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Adenosinergic

The Experts below are selected from a list of 2313 Experts worldwide ranked by ideXlab platform

Akio Ohta – 1st expert on this subject based on the ideXlab platform

  • hostile hypoxia a2 Adenosinergic tumor biology as the next barrier to overcome for tumor immunologists
    Cancer immunology research, 2014
    Co-Authors: Michail V Sitkovsky, Dmitriy Lukashev, Stephen Hatfield, Bryan Belikoff, Robert Abbott, Akio Ohta

    Abstract:

    Hypoxia-driven, A2A adenosine receptor (A2AR)–mediated (hypoxia–A2-Adenosinergic), T-cell–autonomous immunosuppression was first recognized as critical and nonredundant in protecting normal tissues from inflammatory damage and autoimmunity. However, this immunosuppressive mechanism can be highjacked by bacteria and tumors to provide misguided protection for pathogens and cancerous tissues. Inhibitors of the hypoxia–A2-Adenosinergic pathway represent a conceptually novel type of immunologic coadjuvants that could be combined with cancer vaccines, adoptive cell transfer, and/or blockade of negative immunologic regulators to further prolong patient survival and to minimize treatment-related side effects. In support of this approach are preclinical studies and findings that some human cancers are resistant to chemotherapies and immunotherapies due to the tumor-generated extracellular adenosine and A2AR on antitumor T and natural killer (NK) cells. Among the coadjuvants are (i) antagonists of A2AR, (ii) extracellular adenosine-degrading drugs, (iii) inhibitors of adenosine generation by CD39/CD73 ectoenzymes, and (iv) inhibitors of hypoxia–HIF-1α signaling. Combining these coadjuvants with CTLA-4 and/or PD-1 blockade is expected to have additive or even synergistic effects of targeting two different antitumor protective mechanisms. It is expected that even after multicombinatorial blockade of negative immunologic regulators, the antitumor T and NK cells would still be vulnerable to inhibition by hypoxia and A2AR. Yet to be tested is the potential capacity of coadjuvants to minimize the side effects of CTLA-4 and/or PD-1 blockade by decreasing the dose of blocking antibodies or by eliminating the need for dual blockade. Cancer Immunol Res; 2(7); 598–605. ©2014 AACR .

  • the antihypoxia Adenosinergic pathogenesis as a result of collateral damage by overactive immune cells
    Journal of Leukocyte Biology, 2009
    Co-Authors: Stephen Hatfield, Michail V Sitkovsky, Dmitriy Lukashev, Bryan Belikoff, Akio Ohta

    Abstract:

    Here, we attract attention to the possibility of iatrogenic exacerbation of immune-mediated tissue damage as a result of the unintended weakening of the tissue-protecting, hypoxia-Adenosinergic pathway. These immunosuppressive, anti-inflammatory pathways play a critical and nonredundant role in the protection of normal tissues from collateral damage during an inflammatory response. We believe that it is the tissue hypoxia associated with inflammatory damage that leads to local inhibition of overactive immune cells by activating A2AR and A2BR and stabilizing HIF-1 .W e show in an animal model of acute lung injury that oxygenation (i.e., inspiring supplemental oxygen) reverses tissue hypoxia and exacerbates ongoing inflammatory lung tissue damage. However, little has been done to carefully investigate and prevent this in a clinical setting. Similarly, the consumption of caffeine antagonizes A2ARs, resulting in exacerbation of ongoing acute inflammation. It is suggested that although the elimination of hypoxia-Adenosinergic immunosuppression is desirable to improve vaccines, it is important to take into account the unintentional effects of supplemental oxygen and caffeine, which may increase collateral, inflammatory tissue damage. J. Leukoc. Biol. 86: 545–548; 2009.

