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1. Prospective phase II trial of preoperative hypofractionated proton therapy for extremity and truncal soft tissue sarcoma: the PRONTO study rationale and design

Author

Emile Gogineni, Hao Chen, Chen Hu, Karim Boudadi, Jessica Engle, Adam Levine, and Curtiland Deville

Subjects
Sarcoma, Extremity, Preoperative, Neoadjuvant, Hypofractionated, Radiation, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma. Methods Our study titled “PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)” is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2–12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response. Discussion PRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting. Trial registration: NCT05917301 (registered 23/6/2023).

Published
2024
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2. Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures

Author

Drew M Pardoll, Evan Lipson, John-William Sidhom, Karim Boudadi, Robert Anders, Dung T Le, Luis A Diaz, Nicolas Llosa, Janis Taube, Lingling Chen, Teniola F Oke, Christian F Meyer, Laurene S Cheung, Thomas B Schaffer, Jillian T Ngo, John McMahon Gross, and Holly Kemberling

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Undifferentiated pleomorphic sarcoma (UPS), an aggressive soft-tissue sarcoma of adults, has been characterized by low tumor mutational burden (TMB) and high copy number alterations. Clinical trials of programmed death-1 (PD-1) blockade in UPS have reported widely varying efficacy. We describe two patients with recurrent scalp UPS that experienced clinical benefit from PD-1 blockade. These tumors had high TMB with a UV-induced mutational pattern. Analysis of additional head and neck UPS cases identified five out of seven tumors with high TMB and an ultraviolet (UV) mutational signature. Head and neck UPS tumors also had increased programmed death-ligand 1 (PD-L1) expression and CD8+ T cell infiltration as compared with UPS tumors arising from other sites. In summary, we found that UPS tumors of the head and neck, but not elsewhere, have a PD-L1+, T-cell-inflamed tumor microenvironment and high TMB, suggesting that these tumors represent a distinct genetic subgroup of UPS for which immune checkpoint inhibitor therapy might be effective.

Published
2021
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4. Diffuse Hypopigmentation Followed by Hyperpigmentation in an African American Woman with Hemangiopericytoma Treated with Dasatinib

Author

Karim Boudadi and Rashmi Chugh

Subjects
sarcoma, skin pigmentation, tyrosine kinase inhibitor (tki), Medicine
Abstract

Dasatinib is a second-generation multi-target tyrosine kinase inhibitor (TKI) that has activity against many imatinib-resistant BCR-ABL mutant forms, Src, and c-Kit tyrosine kinases. While skin hypopigmentation is a well recognized adverse effect of first generation TKIs; it has rarely been reported with dasatinib. We report a unique case of diffuse cutaneous hypopigmentation induced by dasatinib followed by hyperpigmentation occurring in the same patient. A 52-year-old African American female with a history of metastatic hemangiopericytoma was initiated on dasatinib as part of a clinical trial. After 2 months of treatment, she developed generalized skin hypopigmentation. Within 1 month of discontinuing the drug, the patient’s skin pigmentation returned to normal. However, she then developed diffuse skin hyperpigmentation over the next couple of months. The hyperpigmentation was self-limited, and eventually resolved after several months.

Published
2014
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5. Nivolumab plus ipilimumab, with or without enzalutamide, in AR‐V7‐expressing metastatic castration‐resistant prostate cancer: A phase‐2 nonrandomized clinical trial

Author

Karim Boudadi, Wei Fu, Joseph D. Schonhoft, Jun Luo, Eugene Shenderov, Mario A. Eisenberger, Drew M. Pardoll, Michael A. Carducci, Rana Harb, Alice Jordan, Emmanuel S. Antonarakis, James R. Eshleman, Rana Sullivan, Donna Dowling, Adam Jendrisak, Hao Wang, and Charles G. Drake

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Urology, Phases of clinical research, Antineoplastic Agents, Ipilimumab, Gastroenterology, Article, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, Internal medicine, Nitriles, Phenylthiohydantoin, medicine, Humans, Protein Isoforms, Enzalutamide, Adverse effect, Immune Checkpoint Inhibitors, business.industry, Hazard ratio, Androgen Antagonists, Prognosis, medicine.disease, Prostatic Neoplasms, Castration-Resistant, Nivolumab, Treatment Outcome, 030104 developmental biology, Oncology, chemistry, Receptors, Androgen, 030220 oncology & carcinogenesis, Benzamides, Cohort, Drug Therapy, Combination, business, medicine.drug
Abstract

Background AR-V7-positive metastatic prostate cancer is a lethal phenotype with few treatment options and poor survival. Methods The two-cohort nonrandomized Phase 2 study of combined immune checkpoint blockade for AR-V7-expressing metastatic castration-resistant prostate cancer (STARVE-PC) evaluated nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg), without (Cohort 1) or with (Cohort 2) the anti-androgen enzalutamide. Co-primary endpoints were safety and prostate-specific antigen (PSA) response rate. Secondary endpoints included time-to-PSA-progression-free survival (PSA-PFS), time-to-clinical/radiographic-PFS, objective response rate (ORR), PFS lasting greater than 24 weeks, and overall survival (OS). Results Thirty patients were treated with ipilimumab plus nivolumab (N = 15, Cohort 1, previously reported), or ipilimumab plus nivolumab and enzalutamide (N = 15, Cohort 2) in patients previously progressing on enzalutamide monotherapy. PSA response rate was 2/15 (13%) in cohort 1 and 0/15 in cohort 2, ORR was 2/8 (25%) in Cohort 1 and 0/9 in Cohort 2 in those with measureable disease, median PSA-PFS was 3.0 (95% confidence interval [CI]: 2.1-NR) in cohort 1 and 2.7 (95% CI: 2.1-5.9) months in cohort 2, and median PFS was 3.7 (95% CI: 2.8-7.5) in cohort 1 and 2.9 (95% CI: 1.3-5.8) months in cohort 2. Three of 15 patients in cohort 1 (20%, 95% CI: 7.1%-45.2%) and 4/15 patients (26.7%, 95% CI: 10.5%-52.4%) in cohort 2 achieved a durable PFS lasting greater than 24 weeks. Median OS was 8.2 (95% CI: 5.5-10.4) in cohort 1 and 14.2 (95% CI: 8.5-NA) months in cohort 2. Efficacy results were not statistically different between cohorts. Grade-3/4 adverse events occurred in 7/15 cohort 1 patients (46%) and 8/15 cohort 2 patients (53%). Combined cohort (N = 30) baseline alkaline phosphatase and cytokine analysis suggested improved OS for patients with lower alkaline phosphatase (hazards ratio [HR], 0.30; 95% CI: 0.11-0.82), lower circulating interleukin-7 (IL-7) (HR, 0.24; 95% Cl: 0.06-0.93) and IL-6 (HR, 0.13; 95% Cl: 0.03-0.52) levels, and higher circulating IL-17 (HR, 4.53; 95% CI: 1.47-13.93) levels. There was a trend towards improved outcomes in men with low sPD-L1 serum levels. Conclusion Nivolumab plus ipilimumab demonstrated only modest activity in patients with AR-V7-expressing prostate cancer, and was not sufficient to justify further exploration in unselected patients. Stratification by baseline alkaline phosphatase and cytokines (IL-6, -7, and -17) may be prognostic for outcomes to immunotherapy.

Published
2021

6. Dynamic cell free HPV DNA is an early measure of treatment responsiveness in patients receiving induction chemotherapy for HPV-related head and neck cancer

Author

Linda (Yilin) Cao, Ana Ponce Kiess, Michael Hwang, Karim Boudadi, Vassiliki Saloura, Austin Mattox, Emily Gramiccioni, David Schmitt, Jennifer Preston, Anna Malgorzata Starus, Frederick S. Jones, Tanguy Y. Seiwert, and Harry Quon

Subjects
Cancer Research, Oncology
Abstract

6062 Background: Induction chemotherapy (IC) is being studied as a chemoradiation (CRT) de-intensification strategy in HPV-related head and neck cancer (HNC), but using imaging response for eligibility selection is distinctly limited by delayed correlation with biological response and difficulty in distinguishing active tumor from treatment effect. We report serial cell free HPV DNA (cfHPV DNA) dynamics as a quantitative measure of early treatment responsiveness for HPV-related HNC patients receiving IC followed by CRT. Methods: Patients with high-risk HPV-positive (by in situ hybridization), locally advanced HNC who received IC followed by definitive CRT were enrolled starting on Sept 26, 2021. Patients received 1-2 cycles of platinum/taxane IC prior to initiating standard-dose CRT. Peripheral blood cfHPV DNA levels were measured biweekly during IC and weekly during CRT with the SafeSEQ HPV test from Sysmex Inostics, an NGS-based, CLIA-certified assay designed to sensitively detect and quantify HPV16 and HPV18 DNA in plasma. Tumor volumes were assessed on the pre- and post-IC planning CT scans by the treating radiation oncologist. Results: To date, 72 plasma samples have been processed across 11 enrolled patients with median age 66 years (range: 35-79). The primary disease sites included 7 oropharynx (OPX), 1 sinonasal, 2 nasopharyngeal, and 1 larynx. All patients had at least cT3 disease or cN3 disease (AJCC 8), with 6 patients having cT4 disease. Five (45.5%) have a smoking history, each > 10 pack-years. We report cfHPV DNA and tumor volume measurements at key timepoints for the 8 patients who have completed IC below. Conclusions: Serial cfHPV DNA identifies a group of locally advanced HPV-related HNC patients who have complete/near-complete cfDNA clearance during IC. This may provide an earlier readout of individualized treatment responsiveness compared to radiologic assessment, and may therefore be a preferred metric for CRT de-intensification eligibility. Clearance velocity will be evaluated with our granular biweekly IC and weekly CRT cfHPV DNA dataset to help further elucidate tumor response kinetics with this paradigm. [Table: see text]

