Institution
University of Texas Southwestern Medical Center
Healthcare•Dallas, 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.
Topics: Population, Cancer, Medicine, Gene, Receptor
Papers published on a yearly basis
Papers
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TL;DR: There is an urgent need for randomized, controlled, long-term studies on the efficacy of SCS involving larger patient sample sizes and, in general, SCS was a safe and effective treatment for a variety of chronic neuropathic conditions.
Abstract: Object. The purpose of this report was to examine the available literature to determine the safety and efficacy of spinal cord stimulation (SCS) for the treatment of chronic pain of the trunk and limbs. Methods. The author identified 68 studies that fulfilled the efficacy inclusion/exclusion criteria, grouped on the basis of pain indication, with an overall population of 3679 patients. Fifty-one studies fulfilled all safety inclusion/exclusion criteria. Based on the literature review, the author found that SCS had a positive, symptomatic, long-term effect in cases of refractory angina pain, severe ischemic limb pain secondary to peripheral vascular disease, peripheral neuropathic pain, and chronic low-back pain, and that, in general, SCS was a safe and effective treatment for a variety of chronic neuropathic conditions. Conclusions. Despite the positive findings, there is an urgent need for randomized, controlled, long-term studies on the efficacy of SCS involving larger patient sample sizes.
698 citations
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TL;DR: Cell-aut autonomous and non-cell-autonomous functions for HDAC1 and HDAC2 in the control of myocardial growth, morphogenesis, and contractility are revealed, which reflect partially redundant roles of these enzymes in tissue-specific transcriptional repression.
Abstract: Histone deacetylases (HDACs) tighten chromatin structure and repress gene expression through the removal of acetyl groups from histone tails. The class I HDACs, HDAC1 and HDAC2, are expressed ubiquitously, but their potential roles in tissue-specific gene expression and organogenesis have not been defined. To explore the functions of HDAC1 and HDAC2 in vivo, we generated mice with conditional null alleles of both genes. Whereas global deletion of HDAC1 results in death by embryonic day 9.5, mice lacking HDAC2 survive until the perinatal period, when they succumb to a spectrum of cardiac defects, including obliteration of the lumen of the right ventricle, excessive hyperplasia and apoptosis of cardiomyocytes, and bradycardia. Cardiac-specific deletion of either HDAC1 or HDAC2 does not evoke a phenotype, whereas cardiac-specific deletion of both genes results in neonatal lethality, accompanied by cardiac arrhythmias, dilated cardiomyopathy, and up-regulation of genes encoding skeletal muscle-specific contractile proteins and calcium channels. Our results reveal cell-autonomous and non-cell-autonomous functions for HDAC1 and HDAC2 in the control of myocardial growth, morphogenesis, and contractility, which reflect partially redundant roles of these enzymes in tissue-specific transcriptional repression.
697 citations
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TL;DR: It is demonstrated that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC, demonstrating critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of mi R-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR -122 inhibition therapy for HCV.
Abstract: miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, delivery of miR-122 to a MYC-driven mouse model of HCC strongly inhibited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.
697 citations
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Medical University of South Carolina1, Wake Forest University2, Emory University3, Indiana University4, Indiana University – Purdue University Indianapolis5, University of Texas Southwestern Medical Center6, Virginia Commonwealth University7, Imperial College Healthcare8, University of Texas MD Anderson Cancer Center9, Case Western Reserve University10
TL;DR: The accuracy of CTC varied considerably between centers and did not improve as the study progressed, suggesting that this method is not yet ready for widespread clinical application.
