TY - JOUR AU - Palma-Álvarez, Raul Felipe AU - Barta, Csaba AU - Carpentier, Pieter Jan AU - Carruthers, Susan AU - Crunelle, Cleo L. AU - Demetrovics, Zsolt AU - Dom, Geert AU - Faraone, Stephen V. AU - Franck, Johan AU - Johnson, Brian AU - Kapitány-Fövény, Máté AU - Kaye, Sharlene AU - Konstenius, Maija AU - Matthys, Frieda AU - Moggi, Franz AU - Møller, Merete AU - Schellekens, Arnt AU - Skutle, Arvid AU - van de Glind, Geurt AU - van Emmerik-van Oortmerssen, Katelijne AU - Verspreet, Sofie AU - Schoevers, Robert A. AU - Wallhed, Sara AU - Levin, Frances R. AU - Grau-López, Lara AU - Casas, Miguel AU - van den Brink, Wim AU - Ramos-Quiroga, Josep Antoni TI - Validity of the ADHD module of the Mini International Neuropsychiatric Interview PLUS for screening of adult ADHD in treatment seeking substance use disorder patients: ADHD screening with MINI-Plus JF - REVISTA DE PSIQUIATRIA Y SALUD MENTAL J2 - REV PSIQUIATR SALUD VL - 16 PY - 2023 IS - 1 SP - 11 EP - 15 PG - 7 SN - 1888-9891 DO - 10.1016/j.rpsm.2020.04.013 UR - https://m2.mtmt.hu/api/publication/31356898 ID - 31356898 LA - English DB - MTMT ER - TY - JOUR AU - Yousef, M. AU - Szabó, Ildikó AU - Murányi, József AU - Illien, Françoise AU - Soltész, Dóra AU - Bató, Csaba AU - Tóth, Gabriella AU - Batta, Gyula Gábor (Ifj.) AU - Nagy, Péter AU - Sagan, Sandrine AU - Bánóczi, Zoltán TI - Cell-Penetrating Dabcyl-Containing Tetraarginines with Backbone Aromatics as Uptake Enhancers JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 1 PG - 20 SN - 1999-4923 DO - 10.3390/pharmaceutics15010141 UR - https://m2.mtmt.hu/api/publication/33538163 ID - 33538163 N1 - Funding Agency and Grant Number: ELTE Thematic Excellence Programme 2020; National Research, Development and Innovation Office [TKP2020-IKA-05]; Tempus Public Foundation for the Stipendium Hungaricum Scholarship funding; French-Hungarian Intergovernmental program [2018-2.1.13-TET-FR-2018-00007]; National Research, Development and Innovation Office [K138075, K133421, K124813] Funding text: We kindly appreciate the support from the ELTE Thematic Excellence Programme 2020 supported by National Research, Development and Innovation Office-TKP2020-IKA-05, and the Tempus Public Foundation for the Stipendium Hungaricum Scholarship funding. This work was supported by French-Hungarian Intergovernmental program (2018-2.1.13-TET-FR-2018-00007) and by the National Research, Development and Innovation Office (K138075, K133421, K124813). AB - Cell-penetrating peptides represent an emerging class of carriers capable of effective cellular delivery. This work demonstrates the preparation and investigation of efficient CPPs. We have already shown that the presence of 4-((4-(dimethylamino)phenyl)azo)benzoic acid (Dabcyl) and Trp greatly increase the uptake of oligoarginines. This work is a further step in that direction. We have explored the possibility of employing unnatural, aromatic amino acids, to mimic Trp properties and effects. The added residues allow the introduction of aromaticity, not as a side-chain group, but rather as a part of the sequence. The constructs presented exceptional internalization on various cell lines, with an evident structure–activity relationship. The CPPs were investigated for their entry mechanisms, and our peptides exploit favorable pathways, yet one of the peptides relies highly on direct penetration. Confocal microscopy studies have shown selectivity towards the cell lines, by showing diffuse uptake in FADU cells, while vesicular uptake takes place in SCC-25 cell line. These highly active CPPs have proved their applicability in cargo delivery by successfully delivering antitumor drugs into MCF-7 and MDA-MB-231 cells. The modifications in the sequences allow the preparation of short yet highly effective constructs able to rival