CCL

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1.

001-es BibID:BIBFORM074858
Első szerző:Aalto, Yan
Cím:Distinct gene expression profiling in chronic lymphocytic leukemia with 11q23 deletion / Y. Aalto, W. El-Rifai, L. Vilpo, J. Ollila, B. Nagy, M. Vihinen, J. Vilpo, S. Knuutila
Dátum:2001
ISSN:0887-6924
Megjegyzések:Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with regard to its clinical course. The limitations of the methods currently available for prognostic assessment in CLL do not allow accurate prediction of the risk of disease progression in individual patients. The recently developed cDNA array technique provides a unique opportunity to study gene expression in various malignancies. To identify new molecular markers for prognostication of CLL patients, we analyzed cDNA arrays by using hierarchical clustering and standard statistic t-test on 34 CLL patients. We found significant expression differences in 78 genes compared to the reference tonsillar B lymphocytes. A cluster of genes, LCP1, PARP, BLR1, DEK, NPM, MCL1, SLP76, STAM, HIVEP1, EVI2B, CD25, HTLF, HIVEP2, BCL2, MNDA, PBX3, EB12, TCF1, CGRP, CD14, ILB, GZMK, GPR17 and CD79B, was associated (P < 0.05) with the unfavorable 11q deletion and also with the unfavorable Binet stages B and C. We present here gene expression profiling that is associated with CLL patients with the 11q23 deletion. Many of the genes in the cluster have not previously been shown to be related to the initiation or progression of CLL. These novel findings provide fundamental information for further attempts to understand the interaction of the clustered genes in the leukomogenesis of CLL in order to better design treatments aimed at specific molecular target(s).
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
gene expression
deletion 11q23
CLL
Megjelenés:Leukemia. - 15 : 11 (2001), p. 1721-1728. -
További szerzők:El-Rifai, Wa'el Vilpo, L. Ollila, Juha Nagy Bálint (1956-) (molekuláris genetikus) Vihinen, Mauno Vilpo, Juhani Knuutila, Sakari
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2.

001-es BibID:BIBFORM065333
Első szerző:Cerisano, Vanessa
Cím:Molecular mechanisms of CD99-induced caspase-independent cell death and cell-cell adhesion in Ewing's sarcoma cells : actin and zyxin as key intracellular mediators / Vanessa Cerisano, Yan Aalto, Stefania Perdichizzi, Ghislaine Bernard, Maria Cristina Manara, Stefania Benini, Giovanna Cenacchi, Paola Preda, Giovanna Lattanzi, Bálint Nagy, Sakari Knuutila, Mario Paolo Colombo, Alain Bernard, Piero Picci, Katia Scotlandi
Dátum:2004
ISSN:0950-9232
Megjegyzések:CD99 is a unique 32-kDa cell surface molecule with broad cellular expression but still poorly understood biological functions. In cancer cells, CD99 is highly expressed in virtually all Ewing's sarcoma (ES). Engagement of CD99 induces fast homotypic aggregation of ES cells and caspase-independent apoptosis. In this study, we analysed signal transduction after CD99 engagement on ES cells. Findings obtained with selective inhibitors indicated that only actin cytoskeleton integrity was essential for cell-cell adhesion and apoptosis of ES cells. Indeed, CD99 stimulation induced actin repolymerization, further supporting the role of cytoskeleton in CD99 signaling. Gene expression profiling of ES cells after CD99 engagement showed modulation in the expression of 32 genes. Among the pool of upregulated genes reported to be involved in cell adhesion, we chose to analyse the role of zyxin, a cytoplasmic adherens junction protein found to play a role in the regulation of the actin cytoskeleton. Overexpression of zyxin after CD99 ligation was confirmed by real-time PCR and Western blot. Treatment of ES cells with zyxin antisense oligonucleotides inhibited CD99-induced cell aggregation and apoptosis, suggesting a functional role for this protein. Therefore, our findings indicate that CD99 functions occur through reorganization of cytoskeleton and identify actin and zyxin as the early signaling events driven by CD99 engagement.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
CD-99
induced
caspase
independent
cell death
Ewing's sarcoma
Megjelenés:Oncogene. - 23 : 33 (2004), p. 5664-5674. -
További szerzők:Aalto, Yan Perdichizzi, Stefania Bernard, Ghislaine Manara, Maria Cristina Benini, Stefania Cenacchi, Giovanna Preda, Paola Lattanzi, Giovanna Nagy Bálint (1956-) (molekuláris genetikus) Knuutila, Sakari Colombo, Mario Paolo Bernard, Alain Picci, Piero Scotlandi, Katia
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3.

