Biomedical subjects

A Vacca

Publications and source records attributed to A Vacca.

At least 19 recordsLinked to original sources

PubMed2007

In vivo inhibition of human hepatocellular carcinoma related angiogenesis by vinblastine and rapamycin.

This paper illustrates the use of the chick embryo chorioallantoic membrane (CAM) assay to determine the single and combined antiangiogenic effects of very low doses of vinblastine (VBL) and rapamycin (RAP) in human hepatocellular carcinoma (HCC). The angiogenic response induced by human HCC biopsy specimens was inhibited by each drug and sinergistically by their combination. Morever, immunohistochemical detection of microvessels with anti-CD31 mAB showed that their area was significantly lower in specimens treated with VBL and RAP in combination. Sinergy on the part of these well-known drugs when used in combination as antiangiogenics at very low doses may be of significance in the designing of new ways of treating HCC.

Angiogenesis Inhibitors↗

PubMed2006

Neridronate inhibits angiogenesis in vitro and in vivo.

The effects of the amino-bisphosphonate neridronate on endothelial cell functions involved in angiogenesis, namely, proliferation and morphogenesis on Matrigel were tested in vitro, whereas its effects on angiogenesis were studied in vivo, by using the chick embryo chorioallantoic membrane (CAM) assay. In vitro, neridronate inhibited endothelial cell proliferation in a dose-dependent fashion, peaking at 30 microM. At the same concentration, neridronate inhibited fibroblast growth factor-2 (FGF-2)-induced capillary-like tube formation in the morphogenesis assay on Matrigel. In vivo, when tested in the CAM assay, neridronate again displayed the capability to inhibit FGF-2-induced angiogenesis. Overall, these results suggest that anti-angiogenesis by neridronate could be used to treat a wide spectrum of angiogenesis-dependent diseases, including certain chronic inflammatory diseases and cancer.

Angiogenesis Inhibitors↗

PubMed2006

The history of the angiogenic switch concept.

Spontaneously arising tumor cells are not usually angiogenic at first. The phenotypic switch to angiogenesis is usually accomplished by a substet that induces new capillaries that then converge toward the tumor. The switch clearly involves more than simple upregulation of angiogenic activity and is thought to be the result of a net balance of positive and negative regulators. Tumor growth is although to require disruption of this balance and hence this switch must turned on for cancer progression. Progenitor endothelial cells, the crosstalk between angiogenic factors and their receptors and the interaction between vasculogenesis and lymphangiogenesis are all factors that may contribute to the switch. Its promotion is also the outcome of genetic instability resulting in the emergence of tumor cell lines. This review describes the history of the angiogenic switch illustrated in the literature and with particular reference to the three transgenic mouse models, namely RIP1-TAG2, keratin-14 (K14) (human papilloma virus) HPV16 and papilloma virus, used for stage-specific assessment of the effects of antiangiogenic and antitumorigenic agents.

Animals↗

PubMed2006

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-gamma.

Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-gamma (IFN-gamma) gene transfer dampens ACN tumorigenicity. As IFN-gamma represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-gamma and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-gamma xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-gamma xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-gamma was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds.

Animals↗

PubMed2006

Increased matrix-metalloproteinase-2 and matrix-metalloproteinase-9 expression in the brain of dystrophic mdx mouse.

Brain edema and severe alterations of the glial and endothelial cells have recently been demonstrated in the dystrophin-deficient mdx mouse, an experimental model of Duchenne muscular dystrophy, and an increase in microvessel density in patients affected by Duchenne muscular dystrophy has also been shown. In order to further elucidate the mechanisms underlying the angiogenetic processes occurring in Duchenne muscular dystrophy, in this study we analyzed matrix-metalloproteinase-2 and -9 expression in the brain of 20-month-old mdx and control mice by means of immunohistochemistry, in situ hybridization, immunoblotting and gelatin zymography. Moreover, we studied vascular endothelial growth factor expression by means of Western blot and immunohistochemistry, and by dual immunofluorescence using anti-vascular endothelial growth factor and anti matrix-metalloproteinase-2 and-9 antibodies. Ultrastructural features of the brain choroidal plexuses were evaluated by electron microscopy. Spatial relationships between endothelium and astrocyte processes were studied by confocal laser microscopy, using an anti-CD31 antibody as a marker of endothelial cells, and anti-glial fibrillary acidic protein (GFAP) as a marker of glial cells. The results demonstrate that high expression of matrix-metalloproteinase-2 and matrix-metalloproteinase-9 protein content occurs in mdx brain and in choroidal plexuses where, by in situ hybridization, matrix-metalloproteinase-2 and matrix-metalloproteinase-9 mRNA was localized in the epithelial cells. Moreover, matrix-metalloproteinase-2 mRNA was found in both mdx perivascular astrocytes and blood vessels, while matrix-metalloproteinase-9 mRNA was localized in mdx vessels. Through zymography, increased expression of matrix-metalloproteinase-2 and matrix-metalloproteinase-9 was found in mdx brain compared with the controls. These enhanced matrix-metalloproteinase levels in mdx mice were found to be associated with increased vascular endothelial growth factor expression, as determined by immunoblotting and immunocytochemistry and with ultrastructural alterations of the mdx choroidal epithelial cells and brain vessels, as previously reported [Nico B, Frigeri A, Nicchia GP, Corsi P, Ribatti D, Quondamatteo F, Herken R, Girolamo F, Marzullo A, Svelto M, Roncali L (2003) Severe alterations of endothelial and glial cells in the blood-brain barrier of dystrophic mdx mice. Glia 42:235-251]. Indeed, in the mdx epithelial cells of the plexuses, the apical microvilli were located on the lateral membranes, whereas in the controls they were uniformly distributed over the free ventricular surface. Moreover, by dual immunofluorescence, a colocalization of vascular endothelial growth factor and matrix-metalloproteinase-2 and matrix-metalloproteinase-9 was found in the ependymal and epithelial cells of plexuses in mdx mice and, under confocal laser microscopy, mdx CD-31 positive vessels were enveloped by less GFAP-positive astrocyte processes than the controls. Overall, these data point to a specific pathogenetic role of matrix-metalloproteinase-2 and matrix-metalloproteinase-9 in neurological dysfunctions associated with Duchenne muscular dystrophy.