Published
2022

7. Anti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures

Author

Teniola Oke, Thomas B. Schaffer, Evan J. Lipson, Dung T. Le, Christian F. Meyer, Lingling Chen, John Mc Mahon Gross, Laurene S. Cheung, Jillian T. Ngo, Nicolas J. Llosa, Janis M. Taube, Holly Kemberling, Karim Boudadi, John-William Sidhom, Robert A. Anders, Drew M. Pardoll, and Luis A. Diaz

Subjects
0301 basic medicine, Male, Cancer Research, sarcoma, medicine.medical_treatment, Immunology, Programmed Cell Death 1 Receptor, Case Report, medicine.disease_cause, Undifferentiated Pleomorphic Sarcoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Biomarkers, Tumor, Immunology and Allergy, Humans, RC254-282, Pharmacology, Mutation, Tumor microenvironment, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell Differentiation, Immunotherapy, Middle Aged, medicine.disease, Blockade, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Scalp, tumor biomarkers, Cancer research, Molecular Medicine, Sarcoma, business, CD8
Abstract

Undifferentiated pleomorphic sarcoma (UPS), an aggressive soft-tissue sarcoma of adults, has been characterized by low tumor mutational burden (TMB) and high copy number alterations. Clinical trials of programmed death-1 (PD-1) blockade in UPS have reported widely varying efficacy. We describe two patients with recurrent scalp UPS that experienced clinical benefit from PD-1 blockade. These tumors had high TMB with a UV-induced mutational pattern. Analysis of additional head and neck UPS cases identified five out of seven tumors with high TMB and an ultraviolet (UV) mutational signature. Head and neck UPS tumors also had increased programmed death-ligand 1 (PD-L1) expression and CD8+ T cell infiltration as compared with UPS tumors arising from other sites. In summary, we found that UPS tumors of the head and neck, but not elsewhere, have a PD-L1+, T-cell-inflamed tumor microenvironment and high TMB, suggesting that these tumors represent a distinct genetic subgroup of UPS for which immune checkpoint inhibitor therapy might be effective.

Published
2021

8. The efficacy of anti-PD-1 immune checkpoint inhibitor in nasopharyngeal carcinoma

Author

Jong Chul Park, Karim Boudadi, Won Jin Ho, Julia Durbeck, and Hyunseok Kang

Subjects
Adult, Male, Cancer Research, Nasopharyngeal Carcinoma, Adolescent, business.industry, Immune checkpoint inhibitors, Anti pd 1, Middle Aged, medicine.disease, Young Adult, Oncology, Nasopharyngeal carcinoma, medicine, Cancer research, Humans, Female, Oral Surgery, business, Immune Checkpoint Inhibitors, Aged
Published
2020

9. Ipilimumab plus nivolumab and DNA-repair defects in AR-V7-expressing metastatic prostate cancer

Author

Michael A. Carducci, Daniel L. Suzman, Brendan A. Veeneman, Rana Sullivan, Thomas R. Nirschl, Ryon P. Graf, Jun Luo, Ryan Dittamore, Charles G. Drake, Mario A. Eisenberger, Emmanuel S. Antonarakis, Michael C. Haffner, James R. Eshleman, Rana Harb, Hao Wang, Wei Fu, Yipeng Wang, Karim Boudadi, James R. White, Brandon Luber, Scott A. Tomlins, Victor E. Velculescu, John L. Silberstein, Alan K. Meeker, Valsamo Anagnostou, Noushin Niknafs, Adam Jendrisak, and Donna Dowling

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, DNA repair, Ipilimumab, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Circulating tumor cell, Prostate, Internal medicine, medicine, ipilimumab, nivolumab, business.industry, Microsatellite instability, prostate cancer, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Population study, Nivolumab, AR-V7, business, ERCC4, Research Paper, medicine.drug
Abstract

AR-V7-expressing metastatic prostate cancer is an aggressive phenotype with poor progression-free survival (PFS) and overall survival (OS). Preliminary evidence suggests that AR-V7-positive tumors may be enriched for DNA-repair defects, perhaps rendering them more sensitive to immune-checkpoint blockade. We enrolled 15 metastatic prostate cancer patients with AR-V7-expressing circulating tumor cells into a prospective phase-2 trial. Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, then maintenance nivolumab 3 mg/kg every 2 weeks. Targeted next-generation sequencing was performed to determine DNA-repair deficiency (DRD) status. Outcomes included PSA response rates, objective response rates (ORR), PSA progression-free survival (PSA-PFS), clinical/radiographic PFS and OS. Median age of participants was 65, median PSA was 115 ng/mL, 67% had visceral metastases, and 60% had ≥4 prior systemic therapies. Six of 15 men (40%) had DRD mutations (three in BRCA2, two in ATM, one in ERCC4; none had microsatellite instability). Overall, the PSA response rate was 2/15 (13%), ORR was 2/8 (25%) in those with measurable disease, median PSA-PFS was 3.0 (95%CI 2.1–NR) months, PFS was 3.7 (95%CI 2.8–7.5) months, and OS was 8.2 (95%CI 5.5–10.4) months. Outcomes appeared generally better in DRD+ vs. DRD– tumors with respect to PSA responses (33% vs. 0%; P=0.14, nonsignificant), ORR (40% vs. 0%; P=0.46, nonsignificant), PSA-PFS (HR 0.19; P

Published
2018

10. Immune checkpoint inhibitor in nasopharyngeal carcinoma: Multi-institution experience

Author

Karim Boudadi, Julia Durbeck, Won Jin Ho, Hyunseok Kang, Lori J. Wirth, John W. Clark, and Jong Chul Park

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Nasopharyngeal carcinoma, business.industry, Immune checkpoint inhibitors, Standard treatment, Internal medicine, medicine, Cytotoxic chemotherapy, medicine.disease, business
Abstract

6538 Background: The current standard treatment for unresectable recurrent/metastatic (R/M) nasopharyngeal carcinoma (NPC) is cytotoxic chemotherapy but prognosis remains poor. Recent phase I-II trials of anti-PD-1 therapy (aPD-1) have demonstrated promising activity in R/M NPC, but the published experience is primarily limited to Epstein-Barr virus (EBV) positive tumors in the Asian population. Here we report our three institutional real-world experience with aPD-1 in patients (pts) with R/M NPC. Methods: A retrospective analysis was conducted after IRB approval at the Massachusetts General, Johns Hopkins, and University California San Francisco Hospitals. Demographic and clinical data was collected on pts with R/M NPC who received aPD-1 at the participating institutions. Objective response rate (ORR) was the primary outcome of interest and progression free survival (PFS) and overall survival were secondary outcomes. Univariate and multivariate analyses were conducted to assess association between clinicopathologic factors and outcomes, using logistic regression models. Results: A total of 36 pts were identified: 20 pts were treated with pembrolizumab and 16 with nivolumab. Median age was 50 (15-74). Twenty-nine (81%) were male. Twenty pts (56%) were Asian. Twenty-nine pts (81%) had EBV positive disease. Nine (25%) had aPD-1 as first-line therapy (1L). Molecular profiling results were available in 16 pts: TP53 mutation was the most common alteration (25%) and was limited to EBV negative tumors. Median total mutational burden (TMB) was 3/Mb (1-28). Median PD-L1 expression was 10% (0-90). Median follow up was 13.9 months (mos). Objective response was evaluable in all 36 pts: 9 pts achieved objective response (ORR 25.0%, 95% CI 12.1-42.2) with 2 complete responses: EBV positive vs. negative (27.6% vs. 14.2%, P=0.472), Asian vs. non-Asian (25% vs. 25%, P=1.000), and 1L vs. >1L (33.3% vs. 22.2%, P=0.511). Thirteen pts had stable disease (disease control rate 61.1%). Responses were seen in both TMB high (28/Mb) and low (1/Mb) tumors and no association with PD-L1 expression was observed. One-year survival rate was 81.3%. EBV positive pts had a trend towards better survival (84.8 vs. 66.7, P=0.640). Median PFS was 5.5 mos and not different between EBV positive vs. negative pts (5.6 vs. 4.0 mos, P=0.919). Conclusions: Our multi-institutional real-world experience with checkpoint inhibitor therapy in R/M NPC confirms that a similar degree of activity is seen as reported in the phase I-II experience in diverse races, but efficacy seems more prominent in EBV positive disease.

