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1.

001-es BibID:BIBFORM065233
Első szerző:Canestraro, Martina
Cím:Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL60 cell line and primary blasts from patients affected by myeloproliferative disorders / Martina Canestraro, Sara Galimberti, Hakan Savli, Giuseppe Alberto Palumbo, Daniele Tibullo, Balint Nagy, Francesca Guerrini, Simona Piaggi, Naci Cine, Maria Rita Metelli, Mario Petrini
Dátum:2010
ISSN:0165-4608
Megjegyzések:Both arsenic trioxide (ATO) and bortezomib show separate antileukemic activity. With the purpose of evaluating whether the combination of ATO and bortezomib would be an option for patients with acute leukemia, we incubated HL60 leukemic cells with ATO alone and in combination with bortezomib. ATO and bortezomib cooperated to induce cell death and to inhibit proliferation and apoptosis in a synergistic way. The combined treatment resulted in a stronger activation of caspase 8 and 9, moderate activation of caspase 3, and increased expression of Fas and tumor necrosis factor?related apoptosis-inducing ligand (TRAIL)-DR5 receptors. When bortezomib was added, some proapoptotic genes (CARD9, TRAIL) were upregulated, and some antiapoptotic genes (BCL2, BCL3, FLICE) were downregulated. When coincubated, approximately 80% of cells showed altered mitochondrial membrane permeability. Moreover, ATO alone and in combination with bortezomib abrogated DNA-binding activity of nuclear factor kappa beta (NF-?B). Gene expression assays showed that more deregulated genes were related to proliferation of leukocytes, tumorigenesis, control of cell cycle, hypoxia and oxidative stress, cytokines, PI3K-AKT, ERK-MAPK, EGF pathways, and ubiquitination. Finally, in three cases of acute myeloid leukemia, the addition of bortezomib to ATO significantly increased cytotoxicity. We conclude that the combination of bortezomib and ATO may be efficacious in the treatment of myeloid disorders.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
bortezomib
synergestic
antiproliferative
Megjelenés:Cancer Genetics And Cytogenetics 199 : 2 (2010), p. 110-120. -
További szerzők:Galimberti, Sara Savlı, Hakan Palumbo, Giuseppe Alberto Tibullo, Daniele Nagy Bálint (1956-) (molekuláris genetikus) Guerrini, Francesca Piaggi, Simona Cine, Naci Metelli, Maria Rita Petrini, Mario
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2.

001-es BibID:BIBFORM074836
Első szerző:Cine, Naci
Cím:Effects of curcumin on global gene expression profiles in the highly invasive human breast carcinoma cell line MDA?MB 231 : a gene network-based microarray analysis / Naci Cine, Pornngarm Limtrakul, Deniz Sunnetci, Balint Nagy, Hakan Savli
Dátum:2012
ISSN:1792-0981 1792-1015
Megjegyzések:Curcumin, or diferuloylmethane, is a major chemical component of turmeric (Curcuma longa Linn.) that has been consumed as a dietary spice through the ages. This yellow-colored polyphenol has a notably wide range of beneficial properties, including anti-inflammatory, antioxidant, antitumoral, anti-invasive and anti-metastatic activity. In the present study, microarray gene expression analysis was applied to identify the curcumin-regulated genes in a highly invasive human breast carcinoma cell line (MDA-MB 231). Cells were cultured with curcumin (20 ?M) for 24 h; total RNA was isolated and hybridized to Whole Human Genome Microarray slides. Gene set enrichment analyses on our whole genome expression data revealed downregulation of the EGF pathway elements following curcumin treatment. Furthermore, gene network analysis identified a significantly relevant network among the differentially expressed genes, centered on the EGR1 and FOS genes. The members of these pathways and networks play an essential role in the regulation of cancer cell growth and development; the majority exhibited decreased expression levels following treatment with curcumin. These observations suggest that curcumin is an excellent candidate for the prevention and treatment of breast cancer.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
curcumin
gene expression
breast
carcinoma
Megjelenés:Experimental and Therapeutic Medicine. - 5 : 1 (2012), p. 23-27. -
További szerzők:Limtrakul, Pornngarm Sunnetci, Deniz Nagy Bálint (1956-) (molekuláris genetikus) Savlı, Hakan
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3.