  • the Adenosinergic immunomodulatory drugs
    Current Opinion in Pharmacology, 2009
    Co-Authors: Akio Ohta, Michail V Sitkovsky

    Abstract:

    Hypoxia-driven increase of extracellular adenosine in local tissue microenvironments of inflamed and cancerous tissues plays a critical role in the regulation of tissue destruction by activated immune cells. Accumulated data suggest that injection or consumption of A2A adenosine receptor (A2AR) antagonists may represent a drug treatment that diminishes adenosine-mediated immunosuppression. Since this, in turn, enhances the immune response, inhibition of adenosine-A2AR signaling may be a promising approach to enhance anti-tumor or anti-pathogen immune response. Patients with disorders characterized by excessive inflammation may be at risk to A2AR antagonists (e.g. caffeine) because of the effect to increase inflammatory damage secondary to enhanced immunity. On the other hand, enhancement of hypoxia-Adenosinergic immunomodulatory pathways may be beneficial to prevent inflammatory tissue destruction.

Michail V Sitkovsky – 2nd expert on this subject based on the ideXlab platform

  • hostile hypoxia a2 Adenosinergic tumor biology as the next barrier to overcome for tumor immunologists
    Cancer immunology research, 2014
    Co-Authors: Michail V Sitkovsky, Dmitriy Lukashev, Stephen Hatfield, Bryan Belikoff, Robert Abbott, Akio Ohta

    Abstract:

    Hypoxia-driven, A2A adenosine receptor (A2AR)–mediated (hypoxia–A2-Adenosinergic), T-cell–autonomous immunosuppression was first recognized as critical and nonredundant in protecting normal tissues from inflammatory damage and autoimmunity. However, this immunosuppressive mechanism can be highjacked by bacteria and tumors to provide misguided protection for pathogens and cancerous tissues. Inhibitors of the hypoxia–A2-Adenosinergic pathway represent a conceptually novel type of immunologic coadjuvants that could be combined with cancer vaccines, adoptive cell transfer, and/or blockade of negative immunologic regulators to further prolong patient survival and to minimize treatment-related side effects. In support of this approach are preclinical studies and findings that some human cancers are resistant to chemotherapies and immunotherapies due to the tumor-generated extracellular adenosine and A2AR on antitumor T and natural killer (NK) cells. Among the coadjuvants are (i) antagonists of A2AR, (ii) extracellular adenosine-degrading drugs, (iii) inhibitors of adenosine generation by CD39/CD73 ectoenzymes, and (iv) inhibitors of hypoxia–HIF-1α signaling. Combining these coadjuvants with CTLA-4 and/or PD-1 blockade is expected to have additive or even synergistic effects of targeting two different antitumor protective mechanisms. It is expected that even after multicombinatorial blockade of negative immunologic regulators, the antitumor T and NK cells would still be vulnerable to inhibition by hypoxia and A2AR. Yet to be tested is the potential capacity of coadjuvants to minimize the side effects of CTLA-4 and/or PD-1 blockade by decreasing the dose of blocking antibodies or by eliminating the need for dual blockade. Cancer Immunol Res; 2(7); 598–605. ©2014 AACR .

  • the antihypoxia Adenosinergic pathogenesis as a result of collateral damage by overactive immune cells
    Journal of Leukocyte Biology, 2009
    Co-Authors: Stephen Hatfield, Michail V Sitkovsky, Dmitriy Lukashev, Bryan Belikoff, Akio Ohta

    Abstract:

    Here, we attract attention to the possibility of iatrogenic exacerbation of immune-mediated tissue damage as a result of the unintended weakening of the tissue-protecting, hypoxia-Adenosinergic pathway. These immunosuppressive, anti-inflammatory pathways play a critical and nonredundant role in the protection of normal tissues from collateral damage during an inflammatory response. We believe that it is the tissue hypoxia associated with inflammatory damage that leads to local inhibition of overactive immune cells by activating A2AR and A2BR and stabilizing HIF-1 .W e show in an animal model of acute lung injury that oxygenation (i.e., inspiring supplemental oxygen) reverses tissue hypoxia and exacerbates ongoing inflammatory lung tissue damage. However, little has been done to carefully investigate and prevent this in a clinical setting. Similarly, the consumption of caffeine antagonizes A2ARs, resulting in exacerbation of ongoing acute inflammation. It is suggested that although the elimination of hypoxia-Adenosinergic immunosuppression is desirable to improve vaccines, it is important to take into account the unintentional effects of supplemental oxygen and caffeine, which may increase collateral, inflammatory tissue damage. J. Leukoc. Biol. 86: 545–548; 2009.

