TY - JOUR
T1 - Analysis of protein tyrosine kinases expression in the melanoma metastases of patients treated with Imatinib Mesylate (STI571, Gleevec™)
AU - Ivan, Doina
AU - Niveiro, Maria
AU - Diwan, A. Hafeez
AU - Eton, Omar
AU - Kim, Kevin B.
AU - Lacey, Carol
AU - Gonzalez, Cipriano
AU - Prieto, Victor G.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/4
Y1 - 2006/4
N2 - Background: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases. Methods: Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-α (PDGFR-α) and PDGFR-β] expression before and after being treated with Gleevec @ 400 mg bid for 2 weeks. Both, percentage of positive cells and staining intensity were evaluated. Results: We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-α and -β had the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs, namely c-abl, ARG, PDGFR-α, and β. Conclusions: Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction of PTKs expression under anti-tyrosine kinases treatment, suggesting its potential role in melanoma treatment.
AB - Background: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases. Methods: Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-α (PDGFR-α) and PDGFR-β] expression before and after being treated with Gleevec @ 400 mg bid for 2 weeks. Both, percentage of positive cells and staining intensity were evaluated. Results: We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-α and -β had the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs, namely c-abl, ARG, PDGFR-α, and β. Conclusions: Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction of PTKs expression under anti-tyrosine kinases treatment, suggesting its potential role in melanoma treatment.
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U2 - 10.1111/j.0303-6987.2006.00432.x
DO - 10.1111/j.0303-6987.2006.00432.x
M3 - Article
C2 - 16630177
AN - SCOPUS:33645405597
SN - 0303-6987
VL - 33
SP - 280
EP - 285
JO - Journal of cutaneous pathology
JF - Journal of cutaneous pathology
IS - 4
ER -