sally J. DeNardo, Maximilian Diehn, Paul J. Donald, Ira J. Dunkel, Mark Dunphy, Linda R. Duska, Sharon C. Dutton, Michael S.B. Edwards, Diana L. Farmer, Edith J. Filion, Nancy J. Fischbein, George A. Fisher, Paul Graham Fisher, James M. Ford, Barbara Fowble, Jennifer M. Fu, Karen K. Fu, Zvi Y. Fuks, Ignacio Azinovic Gamo, Kristen N. Ganjoo, Amato J. Giaccia, Iris C. Gibbs, Michael T. Gillin, Michelle S. Ginsberg, Brian J. Goldsmith, Daniel R. Gomez, Karyn Goodman, Alexander R. Gottschalk, Edward E. Graves, Sheryl Green, Roy C. Grekin, Ravinder K. Grewal, Leonard L. Gunderson, Philip H. Gutin, Daphne A. Haas-Kogan, Michael G. Haddock, Ester M. Hammond, Paul M. Harari, Louis B. Harrison, Lauren C. Harshman, Melanie G. Gephart Hayden, Russell W. Hinerman, Alice Y. Ho, Richard T. Hoppe, Sandra J. Horning, Hedvig Hricak, Annie Hsu, I-Chow Joe Hsu, Kenneth S. Hu, Melissa M. Hudson, John L. Humm, Peter Johannet, Michael J. Kaplan, Daniel S. Kapp, Mohammed Kashani-Sabet, Laurence Katznelson, Noah D. Kauff, Paul J. Keall, Youn H. Kim, Christopher R. King, Susan J. Knox, Cameron J. Koch, Marisa M. Kollmeier, Albert Koong, Lee M. Krug, Pamela L. Kunz, Michael P. La Quaglia, David A. Larson, Steven Larson, Edward R. Laws, Quynh-Thu Le, Andrew K. Lee, Nancy Lee, Gloria C. Li, Patricia Lillis-Hearne, C. Clifton Ling, David E. Linstadt, Jay S. Loeffler, Billy W. Loo, Thomas LoSasso, Gikas S. Mageras, Lawrence Margolis, Brian P. Marr, Katherine K. Matthay, Sean M. McBride, Beryl McCormick, Michael W. McDermott, Michelle Melisko, Karine Michaud, Robert C. Miller, Bruce D. Minsky, Kavita K. Mishra, Radhe Mohan, Robert J. Myerson, Subir Nag, Jean L. Nakamura, Ashwatha Narayana, Dattatreyudu Nori, Jeffrey A. Norton, Colin G. Orton, Matthew B. Parliament, Paula L. Petti, Theodore Locke Phillips, Carlos E. Pineda, Isabel M. Pires, Jean Pouliot, Joseph Presti, Jeanne M. Quivey, Andrew Quon, Rachel Rabinovitch, Lawrence Recht, Sunil A. Reddy, Andreas Rimner, Mack Roach, Jonathan E. Rosenberg, Seth A. Rosenthal, Kenneth E. Rosenzweig, Lawrence N. Rothenberg, Daniel Ruan, Anthony H. Russell, Janice Ryu, Amy C. Schefler, Tracey E. Schefter, Daniela Schulz-Ertner, Karen D. Schupak, Granger R. Scruggs, Roy B. Sessions, Dennis C. Shrieve, Eric J. Small, Penny K. Sneed, Marnee M. Spierer, Sandy Srinivas, Paul Stauffer, Richard G. Stock, Xiaorong Sun, Susan M. Swetter, Patrick S. Swift, Margaret A. Tempero, Hirohiko Tsujii, Francesco Tuniz, Raul C. Urtasun, Alan P. Venook, Lynn J. Verhey, Raquel Wagman, Kent Wallner, Robert Warren, Irving L. Weissman, Mark L. Welton, Moody D. Wharam, George David Wilson, Paul F. Wilson, Suzanne L. Wolden, Shiao Y. Woo, Ping Xia, Lei Xing, Joachim Yahalom, Yoshiya Yamada, Sue S. Yom, and Michael J. Zelefsky

Published
2010
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17. Enhanced 4D cone-beam CT with inter-phase motion model

Author

Tianfang, Li, Albert, Koong, and Lei, Xing

Subjects
Respiratory Mechanics, Humans, Radiographic Image Interpretation, Computer-Assisted, Models, Theoretical, Tomography, X-Ray Computed
Abstract

Four-dimensional (4D) cone-beam CT (CBCT) is commonly obtained by respiratory phase binning of the projections, followed by independent reconstructions of the rebinned data in each phase bin. Due to the significantly reduced number of projections per reconstruction, the quality of the 4DCBCT images is often degraded by view-aliasing artifacts easily seen in the axial view. Acquisitions using multiple gantry rotations or slow gantry rotation can increase the number of projections and substantially improve the 4D images. However, the extra cost of the scan time may set fundamental limits to their applications in clinics. Improving the trade-off between image quality and scan time is the key to making 4D onboard imaging practical and more useful. In this article, we present a novel technique toward high-quality 4DCBCT imaging without prolonging the acquisition time, referred to as the "enhanced 4DCBCT". The method correlates the data in different phase bins and integrates the internal motion into the 4DCBCT image formulation. Several strategies of the motion derivation are discussed, and the resultant images are assessed with numerical simulations as well as a clinical case.

