The Experts below are selected from a list of 5616 Experts worldwide ranked by ideXlab platform

Vincent Waihin Yuen - One of the best experts on this subject based on the ideXlab platform.

  • adaptive and constitutive activations of malic enzymes confer liver cancer multi Layered Protection against ros
    Hepatology, 2021
    Co-Authors: Derek Lee, Misty Shuo Zhang, Felice Hoching Tsang, Macus Haoran Bao, Robin Kitho Lai, David Kungchun Chiu, Aki Puiwah Tse, Cheukting Law, Cerise Yuenki Chan, Vincent Waihin Yuen
    Abstract:

    HCC undergoes active metabolic reprogramming. Reactive oxygen species (ROS) are excessively generated in cancer cells and are neutralized by NADPH. Malic enzymes (MEs) are the less studied NADPH producers in cancer. We found that ME1 but not ME3 was regulated by the typical oxidative stress response pathway mediated by kelch-like ECH associated protein 1 (KEAP1)/ nuclear factor erythroid 2-related factor (NRF2). Surprisingly, ME3 was constitutively induced by super-enhancers. Disruption of any ME regulatory pathways decelerated HCC progression and sensitized HCC to Sorafenib. Therapeutically, simultaneous blockade of NRF2 and super-enhancer complex completely impeded HCC growth. Here we show that super-enhancer allows cancer cells to counteract the intrinsically high level of ROS through constitutively activating ME3 expression. When HCC cells encounter further episodes of ROS insult, NRF2 allows cancer cells to adapt by transcriptionally activating ME1. In conclusion: Our study reveals the complementary regulatory mechanisms which control MEs and provide cancer cells multiple layers of defence against oxidative stress. Targeting both regulatory mechanisms represents a potential therapeutic approach for HCC treatment.

Metin Cakanyildirim - One of the best experts on this subject based on the ideXlab platform.

  • network externalities Layered Protection and it security risk management
    Decision Support Systems, 2007
    Co-Authors: Metin Cakanyildirim
    Abstract:

    This paper considers two important issues related to security risk management. First, the presence of network externalities in security risks. Second, the distinction of general (network) and system-specific Protection measures. We found the optimal allocation of security resources (investments) in protecting every system in an organization. The results show that the consideration of network externalities and Layered Protection changes the risk mitigation decisions significantly. In addition, accurate estimation of system risk plays a critical role in the success of risk management. Otherwise, the use of a uniform baseline Protection approach may be more desirable when the misjudgment of relative system risks is likely to occur.

Derek Lee - One of the best experts on this subject based on the ideXlab platform.

  • adaptive and constitutive activations of malic enzymes confer liver cancer multi Layered Protection against ros
    Hepatology, 2021
    Co-Authors: Derek Lee, Misty Shuo Zhang, Felice Hoching Tsang, Macus Haoran Bao, Robin Kitho Lai, David Kungchun Chiu, Aki Puiwah Tse, Cheukting Law, Cerise Yuenki Chan, Vincent Waihin Yuen
    Abstract:

    HCC undergoes active metabolic reprogramming. Reactive oxygen species (ROS) are excessively generated in cancer cells and are neutralized by NADPH. Malic enzymes (MEs) are the less studied NADPH producers in cancer. We found that ME1 but not ME3 was regulated by the typical oxidative stress response pathway mediated by kelch-like ECH associated protein 1 (KEAP1)/ nuclear factor erythroid 2-related factor (NRF2). Surprisingly, ME3 was constitutively induced by super-enhancers. Disruption of any ME regulatory pathways decelerated HCC progression and sensitized HCC to Sorafenib. Therapeutically, simultaneous blockade of NRF2 and super-enhancer complex completely impeded HCC growth. Here we show that super-enhancer allows cancer cells to counteract the intrinsically high level of ROS through constitutively activating ME3 expression. When HCC cells encounter further episodes of ROS insult, NRF2 allows cancer cells to adapt by transcriptionally activating ME1. In conclusion: Our study reveals the complementary regulatory mechanisms which control MEs and provide cancer cells multiple layers of defence against oxidative stress. Targeting both regulatory mechanisms represents a potential therapeutic approach for HCC treatment.

Robin Kitho Lai - One of the best experts on this subject based on the ideXlab platform.

  • adaptive and constitutive activations of malic enzymes confer liver cancer multi Layered Protection against ros
    Hepatology, 2021
    Co-Authors: Derek Lee, Misty Shuo Zhang, Felice Hoching Tsang, Macus Haoran Bao, Robin Kitho Lai, David Kungchun Chiu, Aki Puiwah Tse, Cheukting Law, Cerise Yuenki Chan, Vincent Waihin Yuen
    Abstract:

    HCC undergoes active metabolic reprogramming. Reactive oxygen species (ROS) are excessively generated in cancer cells and are neutralized by NADPH. Malic enzymes (MEs) are the less studied NADPH producers in cancer. We found that ME1 but not ME3 was regulated by the typical oxidative stress response pathway mediated by kelch-like ECH associated protein 1 (KEAP1)/ nuclear factor erythroid 2-related factor (NRF2). Surprisingly, ME3 was constitutively induced by super-enhancers. Disruption of any ME regulatory pathways decelerated HCC progression and sensitized HCC to Sorafenib. Therapeutically, simultaneous blockade of NRF2 and super-enhancer complex completely impeded HCC growth. Here we show that super-enhancer allows cancer cells to counteract the intrinsically high level of ROS through constitutively activating ME3 expression. When HCC cells encounter further episodes of ROS insult, NRF2 allows cancer cells to adapt by transcriptionally activating ME1. In conclusion: Our study reveals the complementary regulatory mechanisms which control MEs and provide cancer cells multiple layers of defence against oxidative stress. Targeting both regulatory mechanisms represents a potential therapeutic approach for HCC treatment.

Misty Shuo Zhang - One of the best experts on this subject based on the ideXlab platform.

  • adaptive and constitutive activations of malic enzymes confer liver cancer multi Layered Protection against ros
    Hepatology, 2021
    Co-Authors: Derek Lee, Misty Shuo Zhang, Felice Hoching Tsang, Macus Haoran Bao, Robin Kitho Lai, David Kungchun Chiu, Aki Puiwah Tse, Cheukting Law, Cerise Yuenki Chan, Vincent Waihin Yuen
    Abstract:

    HCC undergoes active metabolic reprogramming. Reactive oxygen species (ROS) are excessively generated in cancer cells and are neutralized by NADPH. Malic enzymes (MEs) are the less studied NADPH producers in cancer. We found that ME1 but not ME3 was regulated by the typical oxidative stress response pathway mediated by kelch-like ECH associated protein 1 (KEAP1)/ nuclear factor erythroid 2-related factor (NRF2). Surprisingly, ME3 was constitutively induced by super-enhancers. Disruption of any ME regulatory pathways decelerated HCC progression and sensitized HCC to Sorafenib. Therapeutically, simultaneous blockade of NRF2 and super-enhancer complex completely impeded HCC growth. Here we show that super-enhancer allows cancer cells to counteract the intrinsically high level of ROS through constitutively activating ME3 expression. When HCC cells encounter further episodes of ROS insult, NRF2 allows cancer cells to adapt by transcriptionally activating ME1. In conclusion: Our study reveals the complementary regulatory mechanisms which control MEs and provide cancer cells multiple layers of defence against oxidative stress. Targeting both regulatory mechanisms represents a potential therapeutic approach for HCC treatment.