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B Nico

Publications and source records attributed to B Nico.

At least 37 records · Page 2Linked to original sources
PubMed2003

Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma.

BACKGROUND: The importance of angiogenesis in melanoma has been controversial and is not homogeneous. Mast cell density (MCD) is highly correlated with the extent of both normal and pathological angiogenesis, such as that in chronic inflammatory diseases and tumours. METHODS: We evaluated the prognostic significance of tumour microvascular density (MVD) and MCD in 25 advanced melanoma patients after resection and a 4-5-year follow up: 48% of the patients were alive and free of metastases (good prognostic subgroup); 16% had developed regional nodal metastases (intermediate prognostic subgroup); and 36% had died (poor prognostic subgroup). Tissues samples were investigated immunohistochemically to count microvessels and mast cells with an antifactor VIII and an antitryptase antibody, respectively. RESULTS: Immunohistological staining showed a higher number of microvessels and mast cells in melanoma lesions of poor prognosis as compared with intermediate prognosis and with good prognosis, respectively. CONCLUSIONS: These data agree with those showing a close relationship between MCD and angiogenesis during tumour progression and demonstrate, for the first time, a prognostic significance of MCD in human melanoma.

Adult↗
PubMed2003

Erythropoietin as an angiogenic factor in gastric carcinoma.

AIMS: Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of erythropoietin (Epo) in angiogenesis has not been completely clarified, although its involvement has been reported. In this study we correlated microvascular density and Epo receptor (Epo-R) expression in endothelial and tumour cells with histopathological type in gastric cancer. METHODS AND RESULTS: Specimens of primary gastric adenocarcinomas obtained from 40 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti-CD31 and anti-Epo-R antibodies. Stage IV gastric carcinoma had a higher degree of vascularization than other stages, and Epo-R expression in both endothelial and tumour cells increased in parallel with malignancy grade and was highly correlated with the extent of angiogenesis. CONCLUSIONS: Epo-R level correlates with angiogenesis and progression of patients with gastric carcinoma and we suggest that Epo might have a trophic effect on the vasculature of the gastrointestinal tract. Understanding mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an anti-angiogenic therapy in patients with gastric cancer.

Adenocarcinoma↗
PubMed2002

Angiogenesis and anti-angiogenesis in neuroblastoma.

Angiogenesis is a biological process by which new capillaries are formed from pre-existing vessels. It occurs in physiological and pathological conditions, such as tumours, where a specific critical turning point is the transition from the avascular to the vascular phase. Tumour angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells that able to stimulate the growth of the host's blood vessels. This review summarises the literature concerning the relationship between angiogenesis and progression in human neuroblastoma, the most common extracranial solid tumour of infancy and childhood. It is becoming increasingly evident that agents which interfere with blood vessel formation also block tumour progression. Accordingly, anti-angiogenic tumour therapy has gained much interest in preclinical and clinical assessments. The recent applications of anti-angiogenic agents which interfere or block neuroblastoma progression are reviewed.

Angiogenesis Inhibitors↗
PubMed2002

Correlation of bone marrow angiogenesis and mast cells with tryptase activity in myelodysplastic syndromes.

Bone marrow samples from 30 patients with myelodysplastic syndromes (MDS) grouped according to the International Prognostic Scoring System for MDS were investigated for counts of microvessels, total metachromatic mast cells (MC) and MC expressing tryptase, an angiogenesis-inducing molecule. Counts were higher in patients with a poor prognosis. The observation of a high correlation between microvessel counts and both total metachromatic and tryptase-reactive MC in all samples suggests that angiogenesis in MDS increases with their progression and that MC may intervene in the angiogenic response in MDS through tryptase contained in their secretory granules.

Antigens, CD34↗
PubMed2001

Chorioallantoic membrane capillary bed: a useful target for studying angiogenesis and anti-angiogenesis in vivo.

