{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:11:55Z","timestamp":1792602715085,"version":"4.5.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,4,21]]},"abstract":"<jats:p>\n                    Recent studies suggest that tumor-associated CD11b\n                    <jats:sup>+<\/jats:sup>\n                    Gr1\n                    <jats:sup>+<\/jats:sup>\n                    myeloid cells contribute to refractoriness to antiangiogenic therapy with an anti-VEGF-A antibody. However, the mechanisms of peripheral mobilization and tumor-homing of CD11b\n                    <jats:sup>+<\/jats:sup>\n                    Gr1\n                    <jats:sup>+<\/jats:sup>\n                    cells are unclear. Here, we show that, compared with other cytokines [granulocyte-macrophage colony stimulating factor (GM-CSF), stromal derived factor 1\u03b1, and placenta growth factor], G-CSF and the G-CSF-induced Bv8 protein have preferential expression in refractory tumors. Treatment of refractory tumors with the combination of anti-VEGF and anti-G-CSF (or anti-Bv8) reduced tumor growth compared with anti-VEGF-A monotherapy. Anti-G-CSF treatment dramatically suppressed circulating or tumor-associated CD11b\n                    <jats:sup>+<\/jats:sup>\n                    Gr1\n                    <jats:sup>+<\/jats:sup>\n                    cells, reduced Bv8 levels, and affected the tumor vasculature. Conversely, G-CSF delivery to animals bearing anti-VEGF sensitive tumors resulted in reduced responsiveness to anti-VEGF-A treatment through induction of Bv8-dependent angiogenesis. We conclude that, at least in the models examined, G-CSF expression by tumor or stromal cells is a determinant of refractoriness to anti-VEGF-A treatment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0902280106","type":"journal-article","created":{"date-parts":[[2009,4,3]],"date-time":"2009-04-03T22:43:05Z","timestamp":1238798585000},"page":"6742-6747","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":427,"title":["G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models"],"prefix":"10.1073","volume":"106","author":[{"given":"Farbod","family":"Shojaei","sequence":"first","affiliation":[{"name":"Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Wu","sequence":"additional","affiliation":[{"name":"Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Qu","sequence":"additional","affiliation":[{"name":"Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Kowanetz","sequence":"additional","affiliation":[{"name":"Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Yu","sequence":"additional","affiliation":[{"name":"Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Tan","sequence":"additional","affiliation":[{"name":"Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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