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1.

001-es BibID:BIBFORM005174
035-os BibID:(scopus)38349044364 (wos)000253278400023
Első szerző:Barok Márk (biofizikus)
Cím:Trastuzumab decreases the number of circulating and disseminated tumor cells despite trastuzumab resistance of the primary tumor / Márk Barok, Margit Balázs, Péter Nagy, Zsuzsa Rákosy, Andrea Treszl, Enikő Tóth, István Juhász, John W. Park, Jorma Isola, György Vereb, János Szöllősi
Dátum:2008
ISSN:304-3835 (Print)
Megjegyzések:We have recently shown that despite of the fact that the ErbB2-positive JIMT-1 human breast cancer cells intrinsically resistant to trastuzumab in vitro, trastuzumab inhibited the outgrowth of early phase JIMT-1 xenografts in SCID mice via antibody-dependent cellular cytotoxicity (ADCC). Here we show that trastuzumab significantly reduces the number of circulating and disseminated tumor cells (CTCs and DTCs) in this xenograft model system at a time when the primary tumor is already unresponsive to trastuzumab. This observation suggests that ErbB2 positive CTCs and DTCs might be sensitive to trastuzumab-mediated ADCC even if when the primary tumor is already non-responsive. Thus, trastuzumab treatment might also be beneficial in the case of patients with breast cancer that is already trastuzumab resistant.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
analysis
Animals
antagonists and inhibitors
Antibodies
Antibodies, Monoclonal
Antigens
Antigens, CD45
Antineoplastic Agents
article
Biophysics
blood
Bone Marrow
Breast Neoplasms
Cell Line, Tumor
Cells
Chromosomes, Human,X
drug effects
Drug Resistance, Neoplasm
drug therapy
EGFR
Epidermal Growth Factor
ErbB2
Female
genetics
Histocompatibility Antigens
Histocompatibility Antigens Class I
Human
Humans
Hungary
Immunohistochemistry
immunology
In Situ Hybridization,Fluorescence
In Vitro
metabolism
Mice
Mice, Scid
mouse
Neoplasm Circulating Cells
Neoplasm Metastasis
pathology
pharmacology
Receptor, Epidermal Growth Factor
Research
Research Support
Support
therapeutic use
Time Factors
Trastuzumab resistance
Xenograft Model Antitumor Assays
egyetemen (Magyarországon) készült közlemény
Megjelenés:Cancer Letters. - 260 : 1-2 (2008), p. 198-208. -
További szerzők:Balázs Margit (1952-) (sejtbiológus, molekuláris genetikus) Nagy Péter (1971-) (biofizikus) Rákosy Zsuzsa (1978-) (sejtbiológus, molekuláris biológus, genetikus) Treszl Andrea (1974-) (molekuláris biológus) Tóth Enikő Juhász István (1956-) (bőrgyógyász, bőrsebész, kozmetológus, klinikai onkológus) Park, John W. Isola, Jorma Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus)
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2.

001-es BibID:BIBFORM001053
035-os BibID:(scopus)34447298092 (wos)000248154300017
Első szerző:Barok Márk (biofizikus)
Cím:Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance / Barok M., Isola J., Pályi-Krekk Zs., Nagy P., Juhász I., Vereb Gy., Kauraniemi P., Kapanen A., Tanner M., Vereb Gy., Szöllősi J.
Dátum:2007
Megjegyzések:Trastuzumab is a recombinant antibody drug that is widely used for the treatment of breast cancer. Despite encouraging clinical results, some cancers are primarily resistant to trastuzumab, and a majority of those initially responding become resistant during prolonged treatment. The mechanisms of trastuzumab resistance have not been fully understood. We examined the role of antibody-dependent cellular cytotoxicity (ADCC) using JIMT-1 cells that are ErbB2 positive but intrinsically resistant to trastuzumab in vitro. Unexpectedly, in experiments mimicking adjuvant therapy of submacroscopic disease in vivo (JIMT-1 cells inoculated s.c. in severe combined immunodeficiency mice), trastuzumab was able to inhibit the outgrowth of macroscopically detectable xenograft tumors for up to 5-7 weeks. The effect is likely to be mediated via ADCC because trastuzumab-F(ab')(2) was ineffective in this model. Moreover, in vitro ADCC reaction of human leukocytes was equally strong against breast cancer cells intrinsically sensitive (SKBR-3) or resistant (JIMT-1) to trastuzumab or even against a subline of JIMT-1 that was established from xenograft tumors growing despite trastuzumab treatment. These results suggest that ADCC may be the predominant mechanism of trastuzumab action on submacroscopic tumor spread. Thus, measuring the ADCC activity of patient's leukocytes against the tumor cells may be a relevant predictor of clinical trastuzumab responsiveness in vivo.
Tárgyszavak:Orvostudományok Természettudományok Elméleti orvostudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
ErbB2 receptor
trastuzumab
breast cancer
antibody therapy
Megjelenés:Molecular Cancer Therapeutics. - 6 : 7 (2007), p. 2065-2072. -
További szerzők:Isola, Jorma Pályiné Krekk Zsuzsanna (1974-) (molekuláris biológus) Nagy Péter (1971-) (biofizikus) Juhász István (1956-) (bőrgyógyász, bőrsebész, kozmetológus, klinikai onkológus) Vereb György (1938-) (biokémikus, sejtbiológus) Kauraniemi, Päivikki Kapanen, Anita I. Tanner, Minna Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus)
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3.

