Discovery and targeting of a noncanonical mechanism of sarcoma resistance to ADI-PEG20 mediated by the microenvironment
CONCLUSIONS: Noncanonical, ASS1-independent tumor resistance to ADI-PEG20 is driven by the microenvironment. This mechanism can be targeted by either the macropinocytosis inhibitor imipramine or the autophagy inhibitor chloroquine. These safe, widely available drugs should be added to current clinical trials to overcome microenvironmental arginine support of tumors and improve patient outcomes.PMID:37339179 | DOI:10.1158/1078-0432.CCR-22-2642 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - June 20, 2023 Category: Cancer & Oncology Authors: Leonard C Rogers Jeff C Kremer Caitlyn B Brashears Zongtao Lin Zhixian Hu Alliny C S Bastos Adriana Baker Nicole Fettig Dong Zhou Kooresh I Shoghi Carina A Dehner John S A Chrisinger John S Bomalaski Benjamin A Garcia Toshinao Oyama Eileen P White Brian A Source Type: research
Discovery and targeting of a noncanonical mechanism of sarcoma resistance to ADI-PEG20 mediated by the microenvironment
CONCLUSIONS: Noncanonical, ASS1-independent tumor resistance to ADI-PEG20 is driven by the microenvironment. This mechanism can be targeted by either the macropinocytosis inhibitor imipramine or the autophagy inhibitor chloroquine. These safe, widely available drugs should be added to current clinical trials to overcome microenvironmental arginine support of tumors and improve patient outcomes.PMID:37339179 | DOI:10.1158/1078-0432.CCR-22-2642 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - June 20, 2023 Category: Cancer & Oncology Authors: Leonard C Rogers Jeff C Kremer Caitlyn B Brashears Zongtao Lin Zhixian Hu Alliny C S Bastos Adriana Baker Nicole Fettig Dong Zhou Kooresh I Shoghi Carina A Dehner John S A Chrisinger John S Bomalaski Benjamin A Garcia Toshinao Oyama Eileen P White Brian A Source Type: research
Will EGFRvIII and neuronal-derived EGFR be targets for imipramine?
Tricyclic antidepressant (TCA) is an old and well-established therapeutic agent with a good safety profile, making them an excellent candidate for repurposing. In light of the growing understanding of the importance of nerves in the development and progression of cancer, attention is now being turned to using nerve-targeting drugs for the treatment of cancer, particularly TCAs. However, the specific mechanism by which antidepressants affect the tumor microenvironment of glioblastoma multiforme (GBM) is still unclear. Here, we combined bulk RNA sequencing, network pharmacology, single-cell sequencing, molecular docking and ...
Source: Frontiers in Pharmacology - May 30, 2023 Category: Drugs & Pharmacology Source Type: research
Response to letter to the Editor re A prospective and randomized study comparing the use of alarms, desmopressin and imipramine in the treatment of monosymptomatic nocturnal enuresis
First, I would like to thank the authors of this commentary on our manuscript for their interest and contributions. We apologize for the typos, but here are the point-by-point corrections.Regarding the age range of the of study participants which was noted to be inconsistent, the inclusion criteria were: Age between 6 and 16 years old.Regarding the concern of the number wet nights per week as mentioned, Table 1 should read as the nights wet per month instead of week. We did not differentiate between more than one loss of urine per night.Regarding the concern raised about Tables 1 and 2 showing the same absolute value of be...
Source: Journal of Pediatric Urology - May 3, 2023 Category: Urology & Nephrology Authors: Marcos Figueiredo Mello Tags: Letter to the Editor Source Type: research
Re: A prospective and randomized study comparing the use of alarms, desmopressin and imipramine in the treatment of monosymptomatic nocturnal enuresis
We read with great interest the recent contribution of Dr. Mello et al. in their study, entitled “A prospective and randomized study comparing the use of alarms, desmopressin and imipramine in the treatment of monosymptomatic nocturnal enuresis” [1].They showed that the use of alarms is the most effective treatment of monosymptomatic enuresis (MNE) with superior results when compared to des mopressin and imipramine [1]. But we would like to contribute some points regarding their paper. (Source: Journal of Pediatric Urology)
Source: Journal of Pediatric Urology - April 21, 2023 Category: Urology & Nephrology Authors: Rong Dai, Changkai Deng Tags: Letter to the Editor Source Type: research
1023 Dengue virus serotype 1 and serotype 2 and their nonstructural protein 1 may induce discrepant activation pattern of inflammation and pyroptosis in dermal fibroblasts
This study was designed to elucidate the immunopathogensis of the initial infection stage by infecting human dermal fibroblasts WS1 cells with DENV-1 and DENV-2. The results showed several discrepancies, which included stronger innate inflammatory response and cell death in the DENV-2 infected WS1 cells, and higher level of pyroptosis in the DENV-1 infected WS1 cells. Reduced DENV-mediated caspase-1 and IL-beta cleavage in the pyroptosis pathway by both caspase-1 inhibitor Ac-YVAD-cmk and imipramine were found, which of both also downregulated DENV virion production in the WS1 cells. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 17, 2023 Category: Dermatology Authors: W. Sung, K. Wei, T. Chang Source Type: research
Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
Functional and targeted proteomics characterization of a human primary endothelial cell model of the blood-brain barrier (BBB) for drug permeability studies
Toxicol Appl Pharmacol. 2023 Mar 12:116456. doi: 10.1016/j.taap.2023.116456. Online ahead of print.ABSTRACTThe blood-brain barrier (BBB) protects the brain from toxins but hinders the penetration of neurotherapeutic drugs. Therefore, the blood-to-brain permeability of chemotherapeutics must be carefully evaluated. Here, we aimed to establish a workflow to generate primary cultures of human brain microvascular endothelial cells (BMVECs) to study drug brain permeability and bioavailability. Furthermore, we characterized and validated this BBB model in terms of quantitative expression of junction and drug-transport proteins, ...
