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https://read.qxmd.com/read/30712808/modulating-the-microbiome-to-improve-therapeutic-response-in-cancer
#1
REVIEW
Jennifer L McQuade, Carrie R Daniel, Beth A Helmink, Jennifer A Wargo
Although novel therapies, including immunotherapy, have dramatically improved outcomes for many patients with cancer, overall outcomes are heterogeneous and existing biomarkers do not reliably predict response. To date, predictors of response to cancer therapy have largely focused on tumour-intrinsic features; however, there is growing evidence that other host factors (eg, host genomics and the microbiome) can substantially affect therapeutic response. The microbiome, which refers to microbiota within a host and their collective genomes, is becoming increasingly recognised for its influence on host immunity, as well as therapeutic responses to cancer treatment...
February 2019: Lancet Oncology
https://read.qxmd.com/read/30705399/accuracy-of-preterm-infant-weight-gain-velocity-calculations-vary-depending-on-method-used-and-infant-age-at-time-of-measurement
#2
Tanis R Fenton, Ian J Griffin, Angela Hoyos, Sharon Groh-Wargo, Diane Anderson, Richard A Ehrenkranz, Thibault Senterre
BACKGROUND: We examined preterm infants' weight gain velocity (WGV) to determine how much calculation methods influences actual WGV during the first 28 days of life. METHODS: WGV methods (Average 2-point, Exponential 2-point, Early 1-point, and Daily) were calculated weekly and for various start times (birth, nadir, regain, day 3 and day 7) to 28 days of age for 103 preterm < 1500 gram infants, with daily weights. RESULTS: Range of WGV estimates decreased 10-22 g/kg/day to 15...
January 25, 2019: Pediatric Research
https://read.qxmd.com/read/30679251/donor-breast-milk-for-the-preterm-infant-your-questions-answered
#3
Stephanie Merlino-Barr, Sharon Groh-Wargo
Expressed breast milk (EBM) is the gold standard of infant nutrition, but is not always available for use for preterm infants in the NICU setting. Donor breast milk (DBM) is often a preferred alternative for preterm and very low birth weight (VLBW) infants when maternal milk is not available. This article discusses the composition of DBM, reviews its advantages compared to formula, discusses challenges related to its long-term use, and identifies strategies to utilize DBM in the context of total nutritional management of preterm and VLBW infants...
January 2019: Neonatal Network: NN
https://read.qxmd.com/read/30635425/comparison-of-immune-infiltrates-in-melanoma-and-pancreatic-cancer-highlights-vista-as-a-potential-target-in-pancreatic-cancer
#4
Jorge Blando, Anu Sharma, Maria Gisela Higa, Hao Zhao, Luis Vence, Shalini S Yadav, Jiseong Kim, Alejandro M Sepulveda, Michael Sharp, Anirban Maitra, Jennifer Wargo, Michael Tetzlaff, Russell Broaddus, Matthew H G Katz, Gauri R Varadhachary, Michael Overman, Huamin Wang, Cassian Yee, Chantale Bernatchez, Christine Iacobuzio-Donahue, Sreyashi Basu, James P Allison, Padmanee Sharma
Immune checkpoint therapy (ICT) has transformed cancer treatment in recent years; however, treatment response is not uniform across tumor types. The tumor immune microenvironment plays a critical role in determining response to ICT; therefore, understanding the differential immune infiltration between ICT-sensitive and ICT-resistant tumor types will help to develop effective treatment strategies. We performed a comprehensive analysis of the immune tumor microenvironment of an ICT-sensitive tumor (melanoma, n = 44) and an ICT-resistant tumor (pancreatic cancer, n = 67)...
January 11, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30633907/defining-t-cell-states-associated-with-response-to-checkpoint-immunotherapy-in-melanoma
#5
Moshe Sade-Feldman, Keren Yizhak, Stacey L Bjorgaard, John P Ray, Carl G de Boer, Russell W Jenkins, David J Lieb, Jonathan H Chen, Dennie T Frederick, Michal Barzily-Rokni, Samuel S Freeman, Alexandre Reuben, Paul J Hoover, Alexandra-Chloé Villani, Elena Ivanova, Andrew Portell, Patrick H Lizotte, Amir R Aref, Jean-Pierre Eliane, Marc R Hammond, Hans Vitzthum, Shauna M Blackmon, Bo Li, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, Zachary A Cooper, Cloud P Paweletz, David A Barbie, Anat Stemmer-Rachamimov, Keith T Flaherty, Jennifer A Wargo, Genevieve M Boland, Ryan J Sullivan, Gad Getz, Nir Hacohen
No abstract text is available yet for this article.
