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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#_5 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#_4 http://www.w3.org/ns/prov#value As soon as these tumours are re-vascularized, they become extremely aggressive - patients who are diagnosed with glioblastomas have a median survival of only 1 year. In summary, microvessel density is only a useful prognostic marker for some cancer types. Overcoming angiogenic dependency? In contrast to tumour cells that are, by nature, genetically unstable and heterogeneous, endothelial cells are normal diploid cells that do not acquire mutations, and therefore should not become resistant to therapy. This rationale stimulated researchers to dream of a pantumour therapy focused on blood-vessel ablation. This dream, however, seems to be naive. Both animal and preliminary human clinical trials revealed that different tumours respond differently to anti-angiogenic therapy. Do these differences in response depend on the type or amount of angiogenic molecules that are expressed, or on other intrinsic tumour-cell characteristics, such as oncogene expression or resistance to hypoxia? Does anti-angiogenic therapy simply select for tumour cells that can grow at very low oxygen levels,without initiating neoangiogenesis or that use alternative pathways to circumvent neovascularization? Initial findings indicate that these effects might indeed happen in some tumour types.Anti-VEGF therapy in a rat model of glioblastoma resulted in decreased tumour vessel density and increased apoptosis.However, treatment also led to the increased co-option of existing blood vessels, circumventing the necessity of the tumour to initiate angiogenesis62. Examples of emerging resistance to anti-angiogenesis therapy include studies that showed that glioblastomas become resistant to TSP1 therapy63, renal-cell carcinomas become insenstitive to thalidomide64 and tumours that lose p53 expression become less responsive to combinations of low-dose cytotoxic and anti-angiogenic agents65. http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/12778130 http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/12778130 http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#_4 http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU#pubinfo http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU http://purl.org/dc/terms/created 2014-07-03T14:32:02.678+02:00 http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RA7pAo-j7MdU6YI9QZfB6D9AvTfd98CycD4IVACdjfJhU http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234