The chick embryo chorioallantoic membrane (CAM) is an extraembryonic membrane that is commonly used in vivo to study both angiogenesis and anti-angiogenesis. This review 1) summarizes the current knowledge about the structure of the CAM's capillary bed; 2) discusses the controversy about the existence of a single blood sinus or a capillary plexus underlying the chorionic epithelium; 3) describes a new model of the CAM vascular growth, namely the intussusceptive mode; 4) reports findings regarding the role played by endogenous fibroblast growth factor-2 in CAM vascularization; and 5) addresses the use and limitations of the CAM as a model for studying angiogenesis and anti-angiogenesis.

Allantois↗
PubMed2001

Postnatal vasculogenesis.

It is generally accepted that vasculogenesis is limited to early embryogenesis and is believed not to occur in adult, whereas angiogenesis occurs in both the developing embryo and postnatal life. However, the distinction between them is not absolute, because both require endothelial cell proliferation and migration and three-dimensional reorganization of newly formed blood vessels, nor are they mutually exclusive, inasmuch as angioblasts can be incorporated into expanding pre-existing blood vessels. Recent observations indicate that vasculogenesis may not be restricted to early embryogenesis, but may also have a physiological role or contribute to the pathology of vascular diseases in adults. The major evidence in favor of this new view comes from: (i) demonstration of the presence of circulating endothelial cells and endothelial precursor cells; (ii) newly described mechanisms of blood vessel formation in tumor growth. The potential biomedical applications of endothelial precursor cells and the new opportunities for the development of new forms of tumor-targeted treatments are discussed.

Animals↗
PubMed2001

Vascular endothelial growth factor and vascular endothelial growth factor receptor-2 expression in the chick embryo area vasculosa.

Vascular endothelial growth factor is an angiogenic factor in vivo and in vitro that plays a crucial role in the control of blood vessel development and in pathological angiogenesis. The vascularized extraembryonic membranes of the chick embryo include the area vasculosa and the chorioallantoic membrane. In this study, we investigated the expression of vascular endothelial growth factor and of its receptor-2, specifically expressed by the endothelial cells, in the chick area vasculosa at days 6, 10 and 14 of incubation. Our results indicate that, in all the three developmental stages examined, vascular endothelial growth factor is clearly expressed in the endodermal cells immediately adjacent to the mesodermal endothelial cells which, in turn, expressed vascular endothelial growth factor receptor-2. These observations suggest that during the development of the vascular system, endodermal cells, expressing vascular endothelial growth factor, initiate angiogenesis by stimulating directly mesodermal cells, which express vascular endothelial growth factor receptor-2. Moreover, our data demonstrate that vascular endothelial growth factor receptor-2 expression is also maintained by endothelial cells in the later stages of development, until day 14 of incubation. In accord with other literature data, this suggests that vascular endothelial growth factor is required not only for proliferation, but also for the survival of endothelial cells.

Allantois↗
PubMed2001

Microvessel overexpression of aquaporin 1 parallels bone marrow angiogenesis in patients with active multiple myeloma.

The erythrocyte water channel aquaporin 1 (AQP1) is expressed in multiple absorptive and secretory epithelia including the capillary endothelia. Immunoblot analysis showed that bone marrow biopsies of patients with active multiple myeloma (MM) display significantly higher levels of AQP1 than those from patients with non-active MM, whose values are higher, but to a lesser extent, than those of patients with monoclonal gammopathies of undetermined significance (MGUS). Values of MGUS overlapped those of patients with anaemia as a result of iron or vitamin B12 deficiencies (called 'benign anaemias'). Immunohistochemistry and computerized image analysis of AQP1 highlighted bone marrow microvessels whose area per microscopic field was significantly greater in patients with active MM, and always larger than and closely correlated with the microvessel area when assessed with factor VIII-related antigen/von Willebrand's factor (FVIII-VWF). The intensity of AQP1 expression by microvessels evaluated using image analysis was significantly greater in active than non-active MM and in the latter over MGUS or benign anaemias. It is suggested that, among plasma cell tumours, AQP1 expression is preferentially associated with microvessels of MM and that the highest degree of expression occurs in active MM in step with enhanced angiogenesis, in which AQP1 recognizes more immature neovessels than FVIII-VWF. It may, perhaps, favour angiogenesis in a positive loop and, hence, MM progression, and thus be applied for therapeutic vascular targeting.