the penetration of well-known CPPs such as octaarginine (Arg8). LA - English DB - MTMT ER - TY - JOUR AU - Varga, Attila AU - Nguyen, Minh Tu AU - Pénzes, Kinga AU - Bátai, Bence AU - Gyulavári, Pál AU - Gurbi, Bianka AU - Murányi, József AU - Csermely, Péter AU - Csala, Miklós AU - Vántus, Tibor AU - Sőti, Csaba TI - Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 2 PG - 15 SN - 2073-4409 DO - 10.3390/cells12020212 UR - https://m2.mtmt.hu/api/publication/33541689 ID - 33541689 N1 - Department of Molecular Biology, Semmelweis University, Budapest, 1094, Hungary MTA-SE Pathobiochemistry Research Group, Semmelweis University, Budapest, 1094, Hungary Institute of Medical Microbiology, Semmelweis University, Budapest, 1089, Hungary HCEMM-SU Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, 1085, Hungary IQVIA Hungary, Budapest, 1117, Hungary Cited By :2 Export Date: 24 August 2024 Correspondence Address: Varga, A.; Department of Molecular Biology, Hungary; email: varga.attila@med.semmelweis-univ.hu Correspondence Address: Sőti, C.; Department of Molecular Biology, Hungary; email: soti.csaba@med.semmelweis-univ.hu AB - Prostate cancer metastasis is a significant cause of mortality in men. PKD3 facilitates tumor growth and metastasis, however, its regulation is largely unclear. The Hsp90 chaperone stabilizes an array of signaling client proteins, thus is an enabler of the malignant phenotype. Here, using different prostate cancer cell lines, we report that Hsp90 ensures PKD3 conformational stability and function to promote cancer cell migration. We found that pharmacological inhibition of either PKDs or Hsp90 dose-dependently abrogated the migration of DU145 and PC3 metastatic prostate cancer cells. Hsp90 inhibition by ganetespib caused a dose-dependent depletion of PKD2, PKD3, and Akt, which are all involved in metastasis formation. Proximity ligation assay and immunoprecipitation experiments demonstrated a physical interaction between Hsp90 and PKD3. Inhibition of the chaperone–client interaction induced misfolding and proteasomal degradation of PKD3. PKD3 siRNA combined with ganetespib treatment demonstrated a specific involvement of PKD3 in DU145 and PC3 cell migration, which was entirely dependent on Hsp90. Finally, ectopic expression of PKD3 enhanced migration of non-metastatic LNCaP cells in an Hsp90-dependent manner. Altogether, our findings identify PKD3 as an Hsp90 client and uncover a potential mechanism of Hsp90 in prostate cancer metastasis. The molecular interaction revealed here may regulate other biological and pathological functions. LA - English DB - MTMT ER - TY - JOUR AU - Gurbi, Bianka AU - Brauswetter, Diána AU - Pénzes, Kinga AU - Varga, Attila AU - Krenács, Tibor AU - Dános, Kornél AU - Birtalan, Ede AU - Tamás, László AU - Csala, Miklós TI - MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 3 PG - 19 SN - 1661-6596 DO - 10.3390/ijms24032782 UR - https://m2.mtmt.hu/api/publication/33610921 ID - 33610921 N1 - Export Date: 10 May 2025; Cited By: 5 AB - The poor prognosis of head-and-neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable prognostic and predictive markers. The Ras/Raf/MEK/ERK signaling pathway is often activated by overexpressed epidermal growth factor receptor (EGFR) and stimulates the progression of HNSCCs. Our research was performed on three human papillomavirus (HPV)-negative HNSCC-cell lines: Detroit 562, FaDu and SCC25. Changes in cell viability upon EGFR and/or MEK inhibitors were measured by the MTT method. The protein-expression and phosphorylation profiles of the EGFR-initiated signaling pathways were assessed using Western-blot analysis. The EGFR expression and pY1068-EGFR levels were also studied in the patient-derived HNSCC samples. We found significant differences between the sensitivity