The Experts below are selected from a list of 4527 Experts worldwide ranked by ideXlab platform
T L Ratliff - One of the best experts on this subject based on the ideXlab platform.
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Cholesterol Esterification inhibition suppresses prostate cancer metastasis by impairing the wnt β catenin pathway
Molecular Cancer Research, 2018Co-Authors: Hyeon Jeong Lee, T L Ratliff, Renee E. Vickman, Rui Liu, Abigail Durkes, Bennett D. Elzey, Shuhua Yue, Xiaoqi Liu, Jixin ChengAbstract:Dysregulation of Cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of Cholesterol Esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intracardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. In addition, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of Cholesterol Esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These results collectively validate Cholesterol Esterification as a novel metabolic target for treating metastatic prostate cancer. Mol Cancer Res; 16(6); 974-85. ©2018 AACR.
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Cholesterol Esterification Inhibition Suppresses Prostate Cancer Metastasis by Impairing the Wnt/β-catenin Pathway
Molecular cancer research : MCR, 2018Co-Authors: Hyeon Jeong Lee, Renee E. Vickman, Rui Liu, Abigail Durkes, Bennett D. Elzey, Shuhua Yue, Xiaoqi Liu, T L RatliffAbstract:Dysregulation of Cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of Cholesterol Esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intracardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. In addition, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of Cholesterol Esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These results collectively validate Cholesterol Esterification as a novel metabolic target for treating metastatic prostate cancer. Mol Cancer Res; 16(6); 974-85. ©2018 AACR.
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Abrogating Cholesterol Esterification suppresses growth and metastasis of pancreatic cancer
Oncogene, 2016Co-Authors: J Li, D Gu, B Song, S Bandyopadhyay, S Chen, S F Konieczny, T L Ratliff, J-x ChengAbstract:Cancer cells are known to execute reprogramed metabolism of glucose, amino acids and lipids. Here, we report a significant role of Cholesterol metabolism in cancer metastasis. By using label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines, mediated by acyl-CoA Cholesterol acyltransferase-1 (ACAT-1) enzyme. Expression of ACAT-1 showed a correlation with poor patient survival. Abrogation of Cholesterol Esterification, either by an ACAT-1 inhibitor or by shRNA knockdown, significantly suppressed tumor growth and metastasis in an orthotopic mouse model of pancreatic cancer. Mechanically, ACAT-1 inhibition increased intracellular free Cholesterol level, which was associated with elevated endoplasmic reticulum stress and caused apoptosis. Collectively, our results demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting Cholesterol Esterification.
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Avasimibe encapsulated in human serum albumin blocks Cholesterol Esterification for selective cancer treatment.
ACS nano, 2015Co-Authors: Steve Seung-young Lee, T L Ratliff, Jien Nee Tai, Kinam Park, Jixin ChengAbstract:Undesirable side effects remain a significant challenge in cancer chemotherapy. Here we report a strategy for cancer-selective chemotherapy by blocking acyl-CoA Cholesterol acyltransferase-1 (ACAT-1)-mediated Cholesterol Esterification. To efficiently block Cholesterol Esterification in cancer in vivo, we developed a systemically injectable nanoformulation of avasimibe (a potent ACAT-1 inhibitor), called avasimin. In cell lines of human prostate, pancreatic, lung, and colon cancer, avasimin significantly reduced cholesteryl ester storage in lipid droplets and elevated intracellular free Cholesterol levels, which led to apoptosis and suppression of proliferation. In xenograft models of prostate cancer and colon cancer, intravenous administration of avasimin caused the concentration of avasimibe in tumors to be 4-fold higher than the IC50 value. Systemic treatment of avasimin notably suppressed tumor growth in mice and extended the length of survival time. No adverse effects of avasimin to normal cells and organs were observed. Together, this study provides an effective approach for selective cancer chemotherapy by targeting altered Cholesterol metabolism of cancer cells.
Matthew W. Spence - One of the best experts on this subject based on the ideXlab platform.