Published
2020

11. Laryngeal Cancer: Organ Preservation Strategies

Author

Arlene A. Forastiere, Steven B. Chinn, Randal S. Weber, Avraham Eisbruch, Jae Y. Lee, and Karim Boudadi

Subjects
Oncology, medicine.medical_specialty, business.industry, Internal medicine, medicine, Cancer, business, medicine.disease
Published
2018

12. Pharmacodynamic study of the oral hedgehog pathway inhibitor, vismodegib, in patients with metastatic castration-resistant prostate cancer

Author

Daniel L. Suzman, Angelo M. DeMarzo, Mario A. Eisenberger, Hao Wang, Rana Sullivan, Karim Boudadi, Emmanuel S. Antonarakis, Rana Harb, Robert M. Hughes, Stephanie Glavaris, Benjamin L. Maughan, Channing J. Paller, Ashely Ross, and Brandon Luber

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Pyridines, Vismodegib, Castration resistant, Toxicology, medicine.disease_cause, Zinc Finger Protein GLI1, Article, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, medicine, Humans, Pharmacology (medical), In patient, Anilides, Hedgehog Proteins, Hedgehog, Aged, Pharmacology, business.industry, Middle Aged, Prostate-Specific Antigen, medicine.disease, Hedgehog signaling pathway, Prostatic Neoplasms, Castration-Resistant, 030104 developmental biology, 030220 oncology & carcinogenesis, business, Carcinogenesis, medicine.drug
Abstract

Hedgehog (Hh) pathway signaling has been implicated in prostate cancer tumorigenesis and metastatic development and may be upregulated even further in the castration-resistant state. We hypothesized that antagonism of the Hh pathway with vismodegib in men with metastatic castration-resistant prostate cancer (mCRPC) would result in pathway engagement, inhibition and perhaps induce measurable clinical responses in patients.This is a single-arm study of oral daily vismodegib in men with mCRPC. All patients were required to have biopsies of the tumor and skin (a surrogate tissue) at baseline and after 4 weeks of therapy. Ten patients were planned for enrollment. The primary outcome was the pharmacodynamic assessment of Gli1 mRNA suppression with vismodegib in tumor tissue. Secondary outcomes included PSA response rates, progression-free survival (PFS), overall survival (OS) and safety.Nine patients were enrolled. Gli1 mRNA was significantly suppressed by vismodegib in both tumor tissue (4/7 evaluable biopsies, 57%) and benign skin biopsies (6/8 evaluable biopsies, 75%). The median number of treatment cycles completed was three, with a median PFS of 1.9 months (95% CI 1.3, NA), and a median OS of 7.04 months (95% CI 3.4, NA). No patient achieved a PSA reduction or a measurable tumor response. Safety data were consistent with the known toxicities of vismodegib.Hh signaling, as measured by Gli1 mRNA expression in mCRPC tissues, was suppressed with vismodegib in the majority of patients. Despite this pharmacodynamic response that indicated target inhibition in some patients, there was no apparent signal of clinical activity. Vismodegib will not be developed further as monotherapy in mCRPC.