January 10, 2019: Cell
https://read.qxmd.com/read/30533649/draft-genome-sequences-of-two-cystic-fibrosis-strains-of-stenotrophomonas-maltophilia-au30115-and-au32848
#6
Korin Eckstrom, Graham G Willsey, John J LiPuma, Matthew J Wargo
Stenotrophomonas maltophilia is an opportunistic pathogen causing airway infection in people with cystic fibrosis (CF). Here, we report the draft genome sequences of two S. maltophilia strains, AU30115 and AU32848, recovered from CF patients.
September 2018: Microbiology resource announcements
https://read.qxmd.com/read/30516809/prevention-and-treatment-of-opioid-misuse-and-addiction-a-review
#7
Nora D Volkow, Emily B Jones, Emily B Einstein, Eric M Wargo
Importance: More than 42 000 Americans died of opioid overdoses in 2016, and the fatalities continue to increase. This review analyzes the factors that triggered the opioid crisis and its further evolution, along with the interventions to manage and prevent opioid use disorder (OUD), which are fundamental for curtailing the opioid crisis. Observations: Opioid drugs are among the most powerful analgesics but also among the most addictive. The current opioid crisis, initially triggered by overprescription of opioid analgesics, which facilitated their diversion and misuse, has now expanded to heroin and illicit synthetic opioids (fentanyl and its analogues), the potency of which further increases their addictiveness and lethality...
December 5, 2018: JAMA Psychiatry
https://read.qxmd.com/read/30479380/author-correction-fecal-microbiota-transplantation-for-refractory-immune-checkpoint-inhibitor-associated-colitis
#8
Yinghong Wang, Diana H Wiesnoski, Beth A Helmink, Vancheswaran Gopalakrishnan, Kati Choi, Hebert L DuPont, Zhi-Dong Jiang, Hamzah Abu-Sbeih, Christopher A Sanchez, Chia-Chi Chang, Edwin R Parra, Alejandro Francisco-Cruz, Gottumukkala S Raju, John R Stroehlein, Matthew T Campbell, Jianjun Gao, Sumit K Subudhi, Dipen M Maru, Jorge M Blando, Alexander J Lazar, James P Allison, Padmanee Sharma, Michael T Tetzlaff, Jennifer A Wargo, Robert R Jenq
In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.
November 27, 2018: Nature Medicine
https://read.qxmd.com/read/30388456/defining-t-cell-states-associated-with-response-to-checkpoint-immunotherapy-in-melanoma
#9
Moshe Sade-Feldman, Keren Yizhak, Stacey L Bjorgaard, John P Ray, Carl G de Boer, Russell W Jenkins, David J Lieb, Jonathan H Chen, Dennie T Frederick, Michal Barzily-Rokni, Samuel S Freeman, Alexandre Reuben, Paul J Hoover, Alexandra-Chloé Villani, Elena Ivanova, Andrew Portell, Patrick H Lizotte, Amir R Aref, Jean-Pierre Eliane, Marc R Hammond, Hans Vitzthum, Shauna M Blackmon, Bo Li, Vancheswaran Gopalakrishnan, Sangeetha M Reddy, Zachary A Cooper, Cloud P Paweletz, David A Barbie, Anat Stemmer-Rachamimov, Keith T Flaherty, Jennifer A Wargo, Genevieve M Boland, Ryan J Sullivan, Gad Getz, Nir Hacohen
Treatment of cancer has been revolutionized by immune checkpoint blockade therapies. Despite the high rate of response in advanced melanoma, the majority of patients succumb to disease. To identify factors associated with success or failure of checkpoint therapy, we profiled transcriptomes of 16,291 individual immune cells from 48 tumor samples of melanoma patients treated with checkpoint inhibitors. Two distinct states of CD8+ T cells were defined by clustering and associated with patient tumor regression or progression...
