Browsing by Subject "Vascular endothelial growth factor"

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    Expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 in primary and recurrent WHO grade III meningiomas
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Baumgarten, Peter; Brokinkel, Benjamin; Zinke, Jenny; Zachskorn, Cornelia; Ebel, Heinrich; Albert, Friedrich K.; Stummer, Walter; Plate, Karl H.; Harter, Patrick N.; Hasselblatt, Martin; Mittelbronn, Michel
    WHO grade III meningiomas are malignant neoplasms for which new and more targeted treatment strategies are urgently needed. Although clinical trials investigating anti-angiogenic vascular endothelial growth factor (VEGF) targeted therapies are currently recruiting, knowledge about the expression of VEGF and VEGF receptors remains to be determined. Methods: We investigated the expression of VEGF and its receptors VEGFR1 and VEGFR2 in 32 WHO grade III meningioma samples by immunohistochemistry. Furthermore, we performed in-situ hybridisation for VEGF. Results: We found low VEGF expression in tumor and endothelial cells. Highest VEGF expression levels were seen in peri-necrotic tumor cells potentially suffering from hypoxia. VEGFR1 and 2 were virtually absent on tumor cells, although endothelial cells displayed significantly higher levels reaching stronger expression for VEGFR2 than VEGFR1. Conclusions: Our findings showing constant expression levels of VEGFR2 in endothelial cells serve as a first indication that the use of small tyrosine kinase inhibitors such as Sunitinib directly targeting the VEGF-receptors might be worth testing, also in the clincial context in cases of therapy-refractory meningiomas. Further investigations are needed to study the response to drugs targeting the VEGF pathway in relation to the expression profile of VEGF and its receptors in high grade meningiomas.
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    The hypertrophic chondrocyte: To be or not to be
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Hallett, Shawn A.; Ono, Wanida; Ono, Noriaki
    Hypertrophic chondrocytes are the master regulators of endochondral ossification; however, their ultimate cell fates cells remain largely elusive due to their transient nature. Historically, hypertrophic chondrocytes have been considered as the terminal state of growth plate chondrocytes, which are destined to meet their inevitable demise at the primary spongiosa. Chondrocyte hypertrophy is accompanied by increased organelle synthesis and rapid intracellular water uptake, which serve as the major drivers of longitudinal bone growth. This process is delicately regulated by major signaling pathways and their target genes, including growth hormone (GH), insulin growth factor-1 (IGF-1), indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), bone morphogenetic proteins (BMPs), sex determining region Y-box 9 (Sox9), runt-related transcription factors (Runx) and fibroblast growth factor receptors (FGFRs). Hypertrophic chondrocytes orchestrate endochondral ossification by regulating osteogenic-angiogenic and osteogenic-osteoclastic coupling through the production of vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and matrix metallopeptidases-9/13 (MMP-9/13). Hypertrophic chondrocytes also indirectly regulate resorption of the cartilaginous extracellular matrix, by controlling formation of a special subtype of osteoclasts termed "chondroclasts". Notably, hypertrophic chondrocytes may possess innate potential for plasticity, reentering the cell cycle and differentiating into osteoblasts and other types of mesenchymal cells in the marrow space. We may be able to harness this unique plasticity for therapeutic purposes, for a variety of skeletal abnormalities and injuries. In this review, we discuss the morphological and molecular properties of hypertrophic chondrocytes, which carry out important functions during skeletal growth and regeneration.
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    Vascular endothelial growth factor (VEGF), transforming growth factor-ß (TGFß), and interleukin-6 (IL-6) in experimental herpesvirus retinopathy: association with inflammation and viral infection
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Vinores, S. A.; Derevjanik, N. L.; Shi, A.; Vinores, M. A.; Klein, D. A.; Whittum Hudson, J. A.
    Ex pe rime nt a l he rpesv iru s retin opa th y prese nts a uniqu e model of a transient infl ammatory response in the virus-injected eye and subsequent acute retin al nec rosis a nd c hr o ni c infl amm ati o n in th e co nt ra late ral eye . For 6 days after in fec ti on, VEG F. TGH \, a nd T GF13 2 we re assoc ia ted o nl y w ith infl ammatory cells in the injected eye. By 6 days (after viral anti ge ns we re no longe r detected), VEG F and TGF132 we re upregul ated in retinas of injected eyes until 8- 10 days. In co ntr alate ra l eyes, VEG F was first demonstrated in th e re tin a at 6-7 days (pri or to th e appea rance of vira l antige ns) and TGF13 2 at 7-8 days. Staining fo r these factors was also evident around areas of necrosis. The VEGF receptor, fit-I , was associated with ganglion cells and the inner nuclear laye r of normal and ex perimental mi ce and it was also demonstrated around areas of necrosis. Another VEG F receptor, flk-] , was loca li zed to MUlle r ce ll processes and th e oute r plex ifo rm layer in no rm al and ex pe rime nta l mi ce . Coin cident with VEGF upregul ation in the retinas of herpesvirus-l injected mice, there was increased fl k-1 in ganglion ce lls and the inner and out er nuclear laye rs. IL6 was assoc iated with Mull er ce ll endfeet in normal mice. Following unilateral intraocular inocul ation, IL-6 sp read alo ng th e Miill e r ce ll processes and some astrocytes demonstra ted IL-6 in both eyes at 6-8 days. T he pr ese nt stu dy demo nstr ates that intr aoc ul a r inocul ation of herpesvirus is suffi cient to induce VEGF, flk-l , TGFI32, and IL-6 in the retin as of inj ected and contralateral eyes. Furth er investigation of common signaling pathways fo r these fac tors during responses to viral in fect ion and th e deve lopme nt of ac ute ret in al necrosis could prov ide in formation use ful fo r therapeutic intervention in human herpesviru retinopathy.
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    VEGF-A/VEGF-B/VEGF-C expressions in non- hereditary, non-metastatic phaeochromocytoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Abe, Ichiro; Islam, Farhadul; Lo, Chung Yau; Liew, Victor; Pillai, Suja; Lam, Alfred K.
    . Vascular endothelial growth factor (VEGF) is important in pathogenesis of different cancers. The aim of this study is to investigate the relationships between different VEGFs and clinicopathological factors in patients with phaeochromocytomas. Twenty patients (10 men; 10 women) with non-hereditary, non-metastatic phaeochromocytomas were examined for VEGF mRNA expressions by polymerase chain reaction. The expressions were correlated with the clinical and pathological factors of the patients. In addition, mouse double minute 2 (MDM2) expression in these tumours were studied by immunohistochemistry. High expressions of VEGF-A, VEGF-B, and VEGF-C mRNA were detected in 11 (55%), 9 (45%), and 9 (45%) of the tumours respectively. High expression of VEGF-A in phaeochromocytomas was significantly correlated with the tumour size (p=0.025) but did not correlate with patients' age, gender, and tumour laterality. Besides, there was a trend of VEGF-A expression correlated with MDM2 expression (p=0.064). On the other hand, expressions of VEGF-B and VEGF-C were not significantly correlated with tumour size, patients' age, gender, tumour laterality, and MDM2 expression. In addition, high expressions of VEGF-B and VEGF-A were associated with increase of tumour size (p=0.042). Co-expression of different VEGFs did not correlate with MDM2 expression. To conclude, there is a role for VEGF-A/VEGF-B/VEGF-C in the pathogenesis of nonhereditary, non-metastatic phaeochromocytomas.