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1.

001-es BibID:BIBFORM004856
Első szerző:Bagossi Péter (biokémikus, vegyész)
Cím:Molecular modeling of nearly full-length ErbB2 receptor / Bagossi, P., Horvath, G., Vereb, G., Szollosi, J., Tozser, J.
Dátum:2005
ISSN:0006-3495
Megjegyzések:Members of the epidermal growth factor receptor family play important roles in various cellular processes, both in physiological and in pathological conditions. Dimerization and autophosphorylation of these receptor tyrosine kinases are key events of signal transduction. Details of the molecular events of the signaling are not entirely known. To facilitate the understanding of receptor structure and function at the molecular level, a molecular model was built for the nearly full-length ErbB2 dimer. Modeling was based on the x-ray or nuclear-magnetic resonance structures of extracellular, transmembrane, and intracellular domains. The extracellular domain was positioned above the cell membrane based on the distance determined from experimentally measured fluorescence resonance energy transfer. Favorable dimerization interactions are predicted for the extracellular, transmembrane, and protein kinase domains in the model of a nearly full-length dimer of ErbB2, which may act in a coordinated fashion in ErbB2 homodimerization, and also in heterodimers of ErbB2 with other members of the ErbB family
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
analysis
Cell Line, Tumor
Cell Membrane
chemistry
Comparative Study
Computer Simulation
Dimerization
Energy Transfer
Epidermal Growth Factor
Fluorescence
Fluorescence Resonance Energy Transfer
Humans
Hungary
Lipid Bilayers
methods
Models, Chemical
Models, Molecular
Neoplasms
Protein Conformation
Protein Structure, Tertiary
Receptor, erbB-2
Research
Signal Transduction
Structure-Activity Relationship
Support
ultrastructure
Megjelenés:Biophysical Journal. - 88 : 2 (2005), p. 1354-1363. -
További szerzők:Horváth Gábor (1974-) (biofizikus) Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész)
Internet cím:elektronikus változat
Borító:

2.