Adult↗
PubMed2001

Mast cells and their secretory granules are angiogenic in the chick embryo chorioallantoic membrane.

BACKGROUND: Many data suggest that the density of mast cells is highly correlated with the extent of both normal and pathological angiogenesis. OBJECTIVE: In this study we have compared in an in vivo assay, the chick embryo chorioallantoic membrane, the angiogenic potential of mast cell suspensions isolated from rats, degranulated mast cells and their secretory granules. METHODS: Gelatin sponges adsorbed with cell suspensions of rat mast cells, degranulated mast cells and their secretory granules were implanted on the top of the chorioallantoic membrane at day 8 of incubation. At day 12 the angiogenic response was evaluated macroscopically, microscopically and by a morphometric method of 'point counting'. RESULTS: Isolated mast cells and their secretory granules, but not degranulated mast cells, induced an angiogenic response in the chorioallantoic membrane. The addition of antifibroblast growth factor-2 or antivascular endothelial growth factor antibodies reduced the angiogenic response of both mast cells and their secretory granules by 50% and 30%, respectively. CONCLUSION: These data support the evidence that the angiogenic properties of mast cells depend on the angiogenic molecules contained in their secretory granules and indicate that fibroblast growth factor-2 and vascular endothelial growth factor are the angiogenic cytokines primarily and perhaps synergistically responsible for this vasoproliferative activity.

Allantois↗
PubMed2001

In vitro modulation of adhesion molecules, adhesion phenomena, and fluid phase endocytosis on human umbilical vein endothelial cells and brain-derived microvascular endothelium by IFN-beta 1a.

Administration of interferon-beta (IFN-beta) in multiple sclerosis (MS) patients provides clinical benefits, although its mechanism(s) of action are not completely understood. We addressed the issue of whether concentrations of IFN-beta1a close to those reached in the serum of treated MS patients could modulate either adhesion molecules or adhesion of peripheral blood mononuclear cells (PBMC) as well as fluid phase endocytosis (FPE) in human umbilical vein endothelial cells (HUVEC) and in brain-derived microvascular endothelial cells (HBMEC). Adhesion was assessed by flow cytometry, and FPE was evaluated by peroxidase uptake. In our study, 200 U/ml IFN-beta1a induced a reduction in adhesion of PBMC to HUVEC. The information reported herein may contribute to further elucidating some of the mechanisms of action of IFN-beta on vascular endothelium.

Adjuvants, Immunologic↗
PubMed2001

In vivo absence of synergism between fibroblast growth factor-2 and vascular endothelial growth factor.

Fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) are potent angiogenesis inducers in vivo and in vitro and may act in synergy. This possibility has been investigated by their simultaneous administration in the chick embryo chorioallantoic membrane (CAM) assay. Macroscopic and microscopic quantification of the angiogenic response 4 days after administration clearly demonstrated the absence of synergism. When FGF-2 or VEGF concentration was fixed at 0.25 microg/embryo, the simultaneous addition of increasing concentration (0.25, 0.50, 1.0 microg/embryo) of VEGF or FGF-2 did not stimulate a synergistic dose-dependent angiogenic response. In both conditions, the angiogenic response overlapped that induced by the two growth factors administered alone. It is suggested that exogenous administration of FGF-2 and VEGF in the CAM assay may induce an activation of endogenous angiogenic factors, such as FGF-2, and endogenous inhibitors of angiogenesis, such as nitric oxide, normally expressed in the CAM during the development of its vascular tree. Thus, in an in vivo system, evaluation of synergistic action between two cytokines and discrimination of their specific activity are more difficult than in an in vitro assay.

Animals↗
PubMed2001

Aquaporin-4 deficiency in skeletal muscle and brain of dystrophic mdx mice.