001-es BibID:BIBFORM065331
Első szerző:Ferrer, Anna
Cím:Different gene expression in immunoglobulin-mutated and immunoglobulin-unmutated forms of chronic lymphocytic leukemia / Anna Ferrer, Juha Ollila, Gerard Tobin, Bálint Nagy, Ulf Thunberg, Yan Aalto, Mauno Vihinen, Juhani Vilpo, Richard Rosenquist, Sakari Knuutila
Dátum:2004
ISSN:0165-4608
Megjegyzések:The mutation status of the immunoglobulin heavy chain variable regions (IgVH) has been found to be a good prognostic indicator for B-cell chronic lymphocytic leukemia (CLL) because unmutated VH genes are associated with rapid disease progression and shorter survival time. To study the differences in gene expression between the Ig-unmutated and Ig-mutated CLL subtypes, we performed gene expression profiling on 31 CLL cases and investigated the VH gene mutation status by sequencing. The array data showed that the greatest variances between the unmutated (20 cases) and the mutated (11 cases) group were in expressions of ZAP70, RAF1, PAX5, TCF1, CD44, SF1, S100A12, NUP214, DAF, GLVR1, MKK6, AF4, CX3CR1, NAFTC1, and HEX. ZAP70 was significantly more expressed in the Ig-unmutated CLL group, whereas the expression of all the other genes was higher in the Ig-mutated cases. These results corroborate a recent finding, according to which the expression of ZAP70 can predict the VH mutation status and suggest that RAF1, PAX5, and other differentially expressed genes may offer good markers for differentiating unmutated cases from mutated cases and thus serve as prognostic markers.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
gene
expression
immunoglobulin
mutated
unmutated
CLL
Megjelenés:Cancer Genetics And Cytogenetics. - 153 : 1 (2004), p. 69-72. -
További szerzők:Ollila, Juha Tobin, Gerard Nagy Bálint (1956-) (molekuláris genetikus) Thunberg, Ulf Aalto, Yan Vihinen, Mauno Vilpo, Juhani Rosenquist, Richard Knuutila, Sakari
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4.

001-es BibID:BIBFORM065340
Első szerző:Nagy Bálint (molekuláris genetikus)
Cím:Abnormal expression of apoptosis-related genes in haematological malignancies : overexpression of MYC is poor prognostic sign in mantle cell lymphoma / Bálint Nagy, Tuija Lundán, Marcelo L. Larramendy, Yan Aalto, Ying Zhu, Tarja Niini, Henrik Edgren, Anna Ferrer, Juhani Vilpo, Erkki Elonen, Kim Vettenranta, Kaarle Franssila, Sakari Knuutila
Dátum:2003
ISSN:0007-1048
Megjegyzések:The expression of apoptosis-related genes BCL2, BAX, BCL2L1, BCL2A1, MCL1, DAPK1 and MYC was studied by quantitative real-time polymerase chain reaction on total RNA samples from patients with acute lymphoblastic leukaemia (ALL, n = 16), acute myeloid leukaemia (AML, n = 27), chronic myeloid leukaemia (CML, n = 12), mantle cell lymphoma (MCL, n = 19) and chronic lymphoid leukaemia (CLL, n = 32). BCL2, BAX, BCL2A1, MCL1, DAPK1 and MYC were overexpressed in all patient groups. BCL2L1 was underexpressed in CLL and CML, but not in AML, ALL and MCL. MCL1 levels were significantly higher in CD13 and CD33-positive ALL, and in CD56-positive AML samples. BCL2, BCL2L1, BCL2A1 and MCL1 were overexpressed and DAPK1 was underexpressed in CLL samples with a 11q23 deletion. MYC overexpression was significantly associated with shorter overall survival in MCL (P < 0.01). AML patients with a normal karyotype showed a higher frequency of BCL2A1 overexpression (P < 0.001) than those with an abnormal karyotype.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
mantle cell
lymphoma
gene expression
myc
prognostic
Megjelenés:British Journal Of Haematology. - 120 (2003), p. 434-441. -
További szerzők:Lundán, Tuija Larramendy, Marcelo L. Aalto, Yan Zhu, Ying Niini, Tarja Edgren, Henrik Ferrer, Anna Vilpo, Juhani Elonen, Erkki Vettenranta, Kim Franssila, Kaarle Knuutila, Sakari
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5.