Published
2016

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

Author

Andreas Lundqvist, Vincent van Hoef, Xiaonan Zhang, Erik Wennerberg, Julie Lorent, Kristina Witt, Laia Masvidal Sanz, Shuo Liang, Shannon Murray, Ola Larsson, Rolf Kiessling, Yumeng Mao, John-William Sidhom, Catherine A. Bessell, Jonathan Havel, Jonathan Schneck, Timothy A. Chan, Eliot Sachsenmeier, David Woods, Anders Berglund, Rupal Ramakrishnan, Andressa Sodre, Jeffrey Weber, Roberta Zappasodi, Yanyun Li, Jingjing Qi, Philip Wong, Cynthia Sirard, Michael Postow, Walter Newman, Henry Koon, Vamsidhar Velcheti, Margaret K. Callahan, Jedd D. Wolchok, Taha Merghoub, Lawrence G. Lum, Minsig Choi, Archana Thakur, Abhinav Deol, Gregory Dyson, Anthony Shields, Cara Haymaker, Marc Uemura, Ravi Murthy, Marihella James, Daqing Wang, Julie Brevard, Catherine Monaghan, Suzanne Swann, James Geib, Mark Cornfeld, Srinivas Chunduru, Sudhir Agrawal, Cassian Yee, Jennifer Wargo, Sapna P. Patel, Rodabe Amaria, Hussein Tawbi, Isabella Glitza, Scott Woodman, Wen-Jen Hwu, Michael A. Davies, Patrick Hwu, Willem W. Overwijk, Chantale Bernatchez, Adi Diab, Erminia Massarelli, Neil H. Segal, Vincent Ribrag, Ignacio Melero, Tara C. Gangadhar, Walter Urba, Dirk Schadendorf, Robert L. Ferris, Roch Houot, Franck Morschhauser, Theodore Logan, Jason J. Luke, William Sharfman, Fabrice Barlesi, Patrick A. Ott, Laura Mansi, Shivaani Kummar, Gilles Salles, Cecilia Carpio, Roland Meier, Suba Krishnan, Dan McDonald, Matthew Maurer, Xuemin Gu, Jaclyn Neely, Satyendra Suryawanshi, Ronald Levy, Nikhil Khushalani, Jennifer Wu, Jinyu Zhang, Fahmin Basher, Mark Rubinstein, Mark Bucsek, Guanxi Qiao, Cameron MacDonald, Bonnie Hylander, Elizabeth Repasky, Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Kyle Toth, Megan Meek, Elizabeth Garrett-Mayer, Michael Nishimura, Chrystal Paulos, Craig Beeson, Xuezhong Yu, Shikhar Mehrotra, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nicole Scharping, Ashley V. Menk, Rebecca Moreci, Ryan Whetstone, Rebekah Dadey, Simon Watkins, Robert Ferris, Greg M. Delgoffe, Jonathan Peled, Sean Devlin, Anna Staffas, Melissa Lumish, Kori Porosnicu Rodriguez, Katya Ahr, Miguel Perales, Sergio Giralt, Ying Taur, Eric Pamer, Marcel R. M. van den Brink, Robert Jenq, Nicola Annels, Hardev Pandha, Guy Simpson, Hugh Mostafid, Kevin Harrington, Alan Melcher, Mark Grose, Bronwyn Davies, Gough Au, Roberta Karpathy, Darren Shafren, Jacob Ricca, Dmitriy Zamarin, Luciana Batista, Florence Marliot, Angela Vasaturo, Sabrina Carpentier, Cécile Poggionovo, Véronique Frayssinet, Jacques Fieschi, Marc Van den Eynde, Franck Pagès, Jérôme Galon, Fabienne Hermitte, Sean G. Smith, Khue Nguyen, Sruthi Ravindranathan, Bhanu Koppolu, David Zaharoff, Gustavo Schvartsman, Roland Bassett, Jennifer L. McQuade, Lauren E. Haydu, Douglas Kline, Xiufen Chen, Dominick Fosco, Justin Kline, Abigail Overacre, Maria Chikina, Erin Brunazzi, Gulidanna Shayan, William Horne, Jay Kolls, Tullia C. Bruno, Creg Workman, Dario Vignali, Prasad S. Adusumilli, Ephraim A Ansa-Addo, Zihai Li, Andrew Gerry, Joseph P. Sanderson, Karen Howe, Roslin Docta, Qian Gao, Eleanor A. L. Bagg, Nicholas Tribble, Miguel Maroto, Gareth Betts, Natalie Bath, Luca Melchiori, Daniel E. Lowther, Indu Ramachandran, Gabor Kari, Samik Basu, Gwendolyn Binder-Scholl, Karen Chagin, Lini Pandite, Tom Holdich, Rafael Amado, Hua Zhang, John Glod, Donna Bernstein, Bent Jakobsen, Crystal Mackall, Ryan Wong, Jonathan D. Silk, Katherine Adams, Garth Hamilton, Alan D. Bennett, Sara Brett, Junping Jing, Adriano Quattrini, Manoj Saini, Guy Wiedermann, Joanna Brewer, MyLinh Duong, An Lu, Peter Chang, Aruna Mahendravada, Nicholas Shinners, Kevin Slawin, David M. Spencer, Aaron E. Foster, J. Henri Bayle, Cristina Bergamaschi, Sinnie Sin Man Ng, Bethany Nagy, Shawn Jensen, Xintao Hu, Candido Alicea, Bernard Fox, Barbara Felber, George Pavlakis, Jessica Chacon, Tori Yamamoto, Thomas Garrabrant, Luis Cortina, Daniel J. Powell, Marco Donia, Julie Westerlin Kjeldsen, Rikke Andersen, Marie Christine Wulff Westergaard, Valentina Bianchi, Mateusz Legut, Meriem Attaf, Garry Dolton, Barbara Szomolay, Sascha Ott, Rikke Lyngaa, Sine Reker Hadrup, Andrew Kelvin Sewell, Inge Marie Svane, Aaron Fan, Takumi Kumai, Esteban Celis, Ian Frank, Amanda Stramer, Michelle A. Blaskovich, Seth Wardell, Maria Fardis, James Bender, Michael T. Lotze, Stephanie L. Goff, Nikolaos Zacharakis, Yasmine Assadipour, Todd D. Prickett, Jared J. Gartner, Robert Somerville, Mary Black, Hui Xu, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John Wunderlich, Paul F. Robbins, Steven Rosenberg, Steven A. Feldman, Kasia Trebska-McGowan, Parisa Malekzadeh, Eden Payabyab, Richard Sherry, Aishwarya Gokuldass, Charlene Kopits, Brian Rabinovich, Daniel S. Green, Olena Kamenyeva, Kathryn C. Zoon, Christina M. Annunziata, Joanne Hammill, Christopher Helsen, Craig Aarts, Jonathan Bramson, Yui Harada, Yoshikazu Yonemitsu, Kenneth Mwawasi, Galina Denisova, Rajanish Giri, Benjamin Jin, Tracy Campbell, Lindsey M. Draper, Sanja Stevanovic, Zhiya Yu, Bianca Weissbrich, Nicholas P. Restifo, Cornelia L. Trimble, Christian S. Hinrichs, Kwong Tsang, Massimo Fantini, James W. Hodge, Rika Fujii, Ingrid Fernando, Caroline Jochems, Christopher Heery, James Gulley, Patrick Soon-Shiong, Jeffrey Schlom, Weiqing Jing, Jill Gershan, Grace Blitzer, James Weber, Laura McOlash, Bryon D. Johnson, Simin Kiany, Huang Gangxiong, Eugenie S. Kleinerman, Michael Klichinsky, Marco Ruella, Olga Shestova, Saad Kenderian, Miriam Kim, John Scholler, Carl H. June, Saar Gill, Duane Moogk, Shi Zhong, Ivan Liadi, William Rittase, Victoria Fang, Janna Dougherty, Arianne Perez-Garcia, Iman Osman, Cheng Zhu, Navin Varadarajan, Alan Frey, Michelle Krogsgaard, Daniel Landi, Kristen Fousek, Malini Mukherjee, Ankita Shree, Sujith Joseph, Kevin Bielamowicz, Tiara Byrd, Nabil Ahmed, Meenakshi Hegde, Sylvia Lee, David Byrd, John Thompson, Shailender Bhatia, Scott Tykodi, Judy Delismon, Liz Chu, Siddiq Abdul-Alim, Arpy Ohanian, Anna Marie DeVito, Stanley Riddell, Kim Margolin, Isabelle Magalhaes, Jonas Mattsson, Michael Uhlin, Satoshi Nemoto, Patricio Pérez Villarroel, Ryosuke Nakagawa, James J. Mule, Adam W. Mailloux, Melinda Mata, Phuong Nguyen, Claudia Gerken, Christopher DeRenzo, Stephen Gottschalk, Mélissa Mathieu, Sandy Pelletier, John Stagg, Simon Turcotte, Nicholas Minutolo, Prannda Sharma, Andrew Tsourkas, Nadine Mockel-Tenbrinck, Daniela Mauer, Katharina Drechsel, Carola Barth, Katharina Freese, Ulrike Kolrep, Silke Schult, Mario Assenmacher, Andrew Kaiser, John Mullinax, MacLean Hall, Julie Le, Krithika Kodumudi, Erica Royster, Allison Richards, Ricardo Gonzalez, Amod Sarnaik, Shari Pilon-Thomas, Morten Nielsen, Anders Krarup-Hansen, Dorrit Hovgaard, Michael Mørk Petersen, Anand Chainsukh Loya, Niels Junker, Charlotte Rivas, Robin Parihar, Cliona M. Rooney, Haiying Qin, Sang Nguyen, Paul Su, Chad Burk, Brynn Duncan, Bong-Hyun Kim, M. Eric Kohler, Terry Fry, Arjun A. Rao, Noam Teyssier, Jacob Pfeil, Nikolaos Sgourakis, Sofie Salama, David Haussler, Sarah A. Richman, Selene Nunez-Cruz, Zack Gershenson, Zissimos Mourelatos, David Barrett, Stephan Grupp, Michael Milone, Alba Rodriguez-Garcia, Matthew K. Robinson, Gregory P. Adams, João Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascón, Suvi Parviainen, Marjukka Antilla, Akseli Hemminki, Jyothi Sethuraman, Laurelis Santiago, Jie Qing Chen, Zhimin Dai, Huizi Sha, Shu Su, Naiqing Ding, Baorui Liu, Anna Pasetto, Sarah R. Helman, Steven A. Rosenberg, Melissa Burgess, Hui Zhang, Tien Lee, Hans Klingemann, Paul Nghiem, John M. Kirkwood, John M. Rossi, Marika Sherman, Allen Xue, Yueh-wei Shen, Lynn Navale, James N. Kochenderfer, Adrian Bot, Anandaraman Veerapathran, Doris Wiener, Edmund K. Waller, Jian-Ming Li, Christopher Petersen, Bruce R. Blazar, Jingxia Li, Cynthia R. Giver, Ziming Wang, Steven K. Grossenbacher, Ian Sturgill, Robert J. Canter, William J. Murphy, Congcong Zhang, Michael C. Burger, Lukas Jennewein, Anja Waldmann, Michel Mittelbronn, Torsten Tonn, Joachim