P. Salven - Academia.edu (original) (raw)
Papers by P. Salven
Cancer Research
tumor tissuesbecauseof the lack of molecularmarkers. Here, monoclonal antibodies against the extr... more tumor tissuesbecauseof the lack of molecularmarkers. Here, monoclonal antibodies against the extracellular domain of the vascular endothelial growth factor-C receptor that we have named VEGFR-3 were found to specifically stain endothelial cells of lymphatic vessels and vessels around tumors such as lymphoma and in situ breast carcinoma. Interestingly, the spindle cells of several cutaneous nodular AIDS-associated Kaposi's sar come and the endothelium around the nodules were also VEGFR-3 positive. The first specific molecular marker for the lymphatic endothe ilum should provide a useful tool for the analysis of lymphatic vessels in maligp@nt tumors and their metastases and the cellular origin and differ entlatlon of Kaposi's sarcomas.
British Journal of Cancer, 1997
Clinical cancer research : an official journal of the American Association for Cancer Research, 2001
Multiple hemangioblastomas (HBs) of the central nervous system (CNS) and retina are associated wi... more Multiple hemangioblastomas (HBs) of the central nervous system (CNS) and retina are associated with von Hippel-Lindau disease (VHL) and also predispose individuals to renal cell carcinomas and visceral cysts. In VHL, microsurgery or radiosurgery cannot prevent new HBs from arising in the CNS or coagulation of retinal HBs. Multiple but thus far asymptomatic HBs pose a therapeutic problem. IFN-alpha-2a has antiangiogenic activity with an especially favorable effect on life-threatening hemangiomas of the liver in children. This is the first study to assess the efficacy of IFN-alpha-2a in treatment of asymptomatic HBs of the CNS and retina. Four patients (three with VHL) with a combined total of 15 HBs of the CNS, 3 HBs of the retina, and 14 renal and 2 pancreatic cysts were treated with s.c. IFN-alpha-2a for 12 months at 3 x 10(6) IU, 3 times/week. Baseline workup consisted of detailed neurological, ophthalmological, and radiological examinations. Follow-up studies at 3, 13, and 21 mon...
Blood, Jan 15, 1999
Basic fibroblast growth factor (bFGF) is a secreted multifunctional cytokine and a potent stimula... more Basic fibroblast growth factor (bFGF) is a secreted multifunctional cytokine and a potent stimulator of angiogenesis in vivo. Elevated bFGF concentrations have been detected in the serum and urine of cancer patients. We measured bFGF by enzyme-linked immunosorbent assay from sera taken from 160 non-Hodgkin's lymphoma (NHL) patients before treatment and stored at -20 degrees C. The patients had been observed for at least 5 years or until death. Serum bFGF concentrations (S-bFGF) ranged from undetectable to 34.7 pg/mL (median, 3.3 pg/mL). S-bFGF was detectable with a similar frequency in all subtypes of NHL. A high pretreatment S-bFGF was associated with poor overall survival. The 5-year survival rate of the patients within the highest quartile of S-bFGF concentrations (S-bFGF = 5.5 pg/mL) was only 39%, in contrast to a 60% survival rate of the patients with lower S-bFGF (P =.019). A high S-bFGF (within the highest quartile) was associated with poor outcome also in large-cell diff...
Blood, Jan 15, 1997
Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which ... more Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which is induced by hypoxia and is angiogenic in vivo. Recently, elevated serum concentrations of VEGF (S-VEGF) have been reported in patients with cancers of various histologies. However, the prognostic significance of S-VEGF in human cancer is unknown and the origin of S-VEGF remains unsettled. We measured S-VEGF by enzyme-linked immunosorbent assay from sera taken from 82 patients with non-Hodgkin's lymphoma before treatment and stored for 9 to 15 years at -20 degrees C. All but one of the patients had been followed-up for at least 5 years or until death. S-VEGF ranged from 15 to 964 pg/mL; median, 228 pg/mL; mean, 291 pg/mL. A higher than the median S-VEGF level was associated with a poor World Health Organization performance status, a high International Prognostic Index, a high serum lactate dehydrogenase level, and a large cell histology. Patients with lower than the median S-VEGF at...