Animals↗

PubMed2006

Importance of the bone marrow microenvironment in inducing the angiogenic response in multiple myeloma.

Tumor microenvironment is essential for tumor cell proliferation, angiogenesis, invasion and metastasis through its provision of survival signals, secretion of growth and pro-angiogenic factors, and direct adhesion molecule interactions. This review examines its importance in the induction of an angiogenic response in multiple myeloma (MM). The encouraging results of preclinical and clinical trials in which MM has been treated by targeting the tumor microenvironment are also discussed.

Animals↗

PubMed2006

Stephen Paget and the 'seed and soil' theory of metastatic dissemination.

The outcome of cancer metastasis depends on multiple interactions between selected metastatic cells and homeostatic mechanisms unique to some organ microenvironments. The English surgeon Stephen Paget (1855-1926) is credited with being the first to postulate the important role played by microenvironment in metastasis formation. The concept of his 'seed and soil' theory has been supported and confirmed by numerous publications. This review article summarises the most important literature data about this matter.

England↗

PubMed2006

Decision-making in adult thalassemia patients undergoing unrelated bone marrow transplantation: quality of life, communication and ethical issues.

Bone marrow transplantation (BMT) represents a potentially curative treatment of thalassemia. For patients without an HLA-identical sibling donor, recourse to an unrelated donor is a practicable option but the candidates and their families are faced with a difficult decision. They can either choose to continue the supportive therapy, with no chance of definitive cure, or they accept the mortality risk of BMT in the hope of obtaining a definitive resolution of the disease. We investigated the communication strategies and the post transplantation quality of life (QoL) in 19 adult thalassemia patients surviving after an unrelated donor BMT. The patients were given two questionnaires: a questionnaire to evaluate pre-transplantation communication factors and the EORTC QLQ-C30 questionnaire to assess global QoL. All patients were satisfied with the communication modalities employed by the physicians. The global post transplantation QoL in our patient cohort was found to be good. The approach used in this study may offer a contribution to understanding the decision-making process leading to the choice of a treatment with a high mortality risk for a chronic, non-malignant disease. Finally, some ethical issues of this therapeutic approach are briefly addressed.

Adolescent↗

PubMed2006

Bone marrow angiogenesis in multiple myeloma.

Angiogenesis is a constant hallmark of multiple myeloma (MM) progression and has prognostic potential. It is induced by plasma cells via angiogenic factors with the transition from monoclonal gammopathy of undetermined significance (MGUS) to MM, and probably with loss of angiostatic activity on the part of MGUS. The pathophysiology of MM-induced angiogenesis is complex and involves both direct production of angiogenic cytokines by plasma cells and their induction within the microenvironment. The latter are secreted by stromal cells, endothelial cells (EC) and osteoclasts, and promote plasma cell growth, survival and migration, as well as paracrine cytokine secretion and angiogenesis in the bone marrow milieu. Angiogenesis is also supported by inflammatory cells following their recruitment and activation by plasma cells. Finally, circulating EC and endothelial precursor cells (EPC) contribute to the neovascularization, and the presence of EPC suggests that vasculogenesis (new vessel formation from EPC) may also contribute to the full MM vascular tree.

Animals↗

PubMed2006

Allergic reactions to inhalant glucocorticosteroids: a hot topic for pneumologists and allergologists.

