The Experts below are selected from a list of 28929 Experts worldwide ranked by ideXlab platform
Jack Cm Wong - One of the best experts on this subject based on the ideXlab platform.
-
abstract 689 downregulation of timp2 via hif 1a mir 210 hif 3a regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma
Cancer Research, 2016Co-Authors: Alan Kl Kai, Lo Kong Chan, Joyce Man-fong Lee, Carmen Cl Wong, Jack Cm WongAbstract:Cancer metastasis is a multi-step process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases 2 (TIMP2) in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly downregulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.1%; 23/56) in human HCCs as compared to the corresponding non-tumorous livers and was significantly associated with direct liver invasion into the adjacent liver parenchyma and poorer survival outcomes of the HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced the cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Furthermore, using orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line MHCC-97L not only significantly reduced the incidence of tumor microsatellite formation and venous invasion in the primary hepatic tumor xenografts, but also pulmonary metastasis, suggesting that both extrahepatic and intrahepatic metastasis in HCC was suppressed by TIMP2 expression. Mechanistically, TIMP2 suppression in a hypoxic environment was induced through a regulatory Feedback Circuit consisting of HIF-1a, miR-210 and HIF-3a. Taken altogether, our findings established that TIMP2 was frequently downregulated in human HCCs and its downregulation was associated with aggressive behavior and poorer patients’ outcome. Its suppression was under the regulation of a novel Feedback Circuit consisting of HIF-1a/ miR-210/ HIF-3a. Overall, our study has provided solid in vitro and in vivo evidence that TIMP2 is an important regulator of ECM degradation and HCC metastasis. These findings demonstrated that perturbation of the dynamic HIF-1a signaling Circuit by miR-210 inhibitor abolished TIMP2 downregulation and suppressed HCC cell invasion. They also support the notion that targeting against HIF-1a signaling is a promising direction to tackle the hypoxic responses in HCC elicited by transarterial chemo-embolization (TACE) treatment to HCC patients. Citation Format: Alan KL Kai, Lo Kong Chan, Regina CL Lo, Joyce Lee, Carmen CL Wong, Jack CM Wong, Irene OL Ng. Downregulation of TIMP2 via HIF-1a/miR-210/HIF-3a regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 689.
Taihaur Kuo - One of the best experts on this subject based on the ideXlab platform.
-
A Monolithic Capacitor-Current-Controlled Hysteretic Buck Converter With Transient-Optimized Feedback Circuit
IEEE Journal of Solid-State Circuits, 2015Co-Authors: Shihhsiung Chien, Tinghsuan Hung, Szuyu Huang, Taihaur KuoAbstract:This paper proposes a monolithic capacitor-current-controlled hysteretic buck converter with a transient-optimized Feedback Circuit (TOFC) for compact-sized portable devices. The proposed TOFC simultaneously optimizes both load and dynamic voltage scaling (DVS) transient responses to minimize output voltage undershoot/overshoot and settling time. In addition, a transient-hold (TH) technique, which prevents transient response optimization from being affected by the error amplifier without increasing the compensation capacitance, is also proposed to save chip area. This work is implemented in a 0.35 μm CMOS process with a chip area of 0.88 mm 2 . Measurement results show that, for a 500 mA load transient, the output voltage settles in 0.9 μs with an undershoot/overshoot of less than 35 mV. For a 0.6-V DVS transient, output voltage settles in 3 μs with negligible undershoot/overshoot. Moreover, 96% peak efficiency is measured at 500 mW output power.
-
a monolithic capacitor current controlled hysteretic buck converter with transient optimized Feedback Circuit
Asian Solid-State Circuits Conference, 2014Co-Authors: Shihhsiung Chien, Tinghsuan Hung, Szuyu Huang, Taihaur KuoAbstract:This paper proposes a monolithic capacitor-current-controlled hysteretic buck converter with a transient-optimized Feedback Circuit (TOFC) and a transient-hold (TH) technique. The proposed TOFC simultaneously optimizes both load and dynamic voltage scaling (DVS) transient responses. In addition, the proposed TH technique significantly reduces the required compensation capacitance to save chip area. Implemented in a 0.35-μm CMOS process, this work occupies 0.88 mm2. Measured results show that, for 500-mA step-up load current, output voltage is settled within 0.9 μs, and for 0.6-V DVS, output voltage is settled within 3 μs. Peak efficiency of 96% is measured at 500 mW output power.
Gero Miesenbock - One of the best experts on this subject based on the ideXlab platform.