001-es BibID:BIBFORM042481
035-os BibID:(scopus)40049093067 (wos)000253576200006
Első szerző:Fazekas Zsolt (biofizikus)
Cím:Two-sided fluorescence resonance energy transfer for assessing molecular interactions of up to three distinct species in confocal microscopy / Zsolt Fazekas, Miklós Petrás, Ákos Fábián, Zsuzsanna Pályi-Krekk, Péter Nagy, Sándor Damjanovich, György Vereb, János Szöllősi
Dátum:2008
ISSN:1552-4922 1552-4930
Megjegyzések:The role of the expression patterns of proteins involved in oncogenesis can be understood after characterizing their multimolecular interactions. Conventional FRET methods permit the analysis of interaction between two molecular species at the most, which necessitates the introduction of new approaches for studying multicomponent signaling complexes. Flow cytometric as well as microscopic donor (dbFRET) and acceptor (abFRET) photobleaching FRET measurements were performed to determine the association states of ErbB2, b1-integrin, and CD44 receptors. Based on consecutively applied abFRET and dbFRET methods (two-sided FRET), the relationship of b1-integrin?ErbB2 heteroassociation to ErbB2 homoassociation and of b1-integrin?ErbB2 heteroassociation to ErbB2?CD44 heteroassociation was studied by correlating pixel-by-pixel FRET values of the corresponding abFRET and dbFRET images in contour plots. Anticorrelation was observed between b1-integrin?ErbB2 heteroassociation and ErbB2 homoassociation on trastuzumab sensitive N87 and SK-BR-3 cells, while modest positive correlation was found between b1-integrin?ErbB2 and ErbB2?CD44 heteroassociationon trastuzumab resistant MKN-7 cells. The FRET efficiency values of b1-integrin?ErbB2 heteroassociation were markedly higher at the focal adhesion regions on attachedcells than those measured by flow cytometry on detached cells. In conclusion, we implemented an experimental set-up termed two-sided FRET for correlating two pairwiseinteractions of three arbitrarily chosen molecular species. On the basis of our results, we assume that the homoassociation state of ErbB2 is dynamically modulated by its interaction with b1-integrins.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
beta1-integrin
abFRET
analysis
Biophysics
Carcinoma
CD44
Cell Adhesion
Cell Adhesion Molecules
Cell Line
Cells
Cholera Toxin
Confocal
Confocal microscopy
cytology
dbFRET
Energy Transfer
ErbB2
Flow Cytometry
Fluorescein
Fluorescence
fluorescence microscopy
Fluorescence Resonance Energy Transfer
FRET
Hiv-1
Human
Hungary
Image Cytometry
Image Processing
Kinetics
Laser scanning confocal microscopy
Luminescence
methods
Microscopy
Photobleaching
Protein-protein interactions
Proteins
Receptor tyrosine kinase
Research
Signal Transduction
Software
therapy
Trastuzumab resistance
tsFRET
Tyrosine
egyetemen (Magyarországon) készült közlemény
Megjelenés:Cytometry Part A. - 73 : 3 (2008), p. 209-219. -
További szerzők:Petrás Miklós (1977-) (orvos) Fábián Ákos István (1982-) (aneszteziológus) Pályiné Krekk Zsuzsanna (1974-) (molekuláris biológus) Nagy Péter (1971-) (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus) Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus)
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4.

