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Olivier Ethgen, Vanessa Rémy, Katherine Wargo
Immunization has been shown to be the most effective disease prevention measure of all time, apart from water purification. However, vaccination programs remain highly vulnerable to budget cuts as their benefits may not be immediately and fully identifiable. Therefore, monitoring of healthcare expenditures allocated to prevention and vaccination is critical. This letter updates our previous observation of expenditure for prevention and vaccine programs in eight European countries by adding data from 2014, where available...
July 30, 2018: Human Vaccines & Immunotherapeutics
Anu Sharma, Sumit K Subudhi, Jorge Blando, Jorge Scutti, Luis Vence, Jennifer A Wargo, James P Allison, Antoni Ribas, Padmanee Sharma
PURPOSE: CTLA-4 was the first inhibitory immune checkpoint to be identified. Two monoclonal antibodies, ipilimumab (IgG1) and tremelimumab (IgG2), which block the function of CTLA-4, have demonstrated durable clinical activity in a subset of patients with advanced solid malignancies by augmenting effector T cell-mediated immune responses. Studies in mice suggest that anti-CTLA-4 monoclonal antibodies may also selectively deplete intratumoral FOXP3+ regulatory T cells via an Fc-dependent mechanism...
July 27, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
M T Tetzlaff, J L Messina, J E Stein, X Xu, R N Amaria, C Blank, B Van De Wiel, P M Ferguson, R V Rawson, M I Ross, A J Spillane, J E Gershenwald, R P M Saw, T Mitchell, A M Menzies, G V Long, J A Wargo, M A Davies, V G Prieto, J M Taube, R A Scolyer
Background: Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical to standardize pathologic assessment and reporting of tumor response after this treatment. Methods: The International Neoadjuvant Melanoma Consortium meetings in 2016 and 2017 assembled pathologists from academic centers to develop consensus guidelines for pathologic examination and reporting of surgical specimens from AJCC (8th Edition) stage IIIB/C/D or oligometastatic stage IV melanoma patients treated with neoadjuvant targeted or immune therapy...
June 25, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Beth A Helmink, Pierre-Olivier Gaudreau, Jennifer A Wargo
Four studies recently reported in the New England Journal of Medicine highlight advances in treatment with immune checkpoint blockade across the cancer care continuum. These findings demonstrate efficacy of these agents in the treatment of early and late-stage disease, as monotherapy or in combination, and in addition to-or in place of-standard front-line therapy.
June 19, 2018: Immunity
Nora D Volkow, Eric M Wargo
No abstract text is available yet for this article.
June 19, 2018: Annals of Internal Medicine
M Farah, P Nagarajan, J L Curry, Z Tang, T-B Kim, P P Aung, C A Torres-Cabala, A K Eterovic, J A Wargo, V G Prieto, M T Tetzlaff
Spitzoid neoplasms pose diagnostic difficulties because their morphology is not consistently predictive of their biologic potential. Recent advances in the molecular characterization of these tumours provide a framework by which they can now begin to be categorized. In particular, spitzoid lesions with ALK rearrangement have been specifically associated with a characteristic plexiform growth pattern of intersecting fascicles of amelanotic spindled melanocytes. We report a case of an 87-year-old man with a 3-cm nodule on his mid-upper back comprised of an intradermal proliferation of fusiform amelanotic melanocytes arranged in intersecting fascicles with occasional peritumoural clefts...
June 13, 2018: British Journal of Dermatology
Marie-Andrée Forget, Cara Haymaker, Kenneth R Hess, Yuzhong Jeff Meng, Caitlin Creasy, Tatiana Karpinets, Orenthial J Fulbright, Jason Roszik, Scott E Woodman, Young Uk Kim, Donastas Sakellariou-Thompson, Ankit Bhatta, Arely Wahl, Esteban Flores, Shawne T Thorsen, René J Tavera, Renjith Ramachandran, Audrey M Gonzalez, Christopher L Toth, Seth Wardell, Rahmatu Mansaray, Vruti Patel, Destiny Joy Carpio, Carol Vaughn, Chantell M Farinas, Portia G Velasquez, Wen-Jen Hwu, Sapna P Patel, Michael A Davies, Adi Diab, Isabella C Glitza, Hussein Tawbi, Michael K Wong, Suzanne Cain, Merrick I Ross, Jeffrey E Lee, Jeffrey E Gershenwald, Anthony Lucci, Richard Royal, Janice N Cormier, Jennifer A Wargo, Laszlo G Radvanyi, Carlos A Torres-Cabala, Rameen Beroukhim, Patrick Hwu, Rodabe N Amaria, Chantale Bernatchez
Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence. Experimental Design: Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival, and progression-free survival...
