Basic Informations

C.V

Shehata IbRAHIM aNWAR
1-1-1985
pHd GIFU UNIVERSITY

Master Title

Pathological Study on brain affection of small ruminants

Master Abstract

Pathological study on mechanisms of malignant proliferation of canine hemangiosarcomas Canine hemangiosarcoma (HSA) is a progressive endothelial cell (ECs) malignant neoplasm of dogs, resembling human angiosarcoma (AS) with poor prognosis. Despite their vascular origin, even the addition of novel anti-angiogenic drugs has shown a minimal to absent response in HSA. Thus, very little therapeutic progress has been made over the past several decades to increase the progression-free survival or overall patient survival of individuals suffering from this sarcoma, and effective therapeutics against this disease are desperately needed. There is increasing evidence that dysregulation of molecular pathways governing angiogenesis may be important in the biology of HSAs. Stand on the shoulders of this hypothesis, intensive research is needed to get deep understanding the role of angiogenic pathways in the biology of ECs. malignancies, and finding therapies targeting HSA and AS. In chapter 1, immunohistochemistry was utilised to confirm that newly formed vascular ECs express both urokinase plasminogen activator (uPA) and its receptor uPAR in granulation tissue. In contrast, quiescent ECs within normal dermal tissues were negative for these markers. Thus, the uPA and uPAR system are considered that it plays an important role in pathophysiological angiogenesis. Moreover, IHC analysis was performed for detection of uPA and uPAR proteins in clinical HSA and HA samples obtained from dogs. The expression of uPA and uPAR was significantly higher among HSAs than HAs. In addition, the expression of both ligand and receptor in HSA neoplastic endothelial cells seems to have a phenotype similar to that of active ECs during pathophysiological angiogenesis. Binding of uPA to its receptor promotes uPA activity, which then enhances the activation of plasminogen to plasmin. As a result, the detection of expression of both the ligand and the receptor within individual tumour cells indicates that the cells are likely capable of regulating plasminogen activation via uPA/uPAR production. The correlation between uPA/uPAR expression and the Ki67 labelling index was estimated in the HSA and HA tissues. Expression of both molecules was significantly higher in HSAs than in cutaneous HAs The average Ki67 labelling index of the uPA (+)/uPAR (+) HSAs was significantly higher than that of uPA (-)/uPAR (+) HSAs and HA tissues These results suggest that uPA and uPAR play a significant role in the malignant proliferation of canine HSA, regardless of the primary origin of the tumour. In chapter one, Immunohistochemistry was used to assess the expression of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in canine primary haemangiosarcomas (HSAs), canine cutaneous haemangiomas (HAs) and in control sections of canine cutaneous granulation tissue. In chapter 2, the expression levels of peroxiredoxin-6 (PRDX6) in spontaneous canine HSAs and HAs was investigated by IHC. analysis, identifying marked significant expression of this protein in canine HSAs than HAs. Furthermore, both PRDX6 mRNA and protein were overexpressed in HSA cell lines compared to normal canine endothelial cells. Notably, the small interfering RNA-induced downregulation of PRDX6 in HSA cell lines promoted apoptosis in the HSA cell lines. Suggesting that PRDX6 suppression increased the cytotoxicity of these cells and it might play an important cytoprotective role. The finding of the present studies indicates that uPA, uPAR, and PRDX-6 genes may be novel targets for the therapy of canine HSA, and in vivo models are needed to support further research into the therapy of canine HSA.

PHD Title

Pathological Study on Mechanisms of Malignant Proliferation of Canine Hemangiosarcomas

PHD Abstract

Pathological study on mechanisms of malignant proliferation of canine hemangiosarcomas Canine hemangiosarcoma (HSA) is a progressive endothelial cell (ECs) malignant neoplasm of dogs, resembling human angiosarcoma (AS) with poor prognosis. Despite their vascular origin, even the addition of novel anti-angiogenic drugs has shown a minimal to absent response in HSA. Thus, very little therapeutic progress has been made over the past several decades to increase the progression-free survival or overall patient survival of individuals suffering from this sarcoma, and effective therapeutics against this disease are desperately needed. There is increasing evidence that dysregulation of molecular pathways governing angiogenesis may be important in the biology of HSAs. Stand on the shoulders of this hypothesis, intensive research is needed to get deep understanding the role of angiogenic pathways in the biology of ECs. malignancies, and finding therapies targeting HSA and AS. In chapter 1, immunohistochemistry was utilised to confirm that newly formed vascular ECs express both urokinase plasminogen activator (uPA) and its receptor uPAR in granulation tissue. In contrast, quiescent ECs within normal dermal tissues were negative for these markers. Thus, the uPA and uPAR system are considered that it plays an important role in pathophysiological angiogenesis. Moreover, IHC analysis was performed for detection of uPA and uPAR proteins in clinical HSA and HA samples obtained from dogs. The expression of uPA and uPAR was significantly higher among HSAs than HAs. In addition, the expression of both ligand and receptor in HSA neoplastic endothelial cells seems to have a phenotype similar to that of active ECs during pathophysiological angiogenesis. Binding of uPA to its receptor promotes uPA activity, which then enhances the activation of plasminogen to plasmin. As a result, the detection of expression of both the ligand and the receptor within individual tumour cells indicates that the cells are likely capable of regulating plasminogen activation via uPA/uPAR production. The correlation between uPA/uPAR expression and the Ki67 labelling index was estimated in the HSA and HA tissues. Expression of both molecules was significantly higher in HSAs than in cutaneous HAs The average Ki67 labelling index of the uPA (+)/uPAR (+) HSAs was significantly higher than that of uPA (-)/uPAR (+) HSAs and HA tissues These results suggest that uPA and uPAR play a significant role in the malignant proliferation of canine HSA, regardless of the primary origin of the tumour. In chapter one, Immunohistochemistry was used to assess the expression of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in canine primary haemangiosarcomas (HSAs), canine cutaneous haemangiomas (HAs) and in control sections of canine cutaneous granulation tissue. In chapter 2, the expression levels of peroxiredoxin-6 (PRDX6) in spontaneous canine HSAs and HAs was investigated by IHC. analysis, identifying marked significant expression of this protein in canine HSAs than HAs. Furthermore, both PRDX6 mRNA and protein were overexpressed in HSA cell lines compared to normal canine endothelial cells. Notably, the small interfering RNA-induced downregulation of PRDX6 in HSA cell lines promoted apoptosis in the HSA cell lines. Suggesting that PRDX6 suppression increased the cytotoxicity of these cells and it might play an important cytoprotective role. The finding of the present studies indicates that uPA, uPAR, and PRDX-6 genes may be novel targets for the therapy of canine HSA, and in vivo models are needed to support further research into the therapy of canine HSA.