001-es BibID:BIBFORM004864
035-os BibID:(scopus)26444452209 (wos)000232299300016
Első szerző:Friedländer Elza (biofizikus)
Cím:Signal transduction of erbB receptors in trastuzumab (Herceptin) sensitive and resistant cell lines : local stimulation using magnetic microspheres as assessed by quantitative digital microscopy / Friedlander, E., Arndt-Jovin, D. J., Nagy, P., Jovin, T. M., Szollosi, J., Vereb, G.
Dátum:2005
ISSN:1552-4922
Megjegyzések:ErbB2 (HER-2), a member of the epidermal growth factor (EGF) receptor family, is a class I transmembrane receptor tyrosine kinase. Although erbB2 has no known physiologic ligand, it can form complexes with other members of the family and undergo transactivation of its very potent kinase activity, thereby initiating downstream signaling and cell proliferation. ErbB2 is a frequent pathologic marker in ductal invasive breast carcinomas and is targeted by using a specific humanized monoclonal antibody, trastuzumab (Herceptin). The antibody is effective in only 20% to 50% of erbB2-positive tumors, and this resistance, as yet poorly understood, constitutes a major therapeutic challenge. METHODS: Magnetic microspheres coated with ligands or antibodies are widely used for separation of proteins and cells and allow localized, high intensity, and precisely timed stimulation of cells. We used EGF- and trastuzumab-covered paramagnetic microspheres, quantitative confocal laser scanning microscopy, and digital image processing to investigate the (trans)activation of and local signal propagation from erbB1 and erbB2 on trastuzumab sensitive and resistant carcinoma cell lines expressing these receptors at high levels. RESULTS: On A431 cells expressing high levels of endogenous erbB1 and transfected erbB2-mYFP (A4-erbB2-mYFP F4 cell line), EGF-coupled-microspheres activated erbB1 and transactivated erbB2-mYFP. In two other cell lines with comparable erbB2 expression but lower levels of erbB1, EGF microspheres transactivated erbB2 less efficiently. Trastuzumab in solution activated erbB2 on A4-erbB2-mYFP and the trastuzumab sensitive SKBR-3 cells, but only negligibly on the resistant JIMT-1 cells that showed a 10 times higher K(d) for the antibody. Nevertheless, pronounced erbB2 activation and tyrosine phosphorylation could be detected after stimulation with trastuzumab-coupled microspheres in all cell lines, although transactivation of erbB1 was negligible. Receptor phosphorylation was restricted to the immediate proximity of the microspheres, i.e., receptor clusters external to these locations remained inactive. CONCLUSION: ErbB1 ligand and erbB2 specific antibody attached to magnetic microspheres are efficient tools in assessing erbB activation, localized signal propagation, and erbB heterodimer formation. Trastuzumab coupled to microspheres is more efficient at accessing erbB2 and activating it than trastuzumab in solution
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Animals
Antibodies
Antibodies,Monoclonal
Biophysics
Carcinoma
Cell Line
Cell Line,Tumor
Cell Proliferation
Cells
chemistry
drug effects
Drug Resistance,Neoplasm
Epidermal Growth Factor
genetics
Humans
Hungary
Ligands
Magnetics
metabolism
methods
Microscopy
Microspheres
pharmacology
Phosphorylation
Proteins
Receptor,erbB-2
Research
Signal Transduction
Solubility
Support
Trans-Activation (Genetics)
Megjelenés:Cytometry. Part A. - 67 : 2 (2005), p. 161-171. -
További szerzők:Arndt-Jovin, Donna J. Nagy Péter (1971-) (biofizikus) Jovin, Thomas M. Szöllősi János (1953-) (biofizikus) Vereb György (1965-) (biofizikus, orvos)
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DOI
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5.