-
Sparse, Decorrelated Odor Coding in the Mushroom Body Enhances Learned Odor Discrimination
2016Co-Authors: Andrew C. Lin, Alexei M Bygrave, Alix De Calignon, Tzumin Lee, Gero MiesenbockAbstract:Sparse coding may be a general strategy of neural systems to augment memory capacity. In Drosophila, sparse odor coding by the Kenyon cells of the mushroom body is thought to generate a large number of precisely addressable locations for the storage of odor-specific memories. However, it remains untested how sparse coding relates to behavioral performance. Here we demonstrate that sparseness is controlled by a negative Feedback Circuit between Kenyon cells and the GABAergic anterior paired lateral (APL) neuron. Systematic activation and blockade of each leg of this Feedback Circuit show that Kenyon cells activate APL and APL inhibits Kenyon cells. Disrupting the Kenyon cell-APL Feedback loop decreases the sparseness of Kenyon cell odor responses, increases inter-odor correlations, and prevents flies from learning to discriminate similar, but not dissimilar, odors. These results suggest that Feedback inhibition suppresses Kenyon cell activity to maintain sparse, decorrelated odor coding and thus the odor-specificity of memories
-
sparse decorrelated odor coding in the mushroom body enhances learned odor discrimination
Nature Neuroscience, 2014Co-Authors: Andrew C. Lin, Alexei M Bygrave, Alix De Calignon, Tzumin Lee, Gero MiesenbockAbstract:Sparse coding may be a general strategy of neural systems for augmenting memory capacity. In Drosophila melanogaster, sparse odor coding by the Kenyon cells of the mushroom body is thought to generate a large number of precisely addressable locations for the storage of odor-specific memories. However, it remains untested how sparse coding relates to behavioral performance. Here we demonstrate that sparseness is controlled by a negative Feedback Circuit between Kenyon cells and the GABAergic anterior paired lateral (APL) neuron. Systematic activation and blockade of each leg of this Feedback Circuit showed that Kenyon cells activated APL and APL inhibited Kenyon cells. Disrupting the Kenyon cell-APL Feedback loop decreased the sparseness of Kenyon cell odor responses, increased inter-odor correlations and prevented flies from learning to discriminate similar, but not dissimilar, odors. These results suggest that Feedback inhibition suppresses Kenyon cell activity to maintain sparse, decorrelated odor coding and thus the odor specificity of memories.
Lo Kong Chan - One of the best experts on this subject based on the ideXlab platform.
-
down regulation of timp2 by hif 1α mir 210 hif 3α regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma
Hepatology, 2016Co-Authors: Alan Ka-lun Kai, Lo Kong Chan, Joyce Man-fong Lee, Carmen Chak-lui Wong, Jack Chun-ming WongAbstract:Cancer metastasis is a multistep process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling, which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases (TIMP) 2 in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly down-regulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.8%; 23 of 55) in human HCCs and was significantly associated with liver invasion and poorer survival outcomes of HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Using an orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line, MHCC-97L, significantly reduced HCC progression as well as pulmonary metastasis. Mechanistically, TIMP2 suppression, in a hypoxic environment, was induced through a regulatory Feedback Circuit consisting of hypoxia-inducible factor (HIF) 1 alpha, microRNA-210 (miR-210), and HIF-3α. Conclusion: TIMP2 is frequently down-regulated in human HCCs and its down-regulation is associated with aggressive tumor behavior and poorer patient outcome. Its suppression is under the regulation of a novel Feedback Circuit consisting of HIF-1α/miR-210/HIF-3α. TIMP2 is an important regulator of ECM degradation and HCC metastasis. (Hepatology 2016;64:473-487)
-
abstract 689 downregulation of timp2 via hif 1a mir 210 hif 3a regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma
Cancer Research, 2016Co-Authors: Alan Kl Kai, Lo Kong Chan, Joyce Man-fong Lee, Carmen Cl Wong, Jack Cm WongAbstract:Cancer metastasis is a multi-step process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases 2 (TIMP2) in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly downregulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.1%; 23/56) in human HCCs as compared to the corresponding non-tumorous livers and was significantly associated with direct liver invasion into the adjacent liver parenchyma and poorer survival outcomes of the HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced the cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Furthermore, using orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line MHCC-97L not only significantly reduced the incidence of tumor microsatellite formation and venous invasion in the primary hepatic tumor xenografts, but also pulmonary metastasis, suggesting that both extrahepatic and intrahepatic metastasis in HCC was suppressed by TIMP2 expression. Mechanistically, TIMP2 suppression in a hypoxic environment was induced through a regulatory Feedback Circuit consisting of HIF-1a, miR-210 and HIF-3a. Taken altogether, our findings established that TIMP2 was frequently downregulated in human HCCs and its downregulation was associated with aggressive behavior and poorer patients’ outcome. Its suppression was under the regulation of a novel Feedback Circuit consisting of HIF-1a/ miR-210/ HIF-3a. Overall, our study has provided solid in vitro and in vivo evidence that TIMP2 is an important regulator of ECM degradation and HCC metastasis. These findings demonstrated that perturbation of the dynamic HIF-1a signaling Circuit by miR-210 inhibitor abolished TIMP2 downregulation and suppressed HCC cell invasion. They also support the notion that targeting against HIF-1a signaling is a promising direction to tackle the hypoxic responses in HCC elicited by transarterial chemo-embolization (TACE) treatment to HCC patients. Citation Format: Alan KL Kai, Lo Kong Chan, Regina CL Lo, Joyce Lee, Carmen CL Wong, Jack CM Wong, Irene OL Ng. Downregulation of TIMP2 via HIF-1a/miR-210/HIF-3a regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 689.
