103 results on '"Mark E. Smolkin"'
Search Results
2. Data from Effect of Granulocyte/Macrophage Colony-Stimulating Factor on Circulating CD8+ and CD4+ T-Cell Responses to a Multipeptide Melanoma Vaccine: Outcome of a Multicenter Randomized Trial
- Author
-
Kimberly A. Chianese-Bullock, John M. Kirkwood, Marc E. Boisvert, William W. Grosh, Naomi B. Haas, Merrick I. Ross, Mark E. Smolkin, Walter C. Olson, Gina R. Petroni, and Craig L. Slingluff
- Abstract
Purpose: Granulocyte/macrophage colony-stimulating factor (GM-CSF) administered locally together with vaccines can augment T-cell responses in animal models. Human experience has been limited to small and uncontrolled trials. Thus, a multicenter randomized phase II trial was done to determine whether local administration of GM-CSF augments immunogenicity of a multipeptide vaccine. It also assessed immunogenicity of administration in one versus two vaccine sites.Experimental Design: One hundred twenty-one eligible patients with resected stage IIB to IV melanoma were vaccinated with 12 MHC class Irestricted melanoma peptides to stimulate CD8+ T cells plus a HLA-DRrestricted tetanus helper peptide to stimulate CD4+ T cells, emulsified in incomplete Freund's adjuvant, with or without 110 g GM-CSF. Among 119 evaluable patients, T-cell responses were assessed by IFN- ELIspot assay and tetramer analysis. Clinical outcomes were recorded.Results: CD8+ T-cell response rates to the 12 MHC class Irestricted melanoma peptides (by day 50) with or without GM-CSF were 34 and 73, respectively (P < 0.001), by direct ELIspot assay. Tetramer analyses corroborated the functional data. CD4+ T-cell responses to tetanus helper peptide were higher without GM-CSF (95 versus 77; P = 0.005). There was no significant difference by number of vaccine sites. Three-year overall and disease-free survival estimates (95 confidence interval) were 76 (67-83) and 52 (43-61), respectively, with too few events to assess differences by study group.Conclusions: High immune response rates for this multipeptide vaccine were achieved, but CD8+ and CD4+ T-cell responses were lower when administered with GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans. (Clin Cancer Res 2009;15(22):703644)
- Published
- 2023
3. Supplementary Methods from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
PDF file - 155K
- Published
- 2023
4. CCR Translation for the Article from Effect of Granulocyte/Macrophage Colony-Stimulating Factor on Circulating CD8+ and CD4+ T-Cell Responses to a Multipeptide Melanoma Vaccine: Outcome of a Multicenter Randomized Trial
- Author
-
Kimberly A. Chianese-Bullock, John M. Kirkwood, Marc E. Boisvert, William W. Grosh, Naomi B. Haas, Merrick I. Ross, Mark E. Smolkin, Walter C. Olson, Gina R. Petroni, and Craig L. Slingluff
- Abstract
CCR Translation for the Article from Effect of Granulocyte/Macrophage Colony-Stimulating Factor on Circulating CD8+ and CD4+ T-Cell Responses to a Multipeptide Melanoma Vaccine: Outcome of a Multicenter Randomized Trial
- Published
- 2023
5. Supplementary Table S1. Toxicities. from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
Detail of treatment-related toxicities.
- Published
- 2023
6. Supplementary Figure 3 from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
PDF file - 126K, Detailed data are shown for selected proteins assayed by RPPA.
- Published
- 2023
7. Supplementary Figure 1 from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
PDF file - 39K, Lymphocyte counts for all patients on study - detail.
- Published
- 2023
8. Data from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
Purpose: A CTEP-sponsored phase II trial was conducted to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) and bevacizumab in patients with advanced melanoma.Experimental Design: Patients with unresectable stage III to IV melanoma were treated intravenously with temsirolimus 25 mg weekly and bevacizumab 10 mg every 2 weeks. Adverse events were recorded using CTCAE v3.0. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and overall survival was recorded. Correlative studies measured protein kinases and histology of tumor biopsies and immune function in peripheral blood.Results: Seventeen patients were treated. Most patients tolerated treatment well, but 2 had grade 4 lymphopenia and 1 developed reversible grade 2 leukoencephalopathy. Best clinical response was partial response (PR) in 3 patients [17.7%, 90% confidence interval (CI) 5, 0–39.6], stable disease at 8 weeks (SD) in 9 patients, progressive disease (PD) in 4 patients, and not evaluable in 1 patient. Maximal response duration for PR was 35 months. Ten evaluable patients had BRAFWT tumors, among whom 3 had PRs, 5 had SD, and 2 had PD. Correlative studies of tumor biopsies revealed decreased phospho-S6K (d2 and d23 vs. d1, P < 0.001), and decreased mitotic rate (Ki67+) among melanoma cells by d23 (P = 0.007). Effects on immune functions were mixed, with decreased alloreactive T-cell responses and decreased circulating CD4+FoxP3+ cells.Conclusion: These data provide preliminary evidence for clinical activity of combination therapy with temsirolimus and bevacizumab, which may be greater in patients with BRAFwt melanoma. Mixed effects on immunologic function also support combination with immune therapies. Clin Cancer Res; 19(13); 3611–20. ©2013 AACR.
- Published
- 2023
9. Supplementary Text. from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
Supplemental text for Methods and Results.
- Published
- 2023
10. Supplementary Data from Effect of Granulocyte/Macrophage Colony-Stimulating Factor on Circulating CD8+ and CD4+ T-Cell Responses to a Multipeptide Melanoma Vaccine: Outcome of a Multicenter Randomized Trial
- Author
-
Kimberly A. Chianese-Bullock, John M. Kirkwood, Marc E. Boisvert, William W. Grosh, Naomi B. Haas, Merrick I. Ross, Mark E. Smolkin, Walter C. Olson, Gina R. Petroni, and Craig L. Slingluff
- Abstract
Supplementary Data from Effect of Granulocyte/Macrophage Colony-Stimulating Factor on Circulating CD8+ and CD4+ T-Cell Responses to a Multipeptide Melanoma Vaccine: Outcome of a Multicenter Randomized Trial
- Published
- 2023
11. Supplementary Figure 2 from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
PDF file - 208K, Blood cell counts for all patients on study, except lymphocytes.
- Published
- 2023
12. Supplementary Figure 3. Selected RPPA data from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
Detailed data are shown for selected proteins assayed by RPPA.
- Published
- 2023
13. Supplementary Figure S1. Lymphocyte counts from Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Michael J. Weber, Jeffrey E. Gershenwald, Prahlad Ram, Gulsun Erdag, Sofia M. Shea, Lainie Martin, Anthony J. Olszanski, Aubrey G. Wagenseller, Geoffrey R. Weiss, William W. Grosh, Cheryl Murphy Chase, Alison Gaucher, Walter C. Olson, Mark E. Smolkin, Amber L. Shada, Kimberly A. Chianese-Bullock, David L. Brautigan, Kerrington R. Molhoek, Gina R. Petroni, and Craig L. Slingluff
- Abstract
Lymphocyte counts for all patients on study - detail
- Published
- 2023
14. Supplementary Tables 1-4, Figure 1 from Immunotype and Immunohistologic Characteristics of Tumor-Infiltrating Immune Cells Are Associated with Clinical Outcome in Metastatic Melanoma
- Author
-
Craig L. Slingluff, James W. Patterson, Lynn T. Dengel, Sofia M. Shea, Donna H. Deacon, Mark E. Smolkin, Jochen T. Schaefer, and Gulsun Erdag
- Abstract
PDF file - 118K
- Published
- 2023
15. Somatic mutations show no clear association with red blood cell or human leukocyte antigen alloimmunization in de novo or therapy-related myelodysplastic syndrome
- Author
-
Brian D. Adkins, Ajay Mehta, Margaret Selesky, Stephany Vittitow, Mark E. Smolkin, Sarah J. Ratcliffe, and Chance J. Luckey
- Subjects
Immunology ,Immunology and Allergy ,Hematology - Abstract
Myelodysplastic syndrome (MDS) is a marrow failure disease. As patients often require chronic transfusion, many develop red blood cell (RBC) alloimmunization or immune-mediated platelet refractoriness. MDS represents a spectrum of diseases with specific categorizations and genetic abnormalities, and we set out to determine if these characteristics predispose patients to antibody formation.A natural language search identified MDS patients with pre-transfusion testing from 2015 to 2020. Marrow reports, cytogenetic results, and next-generation sequencing panels were gathered. Transfusion history and testing were collected from the laboratory information system.The group consisted of 226 biopsy-proven MDS patients. The prevalence of RBC alloimmunization was 11.1% (25 of 226). Half (23 of 46) of all RBC alloantibodies were against Rh (C, c, E, e) and Kell (K) antigens. There was a relative enrichment for JAK2 positivity among the RBC alloimmunized group. A total of 7.1% (16 of 226) of patients had immune-mediated platelet refractoriness and had increased transfusion requirements (p ≤ 0.01). No disease type or genetic abnormality was significantly associated with alloimmunization or immune-mediated platelet refractoriness.While JAK2 specific mutations were enriched among RBC alloimmunized patients, this association failed to reach statistical significance in our single-center cohort. Further study using larger patient cohorts is warranted. Overall, this cohort of MDS patients had very similar RBC alloimmunization prevalence and anti-RBC antibody specificities as other recent literature. Our data reinforce the finding that MDS patients are at greater risk for alloimmunization and support the use of extended phenotype matching for these at-risk patients.
- Published
- 2022
16. Specialty-Specific Readmission Risk Models Outperform General Models in Estimating Hepatopancreatobiliary Surgery Readmission Risk
- Author
-
Florence E. Turrentine, Timothy L. McMurry, R. Scott Jones, Mark E. Smolkin, and Victor M. Zaydfudim
- Subjects
medicine.medical_specialty ,Receiver operating characteristic ,business.industry ,medicine.medical_treatment ,Gastroenterology ,Specialty ,Nomogram ,Surgery ,Acs nsqip ,Pancreatectomy ,Medicine ,Derivation ,Hepatectomy ,business ,Readmission risk - Abstract
BACKGROUND Readmissions are costly and inconvenient for patients, and occur frequently in hepatopancreatobiliary (HPB) surgery practice. Readmission prediction tools exist, but most have not been designed or tested in the HPB patient population. METHODS Pancreatectomy and hepatectomy operation-specific readmission models defined as subspecialty readmission risk assessments (SRRA) were developed using clinically relevant data from merged 2014-15 ACS NSQIP Participant Use Data Files and Procedure Targeted datasets. The two derived procedure-specific models were tested along with 6 other readmission models in institutional validation cohorts in patients who had pancreatectomy or hepatectomy, respectively, between 2013 and 2017. Models were compared using area under the receiver operating characteristic curves (AUC). RESULTS A total of 16,884 patients (9169 pancreatectomy and 7715 hepatectomy) were included in the derivation models. A total of 665 patients (383 pancreatectomy and 282 hepatectomy) were included in the validation models. Specialty-specific readmission models outperformed general models. AUC characteristics of the derived pancreatectomy and hepatectomy SRRA (pancreatectomy AUC=0.66, hepatectomy AUC=0.74), modified Readmission After Pancreatectomy (AUC=0.76), and modified Readmission Risk Score for hepatectomy (AUC=0.78) outperformed general models for readmission risk: LOS/2 + ASA integer-based score (pancreatectomy AUC=0.58, hepatectomy AUC=0.66), LACE Index (pancreatectomy AUC=0.54, hepatectomy AUC=0.62), Unplanned Readmission Nomogram (pancreatectomy AUC=0.52, hepatectomy AUC=0.55), and institutional ARIA (pancreatectomy AUC=0.46, hepatectomy AUC=0.58). CONCLUSION HPB readmission risk models using 30-day subspecialty-specific data outperform general readmission risk tools. Hospitals and practices aiming to decrease readmissions in HPB surgery patient populations should use specialty-specific readmission reduction strategies.