Breast Cancer Research and Treatment, 1999
Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular ... more Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. Many types of malignant human tumors have been shown to produce VEGF. Recently, increased serum concentrations of VEGF (S-VEGF) have been reported in patients with various types of cancer, and high S-VEGF levels have also been associated with unfavorable prognosis. We have now measured S-VEGF in sera taken from 105 patients with a benign breast tumor or breast cancer. None of the women with a benign breast tumor had S-VEGF higher than 328 pg/ml (median, 57 pg/ml) whereas S-VEGF levels in metastatic breast cancer ranged from 7 to 1347 pg/ml (median, 186 pg/ml; P = 0.0018), and in locoregional breast cancer from 11 to 539 pg/ml (median, 104 pg/ml; P = 0.13). S-VEGF was higher in patients with locoregional ductal cancer (median, 107 pg/ml) than in those with locoregional lobular cancer (median, 44 pg/ml; P = 0.029) or in patients with benign breast tumor (median, 57 pg/ml; P = 0.033). Patients with metastatic cancer undergoing therapy had lower S-VEGF than those who had symptomatic treatment only (P = 0.021). The results indicate that dissemination of breast cancer may be accompanied by an elevation of circulating VEGF and that primary ductal cancers are associated with higher S-VEGF levels than lobular cancers or benign breast lesions.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2007
Objective-Interplay between inflammation and angiogenesis is important in pathological reparative... more Objective-Interplay between inflammation and angiogenesis is important in pathological reparative processes such as arteriosclerosis. We investigated how the two vascular endothelial growth factor receptors VEGFR-1 and -2 regulate these events in chronically rejecting cardiac allografts. Methods and Results-Chronic rejection in mouse cardiac allografts induced primitive myocardial, adventitial, and intimal angiogenesis with endothelial expression of CD31, stem cell marker c-kit, and VEGFR-2. Experiments using marker gene mice or rats as cardiac allograft recipients revealed that replacement of cardiac allograft endothelial cells with recipient bone marrow-or non-bone marrow-derived cells was rare and restricted only to sites with severe injury. Targeting VEGFR-1 with neutralizing antibodies in mice reduced allograft CD11b ϩ myelomonocyte infiltration and allograft arteriosclerosis. VEGFR-2 inhibition prevented myocardial c-kit ϩ and CD31 ϩ angiogenesis in the allograft, and decreased allograft inflammation and arteriosclerosis. Conclusions-These results suggest interplay of inflammation, primitive donor-derived myocardial angiogenesis, and arteriosclerosis in transplanted hearts, and that targeting VEGFR-1 and -2 differentially regulate these pathological reparative processes. (Arterioscler Thromb Vasc Biol. 2007;27:819-825.)
Acta Ophthalmologica, 2015
Cancer Research
tumor tissuesbecauseof the lack of molecularmarkers. Here, monoclonal antibodies against the extr... more tumor tissuesbecauseof the lack of molecularmarkers. Here, monoclonal antibodies against the extracellular domain of the vascular endothelial growth factor-C receptor that we have named VEGFR-3 were found to specifically stain endothelial cells of lymphatic vessels and vessels around tumors such as lymphoma and in situ breast carcinoma. Interestingly, the spindle cells of several cutaneous nodular AIDS-associated Kaposi's sar come and the endothelium around the nodules were also VEGFR-3 positive. The first specific molecular marker for the lymphatic endothe ilum should provide a useful tool for the analysis of lymphatic vessels in maligp@nt tumors and their metastases and the cellular origin and differ entlatlon of Kaposi's sarcomas.
British Journal of Cancer, 1997
Clinical cancer research : an official journal of the American Association for Cancer Research, 2001
Multiple hemangioblastomas (HBs) of the central nervous system (CNS) and retina are associated wi... more Multiple hemangioblastomas (HBs) of the central nervous system (CNS) and retina are associated with von Hippel-Lindau disease (VHL) and also predispose individuals to renal cell carcinomas and visceral cysts. In VHL, microsurgery or radiosurgery cannot prevent new HBs from arising in the CNS or coagulation of retinal HBs. Multiple but thus far asymptomatic HBs pose a therapeutic problem. IFN-alpha-2a has antiangiogenic activity with an especially favorable effect on life-threatening hemangiomas of the liver in children. This is the first study to assess the efficacy of IFN-alpha-2a in treatment of asymptomatic HBs of the CNS and retina. Four patients (three with VHL) with a combined total of 15 HBs of the CNS, 3 HBs of the retina, and 14 renal and 2 pancreatic cysts were treated with s.c. IFN-alpha-2a for 12 months at 3 x 10(6) IU, 3 times/week. Baseline workup consisted of detailed neurological, ophthalmological, and radiological examinations. Follow-up studies at 3, 13, and 21 mon...