May 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
J Dako, J Buzzard, M Jain, R Pandey, S Groh-Wargo, P Shekhawat
BACKGROUND: Necrotizing Enterocolitis (NEC) is a multifactorial condition where PRBC transfusion is associated with necrotizing enterocolitis (TANEC) in about a third of all cases of NEC. We have investigated the role of feeding practices in incidence of TANEC. We sought to compare infants diagnosed with TANEC versus infants diagnosed with classic NEC and investigated the effects of a standardized slow enteral feeding (SSEF) protocol on TANEC incidence as well as the effects of SSEF on growth of infants with NEC...
May 23, 2018: Journal of Neonatal-perinatal Medicine
Wilson M Compton, Eric M Wargo
No abstract text is available yet for this article.
June 5, 2018: Annals of Internal Medicine
Anna Maria Hibbs, Kristie Ross, Leigh Ann Kerns, Carol Wagner, Mamta Fuloria, Sharon Groh-Wargo, Teresa Zimmerman, Nori Minich, Curtis Tatsuoka
Importance: Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. Objective: To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing. Design, Setting, and Participants: A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks' gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017...
May 22, 2018: JAMA: the Journal of the American Medical Association
Miles C Andrews, Alexandre Reuben, Vancheswaran Gopalakrishnan, Jennifer A Wargo
Cancer research has seen unprecedented advances over the past several years, with tremendous insights gained into mechanisms of response and resistance to cancer therapy. Central to this has been our understanding of crosstalk between the tumor and the microenvironment, with the recognition that complex interactions exist between tumor cells, stromal cells, overall host immunity, and the environment surrounding the host. This is perhaps best exemplified in cancer immunotherapy, where numerous studies across cancer types have illuminated our understanding of the genomic and immune factors that shape responses to therapy...
2018: Frontiers in Immunology
Meghan J Mooradian, Alexandre Reuben, Peter A Prieto, Mehlika Hazar-Rethinam, Dennie T Frederick, Brandon Nadres, Adriano Piris, Vikram Juneja, Zachary A Cooper, Arlene H Sharpe, Ryan B Corcoran, Keith T Flaherty, Donald P Lawrence, Jennifer A Wargo, Ryan J Sullivan
Background : Approximately 50% of melanomas harbor BRAF mutations. Treatment with BRAF +/- MEK inhibition is associated with favorable changes in the tumor microenvironment thus providing the rationale for combining targeted agents with immunotherapy. Methods : Patients with unresectable Stage III or IV BRAFV600E mutant melanoma were enrolled in a single-center prospective study (n = 6). Patients were eligible to receive two courses of HD-IL-2 and vemurafenib twice daily. The primary endpoint was progression-free survival (PFS) with secondary objectives including overall survival (OS), response rates (RR), and safety of combination therapy as compared to historical controls...
2018: Oncoimmunology
Graham G Willsey, Sebastian Ventrone, Kristin C Schutz, Aaron M Wallace, John W Ribis, Benjamin T Suratt, Matthew J Wargo
The interactions between Klebsiella pneumoniae and the host environment at the site of infection are largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this ecological transition, we characterized the transcriptional response of K. pneumoniae MGH 78578 to purified pulmonary surfactant. This work revealed changes within the K. pneumoniae transcriptome that likely contribute to host colonization, adaptation, and virulence in vivo Notable transcripts expressed under these conditions include genes involved in capsule synthesis, lipopolysaccharide modification, antibiotic resistance, biofilm formation, and metabolism...
July 2018: Infection and Immunity
Maya Farah, Priyadharsini Nagarajan, Carlos A Torres-Cabala, Jonathan L Curry, Rodabe N Amaria, Jennifer Wargo, Hussein Tawbi, Doina Ivan, Victor G Prieto, Michael T Tetzlaff, Phyu P Aung
Epithelioid cells with foamy cytoplasm (histiocytoid features) are typical histopathologic findings among benign and malignant histiocytic neoplasms such as xanthoma and atypical fibroxanthoma. However, these changes are unusual in melanoma, which is typically composed of nested and variably pigmented atypical epithelioid cells. Here, we report a patient with metastatic melanoma in lymph nodes presenting with prominent balloon cell/histiocytoid features expressing melanocytic markers, after treatment with nivolumab...