- Published
- 2021
17. Characterization and comparison of innate and adaptive immune responses at vaccine sites in melanoma vaccine clinical trials
- Author
-
Marit M. Melssen, Alexander F. Koeppel, Donna H. Deacon, Gina R. Petroni, Craig L. Slingluff, Alexandra W. Hickman, Max O. Meneveau, Katia Sol-Church, Mark E. Smolkin, Joel Pinczewski, Karlyn Pollack, and Stephen D. Turner
- Subjects
Cancer Research ,Myeloid ,business.industry ,animal diseases ,medicine.medical_treatment ,Melanoma ,Immunology ,TLR9 ,chemical and pharmacologic phenomena ,medicine.disease ,Melanoma Vaccine ,Vaccination ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Oncology ,TLR4 ,Immunology and Allergy ,Medicine ,business ,Adjuvant ,030215 immunology - Abstract
The strength and durability of systemic anti-tumor immune responses induced by cancer vaccines depends on adjuvants to support an immunogenic vaccine site microenvironment (VSME). Adjuvants include water-in-oil emulsions with incomplete Freund's adjuvant (IFA) and combinations of toll-like receptor (TLR) agonists, including a preparation containing TLR4 and TLR9 agonists with QS-21 (AS15). IFA-containing vaccines can promote immune cell accumulation at the VSME, whereas effects of AS15 are largely unexplored. Therefore, we assessed innate and adaptive immune cell accumulation and gene expression at the VSME after vaccination with AS15 and compared to effects with IFA. We hypothesized that AS15 would promote less accumulation of innate and adaptive immune cells at the VSME than IFA vaccines. In two clinical trials, patients with resected high-risk melanoma received either a multipeptide vaccine with IFA or a recombinant MAGE-A3 protein vaccine with AS15. Vaccine site biopsies were obtained after one or multiple vaccines. T cells accumulated early after vaccines with AS15, but this was not durable or of the same magnitude as vaccination in IFA. Vaccines with AS15 increased durable expression of DC- and T cell-related genes, as well as PD-L1 and IDO1, suggesting complex activation and regulation of innate and adaptive immune function with AS15. These changes were generally greater with vaccines containing IFA, but IFA induced reduction in myeloid suppressor cells markers. Evidence of tertiary lymphoid structure (TLS) formation was observed with both adjuvants. Our findings highlight adjuvant-dependent changes in immune features at the VSME that may impact systemic immune responses.
- Published
- 2021
18. Lower volume, more impairment: reduced cholinergic basal forebrain grey matter density is associated with impaired cognition in Parkinson disease
- Author
-
Mark E. Smolkin, Joseph L. Flanigan, Carol A. Manning, T. Jason Druzgal, Scott A. Sperling, Matthew J. Barrett, Jamie C. Blair, and Cody S Freeman
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Neuroimaging ,Neuropsychological Tests ,Grey matter ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Dementia ,Cognitive Dysfunction ,Gray Matter ,030304 developmental biology ,0303 health sciences ,Basal forebrain ,medicine.diagnostic_test ,business.industry ,Montreal Cognitive Assessment ,Parkinson Disease ,Cognition ,Retrospective cohort study ,Neuropsychological test ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Cholinergic Neurons ,Psychiatry and Mental health ,medicine.anatomical_structure ,Basal Nucleus of Meynert ,Case-Control Studies ,Disease Progression ,Cholinergic ,Female ,Surgery ,Neurology (clinical) ,Atrophy ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveA major contributor to dementia in Parkinson disease (PD) is degeneration of the cholinergic basal forebrain. This study determined whether cholinergic nucleus 4 (Ch4) density is associated with cognition in early and more advanced PD.MethodsWe analysed brain MRIs and neuropsychological test scores for 228 newly diagnosed PD participants from the Parkinson’s Progression Markers Initiative (PPMI), 101 healthy controls from the PPMI and 125 more advanced PD patients from a local retrospective cohort. Cholinergic basal forebrain nuclei densities were determined by applying probabilistic maps to MPRAGE T1 sequences processed using voxel-based morphometry methods. Relationships between grey matter densities and cognitive scores were analysed using correlations and linear regression models.ResultsIn more advanced PD, greater Ch4 density was associated with Montreal Cognitive Assessment (MoCA) score (β=14.2; 95% CI=1.5 to 27.0; p=0.03), attention domain z-score (β=3.2; 95% CI=0.8 to 5.5; p=0.008) and visuospatial domain z-score (β=7.9; 95% CI=2.0 to 13.8; p=0.009). In the PPMI PD cohort, higher Ch4 was associated with higher scores on MoCA (β=9.2; 95% CI=1.9 to 16.5; p=0.01), Judgement of Line Orientation (β=20.4; 95% CI=13.8 to 27.0; pConclusionIn de novo and more advanced PD, lower Ch4 density is associated with impaired global cognition, attention and visuospatial function.
- Published
- 2019
19. PD-L1 expression in tumor cells and the immunologic milieu of bladder carcinomas: a pathologic review of 165 cases
- Author
-
Henry F. Frierson, Jonathan J. Davick, Alejandro A. Gru, and Mark E. Smolkin
- Subjects
0301 basic medicine ,Urothelial Cell ,medicine.drug_class ,medicine.medical_treatment ,Adenocarcinoma ,Cystectomy ,Monoclonal antibody ,B7-H1 Antigen ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,PD-L1 ,Biomarkers, Tumor ,medicine ,Humans ,Carcinoma, Small Cell ,Neoplasm Staging ,Carcinoma, Transitional Cell ,Bladder cancer ,Tissue microarray ,biology ,business.industry ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,Transitional cell carcinoma ,Urinary Bladder Neoplasms ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Cancer research ,biology.protein ,Neoplasm Grading ,Urothelium ,business - Abstract
Programmed death ligand 1 (PD-L1) is a transmembrane protein that plays a major role in immune suppression. Its interaction with the receptor PD-1 results in downregulation of antitumoral immunity. Humanized monoclonal antibodies that interrupt the PD-L1/PD-1 interaction have shown therapeutic efficacy in patients with advanced urothelial cancer. However, immunohistochemical staining of PD-L1 in bladder tumors and its relationship to tumor histologic type, grade, and overall survival has been incompletely analyzed. Slides from 165 cystectomy specimens were reviewed for tumor type, grade of urothelial carcinoma, pathologic stage, and overall survival. A tissue microarray (TMA) using four 0.6 mm cores from each case was constructed. Immunohistochemistry was performed on the TMA using a variety of new PD-L1 antibodies and platforms now widely available. For each case, the percent of tumor cells positive for PD-L1 and the percent of positive immune cells were scored. The overall number of bladder cancers positive for PD-L1 depended on the antibody/platform combination used and the threshold for considering a tumor "PD-L1-positive." Squamous cell carcinomas (SCCs) of the bladder demonstrated PD-L1 positivity more frequently than urothelial cell carcinomas (UCCs). High-grade UCCs were positive for PD-L1 on tumor cells more frequently than low-grade UCCs. There was no difference in survival between PD-L1-positive and PD-L1-negative bladder cancers in our study. Further studies should consider examining the predictive significance of PD-L1 IHC in bladder cancers.
- Published
- 2018
20. Predictors of early, recurrent, and intractable seizures in low-grade glioma
- Author
-
M. Beatriz S. Lopes, Jasmin Jo, Kathryn S. Nevel, Mark E. Smolkin, David Schiff, and Ryan Sutyla
- Subjects
medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Significant difference ,Medicine (miscellaneous) ,Original Articles ,medicine.disease ,Preoperative care ,Idh mutation ,Internal medicine ,Glioma ,medicine ,Low-Grade Glioma ,business ,Survival analysis ,Intractable seizures - Abstract
Background Seizures are common among patients with low-grade glioma (LGG) and can significantly affect morbidity. We sought to determine the association between the clinical and molecular factors with seizure incidence and refractoriness in LGG patients. Methods We conducted a retrospective review at the University of Virginia in patients with LGG (World Health Organization, WHO Grade II) evaluated between 2002 and 2015. Descriptive statistics were calculated for variables of interest, and the Kaplan-Meier method was used to estimate survival curves, which were compared with the log-rank test. Results A total of 291 patients were included; 254 had molecular testing performed for presence of an isocitrate dehydrogenase (IDH) mutation and/or 1p/19q codeletion. Sixty-eight percent of patients developed seizures prior to LGG diagnosis; 41% of all patients had intractable seizures. Using WHO 2016 integrated classification, there was no significant difference in seizure frequency during preoperative and postoperative periods or in developing intractable seizures, though a trend toward increased preoperative seizure incidence among patients with the IDH mutation was identified (P = .09). Male sex was significantly associated with higher seizure incidence during preoperative (P < .001) and postoperative periods (P < .001); men were also more likely to develop intractable seizures (P = .01). Conclusions Seizures are common among patients with LGG. Differences in preoperative or postoperative and intractable seizure rates by WHO 2016 classification were not detected. Our data showed a trend toward higher seizure incidence preoperatively in patients with IDH-mutant LGG. We describe a unique association between male sex and seizure incidence and intractability that warrants further study.