001-es BibID:BIBFORM006044
Első szerző:Matkó János (biológus)
Cím:Biphasic effect of extracellular ATP on the membrane potential of mouse thymocytes / Matko J., Nagy P., Panyi G., Vereb G. Jr., Bene L., Matyus L., Damjanovich S.
Dátum:1993
Megjegyzések:Extracellular ATP induced changes in the membrane potential of thymocytes from BALB/c mice were analyzed. At concentrations below 0.1 mM, ATP hyperpolarizes the cell membrane on the time scale of development of the Ca(2+)-signal. After a longer time hyperpolarization turns to depolarization. ATP concentrations higher than 0.5 mM caused rapid depolarization without previous hyperpolarization. Verapamil, quinine or the absence of extracellular Ca2+ blocked the hyperpolarization by ATP. In Na(+)-free medium the magnitude of depolarization decreased. Our data suggest a contribution of Ca(2+)-activated K+ channels to the hyperpolarizing effect of ATP at lower concentrations. The direction of membrane potential changes is determined presumably by a sensitive balance of ATP-receptor mediated Ca(2+)- and Na(+)-influx and the Ca(2+)-activated K(+)-channel activity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adenosine Triphosphate
Animal
Biophysics
Cell Membrane
cytology
drug effects
Hungary
Kinetics
Membrane Potentials
Mice
Mice,Inbred BALB C
pharmacology
physiology
Quinine
Support,Non-U.S.Gov't
Thymus Gland
Verapamil
Megjelenés:Biochemical and Biophysical Research Communications. - 191 : 2 (1993), p. 378-384. -
További szerzők:Nagy Péter (1971-) (biofizikus) Panyi György (1966-) (biofizikus) Vereb György (1965-) (biofizikus, orvos) Bene László (1963-) (biofizikus) Mátyus László (1956-) (biofizikus) Damjanovich Sándor (1936-2017) (biofizikus)
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DOI
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6.

001-es BibID:BIBFORM042484
035-os BibID:(scopus)23844475901 (wos)000231845600013
Első szerző:Mocanu, Maria-Magdalena
Cím:Associations of ErbB2, beta1-integrin and lipid rafts on Herceptin (Trastuzumab) resistant and sensitive tumor cell lines / Maria-Magdalena Mocanu, Zsolt Fazekas, Miklós Petrás, Péter Nagy, Zsolt Sebestyén, Jorma Isola, József Tímár, John W. Park, György Vereb, János Szöllősi
Dátum:2005
ISSN:0304-3835
Megjegyzések:ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2 association patterns involving integrins and lipid rafts. Flow cytometric FRET and confocal microscopic measurements revealed colocalization and molecular proximity between b1-integrins and ErbB2, as well as their association with lipid rafts. A weak functional interaction between ErbB2 and b1-integrin and the fact that ErbB2 did not co-patch with b1-integrins uponcrosslinking imply that ErbB2 and b1-integrin define two distinct molecular association clusters from a functional point of view. Although Herceptin-sensitive cell lines expressed more ErbB2 and fewer b1-integrin molecules on their surface than their resistant counterparts, this finding probably does not explain the Herceptin resistant phenotype due to the weak interaction between b1-integrins and ErbB2. Our results imply that the true significance of the expression profile of proteins involved inoncogenesis can only be understood after characterizing their molecular interactions.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Antibodies
Antibodies,Monoclonal
Antigens,CD29
Biophysics
Breast Neoplasms
Cell Line
Cell Membrane
Drug Resistance,Neoplasm
Humans
Hungary
Membrane Microdomains
metabolism
pathology
pharmacology
Phenotype
physiology
Proteins
Receptor,erbB-2
Research
Support
Tumor Cells,Cultured
egyetemen (Magyarországon) készült közlemény
Megjelenés:Cancer Letters. - 227 : 2 (2005), p. 201-212. -
További szerzők:Fazekas Zsolt (1971-) (biofizikus) Petrás Miklós (1977-) (orvos) Nagy Péter (1971-) (biofizikus) Sebestyén Zsolt Isola, Jorma Timár József Park, John W. Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus)
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DOI
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7.

001-es BibID:BIBFORM111996
Első szerző:Nagy Péter (biofizikus)
Cím:Novel single cell fluorescence approaches in the investigation of signaling at the cellular level / Péter Nagy, György Vereb, Janine N. Post, Elza Friedländer, János Szőllősi
Dátum:2005
ISSN:0932-2353
ISBN:9783540250647
Tárgyszavak:Orvostudományok Elméleti orvostudományok könyvfejezet
könyvrészlet
Megjelenés:Biophysical aspects of transmembrane signaling / szerk. Damjanovich Sándor. - p. 33-70. -
További szerzők:Vereb György (1965-) (biofizikus, orvos) Post, Janine N. Friedländer Elza (1980-) (biofizikus) Szöllősi János (1953-) (biofizikus)
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8.