001-es BibID:BIBFORM065339
Első szerző:Nagy Bálint (molekuláris genetikus)
Cím:Lymphotoxin [béta] expression is high in chronic lymphocytic leukemia but low in small lymphocytic lymphoma : a quantitative real-time reverse transcriptase polymerase chain reaction analysis / Bálint Nagy, Anna Ferrer, Marcelo L. Larramendy, Sara Galimberti, Yan Aalto, Silvia Casas, Juhani Vilpo, Tapani Ruutu, Kim Vettenranta, Kaarle Franssila, Sakari Knuutila
Dátum:2003
ISSN:0390-6078
Megjegyzések:The lymphotoxin beta (LTB) gene, localized to the major histocompatibility complex region on chromosome 6p21.3, has an important role in the formation of germinal center reactions and regulation of immune response and apoptosis. Our aim was to determine LTB gene expression in different hematologic neoplasias. DESIGN AND METHODS: We determined the expression of LTB using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) on a series of RNA samples from CD3(+) T cells and CD19(+) B cells isolated from peripheral blood (n=7); CD19(+) B cells isolated from lymph nodes (n=11) and from patients with acute lymphoblastic leukemia (ALL; n=16), acute myeloid leukemia (AML; n=43), chronic myeloid leukemia (CML; n=12), mantle cell lymphoma (MCL; n=19), chronic lymphocytic leukemia (CLL; n=32) and small lymphocytic lymphoma (SLL; n=22). RESULTS: The expression level of LTB in CD3(+) T cells and CD19(+) B cells isolated from blood was ten to forty times lower than that in normal CD19(+) B cells isolated from lymph nodes. In malignant myeloid cells the expression levels were very low, whereas in malignant lymphoid cells the expression was higher than in myeloid cells, being highest in MCL and CLL (20.2+/-14.0 ng/microL and 81.0+/-116.3 ng/microL) and low in SLL (4.5+/-3.6 ng/microL; p=0.001). We did not find correlations between LTB expression and hematoclinical parameters (risk groups, immunophenotypes and overall survival). INTERPRETATION AND CONCLUSIONS: A distinct difference in expression of LTB in CLL and SLL indicates that these morphologically similar B-cell malignancies are molecularly different. Further studies are needed to investigate the prognostic value of LTB and any role that LTB may have in determining whether the malignant B cells manifest a leukemia or lymphoma.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
real-time
PCR
CLL
SLL
lyphotoxin
gene
expression
Megjelenés:Haematologica-The Hematology Journal. - 88 (2003), p. 654-658. -
További szerzők:Ferrer, Anna Larramendy, Marcelo L. Galimberti, Sara Aalto, Yan Casas, Silvia Vilpo, Juhani Ruutu, Tapani Vettenranta, Kim Franssila, Kaarle Knuutila, Sakari
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6.

