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001-es BibID:	BIBFORM096377
035-os BibID:	(cikkazonosító)8869 (scopus)85112763543 (wos)000689059300001
Első szerző:	Kiss Alexandra (klinikai laboratóriumi kutató)
Cím:	NMNAT1 Is a Survival Factor in Actinomycin D-Induced Osteosarcoma Cell Death / Alexandra Kiss, Csaba Csikos, Zsolt Regdon, Zsuzsanna Polgár, László Virág, Csaba Hegedűs
Dátum:	2021
ISSN:	1661-6596 1422-0067
Megjegyzések:	Osteosarcoma is a frequent and extremely aggressive type of pediatric cancer. New therapeutic approaches are needed to improve the overall survival of osteosarcoma patients. Our previous results suggest that NMNAT1, a key enzyme in nuclear NAD+ synthesis, facilitates the survival of cisplatin-treated osteosarcoma cells. A high-throughput cytotoxicity screening was performed to identify novel pathways or compounds linked to the cancer-promoting role of NMNAT1. Nine compounds caused higher toxicity in the NMNAT1 KO U2OS cells compared to their wild type counterparts, and actinomycin D (ActD) was the most potent. ActD-treatment of NMNAT1 KO cells increased caspase activity and secondary necrosis. The reduced NAD+ content in NMNAT1 KO cells was further decreased by ActD, which partially inhibited NAD+ -dependent enzymes, including the DNA nick sensor enzyme PARP1 and the NAD+ -dependent deacetylase SIRT1. Impaired PARP1 activity increased DNA damage in ActD-treated NMNAT1 knockout cells, while SIRT1 impairment increased acetylation of the p53 protein, causing the upregulation of pro-apoptotic proteins (NOXA, BAX). Proliferation was decreased through both PARP- and SIRT-dependent pathways. On the one hand, PARP inhibitors sensitized wild type but not NMNAT1 KO cells to ActD-induced anti-clonogenic effects; on the other hand, over-acetylated p53 induced the expression of the antiproliferative p21 protein leading to cell cycle arrest. Based on our results, NMNAT1 acts as a survival factor in ActD-treated osteosarcoma cells. By inhibiting both PARP1- and SIRT1-dependent cellular pathways, NMNAT1 inhibition can be a promising new tool in osteosarcoma chemotherapy.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk NAD+ NMNAT1 actinomycin D chemotherapy apoptosis PARP1 SIRT1 osteosarcoma cancer high throughput screening
Megjelenés:	International Journal of Molecular Sciences. - 22 : 16 (2021), p. 1-17. -
További szerzők:	Csikos Csaba (1997-) (orvos) Regdon Zsolt (1988-) (biokémikus, molekuláris biológus) Polgár Zsuzsanna (1978-) (agrármérnök, biotechnológus) Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00020 GINOP GINOP-2.3.2-15-2016-00048 GINOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM117633
035-os BibID:	(cikkazonosító)664 (WoS)001141423100001 (Scopus)85182205296
Első szerző:	Trencsényi György (biológus, biokémikus, molekuláris biológus)
Cím:	Targeted Radium Alpha Therapy in the Era of Nanomedicine: In Vivo Results / György Trencsényi, Csaba Csikos, Zita Képes
Dátum:	2024
ISSN:	1422-0067
Megjegyzések:	Targeted alpha-particle therapy using radionuclides with alpha emission is a rapidly developing area in modern cancer treatment. To selectively deliver alpha-emitting isotopes to tumors, targeting vectors, including monoclonal antibodies, peptides, small molecule inhibitors, or other biomolecules, are attached to them, which ensures specific binding to tumor-related antigens and cell surface receptors. Although earlier studies have already demonstrated the anti-tumor potential of alpha-emitting radium (Ra) isotopes-Radium-223 and Radium-224 (Ra-223/224)-in the treatment of skeletal metastases, their inability to complex with target-specific moieties hindered application beyond bone targeting. To exploit the therapeutic gains of Ra across a wider spectrum of cancers, nanoparticles have recently been embraced as carriers to ensure the linkage of Ra-223/224 to target-affine vectors. Exemplified by prior findings, Ra was successfully bound to several nano/microparticles, including lanthanum phosphate, nanozeolites, barium sulfate, hydroxyapatite, calcium carbonate, gypsum, celestine, or liposomes. Despite the lengthened tumor retention and the related improvement in the radiotherapeutic effect of Ra-223/224 coupled to nanoparticles, the in vivo assessment of the radiolabeled nanoprobes is a prerequisite prior to clinical usage. For this purpose, experimental xenotransplant models of different cancers provide a well-suited scenario. Herein, we summarize the latest achievements with Ra-223/224-doped nanoparticles and related advances in targeted alpha radiotherapy.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk nanoparticles preclinical Radium-223/224 (223/224Ra) targeted alpha-particle therapy xenotransplants
Megjelenés:	International Journal Of Molecular Sciences. - 25 : 1 (2024), p. 1-30. -
További szerzők:	Csikos Csaba (1997-) (orvos) Képes Zita (1991-) (orvos)
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: