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 nove...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 2weeks. 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-αand -βhad 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.展开更多
Imatinib (Gleevec ), Novartis Pharmaceuticals Corp, East Hanover, NJ) is wi dely used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. To our knowledge, only one case report of h...Imatinib (Gleevec ), Novartis Pharmaceuticals Corp, East Hanover, NJ) is wi dely used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. To our knowledge, only one case report of histologically proven Imatinib- induced hepatotoxicity has been reported. We describe another case of hepatotoxicity in a 22- year- old woman including the histopathologic changes and the clinical course after the discontinuation of Imatinib.展开更多
文摘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 2weeks. 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-αand -βhad 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.
文摘Imatinib (Gleevec ), Novartis Pharmaceuticals Corp, East Hanover, NJ) is wi dely used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. To our knowledge, only one case report of histologically proven Imatinib- induced hepatotoxicity has been reported. We describe another case of hepatotoxicity in a 22- year- old woman including the histopathologic changes and the clinical course after the discontinuation of Imatinib.