July 2018: Journal of Cutaneous Pathology
Nora D Volkow, Janet Woodcock, Wilson M Compton, Douglas C Throckmorton, Phil Skolnick, Sharon Hertz, Eric M Wargo
The FDA's "abstinence" outcome measure for approval of new medications to treat opioid-use disorders has been difficult to achieve; developing and validating alternative meaningful outcomes could facilitate drug development.
March 28, 2018: Science Translational Medicine
Tatiana V Karpinets, Vancheswaran Gopalakrishnan, Jennifer Wargo, Andrew P Futreal, Christopher W Schadt, Jianhua Zhang
Studies of microbial communities by targeted sequencing of rRNA genes lead to recovering numerous rare low-abundance taxa with unknown biological roles. We propose to study associations of such rare organisms with their environments by a computational framework based on transformation of the data into qualitative variables. Namely, we analyze the sparse table of putative species or OTUs (operational taxonomic units) and samples generated in such studies, also known as an OTU table, by collecting statistics on co-occurrences of the species and on shared species richness across samples...
2018: Frontiers in Microbiology
Jamie A Meadows, Graham G Willsey, Matthew J Wargo
The opportunistic pathogen Pseudomonas aeruginosa can metabolize carnitine and O-acylcarnitines, which are abundant in host muscle and other tissues. Acylcarnitines are metabolized to carnitine and a fatty acid. The liberated carnitine and its catabolic product, glycine betaine, can be used as osmoprotectants, to induce the secreted phospholipase C PlcH, and as sole carbon, nitrogen and energy sources. P. aeruginosa is incapable of de novo synthesis of carnitine and acylcarnitines, therefore they must be imported from an exogenous source...
April 2018: Microbiology
Emily Z Keung, Esosa U Ukponmwan, Alexandria P Cogdill, Jennifer A Wargo
Unprecedented advances in the treatment of cancer have occurred through the use of immunotherapy, with several agents currently approved by the Food and Drug Administration (FDA) for the treatment of widespread metastatic disease across cancer types. Immune checkpoint blockade represents a particularly promising class of agents that block inhibitory molecules on the surface of T cells, resulting in their activation and propagation of an immune response. Treatment with these agents may re-invigorate anti-tumor immunity, resulting in therapeutic responses, and use of these agents currently is being studied in the adjuvant setting...
July 2018: Annals of Surgical Oncology
Lu Huang, Shruti Malu, Jodi A McKenzie, Miles C Andrews, Amjad H Talukder, Trang Tieu, Tatiana Karpinets, Cara Haymaker, Marie-Andrée Forget, Leila J Williams, Zhe Wang, Rina M Mbofung, Zhi-Qiang Wang, Richard Eric Davis, Roger S Lo, Jennifer A Wargo, Michael A Davies, Chantale Bernatchez, Timothy Heffernan, Rodabe N Amaria, Anil Korkut, Weiyi Peng, Jason Roszik, Gregory Lizée, Scott E Woodman, Patrick Hwu
Purpose: Cancer immunotherapy has shown promising clinical outcomes in many patients. However, some patients still fail to respond, and new strategies are needed to overcome resistance. The purpose of this study was to identify novel genes and understand the mechanisms that confer resistance to cancer immunotherapy. Experimental Design: To identify genes mediating resistance to T-cell killing, we performed an open reading frame (ORF) screen of a kinome library to study whether overexpression of a gene in patient-derived melanoma cells could inhibit their susceptibility to killing by autologous tumor-infiltrating lymphocytes (TIL)...
July 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L McQuade, Roger J Liang, Mingguang Liu, Whijae Roh, Dzifa Y Duose, Fernando C L Carapeto, Jun Li, Jessica L F Teh, Andrew E Aplin, Merry Chen, Jianhua Zhang, Alexander J Lazar, Michael A Davies, P Andrew Futreal, Rodabe N Amaria, David Y Zhang, Jennifer A Wargo, Lawrence N Kwong
Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS -mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed...
May 2018: Cancer Discovery
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