Blood, Jan 15, 1999
Basic fibroblast growth factor (bFGF) is a secreted multifunctional cytokine and a potent stimula... more Basic fibroblast growth factor (bFGF) is a secreted multifunctional cytokine and a potent stimulator of angiogenesis in vivo. Elevated bFGF concentrations have been detected in the serum and urine of cancer patients. We measured bFGF by enzyme-linked immunosorbent assay from sera taken from 160 non-Hodgkin's lymphoma (NHL) patients before treatment and stored at -20 degrees C. The patients had been observed for at least 5 years or until death. Serum bFGF concentrations (S-bFGF) ranged from undetectable to 34.7 pg/mL (median, 3.3 pg/mL). S-bFGF was detectable with a similar frequency in all subtypes of NHL. A high pretreatment S-bFGF was associated with poor overall survival. The 5-year survival rate of the patients within the highest quartile of S-bFGF concentrations (S-bFGF = 5.5 pg/mL) was only 39%, in contrast to a 60% survival rate of the patients with lower S-bFGF (P =.019). A high S-bFGF (within the highest quartile) was associated with poor outcome also in large-cell diff...
Blood, Jan 15, 1997
Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which ... more Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which is induced by hypoxia and is angiogenic in vivo. Recently, elevated serum concentrations of VEGF (S-VEGF) have been reported in patients with cancers of various histologies. However, the prognostic significance of S-VEGF in human cancer is unknown and the origin of S-VEGF remains unsettled. We measured S-VEGF by enzyme-linked immunosorbent assay from sera taken from 82 patients with non-Hodgkin's lymphoma before treatment and stored for 9 to 15 years at -20 degrees C. All but one of the patients had been followed-up for at least 5 years or until death. S-VEGF ranged from 15 to 964 pg/mL; median, 228 pg/mL; mean, 291 pg/mL. A higher than the median S-VEGF level was associated with a poor World Health Organization performance status, a high International Prognostic Index, a high serum lactate dehydrogenase level, and a large cell histology. Patients with lower than the median S-VEGF at...
Breast Cancer Research and Treatment, 1999
Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular ... more Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. Many types of malignant human tumors have been shown to produce VEGF. Recently, increased serum concentrations of VEGF (S-VEGF) have been reported in patients with various types of cancer, and high S-VEGF levels have also been associated with unfavorable prognosis. We have now measured S-VEGF in sera taken from 105 patients with a benign breast tumor or breast cancer. None of the women with a benign breast tumor had S-VEGF higher than 328 pg/ml (median, 57 pg/ml) whereas S-VEGF levels in metastatic breast cancer ranged from 7 to 1347 pg/ml (median, 186 pg/ml; P = 0.0018), and in locoregional breast cancer from 11 to 539 pg/ml (median, 104 pg/ml; P = 0.13). S-VEGF was higher in patients with locoregional ductal cancer (median, 107 pg/ml) than in those with locoregional lobular cancer (median, 44 pg/ml; P = 0.029) or in patients with benign breast tumor (median, 57 pg/ml; P = 0.033). Patients with metastatic cancer undergoing therapy had lower S-VEGF than those who had symptomatic treatment only (P = 0.021). The results indicate that dissemination of breast cancer may be accompanied by an elevation of circulating VEGF and that primary ductal cancers are associated with higher S-VEGF levels than lobular cancers or benign breast lesions.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2007
Objective-Interplay between inflammation and angiogenesis is important in pathological reparative... more Objective-Interplay between inflammation and angiogenesis is important in pathological reparative processes such as arteriosclerosis. We investigated how the two vascular endothelial growth factor receptors VEGFR-1 and -2 regulate these events in chronically rejecting cardiac allografts. Methods and Results-Chronic rejection in mouse cardiac allografts induced primitive myocardial, adventitial, and intimal angiogenesis with endothelial expression of CD31, stem cell marker c-kit, and VEGFR-2. Experiments using marker gene mice or rats as cardiac allograft recipients revealed that replacement of cardiac allograft endothelial cells with recipient bone marrow-or non-bone marrow-derived cells was rare and restricted only to sites with severe injury. Targeting VEGFR-1 with neutralizing antibodies in mice reduced allograft CD11b ϩ myelomonocyte infiltration and allograft arteriosclerosis. VEGFR-2 inhibition prevented myocardial c-kit ϩ and CD31 ϩ angiogenesis in the allograft, and decreased allograft inflammation and arteriosclerosis. Conclusions-These results suggest interplay of inflammation, primitive donor-derived myocardial angiogenesis, and arteriosclerosis in transplanted hearts, and that targeting VEGFR-1 and -2 differentially regulate these pathological reparative processes. (Arterioscler Thromb Vasc Biol. 2007;27:819-825.)
Acta Ophthalmologica, 2015