Angiogen + Inflam
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| Folkman 1971 | Hypothesized that tumour growth depends on angiogenesis. Widely ignored at the time.
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| Hurwitz 2004 | Clinical trials showing efficacy of avastin, a known vegf inhibitor, in trials against colorectal cancer. Slight increase in hypertension when added to chemotherapy but no other clear safety issues highlighted, possible slight increased risk of bleeding.
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| Klagsbrun 2005 | Review of nerve ligand-receptor pairs in angiogenic migration
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| Klement 2009 | Pro-angiogenic factors incr (labelled VEGF) and anti-angiogenic decr in platelets before levels change in serum/plasme. Released by degranulation when platelet adheres to abnormal vessels. Non-angiogenic dormant tumours only incr anti-angiogenic proteins.
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| Greene 2003 | Shows liver size increases beyond original when given FGF or VEGF and slows when a selective endothelial cell inhibitor is given from day of surgery in both cases. Angiogenic factors given intraperitoneal, inhibitors given subcutaneously
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| Kolonin 2004 | Used diet-induced mouse obesity. Caused selective apoptosis of WAT vasculature by an apoptotic peptide using prohibitin as a receptor (found in WAT vasculature). Surprisingly no fatty liver issues. Seemed to incr fat metabolism rather than reducing intake
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| Fulcher 1998 | Downs patients get less diabetic retinopathy, small sample but very high prevalence in long term diabetes. (also get less cancer, not discovered here)
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| Zorick 2001 | Found incr circulating endostatin. Variability is great within unaffected population so levels may be protective in some without Downs. Levels within Downs syndrome also vary greatly. May explain Downs resistance to cancer.
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| Lourenco 2006 | Polymorphism in endostatin associated with increased risk of breast cancer, case control study.
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| Sund 2005 | Used tetracycline inducible endostatin transfection to show that a 1.6 fold increase in circulating endostatin caused a 3 fold reduction in tumour growth. Increased level mimics Downs.
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| Sommer 1991 | African-Americans are protected from age-related amcular degeneration
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| Beecken 2001 | Despite common beliefs slow growing tumours also respond to angiogenesis inhibitors as do faster growing highly vascular tumours. Indicates higher doses may be good in vascular tumours as pro-vascular factors are upregulated.
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| Jain 2005 | I think it’s originally his idea, proposes increased drug delivery due to consolidation and 'normalisation' of the new blood vessels and pruning of leaky vessels.
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| Teicher 1994 | Increased oxygenation and sensitivity to radiotherapy after anti-angiogenic therapy
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| Browder 2000 | Induced drug resistance in tumours by repeated exposure to single v. high doses of chemo. Showed these tumours were still treatable when chemo was targeted to vessels as endothelium isnt resistant. Augmentable by angiogenesis inhibitors
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| Folkman 2007 | Review of angiogenesis and its possible roles in therapy
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| Deshpande 2010 | Bitter taste receptors activation causes airway dilation by opening K+ channels. Found expression of multiple isoforms although not all. Blocking these receptors inhibited response to bitter tastants. Response also blockable by PLC and Gby inhibitors.
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| Derendorf 2007 | Ciclesonide is an inhaled corticosteroid
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| De Bosscher 2010 | Review of future glucocorticoid receptor agonists. Future drugs may be biased agonists, receptor modulators or less able to desensitise. Future success of biased agonism depends on how reliant the effects of glucocorticoids are on transactivation.
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| Linden 2003 | VIP agonist has bronchodilator action but is not as good as beta agonists. Only acts short term in humans despite being longer lasting than beta blockers in guinea pigs.
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| Buckley 2011 | EP2 is the bronchodilating receptor for PGE in most animals but humans seem to use EP4 like rats as EP2 agonists failed. Study used specific agonists and antagonists to relax/contract human airway strips, results were same airway sizes. EP3 is irritating.
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| Evans 1996 | Leukotriene antagonists used but worse than inhaled steroids. LTB4 antagonist had no benefit on function but reduced neutrophils in bronchoalveolar lavage. Raises questions about importance of neutrophils. LTB4 also mediates mast and T cell chemotaxis.
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| Karin 2004 | Review of NFkB as a target. Success so far is through inhibiting breakdown of IkB which retains NFkB in cytoplasm, although non-selective. DNA binding inhibitors too large and polar. IKK (IkB kinase) needed for pathway, may be a selective target.
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| Hajra et al 2000 | NF-kB upregulated more in regions likely to form atherosclerotic lesions in the aorta. Not-uniformly upregulated. Used LPS to stimulate NF-kB expression. CAM adhesion molecules upregulated. Used immunostaining throughout
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