November 1, 2018: Cell
https://read.qxmd.com/read/30373963/enteral-fish-oil-supplementation-in-the-resolution-of-parenteral-nutrition-associated-cholestasis
#10
A Thavamani, M J Mhanna, S Groh-Wargo, R Gulati, P S Shekhawat
OBJECTIVE: To analyze safety, tolerance and efficacy of enteral omega-3 fatty acids (FAs) in the resolution of Parenteral Nutrition Associated Cholestasis (PNAC) and postnatal growth among preterm neonates. STUDY DESIGN: This is a single center retrospective case-control study of all neonates born less than 32 weeks of gestation and developed PNAC (Direct bilirubin >2 mg/dl). Infants who received enteral omega-3 FAs supplementation (1 g/Kg/d) served as cases and were compared with gestational age, gender and direct bilirubin level matched controls that did not receive enteral omega-3 FAs supplementation...
October 22, 2018: Journal of Neonatal-perinatal Medicine
https://read.qxmd.com/read/30361511/publisher-correction-neoadjuvant-immune-checkpoint-blockade-in-high-risk-resectable-melanoma
#11
Rodabe N Amaria, Sangeetha M Reddy, Hussein A Tawbi, Michael A Davies, Merrick I Ross, Isabella C Glitza, Janice N Cormier, Carol Lewis, Wen-Jen Hwu, Ehab Hanna, Adi Diab, Michael K Wong, Richard Royal, Neil Gross, Randal Weber, Stephen Y Lai, Richard Ehlers, Jorge Blando, Denái R Milton, Scott Woodman, Robin Kageyama, Daniel K Wells, Patrick Hwu, Sapna P Patel, Anthony Lucci, Amy Hessel, Jeffrey E Lee, Jeffrey Gershenwald, Lauren Simpson, Elizabeth M Burton, Liberty Posada, Lauren Haydu, Linghua Wang, Shaojun Zhang, Alexander J Lazar, Courtney W Hudgens, Vancheswaran Gopalakrishnan, Alexandre Reuben, Miles C Andrews, Christine N Spencer, Victor Prieto, Padmanee Sharma, James Allison, Michael T Tetzlaff, Jennifer A Wargo
In the version of this article originally published, there was an error in Fig. 1. In the neoadjuvant phase column, the n values for arms A and B were both reported to be 20. The n values for arms A and B were actually 12 and 11, respectively. Also, the URL underlying the accession code in the data availability section was incorrect. The URL was originally https://www.ebi.ac.uk/ega/studies/EGAS00001002698. It should have been https://www.ebi.ac.uk/ega/studies/EGAS00001003178. The errors have been corrected in the print, HTML and PDF versions of this article...
October 25, 2018: Nature Medicine
https://read.qxmd.com/read/30361510/author-correction-neoadjuvant-immune-checkpoint-blockade-in-high-risk-resectable-melanoma
#12
Rodabe N Amaria, Sangeetha M Reddy, Hussein A Tawbi, Michael A Davies, Merrick I Ross, Isabella C Glitza, Janice N Cormier, Carol Lewis, Wen-Jen Hwu, Ehab Hanna, Adi Diab, Michael K Wong, Richard Royal, Neil Gross, Randal Weber, Stephen Y Lai, Richard Ehlers, Jorge Blando, Denái R Milton, Scott Woodman, Robin Kageyama, Daniel K Wells, Patrick Hwu, Sapna P Patel, Anthony Lucci, Amy Hessel, Jeffrey E Lee, Jeffrey Gershenwald, Lauren Simpson, Elizabeth M Burton, Liberty Posada, Lauren Haydu, Linghua Wang, Shaojun Zhang, Alexander J Lazar, Courtney W Hudgens, Vancheswaran Gopalakrishnan, Alexandre Reuben, Miles C Andrews, Christine N Spencer, Victor Prieto, Padmanee Sharma, James Allison, Michael T Tetzlaff, Jennifer A Wargo
In the version of this article originally published, there was an error in Fig. 2b. RECIST ORR and pCR were both listed as 25%. RECIST ORR was actually 73%, and pCR was 45%. Also, an author's name was incorrect in the author list. Danny K. Wells should have been listed as Daniel K. Wells. The errors have been corrected in the print, HTML and PDF versions of this article.