  • the Adenosinergic immunomodulatory drugs
    Current Opinion in Pharmacology, 2009
    Co-Authors: Akio Ohta, Michail V Sitkovsky

    Abstract:

    Hypoxia-driven increase of extracellular adenosine in local tissue microenvironments of inflamed and cancerous tissues plays a critical role in the regulation of tissue destruction by activated immune cells. Accumulated data suggest that injection or consumption of A2A adenosine receptor (A2AR) antagonists may represent a drug treatment that diminishes adenosine-mediated immunosuppression. Since this, in turn, enhances the immune response, inhibition of adenosine-A2AR signaling may be a promising approach to enhance anti-tumor or anti-pathogen immune response. Patients with disorders characterized by excessive inflammation may be at risk to A2AR antagonists (e.g. caffeine) because of the effect to increase inflammatory damage secondary to enhanced immunity. On the other hand, enhancement of hypoxia-Adenosinergic immunomodulatory pathways may be beneficial to prevent inflammatory tissue destruction.

Maria Jose Da Silva Fernandes – 3rd expert on this subject based on the ideXlab platform

  • Modulation of Seizures and Synaptic Plasticity by Adenosinergic Receptors in an Experimental Model of Temporal Lobe Epilepsy Induced by Pilocarpine in Rats
    Epilepsia, 2020
    Co-Authors: Eduardo Paulo Morowsky Vianna, Alice T Ferreira, Flavia Dona, Esper A Cavalheiro, Maria Jose Da Silva Fernandes

    Abstract:

    Purpose: Adenosine is a major negative neuromodulator of synaptic activity in the central nervous system and can exert anticonvulsant and neuroprotective effects in many experimental models of epilepsy. Extracellular adenosine can be formed by a membrane-anchored enzyme ecto-5′-nucleotidase. the purposes of this study were to characterize the role of adenosine receptors in modulating status epilepticus (SE) induced by pilocarpine and evaluate its neuroprotective action. Ecto-5′-nucleotidase activity was studied during the different phases of pilocarpine-induced epilepsy in rats.Methods: Adult rats were pretreated with different Adenosinergic agents to evaluate the latency and incidence of SE induced by pilocarpine in rats. the neuroprotective effect also was evaluated.Results: A proconvulsant effect was observed with DPCPX and DMPX that reduced the latency of SE in almost all rats. Pretreatment with the MRS 1220 did not alter the incidence of SE but reduced the latency to develop SE. An anticonvulsant and neuroprotective effect was detected with R-PIA. Rats pretreated with R-PIA had a decreased number of apoptotic cells in the hippocampus, whereas Pretreatment with DPCPX did not modify the hippocampal damage. An intensification of neuronal death was observed in the dentate gyrus and CA3 when rats were pretreated with DMPX. MRS-1220 did not modify the number of apoptotic cells in the hippocampus. An increase in the ecto-5′-nucleotidase staining was detected in the hippocampus during silent and chronic phases.Conclusions: the present data show that adenosine released during pilocarpine-induced SE via A1-receptor stimulation can exhibit neuroprotective and anticonvulsant roles. Similar effects could also be inferred with A2a and A3 Adenosinergic agents, but further experiments are necessary to confirm their roles. Ecto-5′-nucleotidase activity during silent and chronic phases might have a role in blocking spontaneous seizures by production of inhibitory neuromodulator adenosine, besides taking part in the mechanism that controls sprouting.UNIFESP, Dept Neurol & Neurocirurg, BR-04023900 São Paulo, BrazilUNIFESP, Disc Neurol Expt, BR-04023900 São Paulo, BrazilUNIFESP, Dept Biofis, BR-04023900 São Paulo, BrazilUNIFESP, Dept Neurol & Neurocirurg, BR-04023900 São Paulo, BrazilUNIFESP, Disc Neurol Expt, BR-04023900 São Paulo, BrazilUNIFESP, Dept Biofis, BR-04023900 São Paulo, BrazilWeb of Scienc

  • Modulation of seizures and synaptic plasticity by Adenosinergic receptors in an experimental model of temporal lobe epilepsy induced by pilocarpine in rats.
    Epilepsia, 2020
    Co-Authors: Eduardo Paulo Morowsky Vianna, Alice T Ferreira, Flavia Dona, Esper A Cavalheiro, Maria Jose Da Silva Fernandes

