Regression of Human Breast Carcinoma in Nude Mice after Ad Gene Therapy Is Mediated by Tumor Vascular Endothelial Cell Apoptosis.

Two vascular endothelial growth factor (VEGF) receptors, FLT-1 and KDR, are expressed preferentially in proliferating endothelium. There is increasing evidence that recombinant, soluble VEGF receptor domains interfering with VEGF signaling may inhibit in vivo neoangiogenesis, tumor growth and metastatic spread. We hypothesized that a soluble form of FLT-1 receptor (sFLT-1) could inhibit the growth of pre-established tumors via an anti-angiogenic mechanism.

TRPM7 is overexpressed in human IBD-related and sporadic colorectal cancer and correlates with tumor grade.

Background: Inflammatory bowel disease (IBD) predisposes to colorectal cancer (CRC) with some specific features that distinguish it from sporadic CRC. Magnesium (Mg) homeostasis is severely compromised in IBD patients, which may affect both inflammation and tumor development. Efficient transcellular Mg transport in intestinal cells depends on the transient receptor potential melastatin (TRPM) channels type 6 and 7, but their expression has never been investigated in the context of IBD-related CRC.

Molecular mechanisms of cardioprotective effects mediated by transplanted cardiac ckit cells through the activation of an inflammatory hypoxia-dependent reparative response.

The regenerative effects of cardiac ckit stem cells (ckitCSCs) in acute myocardial infarction (MI) have been studied extensively, but how these cells exert a protective effect on cardiomyocytes is not well known. Growing evidences suggest that in adult stem cells injury triggers inflammatory signaling pathways which control tissue repair and regeneration. Aim of the present study was to determine the mechanisms underlying the cardioprotective effects of ckitCSCs following transplantation in a murine model of MI.

MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis.

MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgDCD27 memory B-cell population in ACPA RA.

CdSe/CdS semiconductor quantum rods as robust fluorescent probes for paraffin-embedded tissue imaging.

Immunofluorescence techniques on formalin fixed paraffin-embedded sections allow for the evaluation of the expression and spatial distribution of specific markers in patient tissue specimens or for monitoring the fate of labeled cells after in vivo injection. This technique suffers however from the auto-fluorescence background signal of the embedded tissue that eventually confounds the analysis. Here we show that rod-like semiconductor nanocrystals (QRs), intramuscularly injected in living mice, could be clearly detected by confocal microscopy in formalin fixed paraffin-embedded tissue sections.

HMGB1 attenuates cardiac remodelling in the failing heart via enhanced cardiac regeneration and miR-206-mediated inhibition of TIMP-3.

Aims: HMGB1 injection into the mouse heart, acutely after myocardial infarction (MI), improves left ventricular (LV) function and prevents remodeling. Here, we examined the effect of HMGB1 in chronically failing hearts.

Methods And Results: Adult C57 BL16 female mice underwent coronary artery ligation; three weeks later 200 ng HMGB1 or denatured HMGB1 (control) were injected in the peri-infarcted region of mouse failing hearts.

Role of HIF-1alpha in proton-mediated CXCR4 down-regulation in endothelial cells.

Aims: Acidification is associated with a variety of pathological and physiological conditions. In the present study, we aimed at investigating whether acidic pH may regulate endothelial cell (EC) functions via the chemokine receptor CXCR4, a key modulator of EC biological activities.

Methods And Results: Exposure of ECs to acidic pH reversibly inhibited mRNA and protein CXCR4 expression, CXCL12/stromal cell-derived factor (SDF)-1-driven EC chemotaxis in vitro, and CXCR4 expression and activation in vivo in a mouse model.

Myocardial infarction induces embryonic reprogramming of epicardial c-kit(+) cells: role of the pericardial fluid.

Stem cells expressing c-kit have been identified in the adult epicardium. In mice, after myocardial infarction, these cells proliferate, migrate to the injury site and differentiate toward myocardial and vascular phenotype. We hypothesized that, acutely after myocardial infarction, pericardial sac integrity and pericardial fluid (PF) may play a role on epicardial cell gene expression, proliferation and differentiation.

Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions.

Background: Reported data indicate that cancer cells have increased rates of glucose metabolism, as determined by 18FDG-PET imaging in patients with malignancies. The results of many studies have demonstrated that the expression of glucose transporters, especially Glut-1, is increased in a variety of malignancies. This study was undertaken to assess the differential expression of Glut-1 and Glut-3 by benign and malignant melanocytic lesions.

CXCL13 is highly produced by Sézary cells and enhances their migratory ability via a synergistic mechanism involving CCL19 and CCL21 chemokines.

Chemokine and chemokine receptors expressed by normal and neoplastic lymphocytes play a key role in cell recruitment into skin and lymph nodes. The aim of this study was to get further insights into the role of chemokines in pathogenesis and progression of cutaneous T-cell lymphoma (CTCL) with particular regard to Sézary Syndrome (SS), a CTCL variant with blood involvement. Here, we show that functional CXCL13 homeostatic chemokine is strongly up-regulated in SS cells, well-detectable in skin lesions and lymph nodes, and measurable at high concentration in plasma of SS patients, at different levels during disease progression.

High-mobility group box 1 protein in human and murine skin: involvement in wound healing.

High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory responses and tissue repair. In this study, it was examined whether HMGB1 plays a role in skin wound repair both in normoglycemic and diabetic mice. HMGB1 was detected in the nucleus of skin cells, and accumulated in the cytoplasm of epidermal cells in the wounded skin.