Allergic contact dermatitis to topical glucocorticosteroids (GCS) is a delayed type cell-mediated hypersensitivity reaction; it is frequently observed in dermatological and allergological practice, although its incidence is likely underestimated. By contrast, allergic contact sensitization to inhalant GCS is virtually unknown to most pneumologists. Here, we review some cases of adverse reactions to inhalant GCS in terms of pathogenetic mechanisms, risk factors, epidemiology, and allergic cross-sensitivity. In fact, this particular form of sensitization to drugs that have a wide spectrum of use in pneumological practice deserves more attention than in the past.

Administration, Inhalation↗

PubMed2006

Levocetirizine in the treatment of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Chronic urticaria is a common skin condition. It is frequently a disabling disease because of the persistence of clinical symptoms, the unpredictable course and its negative influence on the quality of life. OBJECTIVES: To determine whether levocetirizine is efficacious in the treatment of chronic idiopathic urticaria. METHODS: A randomized, double-blind, placebo-controlled study was conducted in 106 patients with a diagnosis of chronic idiopathic urticaria. A 1-week single blind placebo run-in period (baseline) was followed by a 6-week double blind active treatment period. The patients were randomized to receive one of the following treatments once daily: (a) oral levocetirizine 5 mg, or (b) oral placebo. The study ended after another 1-week single blind placebo washout period. RESULTS: The evaluable population consisted of 100 patients. Levocetirizine administered once daily is effective and well tolerated in the treatment of the symptoms of chronic idiopathic urticaria and in improving the patient's quality of life. Levocetirizine was superior to placebo in reducing the mean total symptoms score as well as individual symptoms, the number of daily episodes and the number of weals, the overall severity of symptoms and the quality of life. The significant beneficial effects of levocetirizine lasted only during the active trial, while at follow-up there was a significant worsening of all the variables evaluated in this study, after the end of the active trial (week 7). CONCLUSIONS: A global assessment indicates that levocetirizine 5 mg once daily is an effective agent in patients with chronic idiopathic urticaria, as its action provides a rapid and satisfactory control of the symptoms and measures of subjective disease, although this is limited to the duration of treatment.

Adult↗

PubMed2006

Desloratadine in combination with montelukast suppresses the dermographometer challenge test papule, and is effective in the treatment of delayed pressure urticaria: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Delayed pressure urticaria (DPU) comes under the heading of physical urticaria. Characteristically itchy, tender or painful weals occur at sites of local pressure including the waistband, soles of the feet and palms of the hands. Lesion onset is typically 3-12 h after the application of pressure, and lesions may persist for more than 24 h. The treatment of DPU is often unsatisfactory. OBJECTIVES: To determine the efficacy of desloratadine and montelukast in the treatment of DPU. METHODS: The study was conducted in 36 subjects affected by DPU. A challenge test with a dermographometer was administered to confirm the diagnosis. After diagnosis, patients were randomized to receive the following treatment once daily for 2 weeks: (i) oral desloratadine 5 mg plus oral placebo; (ii) oral desloratadine 5 mg plus montelukast 10 mg; and (iii) oral placebo alone. RESULTS: At rechallenge, patients from the treatment groups (desloratadine plus montelukast group and desloratadine alone group) demonstrated a significant reduction in mean diameter of papules after 70 s of pressure compared with the placebo group (P < 0.05). Moreover, patients treated with desloratadine plus montelukast showed a significant reduction in mean diameter of papules at 70 s of pressure compared with those treated with desloratadine alone (P < 0.05). In addition, the combination was effective in improving clinical parameters (erythema, oedema and pruritus, and number of separate urticarial episodes). CONCLUSIONS: This study has demonstrated that both desloratadine alone and desloratadine plus montelukast administered once daily yield improvements with respect to the baseline assessment, regarding the suppression of the dermographometer challenge test papule and clinical improvement of urticaria. However, the combination of desloratadine and montelukast was shown to be more efficacious and may therefore be proposed in patients with DPU, in order to avoid corticosteroid therapy.

Acetates↗

PubMed2006

Miller's seminal studies on the role of thymus in immunity.

The thymus is one of the two primary lymphoid organs. It is responsible for the provision of T lymphocytes to the entire body, and provides a unique microenvironment in which T cell precursors (thymocytes) undergo development, differentiation and clonal expansion. This review article summarizes the seminal work of the Australian scientist Francis Albert Pierre Miller concerning the description for the first time of the crucial role of the thymus for normal development of the immune system.

Allergy and Immunology↗

PubMed2006

The contribution of Bruce Glick to the definition of the role played by the bursa of Fabricius in the development of the B cell lineage.

In 1956, Bruce Glick and Timothy Chang reported that the bursa of Fabricius plays an important role in antibody production. Their demonstration that antibody responses are suppressed in the majority of bursectomized chickens became the cornerstone of modern immunology. Bursa research increased considerably during the 1960s and early 1970s.

Allergy and Immunology↗

PubMed2006