endothelin-1 and Hemangiosarcoma

Topics: Aged; Endothelin-1; Female; Hemangiosarcoma; Hormones, Ectopic; Humans; Neoplasms; Paraneoplastic Endocrine Syndromes; Vascular Neoplasms

Hemangiosarcoma (HSA) that originates from vascular endothelial cells is the most common splenic malignant neoplasm in dogs, as it accounts for approximately 20% of all canine soft tissue sarcomas. In this study, inhibitory effects of endothelin receptor antagonists on the growth of HSA cells were examined using cell lines established from canine HSA.. The preproendothelin-1 (PPET-1), endothelin type A receptor (ETA) and endothelin type B receptor (ETB) mRNA expression levels in HSA cell lines (n=5) were analyzed quantitatively by real-time RT-PCR. These levels were compared with those in HSA tissues (n=11) and those in normal splenic tissues (n=6). ETA and ETB protein expression was examined by western blot. The production and secretion of endothelin-1 (ET-1) and big ET-1 by cell lines were analyzed by measuring the levels in the culture medium by ELISA. The inhibitory effects of endothelin receptor antagonists (ambrisentan, BQ788 and bosentan) on cell growth were evaluated by WST-8 assay.. The PPET1 and ETA mRNA expression levels were elevated in HSA tissues and HSA cell lines compared with normal tissues. In cell lines, the production of ET-1 and big ET-1 peptide as well as the expression of ETA protein were detected, but the levels of ETB were not measured. Ambrisentan and bosentan inhibited growth activity in cell lines. Ambrisentan was more effective than bosentan.. These findings demonstrate the importance of the ETA axis in canine HSA as well as the potential of ETA inhibitors in the treatment of canine HSA.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Dog Diseases; Dogs; Doxorubicin; Endothelin Receptor Antagonists; Endothelin-1; Hemangiosarcoma; Phenylpropionates; Pyridazines; Receptor, Endothelin A; Receptor, Endothelin B

Haemangiosarcoma (HSA) is an important malignant neoplasm of dogs that originates from vascular endothelial cells. This study explored the suitability of using serum big endothelin-1 (ET-1) as a tumour marker for canine spontaneous HSA. Serum big ET-1 was measured in dogs with splenic HSA (n = 14), splenic malignant tumours other than HSA (n = 10), benign splenic lesions (n = 11) and normal healthy dogs (n = 17) by ELISA. Serum big ET-1 levels in dogs with HSA were significantly (P < 0.01) higher than in other dogs. High sensitivity (100%, 95% confidence interval 86-100%) and specificity (95%, 95% confidence interval 86-95%) for HSA diagnosis were obtained using a cut-off of 17 pg/mL according to receiver operating characteristic (ROC) curves (area under ROC curve 0.93). PPET1, ETA, VEGF and Hif1-α mRNA expression, measured by real-time PCR, were elevated in HSA compared with normal tissues. These findings suggest that elevated serum big ET-1 could be used as a diagnostic marker for canine HSA.

Topics: Animals; Biomarkers, Tumor; Case-Control Studies; Dog Diseases; Dogs; Endothelin-1; Gene Expression Regulation, Neoplastic; Hemangiosarcoma; Splenic Neoplasms

Haemangiosarcomas of animals are reported mainly in the dog and cat and less commonly in the cow, horse, pig and goat, but no cases have been reported in sheep. These tumours occur more commonly in internal sites than in the subcutis. A large mass in the right flank of a 6-year-old Sardinian sheep showed histopathological features of a haemangiosarcoma. The antibodies anti-Factor VIII-related antigen (FVIII-RAg) and anti-CD31 did not react immunohistochemically with either the normal or the neoplastic endothelial cells, whereas endothelin-1 strongly labelled both the normal and the neoplastic cells at different stages of differentiation. The results emphasize the usefulness of endothelin-1 as a vascular marker in sheep, particularly in the immunohistochemical detection of neoplastic endothelial cells.

Topics: Animals; Biomarkers, Tumor; Endothelin-1; Fatal Outcome; Hemangiosarcoma; Immunohistochemistry; Neoplasm Recurrence, Local; Sheep; Sheep Diseases; Skin Neoplasms

Topics: Arteriovenous Shunt, Surgical; Biomarkers, Tumor; Endothelin-1; Hemangiosarcoma; Humans; Kidney Transplantation; Male; Middle Aged; Renal Dialysis; Skin Neoplasms