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Background/Aim: Chloride intracellular channel protein 1 (CLIC1) activates inflammasomes in rheumatoid (RA) and psoriatic (PsA) arthritis. We studied CLIC1 expression in RA and PsA patients’ skin with vasculitis and its variability depending on the therapy used. Materials and Methods: CLIC1 immunoexpression was evaluated in the vascular (CLIC1-V) and stromal (CLIC1-S) compartments of the RA and PsA skin biopsies of patients treated with methotrexate (MTX), leflunomid (LFN), corticotherapy (CT), or biological therapies. Results: MTX significantly reduced CLIC1-S expression (p=0.016), whereas LFN decreased CLIC1-V (p

Background/aim Angiogenic growth factors expression is not known in the normal cornea. The aim was to study corneal gene expression profile of VEGF and PDGF pathways influencing the avascular state of cornea. Materials and methods cDNA synthesis was performed from mRNA extracted from five fresh pig corneas followed by cDNA synthesis and analysis of VEGF and PDGF pathways by TaqMan Array gene expression profile. Results Normal pig cornea lacks VEGFR2 and VEGFR3 gene expression. MK2 and AKT1 genes were significantly overexpressed (p=0.000684, p=0.050995, respectively). Six PDGF pathway genes were overexpressed: TIAM1 (p=0.047), PIK3CA (p=0.00005), IKBKG (p=0.000006), PAK4 (p=0.034), RAC1 (p=0.000006 and PTGS2, p=0.00375). PDGF A was up-regulated, but not with a statistical significance (p=0.79911), while PDGFRα was down-regulated and PDGFRβ was not expressed. Conclusion Normal cornea avascularity is given by growth factor receptors down-regulation. Rapid corneal neovascularisation is induced by activation of the main angiogenic growth factors that induce angiogenic cascade and vessel recruitment.

Aim To characterize baby hamster kidney fibroblast (BHK 21/C13) cells and test the effects of antibodies against podoplanin and disodium cromolyn on BHK 21/C13 cell line-derived tumors grown on chick embryo chorioallantoic membrane (CAM). Material and methods BHK 21/C13 cell-derived fibrosarcomas developed in hamsters were implanted on CAM and treated with anti-podoplanin antibodies and disodium cromolyn. BHK 21/C13 cell immunophenotype was assessed. Results Fibrosarcoma cells were positive for vimentin, CD117, smooth muscle actin, vascular endothelial growth factor epidermal growth factor receptor, homebox prospero gene 1 and negative for platelet-derived growth factor B, neuron-specific enolase, S100, CD34, Ewing sarcoma and podoplanin. CAM-grown fibrosarcomas were highly sensitive to disodium cromolyn and anti-podoplanin antibodies. Conclusion Immunophenotyping BHK 21/C13 cells and their response to drugs represent the first step in revealing cell line utility and a reliable tool for experimental cancer research.

Aim To assess the onset of early left ventricular (LV) systolic and diastolic function impairment and the subclinical atherosclerosis following chemotherapy in patients diagnosed with acute myeloid leukemia (AML). Materials and Methods: Thirty patients diagnosed with AML with no cardiac history, having LV ejection fraction (LVEF) >50%, were evaluated at baseline and 6 months after starting four cycles of chemotherapy. We measured LV function, global longitudinal strain and subclinical atherosclerosis markers: intima-media thickness (IMT), arterial stiffness aortic pulse wave velocity (PWVAo) and ankle-brachial index (ABI). Results: LVEF had decreased at 6 months after treatment initialization (p

Aim To evaluate the interaction between MCF-7 breast cancer cells and the chick embryo chorioallantoic membrane (CAM) and the ability of bevacizumab to modulate this process. Materials and methods We implanted MCF-7 cells onto CAM and repeatedly added bevacizumab to a subset of eggs. We then evaluated the morphological and immunohistochemical profiles of CAM and MCF-7. Results MCF-7 cells entered the mesoderm and stimulated the mesenchymal cells to acquire vasculogenic and myofibroblastoid features. MCF-7 cells developed an estrogen receptor-, progesterone receptor-, p53- and Ki67-negative status and entered the epithelial-mesenchymal transition. Bevacizumab down-regulated the expression of B-cell lymphoma 2 protein (BCL-2), vascular endothelial growth factor (VEGF) and E-cadherin in MCF-7 and inhibited vasculogenesis. Conclusion MCF-7 cells turn the mesoderm of CAM into a surrogate tumor stroma. CAM induces a triple-negative, non-proliferative but still anti-apoptotic status in MCF-7 cells. Although antivasculogenic, bevacizumab stimulates MCF-7 cells to acquire a more aggressive status.

Background: Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the most common method used for evaluation of angiogenesis, it has several limitations. Our aim was to evaluate MVD and microvessel proliferation (MVP) in a series of invasive breast carcinomas and analyze whether angiogenesis is influenced by the molecular phenotype of each tumor. Materials and Methods: We examined vascular proliferation using double immunohistochemistry (CD34/Ki67) in a series of 54 invasive breast carcinomas and compared the results with standard MVD, molecular subtypes and other classical parameters. Results: Increased MVD and MVP values were recorded in basal-like subtype, but only the MVP value reached significance among this group of patients (p=0.0001). For all cases combined, increased MVP was significantly correlated with negative estrogen receptor (ER) status (p=0.010) and higher histological grade (p=0.002). Conclusion: MVP more accurately reflects the state of angiogenesis in breast cancer, compared with standard MVD. Vascular proliferation was associated with aggressive tumor features, indicating its contribution to tumor progression. The strong association between vascular proliferation and basal-like tumors suggests that this marker can be used for stratification of patients who might benefit from therapies targeting angiogenesis.

Background/Aim: To analyze the interaction between the human mesenchymal stem cells (hMSC) and the chick embryo chorioallantoic membrane (CAM), in order to assess the still obscure process of vasculogenesis. Materials and Methods: We implanted hMSC onto CAM and we analyzed the morphology and the immunohistochemical profile of CAM. Results: hMSC adhered to CAM, few of them entered the chorionic epithelium and the mesoderm and developed a CD44–/Ki67– status. hMSC stimulated the CAM mesenchymal cells (cMSC) to acquire endothelial and pericyte-like features and to generate cord/capillary-like structures (CLS) in the chorionic epithelium and the mesoderm, but they also entered these structures (CD34+/SMA (smooth muscle actin)+ hMSC). Simultaneously, hMSC induced a process of sprouting angiogenesis in the mesoderm, CD105+ hMSC being identified in the proximity of the angiogenic areas. Conclusion: hMSC and CAM establish a genuine hotspot of vasculogenesis, which may evolve to a valuable experimental model for this research field.