High-dose vascular endothelial growth factor increases surfactant protein gene expressions in preterm rat lung

2007 ◽  
Vol 83 (9) ◽  
pp. 581-584 ◽  
Author(s):  
Chung-Ming Chen ◽  
Leng-Fang Wang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Gene ◽  
Surfactant Protein ◽  
High Dose ◽  
Vascular Endothelial ◽  
Rat Lung ◽  
Gene Expressions ◽  
Endothelial Growth Factor

Effective Strategies for Management of Hypertension After Vascular Endothelial Growth Factor Signaling Inhibition Therapy: Results From a Phase II Randomized, Factorial, Double-Blind Study of Cediranib in Patients With Advanced Solid Tumors

2009 ◽  
Vol 27 (36) ◽  
pp. 6152-6159 ◽  
Author(s):  
Marlies H.G. Langenberg ◽  
Carla M.L. van Herpen ◽  
Johann De Bono ◽  
Jan H.M. Schellens ◽  
Clemens Unger ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Severe Hypertension ◽  
Hypertension Management ◽  
High Dose ◽  
Vascular Endothelial ◽  
Advanced Solid Tumors ◽  
Vegf Signaling ◽  
Management Protocol ◽  
Endothelial Growth Factor

Purpose Hypertension is a commonly reported adverse effect after administration of vascular endothelial growth factor (VEGF) inhibitors. Cediranib is a highly potent and selective VEGF signaling inhibitor of all three VEGFRs. This study prospectively investigated hypertension management to help minimize dose interruptions/reductions to maximize cediranib dose intensity. Patients and Methods Patients (n = 126) with advanced solid tumors were randomly assigned to one of four groups: cediranib 30 or 45 mg/d with or without antihypertensive prophylaxis. All patients developing hypertension on cediranib treatment were treated with a standardized, predefined hypertension management protocol. Results Cediranib was generally well tolerated, and all groups achieved high-dose intensities in the first 12 weeks (> 74% in all groups). Antihypertensive prophylaxis did not result in fewer dose reductions or interruptions. Increases in blood pressure, including moderate and severe readings of hypertension, were seen early in treatment in all groups and successfully managed. Severe hypertension occurred in one patient receiving prophylaxis versus 18 in the nonprophylaxis groups. Overall, there were nine partial responses, and 38 patients experienced stable disease ≥ 8 weeks. Conclusion To our knowledge, this is the first prospective investigation of hypertension management during administration of a VEGF signaling inhibitor. All four regimens were well tolerated with high-dose intensities and no strategy was clearly superior. The current cediranib hypertension management protocol appears to be effective in managing hypertension compared with previous cediranib studies where no plan was in place, and early recognition and treatment of hypertension is likely to reduce the number of severe hypertension events. This protocol is included in all ongoing cediranib clinical studies.

scholarly journals Estrogen Receptor-α Overexpression Suppresses 17β-Estradiol-Mediated Vascular Endothelial Growth Factor Expression and Activation of Survival Kinases

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3881-3889 ◽  
Author(s):  
Shameena Bake ◽  
Lijiang Ma ◽  
Farida Sohrabji
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Estrogen Receptor ◽  
Growth Factors ◽  
Growth Factor ◽  
Cell Line ◽  
Female Rats ◽  
High Dose ◽  
Vascular Endothelial ◽  
17Β Estradiol ◽  
Endothelial Growth Factor

Estrogen and its receptors influence growth and differentiation by stimulating the production and secretion of growth factors. Our previous studies indicate an increased expression of estrogen receptor (ER)-α and decreased growth factor synthesis in the olfactory bulb of reproductive senescent female rats as compared with young animals. The present study tests the hypothesis that abnormal overexpression of ERα contributes to decreased growth factor synthesis. We developed the HeLa-Tet-On cell line stably transfected with ERα (HTERα) that expresses increasing amounts of ERα with increasing doses of doxycycline (Dox). Increasing doses of Dox had no effect on vascular endothelial growth factor (VEGF) secretion in HTERα cells. However, in the presence of 40 nm 17β-estradiol, VEGF secretion increased in low-dose Dox-exposed HTERα cultures, which was attenuated by the ERα antagonist, 1,3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]1H-pyrazole dihydrochloride. However, at high-dose Dox and, consequently, high ERα levels, estradiol failed to increase VEGF. In the HeLa X6 cell line in which the Tet-On construct is upstream of an unrelated gene (Pitx2A), estradiol failed to induce VEGF at any Dox dose. Furthermore, in the HTERα cell line, estradiol selectively down-regulates phospho-ERK2 and phospho-Akt at high ERα expression. This study clearly demonstrates that the dose of receptor critically mediates estradiol’s ability to regulate growth factors and survival kinases. The present data also support the hypothesis that 17β-estradiol treatment to an ERα overexpressing system, such as the senescent brain, could reverse the normally observed beneficial effect of estrogen.

scholarly journals Serum Vascular Endothelial Growth Factor and Fibronectin Predict Clinical Response to High-Dose Interleukin-2 Therapy

2009 ◽  
Vol 27 (16) ◽  
pp. 2645-2652 ◽  
Author(s):  
Marianna Sabatino ◽  
Seunghee Kim-Schulze ◽  
Monica C. Panelli ◽  
David Stroncek ◽  
Ena Wang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Clinical Response ◽  
Interleukin 2 ◽  
High Dose ◽  
Vascular Endothelial ◽  
Soluble Factors ◽  
Factors Associated ◽  
Predictors Of Response ◽  
Endothelial Growth Factor

Purpose High-dose interleukin-2 (IL-2) induces durable therapeutic responses in a small subset of patients with metastatic melanoma and renal cell carcinoma, but simple pretreatment predictors of response have not been identified. Patients and Methods To identify predictive biomarkers of clinical response, sera from patients treated with high-dose IL-2 were collected for analysis using a customized, multiplex antibody-targeted protein array platform that surveyed expression of soluble factors associated with tumor immunobiology. Soluble factors associated with clinical responses were analyzed using a multivariate permutation test, and survival outcomes were determined using Kaplan-Meier and log-rank tests. Results A training set from 10 patients identified 68 potentially relevant soluble factors that were then tested in an independent validation set of 49 patients. Class comparison revealed a cluster of 11 biomarkers that were associated with therapeutic outcome. Vascular endothelial growth factor (VEGF) and fibronectin were identified as independent predictors of response. In particular, high levels of these proteins were correlated with lack of clinical response and decreased overall survival. Conclusion Serum VEGF and fibronectin are easily measured pretreatment biomarkers that could serve to exclude patients unlikely to respond to IL-2 therapy.

LPS-INDUCED VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION IN RAT LUNG PERICYTES

Shock ◽  
2008 ◽  
Vol 30 (1) ◽  
pp. 92-97 ◽  
Author(s):  
Chang Oh Kim ◽  
Ae Jung Huh ◽  
Myung Soo Kim ◽  
Bum Sik Chin ◽  
Sang Hoon Han ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Rat Lung ◽  
Factor Expression ◽  
Growth Factor Expression ◽  
Endothelial Growth Factor
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