In vivo perspective study about the effects of weekly low dose administration of zoledronic acid (ZA) on angiogenesis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3558-3558
Author(s):  
D. Santini ◽  
B. Vincenzi ◽  
F. Battistoni ◽  
S. Galluzzo ◽  
L. Rocci ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Cancer Patients ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Low Doses ◽  
Dose Administration ◽  
Before And After ◽  
Endothelial Growth Factor ◽  
First Time

3558 Purpose: Recent data have demonstrated in preclinical tumor models an antiangiogenic and antitumor activity of low weekly doses of ZA. As a consequence, the purpose of this study was to confirm these data, evaluating in cancer patients the modifications in angiogenic cytokines levels following repeated weekly low doses of ZA. Experimental Design: 26 consecutive cancer patients with bone metastases treated, for the first time, with four weekly doses of 1 mg of ZA followed by standard doses (4 mg every 28 days) were prospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) at different time points: just before and after 1, 7, 14, 21, 28, 56 and 84 days following the first disphosphonate infusion. Results: Basal serum VEGF median levels were significantly decreased just after 7 days (-29.7%) (with only one weekly infusion) (P=0.038), This significant decrease of circulating VEGF levels persisted 14(-33.2%), 21 (-39.4%), 28(-31.8%), 56(-33.6%) and 84(-27.9%) days after the first infusion (respectively, P=0.002, P=0.001, P=0.008, P=0.002, P=0.014). Conclusions: This study confirms, for the first time in humans, that weekly low doses of zoledronic acid could have antiangiogenic properties through a significant and long lasting decrease of VEGF serum levels. No significant financial relationships to disclose.

Human recombinant erythropoietic agents (rHuEPO) do not induce changes in circulating levels of endoglin and vascular endothelial growth factor (VEGF) in anaemic cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19569-19569
Author(s):  
A. Ocana ◽  
A. Rodríguez-Barbero ◽  
M. Pericacho ◽  
L. Bellido ◽  
E. Fonseca ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Patients ◽  
Serum Levels ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Wilcoxon Rank Sum Test ◽  
Before And After ◽  
Endothelial Growth Factor ◽  
Circulating Levels

19569 Background: The expression of Erythropoietin (EPO) receptors on cancer cells and the correlation of EPO receptor levels with angiogenesis and progression in some cancers have suggested that EPO could acts directly as an angiogenic factor. The purpose of this study was to assess the effect of treatment with human recombinant erythropoietic agents (rHuEPO) in cancer patients with chemotherapy-induced anaemia on Endoglin and Vascular Endothelial Growth Factor (VEGF) circulating levels as a possible marker of angiogenesis. Methods: Endoglin and VEGF were measured in serum samples from 25 cancer patients with chemotherapy-induced anaemia before and after 3 to 4 weeks of treatment with rHuEPO (Epoetin alfa 150 UI/Kg three times per week; darbepoetin alfa 150 mcg/weekly). A group of 28 healthy voluntaries were used as control. Endoglin and VEGF were analyzed using an ELISA commercial Kit (R&D Systems; Ciudad-Pais). T- student test was used to study the association between variables. Paired comparisons before and after treatment were performed using the Wilcoxon rank-sum test. Results: VEGF serum levels were significantly higher in cancer patients than in controls (476,66±72,56 pg/ml versus 227,34±24,58 pg/ml, p<0.001, respectively). Endoglin levels were significantly higher in patients than controls, although this difference did not reach statistical significance (4.75±0.30ng/ml versus 4.18±0.12 ng/ml, p=0.075). Similar results were found in the different subgroups of patients (Breast cancer, endoglin p=0.019; VEGF p=0.009; Colon cancer, endoglin p=0.084; VEGF p<0.001). Using the Wilcoxon rank-sum test no statistically significant differences in endoglin (p=0.510) and VEGF (p=0.313) serum levels were found between samples obtained before and after treatment with rHuEPO agents. When considering the type of rHuEPO, no differences were observed. In a similar manner, no difference was observed depending on chemotherapy regimen or cancer type. Conclusions: Although the follow up is short and the number of patients is small, our exploratory results do not support that rHuEpo treatment in anaemic cancer patients induce angiogenic serum markers. No significant financial relationships to disclose.