001-es BibID:BIBFORM059574
Első szerző:Nagy Péter (biofizikus)
Cím:Measuring FRET in flow cytometry and microscopy / Péter Nagy, György Vereb, Sándor Damjanovich, László Mátyus, János Szöllősi
Dátum:2006
Tárgyszavak:Orvostudományok Elméleti orvostudományok könyvfejezet
Flow Cytometry
Microscopy
Megjelenés:Current Protocols in Cytometry. - p. 1-13.
További szerzők:Vereb György (1965-) (biofizikus, orvos) Damjanovich Sándor (1936-2017) (biofizikus) Mátyus László (1956-) (biofizikus) Szöllősi János (1953-) (biofizikus)
Pályázati támogatás:OTKA-F049025
OTKA
OTKA-T043509
OTKA
OTKA-T043061
OTKA
OTKA-T037831
OTKA
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Borító:

9.

001-es BibID:BIBFORM004878
035-os BibID:(scopus)26444586247 (wos)000232299300007
Első szerző:Nagy Péter (biofizikus)
Cím:Novel calibration method for flow cytometric fluorescence resonance energy transfer measurements between visible fluorescent proteins / Nagy, P., Bene, L., Hyun, W. C., Vereb, G., Braun, M., Antz, C., Paysan, J., Damjanovich, S., Park, J. W., Szollosi, J.
Dátum:2005
ISSN:1552-4922
Megjegyzések:The combination of fluorescence resonance energy transfer (FRET) and flow cytometry offers a statistically firm approach to study protein associations. Fusing green fluorescent protein (GFP) to a studied protein usually does not disturb the normal function of a protein, but quantitation of FRET efficiency calculated between GFP derivatives poses a problem in flow cytometry. METHODS: We generated chimeras in which cyan fluorescent protein (CFP) was separated by amino acid linkers of different sizes from yellow fluorescent protein (YFP) and used them to calibrate the cell-by-cell flow cytometric FRET measurements carried out on two different dual-laser flow cytometers. Then, CFP-Kip1 was coexpressed in yeast cells with YFP and cyclin-dependent kinase-2 (Cdk2) and served as a positive control for FRET measurements, and CFP-Kip1 coexpressed with a random peptide fused to YFP was the negative control. RESULTS: We measured donor, direct, and sensitized acceptor fluorescence intensities and developed a novel way to calculate a factor (alpha) that characterized the fluorescence intensity of acceptor molecules relative to the same number of excited donor molecules, which is essential for quantifying FRET efficiency. This was achieved by calculating FRET efficiency in two different ways and minimizing the squared difference between the two results by changing alpha. Our method reliably detected the association of Cdk2 with its inhibitor, Kip1, whereas the nonspecific FRET efficiency between Cdk2 and a random peptide was negligible. We identified and sorted subpopulations of yeast cells showing interaction between the studied proteins. CONCLUSIONS: We have described a straightforward novel calibration method to accurately quantitate FRET efficiency between GFP derivatives in flow cytometry
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
analysis
Biophysics
Calibration
Cells
chemistry
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase Inhibitor p27
Energy Transfer
Flow Cytometry
Fluorescence
Fluorescence Resonance Energy Transfer
Hungary
metabolism
methods
Protein Binding
Proteins
Research
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Support
Megjelenés:Cytometry. Part A. - 67 : 2 (2005), p. 86-96. -
További szerzők:Bene László (1963-) (biofizikus) Hyun, William C. Vereb György (1965-) (biofizikus, orvos) Braun, Manuel Antz, Christof Paysan, Jacques Damjanovich Sándor (1936-2017) (biofizikus) Park, John W. Szöllősi János (1953-) (biofizikus)
Internet cím:elektronikus változat
DOI
Borító:

10.