Spontaneous myogenic differentiation of Flk-1-positive cells from adult pancreas and other nonmuscle tissues.

At the embryonic or fetal stages, autonomously myogenic cells (AMCs), i.e., cells able to spontaneously differentiate into skeletal myotubes, have been identified from several different sites other than skeletal muscle, including the vascular compartment.

Identification of myocardial and vascular precursor cells in human and mouse epicardium.

During cardiac development, the epicardium is the source of multipotent mesenchymal cells, which give rise to endothelial and smooth muscle cells in coronary vessels and also, possibly, to cardiomyocytes. The aim of the present study was to determine whether stem cells are retained in the adult human and murine epicardium and to investigate the regenerative potential of these cells following acute myocardial infarction. We show that c-kit(+) and CD34(+) cells can indeed be detected in human fetal and adult epicardium and that they represent 2 distinct populations.

Multiple effects of high mobility group box protein 1 in skeletal muscle regeneration.

Objective: High mobility group box 1 protein (HMGB1) is a cytokine released by necrotic and inflammatory cells in response to injury. We examined the role of HMGB1 in skeletal muscle regeneration after hindlimb ischemia.

Methods And Results: Unilateral hindlimb ischemia was induced in mice by femoral artery dissection.

Role of rat alpha adducin in angiogenesis: null effect of the F316Y polymorphism.

Objective: Rat alpha adducin point mutation (F316Y) has been associated with primary systemic arterial hypertension. As microcirculatory abnormalities are present in most forms of hypertension, the aim of the present study was to investigate whether rat alpha adducin may regulate endothelial cell (EC) functions in vitro and in vivo.

Methods And Results: The overexpression of rat wild type alpha adducin (WT-Add1) in ECs induced capillary-like structure development in Matrigel in vitro and enhanced capillary formation in Matrigel implants in vivo in CD1 mice.

Laminar shear stress inhibits CXCR4 expression on endothelial cells: functional consequences for atherogenesis.

Laminar shear stress (LSS) represents a major athero-protective stimulus. However, the mechanisms for this effect are poorly characterized. As chemokine receptors modulate endothelial cell functions, we hypothesized that at least some LSS effects on endothelial cells (ECs) may be due to LSS-dependent changes in chemokine receptor expression and function.

Telomerase mediates vascular endothelial growth factor-dependent responsiveness in a rat model of hind limb ischemia.

Telomere dysfunction contributes to reduced cell viability, altered differentiation, and impaired regenerative/proliferative responses. Recent advances indicate that telomerase activity confers a pro-angiogenic phenotype to endothelial cells and their precursors. We have investigated whether telomerase contributes to tissue regeneration following hind limb ischemia and vascular endothelial growth factor 165 (VEGF(165)) treatment.

Enhanced arteriogenesis and wound repair in dystrophin-deficient mdx mice.

Background: The absence of functional dystrophin in Duchenne muscular dystrophy (DMD) patients and in mdx mice results in progressive muscle degeneration associated with necrosis, fibrosis, and inflammation. Because vascular supply plays a key role in tissue repair, we examined whether new blood vessel development was altered in mdx mice.

Methods And Results: In a model of hindlimb ischemia on femoral artery dissection, hindlimb perfusion, measured by laser Doppler imaging, was higher in mdx mice (0.

p21(Waf1/Cip1/Sdi1) mediates shear stress-dependent antiapoptotic function.

Objective: The antiapoptotic effect of p21(Waf1/Cip1/Sdi1) (p21) was examined in human umbilical vein endothelial cells (HUVEC) exposed to laminar shear stress (SS) or to the nitric oxide donor sodium nitroprusside (SNP) and in a mouse model of hindlimb ischemia.

Methods: In vitro: Cells were cultured without serum and in the presence of cobalt chloride to simulate hypoxia for 12 h (T0). Shear stress was applied to endothelial cells for additional 12 h.

Vascular endothelial growth factor modulates skeletal myoblast function.

Vascular endothelial growth factor (VEGF) expression is enhanced in ischemic skeletal muscle and is thought to play a key role in the angiogenic response to ischemia. However, it is still unknown whether, in addition to new blood vessel growth, VEGF modulates skeletal muscle cell function. In the present study immunohistochemical analysis showed that, in normoperfused mouse hindlimb, VEGF and its receptors Flk-1 and Flt-1 were expressed mostly in quiescent satellite cells.

The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway.

Several chemokines have been shown to regulate cellular apoptosis following discrete stimuli. It was previously demonstrated that the CC chemokine CCL1 (I-309) rescues thymic lymphoma cells from apoptosis by unknown mechanisms. The aim of our study was to characterize the role of the CC chemokine receptor 8 (CCR8), the only described receptor for CCL1, in the rescue of murine thymic lymphoma cells and murine thymocytes from dexamethasone (dex)-induced apoptosis.

Age-dependent effects of repeated immunization with a first generation adenovirus vector on the immune response and transgene expression in young and old rats.

We evaluated the kinetics of transgene expression and humoral and cellular immune responses against viral antigens and the product of the reporter gene LacZ in young (4 months) and old (20 months) Wistar rats. Animals received the intramuscular injection of a recombinant E1-deleted human type 5 adenovirus encoding beta-gal (Ad-LacZ) on days 0 and 30. The transgene expression evaluated on day 2 after infection revealed a significantly higher beta-gal activity in young than in old animals (1.