- Published
- 2021
21. Ventricular Arrhythmia Burden and Relationship to Interdialytic Period in Dialysis Patients with Cardiac Devices
- Author
-
Evan Harmon, Brittney Heard, Brendan T. Bowman, Mark E. Smolkin, Sula Mazimba, J. Michael Mangrum, Sarah J. Ratcliffe, and Nishaki Mehta
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Ventricular pacing ,Dialysis patients ,medicine.disease ,Sudden cardiac death ,Device therapy ,Internal medicine ,Cardiology ,Medicine ,In patient ,Hemodialysis ,Icd shocks ,business - Abstract
Background: Sudden cardiac death (SCD) is a major driver of mortality in patients with end-stage renal disease (ESRD) on hemodialysis (HD). The degree to which ventricular arrhythmias (VA) play a role in SCD in ESRD patients is unclear. Objective: Use cardiac implantable electronic devices (CIEDs) to clarify VA burden in ESRD patients overall and in relation to interdialytic cycle. Methods: We identified 44 patients at a single academic center with CIEDs, 22 on HD, along with 22 age- and sex-matched controls. Device interrogations from 11/13/14 – 4/8/19 were reviewed. Results: Overall, there were no differences in HD patients and controls in adjusted overall event rate (HD 9.81 x 10-5 ± 1.5 x 10-3 events/patient-hours vs control 3.71 x 10-5 ± 9.1 x 10-4 events/patient-hours, p = 0.902), or proportion of patients experiencing VA event (HD 45.4% vs control 63.6%, p = 0.226). There was no difference in ventricular pacing burden. Controls were more likely to require device therapy for VT/VF episodes (total ATP episodes 2/38 in HD vs 10/22 in controls, p < 0.01, total ICD shocks 10/38 in HD vs 17/22 in controls, p < 0.01). HD patients were most likely to experience VA within 12-hours of HD completion (p < 0.01), and the vast majority of events were NSVT. Conclusion: VA and ventricular pacing burden was similar by CIED analysis between groups. In HD patients, VA were likely to occur within the first 12 hours post-dialysis, were primarily NSVT, and were unlikely to require device therapy.
- Published
- 2021
22. Prediction of Prolonged Intensive Care Unit Length of Stay Following Cardiac Surgery
- Author
-
Gorav Ailawadi, Mark E. Smolkin, Sarah J. Ratcliffe, Nicholas R. Teman, Leora T. Yarboro, Mathew Hulse, Jared P. Beller, William Z. Chancellor, and Evan P. Rotar
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Model for End-Stage Liver Disease ,law ,Risk Factors ,medicine ,Humans ,Myocardial infarction ,Cardiac Surgical Procedures ,Intra-aortic balloon pump ,COPD ,Framingham Risk Score ,Receiver operating characteristic ,business.industry ,Thoracic Surgery ,General Medicine ,Length of Stay ,medicine.disease ,Intensive care unit ,Cardiac surgery ,Intensive Care Units ,Treatment Outcome ,030228 respiratory system ,Emergency medicine ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVES: Intensive care unit (ICU) costs comprise a significant proportion of the total inpatient charges for cardiac surgery. No reliable method for predicting intensive care unit length of stay following cardiac surgery exists, making appropriate staffing and resource allocation challenging. We sought to develop a predictive model to anticipate prolonged ICU length of stay (LOS). METHODS: All patients undergoing coronary artery bypass grafting (CABG) and/or valve surgery with a Society of Thoracic Surgeons (STS) predicted risk score were evaluated from an institutional STS database. Models were developed using 2014–2017 data; validation used 2018–2019 data. Prolonged ICU LOS was defined as requiring ICU care for at least three days postoperatively. Predictive models were created using lasso regression and relative utility compared. RESULTS: A total of 3,283 patients were included with 1669 (50.8%) undergoing isolated CABG. Overall, 32% of patients had prolonged ICU LOS. Patients with comorbid conditions including severe COPD (53% vs. 29%, p
- Published
- 2021
23. Specialty-Specific Readmission Risk Models Outperform General Models in Estimating Hepatopancreatobiliary Surgery Readmission Risk
- Author
-
Florence E, Turrentine, Timothy L, McMurry, Mark E, Smolkin, R Scott, Jones, and Victor M, Zaydfudim
- Subjects
Pancreatectomy ,Postoperative Complications ,ROC Curve ,Risk Factors ,Hepatectomy ,Humans ,Patient Readmission ,Retrospective Studies - Abstract
Readmissions are costly and inconvenient for patients, and occur frequently in hepatopancreatobiliary (HPB) surgery practice. Readmission prediction tools exist, but most have not been designed or tested in the HPB patient population.Pancreatectomy and hepatectomy operation-specific readmission models defined as subspecialty readmission risk assessments (SRRA) were developed using clinically relevant data from merged 2014-15 ACS NSQIP Participant Use Data Files and Procedure Targeted datasets. The two derived procedure-specific models were tested along with 6 other readmission models in institutional validation cohorts in patients who had pancreatectomy or hepatectomy, respectively, between 2013 and 2017. Models were compared using area under the receiver operating characteristic curves (AUC).A total of 16,884 patients (9169 pancreatectomy and 7715 hepatectomy) were included in the derivation models. A total of 665 patients (383 pancreatectomy and 282 hepatectomy) were included in the validation models. Specialty-specific readmission models outperformed general models. AUC characteristics of the derived pancreatectomy and hepatectomy SRRA (pancreatectomy AUC=0.66, hepatectomy AUC=0.74), modified Readmission After Pancreatectomy (AUC=0.76), and modified Readmission Risk Score for hepatectomy (AUC=0.78) outperformed general models for readmission risk: LOS/2 + ASA integer-based score (pancreatectomy AUC=0.58, hepatectomy AUC=0.66), LACE Index (pancreatectomy AUC=0.54, hepatectomy AUC=0.62), Unplanned Readmission Nomogram (pancreatectomy AUC=0.52, hepatectomy AUC=0.55), and institutional ARIA (pancreatectomy AUC=0.46, hepatectomy AUC=0.58).HPB readmission risk models using 30-day subspecialty-specific data outperform general readmission risk tools. Hospitals and practices aiming to decrease readmissions in HPB surgery patient populations should use specialty-specific readmission reduction strategies.
- Published
- 2020
24. Determining the Association Between Unplanned Reoperation and Readmission in Selected General Surgery Operations
- Author
-
Victor M. Zaydfudim, Mark E. Smolkin, Florence E. Turrentine, Timothy L. McMurry, R. Scott Jones, and John P. Davis
- Subjects
Reoperation ,medicine.medical_specialty ,medicine.medical_treatment ,Logistic regression ,Patient Readmission ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Risk Factors ,medicine ,Unplanned readmission ,Humans ,Colectomy ,Retrospective Studies ,Small bowel resection ,Ventral hernia repair ,business.industry ,General surgery ,Hernia, Ventral ,Acs nsqip ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Surgery ,Gastrectomy ,Index hospitalization ,business - Abstract
Unplanned reoperations and unplanned readmissions can increase morbidity and mortality. Few studies however, have explored the association of reoperation and readmission among general surgery patients. Our aim was to examine this relationship in selected abdominal operations.Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files from 2014 to 2018 were utilized. Six groups of operations, defined by ACS NSQIP procedure codes for ventral hernia repair, colectomy, appendectomy, proctectomy, small bowel resection, and gastrectomy, were assessed. Patients discharged ≤ 14 days after operation were included in the study. This time period was selected to reduce ACS NSQIP 30 day post-surgery follow-up bias. Unplanned reoperations were defined as those occurring during the index hospitalization. The primary outcome was unplanned readmission that occurred ≤ 14 days from the date of discharge. Logistic regression models were used to examine variables associated with unplanned readmission for each procedure group.A total of 787,118 patients were included: ventral hernia repair 35.2%, colectomy 30.6%, appendectomy 26.5%, proctectomy 3.7%, small bowel resection 3.2%, and gastrectomy 0.8%. Unplanned reoperation was independently associated with unplanned readmission for ventral hernia repair (OR 2.84, 95% CI 2.28-3.54, P0.001), colectomy (OR 1.58, CI 1.42- 1.76, P0.001), appendectomy (OR 2.91, CI 2.21-3.84, P0.001), and proctectomy (OR 1.41, CI 1.10-1.81, P = 0.006). Other clinically relevant covariates associated with readmission were partially dependent functional status before colectomy (OR 1.34, CI 1.23-1.46, P0.001), ventral hernia repair (OR 1.79, CI 1.54-2.09, P0.001), and small bowel resection (OR 1.44, CI 1.18-1.77, P0.001; and ASA 4/5 classification for colectomy (OR 2.71, CI 2.36-3.11, P0.001), proctectomy (OR 2.10, CI 1.48-2.97, P0.001), ventral hernia repair (OR 8.19, CI 6.78-9.88, P0.001), appendectomy (OR 2.80, CI 2.35-3.34, P0.001), and small bowel resection (OR 3.42, CI 2.20-5.32, P0.001). ASA 2, ASA 3 classification, age, and sex were also associated with unplanned readmission for most procedures.Unplanned reoperations are associated with an increase in unplanned readmission after selected abdominal operations included in this study. This factor should be considered in discharge and follow-up planning to help reduce unplanned readmissions.
- Published
- 2020
25. Characterization and comparison of innate and adaptive immune responses at vaccine sites in melanoma vaccine clinical trials
- Author
-
Marit M, Melssen, Karlyn E, Pollack, Max O, Meneveau, Mark E, Smolkin, Joel, Pinczewski, Alexander F, Koeppel, Stephen D, Turner, Katia, Sol-Church, Alexandra, Hickman, Donna H, Deacon, Gina R, Petroni, and Craig L, Slingluff
- Subjects
Male ,Skin Neoplasms ,T-Lymphocytes ,Freund's Adjuvant ,Vaccination ,Adaptive Immunity ,Middle Aged ,Cancer Vaccines ,Lipids ,Immunity, Innate ,Adjuvants, Immunologic ,Antigens, Neoplasm ,Vaccines, Subunit ,Tumor Microenvironment ,Humans ,Female ,Melanoma - Abstract
The strength and durability of systemic anti-tumor immune responses induced by cancer vaccines depends on adjuvants to support an immunogenic vaccine site microenvironment (VSME). Adjuvants include water-in-oil emulsions with incomplete Freund's adjuvant (IFA) and combinations of toll-like receptor (TLR) agonists, including a preparation containing TLR4 and TLR9 agonists with QS-21 (AS15). IFA-containing vaccines can promote immune cell accumulation at the VSME, whereas effects of AS15 are largely unexplored. Therefore, we assessed innate and adaptive immune cell accumulation and gene expression at the VSME after vaccination with AS15 and compared to effects with IFA. We hypothesized that AS15 would promote less accumulation of innate and adaptive immune cells at the VSME than IFA vaccines. In two clinical trials, patients with resected high-risk melanoma received either a multipeptide vaccine with IFA or a recombinant MAGE-A3 protein vaccine with AS15. Vaccine site biopsies were obtained after one or multiple vaccines. T cells accumulated early after vaccines with AS15, but this was not durable or of the same magnitude as vaccination in IFA. Vaccines with AS15 increased durable expression of DC- and T cell-related genes, as well as PD-L1 and IDO1, suggesting complex activation and regulation of innate and adaptive immune function with AS15. These changes were generally greater with vaccines containing IFA, but IFA induced reduction in myeloid suppressor cells markers. Evidence of tertiary lymphoid structure (TLS) formation was observed with both adjuvants. Our findings highlight adjuvant-dependent changes in immune features at the VSME that may impact systemic immune responses.
