Challenges facing antiangiogenesis therapy: The significant role of hypoxia-inducible factor and MET in development of resistance to anti-vascular endothelial growth factor-targeted therapies

2018 ◽  
Vol 234 (5) ◽  
pp. 5655-5663 ◽  
Author(s):  
Ali Mahdi ◽  
Behrad Darvishi ◽  
Keivan Majidzadeh-A ◽  
Malihe Salehi ◽  
Leila Farahmand
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Significant Role ◽  
Targeted Therapies ◽  
Hypoxia Inducible Factor ◽  
Vascular Endothelial ◽  
Development Of Resistance ◽  
Antiangiogenesis Therapy ◽  
Endothelial Growth Factor

Stathmin 1 plays a role in endometrial decidualisation by regulating hypoxia inducible factor-1α and vascular endothelial growth factor during embryo implantation

2017 ◽  
Vol 29 (8) ◽  
pp. 1530 ◽  
Author(s):  
Jinhai Gou ◽  
Jia Jia ◽  
Juntao Feng ◽  
Xia Zhao ◽  
Tao Yi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Embryo Implantation ◽  
Hypoxia Inducible Factor ◽  
Implantation Site ◽  
Vascular Endothelial ◽  
Stathmin 1 ◽  
Endothelial Growth Factor

The aim of the present study was to explore the potential mechanism underlying stathmin 1 (Stmn1) regulation of embryo implantation, as a continuation of previous proteomic research. Adult healthy female mice were mated naturally with fertile males. Murine uterine tissue was collected during the peri-implantation period. Local expression of Stmn1 during embryo implantation was detected by immunohistochemistry (IHC), which showed that Stmn1 was extensively expressed in endometrial glandular epithelium, vascular endothelium, luminal epithelium and the underlying stromal cells at the implantation site on Day 5. The role of Stmn1 during embryo implantation was evaluated by transient knockdown of Stmn1 in vivo using short interference (si) RNA, and some associated factors including Akt, phosphorylated (p-) Akt, hypoxia-inducible factor (HIF)-1α, prolactin (PRL), insulin-like growth factor binding protein (IGFBP) 1 and vascular endothelial growth factor (VEGF) were examined by western blotting analysis and ELISA. The number of embryos implanted after Stmn1-siRNA infusion into the lumen of one uterine horn was lower than that with normal pregnancies (2.2 ± 1.5 vs 8.6 ± 0.5 respectively; P < 0.05). The expression of VEGF, HIF-1α, p-Akt and the decidualisation biomarkers PRL and IGFBP 1 was upregulated at the implantation site on Day 5, but downregulated after Stmn1-siRNA infusion. These findings suggest that during embryo implantation, knockdown of Stmn1 suppresses decidualisation by inhibiting the expression of p-Akt, HIF-1α and VEGF, thus leading to impaired embryo implantation. These findings provide clues for understanding the complicated process of embryo implantation and the potential role of Stmn1 during embryo implantation.

Beyond the Vascular Endothelial Growth Factor Axis: Update on Role of Imaging in Nonantiangiogenic Molecular Targeted Therapies in Oncology

2015 ◽  
Vol 204 (5) ◽  
pp. 919-932 ◽  
Author(s):  
Stephanie A. Howard ◽  
Michael H. Rosenthal ◽  
Jyothi P. Jagannathan ◽  
Katherine M. Krajewski ◽  
Atul B. Shinagare ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Targeted Therapies ◽  
Vascular Endothelial ◽  
Molecular Targeted Therapies ◽  
Endothelial Growth Factor
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