P. Steinbach, Winfried S. Wels, Jason B. Williams, Yuanyuan Zha, Thomas F. Gajewski, LaTerrica C. Williams, Giedre Krenciute, Mamta Kalra, Chrystal Louis, Gang Xin, David Schauder, Aimin Jiang, Nikhil Joshi, Weiguo Cui, Xue Zeng, Zeguo Zhao, Mohamad Hamieh, Justin Eyquem, Gertrude Gunset, Neil Bander, Michel Sadelain, David Askmyr, Milad Abolhalaj, Kristina Lundberg, Lennart Greiff, Malin Lindstedt, Helen K. Angell, Kyoung-Mee Kim, Seung-Tae Kim, Sung Kim, Alan D. Sharpe, Julia Ogden, Anna Davenport, Darren R. Hodgson, Carl Barrett, Jeeyun Lee, Elaine Kilgour, Jodi Hanson, Richard Caspell, Alexey Karulin, Paul Lehmann, Tameem Ansari, Annemarie Schiller, Srividya Sundararaman, Diana Roen, Mark Ayers, Diane Levitan, Gladys Arreaza, Fang Liu, Robin Mogg, Yung-Jue Bang, Bert O’Neil, Razvan Cristescu, Philip Friedlander, Karl Wassman, Chrisann Kyi, William Oh, Nina Bhardwaj, Svetlana Bornschlegl, Michael P. Gustafson, Dennis A. Gastineau, Ian F. Parney, Allan B. Dietz, Daniel Carvajal-Hausdorf, Nikita Mani, Kurt Schalper, David Rimm, Serena Chang, John Kurland, Christoph Matthias Ahlers, Maria Jure-Kunkel, Lewis Cohen, Holden Maecker, Holbrook Kohrt, Shuming Chen, George Crabill, Theresa Pritchard, Tracee McMiller, Drew Pardoll, Fan Pan, Suzanne Topalian, Patrick Danaher, Sarah Warren, Lucas Dennis, Andrew M. White, Leonard D’Amico, Melissa Geller, Mary L. Disis, Joseph Beechem, Kunle Odunsi, Steven Fling, Roshanak Derakhshandeh, Tonya J. Webb, Sigrid Dubois, Kevin Conlon, Bonita Bryant, Jennifer Hsu, Nancy Beltran, Jürgen Müller, Thomas Waldmann, Rebekka Duhen, Thomas Duhen, Lucas Thompson, Ryan Montler, Andrew Weinberg, Max Kates, Brandon Early, Erik Yusko, Taylor H. Schreiber, Trinity J. Bivalacqua, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R. Kaufman, Andrew Albright, Jonathan Cheng, S. Peter Kang, Veena Shankaran, Sarina A. Piha-Paul, Jennifer Yearley, Tanguy Seiwert, Antoni Ribas, Terrill K. McClanahan, Xinwei Sher, Xiao Qiao Liu, Andrew Joe, Elizabeth Plimack, Alex Forrest-Hay, Cheryl A. Guyre, Kohei Narumiya, Marc Delcommenne, Heather A. Hirsch, Amit Deshpande, Jason Reeves, Jenny Shu, Tong Zi, Jennifer Michaelson, Debbie Law, Elizabeth Trehu, Sriram Sathyanaryanan, Brendan P. Hodkinson, Natalie A. Hutnick, Michael E. Schaffer, Michael Gormley, Tyler Hulett, Carmen Ballesteros-Merino, Christopher Dubay, Michael Afentoulis, Ashok Reddy, Larry David, Kumar Jayant, Swati Agrawal, Rajendra Agrawal, Ghayathri Jeyakumar, Seongho Kim, Heejin Kim, Cynthia Silski, Stacey Suisham, Elisabeth Heath, Ulka Vaishampayan, Natalie Vandeven, Natasja Nielsen Viller, Alison O’Connor, Hui Chen, Bolette Bossen, Eric Sievers, Robert Uger, Lisa Johnson, Hsiang-Fong Kao, Chin-Fu Hsiao, Shu-Chuan Lai, Chun-Wei Wang, Jenq-Yuh Ko, Pei-Jen Lou, Tsai-Jan Lee, Tsang-Wu Liu, Ruey-Long Hong, Staci J. Kearney, Joshua C. Black, Benjamin J. Landis, Sally Koegler, Brooke Hirsch, Roberto Gianani, Jeffrey Kim, Ming-Xiao He, Bingqing Zhang, Nan Su, Yuling Luo, Xiao-Jun Ma, Emily Park, Dae Won Kim, Domenico Copploa, Nishi Kothari, Young doo Chang, Richard Kim, Namyong Kim, Melvin Lye, Ee Wan, Hanna A. Knaus, Sofia Berglund, Hubert Hackl, Judith E. Karp, Ivana Gojo, Leo Luznik, Henoch S. Hong, Sven D. Koch, Birgit Scheel, Ulrike Gnad-Vogt, Karl-Josef Kallen, Volker Wiegand, Linus Backert, Oliver Kohlbacher, Ingmar Hoerr, Mariola Fotin-Mleczek, James M. Billingsley, Yoshinobu Koguchi, Valerie Conrad, William Miller, Iliana Gonzalez, Tomasz Poplonski, Tanisha Meeuwsen, Ana Howells-Ferreira, Rogan Rattray, Mary Campbell, Carlo Bifulco, Keith Bahjat, Brendan Curti, E-K Vetsika, G. Kallergi, Despoina Aggouraki, Z. Lyristi, P. Katsarlinos, Filippos Koinis, V. Georgoulias, Athanasios Kotsakis, Nathan T. Martin, Famke Aeffner, Logan Cerkovnik, Luke Pratte, Rebecca Kim, Joseph Krueger, Amaia Martínez-Usatorre, Camilla Jandus, Alena Donda, Laura Carretero-Iglesia, Daniel E. Speiser, Dietmar Zehn, Nathalie Rufer, Pedro Romero, Anshuman Panda, Janice Mehnert, Kim M. Hirshfield, Greg Riedlinger, Sherri Damare, Tracie Saunders, Levi Sokol, Mark Stein, Elizabeth Poplin, Lorna Rodriguez-Rodriguez, Ann Silk, Nancy Chan, Melissa Frankel, Michael Kane, Jyoti Malhotra, Joseph Aisner, Howard L. Kaufman, Siraj Ali, Jeffrey Ross, Eileen White, Gyan Bhanot, Shridar Ganesan, Anne Monette, Derek Bergeron, Amira Ben Amor, Liliane Meunier, Christine Caron, Antigoni Morou, Daniel Kaufmann, Moishe Liberman, Igor Jurisica, Anne-Marie Mes-Masson, Kamel Hamzaoui, Rejean Lapointe, Ann Mongan, Yuan-Chieh Ku, Warren Tom, Yongming Sun, Alex Pankov, Tim Looney, Janice Au-Young, Fiona Hyland, Jeff Conroy, Carl Morrison, Sean Glenn, Blake Burgher, He Ji, Mark Gardner, Angela R. Omilian, Wiam Bshara, Omilian Angela, Joseph M. Obeid, Gulsun Erdag, Mark E. Smolkin, Donna H. Deacon, James W. Patterson, Lieping Chen, Timothy N. Bullock, Craig L. Slingluff, John T. Loffredo, Raja Vuyyuru, Sophie Beyer, Vanessa M. Spires, Maxine Fox, Jon M. Ehrmann, Katrina A. Taylor, Alan J. Korman, Robert F. Graziano, David Page, Katherine Sanchez, Maritza Martel, Mariana Petaccia De Macedo, Yong Qin, Alex Reuben, Christine Spencer, Michele Guindani, Adriana Racolta, Brian Kelly, Tobin Jones, Nathan Polaske, Noah Theiss, Mark Robida, Jeffrey Meridew, Iva Habensus, Liping Zhang, Lidija Pestic-Dragovich, Lei Tang, Ryan J. Sullivan, Thomas Olencki, Thomas Hutson, Joanna Roder, Shauna Blackmon, Heinrich Roder, John Stewart, Asim Amin, Marc S. Ernstoff, Joseph I. Clark, Michael B. Atkins, Jeffrey Sosman, David F. McDermott, Harriet Kluger, Ruth Halaban, Mario Snzol, Senait Asmellash, Arni Steingrimsson, Chichung Wang, Kristin Roman, Amanda Clement, Sean Downing, Clifford Hoyt, Nathalie Harder, Guenter Schmidt, Ralf Schoenmeyer, Nicolas Brieu, Mehmet Yigitsoy, Gabriele Madonna, Gerardo Botti, Antonio Grimaldi, Paolo A. Ascierto, Ralf Huss, Maria Athelogou, Harald Hessel, Alexander Buchner, Christian Stief, Gerd Binnig, Thomas Kirchner, Shankar Sellappan, Sheeno Thyparambil, Sarit Schwartz, Fabiola Cecchi, Andrew Nguyen, Charles Vaske, Todd Hembrough, Jan Spacek, Michal Vocka, Eva Zavadova, Helena Skalova, Pavel Dundr, Lubos Petruzelka, Nicole Francis, Rau T. Tilman, Arndt Hartmann, Irena Netikova, Julia Stump, Amanda Tufman, Frank Berger, Michael Neuberger, Rudolf Hatz, Michael Lindner, Rachel E. Sanborn, John Handy, Rudolf M. Huber, Hauke Winter, Simone Reu, Cheng Sun, Weihua Xiao, Zhigang Tian, Kshitij Arora, Niyati Desai, Anupriya Kulkarni, Mihir Rajurkar, Miguel Rivera, Vikram Deshpande, David Ting, Katy Tsai, Adi Nosrati, Simone Goldinger, Omid Hamid, Alain Algazi, Paul Tumeh, Jimmy Hwang, Jacqueline Liu, Lawrence Chen, Reinhard Dummer, Michael Rosenblum, Adil Daud, Tsu-Shuen Tsao, Julia Ashworth-Sharpe, Donald Johnson, Srabani Bhaumik, Christopher Bieniarz, Joseph Couto, Michael Farrell, Mahsa Ghaffari, Antony Hubbard, Jerome Kosmeder, Cleo Lee, Erin Marner, Diana Uribe, Hongjun Zhang, Jian Zhang, Wenjun Zhang, Yifei Zhu, Larry Morrison, Takahiro Tsujikawa, Rohan N. Borkar, Vahid Azimi, Sushil Kumar, Guillaume Thibault, Motomi Mori, Edward El Rassi, Daniel R. Clayburgh, Molly F. Kulesz-Martin, Paul W. Flint, Lisa M. Coussens, Lisa Villabona, Giuseppe V. Masucci, Gary Geiss, Brian Birditt, Qian Mei, Alan Huang, Maribeth A. Eagan, Eduardo Ignacio, Nathan Elliott, Dwayne Dunaway, Jaemyeong Jung, Chris Merritt, Isaac Sprague, Philippa Webster, Yan Liang, Jessica Wenthe, Gunilla Enblad, Hannah Karlsson, Magnus Essand, Barbara Savoldo, Gianpietro Dotti, Martin Höglund, Malcolm K. Brenner, Hans Hagberg, Angelica Loskog, Matthew J. Bernett, Gregory L. Moore, Michael Hedvat, Christine Bonzon, Seung Chu, Rumana Rashid, Kendra N. Avery, Umesh Muchhal, John Desjarlais, Matthew Kraman, Katarzyna Kmiecik, Natalie Allen, Mustapha Faroudi, Carlo Zimarino, Mateusz Wydro, Jacqueline Doody, Sreesha P. Srinivasa, Nagaraja Govindappa, Praveen Reddy, Aparajita Dubey, Sankar Periyasamy, Madhukara Adekandi, Chaitali Dey, Mary Joy, Pieter Fokko van Loo, Henrike Veninga, Setareh Shamsili, Mark Throsby, Harry Dolstra, Lex Bakker, Ajjai