Estrogen-Dependent Growth of a Rat Pituitary Tumor Involves, But Does Not Require, a High Level of Vascular Endothelial Growth Factor

2002 ◽  
Vol 227 (7) ◽  
pp. 492-499 ◽  
Author(s):  
Danny Cracchiolo ◽  
Jason W. Swick ◽  
Lucy McKiernan ◽  
Erica Sloan ◽  
Supriya Raina ◽  
...  

Long-term (10-week) treatment of Fischer 344 (F344) rats with the synthetic estrogen diethylstilbestrol (DES) increases the level of vascular endothelial growth factor (VEGF) in the pituitary. This is concurrent with the development of a large tumor of the pituitary of F344 rats. A role for VEGF in estrogendependent pituitary tumor growth is also supported by the fact that pituitary VEGF level is not increased by estrogen treatment in rats of the tumor-resistant Brown Norway (BN) strain. However, VEGF is not increased by estrogen treatment in an F1 hybrid of F344 and BN, even though F1 hybrid rats do form pituitary tumors in response to estrogen. Quantitative trait locus (QLT) mapping reveals that control of estrogen-dependent VEGF expression is linked to the Edpm5 QTL, which was previously identified as a QTL for estrogen-dependent pituitary tumor growth. In contrast, the QTL Edpm2-1 and Edpm9-2, which have been shown to each have a significant effect on estrogendependent pituitary mass of a magnitude similar to Edpm5, do not have any effect on VEGF level. Taken together, our results support the association of VEGF expression with growth of the estrogen-Induced rat pituitary tumor, as has been reported by others, but they also indicate that there is significant pathways of growth regulation that are independent of high-level VEGF expression.

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hanna Lawnicka ◽  
Dorota Ptasinska-Wnuk ◽  
Slawomir Mucha ◽  
Jolanta Kunert-Radek ◽  
Marek Pawlikowski ◽  
...  

The aim of our study was to examine the involvement of renin-angiotensin system (RAS) in estrogen-induced lactotropes proliferation and vascular endothelial growth factor (VEGF) expression in rat pituitary. The study was performed on Fisher 344 rats underwent 8-day treatment with diethylstilboestrol (DES). The proliferation index (PCNA) and VEGF expression in pituitary sections were estimated using immunohistochemical methods. Treatment with DES increased the number of PCNA-positive cells, VEGF-positive cells, and VEGF-positive blood vessels in pituitary. Stimulatory effect of estrogen on cell proliferation and VEGF expression in blood vessels was attenuated by losartan, PD123319, and captopril. VEGF immunoreactivity in pituitary cells of DES-treated rats was decreased by AT1 antagonist and not changed by AT2 blocker and ACE inhibitor. Our findings suggest the involvement of RAS in DES-induced cell proliferation and VEGF expression in pituitary. Both the AT1 and AT2 receptors appear to mediate the estrogen-dependent mitogenic and proangiogenic effects in rat pituitary.


2010 ◽  
Vol 67 (9) ◽  
pp. 747-754 ◽  
Author(s):  
Vesna Gajanin ◽  
Zdenka Krivokuca ◽  
Kristina Kostic ◽  
Radoslav Gajanin ◽  
Igor Sladojevic

Background/Aim. Melanoma is a heterogeneous disease of skin and mucous membranes which shows significant increase in incidence worldwide in the past decades. In the process of forming new blood vessels stimulators of angiogenesis participate. There is an increase production of vascular endothelial growth factor (VEGF-C and VEGF-D), which expression cause change of endothelial cells, and higher degree of tumor's aggressiveness. The aim of this research was to determine the level of VEGF expression in skin melanoma in different body regions and in different primary stages of the disease. Methods. The research was conducted on bioptic materials of skin in 39 patients. On excision-made materials a routine histological preparation was done and following parameters were determined: histological type, alteration thickness (according to Breslow), Clark level, TNM (Tumor Nodus Metastasis) stage (pT), alteration width, thickness of lymphocytic infiltration in the tumor, mitotic index, phase of the tumor growth, presence of ulcerations, cellular type of the tumor, localization and level of VEGF expression. Results. Analysis confirmed that 61.54% of skin melanoma showed a high VEGF expression. Nodular and acral lentiginous melanomas showed more frequently a high level of VEGF expression, while superficial spreading melanoma showed a lower level of VEGF expression (p = 0.032, p < 0.05). A higher level of expression was present in thicker melanomas (higher in the Breslow stage; p = 0.011, p < 0.05). The width of the lesion did not have an influence on the level of VEGF expression in melanoma (U =142.000, p = 0.273). Conclusion. Melanomas show a higher level of VEGF expression. Nodular and acral lentiginous types of melanoma show a high level of VEGF expression, while superficial spreading melanoma shows a lower level of VEGF expression. Melanomas in higher-stage disease (Breslow, Clark, pTNM) show a higher level of VEGF expression.


2002 ◽  
Vol 28 (1) ◽  
pp. 20-23 ◽  
Author(s):  
L ARTESE ◽  
C RUBINI ◽  
G FERRERO ◽  
M FIORONI ◽  
A SANTINELLI ◽  
...  

Circulation ◽  
1998 ◽  
Vol 98 (20) ◽  
pp. 2108-2116 ◽  
Author(s):  
Mayumi Inoue ◽  
Hiroshi Itoh ◽  
Makiko Ueda ◽  
Takahiko Naruko ◽  
Akiko Kojima ◽  
...  

2009 ◽  
Vol 137 (7-8) ◽  
pp. 379-383 ◽  
Author(s):  
Ana Vidovic ◽  
Gradimir Jankovic ◽  
Dragica Tomin ◽  
Maja Perunicic-Jovanovic ◽  
Irena Djunic ◽  
...  

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.


2013 ◽  
Vol 5 (1) ◽  
pp. e2013044 ◽  
Author(s):  
Sameh Samir Fahmey ◽  
Hassan Naguib ◽  
Sanna Abdelshafy ◽  
Rasha Alashry

Background: The β-Thalassemia syndromes are the most common hereditary chronic hemolytic anemia due to impaired globin chain synthesis.  Vascular endothelial growth factor (VEGF) plays several roles in angiogenesis which is a crucial process in the pathogenesis of several inflammatory, autoimmune and malignant diseases .Endothelial damage and inflammation make a significant contribution to the pathophysiology of β-thalassemia. Purpose: The aim of the study was to assess serum VEGF level in children with beta-thalassemia major as a marker of angiogenesis. Methods: Blood samples were collected from 40 patients with thalassemia major and 10 healthy controls and assayed for VEGF by enzyme-linked immunosorbent assay. Results: VEGF level was significantly higher in patients with β-Thalassemia major than healthy controls (p=0.001).In addition, VEGF level was higher in splenectomised thalassemic patients than non splenectomised ones (p=0.001) .However, there were a positive correlation between VEGF and chelation starting age (p=0.008) and a negative correlation between VEGF and frequency of blood transfusion (p=0.002). Conclusion: thalassemia patients, especially splenectomized, have elevated serum levels of VEGF. Early chelation and regular blood transfusion help to decrease serum VEGF and the risk of angiogenesis.  


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