title: Analysis of protein tyrosine kinases expression in the melanoma metastases of patients treated with Imatinib Mesylate (STI571, Gleevec).
abstract: 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-alpha (PDGFR-alpha) and PDGFR-beta] 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-alpha and -beta 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-alpha, and beta.
  
  
  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.
authors.affiliation: Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors.forename: Doina
authors.initials: D
authors.lastname: Ivan
authors.forename: Maria
authors.initials: M
authors.lastname: Niveiro
authors.forename: A Hafeez
authors.initials: AH
authors.lastname: Diwan
authors.forename: Omar
authors.initials: O
authors.lastname: Eton
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Kim
authors.forename: Carol
authors.initials: C
authors.lastname: Lacey
authors.forename: Cipriano
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology* / Q000556:secondary; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; D016315:Proto-Oncogene Proteins c-abl