001-es BibID:BIBFORM065229
035-os BibID:(PMID)21115902
Első szerző:Galimberti, Sara
Cím:ITF2357 Interferes with Apoptosis and Inflammatory Pathways in the HL-60 Model : a Gene Expression Study / Sara Galimberti, Martina Canestraro, Hakan Savli, Giuseppe Alberto Palumbo, Daniele Tibullo, Balint Nagy, Simona Piaggi, Francesca Guerrini, Naci Cine, Maria Rita Metelli, Mario Petrini
Dátum:2010
ISSN:0250-7005
Megjegyzések:Background: Cytotoxic and pro-apoptotic effectsexerted by the histone deacetylase inhibitor ITF2357 havebeen reported in acute myeloid leukemia HL-60 cells. In thecurrent study, its mechanism of action was investigated at themolecular level. Materials and Methods: Cell proliferationwas evaluated by methyl thiazol tetrazolium bromidereduction; apoptosis by annexin V, mitochondrialtransmembrane potential by tetramethylrhodamine ethylester. Functional experiments and gene expressionevaluations were performed by flow cytometry, microarray,and quantitative polymerase chain reaction. Results:Significant cell growth inhibition and increased apoptosiswere observed. ITF2357 reduced protein levels of BCL-2,MCL-1, and BCL-X, and increased levels of BAK. Exposureto ITF2357 did not abrogate NF-?B DNA binding. Aftermicroarray analysis, interleukin-10, interleukin-6, epidermalgrowth factor, peroxisome proliferator-activated receptor(PPAR), transforming growth factor ?, P38 mitogenactivatedprotein kinase, aryl hydrocarbon receptor,xenobiotic metabolism, PPAR/retinoic acid receptor, NF-?B,apoptosis, lipopolysaccharide/interleukin-1, G-proteinreceptor, T-cell receptor, and platelet-derived growth factorwere the de-regulated pathways. Conclusion: This studyshows that ITF2357 influences both proliferation andinflammatory pathways in HL-60 cells; this observationcould have possible applications in clinical practice.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
gene expression
pathways
apoptosis
Inflammatory
Megjelenés:Anticancer Research. - 30 (2010), p. 4025-4035. -
További szerzők:Canestraro, Martina Savlı, Hakan Palumbo, Giuseppe Alberto Tibullo, Daniele Nagy Bálint (1956-) (molekuláris genetikus) Piaggi, Simona Guerrini, Francesca Cine, Naci Metelli, Maria Rita Petrini, Mario
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM065299
Első szerző:Nagy Bálint (molekuláris genetikus)
Cím:Vascular endothelial growth factor (VEGF) polymorphisms in HELLP syndrome patients determined by quantitative real-time PCR and melting curve analyses / Bálint Nagy, Hakan Savli, Attila Molvarec, Tibor Várkonyi, Barbara Rigó, Petronella Hupuczi, János Rigó Jr.
Dátum:2008
ISSN:0009-8981
Megjegyzések:The vascular endothelial growth factor (VEGF) has a critical role in vasculogenesis and vascular permeability in several diseases including preeclampsia. There are at least 30 single nucleotide polymorphic (SNP) places on this gene. VEGF G+405C, C-2578A and C-460T SNPs are known to be related to VEGF production. VEGF polymorphisms were studied in preeclampsia, but not in HELLP syndrome. Therefore, we decided to determine the allele and genotype frequencies of VEGF G+405C, C-460T and C-2578A SNPs in healthy pregnant women and HELLP syndrome patients.METHODS:The authors introduced a quantitative real-time PCR method for the determination of the three VEGF SNPs. Blood samples were collected from 71 HELLP syndrome patients and 93 healthy controls. DNA was isolated by using silica adsorption method. The SNPs were determined by quantitative real-time PCR and melting curve analysis using LightCycler.RESULTS:There were significant differences in the allele and genotype frequencies of VEGF C-460T SNP between the two study groups. The T allele was present in 71.1% in the HELLP group, while in 53.8% in the controls (p=0.0014). The TT genotype occurred significantly more frequently in the HELLP group than in the control group (45.1% vs. 21.5%; p (for genotype frequencies)=0.0011). The TT genotype carriers had an increased risk of HELLP syndrome, which was independent of maternal age and primiparity (adjusted odds ratio (OR)=3.03, 95% confidence interval (CI)=1.51-6.08; p=0.002). Although the VEGF G+405C allele and genotype distributions did not differ significantly between the two groups, the CC genotype carriers were also found to have an increased risk for HELLP syndrome after adjustment for maternal age and primiparity (adjusted OR=3.67, 95% CI=1.05-12.75; p=0.041). The VEGF C-2578A SNP was not associated with HELLP syndrome.CONCLUSIONS:The quantitative real-time PCR combined with melting curve analyses is a fast and reliable method for the determination of VEGF SNPs. We found that the VEGF -460TT and +405CC genotype carriers have an increased risk of HELLP syndrome. As these two SNPs were previously observed to be related to production of the VEGF protein, we suppose that these VEGF polymorphisms -- interacting with other genetic and environmental factors - could play a role in the development of HELLP syndrome.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
VEGF
Polymorphism
HELLP syndrome
Megjelenés:Clinica Chimica Acta. - 389 : 1-2 (2008), p. 126-131. -
További szerzők:Savlı, Hakan Molvarec Attila (szülész-nőgyógyász) Várkonyi Tibor Rigó Barbara (szülész-nőgyógyász) Hupuczi Petronella (anaesthesiológus) Rigó János (1958-) (szülész-nőgyógyász)
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5.