Alva, Juergen Gschwendt, Yohann Loriot, Joaquim Bellmunt, Dai Feng, Christian Poehlein, Thomas Powles, Emmanuel S. Antonarakis, Charles G. Drake, Haiyan Wu, Johann De Bono, Rajat Bannerji, John Byrd, Gareth Gregory, Stephen Opat, Jake Shortt, Andrew J. Yee, Noopur Raje, Seth Thompson, Arun Balakumaran, Shaji Kumar, Brian I. Rini, Toni K. Choueiri, Mariangela Mariani, Laurence Albiges, John B. Haanen, James Larkin, Manuela Schmidinger, Domenico Magazzù, Alessandra di Pietro, Robert J. Motzer, Troels Holz Borch, Per Kongsted, Magnus Pedersen, Özcan Met, Karim Boudadi, Hao Wang, James Vasselli, Jan E. Baughman, Jon Wigginton, Rehab Abdallah, Ashley Ross, Jiwon Park, Steven Grossenbacher, Jesus I. Luna, Sita Withers, William Culp, Mingyi Chen, Arta Monjazeb, Michael S. Kent, Smita Chandran, David Danforth, James Yang, Christopher Klebanoff, Stephanie Goff, Biman Paria, Arvind Sabesan, Abhishek Srivastava, Udai Kammula, Jon Richards, Mark Faries, Robert H. I. Andtbacka, Luis A. Diaz, Dung T. Le, Takayuki Yoshino, Thierry André, Johanna Bendell, Minori Koshiji, Yayan Zhang, S Peter Kang, Bao Lam, Dirk Jäger, Todd M. Bauer, Judy S. Wang, Jean K. Lee, Gulam A. Manji, Ragini Kudchadkar, John S. Kauh, Shande Tang, Naomi Laing, Gerald Falchook, Edward B. Garon, Balazs Halmos, Hui Rina, Natasha Leighl, Sung Sook Lee, William Walsh, Konstanin Dragnev, Bilal Piperdi, Luis Paz-Ares Rodriguez, Nabeegha Shinwari, Ziewn Wei, Mary L Maas, Michael Deeds, Adam Armstrong, Tim Peterson, Sue Steinmetz, Thomas Herzog, Floor J. Backes, Larry Copeland, Maria Del Pilar Estevez Diz, Thomas W. Hare, Warner Huh, Byoung-Gie Kim, Kathleen M. Moore, Ana Oaknin, William Small, Krishnansu S. Tewari, Bradley J. Monk, Ashish M. Kamat, Kijoeng Nam, Maria De Santis, Robert Dreicer, Noah M. Hahn, Rodolfo Perini, Arlene Siefker-Radtke, Guru Sonpavde, Ronald de Wit, J. Alfred Witjes, Stephen Keefe, Dean Bajorin, Philippe Armand, John Kuruvilla, Craig Moskowitz, Mehdi Hamadani, Pier Luigi Zinzani, Sabine Chlosta, Nancy Bartlett, Rachel Sabado, Yvonne Saenger, Loging William, Michael Joseph Donovan, Erlinda Sacris, John Mandeli, Andres M. Salazar, John Powderly, Joshua Brody, John Nemunaitis, Leisha Emens, Amita Patnaik, Ian McCaffery, Richard Miller, Ginna Laport, Andrew L. Coveler, David C. Smith, Juneko E. Grilley-Olson, Sanjay Goel, Shyra J. Gardai, Che-Leung Law, Gary Means, Thomas Manley, Kristen A. Marrone, Gary Rosner, Valsamo Anagnostou, Joanne Riemer, Jessica Wakefield, Cynthia Zanhow, Stephen Baylin, Barbara Gitlitz, Julie Brahmer, Sabina Signoretti, Wenting Li, Charles Schloss, Jean-Marie Michot, Wei Ding, Beth Christian, Patricia Marinello, Margaret Shipp, Yana G. Najjar, null Lin, Lisa H. Butterfield, Ahmad A. Tarhini, Diwakar Davar, Hassane Zarour, Elizabeth Rush, Cindy Sander, Siqing Fu, Todd Bauer, Chris Molineaux, Mark K. Bennett, Keith W. Orford, Kyriakos P. Papadopoulos, Sukhmani K. Padda, Sumit A. Shah, A Dimitrios Colevas, Sujata Narayanan, George A. Fisher, Dana Supan, Heather A. Wakelee, Rhonda Aoki, Mark D. Pegram, Victor M. Villalobos, Jie Liu, Chris H. Takimoto, Mark Chao, Jens-Peter Volkmer, Ravindra Majeti, Irving L. Weissman, Branimir I. Sikic, Wendy Yu, Alison Conlin, Janet Ruzich, Stacy Lewis, Anupama Acheson, Kathleen Kemmer, Kelly Perlewitz, Nicole M. Moxon, Staci Mellinger, Heather McArthur, Trine Juhler-Nøttrup, Jayesh Desai, Ben Markman, Shahneen Sandhu, Hui Gan, Michael L. Friedlander, Ben Tran, Tarek Meniawy, Joanne Lundy, Duncan Colyer, Malaka Ameratunga, Christie Norris, Jason Yang, Kang Li, Lai Wang, Lusong Luo, Zhen Qin, Song Mu, Xuemei Tan, James Song, Michael Millward, Matthew H. G. Katz, Todd W. Bauer, Gauri R. Varadhachary, Nicolas Acquavella, Nipun Merchant, Gina Petroni, Osama E. Rahma, Mei Chen, Yang Song, Markus Puhlmann, Arun Khattri, Ryan Brisson, Christopher Harvey, Jatin Shah, Maria Victoria Mateos, Morio Matsumoto, Hilary Blacklock, Albert Oriol Rocafiguera, Hartmut Goldschmidt, Shinsuke Iida, Dina Ben Yehuda, Enrique Ocio, Paula Rodríguez-Otero, Sundar Jagannath, Sagar Lonial, Uma Kher, Jesus San-Miguel, Moacyr Ribeiro de Oliveira, Habte Yimer, Robert Rifkin, Fredrik Schjesvold, Razi Ghori, Anna Spreafico, Victor Lee, Roger K. C. Ngan, Ka Fai To, Myung Ju Ahn, Quan Sing Ng, Jin-Ching Lin, Ramona F. Swaby, Christine Gause, Sanatan Saraf, Anthony T. C. Chan, Elaine Lam, Nizar M. Tannir, Funda Meric-Bernstam, Matt Gross, Andy MacKinnon, Sam Whiting, Martin Voss, Evan Y. Yu, Mark R. Albertini, Erik A. Ranheim, Jacquelyn A. Hank, Cindy Zuleger, Thomas McFarland, Jennifer Collins, Erin Clements, Sharon Weber, Tracey Weigel, Heather Neuman, Greg Hartig, David Mahvi, MaryBeth Henry, Jacek Gan, Richard Yang, Lakeesha Carmichael, KyungMann Kim, Stephen D. Gillies, Paul M. Sondel, Vivek Subbiah, Lori Noffsinger, Kyle Hendricks, Marnix Bosch, Jay M. Lee, Mi-Heon Lee, Jonathan W. Goldman, Felicita E. Baratelli, Dorthe Schaue, Gerald Wang, Frances Rosen, Jane Yanagawa, Tonya C. Walser, Ying Q. Lin, Sharon Adams, Franco M. Marincola, Paul C. Tumeh, Fereidoun Abtin, Robert Suh, Karen Reckamp, William D. Wallace, Gang Zeng, David A. Elashoff, Sherven Sharma, Steven M. Dubinett, Anna C. Pavlick, Brian Gastman, Brent Hanks, Tibor Keler, Tom Davis, Laura A. Vitale, Elad Sharon, Chihiro Morishima, Martin Cheever, Christopher R. Heery, Joseph W. Kim, Elizabeth Lamping, Jennifer Marte, Sheri McMahon, Lisa Cordes, Farhad Fakhrejahani, Ravi Madan, Rachel Salazar, Maggie Zhang, Christoph Helwig, James L Gulley, Roger Li, John Amrhein, Zvi Cohen, Monique Champagne, Ashish Kamat, M. Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Manel Esteller, Juan Sandoval, Susannah D. Barbee, David I. Bellovin, John C. Timmer, Nebiyu Wondyfraw, Susan Johnson, Johanna Park, Amanda Chen, Mikayel Mkrtichyan, Amir S. Razai, Kyle S. Jones, Chelsie Y. Hata, Denise Gonzalez, Quinn Deveraux, Brendan P. Eckelman, Luis Borges, Rukmini Bhardwaj, Raj K. Puri, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Todd Bartkowiak, Ashvin Jaiswal, Casey Ager, Midan Ai, Pratha Budhani, Renee Chin, David Hong, Michael Curran, William D. Hastings, Maria Pinzon-Ortiz, Masato Murakami, Jason R. Dobson, David Quinn, Joel P. Wagner, Xianhui Rong, Pamela Shaw, Ernesta Dammassa, Wei Guan, Glenn Dranoff, Alexander Cao, Ross B. Fulton, Steven Leonardo, Kathryn Fraser, Takashi O. Kangas, Nadine Ottoson, Nandita Bose, Richard D. Huhn, Jeremy Graff, Jamie Lowe, Keith Gorden, Mark Uhlik, Thomas O’Neill, Jenifer Widger, Andrea Crocker, Li-Zhen He, Jeffrey Weidlick, Karuna Sundarapandiyan, Venky Ramakrishna, James Storey, Lawrence J. Thomas, Joel Goldstein, Henry C. Marsh, Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jim Hartnett, Frank Fan, Mei Cong, Zhi-jie Jey Cheng, Marlon J. Hinner, Rachida-Siham Bel Aiba, Corinna Schlosser, Thomas Jaquin, Andrea Allersdorfer, Sven Berger, Alexander Wiedenmann, Gabriele Matschiner, Julia Schüler, Ulrich Moebius, Christine Rothe, Olwill A. Shane, Brendan Horton, Stefani Spranger, Dayson Moreira, Tomasz Adamus, Xingli Zhao, Piotr Swiderski, Sumanta Pal, Marcin Kortylewski, Alyssa Kosmides, Kevin Necochea, Kathleen M. Mahoney, Sachet A. Shukla, Nikolaos Patsoukis, Apoorvi Chaudhri, Hung Pham, Ping Hua, Xia Bu, Baogong Zhu, Nir Hacohen, Catherine J. Wu, Edward Fritsch, Vassiliki A. Boussiotis, Gordon J. Freeman, Amy E. Moran, Fanny Polesso, Lisa Lukaesko, Emelie Rådestad, Lars Egevad, Berit Sundberg, Lars Henningsohn, Victor Levitsky, William Rafelson, John L. Reagan, Loren Fast, Pottayil Sasikumar, Naremaddepalli Sudarshan, Raghuveer Ramachandra, Nagesh Gowda, Dodheri Samiulla, Talapaneni Chandrasekhar, Sreenivas Adurthi, Jiju Mani, Rashmi Nair, Amit Dhudashia, Nagaraj Gowda, Murali Ramachandra, Alexander Sankin, Benjamin Gartrell, Kerwin Cumberbatch, Hongying Huang, Joshua Stern, Mark Schoenberg, Xingxing Zang, Ryan Swanson, Michael Kornacker, Lawrence Evans, Erika Rickel, Martin Wolfson, Sandrine Valsesia-Wittmann, Tala Shekarian, François Simard, Rodrigo Nailo, Aurélie Dutour, Anne-Catherine Jallas, Christophe Caux, and Aurélien Marabelle