We report a detailed study of AQP4 expression in the neuromuscular system of mdx mice. Immunocytochemical analysis performed by double immunostaining revealed that mdx mice manifest a progressive reduction in AQP4 at the sarcolemmal level of skeletal muscle fast fibers and that type IIB fibers are the first to manifest this reduction in AQP4 expression. No labeling was observed in the cytoplasm of muscle fibers, indicating that the reduction in sarcolemma staining is not associated with an intracellular compartmentalization of mistargeted protein. By Western blot and RT-PCR analysis, we found that whereas the total content of AQP4 protein decreased (by 90% in adult mdx mice), mRNA levels for AQP4 remained unchanged. A similar age-related reduction in AQP4 expression was found in brain astrocytic end-feet surrounding capillaries of mdx mice. Morphometric analysis performed after immunogold electron microscopy indicated a reduction of approximately 85% in gold particles (32+/-2/microm vs. 4.7+/-0.61/microm). Western blot experiments conducted using membrane fractions from brain cortex revealed a strong reduction (of 70%) in AQP4 protein in adult mdx mice, and RT-PCR experiments demonstrated that the reduction was not at transcription level. More interesting was the finding that AQP4 reduction was associated with swelling of astrocytic perivascular processes whose ultrastructural modifications are commonly indicated as an important and early event in the development of brain edema. No apparent reduction in AQP4 was found in mdx stomach and kidney. Our data provide evidence that dystrophin deficiency in mdx mice leads to disturbances in AQP4 assembly in the plasma membrane of fast skeletal muscle fibers and brain astrocytic end-feet, suggesting that changes in the osmotic equilibrium of the neuromuscular apparatus may be involved in the pathology of muscular dystrophy.

Animals↗
PubMed2001

Tissue distribution and membrane localization of aquaporin-9 water channel: evidence for sex-linked differences in liver.

Aquaporin-9 (AQP9) is a water channel membrane protein also permeable to small solutes such as urea, glycerol, and 5-fluorouracil, a chemotherapeutic agent. With the aim of understanding the pathophysiological role of AQP9, we performed an extensive analysis by Western blotting, RT-PCR, and immunolocalization in rat tissues. Western blotting analysis revealed a major band of approximately 32 kD in testis, liver, and brain. Immunofluorescence showed strong expression of AQP9 in the plasma membrane of testis Leydig cells. In liver, AQP9 expression was found to be sex-linked. Male rats had higher levels of AQP9 than female in terms of both protein and mRNA. Moreover, in female livers the expression of AQP9 was mostly confined to perivascular hepatocytes, whereas males showed a more homogeneous hepatocyte staining. No differences in AQP9 expression level related to the age or to protein content of the diet were found, indicating that differences in the liver may be gender-dependent. In the brain, AQP9 expression was found in tanycytes mainly localized in the areas lacking a blood-brain barrier (BBB), such as the circumventricular organs (CVOs) of the third ventricles, the subfornical organ, the hypothalamic regions, and the glial processes of the pineal gland. AQP9 expression in the osmosensitive region of the brain suggests a role in the mechanism of central osmoreception. All these findings show a unique tissue distribution of AQP9 compared to the other known aquaporins.

Animals↗
PubMed2001

Role of aquaporin-4 water channel in the development and integrity of the blood-brain barrier.