- Published
- 2020
26. The impact of cirrhosis and MELD score on postoperative morbidity and mortality among patients selected for liver resection
- Author
-
Victor M. Zaydfudim, Todd B. Bauer, Mark E. Smolkin, Florence E. Turrentine, Timothy L. McMurry, and Reid B. Adams
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,030230 surgery ,Chronic liver disease ,Gastroenterology ,Risk Assessment ,Severity of Illness Index ,Article ,Resection ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Postoperative Complications ,Postoperative risk ,Internal medicine ,medicine ,Hepatectomy ,Humans ,In patient ,Aged ,Retrospective Studies ,business.industry ,Patient Selection ,General Medicine ,Middle Aged ,medicine.disease ,Acs nsqip ,body regions ,Postoperative mortality ,030220 oncology & carcinogenesis ,Surgery ,Female ,Morbidity ,business - Abstract
BACKGROUND: Independent associations between chronic liver disease, MELD, and postoperative outcomes among patients selected for liver resection have not been completely established. We hypothesized independent associations between MELD, cirrhosis, and postoperative mortality. METHODS: Patient-level data from the targeted hepatectomy module and ACS NSQIP PUF during 2014–2015 were merged. Multivariable regression models with interaction effect between MELD and liver texture (normal vs congested/fatty vs cirrhotic) tested the independent effects of covariates on mortality and morbidity. RESULTS: 3,530 patients were included, of whom 668 patients (19%) had cirrhosis. ACS NSQIP defined mortality (3.9%vs1.1%) and morbidity (23.5%vs15.8%) were higher in patients with cirrhosis (both p
- Published
- 2019
27. Nonadherence to Biologic Therapies in Inflammatory Bowel Disease
- Author
-
Mark E. Smolkin, M Ashley Overby, Brian J. Wentworth, Anne Tuskey, Brian W Behm, and Ross C.D. Buerlein
- Subjects
Adult ,Male ,medicine.medical_specialty ,Population ,Pharmacy ,Antibodies, Monoclonal, Humanized ,Inflammatory bowel disease ,Medication Adherence ,Vedolizumab ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Gastrointestinal Agents ,Risk Factors ,Internal medicine ,Adalimumab ,medicine ,Humans ,Immunology and Allergy ,Certolizumab pegol ,education ,Retrospective Studies ,Biological Products ,education.field_of_study ,business.industry ,Gastroenterology ,Middle Aged ,Inflammatory Bowel Diseases ,medicine.disease ,Infliximab ,Surgery ,030220 oncology & carcinogenesis ,Cohort ,Certolizumab Pegol ,Female ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Biologic therapies have proven efficacy in inflammatory bowel disease (IBD). The clinical effectiveness of therapy is dependent in part on medication adherence, and patient non-adherence to biologic therapy is associated with increased risks of disease exacerbation and immunogenicity. The aim of this study was to assess adherence rates and risk factors for non-adherence for different biologic therapies in an IBD population. A retrospective chart review was performed on a cohort of adult IBD patients at our institution prescribed biologic medications from September 2014 to September 2015. Inclusion criteria were: adult age (≥18 yr) and treatment with a biologic medication for ≥3 months. Patients were excluded if they were transitioning care or had a dose interruption secondary to acute illness, surgery, or loss of insurance. Patient demographics and risk factors for non-adherence were assessed. For self-administered therapies, specialty pharmacies were contacted to determine the number of medication shipments each patient received. Adherence was assessed using a modified Medication Possession Ratio (# home medication deliveries or infusions completed divided by the expected # of such events). Statistical analysis was performed using 2-tailed student's T tests and Chi Square tests. One hundred seventy-five patients (mean age 40.1 yr, 61% female, 80% Crohn's) were included in the analysis. Of these patients, 37 (21%) failed to receive at least one scheduled infusion or medication shipment, and 20 (11%) failed to receive greater than 20% of their infusions or medication shipments. Biologic adherence rates were as follows: infliximab 84%, adalimumab 71%, certolizumab pegol 77%, and vedolizumab 87%. Patients receiving facility-administered therapies had significantly higher rates of adherence compared with those patients receiving self-injections (86% facility-administered versus 71% home administered, P = 0.021). Non-adherence was associated with lack of commercial insurance (30% versus 20%, P < 0.001) and was inversely associated with proximity to the medical center (mean mileage 93.6 versus 69.3, P = 0.048). Non-adherent patients were found to have higher rates of psychiatric disease (52% versus 37%), but this was not statistically significant. Non-adherence was not associated with patient age, gender, marital status, or disease activity in this patient population. The rate of biologic non-adherence was 21% in our IBD patient population, which is consistent with rates found in previous studies. Patient adherence was increased with facility-administered therapies (i.e., infliximab, vedolizumab) and commercial insurance, and an inverse relationship between proximity to the medical center and adherence was noted. Vedolizumab adherence was similar to infliximab in this patient population.
- Published
- 2018
28. Errors in Surgical Care: A Case Control Study
- Author
-
John B. Hanks, John P. Davis, Sarah J. Ratcliffe, Mark E. Smolkin, Worthington G. Schenk, Florence E. Turrentine, Katherine M. Marsh, Timothy L. McMurry, R. Scott Jones, and Bruce D. Schirmer
- Subjects
business.industry ,Surgical care ,Case-control study ,Medicine ,Surgery ,Medical emergency ,business ,medicine.disease - Published
- 2021
29. RACE IS ASSOCIATED WITH HEART TRANSPLANTATION BUT NOT MYOCARDIAL RECOVERY IN PATIENTS MANAGED WITH DURABLE LEFT VENTRICULAR ASSIST DEVICES
- Author
-
Daniel Addison, James Keiler, Nishaki Mehta, Sarah J. Ratcliffe, Ebony J. Hilton, Mark A. Fleming, Erik J. Scott, Kenneth C Bilchick, Khadijah Breathett, Mark E. Smolkin, Sula Mazimba, Hunter Mwansa, and Kierah Barnes
- Subjects
Heart transplantation ,medicine.medical_specialty ,Race (biology) ,business.industry ,Internal medicine ,medicine.medical_treatment ,Cardiology ,medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business - Published
- 2021
30. Immunogenicity in humans of a transdermal multipeptide melanoma vaccine administered with or without a TLR7 agonist
- Author
-
William W. Grosh, Max O. Meneveau, Walter C. Olson, Donna H. Deacon, Gina R. Petroni, James W. Patterson, Kevin T. Lynch, Craig L. Slingluff, Elizabeth M. H. Woodson, Mark E. Smolkin, Kimberly A. Chianese-Bullock, and Elise P. Salerno
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Cancer Research ,Skin Neoplasms ,Time Factors ,medicine.medical_treatment ,Freund's Adjuvant ,immunogenicity ,CD8-Positive T-Lymphocytes ,Pharmacology ,Melanoma Vaccine ,Immunogenicity, Vaccine ,vaccine ,Immunology and Allergy ,Medicine ,immunologic ,RC254-282 ,Clinical/Translational Cancer Immunotherapy ,Imiquimod ,clinical trials as topic ,ELISPOT ,Immunogenicity ,Vaccination ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Middle Aged ,Lipids ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Vaccines, Subunit ,Molecular Medicine ,Female ,Melanoma-Specific Antigens ,Adjuvant ,Adult ,Adolescent ,Injections, Intradermal ,Injections, Subcutaneous ,T cell ,Immunology ,Administration, Cutaneous ,Cancer Vaccines ,Young Adult ,Immune system ,Adjuvants, Immunologic ,melanoma ,Humans ,Aged ,business.industry ,Granulocyte-Macrophage Colony-Stimulating Factor ,Toll-Like Receptor 7 ,adjuvants ,Peptide vaccine ,business - Abstract
BackgroundExperimental cancer vaccines are traditionally administered by injection in subcutaneous tissue or muscle, commonly with adjuvants that create chronic inflammatory depots. Injection of melanoma-derived peptides induces T cell responses; however, the depots that form following injection may inhibit optimization of the immune response. In skin, epidermal Langerhans cells (LC) are a dominant source of professional antigen presenting cells. We hypothesized that: (1) applying melanoma-derived peptides topically, in proximity to LC, could be immunogenic and safe, with low vaccine-site toxicity and (2) topical toll-like receptor 7 (TLR7) agonist would increase immunogenicity of the peptide vaccine.MethodsTwelve melanoma peptides plus a tetanus helper peptide were combined with granulocyte macrophage colony stimulating factor (GM-CSF) and were administered topically on days 1, 8, and 15, to 28 patients randomized to one of four adjuvant preparations: (1) incomplete Freund’s adjuvant (IFA); (2) IFA plus a TLR7 agonist (imiquimod) administered on days 0, 7, 14; (3) dimethyl sulfoxide (DMSO) or (4) DMSO+ imiquimod administered on day 0, 7, 14. Every 3 weeks thereafter (x 6), the peptides were combined with GM-CSF and were injected into the dermis and subcutis in an emulsion with IFA. Toxicities were recorded and immune responses assayed by ELIspot.ResultsCD8+ T cell responses to transdermal vaccination in DMSO occurred in 83% of participants in group 3 and 86% in group 4, and responses to vaccination in IFA were observed in 29% of participants in group 1 and 14% in group 2. Overall, 61% of participants had CD4+ T cell immune responses to the tetanus peptide, with large, durable responses in groups 3 and 4. Five of seven participants in group 4 had a severe rash, one that was dose limiting. Ten-year overall survival was 67% and disease-free survival was 44%.ConclusionsThese data provide proof of principle for immunogenicity in humans of transdermal immunization using peptides in DMSO. Further study is warranted into the pharmacokinetics and immunobiology of TLR agonists as vaccine adjuvants during transcutaneous application. Overall survival is high, supporting further investigation of this immunization approach.
