Study on the of Anagrelide on Platelet Factor 4 and Vascular Endothelial Growth Factor Levels in Patients with Essential Thrombocythemia

AbstractAngiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1, and Flt-4, have been found to play an essential role in regulating angiogenesis. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4, and rapamycin+platelet factor-4. The tumors were subsequently subjected to immunohistological protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semi-quantitative scoring method, while the mRNA expression levels were analyzed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4 treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent anti-angiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Download Full-text

Rapamycin as a potent and selective inhibitor of vascular endothelial growth factor receptor in breast carcinoma

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211059673 ◽

2022 ◽

Vol 36 ◽

pp. 205873842110596

Author(s):

Muhammad Shahidan Muhammad Sakri ◽

Tengku Ahmad Damitri Al-Astani Tengku Din ◽

Hasnan Jaafar ◽

Vinod Gopalan ◽

Wan Faiziah Wan Abdul Rahman

Keyword(s):

Vascular Endothelial Growth Factor ◽

Cell Proliferation ◽

Growth Factor ◽

Breast Carcinoma ◽

Platelet Factor 4 ◽

Vascular Endothelial ◽

Platelet Factor ◽

Expression Levels ◽

Endothelial Growth Factor ◽

Mrna Expression Levels

Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Download Full-text

Platelet factor 4 disrupts the intracellular signalling cascade induced by vascular endothelial growth factor by both KDR dependent and independent mechanisms

European Journal of Biochemistry ◽

10.1111/j.1432-1033.2004.04263.x ◽

2004 ◽

Vol 271 (16) ◽

pp. 3310-3318 ◽

Cited By ~ 16

Author(s):

Eric Sulpice ◽

Jean-Olivier Contreres ◽

Julie Lacour ◽

Marijke Bryckaert ◽

Gerard Tobelem

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Platelet Factor 4 ◽

Intracellular Signalling ◽

Vascular Endothelial ◽

Platelet Factor ◽

Endothelial Growth Factor ◽

Signalling Cascade

Download Full-text

Selected Parameters of Angiogenesis and the JAK2, CALR, and MPL Mutations in Patients With Essential Thrombocythemia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617740222 ◽

2018 ◽

Vol 24 (7) ◽

pp. 1056-1060 ◽

Cited By ~ 2

Author(s):

Grażyna Gadomska ◽

Alicja Bartoszewska-Kubiak ◽

Joanna Boinska ◽

Karolina Matiakowska ◽

Katarzyna Ziołkowska ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Essential Thrombocythemia ◽

Leukemia Virus ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Vascular Endothelial ◽

High Concentration ◽

Endothelial Growth Factor ◽

Calr Mutation

The aim of the study was to evaluate selected angiogenic factors in patients with essential thrombocythemia (ET) depending on JAK2V617F, calreticulin gene (CALR) and myeloproliferative leukemia virus oncogene (MPL) mutations. Sixty ET patients and 20 healthy volunteers were enrolled in the study. The following tests were performed: vascular endothelial growth factor- A (VEGF-A), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1),soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), platelet-derived growth factor( PDGF-BB), and stromal-derived factor-1α (SDF-1α). We observed an increased PDGF-BB level in patients with ET compared to the controls. Patients with CALR mutation had significantly higher concentration of PDGF-BB and lower concentration of SDF-1α than patients with JAK2V617F mutation. High concentration of PDGF-BB and low concentration of SDF-1α in patients with CALR(+) ET may indicate a contribution of these chemokines in disturbed Ca2+ metabolism in platelets.

Download Full-text

Inhibition of In Vitro Angiogenesis by Platelet Factor-4–Derived Peptides and Mechanism of Action

Blood ◽

10.1182/blood.v94.3.984.415k31_984_993 ◽

1999 ◽

Vol 94 (3) ◽

pp. 984-993 ◽

Cited By ~ 81

Author(s):

Valérie Jouan ◽

Xavier Canron ◽

Monica Alemany ◽

Jacques P. Caen ◽

Gérard Quentin ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Three Dimensional ◽

Tube Formation ◽

Platelet Factor 4 ◽

Vascular Endothelial ◽

Heparin Binding ◽

Platelet Factor ◽

Endothelial Growth Factor

In this study, we examined in detail the interaction of platelet factor-4 (PF-4) with fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) and the effect of PF-4–derived synthetic peptides. We show that a peptide between amino acids 47 and 70 that contains the heparin-binding lysine-rich site inhibits FGF-2 or VEGF function. This is based on the following observations: PF-4 peptide 47-70 inhibited FGF-2 or VEGF binding to endothelial cells; it inhibited FGF-2 or VEGF binding to FGFRs or VEGFRs in heparan sulfate–deficient CHO cells transfected with FGFR1 (CHOFGFR1) or VEGFR2 (CHOmVEGFR2) cDNA; it blocked proliferation or tube formation in three-dimensional angiogenesis assays; and, finally, it competed with the direct association of 125I-PF-4 with FGF-2 or VEGF, respectively, and inhibited heparin-induced FGF-2 dimerization. A shorter C-terminal peptide (peptide 58-70), which still contained the heparin-binding lysin-rich site, had no effect. Peptide 17-58, which is located in the central part of the molecule, although it does not inhibit FGF-2 or VEGF binding or biologic activity in endothelial cells, inhibited heparin-dependent binding of125I-FGF-2 or 125I-VEGF to CHOmFGFR1 or CHOmVEGFR2 cells, respectively. Shorter peptides (peptides 34-58 and 47-58) did not show any of these effects.

Download Full-text