scispace - formally typeset
Search or ask a question
Institution

University of Texas Southwestern Medical Center

HealthcareDallas, Texas, United States
About: University of Texas Southwestern Medical Center is a healthcare organization based out in Dallas, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 39107 authors who have published 75242 publications receiving 4497256 citations. The organization is also known as: UT Southwestern & UT Southwestern Medical School.


Papers
More filters
Journal ArticleDOI
TL;DR: The notion that in biomembranes selected lipids could laterally aggregate to form more ordered, detergent-resistant lipid rafts into which glycosphingolipid- and cholesterol-rich lipid domains partition is strongly supported by this study.

1,357 citations

Journal ArticleDOI
21 May 2014-JAMA
TL;DR: The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials.
Abstract: Importance Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. Objectives To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. Design, Setting, and Participants From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. Interventions Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. Main Outcomes and Measures Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. Results From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR , 122 (17%); ALK rearrangements, 57 (8%); other EGFR , 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2 ), 19 (3%); BRAF , 16 (2%); PIK3CA , 6 ( MET amplification, 5 ( NRAS , 5 ( MEK1 , 1 ( AKT1 , 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score–adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). Conclusions and Relevance Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. Trial Registration clinicaltrials.gov Identifier:NCT01014286.

1,356 citations

Journal ArticleDOI
TL;DR: Two novel classes of small molecules are discovered that disrupt Wnt pathway responses and contribute to Wnt-independent signal transduction pathways and thus could be broadly exploited for chemical genetics and therapeutic goals.
Abstract: The pervasive influence of secreted Wnt signaling proteins in tissue homeostasis and tumorigenesis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. By screening a diverse synthetic chemical library, we have discovered two new classes of small molecules that disrupt Wnt pathway responses; whereas one class inhibits the activity of Porcupine, a membrane-bound acyltransferase that is essential to the production of Wnt proteins, the other abrogates destruction of Axin proteins, which are suppressors of Wnt/beta-catenin pathway activity. With these small molecules, we establish a chemical genetic approach for studying Wnt pathway responses and stem cell function in adult tissue. We achieve transient, reversible suppression of Wnt/beta-catenin pathway response in vivo, and we establish a mechanism-based approach to target cancerous cell growth. The signal transduction mechanisms shown here to be chemically tractable additionally contribute to Wnt-independent signal transduction pathways and thus could be broadly exploited for chemical genetics and therapeutic goals.

1,353 citations

Journal ArticleDOI
TL;DR: The analyses of systemic and tissue-specific knockout models of ATG genes in mice has led to an explosion of knowledge about the functions of autophagy in mammalian development and differentiation.
Abstract: It has been known for many decades that autophagy, a conserved lysosomal degradation pathway, is highly active during differentiation and development. However, until the discovery of the autophagy-related (ATG) genes in the 1990s, the functional significance of this activity was unknown. Initially, genetic knockout studies of ATG genes in lower eukaryotes revealed an essential role for the autophagy pathway in differentiation and development. In recent years, the analyses of systemic and tissue-specific knockout models of ATG genes in mice has led to an explosion of knowledge about the functions of autophagy in mammalian development and differentiation. Here we review the main advances in our understanding of these functions.

1,348 citations


Authors

Showing all 39410 results

NameH-indexPapersCitations
Eugene Braunwald2301711264576
Joseph L. Goldstein207556149527
Eric N. Olson206814144586
Craig B. Thompson195557173172
Thomas C. Südhof191653118007
Scott M. Grundy187841231821
Michael S. Brown185422123723
Eric Boerwinkle1831321170971
Jiaguo Yu178730113300
John J.V. McMurray1781389184502
Eric J. Nestler178748116947
John D. Minna169951106363
Yuh Nung Jan16246074818
Andrew P. McMahon16241590650
Elliott M. Antman161716179462
Network Information
Related Institutions (5)
Johns Hopkins University School of Medicine
79.2K papers, 4.7M citations

98% related

University of California, San Francisco
186.2K papers, 12M citations

98% related

Baylor College of Medicine
94.8K papers, 5M citations

98% related

National Institutes of Health
297.8K papers, 21.3M citations

98% related

Brigham and Women's Hospital
110.5K papers, 6.8M citations

97% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023114
2022406
20215,247
20204,674
20194,094
20183,400