Haemangiosarcoma (HSA) is a relatively common malignant neoplasm in dogs, accounting for approximately 20% of all soft tissue sarcomas (Smith, 2003) and 4% of all malignant canine neoplasms (Göritz et al., 2013). Although canine HSA can occur at any site, the spleen, right atrium of the heart, liver and skin are the most common primary sites (Smith, 2003). In view of the aggressive behaviour of HSAs, the prognosis is poor, with reported 1 year survival rates of <10% (Hammer et al, 1991, Vail et al, 1995 and Sorenmo et al, 2000). Early diagnosis and treatment of canine HSA is correlated with improved prognosis (Spangler, Culbertson, 1992 and Sorenmo et al, 2000) and therefore a tumour marker for early diagnosis of HSA would be useful.Endothelin-1 (ET-1) is a bioactive peptide originally isolated from vascular endothelial cells (Yanagisawa et al., 1988). ET-1 is expressed in a range of human tumours and is involved in tumourigenesis (Smollich, Wülfing, 2007 and Bagnato, Rosanò, 2008). Blood concentrations of ET-1 are increased in human patients with prostatic, ovarian, breast, intestinal, pulmonary or bone tumours (Nakamuta et al, 1993, Nelson et al, 1995,Ferrari-Bravo et al, 2000 and Simpson et al, 2000), suggesting the potential of serum ET-1 as a tumour marker. We recently demonstrated that serum concentrations of big ET-1, a precursor of ET-1, are higher in canine HSA than in other types of tumours (Fukumoto et al., 2014).In this study, we investigated the potential of big ET-1 as a tumour marker for canine HSA because it is stable in blood and has a longer half-life than ET-1 (Hemsén et al., 1995). We also studied transcriptional correlation of the preproendothelin-1 (PPET-1) gene with the endothelin-related genes for endothelin type A receptor (ETA), endothelin type B receptor (ETB), vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1-α (Hif1-α) in canine HSA.
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