Vascular Endothelial Growth Factor (VEGF) Serum Levels during Cancer Immunotherapy with IL-2: Preliminary Considerations

1998 ◽  
Vol 13 (2) ◽  
pp. 98-101 ◽  
Author(s):  
P. Lissoni ◽  
L. Fumagalli ◽  
L. Giani ◽  
F. Rovelli ◽  
G Confalonieri ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Cell Cancer ◽  
Free Fraction ◽  
Serum Levels ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Neoangiogenesis has been proven to play a fundamental role in promoting cancer spread, and vascular endothelial growth factor (VEGF) is known to represent one of the most important angiogenic factors. The present study was planned to investigate changes in VEGF secretion in cancer patients undergoing immunotherapy with IL-2, with the aim of establishing whether VEGF variations play a role in mediating the IL-2-induced control of neoplastic diseases. The study involved 14 metastatic renal cell cancer patients treated with IL-2 immunotherapy (6 million IU/day subcutaneously for 6 days/week for 4 weeks). The clinical response consisted of partial response (PR) in 3, stable disease (SD) in 6 and progressive disease (PD) in the remaining 5 patients. VEGF serum levels were measured by an enzyme immunoassay designed to determine both bound and unbound VEGF. No significant changes in VEGF mean levels occurred during IL-2 therapy. Moreover, neither in patients with PR or SD nor in those with PD did the mean serum levels of VEGF change significantly in response to IL-2. This preliminary study seems to exclude that changes in the angiogenic factor VEGF may play a role in mediating the therapeutic efficacy of IL-2 cancer immunotherapy. However, since the method of measurement used in our study was designed to detect the total amount of VEGF, it cannot be excluded that changes in the free fraction of the molecule may occur during IL-2 cancer immunotherapy.

scholarly journals Immunotherapy Combined with Metronomic Dosing: An Effective Approach for the Treatment of NSCLC

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1901
Author(s):  
Eleni Skavatsou ◽  
Maria Semitekolou ◽  
Ioannis Morianos ◽  
Theodoros Karampelas ◽  
Nikolaos Lougiakis ◽  
...  
Keyword(s):  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Vascular Endothelial ◽  
Dose Administration ◽  
In Vivo Models ◽  
Pharmacokinetic Properties ◽  
Strong Candidate ◽  
Endothelial Growth Factor

Pioneering studies on tumor and immune cell interactions have highlighted immune checkpoint inhibitors (ICIs) as revolutionizing interventions for the management of NSCLC, typically combined with traditional MTD chemotherapies, which usually lead to toxicities and resistance to treatment. Alternatively, MTR chemotherapy is based on the daily low dose administration of chemotherapeutics, preventing tumor growth indirectly by targeting the tumor microenvironment. The effects of MTR administration of an oral prodrug of gemcitabine (OralGem), alone or with anti-PD1, were evaluated. Relevant in vitro and in vivo models were developed to investigate the efficacy of MTR alone or with immunotherapy and the potential toxicities associated with each dosing scheme. MTR OralGem restricted tumor angiogenesis by regulating thrombospondin-1 (TSP-1) and vascular endothelial growth factor A (VEGFA) expression. MTR OralGem enhanced antitumor immunity by increasing T effector responses and cytokine release, concomitant with dampening regulatory T cell populations. Promising pharmacokinetic properties afforded minimized blood and thymus toxicity and favorable bioavailability upon MTR administration compared to MTD. The combination of MTR OralGem with immunotherapy was shown to be highly efficacious and tolerable, illuminating it as a strong candidate therapeutic scheme for the treatment of NSCLC.

Vascular Endothelial Growth Factor (VEGF) Serum Levels Are Associated With Survival in Early Stages of Lung Cancer Patients

2010 ◽  
Vol 28 (4) ◽  
pp. 393-398 ◽  
Author(s):  
Enrique Carrillo-de Santa Pau ◽  
Fernando Carrillo Arias ◽  
Enrique Caso Pelaez ◽  
Ignacio Muguruza Trueba ◽  
Ignacio Sánchez Hernández ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Patients ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Lung Cancer Patients ◽  
Early Stages ◽  
Endothelial Growth Factor
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