Institution
Charlie Norwood VA Medical Center
Healthcare•Augusta, Georgia, United States•
About: Charlie Norwood VA Medical Center is a healthcare organization based out in Augusta, Georgia, United States. It is known for research contribution in the topics: Autophagy & Kidney. The organization has 349 authors who have published 490 publications receiving 16360 citations. The organization is also known as: Augusta VA Medical Center.
Topics: Autophagy, Kidney, Acute kidney injury, Cancer, Prostate cancer
Papers
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TL;DR: Most interventions reviewed in this paper included common components that were developed through a cognitive behavioral framework and included psychoeducation, cognitive restructuring, goal setting, exposure, and it is possible that these shared features may in part account for symptom reduction.
179 citations
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TL;DR: It is suggested that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO.
Abstract: Renal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUO-associated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/α-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils. Tubular atrophy, apoptosis, nephron loss, and interstitial macrophage infiltration were all inhibited in these mice. Moreover, these mice showed a specific suppression of the expression of a profibrotic factor FGF2 (fibroblast growth factor 2). In vitro, TGFB1 (transforming growth factor β 1) induced autophagy, apoptosis, and FN1 accumulation in primary proximal tubular cells. Inhibition of autophagy suppressed FN1 accumulation and apoptosis, while enhancement of autophagy increased TGFB1-induced-cell death. These results suggest that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO. The profibrotic function of autophagy is related to the regulation on tubular cell death, interstitial inflammation, and the production of profibrotic factors.
171 citations
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French Institute of Health and Medical Research1, Paris Descartes University2, University of Texas Southwestern Medical Center3, Brigham and Women's Hospital4, Charlie Norwood VA Medical Center5, University of Kansas6, University of Paris7, University of Texas MD Anderson Cancer Center8, University of Verona9
TL;DR: It is found that the tumor suppressors TSC1 and TSC2, defects in which underlie the genetic disease Tuberous Sclerosis Complex, drive the mTOR-dependent autophagosomal destruction of the transcriptional activator YAP.
Abstract: Genetic studies have shown that the tuberous sclerosis complex (TSC) 1–TSC2–mammalian target of Rapamycin (mTOR) and the Hippo–Yes-associated protein 1 (YAP) pathways are master regulators of organ size, which are often involved in tumorigenesis. The crosstalk between these signal transduction pathways in coordinating environmental cues, such as nutritional status and mechanical constraints, is crucial for tissue growth. Whether and how mTOR regulates YAP remains elusive. Here we describe a novel mouse model of TSC which develops renal mesenchymal lesions recapitulating human perivascular epithelioid cell tumors (PEComas) from patients with TSC. We identify that YAP is up-regulated by mTOR in mouse and human PEComas. YAP inhibition blunts abnormal proliferation and induces apoptosis of TSC1–TSC2-deficient cells, both in culture and in mosaic Tsc1 mutant mice. We further delineate that YAP accumulation in TSC1/TSC2-deficient cells is due to impaired degradation of the protein by the autophagosome/lysosome system. Thus, the regulation of YAP by mTOR and autophagy is a novel mechanism of growth control, matching YAP activity with nutrient availability under growth-permissive conditions. YAP may serve as a potential therapeutic target for TSC and other diseases with dysregulated mTOR activity.
169 citations
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TL;DR: The Fas-FasL/CTLs and the MLL1-H3K4me3-PD-L1 axis play contrasting roles in pancreatic cancer immune surveillance and evasion.
Abstract: Background: Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mechanism of PD-L1 expression regulation in the context of pancreatic cancer immune evasion. Methods: Pancreatic cancer mouse models and human specimens were used to determine PD-L1 and PD-1 expression and cancer immune evasion. Histone methyltransferase inhibitors, RNAi, and overexpression were used to elucidate the underlying molecular mechanism of PD-L1 expression regulation. All statistical tests were two-sided. Results: PD-L1 is expressed in 60% to 90% of tumor cells in human pancreatic carcinomas and in nine of 10 human pancreatic cancer cell lines. PD-1 is expressed in 51.2% to 52.1% of pancreatic tumor–infiltrating cytotoxic T lymphocytes (CTLs). Tumors grow statistically significantly faster in FasL-deficient mice than in wild-type mice (P = .03–.001) and when CTLs are neutralized (P = .03– Conclusions: The Fas-FasL/CTLs and the MLL1-H3K4me3-PD-L1 axis play contrasting roles in pancreatic cancer immune surveillance and evasion. Targeting the MLL1-H3K4me3 axis is an effective approach to enhance the efficacy of checkpoint immunotherapy against pancreatic cancer.
168 citations
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TL;DR: The most current information on the mechanisms of tumor angiogenesis, proangiogenic and antiang iogenic factors, potential targets and their mechanisms of action, and experimental evidences are summarized, as well as the most recent clinical trial data on antiangIogenic agents for cancer therapy are summarized.
Abstract: The idea of antiangiogenic therapy was the brainchild of Dr. Judah Folkman in the early 1970s. He proposed that by cutting off the blood supply, cancer cells would be deprived of nutrients and, hence, treated. His efforts paid off when bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, was approved as antiangiogenic therapy in 2004 for the treatment of colon cancer. Since then, an array of antiangiogenic inhibitors, either as monotherapy or in combination with other cytotoxic and chemotherapy drugs, have been developed, used in clinical trials, and approved for the treatment of cancer. Despite this important breakthrough, antiangiogenic therapy for cancer met with a number of hurdles on its way to becoming an option for cancer therapy. In this article, we summarize the most current information on the mechanisms of tumor angiogenesis, proangiogenic and antiangiogenic factors, potential targets and their mechanisms of action, and experimental evidences, as well as the most recent clinical trial data on antiangiogenic agents for cancer therapy.
168 citations
Authors
Showing all 353 results
Name | H-index | Papers | Citations |
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Zheng Dong | 70 | 283 | 24123 |
Lin Mei | 69 | 245 | 15903 |
Wen Cheng Xiong | 64 | 194 | 12171 |
Ruth B. Caldwell | 60 | 214 | 12314 |
Darrell W. Brann | 60 | 188 | 11066 |
Steven S. Coughlin | 56 | 303 | 12401 |
Martha K. Terris | 55 | 375 | 12346 |
Susan C. Fagan | 53 | 179 | 10135 |
Adviye Ergul | 48 | 188 | 7678 |
Kebin Liu | 46 | 128 | 7271 |
Maribeth H. Johnson | 45 | 125 | 5189 |
Azza B. El-Remessy | 44 | 123 | 5746 |
Yutao Liu | 43 | 152 | 5657 |
William D. Hill | 41 | 101 | 9870 |
Yuqing Huo | 41 | 114 | 9815 |