Abstract: ContextConventional colonoscopy is the best available method for detection
of colorectal cancer; however, it is invasive and not without risk. Computed
tomographic colonography (CTC), also known as virtual colonoscopy, has been
reported to be reasonably accurate in the diagnosis of colorectal neoplasia
in studies performed at expert centers.ObjectiveTo assess the accuracy of CTC in a large number of participants across
multiple centers.Design, Setting, and ParticipantsA nonrandomized, evaluator-blinded, noninferiority study design of 615
participants aged 50 years or older who were referred for routine, clinically
indicated colonoscopy in 9 major hospital centers between April 17, 2000,
and October 3, 2001. The CTC was performed by using multislice scanners immediately
before standard colonoscopy; findings at colonoscopy were reported before
and after segmental unblinding to the CTC results.Main Outcome MeasuresThe sensitivity and specificity of CTC and conventional colonoscopy
in detecting participants with lesions sized at least 6 mm. Secondary outcomes
included detection of all lesions, detection of advanced lesions, possible
technical confounders, participant preferences, and evidence for increasing
accuracy with experience.ResultsA total of 827 lesions were detected in 308 of 600 participants who
underwent both procedures; 104 participants had lesions sized at least 6 mm.
The sensitivity of CTC for detecting participants with 1 or more lesions sized
at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for
lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results
were significantly lower than those for conventional colonoscopy, with sensitivities
of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants
were without any lesion sized at least 6 mm. The specificity of CTC and conventional
colonoscopy for detecting participants without any lesion sized at least 6
mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions
sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively.
Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC
varied considerably between centers and did not improve as the study progressed.
Participants expressed no clear preference for either technique.ConclusionsComputed tomographic colonography by these methods is not yet ready
for widespread clinical application. Techniques and training need to be improved.
697 citations
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TL;DR: It is argued that telomere shortening in the absence of other alterations may be a potent tumor suppressor mechanism and the evidence for and against the major molecular mechanisms proposed to initiate replicative senescence are discussed.
Abstract: Telomere dynamics are a critical component of both aging and cancer. Telomeres progressively shorten in almost all dividing cells and most human cells do not express or maintain sufficient telomerase activity to fully maintain telomeres. There is accumulating evidence that when only a few telomeres are short, they form end-associations, leading to a DNA damage signal resulting in replicative senescence (a cellular growth arrest, also called the M1 stage). In the absence of cell-cycle checkpoint pathways (e.g. p53 and or p16/Rb), cells bypass M1 senescence and telomeres continue to shorten eventually resulting in crisis (also called the M2 stage). M2 is characterized by many 'uncapped' chromosome ends, end-fusions, chromosome breakage fusion-bridge cycles, mitotic catastrophe and a high fraction of apoptotic cells. In a rare M2 cell, telomerase (a cellular reverse transcriptase) can be reactivated or up-regulated, resulting in indefinite cell proliferation. This cellular immortalization is a potentially rate-limiting step in carcinogenesis that is important for the continuing evolution of most advanced cancers. In this perspective we will present our views on the evidence for telomere dysfunction in aging and in cancer progression. We will argue that telomere shortening in the absence of other alterations may be a potent tumor suppressor mechanism and we will discuss the evidence for and against the major molecular mechanisms proposed to initiate replicative senescence.
696 citations
Authors
Showing all 39410 results
Name | H-index | Papers | Citations |
---|---|---|---|
Eugene Braunwald | 230 | 1711 | 264576 |
Joseph L. Goldstein | 207 | 556 | 149527 |
Eric N. Olson | 206 | 814 | 144586 |
Craig B. Thompson | 195 | 557 | 173172 |
Thomas C. Südhof | 191 | 653 | 118007 |
Scott M. Grundy | 187 | 841 | 231821 |
Michael S. Brown | 185 | 422 | 123723 |
Eric Boerwinkle | 183 | 1321 | 170971 |
Jiaguo Yu | 178 | 730 | 113300 |
John J.V. McMurray | 178 | 1389 | 184502 |
Eric J. Nestler | 178 | 748 | 116947 |
John D. Minna | 169 | 951 | 106363 |
Yuh Nung Jan | 162 | 460 | 74818 |
Andrew P. McMahon | 162 | 415 | 90650 |
Elliott M. Antman | 161 | 716 | 179462 |