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001-es BibID:BIBFORM087405
035-os BibID:(cikkazonosító)5135 (WoS)000554266900001 (Scopus)85088162016
Első szerző:Kotogány Edit
Cím:Imidazo[1,2-b]pyrazole-7-Carboxamide Derivative Induces Differentiation-Coupled Apoptosis of Immature Myeloid Cells Such as Acute Myeloid Leukemia and Myeloid-Derived Suppressor Cells / Edit Kotogány, József Á. Balog, Lajos I. Nagy, Róbert Alföldi, Valeria Bertagnolo, Federica Brugnol, András Demjén, Anita K. Kovács, Péter Batár, Gabriella Mezei, Renáta Szabó, Iván Kanizsai, Csaba Varga, László G. Puskás, Gábor J. Szeben
Dátum:2020
ISSN:1422-0067
Megjegyzések:Chemotherapy-induced differentiation of immature myeloid progenitors, such as acute myeloid leukemia (AML) cells or myeloid-derived suppressor cells (MDSCs), has remained a challenge for the clinicians. Testing our imidazo[1,2-b]pyrazole-7-carboxamide derivative on HL-60 cells, we obtained ERK phosphorylation as an early survival response to treatment followed by the increase of the percentage of the Bcl-xlbright and pAktbright cells. Following the induction of Vav1 and the AP-1 complex, a driver of cellular differentiation, FOS, JUN, JUNB, and JUND were elevated on a concentration and time-dependent manner. As a proof of granulocytic differentiation, the cells remained non-adherent, the expression of CD33 decreased; the granularity, CD11b expression, and MPO activity of HL-60 cells increased upon treatment. Finally, viability of HL-60 cells was hampered shown by the depolarization of mitochondria, activation of caspase-3, cleavage of Z-DEVD-aLUC, appearance of the sub-G1 population, and the leakage of the lactate-dehydrogenase into the supernatant. We confirmed the differentiating effect of our drug candidate on human patient-derived AML cells shown by the increase of CD11b and decrease of CD33+, CD7+, CD206+, and CD38bright cells followed apoptosis (IC50: 80 nM) after treatment ex vivo. Our compound reduced both CD11b+/Ly6C+ and CD11b+/Ly6G+ splenic MDSCs from the murine 4T1 breast cancer model ex vivo.
Tárgyszavak:Orvostudományok Klinikai orvostudományok kutatási jelentés
folyóiratcikk
acute myeloid leukemia
myeloid-derived suppressor cells
differentiation
apoptosis
Megjelenés:International Journal Molecular Sciences. - 21 : 14 (2020), p. 1-27. -
További szerzők:Balog József A. Nagy Lajos István (Szeged) Alföldi Róbert Bertagnolo, Valeria Brugnol, Federica Demjén András Kovács Anita K. Batár Péter (1969-) (belgyógyász, haematológus) Mezei Gabriella (1969-) (belgyógyász) Szabó Renáta Kanizsai Iván Varga Csaba (orvos) Puskás László G. Szeben Gábor J.
Internet cím:DOI
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2.

001-es BibID:BIBFORM059408
Első szerző:Nagy Lajos István (Szeged)
Cím:Curcumin and Its Analogue Induce Apoptosis in Leukemia Cells and Have Additive Effects with Bortezomib in Cellular and Xenograft Models / L. I. Nagy, L. Z. Fehér, G. J. Szebeni, M. Gyuris, P. Sipos, R. Alföldi, B. Ózsvári, L. Hackler Jr., A. Balázs, P. Batár, I. Kanizsai, L. G. Puskás
Dátum:2015
ISSN:2314-6133 2314-6141
Megjegyzések:Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-kappa B, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-kappa B inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
HUMAN MULTIPLE-MYELOMA
FACTOR-KAPPA-B
INHIBITS PROLIFERATION
SIGNALING PATHWAYS
IN-VITRO
CANCER
AGENTS
ANGIOGENESIS
COMBINATION
PROGRESSION
Megjelenés:Biomed Research International. - 2015 (2015), p. 1-11. -
További szerzők:Fehér Liliána Z. (Szeged) Szebeni Gábor János (Szeged) Gyuris Márió Sipos Péter (Szeged) Alföldi Róbert Ózsvári Béla Hackler László Jr. Balázs A. Batár Péter (1969-) (belgyógyász, haematológus) Kanizsai Iván Puskás László G.
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DOI
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3.

001-es BibID:BIBFORM077772
035-os BibID:(cikkazonosító)2845 (WoS)000451641900117 (Scopus)85056048074
Első szerző:Szebeni Gábor János (Szeged)
Cím:Imidazo[1,2-b]pyrazole-7-carboxamides Induce Apoptosis in Human Leukemia Cells at Nanomolar Concentrations / Gábor J. Szebeni, József A. Balog, András Demjén, Róbert Alföldi, Vanessza L. Végi, Liliána Z. Fehér, Imola Mán, Edit Kotogány, Barbara Gubán, Péter Batár, László Hackler Jr., Iván Kanizsai, László G. Puskás
Dátum:2018
ISSN:1420-3049
Megjegyzések:Leukemia, the malignancy of the hematopoietic system accounts for 10% of cancer cases with poor overall survival rate in adults; therefore, there is a high unmet medical need for the development of novel therapeutics. Eight imidazo[1,2-b]pyrazole-7-carboxamides have been tested for cytotoxic activity against five leukemia cell lines: Acute promyelocytic leukemia (HL-60), acute monocytic leukemia (THP-1), acute T-lymphoblastic leukemia (MOLT-4), biphenotypic B myelomonocytic leukemia (MV-4-11), and erythroleukemia (K-562) cells in vitro. Imidazo[1,2-b]pyrazole-7-carboxamides hampered the viability of all five leukemia cell lines with different potential. Optimization through structure activity relationship resulted in the following IC50 values for the most effective lead compound DU385: 16.54 nM, 27.24 nM, and 32.25 nM on HL-60, MOLT-4, MV-4-11 cells, respectively. Human primary fibroblasts were much less sensitive in the applied concentration range. Both monolayer or spheroid cultures of murine 4T1 and human MCF7 breast cancer cells were less sensitive to treatment with 1.5⁻10.8 ?M IC50 values. Flow cytometry confirmed the absence of necrosis and revealed 60% late apoptotic population for MV-4-11, and 50% early apoptotic population for HL-60. MOLT-4 cells showed only about 30% of total apoptotic population. Toxicogenomic study of DU385 on the most sensitive MV-4-11 cells revealed altered expression of sixteen genes as early (6 h), midterm (12 h), and late response (24 h) genes upon treatment. Changes in ALOX5AP, TXN, and SOD1 expression suggested that DU385 causes oxidative stress, which was confirmed by depletion of cellular glutathione and mitochondrial membrane depolarization induction. Imidazo[1,2-b]pyrazole-7-carboxamides reported herein induced apoptosis in human leukemia cells at nanomolar concentrations.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
acute myeloid leukemia
apoptosis
imidazole
pyrazole
toxicogenomics
Megjelenés:Molecules. - 23 : 11 (2018), p. 1-15. -
További szerzők:Balog József A. Demjén András Alföldi Róbert Végi Vanessza L. Fehér Liliána Z. (Szeged) Mán Imola Kotogány Edit Gubán Barbara Batár Péter (1969-) (belgyógyász, haematológus) Hackler László Jr. Kanizsai Iván Puskás László G.
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DOI
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