001-es BibID:BIBFORM065344
Első szerző:Niini, Tarja
Cím:Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia : a cDNA array study / T. Niini, K. Vettenranta, J. Hollmén, M. L. Larramendy, Y. Aalto, H. Wikman, B. Nagy, J. K. Seppänen, A. Ferrer Salvador, H. Mannila, U. M. Saarinen-Pihkala, S. Knuutila
Dátum:2002
ISSN:0887-6924
Megjegyzések:Several specific cytogenetic changes are known to be associated with childhood acute lymphoblastic leukemia (ALL), and many of them are important prognostic factors for the disease. Little is known, however, about the changes in gene expression in ALL. Recently, the development of cDNA array technology has enabled the study of expression of hundreds to thousands of genes in a single experiment. We used the cDNA array method to study the gene expression profiles of 17 children with precursor-B ALL. Normal B cells from adenoids were used as reference material. We discuss the 25 genes that were most over-expressed compared to the reference. These included four genes that are normally expressed only in the myeloid lineages of the hematopoietic cells: RNASE2, GCSFR, PRTN3 and CLC. We also detected over-expression of S100A12, expressed in nerve cells but also in myeloid cells. In addition to the myeloid-specific genes, other over-expressed genes included AML1, LCP2 and FGF6. In conclusion, our study revealed novel information about gene expression in childhood ALL. The data obtained may contribute to further studies of the pathogenesis and prognosis of childhood ALL.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
expression
gene
myeloid
ALL
CDNA
array
Megjelenés:Leukemia. - 16 : 11 (2002), p. 2213-2221. -
További szerzők:Vettenranta, Kim Hollmén, Jaakko Larramendy, Marcelo L. Aalto, Yan Wikman, Harriet Nagy Bálint (1956-) (molekuláris genetikus) Seppänen, Jouni K. Salvador, Aurora Ferrer Mannila, Heikki Saarinen-Pihkala, Ulla Maija Knuutila, Sakari
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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:BIBFORM065337
Első szerző:Xie, Yuntao
Cím:Gene expression profile by blocking the SYT-SSX fusion gene in synovial sarcoma cells. Identification of XRCC4 as a putative SYT-SSX target gene / Yuntao Xie, Maria Törnkvist, Yan Aalto, Gunnar Nilsson, Leonard Girnita, Bálint Nagy, Sakari Knuutila, Olle Larsson
Dátum:2003
ISSN:0950-9232
Megjegyzések:Increasing evidence suggests that the SYT-SSX fusion gene plays an important role in synovial sarcoma development and progression. However, very little is known about the downstream targets of SYT-SSX. In this study, we used antisense oligonucleotides to block the expression of the SYT-SSX fusion gene in synovial sarcoma cells. By comparing SYT-SSX inhibited cells with noninhibited cells, the gene expression profile was analysed using cDNA microarray and established by real-time PCR. Herewith, using a filter containing 1176 cancer-relevant genes, we found that the DNA repair gene XRCC4 and the DNA mismatch repair gene MSH2 were downregulated, whereas the gene encoding for the serine/threonine protein kinase PRK (also known as CNK), and the macrophage inhibitory cytokine MICI (also known as PLAB) were upregulated after the inhibition of SYT-SSX. In comparison, expression of the XRCC4 gene was undergoing the strongest alteration. Consistently, the protein expression of XRCC4 was found to be decreased after SYT-SSX inhibition, whereas there were no detectable changes for the other gene products. Our study provides some clues to elucidate the signaling pathways of the SYT-SSX fusion gene, as well as it demonstrates a valuable model system for search for other SYT-SSX targets.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
gene
expression
synovial
carcinoma
SYT-SSX
fusion gene
Megjelenés:Oncogene. - 22 : 48 (2003), p. 7628-7631. -
További szerzők:Törnkvist, Maria Aalto, Yan Nilsson, Gunnar Girnita, Leonard Nagy Bálint (1956-) (molekuláris genetikus) Knuutila, Sakari Larsson, Olle
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9.

001-es BibID:BIBFORM065342
Első szerző:Zhu, Ying
Cím:Investigatory and analytical approaches to differential gene expression profiling in mantle cell lymphoma / Ying Zhu, Jaakko Hollmén, Riikka Räty, Yan Aalto, Balint Nagy, Erkki Elonen, Juha Kere, Heikki Mannila, Kaarle Franssila, Sakari Knuutila
Dátum:2002
ISSN:0007-1048
Megjegyzések:Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma of B-cell lineage. The blastoid variant of MCL, characterized by high mitotic rate, is clinically more aggressive than common MCL. We used the cDNA array technology to examine the gene expression profiles of both blastoid variant and common MCL. The data was analysed by regression analysis, principal component analysis and the naive Bayes' classifier. Eight genes were identified as differentially deregulated between the two groups. Oncogenes CMYC, BCL2 and PIM1 were upregulated more frequently in the blastoid variant than in common MCL. This implied that the gp130-mediated signal transducer and activator of transcription 3 (STAT3) signalling pathway was involved in the blastoid variant transformation of MCL. Other differentially deregulated genes were TOP1, CD23, CD45, CD70 and NFATC. By using the eight differentially deregulated genes, we created a classifier to distinguish the blastoid variant from common MCL with high accuracy. We also identified 18 genes that were deregulated in both groups. Among them, BCL1, CALLA/CD10 and GRN were suggested to be oncogenes. The products of RGS1, RGS2, ANX2 and CD44H were suggested to promote tumour metastasis. CD66D was suggested to be a tumour suppressor gene.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
gene
expression
mantle cell
lymphoma
Megjelenés:British Journal Of Haematology. - 119 (2002), p. 905-915. -
További szerzők:Hollmén, Jaakko Räty, Riikka Aalto, Yan Nagy Bálint (1956-) (molekuláris genetikus) Elonen, Erkki Kere, Juha Mannila, Heikki Franssila, Kaarle Knuutila, Sakari
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