Tumour vascularity

Delorme S, Knopp M. Non-invasive vascular imaging Assessing tumour vascularity. Eur... 

Maeda, H., Wu, J., Sawa, T., Matsumura, Y., Hori, K., 2000. Tumour vascular permeability and the EPR effect in macromolecular therapeutics a review. Journal of Controlled Release 65, 271-284. 

Miles KA (2003) Perfusion CT for the assessment of tumour vascularity which protocol Br J Radiol 76 S36-S42... 

The indications and contraindications for laser ablation, and the main complications and methods of follow-up are the same as for radiofrequency ablation and microwave coagulation. The procedures are usually guided with CT or ultrasound although MR is sometimes used as well. By inserting up to eight fibres simultaneously it is possible to achieve confluent necrosis of 6-7 cm in diameter. The ultimate burn size is governed by the tumour vascularity and by the vasodilatory response of surrounding normal liver parenchyma. 

ET-1 also stimulates anti-apoptotic signal cascades in fibroblasts, vascular smooth muscles and endothelial cells (via phosphatidylinositol-3-kinase and Akt/pro-tein kinase B). In prostate and ovarian cancer, upregulation of endothelin synthesis and ETA receptors has been associated with a progression of the disease. The inhibiton of ETA receptors results in a reduced tumour growth. In malignant melanoma, ETB receptors are associated with tumour progression. Endothelins can also stimulate apoptosis in stretch-activated vessels via the ETB receptor, which contrasts the above-mentioned effects. The molecular basis for these differential anti- and pro-apoptotic reactions mediated by endothelins remains elusive. 

IkB inhibitory protein kappa B lCAM-1 intercellular adhesion molecule 1 lL-1 interleukin-1 LDL low density lipoprotein MAPKs mitogen activated protein kinases MCP-1 macrophage chemotactic protein 1 M-CSF macrophage colony stimulating factor mmLDL minimally modified LDL NAC A-acetylcysteine NF-kB nuclear factor-kappa B oxLDL oxidised LDL PKC protein kinase C PMA phobol myristate acetate ROS reactive oxygen species TNF-a tumour necrosis factor alpha AM-1 vascular cell adhesion molecule 1... 

McCusker SM, Curran MD, Dynan KB, McCullagh CD, Urquhart DD, Middleton D et al. Association between polymorphism in regulatory region of gene encoding tumour necrosis factor a and risk of Alzheimer s disease and vascular dementia a case-control study. Lancet 2001 357 436 139. 

The major clinical study underpinning product approval was a randomized, double blind study in which 71 CTCL patients were administered the product at one of two dosage levels (9 or 18 [tg kg 1 day ) overall, 30 per cent of patients experienced an objective tumour response. Serious side effects potentially associated with product administration include acute hypersensitivity-type reactions, vascular leak syndrome and visual impairment. Additional adverse reactions include flu-like symptoms, headache, hyper- or hypo-tension, as well as digestive upset. Ontak is manufactured by Seragen Inc. and is distributed by Ligand Pharmaceuticals. 

The antibody brings about its effect by inhibiting angiogenesis (the formation of new blood vessels), a process required to support tumour growth. Specifically, the antibody binds human vascular endothelial growth factor. This prevents the latter from binding to its cell surface receptor, a process central to triggering new blood vessel formation in both normal and diseased tissue. 

Other limitations of mouse/rat models are that tumour growth is different in the animal model compared to the situation in man.Tumour growth is more rapid in the rat/mouse model which has an effect on vascularization and intra-tumoural pressure for example. These factors can, as discussed in Section 8.4, have great impact on tumour penetration and uptake of the MAb-based drug-targeting constructs. 

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