{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:47:53Z","timestamp":1777276073314,"version":"3.51.4"},"reference-count":78,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T00:00:00Z","timestamp":1097539200000},"content-version":"vor","delay-in-days":3268,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[1995,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>One event that accompanies glioma progression is the upregulation of angiogenesis. Low\u2010grade gliomas are moderately vascularized tumors whereas high\u2010grade gliomas show prominent microvascular proliferations and areas of high vascular density. To analyze the molecular mechanisms underlying glioma angiogenesis, we studied the expression of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptors VEGFR\u20101 and VEGFR\u20102 during normal brain development and glioma\u2010induced angiogenesis. Our results suggest a paracrine control of angiogenesis and endothelial cell proliferation that is tightly regulated and transient in the embryonic brain, switched off in the normal adult brain, and turned on in tumor cells (VEGF) and the host vasculature (VEGFR\u20101 and \u22122) during tumor progression. It is unknown how VEGF and VEGF receptors are upregulated during glioma angiogenesis, but there is recent evidence that VEGF as well as endogenous inhibitors of angiogenesis could be under control of the tumor suppressor genes p53 and VHL. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.440150313","type":"journal-article","created":{"date-parts":[[2005,5,12]],"date-time":"2005-05-12T18:23:50Z","timestamp":1115922230000},"page":"339-347","source":"Crossref","is-referenced-by-count":261,"title":["Angiogenesis in malignant gliomas"],"prefix":"10.1002","volume":"15","author":[{"given":"Karl H.","family":"Plate","sequence":"first","affiliation":[]},{"given":"Werner","family":"Risau","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2004,10,12]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-67432-7_1"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116165"},{"key":"e_1_2_1_4_1","first-page":"347","article-title":"Tumor angiogenesis: A quantitative method for histological grading","volume":"48","author":"Brem S.","year":"1972","journal-title":"J. Natl. Cancer Inst."},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.114.2.521"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","unstructured":"Breier G. Clauss M. andRisau W.(1995)Coordinate expression of VEGF\u2010receptor 1 (flt\u20101) and its ligand suggests a paracrine regulation of murine vascular development.Developmental Dynamics(in press).","DOI":"10.1002\/aja.1002040303"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00218913"},{"key":"e_1_2_1_8_1","volume-title":"Intracranial Tumors: Notes Upon a Series of Two Thousand Verified Cases With Surgical\u2010Mortality Percentages Pertaining Thereto","author":"Cushing H.","year":"1932"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7521539"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1312256"},{"key":"e_1_2_1_11_1","first-page":"1471","article-title":"Tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors","volume":"7","author":"Dumont D. J.","year":"1992","journal-title":"Oncogene"},{"key":"e_1_2_1_12_1","first-page":"1293","article-title":"The endothelial\u2010specific receptor tyrosine kinase, tek, is a member of a new subfamily of receptors","volume":"8","author":"Durmont D. J.","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.16.1897"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.5.1275"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(93)90096-G"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(195803\/04)11:2<264::AID-CNCR2820110207>3.0.CO;2-D"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-13-1-18"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/82.1.4"},{"key":"e_1_2_1_19_1","first-page":"153","volume-title":"Cancer Medicine","author":"Folkman J.","year":"1993"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2432664"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)49853-0"},{"key":"e_1_2_1_22_1","first-page":"674","article-title":"p53 mutation and loss of heterozygosity on chromosome 17 and 10 during human astrocytoma progression","volume":"52","author":"Fults D.","year":"1992","journal-title":"Cancer Res."},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)41787-X"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.1.121"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90586-2"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-12-1806"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35712-0"},{"key":"e_1_2_1_28_1","first-page":"6571","article-title":"Enhanced expression of the tie receptor tyrosine kinase messenger RNA in the vascular endothelium of metastatic melanomas","volume":"54","author":"Kaipainen A.","year":"1994","journal-title":"Cancer Res."