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Cultured fibroblasts from patients with Niemann-Pick disease type C and type D exhibit distinct defects in Cholesterol Esterification
Biochimica et biophysica acta, 1992Co-Authors: Harkirat S. Sidhu, David M. Byers, Harold W. Cook, Frederick B. St. C. Palmer, Stella A. R. Rastogi, Matthew W. SpenceAbstract:Abstract The Niemann-Pick group of diseases can be broadly classified into two types based on clinical and biochemical characteristics. Type I is characterized by a primary deficiency of lysosomal sphingomyelinase while Type II may have a defect in the regulation of intracellular Cholesterol metabolism. We have studied Cholesterol Esterification in cultured fibroblasts from patients with two phenotypes of Type II disease: an Acadian population of southwestern Nova Scotia (Canada) with a form of the disease known as Niemann-Pick type D (NPD) and a group of panethnic origin with Niemann-Pick type C (NPC). Addition of whole serum to normal fibroblasts grown initially in lipoprotein-deficient serum caused a rapid (within 6 h) increase in Cholesterol Esterification, reaching maximum values at around 24 h, while NPC fibroblasts showed little increase ( normal. These observations indicate that (a) regulation of Cholesterol Esterification in response to serum lipoproteins (but not 25-hydroxyCholesterol) is abnormal in both NPC and NPD fibroblasts, and (b) the biochemical phenotypes of fibroblasts from NPC and NPD patients are distinct.
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Niemann-Pick Type II fibroblasts exhibit impaired Cholesterol Esterification in response to shingomyelin hydrolysis
Biochimica et biophysica acta, 1992Co-Authors: David M. Byers, Matthew W. Morgan, Harold W. Cook, Frederick B. St. C. Palmer, Matthew W. SpenceAbstract:Abstract Fibroblasts from patients with Niemann-Pick Type II disease, including the panethnic type C (NPC) and Nova Scotia Acadian type D (NPD) forms, exhibit reduced or delayed stimulation of Cholesterol Esterification by low density lipoprotein (LDL). Based on recent evidence that Cholesterol Esterification can also be stimulated by cell surface sphingomyelin hydrolysis, we have compared the response of normal, NPC and NPD fibroblasts to treatment with exogenous sphingomyelinase (SMase). Staphylococcus aureus SMase (> 0.05 U/ml) hydrolyzed over 90% of endogenous sphingomyelin within 1 h and increased incorporation of [ 3 H]oleic acid into Cholesterol-[ 3 H]oleate after an initial lag in all three cell types. However, normal levels of Cholesterol Esterification were not observed for NP Type II fibroblasts: four NPD cell lines exhibited an average of 32% of normal response while Cholesterol Esterification was only 20% in two well-characterized NPC lines. A third NPC line exhibited normal response to SMase despite greater than 90% impairment of LDL-stimuated Cholesterol Esterification. Incubation of fibroblasts with LDL followed by SMase produced a synergistic response, particularly in NPC cells where there was little response to either treatment alone. Chloroquinone abolished LDL-stimulated Cholesterol Esterification in normal fibroblasts but had no effect on the response to SMase, indicating that lysosomal enzymes may not be involved in SMase-mediated Cholesterol Esterification. These results suggest that intracellular processing of Cholesterol derived from either LDL or release from the plasma membrane (by sphingomyelin hydrolysis) is affected in Niemann-Pick Type II cells and that these pathways can complement one another in the stimulation of Cholesterol Esterification.
Jixin Cheng - One of the best experts on this subject based on the ideXlab platform.
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Cholesterol Esterification inhibition suppresses prostate cancer metastasis by impairing the wnt β catenin pathway
Molecular Cancer Research, 2018Co-Authors: Hyeon Jeong Lee, T L Ratliff, Renee E. Vickman, Rui Liu, Abigail Durkes, Bennett D. Elzey, Shuhua Yue, Xiaoqi Liu, Jixin ChengAbstract:Dysregulation of Cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of Cholesterol Esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intracardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. In addition, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of Cholesterol Esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These results collectively validate Cholesterol Esterification as a novel metabolic target for treating metastatic prostate cancer. Mol Cancer Res; 16(6); 974-85. ©2018 AACR.
