scholarly journals The Impact of Experimental Preconditioning Using Vascular Endothelial Growth Factor in Stroke and Subarachnoid Hemorrhage

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sven Oliver Eicker ◽  
Moritz Hoppe ◽  
Nima Etminan ◽  
Stephan Macht ◽  
Jason Perrin ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Subarachnoid Hemorrhage ◽  
Growth Factor ◽  
Infarct Volume ◽  
Vascular Diseases ◽  
Treated Group ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
The Impact ◽  
Major Stroke

Vascular endothelial growth factor (VEGF) stimulating angiogenesis was shown to be a potential novel therapeutic approach for the treatment of ischemic vascular diseases. The goal of the present study was to examine whether transfection of VEGF before occurrence of major stroke (part I) and cerebral vasospasm after experimental subarachnoid hemorrhage (SAH; part II) develops neuroprotective qualities. A total of 25 (part I) and 26 (part II) brains were analyzed, respectively. In part one, a significant reduction of infarct volume in the VEGF-treated stroke animals (43% reduction,P<0.05) could be detected. In part two, significant vasospasm was induced in all hemorrhage groups(P<0.02). Analyzing microperfusion, a significant higher amount of perfused vessels could be detected(P<0.01), whereas no significant effect could be detected towards macroperfusion. Histologically, no infarctions were observed in the VEGF-treated SAH group and the sham-operated group. Minor infarction in terms of vasospasm-induced small lesions could be detected in the control vector transduced group(P=0.05)and saline-treated group(P=0.09). The present study demonstrates the preconditioning impact of systemic intramuscular VEGF injection in animals after major stroke and induced severe vasospasm after SAH.

scholarly journals Prognostic significance of cellular vascular endothelial growth factor (VEGF) expression in the course of chronic myeloid leukaemia

2009 ◽  
Vol 137 (7-8) ◽  
pp. 379-383 ◽  
Author(s):  
Ana Vidovic ◽  
Gradimir Jankovic ◽  
Dragica Tomin ◽  
Maja Perunicic-Jovanovic ◽  
Irena Djunic ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Chronic Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Prognostic Significance ◽  
Chronic Phase ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor ◽  
The Impact

Introduction. Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF) is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown. Objective. The aim of this study was the follow-up of VEGF expression during the course of CML. Methods. We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years). At the commencement of the study, 29 patients were in chronic phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts) and clinical parameters (organomegaly, duration of CP, AP, and BC) of disease progression. Results. The expression of VEGF protein was most pronounced in AP (ANOVA, p=0.033). The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042). Conclusion. Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.

The effect of low serum sodium on treatment outcome to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma: Results from a large international collaboration.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 322-322 ◽  
Author(s):  
F. A. Schutz ◽  
W. Xie ◽  
D. Y. Heng ◽  
F. Donskov ◽  
L. Wood ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Serum Sodium ◽  
Renal Cell ◽  
Vascular Endothelial ◽  
Baseline Serum ◽  
Endothelial Growth Factor ◽  
The Impact ◽  
Low Serum

322 Background: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients (pts) treated with immunotherapy (Jeppesen et al, Br J Cancer. 2010). We sought to investigate the influence of baseline hyponatremia in mRCC pts treated with contemporary vascular endothelial growth factor (VEGF)- targeted therapy in a larger international and multi-institutional database. Methods: Baseline characteristics and outcomes on 855 pts treated with first-line anti-VEGF therapy for mRCC were available from 8 Cancer Centers to study the impact of hyponatremia (defined as serum Na<135 mmol/L) on clinical outcome as measured by overall survival (OS), time to treatment failure (TTF), best response (CR, PR, SD and PD). Results: Median OS after treatment initiation was 16.8 months (mos) (95% CI: 14.9, 18.5 mos), with 334 (39%) of patients remaining alive. Median follow-up in pts alive was 18.8 mos. Median baseline serum sodium was 138 mmol/L (range: 122–159), and hyponatremia was found in 16.7% of pts. On univariate analysis, hyponatremia was associated with shorter OS (6.5 vs. 18.8 mos; HR 2.32 [95% CI: 1.86–2.89], p<0.0001), shorter TTF (2.8 vs. 6.9 mos.; HR 2.20 [95% CI: 1.81–2.68], p<0.0001), and lower disease control rate (DCR) as defined by CR+PR+SD (51.2% vs. 74.6%, OR 0.36 [95% CI: 0.2–0.57], p<0.0001). In multivariate analysis adjusted for MSKCC or Heng's risk criteria (JCO 2009), these effects remain significant with p<0.001 for OS and TTF and p=0.01 for DCR. The results were similar (p<0.001) if sodium was analyzed as a continuous variable. Conclusions: This is the first large multi-institutional report to show that low serum sodium is independently associated with a worse outcome in mRCC pts treated with VEGF-targeted agents. No significant financial relationships to disclose.

T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 501-501
Author(s):  
Thai Huu Ho ◽  
Robert Charles Gagnon ◽  
Yuan Liu ◽  
F. Stephen Hodi ◽  
Sabina Signoretti ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
T Cell ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Treated Group ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Cell Repertoire ◽  
Endothelial Growth Factor

501 Background: Reports have demonstrated an inverse relationship between suppression of immune surveillance mechanisms and activation of the vascular endothelial growth factor receptor (VEGFR) pathway suggesting that T cell repertoires may impact response to VEGFR blockade. We evaluated the association between clinical outcomes and T cell repertoire in metastatic RCC patients receiving a front-line anti-VEGFR, pazopanib. Methods: Pre-treatment RCC tumors were analyzed from VEG105192, a phase III study of mRCC patients randomized (2:1) to pazopanib (paz) 800 mg daily vs placebo (pbo) for TCR gamma (TCRG) and TCR beta (TCRB) CDR3 regions. Using the Adaptive Biotechnologies immunoSEQ Assay, we assessed TCR clonality, a measure of total repertoire represented by expanded clones, and entropy, a measure of evenness and diversity. PD-L1 was evaluated by immunohistochemistry (IHC) H-Scores. The goal of the study was to determine if the repertoire of T cell clones was associated with progression-free survival as a clinical endpoint. Results: In the cohort with available tissue, the median PFS was 10.8 and 5.5 months (mos) for paz and pbo, respectively. TCRB (n = 114) and TCRG (n = 43 pbo, 109 paz) clonality ranged from 0-0.31 and 0-0.98, and entropy from 1-12.1 and 0-10.37, respectively. TCRB and TCRG entropy were highly correlated (Spearman’s R = 0.92, n = 114). Samples from the pbo-treated group with higher TCRG entropy, defined as the top 25th percentile, were associated with an improved median PFS (12.8 months) when compared to the lower 75th percentile (3.1 months, P = 0.023); similar trends were seen for TCRB entropy. Neither entropy nor clonality was associated with maximal reduction in tumor volume in the paz-treated group. PD-L1 H-scores were not associated with entropy or clonality (P > 0.05). Conclusions: Our data suggests that RCC samples with higher entropy are associated with a favorable prognosis. Identification of tumors with restricted TCRB/G chain usage and less diverse repertoire, as represented by lower entropy and higher clonality, may impact responses to VEGFR blockade and requires further study. Clinical trial information: NCT00334282.

Sign in / Sign up

Export Citation Format

Share Document