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_4 label "Selventa" provenance.
_3 value "Nevertheless, every tissue - including tumorigenic tissue - is dependent on adequate oxygen delivery. If oxygen is not sufficiently supplied, a battery of genes are induced by hypoxiainducible transcription factors (HIFs) that allow them to overcome hypoxic conditions34. Angiogenesis and tumour progression? The concept that angiogenesis is required for the expansion of a tumour mass raises the question as to when during tumour progression neovascularization occurs - is it simply a necessity to overcome size limitations, or is it coupled to a specific stage in a tumour's life cycle? There is increasing evidence from a variety of human tumours and mouse models of multistage cancers that angiogenesis can be switched on at different stages of tumour progression, depending on the nature of the tumour and the microenvironment. Historically, tumour-associated angiogenesis was thought to go through two phases, which are separated by the 'angiogenic switch' (FIG. 3). The first is defined as an avascular phase, which corresponds to small and occult lesions of not more than 1-2 mm in diameter. These lesions stay dormant by reaching a steady state between proliferation and apoptosis. Dormant tumours have been discovered during autopsies of individuals who died of causes other than cancer35. This supports the notion that only a very small subset of dormant tumours enter the second phase - the vascular phase - in which exponential tumour growth ensues. This same principle applies to tumour metastasis. Dormant metastases are a clinically difficult problem, as they can sometimes become activated by removal of the primary tumour10. Given the requirement of angiogenesis for growth and progression of dormant lesions, it would be assumed that inhibition of the angiogenic switch could prevent progression of tumours and their metastases. Preventative anti-angiogenic strategies could be especially useful in patients who are at high risk for developing cancer or recurrence of cancer, or development of metastases. A few experimental studies in animals, as well as in clinical trials, have already shown promising results. For example, angiostatin and endostatin reduced the formation of metastases in the Lewis lung cancer mouse model36,37. Linomide, which inhibits angiogenesis induction by various pro-angiogenic factors (such as VEGF, FGF and tumour necrosis factor-a (TNF-a))," provenance.
_3 wasQuotedFrom 12778130 provenance.
assertion hadPrimarySource 12778130 provenance.
large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
large_corpus.bel description "Approximately 61,000 statements." provenance.
assertion wasDerivedFrom large_corpus.bel provenance.
assertion wasDerivedFrom _3 provenance.
large_corpus.bel authoredBy _4 provenance.
large_corpus.bel version "1.4" provenance.