Subjects
Pharmacology, 0303 health sciences, Cancer Research, Side effect, business.industry, medicine.drug_class, Immunology, Phases of clinical research, Monoclonal antibody, Phase i study, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Oncology, Pharmacokinetics, 030220 oncology & carcinogenesis, Molecular Medicine, Immunology and Allergy, Medicine, In patient, Programmed death 1, business, 030304 developmental biology
Published
2016

14. Resistance to Novel Antiandrogen Therapies in Metastatic Castration-Resistant Prostate Cancer

Author

Emmanuel S. Antonarakis and Karim Boudadi

Subjects
0301 basic medicine, Microarray, medicine.drug_class, Review, Bioinformatics, Antiandrogen, lcsh:RC254-282, resistance, chemistry.chemical_compound, Prostate cancer, 03 medical and health sciences, Immune system, Glucocorticoid receptor, 0302 clinical medicine, Downregulation and upregulation, abiraterone, Medicine, Enzalutamide, castration-resistant prostate cancer, 030304 developmental biology, 0303 health sciences, enzalutamide, business.industry, Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, novel androgen-directed therapy, 030104 developmental biology, chemistry, Oncology, 030220 oncology & carcinogenesis, Cancer research, business
Abstract

Despite the introduction of novel therapies that maximally decrease androgen-receptor (AR) signaling activity, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease. Even though abiraterone and enzalutamide represent breakthroughs in the treatment of mCRPC and have demonstrated significant survival benefits, a significant proportion of patients have primary resistance to these agents and virtually all patients develop secondary resistance. While the mechanisms of resistance to these agents are not fully understood, many hypotheses of AR-dependent and AR-independent mechanisms are emerging, including upregulation of AR and cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17), induction of AR splice variants, AR point mutations, upregulation of glucocorticoid receptor, activation of alternative oncogenic signaling pathways, neuroendocrine transformation, and immune evasion via programmed death-ligand 1 upregulation. The aim of this review is to summarize the most clinically relevant mechanisms of resistance to novel androgen-directed agents, focusing on escape from enzalutamide and abiraterone.

Published
2015

15. Phase II neoadjuvant and immunologic study of B7-H3 targeting with enoblituzumab in localized intermediate- and high-risk prostate cancer

Author

Carolyn Chapman, Trinity J. Bivalacqua, Rana Harb, Rehab Abdallah, Drew M. Pardoll, Tanya Skelton O'Neal, Charles G. Drake, Angelo M. DeMarzo, Eugene Shenderov, Emmanuel S. Antonarakis, Mohamad E. Allaf, Hao Wang, Karim Boudadi, and Christian P. Pavlovich

Subjects
0301 basic medicine, Cancer Research, business.industry, SUPERFAMILY, medicine.disease, Immune checkpoint, 03 medical and health sciences, Prostate cancer, 030104 developmental biology, Oncology, Cancer research, Medicine, Cytotoxic T cell, Tumor growth, Multiple tumors, business
Abstract

TPS5099Background: B7-H3 is part of the B7 superfamily and is an immune checkpoint expressed on multiple tumor types. B7-H3 inhibition limits tumor growth by enhancing cytotoxic T lymphocyte functi...

Published
2018

16. Multiple learning parameters differentially regulate olfactory generalization

Author

Venkata Anupama Narla, Thomas A. Cleland, and Karim Boudadi

Subjects
Male, Olfactory system, Sucrose, Conditioning, Classical, Sensory system, Olfaction, Stimulus (physiology), Generalization, Psychological, Article, Food Preferences, Mice, Behavioral Neuroscience, Discrimination, Psychological, Perceptual learning, Animals, Analysis of Variance, Dose-Response Relationship, Drug, Association Learning, Reproducibility of Results, Olfactory Pathways, Generalization (Psychology), Associative learning, Odor, Sweetening Agents, Odorants, Psychology, psychological phenomena and processes, Cognitive psychology
Abstract

Sensory representations depend strongly on the descending regulation of perceptual processing. Generalization among similar stimuli is a fundamental cognitive process that defines the extent of the variance in physical stimulus properties that becomes categorized together and associated with a common contingency, thereby establishing units of meaning. The olfactory system provides an experimentally tractable model system in which to study the interactions of these physical and psychological factors within the framework of their underlying neurophysiological mechanisms. The authors here show that olfactory associative learning systematically regulates gradients of odor generalization. Specifically, increasing odor-reward pairings, odor concentration, or reward quality--each a determinant of associative learning--significantly transformed olfactory generalization gradients, each narrowing the range of variance in odor quality perceived as likely to share the learned contingency of a conditioned odor stimulus. However, differences in the qualitative features of these three transformations suggest that these different determinants of learning are not necessarily theoretically interchangeable. These results demonstrate that odor representations are substantially shaped by experience and descending influences.

Published
2009

17. Diffuse Hypopigmentation Followed by Hyperpigmentation in an African American Woman with Hemangiopericytoma Treated with Dasatinib

Author

Rashmi Chugh and Karim Boudadi

Subjects
medicine.medical_specialty, Pathology, sarcoma, medicine.drug_class, Clinical Biochemistry, lcsh:Medicine, Oncology Section, Tyrosine-kinase inhibitor, tyrosine kinase inhibitor (tki), hemic and lymphatic diseases, medicine, Adverse effect, Hypopigmentation, Hemangiopericytoma, business.industry, lcsh:R, General Medicine, medicine.disease, Dermatology, Hyperpigmentation, Dasatinib, Skin hyperpigmentation, skin pigmentation, medicine.symptom, business, Tyrosine kinase, medicine.drug
Abstract

Dasatinib is a second-generation multi-target tyrosine kinase inhibitor (TKI) that has activity against many imatinib-resistant BCR-ABL mutant forms, Src, and c-Kit tyrosine kinases. While skin hypopigmentation is a well recognized adverse effect of first generation TKIs; it has rarely been reported with dasatinib. We report a unique case of diffuse cutaneous hypopigmentation induced by dasatinib followed by hyperpigmentation occurring in the same patient. A 52-year-old African American female with a history of metastatic hemangiopericytoma was initiated on dasatinib as part of a clinical trial. After 2 months of treatment, she developed generalized skin hypopigmentation. Within 1 month of discontinuing the drug, the patient’s skin pigmentation returned to normal. However, she then developed diffuse skin hyperpigmentation over the next couple of months. The hyperpigmentation was self-limited, and eventually resolved after several months.