of the tumor-cell lines used. The SCC25 line was found to be the most sensitive to the MEK inhibitors, possibly due to the lack of feedback Akt activation through EGFR. By contrast, this feedback activation had an important role in the FaDu cells. The observed insensitivity of the Detroit 562 cells to the MEK inhibitors might have been caused by their PIK3CA mutation. Among HNSCC cell lines, EGFR-initiated signaling pathways are particularly versatile. An ERK/EGFR feedback loop can lead to Akt-pathway activation upon MEK inhibition, and it is related not only to increased amounts of EGFR but also to the elevation of pY1068-EGFR levels. The presence of this mechanism may justify the combined application of EGFR and MEK inhibitors. LA - English DB - MTMT ER - TY - JOUR AU - Özgen, Heval AU - Spijkerman, Renske AU - Noack, Moritz AU - Holtmann, Martin AU - Schellekens, Arnt S A AU - van de Glind, Geurt AU - Banaschewski, Tobias AU - Barta, Csaba AU - Begeman, Alex AU - Casas, Miguel AU - Crunelle, Cleo L AU - Daigre Blanco, Constanza AU - Dalsgaard, Søren AU - Demetrovics, Zsolt AU - den Boer, Jacomine AU - Dom, Geert AU - Eapen, Valsamma AU - Faraone, Stephen V AU - Franck, Johan AU - González, Rafael A AU - Grau-López, Lara AU - Groenman, Annabeth P AU - Hemphälä, Malin AU - Icick, Romain AU - Johnson, Brian AU - Kaess, Michael AU - Kapitány-Fövény, Máté AU - Kasinathan, John G AU - Kaye, Sharlene S AU - Kiefer, Falk AU - Konstenius, Maija AU - Levin, Frances R AU - Luderer, Mathias AU - Martinotti, Giovanni AU - Matthys, Frieda I A AU - Mészáros, Gergely AU - Moggi, Franz AU - Munasur-Naidoo, Ashmita P AU - Post, Marianne AU - Rabinovitz, Sharon AU - Ramos-Quiroga, J Antoni AU - Sala, Regina AU - Shafi, Abu AU - Slobodin, Ortal AU - Staal, Wouter G AU - Thomasius, Rainer AU - Truter, Ilse AU - van Kernebeek, Michiel W AU - Velez-Pastrana, Maria C AU - Vollstädt-Klein, Sabine AU - Vorspan, Florence AU - Young, Jesse T AU - Yule, Amy AU - van den Brink, Wim AU - Hendriks, Vincent TI - Internationale Konsenserklärung zu Screening, Diagnostik und Behandlung von Jugendlichen und Heranwachsenden mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung und gleichzeitigen Störungen durch Substanzgebrauch JF - ZEITSCHRIFT FUR KINDER-UND JUGENDPSYCHIATRIE UND PSYCHOTHERAPIE J2 - Z KINDER JUG-PSYCH VL - 50 PY - 2022 IS - 1 SP - 54 EP - 67 PG - 14 SN - 1422-4917 DO - 10.1024/1422-4917/a000828 UR - https://m2.mtmt.hu/api/publication/32154300 ID - 32154300 N1 - Nyelvi változat (angol nyelvű cikk német fordítása) Eredeti közlemény (MTMT azonosító: 31375206): Özgen H. et al. International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder. Eur Addict Res. 2020;26(4-5):223-232. doi: 10.1159/000508385 Parnassia Addiction Research Centre (PARC), Parnassia Psychiatric Institute, Den Haag, Netherlands Curium, Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, Netherlands Parnassia Addiction Research Centre (PARC), Parnassia Psychiatric Institute, Den Haag, Netherlands LWL-Universitatsklinik Hamm der Ruhr-Universitat Bochum, Hamm, Germany Department of Psychiatry, Donders Institute, Radboud Umc, Nijmegen, Netherlands Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), Radboud Umc, Nijmegen, Netherlands International Collaboration on Adhd and Substance Abuse (ICASA) Foundation, Nijmegen, Netherlands Klinik fur Psychiatrie und Psychotherapie des Kindes-und Jugendalters, Zentralinstitut fur Seelische Gesundheit, Mannheim, Germany Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary Institute of Psychology, Faculty of Humanities and Social Sciences, Pázmány Péter Catholic University, Budapest, Hungary De Hoop Ggz, Dordrecht, Netherlands Department of Psychiatry and Legal Medicine, Autonomous University of Barcelona, Barcelona, Spain Department of