},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90593-2"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1705"},{"key":"e_1_2_1_31_1","first-page":"963","article-title":"Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression","volume":"9","author":"Kieser A.","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/362841a0"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V80.10.2548.2548"},{"key":"e_1_2_1_34_1","first-page":"395","article-title":"The mouse tie receptor tyrosine kinase gene: Expression during embryonic angiogenesis","volume":"9","author":"Korhonen J.","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-83771-5_261"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493574"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2479986"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/351453a0"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.20.9267"},{"key":"e_1_2_1_40_1","first-page":"1631","article-title":"Distinct rat genes with related profiles of expression define a TIE receptor tyrosine kinase family","volume":"8","author":"Maisonpierre P. C.","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90573-9"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/367576a0"},{"key":"e_1_2_1_43_1","first-page":"374","article-title":"Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo","volume":"71","author":"Minchenko A.","year":"1994","journal-title":"Lab. Invest."},{"key":"e_1_2_1_44_1","first-page":"35","article-title":"Hypoxia regulatory elements of the human vascular endothelial growth factor gene","volume":"40","author":"Minchenko A.","year":"1994","journal-title":"Cell. Mol. Biol. Res."},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/371072a0"},{"key":"e_1_2_1_46_1","first-page":"298","article-title":"Sequential loss of suppressor genes for three specific functions during in vivo carcinogenesis","volume":"63","author":"Moroco J. R.","year":"1990","journal-title":"Lab. Invest."},{"key":"e_1_2_1_47_1","first-page":"11","article-title":"NYK\/FLK\u20101: A putative receptor tyrosine kinase isolated from E10 embryonic neuroepithelium is expressed in endothelial cells of the developing embryo","volume":"8","author":"Oelrichs R. B.","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.12.1317"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.12.4.1698"},{"key":"e_1_2_1_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.19.8915"},{"key":"e_1_2_1_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/359845a0"},{"key":"e_1_2_1_52_1","first-page":"5822","article-title":"Upregulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis","volume":"53","author":"Plate K. H.","year":"1993","journal-title":"Cancer Res."},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1994.tb00835.x"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910590415"},{"key":"e_1_2_1_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90238-9"},{"key":"e_1_2_1_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0955-2235(90)90010-H"},{"key":"e_1_2_1_57_1","first-page":"58","volume-title":"The Development of the Vascular System","author":"Risau W.","year":"1991"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(85)90044-6"},{"key":"e_1_2_1_59_1","volume-title":"Pathology of Tumours of the Nervous System","author":"Russel D. S.","year":"1989"},{"key":"e_1_2_1_60_1","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-198011000-00001"},{"key":"e_1_2_1_61_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9355"},{"key":"e_1_2_1_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01889141"},{"key":"e_1_2_1_63_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.119.3.957"},{"key":"e_1_2_1_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.7.2864"},{"key":"e_1_2_1_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.10.4495"},{"key":"e_1_2_1_66_1","first-page":"519","article-title":"Nucleotide sequence and expression of a novel human receptor\u2010type tyrosine kinase (flt) closely related to the fms family","volume":"5","author":"Shibuya M.","year":"1990","journal-title":"Oncogene"},{"key":"e_1_2_1_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/359843a0"},{"key":"e_1_2_1_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90032-9"},{"key":"e_1_2_1_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90534-7"},{"key":"e_1_2_1_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90483-2"},{"key":"e_1_2_1_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99896-0"},{"key":"e_1_2_1_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99049-6"},{"key":"e_1_2_1_73_1","first-page":"40","article-title":"Das Glioblastoma multiforme. Bericht \u00fcber 2611 F\u00e4lle","volume":"6","author":"T\u00f6nnis W.","year":"1959","journal-title":"Acta Neurochir."},{"key":"e_1_2_1_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094-171"},{"key":"e_1_2_1_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47116-5"},{"key":"e_1_2_1_76_1","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-199409000-00012"},{"key":"e_1_2_1_77_1","first-page":"1358","article-title":"Up\u2010regulation of vascular endothelial growth factor and its receptors in von Hippel\u2010Lindau\u2010disease associated and in sporadic hemangioblastomas","volume":"55","author":"Wizigmann\u2010Voos S.","year":"1995","journal-title":"Cancer Res."},{"key":"e_1_2_1_78_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.2.489"},{"key":"e_1_2_1_79_1","first-page":"2683","article-title":"A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt\u20101 and KDR\/Flk\u20101)","volume":"9","author":"Yamane A.","year":"1994","journal-title":"Oncogene"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.440150313","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.440150313","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.440150313","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T12:43:50Z","timestamp":1692708230000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.440150313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,11]]},"references-count":78,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1995,11]]}},"alternative-id":["10.1002\/glia.440150313"],"URL":"https:\/\/doi.org\/10.1002\/glia.440150313","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,11]]}}}