- Published
- 2021
31. More than Just the Number of Brain Metastases: Evaluating the Impact of Brain Metastasis Location and Relative Volume on Overall Survival After Stereotactic Radiosurgery
- Author
-
Jason P. Sheehan, Nirav Patel, Ashley Emery, Daniel M. Trifiletti, Mark E. Smolkin, and Kara D. Romano
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cerebellum ,Multivariate analysis ,medicine.medical_treatment ,Radiography ,Radiosurgery ,Risk Assessment ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Prevalence ,medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Brain Neoplasms ,business.industry ,Hazard ratio ,Virginia ,Middle Aged ,Prognosis ,medicine.disease ,Tumor Burden ,Surgery ,Survival Rate ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Neurology (clinical) ,Radiology ,Brainstem ,business ,030217 neurology & neurosurgery ,Brain metastasis - Abstract
Most evidence describing outcomes of patients with brain metastases is based on number of brain metastases, rather than location or volume. We evaluated the impact of tumor location and relative volume on overall survival (OS) among a large cohort of patients treated with stereotactic radiosurgery.Clinical, radiographic, and dosimetric data were collected on patients treated with first (if multiple) stereotactic radiosurgery for brain metastases. Multivariate analyses were performed to investigate the impact of brain metastasis relative location and volume on OS after stereotactic radiosurgery.Analysis included 300 patients with 817 tumors (116 patients with single brain metastasis). The most common tumor locations were supratentorial (75% of tumors), cerebellar (19%), and brainstem (5%). Median tumor volume was 0.4 mL (range, 0.003-65.0 mL). Tumor-specific factors associated with inferior OS included brainstem location versus both supratentorial and cerebellum locations for particular assumed values of cube root tumor volume (P0.001 for each) and increasing total supratentorial tumor volume (P = 0.004). Patients with supratentorial tumors and cerebellar tumors demonstrated similar OS, and cube root total tumor volume within the cerebellum and brainstem did not predict for OS.The presence of brainstem metastases and cumulative supratentorial tumor volume are adverse features that result in inferior survival. These results can be used to inform patient prognosis and future clinical trial design.
- Published
- 2017
32. A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund’s adjuvant in melanoma patients
- Author
-
Craig L. Slingluff, Nadejda V. Galeassi, Kelly T. Smith, Marit M. Melssen, Kimberly A. Chianese-Bullock, Mark E. Smolkin, Nolan A. Wages, Elizabeth M. Gaughan, Donna H. Deacon, Gina R. Petroni, Nikole Varhegyi, and William W. Grosh
- Subjects
CD4-Positive T-Lymphocytes ,Lipopolysaccharides ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Freund's Adjuvant ,CD8-Positive T-Lymphocytes ,ELIspot ,0302 clinical medicine ,Immunology and Allergy ,Cytotoxic T cell ,Polylysine ,Melanoma ,Peptide vaccine ,ELISPOT ,Toll-Like Receptors ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Lipids ,3. Good health ,Clinical trial ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Vaccines, Subunit ,Incomplete freund’s adjuvant ,Cohort ,Molecular Medicine ,Female ,Adjuvant ,Research Article ,T cell ,Immunology ,CD8 T cells ,Lipopolysaccharide ,Cancer Vaccines ,lcsh:RC254-282 ,03 medical and health sciences ,Immune system ,Adjuvants, Immunologic ,Toll-like receptor ,medicine ,Humans ,Immune response ,Pharmacology ,business.industry ,Poly I-C ,030104 developmental biology ,Carboxymethylcellulose Sodium ,polyICLC ,business ,CD8 - Abstract
Background Cancer vaccines require adjuvants to induce effective immune responses; however, there is no consensus on optimal adjuvants. We hypothesized that toll-like receptor (TLR)3 agonist polyICLC or TLR4 agonist lipopolysaccharide (LPS), combined with CD4 T cell activation, would support strong and durable CD8+ T cell responses, whereas addition of an incomplete Freund’s adjuvant (IFA) would reduce magnitude and persistence of immune responses. Patients and methods Participants with resected stage IIB-IV melanoma received a vaccine comprised of 12 melanoma peptides restricted by Class I MHC (12MP), plus a tetanus helper peptide (Tet). Participants were randomly assigned 2:1 to cohort 1 (LPS dose-escalation) or cohort 2 (polyICLC). Each cohort included 3 subgroups (a-c), receiving 12MP + Tet + TLR agonist without IFA (0), or with IFA in vaccine one (V1), or all six vaccines (V6). Toxicities were recorded (CTCAE v4). T cell responses were measured with IFNγ ELIspot assay ex vivo or after one in vitro stimulation (IVS). Results Fifty-three eligible patients were enrolled, of which fifty-one were treated. Treatment-related dose-limiting toxicities (DLTs) were observed in 0/33 patients in cohort 1 and in 2/18 patients in cohort 2 (11%). CD8 T cell responses to 12MP were detected ex vivo in cohort 1 (42%) and in cohort 2 (56%) and in 18, 50, and 72% for subgroups V0, V1, and V6, respectively. T cell responses to melanoma peptides were more durable and of highest magnitude for IFA V6. Conclusions LPS and polyICLC are safe and effective vaccine adjuvants when combined with IFA. Contrary to the central hypothesis, IFA enhanced T cell responses to peptide vaccines when added to TLR agonists. Future studies will aim to understand mechanisms underlying the favorable effects with IFA. Trial registration The clinical trial Mel58 was performed with IRB (#15781) and FDA approval and is registered with Clinicaltrials.gov on April 25, 2012 (NCT01585350). Patients provided written informed consent to participate. Enrollment started on June 24, 2012. Electronic supplementary material The online version of this article (10.1186/s40425-019-0625-x) contains supplementary material, which is available to authorized users.
- Published
- 2019
33. Functional and Cognitive Status in Clostridium difficile Infection in the Hospitalized Elderly: a Retrospective Study of Two Sites
- Author
-
Leticia Jimenez-Diez-Canseco, Maria-Jose Fernandez-Cotarelo, Mark E. Smolkin, Cirle A. Warren, Maria-Teresa Perez-Pomata, Brian V. Shenal, and Stephanie E. Nagy-Agren
- Subjects
Aged, 80 and over ,Male ,medicine.medical_specialty ,biology ,business.industry ,Retrospective cohort study ,Gut flora ,Clostridium difficile ,biology.organism_classification ,Article ,Hospitalization ,Cognition ,Internal medicine ,Case-Control Studies ,Internal Medicine ,medicine ,Clostridium Infections ,Cognitive status ,Humans ,Cognitive Dysfunction ,Female ,Cognitive impairment ,business ,Aged ,Retrospective Studies - Published
- 2019
34. A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial
- Author
-
Bruce Libby, David R. Brenin, Daniel M. Trifiletti, Gina R. Petroni, Timothy N. Showalter, Kelli A. Reardon, Parchayi Dalal, Anneke T. Schroen, Shayna L. Showalter, and Mark E. Smolkin
- Subjects
Cancer Research ,medicine.medical_treatment ,Brachytherapy ,Breast Neoplasms ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Humans ,Medicine ,Dosimetry ,Radiology, Nuclear Medicine and imaging ,Radiation Injuries ,Radiation treatment planning ,Intraoperative radiation therapy ,Mastectomy ,Aged ,Intraoperative Care ,Radiation ,business.industry ,Radiotherapy Dosage ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,High-Dose Rate Brachytherapy ,Clinical trial ,Radiation therapy ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Feasibility Studies ,Female ,Dose Fractionation, Radiation ,Tomography, X-Ray Computed ,business ,Nuclear medicine ,Radiotherapy, Image-Guided - Abstract
Existing intraoperative radiation therapy (IORT) techniques are criticized for the lack of image guided treatment planning and energy deposition with, at times, poor resultant dosimetry and low radiation dose. We pioneered a novel method of IORT that incorporates customized, computed tomography (CT)-based treatment planning and high-dose-rate (HDR) brachytherapy to overcome these drawbacks: CT-HDR-IORT.A phase 1 study was conducted to demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria included age ≥50 years, invasive or in situ breast cancer, tumor size3 cm, and N0 disease. Patients were eligible before or within 30 days of breast-conserving surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed. CT images were obtained, a customized HDR brachytherapy plan was created, and a dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The catheter was removed, and the skin was closed. The primary endpoints were feasibility and acute toxicity. Feasibility was defined as IORT treatment interval (time from CT acquisition until IORT completion) ≤90 minutes. The secondary endpoints included dosimetry, cosmetic outcome, quality of life, and late toxicity.Twenty-eight patients were enrolled. The 6-month follow-up assessments were completed by 93% of enrollees. The median IORT treatment interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%). There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients (21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic outcomes at the last follow-up visit.CT-HDR-IORT is feasible and safe. This promising approach for a conformal, image-based, higher-dose breast IORT is being evaluated in a phase 2 trial.
- Published
- 2016
35. Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases
- Author
-
Kimberly A. Chianese-Bullock, Anne M. Stowman, Mark E. Smolkin, Nadedja Galeassi, Francesco M. Marincola, Kelly T. Smith, Nolan A. Wages, Lynn T. Dengel, Craig L. Slingluff, Ileana S. Mauldin, Ena Wang, David W. Mullins, Donna H. Deacon, Gina R. Petroni, and Walter C. Olson
- Subjects
Male ,0301 basic medicine ,Enzyme-Linked Immunospot Assay ,Cancer Research ,T-Lymphocytes ,medicine.medical_treatment ,0302 clinical medicine ,Cell Movement ,immune system diseases ,Immunology and Allergy ,Medicine ,Interferon gamma ,Chemokine CCL5 ,Melanoma ,Cells, Cultured ,Aged, 80 and over ,Middle Aged ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Vaccines, Subunit ,CXCL9 ,Female ,Immunotherapy ,medicine.drug ,T cell ,Immunology ,Cancer Vaccines ,Article ,Interferon-gamma ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Immune system ,stomatognathic system ,Antigens, Neoplasm ,Humans ,Immunologic Factors ,CXCL10 ,CXCL11 ,Aged ,Neoplasm Staging ,business.industry ,medicine.disease ,Survival Analysis ,Peptide Fragments ,Chemokine CXCL11 ,Chemokine CXCL10 ,stomatognathic diseases ,030104 developmental biology ,business ,Follow-Up Studies - Abstract
Optimal approaches to induce T cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T cell recruitment and may be induced by IFN. This study tests the hypothesis that intratumoral administration of IFNγ will induce CXCL9-11 and will induce T cell recruitment and anti-tumor immune signatures in melanoma metastases.Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides and received IFNγ intratumorally. Effects on the tumor microenvironment were evaluated in sequential tumor biopsies. Adverse events (AEs) were recorded. T cell responses to vaccination were assessed in PBMC by IFNγ ELISPOT assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression, and gene expression.Vaccination and intratumoral administration of IFNγ were well tolerated. Circulating T cell responses to vaccine were detected in six of nine patients. IFNγ increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone, nor the addition of IFNγ promoted immune cell infiltration or induced anti-tumor immune gene signatures.The melanoma vaccine induced circulating T cell responses, but it failed to infiltrate metastases, thus highlighting the need for combination strategies to support T cell infiltration. A single intratumoral injection of IFNγ induced T cell-attracting chemokines; however, it also induced secondary immune regulation that may paradoxically limit immune infiltration and effector functions. Alternate dosing strategies or additional combinatorial treatments may be needed to promote trafficking and retention of tumor-reactive T cells in melanoma metastases.