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Avasimibe encapsulated in human serum albumin blocks Cholesterol Esterification for selective cancer treatment.
ACS nano, 2015Co-Authors: Steve Seung-young Lee, T L Ratliff, Jien Nee Tai, Kinam Park, Jixin ChengAbstract:Undesirable side effects remain a significant challenge in cancer chemotherapy. Here we report a strategy for cancer-selective chemotherapy by blocking acyl-CoA Cholesterol acyltransferase-1 (ACAT-1)-mediated Cholesterol Esterification. To efficiently block Cholesterol Esterification in cancer in vivo, we developed a systemically injectable nanoformulation of avasimibe (a potent ACAT-1 inhibitor), called avasimin. In cell lines of human prostate, pancreatic, lung, and colon cancer, avasimin significantly reduced cholesteryl ester storage in lipid droplets and elevated intracellular free Cholesterol levels, which led to apoptosis and suppression of proliferation. In xenograft models of prostate cancer and colon cancer, intravenous administration of avasimin caused the concentration of avasimibe in tumors to be 4-fold higher than the IC50 value. Systemic treatment of avasimin notably suppressed tumor growth in mice and extended the length of survival time. No adverse effects of avasimin to normal cells and organs were observed. Together, this study provides an effective approach for selective cancer chemotherapy by targeting altered Cholesterol metabolism of cancer cells.
Andras G. Lacko - One of the best experts on this subject based on the ideXlab platform.
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Plasma lipids and Cholesterol Esterification in Alzheimer's disease.
Mechanisms of ageing and development, 1994Co-Authors: Janice Knebl, Defazio P, Michael Clearfield, Little L, Walter J. Mcconathy, Mcpherson R, Andras G. LackoAbstract:Abstract Eight patients and eight age matched controls were recruited to study parameters related to plasma lipoprotein metabolism in Alzheimer's disease based on previous studies in Down's syndrome (A.G. Lacko et al., Clin. Chim. Acta, 132 (1983) 133). The fractional rate of Cholesterol Esterification (% Cholesterol esterifed per hour) was 16% lower in the patient group compared with controls. Correlational analyses of lecithin/Cholesterol acyltransferase (LCAT) activity and plasma lipids revealed additional differences between the Alzheimer's patients and control subjects. These data are strikingly similar to those obtained earlier with Down's syndrome patients. These data, combined with analyses of cholesteryl ester transfer protein (CETP) levels, suggest that reverse Cholesterol transport in general and CETP activity in particular may be altered in Alzheimer's disease.
Hyeon Jeong Lee - One of the best experts on this subject based on the ideXlab platform.
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Cholesterol Esterification inhibition suppresses prostate cancer metastasis by impairing the wnt β catenin pathway
Molecular Cancer Research, 2018Co-Authors: Hyeon Jeong Lee, T L Ratliff, Renee E. Vickman, Rui Liu, Abigail Durkes, Bennett D. Elzey, Shuhua Yue, Xiaoqi Liu, Jixin ChengAbstract:Dysregulation of Cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of Cholesterol Esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intracardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. In addition, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of Cholesterol Esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These results collectively validate Cholesterol Esterification as a novel metabolic target for treating metastatic prostate cancer. Mol Cancer Res; 16(6); 974-85. ©2018 AACR.
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Cholesterol Esterification Inhibition Suppresses Prostate Cancer Metastasis by Impairing the Wnt/β-catenin Pathway
Molecular cancer research : MCR, 2018Co-Authors: Hyeon Jeong Lee, Renee E. Vickman, Rui Liu, Abigail Durkes, Bennett D. Elzey, Shuhua Yue, Xiaoqi Liu, T L RatliffAbstract:Dysregulation of Cholesterol is a common characteristic of human cancers including prostate cancer. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Inhibition of Cholesterol Esterification in prostate cancer cells significantly suppresses the development and growth of metastatic cancer lesions in both orthotopic and intracardiac injection mouse models. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. In addition, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of Cholesterol Esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These results collectively validate Cholesterol Esterification as a novel metabolic target for treating metastatic prostate cancer. Mol Cancer Res; 16(6); 974-85. ©2018 AACR.