001-es BibID:BIBFORM004713
035-os BibID:(scopus)0037112996 (wos)000179662300005
Első szerző:Nagy Péter (biofizikus)
Cím:Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2 / Nagy, P., Vereb, G., Sebestyen, Z., Horvath, G., Lockett, S. J., Damjanovich, S., Park, J. W., Jovin, T. M., Szollosi, J.
Dátum:2002
Megjegyzések:The ErbB family of transmembrane receptor tyrosine kinases plays an important role in the pathogenesis of many cancers. The four members of the family, ErbB1-4, form various homo- and heterodimers during the course of signal transduction. A second hierarchical level of molecular associations involving 10(2)-10(3) molecules, termed large-scale clustering, has also been identified, but the regulatory factors and biological consequences of such structures have not been systematically evaluated. In this report, we describe the states of association of ErbB2 and their relationship to local ErbB3 density and lipid rafts based on quantitative fluorescence microscopy of SKBR-3 breast cancer cells. Clusters of ErbB2 colocalized with lipid rafts identified by the GM1-binding B subunit of cholera toxin. Pixel-by-pixel analysis of fluorescence resonance energy transfer between labeled antibodies indicated that the homoassociation (homodimerization) of ErbB2 was proportional to the local density of ErbB2 and inversely proportional to that of ErbB3 and of the raft-specific lipid GM1. Crosslinking lipid rafts with the B subunit of cholera toxin caused dissociation of the rafts and ErbB2 clusters, an effect that was independent of the cytoskeletal anchoring of ErbB2. Crosslinking also decreased ErbB2-ErbB3 heteroassociation and the EGF- and heregulin-induced tyrosine phosphorylation of Shc. When cells were treated with the anti-ErbB2 monoclonal antibody 4D5 (parent murine version of Trastuzumab used in the immunotherapy of breast cancer), internalization of the antibody was inhibited by crosslinking of lipid rafts, but the antiproliferative activity of 4D5 was retained and even enhanced. We conclude that local densities of ErbB2 and ErbB3, as well as the lipid environment profoundly influence the association properties and biological function of ErbB2.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Adaptor Proteins,Signal Transducing
Adaptor Proteins,Vesicular Transport
analysis
Antibodies
Antibodies,Monoclonal
Antineoplastic Agents
Biophysics
Breast Neoplasms
Carcinoma
Cell Division
Cell Membrane
Cell Transformation,Neoplastic
Cells
Cholera Toxin
Cytoskeletal Proteins
Dimerization
drug effects
Energy Transfer
Eukaryotic Cells
Female
Fluorescence
Fluorescence Resonance Energy Transfer
genetics
Humans
Hungary
Macromolecular Substances
Membrane Microdomains
metabolism
Microscopy
Oncogene Proteins v-erbB
pharmacology
Phosphorylation
physiology
Protein Binding
Protein-Tyrosine Kinases
Proteins
Receptor Protein-Tyrosine Kinases
Receptor,erbB-2
Receptor,erbB-3
Receptors,Cell Surface
Research
Signal Transduction
Support
Tumor Cells,Cultured
ultrastructure
Megjelenés:Journal of Cell Science. - 115 : Pt 22 (2002), p. 4251-4262. -
További szerzők:Vereb György (1965-) (biofizikus, orvos) Sebestyén Zsolt Horváth Gábor (1974-) (biofizikus) Lockett, Steven J. Damjanovich Sándor (1936-2017) (biofizikus) Park, John W. Jovin, Thomas M. Szöllősi János (1953-) (biofizikus)
Internet cím:elektronikus változat
elektronikus változat
Borító:

11.