- Published
- 2016
36. Orbital Metastases from Breast Cancer: Retrospective Analysis at an Academic Cancer Center
- Author
-
Mark E. Smolkin, Ali El Sayed, Patrick M. Dillon, Tiffany M. Pierson, and Emaculate V. Tebit
- Subjects
Adult ,medicine.medical_specialty ,genetic structures ,Bevacizumab ,medicine.medical_treatment ,Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal Medicine ,medicine ,Humans ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Diplopia ,Brain Neoplasms ,business.industry ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Survival Analysis ,eye diseases ,Surgery ,Radiation therapy ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,030221 ophthalmology & optometry ,Orbital Neoplasms ,Female ,sense organs ,medicine.symptom ,business ,Orbit (anatomy) ,medicine.drug - Abstract
Orbital metastases from breast cancer (BC) are rare, but often debilitating. BC accounts for nearly half of metastases to the orbit. Orbital metastases may be discovered years after the initial diagnosis of BC, and are rare at initial presentation. A search of the institutional data base at an academic cancer center identified BC patients who developed or presented with orbital metastases from 2000 to 2013. Baseline characteristics, treatment modalities, survival and treatment responses were collected from the electronic medical record. There were 20 patients identified with orbital metastases (0.7% of all BC cases). The median age at diagnosis of BC was 49 years; 80% had estrogen positive disease. The interval between the initial diagnosis of BC and the presentation of orbital metastases was 8.5 years (0-19 years). Orbital disease was the initial presentation of BC in two cases. Three patients developed bilateral orbital metastases and seven had accompanying brain metastases. The most common presentation was decreased vision (55%), followed by diplopia (25%). The median survival after orbital metastases was 24 months. Thirteen patients (65%) received local radiation therapy. Of those radiated, 90% reported improvement of orbital symptoms. Other treatments included intraocular bevacizumab, surgery, and systemic therapy. Orbital metastases tend to occur in estrogen receptor positive disease and are often found years after BC onset. Orbital metastases may be associated with the development of brain metastases. Radiotherapy is the preferred local therapy and had high symptom control in this cohort. Oncologists should be aware of the signs of orbital metastases and the treatment options.
- Published
- 2016
37. Prognostic value of albumin in patients with head and neck cancer
- Author
-
David C. Shonka, Mark E. Smolkin, Deepa Danan, Yamil Selman, Zenia Chow, and Mark J. Jameson
- Subjects
0301 basic medicine ,medicine.medical_specialty ,biology ,Proportional hazards model ,business.industry ,Head and neck cancer ,Hazard ratio ,Serum albumin ,Albumin ,Cancer ,Retrospective cohort study ,Perioperative ,medicine.disease ,Gastroenterology ,Surgery ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,biology.protein ,business - Abstract
Objectives/Hypothesis Albumin is an indicator of nutritional status and has been investigated as a predictor of cancer survival and perioperative outcomes. This study investigated the prognostic value of preoperative serum albumin in surgical patients with head and neck cancer (HNC). Study Design Retrospective cohort study. Methods A chart review was performed of patients who underwent HNC resection over a 6-year period at a single institution. Statistical analyses including Cox proportional hazards models, Pearson's correlation, and logistic regression were used to identify relationships between preoperative serum albumin and postoperative outcomes. Albumin was analyzed as a continuous variable. Results A total of 604 patients were studied representing all cancer types. There was no association between albumin and pneumonia, flap complications, or length of stay. Albumin was found to have statistically significant inverse associations with overall survival (OS) (hazard ratio [HR] = 0.685, P
- Published
- 2016
38. The Risk Factors of Readmission in Postoperative Gynecologic Oncology Patients at a Single Institution
- Author
-
Jennie P. Ou, John Nakayama, Linda R. Duska, Mark E. Smolkin, and Caroline Friedman
- Subjects
Adult ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,Genital Neoplasms, Female ,Vomiting ,Nausea ,Anastomotic Leak ,Tissue Adhesions ,Gynecologic oncology ,Postoperative Hemorrhage ,Patient Readmission ,Hospitals, University ,Young Adult ,Risk Factors ,Sepsis ,Humans ,Surgical Wound Infection ,Medicine ,Medical history ,Postoperative Period ,Aged ,Retrospective Studies ,Aged, 80 and over ,Insurance, Health ,business.industry ,Mental Disorders ,General surgery ,Virginia ,Case-control study ,Obstetrics and Gynecology ,Postoperative complication ,Thrombosis ,Retrospective cohort study ,Middle Aged ,Abscess ,Surgery ,Oncology ,Case-Control Studies ,Female ,medicine.symptom ,business - Abstract
IntroductionHospital readmission rates are an important measure of quality care and have recently been tied to reimbursement. This study seeks to identify the risk factors for postoperative readmission in patients treated by a gynecologic oncology service.MethodsA 7-year retrospective review (2007–2013) of all patients operated on by the University of Virginia gynecologic oncology service who were readmitted within 30 days of discharge was performed. Abstracted data included demographics, dates of surgery, operative details, cancer history, and relevant medical history. The readmitted patients (n = 166) were compared with randomly selected controls (n = 168) from the same service in a matching time frame and analyzed using univariate and multivariate models.ResultsIn the study period, 2993 operations were performed. One hundred sixty-six unique patients (5.5%) were readmitted within 30 days of discharge from their operative procedure. On multivariate analysis, the factors that were associated with a higher risk of readmission were a history of psychiatric disease, postoperative complication, type of insurance, surgical modality, and lysis of adhesions at the time of surgery. The most common readmission diagnoses were infection (44%), nausea/vomiting (28%), thrombosis (6%), bowel leak (4%), and bleeding (4%).ConclusionsPostoperative readmissions are a common problem and are increasingly important as a measure of quality. Although patients were generally admitted for infections or gastrointestinal complaints, we also found that individual factors such as mental health and socioeconomic status also contributed. Our data suggest that we can preoperatively identify high-risk individuals for whom extra resources can be directed postoperatively to avoid unnecessary readmissions.
- Published
- 2015
39. MHC-restricted phosphopeptide antigens: preclinical validation and first-in-humans clinical trial in participants with high-risk melanoma
- Author
-
Rebecca C. Obeng, Nikole Varhegyi, Kimberly A. Chianese-Bullock, Gina R. Petroni, Geoffrey R. Weiss, Elizabeth M. Gaughan, Angela L. Ambakhutwala, Emily H. Hall, Kelly T. Smith, Mark Cobbold, Victor H. Engelhard, Kara L. Cummings, Amanda M. Lulu, Paisley T. Myers, Mark E. Smolkin, Nico Buettner, Craig L. Slingluff, Jeffrey Shabanowitz, Kathleen Haden, Donald F. Hunt, and Keira E. Mahoney
- Subjects
Male ,Phosphopeptides ,0301 basic medicine ,Cancer Research ,Skin Neoplasms ,medicine.medical_treatment ,Pilot Projects ,immunogenicity ,CD8-Positive T-Lymphocytes ,Mice ,Immunogenicity, Vaccine ,0302 clinical medicine ,Cancer immunotherapy ,antigens ,vaccine ,Guanine Nucleotide Exchange Factors ,Immunology and Allergy ,RC254-282 ,Clinical/Translational Cancer Immunotherapy ,Aged, 80 and over ,Phosphopeptide ,Immunogenicity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Common Terminology Criteria for Adverse Events ,Middle Aged ,Oncology ,030220 oncology & carcinogenesis ,Vaccines, Subunit ,Molecular Medicine ,Female ,Immunotherapy ,Adult ,Immunology ,Mice, Transgenic ,Cancer Vaccines ,Proof of Concept Study ,03 medical and health sciences ,Breast cancer ,Antigen ,Antigens, Neoplasm ,Cell Line, Tumor ,HLA-A2 Antigen ,melanoma ,medicine ,Animals ,Humans ,Adaptor Proteins, Signal Transducing ,Aged ,Pharmacology ,business.industry ,Cancer ,vaccination ,medicine.disease ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Insulin Receptor Substrate Proteins ,Cancer research ,business ,neoplasm - Abstract
BackgroundPhosphorylated peptides presented by MHC molecules represent a new class of neoantigens expressed on cancer cells and recognized by CD8 T-cells. These peptides are promising targets for cancer immunotherapy. Previous work identified an HLA-A*0201-restricted phosphopeptide from insulin receptor substrate 2 (pIRS2) as one such target. The purpose of this study was to characterize a second phosphopeptide, from breast cancer antiestrogen resistance 3 (BCAR3), and to evaluate safety and immunogenicity of a novel immunotherapic vaccine comprising either or both of these phosphorylated peptides.MethodsPhosphorylated BCAR3 protein was evaluated in melanoma and breast cancer cell lines by Western blot, and recognition by T-cells specific for HLA-A*0201-restricted phosphorylated BCAR3 peptide (pBCAR3126-134) was determined by51Cr release assay and intracellular cytokine staining. Human tumor explants were also evaluated by mass spectrometry for presentation of pIRS2 and pBCAR3 peptides. For the clinical trial, participants with resected stage IIA–IV melanoma were vaccinated 6 times over 12 weeks with one or both peptides in incomplete Freund’s adjuvant and Hiltonol (poly-ICLC). Adverse events (AEs) were coded based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V.4.03, with provision for early study termination if dose-limiting toxicity (DLT) rates exceeded 33%. The enrollment target was 12 participants evaluable for immune response to each peptide. T-cell responses were assessed by interferon-γ ELISpot assay.ResultspBCAR3 peptides were immunogenic in vivo in mice, and in vitro in normal human donors, and T-cells specific for pBCAR3126-134controlled outgrowth of a tumor xenograft. The pIRS21097-1105peptide was identified by mass spectrometry from human hepatocellular carcinoma tumors. In the clinical trial, 15 participants were enrolled. All had grade 1 or 2 treatment-related AEs, but there were no grade 3–4 AEs, DLTs or deaths on study. T-cell responses were induced to the pIRS21097-1105peptide in 5/12 patients (42%, 90% CI 18% to 68%) and to the pBCAR3126-134peptide in 2/12 patients (17%, 90% CI 3% to 44%).ConclusionThis study supports the safety and immunogenicity of vaccines containing the cancer-associated phosphopeptides pBCAR3126-134and pIRS21097-1105, and the data support continued development of immune therapy targeting phosphopeptides. Future studies will define ways to further enhance the magnitude and durability of phosphopeptide-specific immune responses.Trial registration numberNCT01846143
- Published
- 2020
40. Defining the effects of age and gender on immune response and outcomes to melanoma vaccination: a retrospective analysis of a single-institution clinical trials’ experience
- Author
-
Nolan A. Wages, Mark E. Smolkin, Adriana G. Ramirez, Yinin Hu, and Craig L. Slingluff
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Immunology ,Adaptive Immunity ,Cancer Vaccines ,Article ,Disease-Free Survival ,Sex Factors ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Cumulative incidence ,Melanoma ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Age Factors ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Clinical trial ,Vaccination ,Treatment Outcome ,Multivariate Analysis ,Vaccines, Subunit ,Female ,Cancer vaccine ,business ,CD8 - Abstract
The impacts of patient age and gender on immune response (IR) and clinical outcome after cancer vaccines are not known. We hypothesized younger and female patients would have higher IR rates and better survival.Patients with resected stage IIB-IV melanoma in three clinical trials (Mel43, Mel44, Mel48) were vaccinated with 12 melanoma-associated peptides restricted by class I MHC. The cumulative incidence rate of CD8(+) T cell responses (direct interferon-gamma ELIspot assay) by week 7 was compared by age and gender. Overall survival (OS) and disease-free survival (DFS) landmark analyses were compared by Kaplan-Meier estimates and in multivariate analyses.T cell responses were evaluated in 327 patients and detected in 50 % of males and 48 % of females, with no difference in IR by gender or menopausal status. Males had trends toward longer DFS (p = 0.12) and OS (p = 0.09). Cumulative incidence of IR was higher in patients64 years of age versus older patients (p = 0.03). OS and DFS were similar by age group (p0.50). In multivariate modeling, younger age was associated with better IR (OR 0.40, p value 0.003), without an impact of age or gender on clinical outcomes.These data support the hypothesis that older patients are less likely to develop T cell responses to a cancer vaccine. Nonetheless, significant proportions of older patients mount immune responses with comparable survival outcomes. Thus, these data support including older patients in cancer vaccine trials, but suggest value in stratifying patients by age/64 years.
