{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:20:49Z","timestamp":1771003249313,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,3,30]],"date-time":"2006-03-30T00:00:00Z","timestamp":1143676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The platelet\u2010derived growth factor receptor (PDGFR) is a tyrosine kinase, implicated in the development and progression of different tumors, including gliomas. Chemoresistance is a common feature of malignant gliomas. Since receptor tyrosine kinases contribute to chemoresistance in tumors, we addressed whether PDGFR signaling might confer selective growth advantage to chemoresistant cells. The effects of the PDGFR inhibitor STI571 on proliferation and PDGFR signaling were compared in chemosensitive and cisplatin\u2010selected, chemoresistant sublines derived from glioma and from two other PDGFR\u2010expressing tumors (ovarian carcinoma and neuroblastoma). The chemoresistant glioma U87\/Pt cells were twofold more sensitive to STI571 growth\u2010inhibitory effects than the chemosensitive U87 cells, and two\u2010 to threefold more sensitive than five unrelated glioma cell lines. The other two paired cell lines were equally responsive. Sensitization of U87\/Pt cells correlated with upregulation of the PDGF\u2010B isoform and with PDGF\u2010BB\u2010induced Akt overactivation, which was prevented by STI571. STI571 specifically inhibited PDGF\u2010BB\u2010, but not PDGF\u2010AA\u2010 or stem cell factor\u2010mediated signaling. In serum\u2010containing medium, STI571 decreased phospho\u2010Akt in U87\/Pt cells, but not in U87, while activating extracellular signal\u2010regulated kinase (Erk) in both. STI571 antiproliferative effects were partially reverted by constitutively active Akt. Cotreatment with inhibitors of phosphatidylinositol 3\u2032\u2010kinase (PI3K) or mitogen\u2010activated protein kinase kinase (MEK) resulted in enhanced growth inhibition in glioma cells. Our results suggest that increased PDGF\u2010BB signaling may sensitize chemoresistant glioma cells to STI571, suggesting a therapeutic potential for STI571 in patients with malignant gliomas refractory to chemotherapy. Simultaneous blockade of PDGFR and PI3K or Erk pathway may enhance therapeutic targeting in gliomas. J. Cell. Physiol. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.20659","type":"journal-article","created":{"date-parts":[[2006,3,30]],"date-time":"2006-03-30T22:16:59Z","timestamp":1143757019000},"page":"220-228","source":"Crossref","is-referenced-by-count":42,"title":["Increased sensitivity to the platelet\u2010derived growth factor (PDGF) receptor inhibitor STI571 in chemoresistant glioma cells is associated with enhanced PDGF\u2010BB\u2010mediated signaling and STI571\u2010induced Akt inactivation"],"prefix":"10.1002","volume":"208","author":[{"given":"Tiziana","family":"Servidei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Riccardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Sanguinetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Dominici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Riccardi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,4,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2003.11.028"},{"issue":"1","key":"e_1_2_6_3_1","first-page":"139","article-title":"Abl protein\u2010tyrosine kinase inhibitor 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