Abnormal angiogenesis associated with HIF-1α/VEGF signaling pathway in recurrent miscarriage along with therapeutic goals

To investigate the functionality ofA2Badenosine receptor (A2BAR) and the nitric oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the endothelial cell proliferation/migration during preeclampsia, we used human umbilical vein endothelial cells (HUVECs) isolated from normal pregnanciesn=15or pregnancies with preeclampsian=15. Experiments were performed in presence or absence of the nonselective adenosine receptor agonist NECA, theA2BAR selective antagonist MRS-1754, and the nitric oxide synthase (NOS) inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a significant higher protein level ofA2BAR and logEC50for NECA-mediated proliferation than normotensive pregnancies. The stimulatory effect of NECA (10 μM, 24 h) on cell proliferation was prevented by MRS-1754 (5 nM) coincubation only in cells from normotensive pregnancies. Nevertheless, L-NAME (100 μM, 24 h) reduced the NECA-induced cell proliferation/migration in HUVEC from normal pregnancy; however in preeclampsia only NECA-induced cell proliferation was reduced by L-NAME. Moreover, NECA increased protein nitration and abundance of VEGF in cells from normal pregnancy and effect prevented by MRS-1754 coincubation. Nevertheless, in preeclampsia NECA did not affect the protein level of VEGF. In conclusion HUVECs from preeclampsia exhibit elevated protein level ofA2BAR and impairment ofA2BAR-mediated NO/VEGF signaling pathway.

Download Full-text

Targeting the IKKβ/mTOR/VEGF Signaling Pathway as a Potential Therapeutic Strategy for Obesity-Related Breast Cancer

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-12-0180 ◽

2012 ◽

Vol 11 (10) ◽

pp. 2212-2221 ◽

Cited By ~ 21

Author(s):

Chun-Te Chen ◽

Yi Du ◽

Hirohito Yamaguchi ◽

Jung-Mao Hsu ◽

Hsu-Ping Kuo ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Therapeutic Strategy ◽

Vegf Signaling ◽

Vegf Signaling Pathway

Download Full-text

Blood pressure (BP) as a biomarker for sorafenib (S), an inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.2035 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 2035-2035 ◽

Cited By ~ 19

Author(s):

M. L. Maitland ◽

K. Moshier ◽

J. Imperial ◽

K. E. Kasza ◽

T. Karrison ◽

...

Keyword(s):

Steady State ◽

Signaling Pathway ◽

Performance Status ◽

Plasma Concentrations ◽

Cancer Therapeutics ◽

Ecog Performance Status ◽

Treatment Regimens ◽

Vegf Signaling ◽

Vegf Signaling Pathway ◽

State Plasma

2035 Background: Hypertension is a commonly reported toxicity of agents that inhibit the VEGF signaling pathway (VSP). This new class of cancer therapeutics has broad activity, but optimal dosing methods and integration into established treatment regimens could be enhanced by identification of reliable biomarkers. S, a new treatment for advanced renal cell carcinoma, is an orally available inhibitor of multiple VSP kinases including Raf-1 and VEGFR2. To characterize the chronicity and interindividual variability of BP responses to VSP inhibition we collected serial, standardized measures of BP and concurrent steady-state plasma concentrations ([plasma]) of S, from 30 patients (pts). Methods: Pts with advanced solid tumors, ECOG performance status < 2, and screening BP ≤ 140/90 mmHg on no more than one antihypertensive agent took 400mg S twice daily. Prior to therapy and at 3 time points after steady state [plasma] of drug was achieved, pts underwent 24-hour ambulatory BP monitoring with the SunTech Oscar PowerPack 2 (SunTech Medical, Morrisville, North Carolina). Readings were collected every 15 minutes during daytime hours and every 45 minutes overnight. Results: Unweigthed mean and standard deviations (sd) of systolic (SBP) and diastolic (DBP) 24-hr BP measurements were calculated for each pt. for the sessions pre-therapy and when steady state [plasma] S was reached (between days 6–10 after starting treatment). The differences in mean BPs between the two sessions were compared with (and p values reported for) paired t-tests. Regression analysis of [plasma] of S with either DBP or SBP, or change in DBP or SBP, with main effect and interaction terms for albumin, age, and sex revealed no significant correlation between S [plasma] and BP response. Conclusions: BP elevation is a biomarker for VSP inhibition. The known variability (coefficient of variation = 70%) in total S steady state plasma concentrations did not account for the observed variability in BP response. [Table: see text] [Table: see text]

Download Full-text