Published
2007

18. Reducing respiratory motion artifacts in positron emission tomography through retrospective stacking

Author

Brian, Thorndyke, Eduard, Schreibmann, Albert, Koong, and Lei, Xing

Subjects
Pancreatic Neoplasms, Radiographic Image Enhancement, Motion, Phantoms, Imaging, Data Interpretation, Statistical, Positron-Emission Tomography, Respiration, Liver Neoplasms, Humans, Artifacts, Algorithms, Software, Pattern Recognition, Automated
Abstract

Respiratory motion artifacts in positron emission tomography (PET) imaging can alter lesion intensity profiles, and result in substantially reduced activity and contrast-to-noise ratios (CNRs). We propose a corrective algorithm, coined "retrospective stacking" (RS), to restore image quality without requiring additional scan time. Retrospective stacking uses b-spline deformable image registration to combine amplitude-binned PET data along the entire respiratory cycle into a single respiratory end point. We applied the method to a phantom model consisting of a small, hot vial oscillating within a warm background, as well as to 18FDG-PET images of a pancreatic and a liver patient. Comparisons were made using cross-section visualizations, activity profiles, and CNRs within the region of interest. Retrospective stacking was found to properly restore the lesion location and intensity profile in all cases. In addition, RS provided CNR improvements up to three-fold over gated images, and up to five-fold over ungated data. These phantom and patient studies demonstrate that RS can correct for lesion motion and deformation, while substantially improving tumor visibility and background noise.

Published
2006

19. A phase II multi-institutional study to evaluate gemcitabine and fractionated stereotactic body radiotherapy for unresectable, locally advanced pancreatic adenocarcinoma

Author

Joseph M. Herman, Daniel Tandel Chang, Karyn A. Goodman, Aaron Tyler Wild, Dan Laheru, Lei Zheng, Luis A. Diaz, Dung Thi Le, Siva P Raman, Jeffrey P Leal, Muhammad Ali Chaudhry, Elizabeth Sugar, Laurie Ann Columbo, Ashlyn Tom, Maneesha R Limaye, Barish H Edil, Katharine Oteiza, Amy Hacker-Prietz, Christopher Lee Wolfgang, and Albert Koong

Subjects
Cancer Research, Oncology
Abstract

4045 Background: Phase I/II studies with single-fraction (25 Gy) stereotactic body radiotherapy (SBRT) for pancreatic ductal adenocarcinoma (PDA) have shown local progression free survival (LPFS) rates of >90%, but are limited by late GI toxicity and minimal tumor response. We performed a phase II multi-center trial of gemcitabine (GEM) and fractionated SBRT to determine if a high rate of LPFS with reduced toxicity could be achieved. Methods: After multidisciplinary review, 32 pts with locally advanced PDA received GEM in sequence with SBRT (6.6 Gy in 5 consecutive daily fractions, 33 Gy total). LPFS, metastasis free survival (MFS), and overall survival (OS) were measured from date of tissue diagnosis. Objective tumor response (OTR) was assessed by RECIST/PERCIST. EORTC QLQ-C30/PAN26 questionnaires were used to measure QOL. Results: Median f-up was 12 mos (range, 2-23). Mean age was 69.9 yrs (SD, 9.8) and 62% were male. Pts received a mean of 2.2 (SD, 1.0) GEM doses prior to SBRT and 8.3 (SD, 5.6) doses total. All pts completed SBRT. Median OS was 15.9 months (95% CI, 12.7-18.8). Stratification by CA19-9 > or < 90 at diagnosis yielded a hazard ratio of 6.2 for > 90 (p=0.021). Median LPFS has not been reached and median MFS was 10.2 mos (95% CI, 2.9-17.5). LPFS rate at 1 year was 87%. OTR on CT was seen in 41%, while 41% had stable disease and 18% progressed. Tumor metabolic activity decreased in 17/18 patients with pre/post-SBRT PET available. Mean peak SUV was 4.0 pre-SBRT versus 2.4 post-SBRT (p=0.002). Median CA19-9 was reduced from 124.7 prior to SBRT to 43.9 afterwards. Acute toxicity included: grade 2 anorexia (37%), fatigue (28%), nausea (22%), abd pain (19%), weight loss (9%), diarrhea (3%); gr 3 nausea (9%); and gr 4 nausea (6%). Late gr ≥3 GI toxicity was seen in 9%. Mean QOL score 4 wks post-SBRT was similar to baseline (p=0.38). At 6 mos there was a trend towards improved QOL (p=0.07). Conclusions: Fractionated SBRT with GEM achieves high rates of LPFS and tumor response. Minimal grade ≥3 acute and late toxicity was observed. SBRT is more likely to benefit patients with Ca-19-9

Published
2012
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23. Combining deep learning with anatomical analysis for segmentation of the portal vein for liver SBRT planning.