001-es BibID:BIBFORM074834
Első szerző:Savlı, Hakan
Cím:Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39) : a Gene Expression Study / Hakan Savlı, Sara Galimberti, Deniz Sünnetçi, Martina Canestraro, Giuseppe Palumbo, Balint Nagy, Francesco Di Raimondo, Mario Petrini
Dátum:2015
ISSN:1300-7777
Megjegyzések:NTRODUCTION:We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.METHODS:Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR.RESULTS:Bortezomib treatment has shown upregulated DIABLO and NF-?BIB (a NF-?B inhibitor) and downregulated NF-?B1, NF-?B2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.DISCUSSION AND CONCLUSION:Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-?B was observed as an important modulator in leukemic transformation of MDS.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
bortezomib
gene expression
myelodyplastic
Megjelenés:Turkish Journal of Hematology. - 32 : 3 (2015), p. 206-212. -
További szerzők:Galimberti, Sara Sünnetçi, Deniz Canesastraro, Martina Palumbo, Giuseppe Alberto Nagy Bálint (1956-) (molekuláris genetikus) Raimondo, Francesco Di Petrini, Mario
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6.

001-es BibID:BIBFORM065296
Első szerző:Savlı, Hakan
Cím:Gene network and canonical pathway analysis in prostate cancer : a microarray study / Hakan Savli, Attila Szendrői, Imre Romics, Balint Nagy
Dátum:2008
ISSN:1226-3613
Megjegyzések:The molecular mechanism playing a role in the development of prostate cancer (PCA) is not well defined. We decided to determine the changes in gene expression in PCA tissues and to compare them to those in non-cancerous samples. Prostate tissue samples were collected by needle biopsy from 21 PCA and 10 benign prostate hyperplasic (BPH) patients. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined by microarray method. In the progression to PCA, 738 up-regulated and 515 down-regulated genes were detected in samples. Analysis using Ingenuity Pathway Analysis (IPA) software revealed that 466 network and 423 functions-pathways eligible genes were up-regulated, and 363 network and 342 functions-pathways eligible genes were down-regulated. Up-regulated networks were identified around IL-1beta and insulin-like growth factor-1 (IGF-1) genes. The NFKB gene was centered around two up- and down-regulated networks. Up-regulated canonical pathways were assigned and four of them were evaluated in detail: acute phase response, hepatic fibrosis, actin cytoskeleton, and coagulation pathways. Axonal guidance signaling was the most significant down-regulated canonical pathway. Our data provide not only networks between the genes for understanding the biologic properties of PCA but also useful pathway maps for future understanding of disease and the construction of new therapeutic targets.
Tárgyszavak:Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban
Gene
Network
canonical
pathway
prostate cancer
Megjelenés:Experimental And Molecular Medicine. - 40 : 2 (2008), p. 176-. -
További szerzők:Szendrői Attila Romics Imre Nagy Bálint (1956-) (molekuláris genetikus)
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7.

001-es BibID:BIBFORM065345
Első szerző:Savlı, Hakan
Cím:Gene expression analysis of 1,25(OH)2D3-dependent differentiation of HL-60 cells: a cDNA array study / Hakan Savli, Yan Aalto, Bálint Nagy, Sakari Knuutila, Seppo Pakkala
Dátum:2002
ISSN:0007-1048
Megjegyzések:The alterations in gene expression associated with 1,25(OH)2D3-induced differentiation of HL-60 cells were studied in order to identify potential targets for further investigation of the genetic basis of acute myeloid leukaemia. Atlas human haematology filters, including 406 genes (Clontech), were used to study gene expression in response to 1,25(OH)2D3 (concentration, 5 x 10-8 mol/l) for 24 and 72 h. Compared with untreated cells, expression differences were found in 43 genes. Downregulated genes at both time-points were: IL2RA, CMYC, NPM, DEK, AF4, FLI1, htlf, MNDA, BCR, IKAROS, BPI and NFAT4. Upregulated genes at both time-points were IL1B, CD14 and MCL1. CD55, CD58, IRF2, CREB1, ATF4, RAC1, TIAR, KIAA0053, BAT2, BTK, RCK, EV12B and EDN were downregulated at 24 h, while SPI1, MKK3, BTG1 and IL8 were upregulated. At 72 h the upregulated genes were IL1RA, IL2RG, CXCR4, SCYA1, SCYA3, SCYA4, SCYA5, SCYA22, ANX2, CD83 and UPAR. cDNA array results were confirmed on randomly selected genes using quantitative real-time polymerase chain reaction for three upregulated (CXCR4, IL1B and CD14) and three downregulated (DEK, AF4 and FLI1) genes. Gene expression analysis after differentiation induction may provide a tool to study the roles of DEK, AF4 and FLI1 in cell proliferation and differentiation. To demonstrate the genes that initiate differentiation, sequential gene expression analysis has to be performed during the first 24 h of the differentiation process.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
cDNA
microarray
HL-60
gene
expression
Megjelenés:British Journal Of Haematology. - 118 (2002), p. 1065-1070. -
További szerzők:Aalto, Yan Nagy Bálint (1956-) (molekuláris genetikus) Knuutila, Sakari Pakkala, Seppo
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8.