In this study, we have investigated the expression of aquaporin 4 during blood-brain barrier development in the optic tectum of chick embryos and newly hatched chicks, by means of western-blot, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and freeze-fracture and high-resolution immunogold electron microscopy. In the optic tecta of day-14 embryos, western blot analysis revealed an approx. 30 kDa band, immunoreactive for aquaporin-4, which was increased in day-20 embryos and in chicks. Semi-quantitative reverse transcriptase chain reaction experiments showed that there was already a high level of aquaporin-4 mRNA in day-9 embryos as well as in the subsequent stages and in newly hatched chicks. Immunohistochemically, reactivity for aquaporin-4 was detected in the optic tectum of day-14 embryos; similar results were obtained in telencephalon and cerebellum. Ultrastructurally, the microvessels of the tectum showed immunoreactivity for aquaporin-4 on the astroglial endfeet, which discontinuously surrounded endothelial cells joined by immature tight junctions. In the tectum, telencephalon and cerebellum of 20-day embryos and chicks, aquaporin-4 strongly labeled the ependymal cells and the subpial glial membranes, as well as the bodies and processes of astroglial cells. A continuous aquaporin-4 staining was found around the microvessel endothelial cells, which were sealed off from one another by extensive tight junctions. A complete astrocytic sheath, labeled by anti-aquaporin-4 gold particles, enveloped the endothelium-pericyte layer. Orthogonal arrays of particles were observed on fractured astrocytic membranes, starting from embryonic day 14 when the aquaporin-4 immunogold staining revealed clusters of gold particles, often forming square or rectangular clusters. The results showed that aquaporin-4 expression and organization of the intramembrane particles in orthogonal arrays followed the same temporal sequence. Finally, the lipopolysaccharide, a substance that induces blood-brain barrier disruption, determines a remarkable reduction in aquaporin-4 labeling, expressed by a few aquaporin-4 gold particles attached on swollen perivascular glial membranes. All these data show that aquaporin-4 expression occurs in the chick embryonic brain, in parallel with maturation and functioning of the blood-brain barrier and suggest that there is a close relationship between water transport regulation and brain development.

Animals↗
PubMed2001

Coordinate immunoreactivity to vascular endothelial growth factor receptor-2 and its ligand suggests a paracrine regulation during the development of the vascular system in the chick embryo bursa of Fabricius.

The bursa of Fabricius is a lymphoid organ of the chick which plays an important role in the development of the immune system. The role of angiogenic factors in the development of the vascular system of this organ has been poorly investigated. Vascular endothelial growth factor (VEGF) is a major regulator of endothelial cell proliferation, angiogenesis and vascular permeability, and its activities are mediated by two receptors, VEGFR-1 and VEGFR-2. In this study we have investigated by immunohistochemistry the VEGF and VEGFR-2 immunoreactivity in developing bursa of Fabricius. Starting from day 10 of incubation, the endodermal epithelium reacts with VEGF and gives rise to the lymphoid follicles, while the vascular endothelium reacts with VEGFR-2. These data support the view that VEGF acts as a paracrine stimulator of angiogenesis in the avian embryo and confirm the requirement of the endodermal layer for the normal formation of blood vessels by mesodermal cells.

Animals↗
PubMed2001

Angiogenic activity of leptin in the chick embryo chorioallantoic membrane is in part mediated by endogenous fibroblast growth factor-2.

Recently, it has been demonstrated that leptin, the product of the ob gene, playing a key role in the regulation of body weight, is angiogenic in vitro and in vivo. In this study we investigated the angiogenic potential of human leptin in vivo by using the chick embryo chorioallantoic membrane (CAM) assay, with the aim to establish whether this angiogenic activity is partly dependent on endogenous fibroblast growth factor-2 (FGF-2), which is normally expressed during CAM development. Results showed that leptin is able to stimulate angiogenesis and that the angiogenic response is similar to that obtained with FGF-2. The stimulating property of leptin is specific, as the application of anti-leptin antibodies onto the CAM significantly inhibits the angiogenic response. Moreover, this angiogenic activity is in part due to the activation of endogenous FGF-2. The application of anti-FGF-2 antibodies reduces the angiogenic response to leptin by 40%. Our study confirms that leptin is angiogenic in vivo and suggests that, at least in the chick CAM, its activity is in part mediated by the activation of endogenous FGF-2.

Allantois↗
PubMed2000

Inhibition of protein kinase C counteracts TNFalpha-induced intercellular adhesion molecule 1 expression and fluid phase endocytosis on brain microvascular endothelial cells.

TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression and fluid phase endocytosis (FPE) of horseradish peroxidase on brain microvascular endothelial cell (BMEC) culture. The protein kinase C (PKC) inhibitor staurosporin (0. 5-10 nM) antagonized ICAM1 expression and FPE due to TNFalpha, whereas the protein kinase A inhibitor H89 (0.5-10 nM) did not. These findings indicate that a PKC-dependent mechanism may affect TNFalpha signalling on different barrier properties of BMECs.

Animals↗