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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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2.

001-es BibID:BIBFORM005188
Első szerző:Pályiné Krekk Zsuzsanna (molekuláris biológus)
Cím:EGFR and ErbB2 are functionally coupled to CD44 and regulate shedding, internalization and motogenic effect of CD44 / Palyi-Krekk, Z., Barok, M., Kovacs, T., Saya, H., Nagano, O., Szollosi, J., Nagy, P.
Dátum:2008
ISSN:304-3835 (Print)
Megjegyzések:Activation of the ErbB family of receptor tyrosine kinases is involved in a range of human cancers. Transmembrane signaling mediated by ErbB proteins is stimulated by peptide growth factors and is blocked by monoclonal antibodies such as trastuzumab and pertuzumab. ErbB receptors exert their function in conjunction with non-ErbB proteins, e.g. CD44. Here we show that epidermal growth factor (EGF) and heregulin induce CD44 shedding in JIMT-1, an ErbB2-overexpressing cell line resistant to trastuzumab, accompanied by internalization and intramembrane proteolysis of CD44 and enhanced cellular motility. These effects of EGF and heregulin are blocked by pertuzumab. Trastuzumab inhibits the heregulin- and hyaluronan oligosaccharide-induced shedding and internalization of CD44 and their motogenic effect. Trastuzumab also blocks CD44 shedding from JIMT-1 xenograft tumors in vivo. At the same time the internalization rate of trastuzumab is increased by hyaluronan oligosaccharide treatment in vitro. Our experiments point to an unexpected, but potentially important mechanism of action of ErbB receptor-targeted monoclonal antibodies used in the treatment of cancer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Antibodies
article
Biophysics
CD44
Cell Line
EGFR
Epidermal Growth Factor
ErbB2
Human
Hungary
In Vitro
Proteins
Receptor tyrosine kinase
transmembrane signaling
Tyrosine
Megjelenés:Cancer Letters 263 : 2 (2008), p. 231-242. -
További szerzők:Barok Márk (1976-) (biofizikus) Kovács Tamás (1985-) (általános orvos) Saya, Hideyuki Nagano, Osamu Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
Internet cím:elektronikus változat
DOI
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3.

001-es BibID:BIBFORM002762
035-os BibID:(scopus)35448969823 (wos)000251600200021
Első szerző:Pályiné Krekk Zsuzsanna (molekuláris biológus)
Cím:Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer / Palyi-Krekk Z., Barok M., Isola J., Tammi M., Szollosi J., Nagy P.
Dátum:2007
Megjegyzések:Although trastuzumab, a recombinant humanised anti-ErbB2 antibody, is widely used in the treatment of breast cancer, neither its mechanism of action, nor the factors leading to resistance are fully understood. We have previously shown that antibody-dependent cellular cytotoxicity is pivotal in the in vivo effect of trastuzumab against JIMT-1, a cell line showing in vitro resistance to the antibody, and suggested that masking of the trastuzumab-binding epitope by MUC-4, a cell surface mucin, took place. Here, we further explored the role of masking of ErbB2 in connection with CD44 expression and synthesis of its ligand, hyaluronan. We show that high expression of CD44 observed in JIMT-1 cells correlates with ErbB2 downregulation in vivo, while siRNA-mediated inhibition of CD44 expression leads to decreased rate of trastuzumab internalisation and low cell proliferation in vitro. An inhibitor of hyaluronan synthesis, 4-methylumbelliferon (4-MU) significantly reduced the hyaluronan level of JIMT-1 cells both in vivo and in vitro leading to enhanced binding of trastuzumab to ErbB2 and increased ErbB2 down-regulation. Furthermore, the inhibitory effect of trastuzumab on the growth of JIMT-1 xenografts was significantly increased by 4-MU treatment. Our results point to the importance of the CD44-hyaluronan pathway in the escape of tumour cells from receptor-oriented therapy
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Antibodies
Biophysics
Cell Line
Cell Proliferation
Cells
Down-Regulation
Hungary
In Vitro
therapy
Megjelenés:European Journal of Cancer. - 43 : 16 (2007), p. 2423-2433. -
További szerzők:Barok Márk (1976-) (biofizikus) Isola, Jorma Tammi, Markku (kutatóorvos) Szöllősi János (1953-) (biofizikus) Nagy Péter (1971-) (biofizikus)
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4.

001-es BibID:BIBFORM005195
Első szerző:Szöllősi János (biofizikus)
Cím:Role of Egf receptor tyrosine kinases in breast cancer : a biophysical approach / Szollosi, J., Vereb, G., Barok, M., Palyi-Krekk, Z., Nagy, P.
Dátum:2008
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
Receptor tyrosine kinase
Tyrosine
Megjelenés:Cytometry. Part B. - 74B : 6 (2008), p. 385. -
További szerzők:Vereb György (1965-) (absztraktok, könyvfejezetek) Barok Márk (1976-) (biofizikus) Pályiné Krekk Zsuzsanna (1974-) (molekuláris biológus) Nagy Péter (1971-) (biofizikus)(absztraktok)
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