Psychiatry, University Hospital Brussels, Brussel, Belgium Department of Psychiatry, Mental Health and Addictions, Addiction and Dual Diagnosis Section, Hospital Universitari Vall d'Hebron, Barcelona, Spain Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark Institute of Psychology, Elte Eotvos Loránd University, Budapest, Hungary Collaborative Antwerp Psychiatric Research Institute (CAPRI), Antwerp University (UA), Antwerpen, Belgium Academic Unit of Infant Child, Adolescent Psychiatry South West Sydney, University of New South Wales, Sydney, NSW, Australia Department of Psychiatry, Suny Upstate Medical University, Syracuse, NY, United States Child-and Adolescent Department, Piteå Hospital, Region Norrbotten, Piteå, Sweden Centre for Mental Health, Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom East London Nhs Foundation Trust, Child and Adolescent Mental Health Service (CAMHS)-ADHD Clinic, London, United Kingdom Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain Department of Psychology, University of Amsterdam, Amsterdam, Netherlands Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Saint-Louis-Lariboisière-Fernand Widal, Paris, France Inserm U1144, Paris, France Inserm UMR-S1144, Université de Paris, Paris, France Universitatsklinik fur Kinder-und Jugendpsychiatrie und Psychotherapie, Universitat Bern, Bern, Switzerland Klinik fur Kinder-und Jugendpsychiatrie, Zentrum fur Psychosoziale Medizin, Universitatsklinikum Heidelberg, Heidelberg, Germany Faculty of Health Sciences, Semmelweis University, Budapest, Hungary Drug Outpatient Centre, Nyíro Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary Adolescent Mental Health, Justice Health and Forensic Mental Health Network, Sydney, NSW, Australia National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia Klinik fur Abhangiges Verhalten und Suchtmedizin, Zentralinstitut fur Seelische Gesundheit, Mannheim, Germany Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, United States Klinik fur Psychiatrie, Psychosomatik und Psychotherapie, Universitatsklinikum Frankfurt, Goethe Universitat, Frankfurt am Main, Germany Department of Neuroscience Imaging, Clinical Sciences, University .,G. d'Annunzio, Chieti-Pescara, Chieti, Italy Department of Psychiatry, Uz Brussel, Vrije Universiteit Brussel (VUB), Brussel, Belgium Department of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary Universitatsklinik fur Psychiatrie, Universitat Bern, Bern, Switzerland Department of Pharmacy, Nelson Mandela University, Port Elizabeth, South Africa Cipla Medpro Pharmaceuticals, Durban, South Africa Brijder Youth Addiction Treatment, Parnassia Psychiatric Institute, Den Haag, Netherlands School of Criminology and the Unit for Excellence in Research and Study of Addiction (ERSA), Center for Rehabilitation Research, University of Haifa, Haifa, Israel Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain Centre for Psychiatry, Wolfson Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom East London Nhs Foundation Trust, London, United Kingdom Department of Education, Ben-Gurion University, Beer-Sheva, Beer-Sheva, Israel Department of Psychiatry, Radboud University Medical Centre, Nijmegen, Netherlands Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, Netherlands Deutsches Zentrum fur Suchtfragen des Kindes-und Jugendalters, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany Drug Utilization Research Unit (DURU), Department of Pharmacy, Nelson Mandela University, Port Elizabeth, South Africa Department of Psychiatry, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Brussel, Belgium PhD Program in Clinical Psychology, Universidad Carlos Albizu, San Juan, Puerto Rico Département de Psychiatrie et de Médecine Addictologique, Hôpital Fernand Widal, Paris, France Faculté de Médecine, Université