TY - JOUR AU - Farkasinszky, Gergely AU - Péliné Szabó, Judit AU - Károlyi, Péter AU - Rácz, Szilvia AU - Dénes, Noémi AU - Papp, Tamás AU - Király, József AU - Szabó, Zsuzsanna AU - Kertész, István AU - Mező, Gábor AU - Halmos, Gábor AU - Képes, Zita AU - Trencsényi, György TI - In Vivo Imaging of Acute Hindlimb Ischaemia in Rat Model: A Pre-Clinical PET Study JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 16 PY - 2024 IS - 4 SN - 1999-4923 DO - 10.3390/pharmaceutics16040542 UR - https://m2.mtmt.hu/api/publication/34820368 ID - 34820368 AB - Background: To better understand ischaemia-related molecular alterations, temporal changes in angiogenic Aminopeptidase N (APN/CD13) expression and glucose metabolism were assessed with PET using a rat model of peripheral arterial disease (PAD). Methods: The mechanical occlusion of the base of the left hindlimb triggered using a tourniquet was applied to establish the ischaemia/reperfusion injury model in Fischer-344 rats. 2-[18F]FDG and [68Ga]Ga-NOTA-c(NGR) PET imaging performed 1, 3, 5, 7, and 10 days post-ischaemia induction was followed by Western blotting and immunohistochemical staining for APN/CD13 in ischaemic and control muscle tissue extracts. Results: Due to a cellular adaptation to hypoxia, a gradual increase in [68Ga]Ga-NOTA-c(NGR) and 2-[18F]FDG uptake was observed from post-intervention day 1 to 7 in the ischaemic hindlimbs, which was followed by a drop on day 10. Conforming pronounced angiogenic recovery, the NGR accretion of the ischaemic extremities differed significantly from the controls 5, 7, and 10 days after ischaemia induction (p ≤ 0.05), which correlated with the Western blot and immunohistochemical results. No remarkable radioactivity was depicted between the normally perfused hindlimbs of either the ischaemic or the control groups. Conclusions: The PET-based longitudinal assessment of angiogenesis-associated APN/CD13 expression and glucose metabolism during ischaemia may continue to broaden our knowledge on the pathophysiology of PAD. LA - English DB - MTMT ER - TY - JOUR AU - Feró, Orsolya AU - Varga, Dóra AU - Nagy, Éva AU - Karányi, Zsolt AU - Sipos, Éva AU - Engelhardt, József AU - Török, Nóra AU - Balogh, István AU - Vető, Borbála AU - Likó, István AU - Fóthi, Ábel AU - Szabó, Zoltán AU - Halmos, Gábor AU - Vécsei, László AU - Arányi, Tamás AU - Székvölgyi, Lóránt TI - DNA methylome, R-loop and clinical exome profiling of patients with sporadic amyotrophic lateral sclerosis JF - SCIENTIFIC DATA J2 - SCI DATA VL - 11 PY - 2024 IS - 1 PG - 12 SN - 2052-4463 DO - 10.1038/s41597-024-02985-y UR - https://m2.mtmt.hu/api/publication/34534306 ID - 34534306 N1 - MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Molecular and Nanopharmaceutics, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary Doctoral School of Pharmaceutical Sciences, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Department of Molecular Biology, Semmelweis University, Budapest, Hungary Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, H-4032, Hungary Export Date: 13 February 2024; Cited By: 0; Correspondence Address: L. Székvölgyi; MTA-DE Momentum, Genome Architecture and Recombination Research Group, Department of Molecular and Nanopharmaceutics, Faculty of Pharmacy, University of Debrecen, Debrecen, H-4032, Hungary; email: lorantsz@med.unideb.hu; T. Arányi; Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary; email: aranyi.tamas@ttk.hu AB - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the death of motor neurons, the aetiology of which is essentially unknown. Here, we present an integrative epigenomic study in blood samples from seven clinically characterised sporadic ALS patients to elucidate molecular factors associated with the disease. We used clinical exome sequencing (CES) to study DNA variants, DNA-RNA hybrid immunoprecipitation sequencing (DRIP-seq) to assess R-loop distribution, and reduced representation bisulfite sequencing (RRBS) to examine DNA methylation changes. The above datasets were combined to create a comprehensive repository of genetic and epigenetic changes associated with the ALS cases studied. This repository is