001-es BibID:BIBFORM072316
035-os BibID:(WoS)000425895600022 (Scopus)85041571964
Első szerző:Nagyné Szabó Ágnes Timea (vegyész)
Cím:The Effect of Fluorophore Conjugation on Antibody Affinity and the Photophysical Properties of Dyes / Szabó Ágnes, Szendi-Szatmári Tímea, Ujlaky-Nagy László, Rádi Ildikó, Vereb György, Szöllősi János, Nagy Peter
Dátum:2018
ISSN:0006-3495
Megjegyzések:Because the degree of labeling (DOL) of cell-bound antibodies, often required in quantitative fluorescence measurements, is largely unknown, we investigated the effect of labeling with two different fluorophores (AlexaFluor546, AlexaFluor647) in a systematic way using antibody stock solutions with different DOLs. Here, we show that the mean DOL of the cell-bound antibody fraction is lower than that of the stock using single molecule fluorescence measurements. The effect is so pronounced that the mean DOL levels off at approximately two fluorophores/IgG for some antibodies. We developed a method for comparing the average DOL of antibody stocks to that of the isolated, cell-bound fraction based on fluorescence anisotropy measurements confirming the aforementioned conclusions. We created a model in which individual antibody species with different DOLs, present in an antibody stock solution, were assumed to have distinct affinities and quantum yields. The model calculations confirmed that a calibration curve constructed from the anisotropy of antibody stocks can be used for determining the DOL of the bound fraction. The fluorescence intensity of the cell-bound antibody fractions and of the antibody stocks exhibited distinctly different dependence on the DOL. The behavior of the two dyes was systematically different in this respect. Fitting of the model to these data revealed that labeling with each dye affects quantum yield and antibody affinity differentially. These measurements also implied that fluorophores in multiply labeled antibodies exhibit self-quenching and lead to decreased antibody affinity, conclusions directly confirmed by steady-state intensity measurements and competitive binding assays. Although the fluorescence lifetime of antibodies labeled with multiple fluorophores decreased, the magnitude of this change was not sufficient to account for self-quenching indicating that both dynamic and static quenching processes occur involving H-aggregate formation. Our results reveal multiple effects of fluorophore conjugation, which must not be overlooked in quantitative cell biological measurements.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Biophysical Journal. - 114 : 3 (2018), p. 688-700. -
További szerzők:Szendi-Szatmári Tímea (1989-) (molekuláris biológus) Ujlaky-Nagy László (1977-) (biofizikus) Rádi Ildikó Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM020768
Első szerző:Roszik János (biofizikus)
Cím:T-cell synapse formation depends on antigen recognition but not CD3 interaction : studies with TCR : zeta, a candidate transgene for TCR gene therapy / Roszik J., Sebestyén Z., Govers C., Guri Y., Szöor A., Pályi-Krekk Z., Vereb G., Nagy P., Szöllosi J., Debets R.
Dátum:2011
Megjegyzések:T-cell receptors (TCRs) can be genetically modified to improve gene-engineered T-cell responses, a strategy considered critical for the success of clinical TCR gene therapy to treat cancers. TCR:zeta, which is a heterodimer of TCRalpha and beta chains each coupled to complete human CD3zeta, overcomes issues of mis-pairing with endogenous TCR chains, shows high surface expression and mediates antigen-specific T-cell functions in vitro. In the current study, we further characterized TCR:zeta in gene-engineered T cells and assessed whether this receptor is able to interact with surface molecules and drive correct synapse formation in Jurkat T cells. The results showed that TCR:zeta mediates the formation of synaptic areas with antigen-positive target cells, interacts closely with CD8alpha and MHC class I (MHCI), and co-localizes with CD28, CD45 and lipid rafts, similar to WT TCR. TCR:zeta did not closely associate with endogenous CD3epsilon, despite its co-presence in immune synapses, and TCR:zeta showed enhanced synaptic accumulation in T cells negative for surface-expressed TCR molecules. Notably, synaptic TCR:zeta demonstrated lowered densities when compared with TCR in dual TCR T cells, a phenomenon that was related to both extracellular and intracellular CD3zeta domains present in the TCR:zeta molecule and responsible for enlarged synapse areas
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Adoptive Transfer
Antigens
Antigens,CD28
Antigens,CD3
Antigens,CD45
Antigens,CD8
article
Biophysics
Cells
Flow Cytometry
Gene Therapy
genetics
Histocompatibility Antigens
Histocompatibility Antigens Class I
Human
Humans
Hungary
Immunity,Cellular
Immunological Synapses
immunology
In Vitro
Jurkat Cells
lipid raft
LIPID RAFTS
Membrane Microdomains
metabolism
physiology
Receptor-CD3 Complex,Antigen,T-Cell
Receptors,Antigen,T-Cell,alpha-beta
Research
Research Support
Support
Synapses
T-Lymphocytes
therapy
Transgenes
Megjelenés:European Journal of Immunology. - 41 : 5 (2011), p. 1288-1297. -
További szerzők:Sebestyén Zsolt Govers, Coen Guri, Yakir Szöőr Árpád (1984-) (orvos) Pályiné Krekk Zsuzsanna (1974-) (molekuláris biológus) Vereb György (1965-) (biofizikus, orvos) Nagy Péter (1971-) (biofizikus) Szöllősi János (1953-) (biofizikus) Debets, Reno
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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