Source: Toxicology and Applied Pharmacology - March 14, 2023 Category: Toxicology Authors: David Gomez-Zepeda Nicolas Perri ère Fabienne Glacial Meryam Taghi C érina Chhuon Jean-Michel Scherrmann Philippe Sergent Am élie Moreau Claire Denizot Yannick Parmentier Salvatore Cisternino Xavier Decleves Marie-Claude Menet Source Type: research
Functional and targeted proteomics characterization of a human primary endothelial cell model of the blood-brain barrier (BBB) for drug permeability studies
Toxicol Appl Pharmacol. 2023 Mar 12:116456. doi: 10.1016/j.taap.2023.116456. Online ahead of print.ABSTRACTThe blood-brain barrier (BBB) protects the brain from toxins but hinders the penetration of neurotherapeutic drugs. Therefore, the blood-to-brain permeability of chemotherapeutics must be carefully evaluated. Here, we aimed to establish a workflow to generate primary cultures of human brain microvascular endothelial cells (BMVECs) to study drug brain permeability and bioavailability. Furthermore, we characterized and validated this BBB model in terms of quantitative expression of junction and drug-transport proteins, ...
Source: Toxicology and Applied Pharmacology - March 14, 2023 Category: Toxicology Authors: David Gomez-Zepeda Nicolas Perri ère Fabienne Glacial Meryam Taghi C érina Chhuon Jean-Michel Scherrmann Philippe Sergent Am élie Moreau Claire Denizot Yannick Parmentier Salvatore Cisternino Xavier Decleves Marie-Claude Menet Source Type: research
Reduction of intracellular Mg < sup > 2+ < /sup > caused by reactive oxygen species in rat ventricular myocytes
Am J Physiol Cell Physiol. 2023 Mar 13. doi: 10.1152/ajpcell.00490.2022. Online ahead of print.ABSTRACTThe concentration of intracellular free Mg2+ ([Mg2+]i) should be maintained strictly for the regulation of cellular functions. Since reactive oxygen species (ROS) are liable to increase in various pathological conditions and induce cellular damage, we investigated whether ROS affect intracellular Mg2+ homeostasis. We measured [Mg2+]i in ventricular myocytes from Wistar rats using the fluorescent indicator, mag-fura-2. The administration of hydrogen peroxide (H2O2) decreased [Mg2+]iinCa2+-free Tyrode's solution. Intracellu...
Source: Am J Physiol Cell Ph... - March 13, 2023 Category: Cytology Authors: Michiko Tashiro Masato Konishi Makino Watanabe Utako Yokoyama Source Type: research
Reduction of intracellular Mg < sup > 2+ < /sup > caused by reactive oxygen species in rat ventricular myocytes
Am J Physiol Cell Physiol. 2023 Mar 13. doi: 10.1152/ajpcell.00490.2022. Online ahead of print.ABSTRACTThe concentration of intracellular free Mg2+ ([Mg2+]i) should be maintained strictly for the regulation of cellular functions. Since reactive oxygen species (ROS) are liable to increase in various pathological conditions and induce cellular damage, we investigated whether ROS affect intracellular Mg2+ homeostasis. We measured [Mg2+]i in ventricular myocytes from Wistar rats using the fluorescent indicator, mag-fura-2. The administration of hydrogen peroxide (H2O2) decreased [Mg2+]iinCa2+-free Tyrode's solution. Intracellu...
Source: American Journal of Physiology. Cell Physiology - March 13, 2023 Category: Cytology Authors: Michiko Tashiro Masato Konishi Makino Watanabe Utako Yokoyama Source Type: research
Reduction of intracellular Mg < sup > 2+ < /sup > caused by reactive oxygen species in rat ventricular myocytes
Am J Physiol Cell Physiol. 2023 Mar 13. doi: 10.1152/ajpcell.00490.2022. Online ahead of print.ABSTRACTThe concentration of intracellular free Mg2+ ([Mg2+]i) should be maintained strictly for the regulation of cellular functions. Since reactive oxygen species (ROS) are liable to increase in various pathological conditions and induce cellular damage, we investigated whether ROS affect intracellular Mg2+ homeostasis. We measured [Mg2+]i in ventricular myocytes from Wistar rats using the fluorescent indicator, mag-fura-2. The administration of hydrogen peroxide (H2O2) decreased [Mg2+]iinCa2+-free Tyrode's solution. Intracellu...
Source: Am J Physiol Cell Ph... - March 13, 2023 Category: Cytology Authors: Michiko Tashiro Masato Konishi Makino Watanabe Utako Yokoyama Source Type: research