- Published
- 2015
41. Baseline symptoms and basal forebrain volume predict future psychosis in early Parkinson disease
- Author
-
Mark E. Smolkin, Scott A. Sperling, T. Jason Druzgal, Jamie C. Blair, and Matthew J. Barrett
- Subjects
0301 basic medicine ,Male ,Psychosis ,medicine.medical_specialty ,Movement disorders ,Basal Forebrain ,Excessive daytime sleepiness ,Lower risk ,REM sleep behavior disorder ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Medicine ,Humans ,business.industry ,Epworth Sleepiness Scale ,Parkinson Disease ,Odds ratio ,Organ Size ,Middle Aged ,medicine.disease ,Prognosis ,030104 developmental biology ,Psychotic Disorders ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
ObjectiveDetermining baseline predictors of future psychosis in Parkinson disease (PD) may identify those at risk for more rapidly progressive disease, i.e., a more malignant PD subtype.MethodsThis cohort study evaluated 423 patients with newly diagnosed PD collected as part of the Parkinson's Progression Markers Initiative. Psychotic symptoms were assessed with the Movement Disorders Society–Unified Parkinson Disease Rating Scale item 1.2, which assesses hallucinations and psychosis over the past week. At baseline, participants completed the Scales for Outcomes in Parkinson's Disease–Autonomic, the REM Sleep Behavior Disorder (RBD) Screening Questionnaire, and the Epworth Sleepiness Scale. Cholinergic nucleus 4 (Ch4) density was calculated for 228 participants with PD and 101 healthy controls.ResultsMultivariate logistic regression adjusted for age and sex found that greater autonomic symptoms (p = 0.002), RBD (p = 0.021), and excessive daytime sleepiness (EDS) (p = 0.003) at baseline were associated with increased risk of reporting psychotic symptoms on ≥2 occasions. Having 2 or 3 of these baseline symptoms was associated with lower Ch4 density (p = 0.007). In a logistic regression model adjusted for age and sex, higher Ch4 gray matter density was associated with lower risk of reporting psychotic symptoms on ≥2 occasions (odds ratio 0.96 [for an increase in density of 1 unit], p = 0.03).ConclusionsThis study confirms that RBD, EDS, and greater autonomic symptom burden are associated with greater risk of future psychotic symptoms in PD. Reduced Ch4 density at baseline is associated with future psychotic symptoms and a greater burden of RBD, EDS, and autonomic symptoms.
- Published
- 2017
42. Characteristics, correlates, and assessment of psychosis in Parkinson disease without dementia
- Author
-
Binit B. Shah, Scott A. Sperling, Matthew J. Barrett, Mark E. Smolkin, Madaline B. Harrison, and Joseph L. Flanigan
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Psychosis ,Hallucinations ,Disease ,REM Sleep Behavior Disorder ,Neuropsychological Tests ,REM sleep behavior disorder ,Delusions ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Dopamine ,Internal medicine ,medicine ,Dementia ,Humans ,Psychiatry ,Aged ,Aged, 80 and over ,Psychiatric Status Rating Scales ,business.industry ,Symptom burden ,Montreal Cognitive Assessment ,Parkinson Disease ,Middle Aged ,medicine.disease ,030104 developmental biology ,Logistic Models ,Neurology ,Psychotic Disorders ,Autonomic symptoms ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Considering that psychosis in Parkinson disease (PD) is associated with worse outcomes, including dementia, we aimed to study the characteristics, correlates, and assessment of PD psychosis in those without dementia.101 PD subjects without dementia (Montreal Cognitive Assessment ≥21/30) were recruited to participate in a study of neuropsychiatric symptoms in PD. This study included a baseline standard neurological exam and common PD symptom assessments. Using the Scale for the Assessment of Positive Symptoms (SAPS) and separate assessment of visual illusions and sense of presence, NINDS-NIMH criteria for PD psychosis were applied.Of the 33 (32.7%) PD subjects who met diagnostic criteria for psychosis in PD, visual illusions were most common (72.7%), followed by visual hallucinations (39.4%). Adjusted for presence of REM sleep behavior disorder (RBD) (p = 0.097), use of dopamine agonists (OR = 3.7, p = 0.012) and greater autonomic symptom burden (OR = 1.1 (per 1-unit change in score on SCOPA-AUT), p = 0.012) were associated with greater risk of psychosis. Use of dopamine agonists (OR = 5.0, p = 0.007), higher MDS-UPDRS Part II score (OR = 1.1, p = 0.010), and presence of RBD (OR = 4.8, p = 0.012) were independent predictors of visual hallucinations and visual illusions. MDS-UPDRS item 1.2 score ≥1 had highly correlated with the SAPS score (r = 0.65, p 0.0001), but was 42% sensitive and 96% specific for identifying psychosis.This study confirms the association between dopamine agonists and psychosis in PD patients without dementia. The association of RBD, autonomic symptoms, and MDS-UPDRS Part II scores with psychosis underscore its link to brainstem dysfunction and greater PD motor symptom severity.
- Published
- 2017
43. Impact of blood transfusions on patients with head and neck cancer undergoing free tissue transfer
- Author
-
Mark J. Jameson, David C. Shonka, Mark E. Smolkin, Nikole Varhegyi, Stephen R Bakos, and Deepa Danan
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Proportional hazards model ,Hazard ratio ,Head and neck cancer ,Albumin ,Retrospective cohort study ,Free flap ,Hematocrit ,medicine.disease ,Tissue transfer ,Surgery ,Otorhinolaryngology ,medicine ,business - Abstract
Objectives/Hypothesis To determine whether blood transfusions are associated with adverse outcomes in patients with head and neck cancer (HNC) undergoing microvascular free tissue transfer. Study Design Retrospective cohort study. Methods The records of all patients who underwent free flaps for reconstruction after HNC resection from July 2007 through February 2013 at a single institution were reviewed. Rates of overall survival (OS), recurrence free survival (RFS), and postoperative wound infection were determined. Statistical analyses included Cox proportional hazards models and chi-square tests. Results Of 167 patients, 90 received 0 to 2 units of blood and 77 received ≥ 3. After controlling for age, preoperative hemoglobin, preoperative albumin, cancer stage, and adverse pathologic features, transfusion of ≥ 3 (versus 0 to 2) units was associated with poorer OS (P = 0.0006; hazard ratio [HR] = 2.96) and RFS (P = 0.003; HR = 2.35). The rates of wound infection in patients who received 0, 1, 2, or ≥ 3 units were 13.3%, 21.2%, 33.3%, and 31.2%, respectively. There was a statistically significant difference in wound infection rates between those patients receiving 0 to 1 versus ≥ 2 units (P = 0.04). Conclusions Patients who receive ≥ 3 units of blood after free tissue transfer for HNC had a significantly increased risk of death after controlling for age, preoperative hemoglobin and albumin, cancer stage, and adverse pathologic features. Increased transfusions are also associated with higher wound infection rates. The increased tendency to transfuse free flap patients in order to maintain a threshold hematocrit may have a detrimental impact on survival and wound infections and should be revisited. Level of Evidence 2b. Laryngoscope, 125:86–91, 2015
- Published
- 2014
44. Inflammatory Adverse Events are Associated with Disease-Free Survival after Vaccine Therapy among Patients with Melanoma
- Author
-
Gina R. Petroni, Emily J. White, Patrice Y. Neese, Yinin Hu, Mark E. Smolkin, and Craig L. Slingluff
- Subjects
Adult ,Lung Diseases ,Male ,Oncology ,medicine.medical_specialty ,Vitiligo ,CD8-Positive T-Lymphocytes ,Nodular melanoma ,Skin Diseases ,Article ,Antigens, Neoplasm ,Internal medicine ,medicine ,Humans ,Adverse effect ,Melanoma ,Survival rate ,Neoplasm Staging ,Inflammation ,business.industry ,Histocompatibility Antigens Class I ,Hazard ratio ,Immunotherapy, Active ,Common Terminology Criteria for Adverse Events ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Immunology ,Female ,Surgery ,Neoplasm Recurrence, Local ,business ,CD8 ,Follow-Up Studies - Abstract
Multipeptide vaccines for melanoma may cause inflammatory adverse events (IAE). We hypothesize that IAE are associated with a higher rate of immune response (IR) to vaccination and improved clinical outcomes.Adult patients with resected, high-risk (stage IIB to IV) melanoma were vaccinated with a combination of 12 class I major histocompatibility complex (MHC)-restricted melanoma epitopes, and IAE were recorded. A separate category for hypopigmentation (vitiligo) was also assessed. CD8(+) T cell IR was assessed by direct interferon gamma ELISpot analysis. Overall survival and disease-free survival were analyzed by Cox proportional hazard modeling.Out of 332 patients, 57 developed IAE, the majority of which were dermatologic (minimum Common Terminology Criteria for Adverse Events [CTCAE] grade 3). Most nondermatologic IAE were CTCAE grade 1 and 2. Vitiligo developed in 23 patients (7 %). A total of 174 patients (53 %) developed a CD8(+) response. Presence of IAE was significantly associated with development of IR (70 vs. 49 %, p = 0.005) and with disease-free survival (hazard ratio 0.54, p = 0.043). There were no significant associations relating vitiligo or IR alone with clinical outcomes.IAE are associated with a higher rate of CD8(+) T cell response after vaccination therapy for high-risk melanoma. Our findings suggest either that antitumor activity induced by class I MHC-restricted peptide vaccines may depend on immunologic effects beyond simple expansion of CD8(+) T cells or that the intrinsic inflammatory response of patients contributes to clinical outcome in melanoma.