de Paris, Paris, France Fhu NOR-SUD Network of Research in Substance Use Disorders, Paris, France Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia Murdoch Children's Research Institute, Melbourne, VIC, Australia School of Population and Global Health, University of Western Australia, Perth, WA, Australia National Drug Research Institute, Curtin University, Perth, WA, Australia Boston Medical Center, Boston University School of Medicine, Boston, MA, United States Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, Netherlands Curium, Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, Netherlands AB - International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Abstract.Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD. LA - German DB - MTMT ER - TY - JOUR AU - Bőgel, Gábor AU - Murányi, József AU - Szokol, Bálint AU - Kukor, Zoltán AU - Móra , István András AU - Kardon Tamás, Zoltán AU - Őrfi, László AU - Hrabák, András TI - Production of NOS2 and inflammatory cytokines is reduced by selected protein kinase inhibitors with partial repolarization of HL-60 derived and human blood macrophages JF - HELIYON J2 - HELIYON VL - 8 PY - 2022 IS - 1 PG - 16 SN - 2405-8440 DO - 10.1016/j.heliyon.2021.e08670 UR - https://m2.mtmt.hu/api/publication/32574856 ID - 32574856 LA - English DB - MTMT ER - TY - PAT AU - Csámpai, Antal AU - Bárány, Péter Tibor AU - Czuczi, Tamas AU - Kovacs, Imre AU - Adamis, Balint AU - Nemeth, Zsofia AU - Murányi, József AU - Olahne, Szabo Rita AU - Bosze, Szilvia AU - Mezo, Gabor AU - Kőhidai, László AU - Lajkó, Eszter AU - Takács, Angéla AU - Láng, Orsolya AU - Mezo, Diana TI - Synthesis of novel imipridone derivatives and their evaluation for their anticancer activity.. WO2022029459A1 TS - WO2022029459A1 PY - 2022 SP - 91pp. PG - 91 UR - https://m2.mtmt.hu/api/publication/32683354 ID - 32683354 AB - The present invention relates to compds. of formula (I) (I) or pharmaceutically acceptable salts, and stereoisomers thereof, including enantiomers, racemic mixts., mixts. of enantiomers, or combinations thereof, which are applicable for use in treating cancer diseases. The present invention further relates to a pharmaceutical compn. comprising the above compds. [on SciFinder(R)] LA - English DB - MTMT ER - TY - JOUR AU - Czuczi, Tamás AU - Murányi, József AU - Bárány, Péter Tibor AU - Móra , István András AU - Borbély, Adina Noémi AU - Csala, Miklós AU - Csámpai, Antal TI - Synthesis and Antiproliferative Activity of Novel Imipridone–Ferrocene Hybrids with Triazole and Alkyne Linkers JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 15 PY - 2022 IS - 4 PG - 19 SN - 1424-8247 DO - 10.3390/ph15040468 UR - https://m2.mtmt.hu/api/publication/32782717 ID - 32782717 LA - English DB - MTMT ER - TY - JOUR AU - Boel, Annekatrien AU - Veszelyi, Krisztina Nóra AU - Németh, Csilla Emese AU - Beyens, Aude AU - Willaert, Andy AU - Coucke, Paul AU - Callewaert, Bert AU - Margittai, Éva TI - Arterial Tortuosity Syndrome: An Ascorbate Compartmentalization Disorder? JF - ANTIOXIDANTS & REDOX SIGNALING J2 - ANTIOXID REDOX SIGNAL VL - 34 PY - 2021 IS - 11 SP - 875 EP - 889 PG - 15 SN - 1523-0864 DO - 10.1089/ars.2019.7843 UR - https://m2.mtmt.hu/api/publication/30972609 ID - 30972609 AB - Significance: Cardiovascular disorders are the most important cause of morbidity and mortality in the Western world. Monogenic developmental disorders of the heart and vessels are highly valuable to study the physiological and pathological processes in cardiovascular system homeostasis. The arterial tortuosity syndrome (ATS) is a rare, autosomal recessive connective tissue disorder showing lengthening, tortuosity, and stenosis of the large arteries, with a propensity for aneurysm formation. In histopathology, it associates with fragmentation and