    Abstract:

    Adenosine is a major negative neuromodulator of synaptic activity in the central nervous system and can exert anticonvulsant and neuroprotective effects in many experimental models of epilepsy. Extracellular adenosine can be formed by a membrane-anchored enzyme ecto-5′-nucleotidase. The purposes of this study were to characterize the role of adenosine receptors in modulating status epilepticus (SE) induced by pilocarpine and evaluate its neuroprotective action. Ecto-5′-nucleotidase activity was studied during the different phases of pilocarpine-induced epilepsy in rats.
    Adult rats were pretreated with different Adenosinergic agents to evaluate the latency and incidence of SE induced by pilocarpine in rats. The neuroprotective effect also was evaluated.
    A proconvulsant effect was observed with DPCPX and DMPX that reduced the latency of SE in almost all rats. Pretreatment with the MRS 1220 did not alter the incidence of SE but reduced the latency to develop SE. An anticonvulsant and neuroprotective effect was detected with R-PIA. Rats pretreated with R-PIA had a decreased number of apoptotic cells in the hippocampus, whereas pretreatment with DPCPX did not modify the hippocampal damage. An intensification of neuronal death was observed in the dentate gyrus and CA3 when rats were pretreated with DMPX. MRS-1220 did not modify the number of apoptotic cells in the hippocampus. An increase in the ecto-5 -nucleotidase staining was detected in the hippocampus during silent and chronic phases.
    The present data show that adenosine released during pilocarpine-induced SE via A1-receptor stimulation can exhibit neuroprotective and anticonvulsant roles. Similar effects could also be inferred with A2a and A3 Adenosinergic agents, but further experiments are necessary to confirm their roles. Ecto-5 -nucleotidase activity during silent and chronic phases might have a role in blocking spontaneous seizures by production of inhibitory neuromodulator adenosine, besides taking part in the mechanism that controls sprouting.

  • modulation of seizures and synaptic plasticity by Adenosinergic receptors in an experimental model of temporal lobe epilepsy induced by pilocarpine in rats
    Epilepsia, 2005
    Co-Authors: Eduardo Paulo Morowsky Vianna, Alice T Ferreira, Flavia Dona, Esper A Cavalheiro, Maria Jose Da Silva Fernandes

    Abstract:

    Summary: Purpose: Adenosine is a major negative neuromodulator of synaptic activity in the central nervous system and can exert anticonvulsant and neuroprotective effects in many experimental models of epilepsy. Extracellular adenosine can be formed by a membrane-anchored enzyme ecto-5′-nucleotidase. The purposes of this study were to characterize the role of adenosine receptors in modulating status epilepticus (SE) induced by pilocarpine and evaluate its neuroprotective action. Ecto-5′-nucleotidase activity was studied during the different phases of pilocarpine-induced epilepsy in rats.

    Methods: Adult rats were pretreated with different Adenosinergic agents to evaluate the latency and incidence of SE induced by pilocarpine in rats. The neuroprotective effect also was evaluated.

    Results: A proconvulsant effect was observed with DPCPX and DMPX that reduced the latency of SE in almost all rats. Pretreatment with the MRS 1220 did not alter the incidence of SE but reduced the latency to develop SE. An anticonvulsant and neuroprotective effect was detected with R-PIA. Rats pretreated with R-PIA had a decreased number of apoptotic cells in the hippocampus, whereas pretreatment with DPCPX did not modify the hippocampal damage. An intensification of neuronal death was observed in the dentate gyrus and CA3 when rats were pretreated with DMPX. MRS-1220 did not modify the number of apoptotic cells in the hippocampus. An increase in the ecto-5´-nucleotidase staining was detected in the hippocampus during silent and chronic phases.

    Conclusions: The present data show that adenosine released during pilocarpine-induced SE via A1-receptor stimulation can exhibit neuroprotective and anticonvulsant roles. Similar effects could also be inferred with A2a and A3 Adenosinergic agents, but further experiments are necessary to confirm their roles. Ecto-5´-nucleotidase activity during silent and chronic phases might have a role in blocking spontaneous seizures by production of inhibitory neuromodulator adenosine, besides taking part in the mechanism that controls sprouting.