- Published
- 2014
45. Immunologic hierarchy, class II MHC promiscuity, and epitope spreading of a melanoma helper peptide vaccine
- Author
-
William W. Grosh, Andrea Czarkowski, Mark E. Smolkin, Walter C. Olson, Gina R. Petroni, Craig L. Slingluff, Yinin Hu, and Kimberly A. Chianese-Bullock
- Subjects
Cancer Research ,Skin Neoplasms ,T cell ,Molecular Sequence Data ,Immunology ,Human leukocyte antigen ,Major histocompatibility complex ,Cancer Vaccines ,Article ,Epitope ,Epitopes ,HLA Antigens ,MHC class I ,Humans ,Immunology and Allergy ,Medicine ,Amino Acid Sequence ,Melanoma ,Alleles ,biology ,business.industry ,Immunogenicity ,Cell Differentiation ,Virology ,medicine.anatomical_structure ,Oncology ,CD4 Antigens ,Melanoma Helper Peptide Vaccine ,biology.protein ,Peptides ,business ,CD8 - Abstract
Immunization with a combination melanoma helper peptide (6MHP) vaccine has been shown to induce CD4(+) T cell responses, which are associated with patient survival. In the present study, we define the relative immunogenicity and HLA allele promiscuity of individual helper peptides and identify helper peptide-mediated augmentation of specific CD8(+) T cell responses. Thirty-seven participants with stage IIIB-IV melanoma were vaccinated with 6MHP in incomplete Freund's adjuvant. The 6MHP vaccine is comprised of 6 peptides representing melanocytic differentiation proteins gp100, tyrosinase, Melan-A/MART-1, and cancer testis antigens from the MAGE family. CD4(+) and CD8(+) T cell responses were assessed in peripheral blood and in sentinel immunized nodes (SIN) by thymidine uptake after exposure to helper peptides and by direct interferon-γ ELIspot assay against 14 MHC class I-restricted peptides. Vaccine-induced CD4(+) T cell responses to individual epitopes were detected in the SIN of 63 % (22/35) and in the peripheral blood of 38 % (14/37) of participants for an overall response rate of 65 % (24/37). The most frequently immunogenic peptides were MAGE-A3281-295 (49 %) and tyrosinase386-406 (32 %). Responses were not limited to HLA restrictions originally described. Vaccine-associated CD8(+) T cell responses against class I-restricted peptides were observed in 45 % (5/11) of evaluable participants. The 6MHP vaccine induces both CD4(+) and CD8(+) T cell responses against melanoma antigens. CD4(+) T cell responses were detected beyond reported HLA-DR restrictions. Induction of CD8(+) T cell responses suggests epitope spreading and systemic activity mediated at the tumor site.
- Published
- 2014
46. 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
47. 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
48. Male gender is associated with seizure risk in low-grade glioma (LGG) patients
- Author
-
Mark E. Smolkin, Jasmin Jo, M. Beatriz S. Lopes, David Schiff, Ryan Sutyla, and Kathryn Sara Nevel
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Low-Grade Glioma ,business ,Male gender - Abstract
e13520 Background: Up to 90% of LGG patients present with seizures, but the risk of developing seizure is not known. Our goal was to determine the association between clinical and molecular factors with seizure incidence in LGG patients. Methods: Retrospective study from 2/2002-1/2015 involving 291 patients ≥18 years old, with diagnosis of WHO grade II glioma. Intractable seizure was defined as patients needing ≥2 anti-epileptic drugs. Chi-square tests of association were used to test for associations between factors and outcome measures. Results: Study population was 54% men, median age of 51, with oligodendroglioma (47%), oligoastrocytoma (25%), astrocytoma (21%), NOS (7%). Among patients with molecular testing (87%), 32% had IDH mutation (IDHmt) and 1p/19q co-deletion, 37% IDHmt and 1p/19q intact and 18% IDH wildtype LGG. Sixty-eight percent of patients had seizures prior to LGG diagnosis; 41% intractable seizures. A trend toward higher incidence of pre-operative seizure was observed in IDHmt LGG patients (p = 0.09). On univariate analysis (Table), oligodendroglioma was significantly associated with a higher risk of intractable seizures. Male gender was strongly associated with the risk of seizure at presentation, seizure development after surgery, and intractable seizures. Conclusions: Consistent with historical data, the majority of our patients presented with seizure; oligodendroglioma with higher risk of intractable seizures. Unexpectedly, gross resection did not favorably predict seizure outcome, possibly due to our small study population. Our study only showed a trend towards higher seizure occurrence in IDHmt LGG patients. Our finding of association between male gender and seizure risk in LGG patients mirrors that of Pallud et al (Brain 2014) and warrants further investigation into the possible molecular basis of sex differences in epileptogenesis in LGG.[Table: see text]
- Published
- 2019
49. Clinical Activity and Safety of Combination Therapy with Temsirolimus and Bevacizumab for Advanced Melanoma: A Phase II Trial (CTEP 7190/Mel47)
- Author
-
Cheryl Murphy Chase, Geoffrey R. Weiss, Kimberly A. Chianese-Bullock, William W. Grosh, Prahlad T. Ram, Gina R. Petroni, David L. Brautigan, Michael J. Weber, Alison Gaucher, Jeffrey E. Gershenwald, Sofia M. Shea, Anthony J. Olszanski, Gulsun Erdag, Aubrey G Wagenseller, Lainie P. Martin, Mark E. Smolkin, Kerrington R. Molhoek, Craig L. Slingluff, Amber L. Shada, and Walter C. Olson
- Subjects
Adult ,Male ,Proto-Oncogene Proteins B-raf ,Oncology ,Cancer Research ,medicine.medical_specialty ,Combination therapy ,Bevacizumab ,Biopsy ,Antibodies, Monoclonal, Humanized ,Article ,GTP Phosphohydrolases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Melanoma ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Sirolimus ,business.industry ,Membrane Proteins ,Middle Aged ,Phosphoproteins ,medicine.disease ,Temsirolimus ,Surgery ,Clinical trial ,Ki-67 Antigen ,Treatment Outcome ,Response Evaluation Criteria in Solid Tumors ,Mutation ,Female ,business ,Progressive disease ,medicine.drug - Abstract
Purpose: A CTEP-sponsored phase II trial was conducted to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) and bevacizumab in patients with advanced melanoma. Experimental Design: Patients with unresectable stage III to IV melanoma were treated intravenously with temsirolimus 25 mg weekly and bevacizumab 10 mg every 2 weeks. Adverse events were recorded using CTCAE v3.0. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and overall survival was recorded. Correlative studies measured protein kinases and histology of tumor biopsies and immune function in peripheral blood. Results: Seventeen patients were treated. Most patients tolerated treatment well, but 2 had grade 4 lymphopenia and 1 developed reversible grade 2 leukoencephalopathy. Best clinical response was partial response (PR) in 3 patients [17.7%, 90% confidence interval (CI) 5, 0–39.6], stable disease at 8 weeks (SD) in 9 patients, progressive disease (PD) in 4 patients, and not evaluable in 1 patient. Maximal response duration for PR was 35 months. Ten evaluable patients had BRAFWT tumors, among whom 3 had PRs, 5 had SD, and 2 had PD. Correlative studies of tumor biopsies revealed decreased phospho-S6K (d2 and d23 vs. d1, P < 0.001), and decreased mitotic rate (Ki67+) among melanoma cells by d23 (P = 0.007). Effects on immune functions were mixed, with decreased alloreactive T-cell responses and decreased circulating CD4+FoxP3+ cells. Conclusion: These data provide preliminary evidence for clinical activity of combination therapy with temsirolimus and bevacizumab, which may be greater in patients with BRAFwt melanoma. Mixed effects on immunologic function also support combination with immune therapies. Clin Cancer Res; 19(13); 3611–20. ©2013 AACR.
- Published
- 2013
50. Infrared thermography of cutaneous melanoma metastases
- Author
-
Gina R. Petroni, Craig L. Slingluff, Lynn T. Dengel, Amber L. Shada, Scott T. Acton, and Mark E. Smolkin
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Infrared Rays ,Diagnostico diferencial ,Pilot Projects ,Sensitivity and Specificity ,Article ,Metastasis ,Diagnosis, Differential ,Neoplasms ,Biopsy ,Humans ,Medicine ,Melanoma ,neoplasms ,Melanoma diagnosis ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Thermography ,Positron emission tomography ,Cutaneous melanoma ,Feasibility Studies ,Female ,Surgery ,Patient Safety ,business - Abstract
Differentiating melanoma metastasis from benign cutaneous lesions currently requires biopsy or costly imaging, such as positron emission tomography scans. Melanoma metastases have been observed to be subjectively warmer than similarly appearing benign lesions. We hypothesized that infrared (IR) thermography would be sensitive and specific in differentiating palpable melanoma metastases from benign lesions.Seventy-four patients (36 females and 38 males) had 251 palpable lesions imaged for this pilot study. Diagnosis was determined using pathologic confirmation or clinical diagnosis. Lesions were divided into size strata for analysis: 0-5,5-15,15-30, and30 mm. Images were scored on a scale from -1 (colder than the surrounding tissue) to +3 (significantly hotter than the surrounding tissue). Sensitivity and specificity were calculated for each stratum. Logistical challenges were scored.IR imaging was able to determine the malignancy of small (0-5 mm) lesions with a sensitivity of 39% and specificity of 100%. For lesions5-15 mm, sensitivity was 58% and specificity 98%. For lesions15-30 mm, sensitivity was 95% and specificity 100%, and for lesions30 mm, sensitivity was 78% and specificity 89%. The positive predictive value was 88%-100% across all strata, and the negative predictive value was 95% for15-30 mm lesions and 80% for30 mm lesions.Malignant lesions15 mm were differentiated from benign lesions with excellent sensitivity and specificity. IR imaging was well tolerated and feasible in a clinic setting. This pilot study shows promise in the use of thermography for the diagnosis of malignant melanoma with further potential as a noninvasive tool to follow tumor responses to systemic therapies.
- Published
- 2013
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.