001-es BibID:BIBFORM073532
Első szerző:Barok Márk (biofizikus)
Cím:Cancer-derived exosomes from HER2-positive cancer cells carry trastuzumab-emtansine into cancer cells leading to growth inhibition and caspase activation / Mark Barok, Maija Puhka, Gyorgy Vereb, Janos Szollosi, Jorma Isola, Heikki Joensuu
Dátum:2018
ISSN:1471-2407
Megjegyzések:Background: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that carries a cytotoxic drug (DM1) toHER2-positive cancer. The target of T-DM1 (HER2) is present also on cancer-derived exosomes. We hypothesizedthat exosome-bound T-DM1 may contribute to the activity of T-DM1.Methods: Exosomes were isolated from the cell culture medium of HER2-positive SKBR-3 and EFM-192A breast cancercells, HER2-positive SNU-216 gastric cancer cells, and HER2-negative MCF-7 breast cancer cells by serial centrifugationsincluding two ultracentrifugations, and treated with T-DM1. T-DM1 not bound to exosomes was removed using HER2-coated magnetic beads. Exosome samples were analyzed by electron microscopy, flow cytometry and Westernblotting. Binding of T-DM1-containing exosomes to cancer cells and T-DM1 internalization were investigated withconfocal microscopy. Effects of T-DM1-containg exosomes on cancer cells were investigated with the AlamarBluecell proliferation assay and the Caspase-Glo 3/7 caspase activation assay.Results: T-DM1 binds to exosomes derived from HER2-positive cancer cells, but not to exosomes derived fromHER2-negative MCF-7 cells. HER2-positive SKBR-3 cells accumulated T-DM1 after being treated with T-DM1-containgexosomes, and treatment of SKBR-3 and EFM-192A cells with T-DM1-containing exosomes resulted in growth inhibitionand activation of caspases 3 and/or 7.Conclusion: T-DM1 binds to exosomes derived from HER2-positive cancer cells, and T-DM1 may be carried toother cancer cells via exosomes leading to reduced viability of the recipient cells. The results suggest a new mechanismof action for T-DM1, mediated by exosomes derived from HER2-positive cancer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Breast cancer
Trastuzumab-emtansine
T-DM1
HER2
Exosome
Megjelenés:Bmc Cancer. - 18 : 1 (2018), p. 504-516. -
További szerzők:Puhka, Maija Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Isola, Jorma Joensuu, Heikki
Pályázati támogatás:GINOP-2.3.2-15-2016-00020
GINOP
GINOP-2.3.2-15-2016-00050
GINOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM015664
Első szerző:Barok Márk (biofizikus)
Cím:Characterization of a novel, trastuzumab resistant human breast cancer cell line / Barok Mark, Balazs Margit, Lazar Viktoria, Rakosy Zsuzsa, Toth Eniko, Treszl Andrea, Vereb Gyorgy, Colbern G. T., Park J. W., Szollosi Janos
Dátum:2010
ISSN:1945-0508
Megjegyzések:HER2-positive breast cancers represent a distinct phenotype and are intrinsically more aggressive than HER2-negative tumors. Although HER2-targeted therapies have been rationally developed, resistance to these treatments represents a process understood poorly. There are few experimental models that allow studying the molecular mechanism of resistance. Our aim was to characterize a trastuzumab resistant breast cancer cell line (B585) that was established from an invasive ductal carcinoma. B585 grows only in immunodeficient mice as a xenograft. CGH and FISH were used to define cytogenetic alterations, gene-expression analysis and immunohistochemistry were applied to detect RNA and protein expression. By array-CGH focused amplifications were identified for C-MYC, EGFR, ErbB2, CCND1 and TOP2-A oncogenes. ErbB2 was co-amplified with TOP2-A. mRNA overexpression was detected for the amplified genes. ErbB2 protein was overexpressed and showed heterogeneous distribution. In summary, molecular cytogenetic analysis and expression profiling of B585 revealed several new alterations. Based on the experiments performed in SCID mice and the genotypic/phenotypic characteristics, this new in vivo breast cancer xenograft is a valuable model to investigate molecular mechanism of trastuzumab resistance
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
analysis
Animals
Antibodies
Antibodies,Monoclonal
Antineoplastic Agents
article
Biophysics
Breast Neoplasms
Carcinoma
Carcinoma,Ductal,Breast
Cell Line
Cell Line,Tumor
Comparative Genomic Hybridization
Disease Models,Animal
Drug Resistance,Neoplasm
drug therapy
EGFR
ErbB2
Female
Gene Expression
Gene Expression Profiling
genetics
Human
Humans
Hungary
Immunohistochemistry
In Situ Hybridization,Fluorescence
metabolism
Mice
Mice,Scid
Oncogenes
Phenotype
Receptor,erbB-2
Research
Research Support
rna
Support
therapeutic use
therapy
Trastuzumab resistance
OTKA::1
MAB::3.1
Megjelenés:Frontiers In Bioscience (elite edition). - 1 : 2 (2010), p. 627-640. -
További szerzők:Balázs Margit (1952-) (sejtbiológus, molekuláris genetikus) Lázár Viktória (1981-) (molekuláris biológus) Rákosy Zsuzsa (1978-) (sejtbiológus, molekuláris biológus, genetikus) Tóth Enikő Treszl Andrea (1974-) (molekuláris biológus) Vereb György (1965-) (biofizikus, orvos) Colbern, Gail T. Park, John W. Szöllősi János (1953-) (biofizikus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:

4.

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)
Internet cím:elektronikus változat
DOI
Borító:

5.

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)
Internet cím:elektronikus változat
DOI
Borító:

6.

001-es BibID:BIBFORM004832
035-os BibID:(scopus)12144266330 (wos)000225455700015
Első szerző:Citri, Ami
Cím:Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation / Citri, A., Gan, J., Mosesson, Y., Vereb, G., Szollosi, J., Yarden, Y.
Dátum:2004
Megjegyzések:ErbB-2/HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand-induced heterodimers with several growth factor receptors of the ErbB family. Hsp90 and co-chaperones regulate degradation of ErbB-2 but not other ErbB members. Here, we report that the role of Hsp90 in modulating the ErbB network extends beyond regulation of protein stability. The capacity of ErbB-2 to recruit ligand-bound receptors into active heterodimers is limited by Hsp90, which is dissociated from ErbB-2 following ligand-induced heterodimerization. We show that Hsp90 binds a specific loop within the kinase domain of ErbB-2, thereby restraining heterodimer formation and catalytic function. These results define a role for Hsp90 as a molecular switch regulating the ErbB signalling network by limiting formation of ErbB-2-centred receptor complexes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Amino Acid Motifs
Amino Acid Sequence
Dimerization
HSP90 Heat-Shock Proteins
metabolism
Molecular Sequence Data
physiology
Proteins
Receptor,erbB-2
Research
Signal Transduction
Support
Megjelenés:EMBO Reports. - 5 : 12 (2004), p. 1165-1170. -
További szerzők:Gan, Judith Mosesson, Yaron Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus) Yarden, Yosef
Internet cím:elektronikus változat
DOI
Borító:

7.