well-suited to unveil new correlations within individual patients and across the entire patient cohort. The molecular attributes described here are expected to guide further mechanistic studies on ALS, shedding light on the underlying genetic causes and facilitating the development of new epigenetic therapies to combat this life-threatening disease. LA - English DB - MTMT ER - TY - CHAP AU - Halmos, Gábor AU - Szabó, Zsuzsanna AU - Juhász, Éva AU - Andrew, V. Schally ED - Gerald, Litwack TI - Signaling mechanism of growth hormone-releasing hormone receptor T2 - Hormone Receptors: Structures and Functions PB - Academic Press CY - Cambridge, Massachusetts SN - 9780443134555 T3 - VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS, ISSN 0083-6729 ; Volume 123. PY - 2023 SP - 1 EP - 26 PG - 26 DO - 10.1016/bs.vh.2023.06.004 UR - https://m2.mtmt.hu/api/publication/34212323 ID - 34212323 LA - English DB - MTMT ER - TY - JOUR AU - Király, József AU - Szabó, Erzsébet Katalin AU - Fodor, Petra AU - Fejes, Zsolt AU - Nagy, Béla AU - Juhász, Éva AU - Vass, Anna AU - Choudhury, Mahua AU - Kónya, Gábor AU - Halmos, Gábor AU - Szabó, Zsuzsanna TI - Shikonin Causes an Apoptotic Effect on Human Kidney Cancer Cells through Ras/MAPK and PI3K/AKT Pathways JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 18 PG - 22 SN - 1420-3049 DO - 10.3390/molecules28186725 UR - https://m2.mtmt.hu/api/publication/34162579 ID - 34162579 AB - (1) Background: Shikonin, the main ingredient in Chinese herbal medicine, is described as a novel angiogenesis inhibitor, and its anticancer effects have already been studied. Shikonin and its derivatives induce apoptosis and suppress metastasis, which further enhance the effectiveness of chemotherapy. However, their mechanism of function has not been completely elucidated on human renal cancer cells. (2) Methods: In our study, CAKI-2 and A-498 cells were treated with increasing concentrations (2.5–40 µM) of shikonin, when colony formation ability and cytotoxic activity were tested. The changes in the expression of the main targets of apoptotic pathways were measured by RT-qPCR and Western blot. The intracellular levels of miR-21 and miR-155 were quantified by RT-qPCR. (3) Results: Shikonin exerted a dose-dependent effect on the proliferation of the cell lines examined. In 5 µM concentration of shikonin in vitro elevated caspase-3 and -7 levels, the proteins of the Ras/MAPK and PI3K/AKT pathways were activated. However, no significant changes were detected in the miR-21 and miR-155 expressions. (4) Conclusions: Our findings indicated that shikonin causes apoptosis of renal cancer cells by activating the Ras/MAPK and PI3K/AKT pathways. These effects of shikonin on renal cancer cells may bear important potential therapeutic implications for the treatment of renal cancer. LA - English DB - MTMT ER - TY - JOUR AU - Trencsényi, György AU - Halmos, Gábor AU - Képes, Zita TI - Radiolabeled NGR-Based Heterodimers for Angiogenesis Imaging : a Review of Preclinical Studies JF - CANCERS J2 - CANCERS VL - 15 PY - 2023 IS - 18 PG - 22 SN - 2072-6694 DO - 10.3390/cancers15184459 UR - https://m2.mtmt.hu/api/publication/34131187 ID - 34131187 AB - Since angiogenesis/neoangiogenesis has a major role in tumor development, progression and metastatic spread, the establishment of angiogenesis-targeting imaging and therapeutic vectors is of utmost significance. Aminopeptidase N (APN/CD13) is a pivotal biomarker of angiogenic processes abundantly expressed on the cell surface of active vascular endothelial and various neoplastic cells, constituting a valuable target for cancer diagnostics and therapy. Since the asparagine–glycine–arginine (NGR) sequence has been shown to colocalize with APN/CD13, the research interest in NGR-peptide-mediated vascular targeting is steadily growing. Earlier preclinical experiments have already demonstrated the imaging and therapeutic feasibility of NGR-based probes labeled with different positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radionuclides, including Gallium-68 (68Ga), Copper-64 (64Cu), Technetium-99m (99mTc), Lutetium-177 (177Lu), Rhenium-188 (188Re) or Bismuth-213 (213Bi). To