October 25, 2018: Nature Medicine
https://read.qxmd.com/read/30297909/neoadjuvant-immune-checkpoint-blockade-in-high-risk-resectable-melanoma
#13
Rodabe N Amaria, Sangeetha M Reddy, Hussein A Tawbi, Michael A Davies, Merrick I Ross, Isabella C Glitza, Janice N Cormier, Carol Lewis, Wen-Jen Hwu, Ehab Hanna, Adi Diab, Michael K Wong, Richard Royal, Neil Gross, Randal Weber, Stephen Y Lai, Richard Ehlers, Jorge Blando, Denái R Milton, Scott Woodman, Robin Kageyama, Daniel K Wells, Patrick Hwu, Sapna P Patel, Anthony Lucci, Amy Hessel, Jeffrey E Lee, Jeffrey Gershenwald, Lauren Simpson, Elizabeth M Burton, Liberty Posada, Lauren Haydu, Linghua Wang, Shaojun Zhang, Alexander J Lazar, Courtney W Hudgens, Vancheswaran Gopalakrishnan, Alexandre Reuben, Miles C Andrews, Christine N Spencer, Victor Prieto, Padmanee Sharma, James Allison, Michael T Tetzlaff, Jennifer A Wargo
Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment1 ; however, optimal regimens have not been defined. Here we report results from a randomized phase 2 study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma ( NCT02519322 ). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs) and immune correlates of response were assessed...
November 2018: Nature Medicine
https://read.qxmd.com/read/30279173/remodeling-of-the-collagen-matrix-in-aging-skin-promotes-melanoma-metastasis-and-affects-immune-cell-motility
#14
Amanpreet Kaur, Brett L Ecker, Stephen M Douglass, Curtis H Kugel, Marie R Webster, Filipe V Almeida, Rajasekharan Somasundaram, James Hayden, Ehsan Ban, Hossein Ahmadzadeh, Janusz Franco-Barraza, Neelima Shah, Ian A Mellis, Frederick Keeney, Andrew Kossenkov, Hsin-Yao Tang, Xiangfan Yin, Qin Liu, Xiaowei Xu, Mitchell Fane, Patricia Brafford, Meenhard Herlyn, David W Speicher, Jennifer A Wargo, Michael T Tetzlaff, Lauren E Haydu, Arjun Raj, Vivek Shenoy, Edna Cukierman, Ashani T Weeraratna
Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3D skin reconstruction models, and in vivo...
October 2, 2018: Cancer Discovery
https://read.qxmd.com/read/30277012/a-pax3-brn2-rheostat-controls-the-dynamics-of-braf-mediated-mitf-regulation-in-mitf-high-axl-low-melanoma
#15
Michael P Smith, Sareena Rana, Jennifer Ferguson, Emily J Rowling, Keith T Flaherty, Jennifer A Wargo, Richard Marais, Claudia Wellbrock
The BRAF-kinase and the MAPK-pathway are targets of current melanoma therapies. However, MAPK-pathway inhibition results in dynamic changes of down-stream targets that can counteract inhibitor-action not only during treatment, but also in acquired resistant tumours. One such dynamic change involves the expression of the transcription factor MITF, a crucial regulator of cell survival and proliferation in untreated as well as drug-addicted acquired resistant melanoma. Tight control over MITF expression levels is required for optimal melanoma growth, and while it is well established that the MAPK-pathway regulates MITF expression, the actual mechanism is insufficiently understood...
October 1, 2018: Pigment Cell & Melanoma Research
https://read.qxmd.com/read/30249211/phase-ii-study-of-neoadjuvant-checkpoint-blockade-in-patients-with-surgically-resectable-undifferentiated-pleomorphic-sarcoma-and-dedifferentiated-liposarcoma
#16
Emily Z Keung, Alexander J Lazar, Keila E Torres, Wei-Lien Wang, Janice N Cormier, B Ashleigh Guadagnolo, Andrew J Bishop, Heather Lin, Kelly K Hunt, Justin Bird, Valerae O Lewis, Shreyaskumar R Patel, Jennifer A Wargo, Neeta Somaiah, Christina L Roland
BACKGROUND: Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity...