Author

Bulat Ibragimov, Diego Toesca, Daniel Chang, Albert Koong, and Lei Xing

Subjects
DEEP learning, PORTAL vein, RADIOTHERAPY treatment planning
Abstract

Automated segmentation of the portal vein (PV) for liver radiotherapy planning is a challenging task due to potentially low vasculature contrast, complex PV anatomy and image artifacts originated from fiducial markers and vasculature stents. In this paper, we propose a novel framework for automated segmentation of the PV from computed tomography (CT) images. We apply convolutional neural networks (CNNs) to learn the consistent appearance patterns of the PV using a training set of CT images with reference annotations and then enhance the PV in previously unseen CT images. Markov random fields (MRFs) were further used to smooth the results of the enhancement of the CNN enhancement and remove isolated mis-segmented regions. Finally, CNN-MRF-based enhancement was augmented with PV centerline detection that relied on PV anatomical properties such as tubularity and branch composition. The framework was validated on a clinical database with 72 CT images of patients scheduled for liver stereotactic body radiation therapy. The obtained accuracy of the segmentation was 0.83 and 1.08 mm in terms of the median Dice coefficient and mean symmetric surface distance, respectively, when segmentation is encompassed into the PV region of interest. The obtained results indicate that CNNs and anatomical analysis can be used for the accurate segmentation of the PV and potentially integrated into liver radiation therapy planning. [ABSTRACT FROM AUTHOR]

Published
2017
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24. Extracranial Radiosurgery Using the CyberKnife.

Author

Pantaleo Romanelli, Steven D. Chang, Albert Koong, and John R. Adler

Subjects
*RADIOSURGERY, *RADIATION, *MEDICAL imaging systems
Abstract

SUMMARY: Several technical drawbacks can limit the clinical applications of conventional stereotactic radiosurgery: It requires the attachment of a rigid frame that immobilizes the patient and provides a frame of reference for aiming radiation beams, which is uncomfortable to patients, complicates fractional treatment, can impede beam aiming and introduce image artifacts, and generally restricts the application of stereotactic radiosurgery to the cranium and the high cervical spine. The CyberKnife solves these problems by using real-time, computer-based image guidance technology to aim a lightweight LINAC with a highly maneuverable robotic arm to deliver conformal radiation doses to tumors of all shapes, all without a rigid frame. Navigation is accomplished using skeletal features or implanted fiducials, and the system adjusts the aim of radiation beams frequently based on changes in patient position. Recent improvements in the system (ie, the introduction of flat-panel amorphous silicon X-ray cameras) have made it applicable to the treatment of tumors throughout the body, including in organs (eg, lungs and pancreas) that move with respiration. The authors summarize the characteristics of the CyberKnife system, describe their recent work adapting the system to treat extracranial tumors, and provide a brief update of their experience treating adenocarcinoma of the pancreas using the system. [ABSTRACT FROM AUTHOR]

Published
2003
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32. ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth.

Author

Hart, Lori S., Cunningham, John T., Datta, Tatini, Dey, Souvik, Tameire, Feven, Lehman, Stacey L., Bo Qiu, Haiyan Zhang, Cerniglia, George, Meixia Bi, Yan Li, Yan Gao, Huayi Liu, Changhong Li, Maity, Amit, Thomas-Tikhonenko, Andrei, Perl, Alexander E., Albert Koong, Fuchs, Serge Y., and Diehl, J. Alan

Subjects
*ENDOPLASMIC reticulum, *PHYSIOLOGICAL stress, *TUMOR growth, *ONCOGENES, *APOPTOSIS, *CARCINOGENESIS, *LABORATORY mice
Abstract

The proto-oncogene c-Myc paradoxically activates both proliferation and apoptosis. In the pathogenic state, c-Myc-induced apoptosis is bypassed via a critical, yet poorly understood escape mechanism that promotes cellular transformation and tumorigenesis. The accumulation of unfolded proteins in the ER initiates a cellular stress program termed the unfolded protein response (UPR) to support cell survival. Analysis of spontaneous mouse and human lymphomas demonstrated significantly higher levels of UPR activation compared with normal tissues. Using multiple genetic models, we demonstrated that c-Myc and N-Myc activated the PERK/ eIF2a/ATF4 arm of the UPR, leading to increased cell survival via the induction of cytoprotective autophagy. Inhibition of PERK significantly reduced Myc-induced autophagy, colony formation, and tumor formation. Moreover, pharmacologic or genetic inhibition of autophagy resulted in increased Myc-dependent apoptosis. Mechanistically, we demonstrated an important link between Myc-dependent increases in protein synthesis and UPR activation. Specifically, by employing a mouse minute (L24+/-) mutant, which resulted in wild-type levels of protein synthesis and attenuation of Myc-induced lymphomagenesis, we showed that Myc-induced UPR activation was reversed. Our findings establish a role for UPR as an enhancer of c-Myc-induced transformation and suggest that UPR inhibition may be particularly effective against malignancies characterized by c-Myc overexpression. [ABSTRACT FROM AUTHOR]

Published
2012
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