improve the tumor binding affinity and the retention time of single-receptor targeting peptides, NGR motifs containing heterodimers have been introduced to identify multi-receptor overexpressing malignancies. Preclinical studies with various tumor-bearing experimental animals provide useful tools for the investigation of the in vivo imaging behavior of NGR-based heterobivalent ligands. Herein, we review the reported preclinical achievements on NGR heterodimers that could be highly relevant for the development of further target-specific multivalent compounds in diagnostic and therapeutic settings. LA - English DB - MTMT ER - TY - JOUR AU - Szegedi, Krisztián Gábor AU - Szabó, Zsuzsanna AU - Kállai, Judit AU - Király, József AU - Szabó, Erzsébet AU - Bereczky, Zsuzsanna AU - Juhász, Éva AU - Dezső, Balázs AU - Szász, Csaba AU - Zsebik, Barbara AU - Flaskó, Tibor AU - Halmos, Gábor TI - Potential Role of VHL, PTEN, and BAP1 Mutations in Renal Tumors JF - JOURNAL OF CLINICAL MEDICINE J2 - J CLIN MED VL - 12 PY - 2023 IS - 13 SN - 2077-0383 DO - 10.3390/jcm12134538 UR - https://m2.mtmt.hu/api/publication/34083399 ID - 34083399 AB - The genetic profiling of renal tumors has revealed genomic regions commonly affected by structural changes and a general genetic heterogeneity. The VHL, PTEN, and BAP1 genes are often mutated in renal tumors. The frequency and clinical relevance of these mutations in renal tumors are still being researched. In our study, we investigated VHL, PTEN, and BAP1 genes and the sequencing of 24 samples of patients with renal tumors, revealing that VHL was mutated at a noticeable frequency (25%). Six of the investigated samples showed mutations, and one genetic polymorphism (rs779805) was detected in both heterozygote and homozygote forms. PTEN gene mutation was observed in only one sample, and one specimen showed genetic polymorphism. In the case of the BAP1 gene, all of the samples were wild types. Interestingly, VHL mutation was detected in two female patients diagnosed with AML and in one with oncocytoma. We assume that VHL or PTEN mutations may contribute to the development of human renal cancer. However, the overall mutation rate was low in all specimens investigated, and the development and prognosis of the disease were not exclusively associated with these types of genetic alterations. LA - English DB - MTMT ER - TY - CONF AU - Király, József AU - Fodor, Petra AU - Szenthe, Kálmán AU - Szabó, Erzsébet AU - Flaskó, Tibor AU - Szegedi, Krisztián AU - Zsebik, Barbara AU - Szász, Csaba AU - Halmos, Gábor AU - Szabó, Zsuzsanna TI - miRNS-ek és angiogenezis markerek kapcsolatának vizsgálata humán vese karcinómában T2 - Abstract book of the 6th International Cholnoky Symposium PB - Pécsi Tudományegyetem C1 - Pécs PY - 2022 SP - 10 UR - https://m2.mtmt.hu/api/publication/33998813 ID - 33998813 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Király, József AU - Fodor, Petra AU - Szenthe, Kálmán AU - Szabó, Erzsébet AU - Flaskó, Tibor AU - Szegedi, Krisztián AU - Zsebik, Barbara AU - Szász, Csaba AU - Halmos, Gábor AU - Szabó, Zsuzsanna TI - Angiogenezismarkerek és miRNS-ek kapcsolatának vizsgálata humán vesekarcinómában JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 66 PY - 2022 SP - 249 EP - 250 PG - 2 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/33644566 ID - 33644566 LA - Hungarian DB - MTMT ER - TY - CONF AU - Fodor, Petra AU - Király, József AU - Szabó, Zsuzsanna AU - Halmos, Gábor AU - Zsebik, Barbara TI - The potential applicability of quercetin in the treatment of uveal melanoma tumour metastases T2 - Abstract book of the 6th International Cholnoky Symposium PB - Pécsi Tudományegyetem C1 - Pécs PY - 2022 SP - 25 UR - https://m2.mtmt.hu/api/publication/33644517 ID - 33644517 LA - English DB - MTMT ER - TY - JOUR AU - Fodor, Petra AU - Király, József AU - Szabó, Zsuzsanna AU - Halmos, Gábor AU - Zsebik, Barbara TI - Quercetin hatásának vizsgálata metasztatikus uveális melanóma sejtvonalon JF - MAGYAR ONKOLÓGIA J2 - MAGYAR ONKOLÓGIA VL - 66 PY - 2022 SP - 249 SN - 0025-0244 UR - https://m2.mtmt.hu/api/publication/33604518 ID - 33604518 LA - Hungarian DB - MTMT ER -