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Shaheen, N. & Richter, J. (2009). Barrett's oesophagus. Lancet 373(9666): 850-861. , & Frazier, W. (1995). Thrombospondin 1 expression in transformed endothelial cells restores a normal phenotype and suppresses their tumorigenesis. Proc Natl Acad Sci U S A 92(15): 6788-6792. , & Kim, S. (2011). Low expression of claudin-4 is associated with poor prognosis in esophageal squamous cell carcinoma. Ann Surg Oncol 18(1): 273-281. , & Wilding, G. (2005). A phase II multicenter, randomized, double-blind, safety trial assessing the pharmacokinetics, pharmacodynamics, and Molecular Biology Character of Esophageal Cancer 19 efficacy of oral 2-methoxyestradiol capsules in hormone-refractory prostate cancer.

Oncol Rep 2003; 10: 411–4. , B. , Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res 2005; 11: 6190–7. , Primary human fibroblasts induce diverse tumor invasiveness: Involvement of HGF as an important paracrine factor. Jpn J Cancer Res 1996; 87: 1134–1142. M. , Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma. Br J Cancer 2008; 98: 1102–8.

Binding of growth factors to their cognate receptors promote cellular proliferation through signal transduction cascades, initiated by the activation of membrane associated Ras proteins. Ras/Raf/mitogen activated protein kinase (MAPK) is one of the key Ras dependent growth-stimulating signaling cascade activated when growth factors bind their tyrosine kinase receptors, which ultimately leads to the induction of cyclin D1 [87, 88]. Fig. 4. A simplified overview of Ras activation and signaling cascade.

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