September 24, 2018: BMC Cancer
https://read.qxmd.com/read/30231333/combination-immunotherapy-development-in-melanoma
#17
REVIEW
Alexander M M Eggermont, Marka Crittenden, Jennifer Wargo
Melanoma has been the most important cancer to drive immunotherapy development of solid tumors. Since 2010, immunotherapy has been revolutionized by the concept of breaking tolerance. It represents a major paradigm shift and marks the beginning of a new era. The impact of the first immune checkpoint inhibitors, anti-CTLA-4 and anti-PD-1/anti-PD-L1, is unprecedented. In 7 years, it transformed advanced-stage melanoma into a curable disease in over 50% of patients. Another major step has been the development of the combination of BRAF inhibitors plus MEK inhibitors in the treatment of BRAF-mutant melanomas...
May 23, 2018: American Society of Clinical Oncology Educational Book
https://read.qxmd.com/read/30228943/high-expression-of-pd-1-and-pd-l1-in-ocular-adnexal-sebaceous-carcinoma
#18
Thomas J Kandl, Oded Sagiv, Jonathan L Curry, Jing Ning, Junsheng Ma, Courtney W Hudgens, John Van Arnam, Jennifer A Wargo, Bita Esmaeli, Michael T Tetzlaff
Ocular adnexal sebaceous carcinoma (OASC) is an aggressive malignancy that frequently recurs locally and metastasizes. Surgical extirpation may produce significant aesthetic morbidity, and effective systemic therapies for locally advanced or metastatic disease are largely ineffective. Immune checkpoint inhibitors have shown efficacy in the management of several solid tumors where tumor cell PD-L1 expression correlates with improved response. To determine whether OASC might be amenable to immune checkpoint blockade, we performed comprehensive immune profiling for CD3, CD8, PD-1, FOXP3, and PD-L1 in 24 patients with primary OASC...
2018: Oncoimmunology
https://read.qxmd.com/read/30209080/combined-analysis-of-antigen-presentation-and-t-cell-recognition-reveals-restricted-immune-responses-in-melanoma
#19
Shelly Kalaora, Yochai Wolf, Tali Feferman, Eilon Barnea, Erez Greenstein, Dan Reshef, Itay Tirosh, Alexandre Reuben, Sushant Patkar, Ronen Levy, Juliane Quinkhardt, Tana Omokoko, Nouar Qutob, Ofra Golani, Jianhua Zhang, Xizeng Mao, Xingzhi Song, Chantale Bernatchez, Cara Haymaker, Marie-Andrée Forget, Caitlin Creasy, Polina Greenberg, Brett W Carter, Zachary A Cooper, Steven A Rosenberg, Michal Lotem, Ugur Sahin, Guy Shakhar, Eytan Ruppin, Jennifer A Wargo, Nir Friedman, Arie Admon, Yardena Samuels
The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors derived from seven patients with melanoma and characterize their interactions with their tumor-infiltrating lymphocytes (TIL). Our investigation of the antigenic and T-cell landscapes encompassing the TAA and neoantigen signatures, their immune reactivity, and their corresponding T-cell identities provides the first comprehensive analysis of cancer cell T-cell cosignatures, allowing us to discover remarkable antigenic and TIL similarities between metastases from the same patient...
November 2018: Cancer Discovery
https://read.qxmd.com/read/30195561/improved-outcomes-in-preterm-infants-fed-a-nonacidified-liquid-human-milk-fortifier-a-prospective-randomized-clinical-trial
#20
Richard J Schanler, Sharon L Groh-Wargo, Bridget Barrett-Reis, Robert D White, Kaashif A Ahmad, Jeffery Oliver, Geraldine Baggs, Larry Williams, David Adamkin
OBJECTIVE: To compare growth, feeding tolerance, and clinical and biochemical evaluations in human milk-fed preterm infants randomized to receive either an acidified or a nonacidified liquid human milk fortifier. STUDY DESIGN: This prospective, controlled, parallel, multicenter growth and tolerance study included 164 preterm infants (≤32 weeks of gestation, birth weight 700-1500 g) who were randomized to acidified or nonacidified liquid human milk fortifier from study day 1, the first day of fortification, through study day 29 or until hospital discharge...
November 2018: Journal of Pediatrics
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