001-es BibID:BIBFORM065332
Első szerző:Savlı, Hakan
Cím:Real-Time PCR analysis of af4 and dek genes expression in acute promyelocytic leukemia t (15; 17) patients / Hakan Savli, Sema Sirma, Balint Nagy, Melih Aktan, Guncag Dincol, Zafer Salcioglu, Nazan Sarper, Ugur Ozbek
Dátum:2004
ISSN:1226-3613
Megjegyzések:Among several newly identified oncogenes, dek and af4 are attractive targets for researchers interested with leukemia. In this study quantitative Real-Time RT-PCR technique was used to define alterations in expression of dek and af4 genes associated with acute promyelocytic leukaemia (APL) t (15; 17). RNA samples obtained from bone marrow aspirates of fourteen APL patients, cDNA portions were labelled with Syber Green 1 dye and LightCycler analysis have been performed. Expression changes in patients were found not significant in comparison to healthy donors for af4 (P = 0.192) and dek (P = 0.0895). We suggest that af4 gene may have a role in leukomogenesis restricted to lymphoblastic lineage; also further studies must carry on with a larger series of patients in order to understand the relationship between the dek gene and APL. Our study was the first attempt for analysing dek and af4 genes in APL t (15; 17) patients by quantitative Real-Time RT-PCR. This rapid and sensitive method could be used to screen these genes in different types of leukaemia.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
real-time
PCR
AF4
DEK
gene
expression
APL
Megjelenés:Experimental And Molecular Medicine. - 36 : 3 (2004), p. 279-282. -
További szerzők:Sirma, Sema Nagy Bálint (1956-) (molekuláris genetikus) Aktan, Melih Dincol, Guncag Salcioglu, Zafer Sarper, Nazan Ozbek, Ugur
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9.

001-es BibID:BIBFORM065336
Első szerző:Savlı, Hakan
Cím:Real-time PCR analysis of the apoptosis related genes in ATRA treated APL t(15;17) patients / Hakan Savli, Sema Sirma, Balint Nagy, Melih Aktan, Guncag Dincol, Ugur Ozbek
Dátum:2003
ISSN:1226-3613
Megjegyzések:All-trans retinoic acid (ATRA) treatment of the acute promyelocytic leukemia (APL) have subsequently resulted in cell apoptosis, but the molecular mechanism of this effect remains elusive. In order to understand a possible involvement of genes regulating apoptotic signal pathways, expression levels of bcl2, bax, dapk1, myc, bad, wt1, and mcl genes were analyzed during ATRA treatment in five APL patients with t (15;17) using Real- time PCR (LightCycler). Two samples from each patient were compared to each other: primary diagnostic sample and a sample taken at remission. Effect of the ATRA treatment was demonstrated by the concomitant induction of cd14 and il1beta genes in four patients. Also other apoptosis related genes were found down-regulated in general but especially the down regulated levels of wt1 and bax attract attention. Result suggested that ATRA dependent apoptosis of APL was under the control of both internal and external pathways without relationships to the amount of the blast populations. Ratio of bcl2 to bax may be more important for this regulation than the ratio of bcl2 to bad. Either bcl2 family or less known apoptosis related genes as wt1 will still be required to further studies in this setting.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
real-time
PCR
ATRA
apoptosis
APL
Megjelenés:Experimental And Molecular Medicine. - 35 : 5 (2003), p. 454-459. -
További szerzők:Sirma, Sema Nagy Bálint (1956-) (molekuláris genetikus) Aktan, Melih Dincol, Guncag Ozbek, Ugur
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