Joyce Man-fong Lee - One of the best experts on this subject based on the ideXlab platform.
-
down regulation of timp2 by hif 1α mir 210 hif 3α regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma
Hepatology, 2016Co-Authors: Alan Ka-lun Kai, Lo Kong Chan, Joyce Man-fong Lee, Carmen Chak-lui Wong, Jack Chun-ming WongAbstract:Cancer metastasis is a multistep process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling, which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases (TIMP) 2 in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly down-regulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.8%; 23 of 55) in human HCCs and was significantly associated with liver invasion and poorer survival outcomes of HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Using an orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line, MHCC-97L, significantly reduced HCC progression as well as pulmonary metastasis. Mechanistically, TIMP2 suppression, in a hypoxic environment, was induced through a regulatory Feedback Circuit consisting of hypoxia-inducible factor (HIF) 1 alpha, microRNA-210 (miR-210), and HIF-3α. Conclusion: TIMP2 is frequently down-regulated in human HCCs and its down-regulation is associated with aggressive tumor behavior and poorer patient outcome. Its suppression is under the regulation of a novel Feedback Circuit consisting of HIF-1α/miR-210/HIF-3α. TIMP2 is an important regulator of ECM degradation and HCC metastasis. (Hepatology 2016;64:473-487)
-
abstract 689 downregulation of timp2 via hif 1a mir 210 hif 3a regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma
Cancer Research, 2016Co-Authors: Alan Kl Kai, Lo Kong Chan, Joyce Man-fong Lee, Carmen Cl Wong, Jack Cm WongAbstract:Cancer metastasis is a multi-step process that involves a series of tumor-stromal interaction, including extracellular matrix (ECM) remodeling which requires a concerted action of multiple proteolytic enzymes and their endogenous inhibitors. This study investigated the role of tissue inhibitor of metalloproteinases 2 (TIMP2) in the context of hepatocellular carcinoma (HCC) metastasis. We found that TIMP2 was the most significantly downregulated member among the TIMP family in human HCCs. Moreover, TIMP2 underexpression was frequent (41.1%; 23/56) in human HCCs as compared to the corresponding non-tumorous livers and was significantly associated with direct liver invasion into the adjacent liver parenchyma and poorer survival outcomes of the HCC patients. Furthermore, stable silencing of TIMP2 in HCC cell lines enhanced the cell invasive ability and ECM degradation associated with formation of invadopodia-like feature, suggesting that TIMP2 is a negative regulator of HCC metastasis. Furthermore, using orthotopic tumor xenograft model, we demonstrated that ectopic expression of TIMP2 open reading frame in the highly metastatic HCC cell line MHCC-97L not only significantly reduced the incidence of tumor microsatellite formation and venous invasion in the primary hepatic tumor xenografts, but also pulmonary metastasis, suggesting that both extrahepatic and intrahepatic metastasis in HCC was suppressed by TIMP2 expression. Mechanistically, TIMP2 suppression in a hypoxic environment was induced through a regulatory Feedback Circuit consisting of HIF-1a, miR-210 and HIF-3a. Taken altogether, our findings established that TIMP2 was frequently downregulated in human HCCs and its downregulation was associated with aggressive behavior and poorer patients’ outcome. Its suppression was under the regulation of a novel Feedback Circuit consisting of HIF-1a/ miR-210/ HIF-3a. Overall, our study has provided solid in vitro and in vivo evidence that TIMP2 is an important regulator of ECM degradation and HCC metastasis. These findings demonstrated that perturbation of the dynamic HIF-1a signaling Circuit by miR-210 inhibitor abolished TIMP2 downregulation and suppressed HCC cell invasion. They also support the notion that targeting against HIF-1a signaling is a promising direction to tackle the hypoxic responses in HCC elicited by transarterial chemo-embolization (TACE) treatment to HCC patients. Citation Format: Alan KL Kai, Lo Kong Chan, Regina CL Lo, Joyce Lee, Carmen CL Wong, Jack CM Wong, Irene OL Ng. Downregulation of TIMP2 via HIF-1a/miR-210/HIF-3a regulatory Feedback Circuit enhances cancer metastasis in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 689.