001-es BibID:BIBFORM050042
035-os BibID:PMID:23504771
Első szerző:Fábián Ákos István (aneszteziológus)
Cím:TripleFRET measurements in flow cytometry / Ákos Fábián, Gábor Horváth, György Vámosi, György Vereb, János Szöllősi
Dátum:2013
Megjegyzések:A frequently used method for viewing protein interactions and conformation, Forster (fluorescence) resonance energy transfer (FRET), has traditionally been restricted to two fluorophores. Lately, several methods have been introduced to expand FRET methods to three species. We present a method that allows the determination of FRET efficiency in three-dye systems on a flow cytometer. TripleFRET accurately reproduces energy transfer efficiency values measured in two-dye systems, and it can indicate the presence of trimeric complexes, which is not possible with conventional FRET methods. We also discuss the interpretation of energy transfer values obtained with tripleFRET in relation to spatial distribution of labeled molecules, specifically addressing the limitations of using total energy transfer to determine molecular distance
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
analysis
Antibodies
Antibodies,Monoclonal,Humanized
article
Biophysics
cell biology
Cell Line
chemistry
cytometry
Dyes
Energy Transfer
ENERGY-TRANSFER
FLOW
Flow Cytometry
Fluorescence
Fluorescence Resonance Energy Transfer
fluorescent dye
Fluorescent Dyes
FRET
Humans
Hungary
Immunoconjugates
immunology
methods
Protein Binding
PROTEIN INTERACTIONS
Research
Research Support
resonance energy transfer
Staining and Labeling
statistics & numerical data
Support
Megjelenés:Cytometry Part A. - 83 : 4 (2013), p. 375-385. -
További szerzők:Horváth Gábor (1974-) (biofizikus) Vámosi György (1967-) (biofizikus) Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus)
Pályázati támogatás:NK 101337
OTKA
K75752
OTKA
TÁMOP-4.2.2-08/1-2008-0019
TÁMOP
TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Receptor tirozin kinázok mint terápiás célpontok : működésük szabályozásának, és a közöttük fellépő molekuláris kölcsönhatások vizsgálata
TÁMOP-4.2.2.A-11/1/KONV-2012-0025
TÁMOP
Baross Gábor Program REG_EA_09-1-2009-0010
Egyéb
K77600
OTKA
K103965
OTKA
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

8.

001-es BibID:BIBFORM043019
035-os BibID:PMID:22997049
Első szerző:Fábián Ákos István (aneszteziológus)
Cím:The hitchhikers guide to cancer stem cell theory : markers, pathways and therapy / Ákos Fábián, György Vereb, János Szöllősi
Dátum:2013
Megjegyzések:Cancer stem cell (CSC) biology is a rapidly developing field within cancer research. CSCs are postulated to be a unique cell population exclusively capable of infinite self renewal, multilineage differentiation and with ability to evade conventional cytotoxic cancer therapy. These traits distinguish CSCs from their more differentiated counterparts, which possess only limited or no potential for self renewal and tumor initiation. Therefore, CSCs would be the driving motor of malignant growth and therapy resistance. Accordingly, successful cancer treatment would need to eliminate this highly potent group of cells, since even small residual numbers would suffice to recapitulate the disease after therapy. Putative CSCs has been identified in a broad range of human malignancies and several cell surface markers have been associated with their stem cell phenotype. Despite all efforts, a pure CSC population has not been isolated and often in vitro clonogenic and in vivo tumorigenic potential is found in several cell populations with occasionally contradictory surface marker signatures. Here, we give a brief overview of recent advances in CSC theory, including the signaling pathways in CSCs that also appear crucial for stem cells homeostasis in normal tissues. We discuss evidence for the interaction of CSCs with the stromal tumor environment. Finally, we review the emerging potentially effective CSC-targeted treatment strategies and their future role in therapy. (c) 2012 International Society for Advancement of Cytometry
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
article
Biophysics
cell biology
cell surface
Cells
cytometry
differentiation
GROWTH
Homeostasis
Human
Hungary
In Vitro
Phenotype
Research
review
stem cell
therapy
Megjelenés:Cytometry. Part A. - 83 : 1 (2013), p. 62-71. -
További szerzők:Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus)
Pályázati támogatás:NK 101337
OTKA
K 75752
OTKA
TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
Receptor tirozin kinázok mint terápiás célpontok: működésük szabályozásának, és a közöttük fellépő molekuláris kölcsönhatások vizsgálata
Baross Gábor Program REG_EA_09-1-2009-0010
Egyéb
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM010349
035-os BibID:(scopus)59049105873 (wos)000262061700007
Első szerző:Fábián Ákos István (aneszteziológus)
Cím:Die Hard : are cancer stem cells the Bruce Willises of tumor biology? / Fabian, A., Barok, M., Vereb, G., Szollosi, J.
Dátum:2009
ISSN:1552-4922 (Print)
Megjegyzések:In recent years, an exponentially growing number of studies have focused on identifying cancer stem cells (CSC) in human malignancies. The rare CSCs could be crucial in controlling and curing cancer: through asymmetric division CSCs supposedly drive tumor growth and evade therapy with the help of traits shared with normal stem cells such as quiescence, self-renewal ability, and multidrug resistance pump activity. Here, we give a brief overview of techniques used to confirm the stem cell-like behavior of putative CSCs and discuss markers and methods for identifying, isolating, and culturing them. We touch on the limitations of each marker and why the combined use of CSC markers, in vitro and in vivo assays may still fail to identify all relevant CSC populations. Finally, the various experimental findings supporting and contradicting the CSC hypothesis are summarized. The large number of tumor types thus far with a subpopulation of uniquely tumorigenic and therapy resistant cells suggests that despite the unanswered questions and inconsistencies, the CSC hypothesis has a legitimate role to play in tumor biology. At the same time, experimental evidence supporting the established alternative theory of clonal evolution can be found as wen. Therefore, a model that describes cancer initiation and progression should combine elements of clonal evolution and CSC theory.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Cells
Human
In Vitro
methods
therapy
Megjelenés:Cytometry. Part A. - 75A : 1 (2009), p. 67-74. -
További szerzők:Barok Márk (1976-) (biofizikus) Vereb György (1965-) (biofizikus, orvos) Szöllősi János (1953-) (biofizikus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:

10.

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)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

11.

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)
Internet cím:elektronikus változat
DOI
Borító:

12.

001-es BibID:BIBFORM005181
035-os BibID:(scopus)40149107884 (wos)000255092200005
Első szerző:Friedländer Elza (biofizikus)
Cím:ErbB-directed immunotherapy : antibodies in current practice and promising new agents / Elza Friedländer, Márk Barok, János Szöllősi, György Vereb
Dátum:2008
Megjegyzések:The ErbB family is well known for its significance in oncogenesis. As bad prognostic markers, overexpressed or mutated ErbB1 and ErbB2 have an important role in the molecular diagnosis of various cancers, but as membrane proteins, expressed often selectively in tumor tissues, they can be targeted with kinase inhibitors or therapeutic antibodies. In addition to trastuzumab, the first humanized antibody that was approved for the therapy of solid tumors by the FDA, now many humanized antibodies are in late clinical trials, or already approved. Conjugation of antibodies with radioactive isotopes, cytotoxic agents or liposomes loaded with chemotherapeutic drugs led to improved therapeutic efficiency over their parent "unarmed" antibodies. Novel, engineered antibody derivates with better pharmacodynamic properties are also available and allow the targeting of ErbB1 or ErbB2 positive cancers in a wider patient population. In this review, we discuss the biological and clinical background of ErbB targeting, and describe the most successful antibodies against ErbB1 (cetuximab, panitumumab, matuzumab, nimotuzumab, ICR62, mAb 528, ch806 and MDX-447) and ErbB2 (trastuzumab, pertuzumab, MDX-H210, 2B1, C6.5xscFv(NM3E2), ertumaxomab and FRP-5 derivates) that are in clinical trials or already approved, along with the various relevant conjugation and engineering strategies. Recent data pertinent to the prevalent problem of clinical resistance to treatment with trastuzumab are also discussed.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
agonists
analysis
Animal
Antibodies
Antibody conjugation
Antibody targeted delivery
Apoptosis
Biophysics
Brain
Carcinoma
Cell Line
Cell Proliferation
Cell Survival
Cells
Clinical trial
Cysteine
diagnosis
Dimerization
Down-Regulation
Drug Resistance
EGFR
Endocytosis
Engineered antibody
Epidermal Growth Factor
Epitopes
ErbB1
ErbB2
Fibroblasts
Glioblastoma
Glioma
Human
Humanized antibody
Hungary
In Vitro
Insulin
Membrane Proteins
Mice
Microscopy
Microspheres
Mutation
Necrosis
Paclitaxel
Phenotype
Phosphorylation
Prevalence
Progesterone
Proteins
radiotherapy
Research
Signal Transduction
therapy
toxicity
Trastuzumab resistance
Tumor Necrosis Factor
Tumor therapy/cancer therapy
Tyrosine
Up-Regulation
Megjelenés:Immunology Letters. - 116 : 2 (2008), p. 126-140. -
További szerzők:Barok Márk (1976-) (biofizikus) Szöllősi János (1953-) (biofizikus) Vereb György (1965-) (biofizikus, orvos)
Internet cím:elektronikus változat
DOI
elektronikus változat
Borító:
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