Published
2014

18. Phase 2 biomarker-driven study of ipilimumab plus nivolumab (Ipi/Nivo) for ARV7-positive metastatic castrate-resistant prostate cancer (mCRPC)

Author

John L. Silberstein, Michael C. Haffner, Donna Dowling, Brandon Luber, Rana Sullivan, Charles G. Drake, Mario A. Eisenberger, Michael A. Carducci, Ryan Dittamore, Hao Wang, Jun Luo, Thomas R. Nirschl, Daniel L. Suzman, James R. Eshleman, Rana Harb, Alan K. Meeker, Emmanuel S. Antonarakis, and Karim Boudadi

Subjects
Oncology, Cancer Research, medicine.medical_specialty, DNA repair, business.industry, 030232 urology & nephrology, Castrate-resistant prostate cancer, Ipilimumab, Aggressive phenotype, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Immunology, medicine, Biomarker (medicine), Nivolumab, business, medicine.drug
Abstract

5035 Background: ARV7+ mCRPC is an aggressive phenotype with a median PFS of 3-4 mo and OS of 7-9 mo. We hypothesized that ARV7+ tumors would be enriched for DNA repair mutations, rendering them more responsive to combined immune checkpoint blockade. Methods: We enrolled 15 mCRPC pts with ARV7+ CTCs (using a CLIA-certified assay) into a single arm phase 2 study. Pts received Nivo 3 mg/kg plus Ipi 1 mg/kg every 3 wk x 4 doses, then maintenance Nivo 3 mg/kg every 2 wk. Targeted sequencing for DNA repair defects was performed on pretreatment tumor biopsies (n=11) or cell-free DNA (n=4). Primary endpoint: PSA50response rate. Secondary endpoints: objective response rate (ORR) in pts with measurable disease, durable PFS (lack of progression ≥24 wk), PSA‐PFS, radiographic (r)PFS, overall survival (OS), and frequency/intensity of AEs. Results: 15 ARV7+ men were enrolled, with median f/u 8.4 (range 1.9–10.5) mo. Median age was 65, 47% had ECOG ≥1, median PSA was 115 ng/mL, 67% had visceral/nodal mets, all had bone mets, and 60% had ≥4 prior regimens for mCRPC. Mean ARV7/AR ratio was 23% (range 3–75%). 6/15 men (40%) had pathogenic DNA repair gene mutations ( BRCA2, ATM, MSH6, FANCM, FANCA, POLH). Overall, the PSA50rate was 1/15 (7%), ORR was 2/8 (25%), durable PFS rate was 3/15 (20%), PSA-PFS was 3.0 (95%CI 2.1–4.9) mo, rPFS was 3.9 (95%CI 2.8–5.5) mo, and OS was 9.5 (95%CI 7.2–NA) mo. Outcomes appeared better in DNA repair deficient (DRD+) tumors vs. DNA repair proficient (DRD–) tumors (TABLE). 15 grade 3-4 treatment-related AEs occurred in 7/15 (46%) men (including 2 hepatitis, 2 colitis, 1 pneumonitis); there were no treatment-related deaths. Conclusions: In this first study targeting ARV7+ mCRPC, treatment with Ipi/Nivo had acceptable safety and encouraging efficacy, particularly in men with DRD+ tumors. DNA repair mutations may be enriched in ARV7+ prostate cancer. Clinical trial information: NCT02601014. [Table: see text]

Published
2017

19. A 62-year-old woman with osteogenic sarcoma in the contralateral breast 15 years after treatment for breast cancer

Author

Suresh C. Sharma, Andres Forero, Sara H. Javid, Vinod Ravi, Anshuma Bansal, Karim Boudadi, Budhi Singh Yadav, Christos Vaklavas, Rashmi Chugh, Benjamin O. Anderson, Shreyaskumar Patel, and Gloria J. Morris

Subjects
medicine.medical_specialty, Osteosarcoma, business.industry, General surgery, Carcinoma, Ductal, Breast, Medical practice, Breast Neoplasms, Neoplasms, Second Primary, Hematology, Middle Aged, medicine.disease, Clinical Practice, Radiography, Breast cancer, Oncology, medicine, Humans, Female, Contralateral breast, Sarcoma, business, After treatment
Abstract

b t g t b t p o t t n c t t v b W i s e m p s a b m o f a t g b d t o o c o t c t e p s e i A f w i d t b s o t b b m c a s s c o At times we encounter clinical problems for which there are no directly applicable evidence-based solutions, but we are compelled by circumstances to act. When doing so we rely on related evidence, general principles of best medical practice, and our experience. Each “Current Clinical Practice” feature article in Seminars in Oncology describes such a challenging presentation and offers treatment approaches from selected specialists. We invite readers’ comments and questions, which, with your approval, will be published in subsequent issues of the Journal. It is hoped that sharing our views and experiences will better inform our management decisions when we next encounter similar challenging patients. Please send your comments on the articles, your challenging cases, and your treatment successes to me at dr.gjmorris@gmail.com. I look forward to a lively discussion.

Published
2013

20. Intercalating docetaxel between novel hormone therapies (NHT) abiraterone and enzalutamide in metastatic castration resistant prostate cancer (mCRPC): Does it resensitize patients to the second NHT agent?

Author

Rosa Nadal, Karim Boudadi, Benjamin L. Maughan, and Emmanuel S. Antonarakis

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Castration resistant, medicine.disease, body regions, 03 medical and health sciences, Prostate cancer, chemistry.chemical_compound, Abiraterone, 030104 developmental biology, Docetaxel, chemistry, Internal medicine, medicine, Enzalutamide, Progression-free survival, business, medicine.drug, Hormone
Abstract

e16550Background: Prior studies with Enza and Abi have suggested decreased response rates and progression free survival when these agents are used sequentially. This suggests that there are mechani...

Published
2016

21. STARVE-PC: Biomarker-driven phase 2 study of ipilimumab plus nivolumab for AR-V7-expressing metastatic castration-resistant prostate cancer (mCRPC)

Author

Hao Wang, Maritza N. Taylor, Rana Sullivan, Alan K. Meeker, Brandon Luber, Charles G. Drake, Rana Harb, John L. Silberstein, Donna Dowling, Daniel L. Suzman, Emmanuel S. Antonarakis, Ryan Dittamore, Jun Luo, and Karim Boudadi

Subjects
Oncology, Cancer Research, medicine.medical_specialty, business.industry, Phases of clinical research, Ipilimumab, Castration resistant, medicine.disease, Abiraterone, chemistry.chemical_compound, Prostate cancer, chemistry, Internal medicine, Immunology, Medicine, Biomarker (medicine), Enzalutamide, Nivolumab, business, medicine.drug
Abstract

TPS5089Background: AR-V7 is an AR splice variant present in ~20% of men with mCRPC, and is associated with poor responses to abiraterone and enzalutamide. Developing effective treatments for AR-V7+...

Published
2016

22. Compensatory responses to age-related decline in odor quality acuity: Cholinergic neuromodulation and olfactory enrichment

Author

Thomas A. Cleland, Sara D. Suffis, Karim Boudadi, Christine E. Boxhorn, Venkata Anupama Narla, Shane T. Peace, Nathalie Mandairon, and Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Aging, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Cognitive decline, Cholinergic neuron, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Environmental enrichment, Basal forebrain, General Neuroscience, Adaptation, Physiological, Olfactory Bulb, Acetylcholine, Cholinergic Neurons, Associative learning, Olfactory bulb, Smell, Endocrinology, Odorants, Cholinergic, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Nerve Net, Geriatrics and Gerontology, Psychology, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology, medicine.drug
Abstract

The perceptual differentiation of odors can be measured behaviorally using generalization gradients. The steepness of these gradients defines a form of olfactory acuity for odor quality that depends on neural circuitry within the olfactory bulb and is regulated by cholinergic activity therein as well as by associative learning. Using this system as a reduced model for age-related cognitive decline, we show that aged mice, while maintaining almost the same baseline behavioral performance as younger mice, are insensitive to the effects of acutely elevated acetylcholine, which sharpens generalization gradients in young adult mice. Moreover, older mice exhibit evidence of chronically elevated acetylcholine levels in the olfactory bulb, suggesting that their insensitivity to further elevated levels of acetylcholine may arise because the maximum capacity of the system to respond to acetylcholine has already been reached. We propose a model in which an underlying, age-related, progressive deficit is mitigated by a compensatory cholinergic feedback loop that acts to retard the behavioral effects of what would otherwise be a substantial age-related decline in olfactory plasticity. We also treated mice with 10-day regimens of olfactory environmental enrichment and/or repeated systemic injections of the acetylcholinesterase inhibitor physostigmine. Each treatment alone sharpened odor quality acuity, but administering both treatments together had no greater effect than either alone. Age was not a significant main effect in this study, suggesting that some capacity for acetylcholine-dependent plasticity is still present in aged mice despite their sharply reduced ability to respond to acute increases in acetylcholine levels. These results suggest a dynamical framework for understanding age-related decline in neural circuit processing in which the direct effects of aging can be mitigated, at least temporarily, by systemic compensatory responses. In particular, a decline in cholinergic efficacy can precede any breakdown in cholinergic production, which may help explain the limited effectiveness of cholinergic replacement therapies in combating cognitive decline.

Published
2011

23. Late relapse in soft tissue sarcoma: Prognostic factors for recurrence after 3 years

Author

Scott M. Schuetze, Lili Zhao, Elizabeth J. Davis, Rashmi Chugh, Laurence H. Baker, and Karim Boudadi

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Soft tissue sarcoma, digestive, oral, and skin physiology, medicine.disease, Surgery, Resection, Oncology, medicine, In patient, business, Late Relapse, human activities
Abstract

10570 Background: In patients (pts) with localized soft tissue sarcoma (STS), 80% of relapses occur within the first 2 years (yrs) after definitive resection. However, relapse after 3 yrs is not un...

Published
2014

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