disorganization of elastic fibers in several tissues, including the arterial wall. ATS is caused by pathogenic variants in SLC2A10 encoding the facilitative glucose transporter (GLUT)10. Critical Issues: Although several hypotheses have been forwarded, the molecular mechanisms linking disrupted GLUT10 activity with arterial malformations are largely unknown. Recent Advances: The vascular and systemic manifestations and natural history of ATS patients have been largely delineated. GLUT10 was identified as an intracellular transporter of dehydroascorbic acid, which contributes to collagen and elastin cross-linking in the endoplasmic reticulum, redox homeostasis in the mitochondria, and global and gene-specific methylation/hydroxymethylation affecting epigenetic regulation in the nucleus. We revise here the current knowledge on ATS and the role of GLUT10 within the compartmentalization of ascorbate in physiological and diseased states. Future Directions: Centralization of clinical, treatment, and outcome data will enable better management for ATS patients. Establishment of representative animal disease models could facilitate the study of pathomechanisms underlying ATS. This might be relevant for other forms of vascular dysplasia, such as isolated aneurysm formation, hypertensive vasculopathy, and neovascularization. Antioxid. Redox Signal. 00, 000-000. LA - English DB - MTMT ER - TY - JOUR AU - Szarka, András AU - Kapuy, Orsolya AU - Lőrincz, Tamás AU - Bánhegyi, Gábor TI - Vitamin C and cell death JF - ANTIOXIDANTS & REDOX SIGNALING J2 - ANTIOXID REDOX SIGNAL VL - 34 PY - 2021 IS - 11 SP - 831 EP - 844 PG - 14 SN - 1523-0864 DO - 10.1089/ars.2019.7897 UR - https://m2.mtmt.hu/api/publication/31363364 ID - 31363364 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Fund of Hungary [K 123752, 129593, 2018-1.2.1-NKP-2018-00005] Funding text: This work was financially supported by the National Research, Development and Innovation Fund of Hungary under Grant K 123752, 129593, 2018-1.2.1-NKP-2018-00005 by the Budapesti Muszakies Gazdasagtudomanyi EgyetemBiotechnology Felsooktatasi Intezmenyi Kivalosagi Program grant. AB - Persistent oxidative stress is a common feature of cancer cells, giving a specific weapon to selectively eliminate them. Ascorbate in pharmacologic concentration can contribute to the suspended formation of hydroxyl radical via the Fenton reaction, thus it can be an important element of the oxidative stress therapy against cancer cells. Recent Advances: The main components of ascorbate induced cell death are DNA double-strand breaks via the production of hydroxyl radical and ATP depletion due to the activation of PARP1. Presumably, DNA damage can be the primary contributor to the anti-cancer activity of pharmacologic ascorbate, as opposed to the rupture of bioenergetics. The caspase independency of high dose ascorbate induced cell death proposed the possible involvement of several types of cell death such as ferroptosis, necroptosis and autophagy.Ascorbate can target at least two key molecular features of cancer cells as a part of the anti-cancer therapy: the intrinsic or acquired resistance to cell death and the dysregulated metabolism of cancer cells. It seems probable that different concentrations of ascorbate alter the nature of induced cell death. Autophagy and necroptosis may play a role at intermediate concentrations, but caspase independent apoptosis may dominate at higher concentrations. However, ascorbate behaves as an effective inhibitor of ferroptosis that may have crucial importance in its possible clinical application.The elucidation of the details and the links between high dose ascorbate induced cancer selective cell death mechanisms may give us a tool to form and apply synergistic cancer therapies. LA - English DB - MTMT ER -