1,721,202 research outputs found
Angiogenic effects of extracellular human immunodeficiency virus type 1 Tat protein and its role in the pathogenesis of AIDS-associated Kaposi's sarcoma
Full text linkThe Tat protein of human immunodeficiency virus (HIV) type 1 is a transactivator of viral gene expression that is required for virus replication and spread. Moreover, Tat is released by acutely HIV-infected cells via a leaderless secretory pathway and in a biologically active form that exerts effects on both HIV-infected and uninfected cells from different organs and systems. This review focuses on the activities of extracellular Tat protein on endothelial cells, on angiogenesis, and on the pathogenesis of AIDS-associated angioproliferative diseases such as Kaposi's sarcoma. In particular, we discuss results from different groups indicating that Tat mimics the proangiogenic activities of extracellular matrix molecules and that it enhances the effects of angiogenic factors
Interactions between endothelial cells and HIV-1.
No full textEndothelial cells (EC) participate in inflammatory and immune reactions by producing and responding to soluble mediators. Human immunodeficiency virus (HIV)-1 profoundly alters the features of EC. In some anatomical districts, they are infected by the virus and may represent a relevant reservoir. During lymphomononuclear cell diapedesis, EC activate virus replication in crossing cells. Direct or indirect damage of EC is particularly relevant in central nervous system, where blood-brain barrier perturbation is pivotal in neuronal degeneration. The observed alterations of EC adhesive properties contribute in altered leukocyte traffic from blood to lymphoid organs and tissues and play a role in the onset of immune surveillance alteration. These alterations of EC functions are relevant for the general vasculopathy, which marks the acquired immunodeficiency syndrome, and in particular are instrumental in the pathogenesis of Kaposi's sarcoma. Here we discuss the biological and molecular activation of EC in HIV-1 infection that represents the basis to understand the pathogenesis of HIV-1 associated vascular diseases
Vaccines (United Kingdom Patent application)
No full textFIELD OF THE INVENTION
The present invention relates to vaccines comprising Tat, biologically active derivatives thereof or precursors therefor, including nucleic acids encoding such, as well as to methods for vaccination comprising the use of such vaccines
Angiogenic properties of human immunodeficiency virus type 1 Tat protein
No full textExtracellular human immunodeficiency virus type 1 (HIV-1) Tat protein promotes growth of spindle cells derived from AIDS-associated Kaposi sarcoma (AIDS-KS), an angioproliferative disease very frequent in HIV-1-infected individuals. Normal vascular cells, progenitors of AIDS-KS cells, proliferate in response to Tat after exposure to inflammatory cytokines, whose levels are augmented in HIV-1-infected individuals and in KS lesions. Here we show that Tat also promotes AIDS-KS and normal vascular cells to migrate and to degrade the basement membrane and stimulates endothelial cell morphogenesis on a matrix substrate. These effects are obtained at picomolar concentrations of exogenous Tat and are promoted by the treatment of the cells with the same inflammatory cytokines stimulating expression of the receptors for Tat, the integrins alpha 5 beta 1 and alpha v beta 3. Thus, under specific circumstances, Tat has angiogenic properties. As Tat and its receptors are present in AIDS-KS lesions, these data may explain some of the mechanisms by which Tat can induce angiogenesis and cooperate in the development of AIDS-KS
HIV protease inhibitors: antiretroviral agents with anti-inflammatory, anti-angiogenic and anti-tumour activity
No full textPharmacological management of Kaposi’s sarcoma.
No full textIntroduction: Kaposi's sarcoma (KS) is an angioproliferative disease that occurs in four clinical-epidemiological forms sharing the same immunological and histopathological features, suggesting common etiological and pathogenic factors. Infection with the human herpesvirus 8, cytokine- and angiogenic factor-induced growth together with an immuno-dysregulated state represent fundamental conditions for the development of this tumor. Despite the recent improvements in KS management, it remains an incurable disease.
Areas covered: The growing knowledge of KS biology provides multiple opportunities for the development of rational, molecularly targeted therapies. The present review summarizes the current management of KS, including local and systemic conventional therapies, and thoroughly describes the results obtained with new pathogenesis-based anti-KS treatments.
Expert opinion: Kaposi's sarcoma represents a paradigm of how the elucidation of disease pathogenesis can drive the development of molecularly targeted treatments. The multifactorial pathogenesis of KS has led to the evaluation of many experimental agents targeting one or more specific factors or pathways involved in the development or progression of the disease. Although targeted therapy so far represents investigational treatment, clinical evaluation of several of these agents is yielding promising results
HIV protease inhibitors as new treatment options for Kaposi's sarcoma
No full textA reduced incidence and regression of Kaposi's sarcoma (KS) and other tumours has been reported in Acquired Immune Deficiency Syndrome (AIDS) patients treated with antiretroviral combination therapies containing Human Immunodeficiency Virus (HIV) protease inhibitors (PIs) such as indinavir or saquinavir. Indeed, evidence indicates that although PIs were designed to selectively inhibit the HIV protease activity, they can interfere with several cellular pathways and can inhibit tumour growth. In particular, our recent results indicate that doses of indinavir or saquinavir similar to those employed to treat AIDS patients can induce regression of experimental KS by directly blocking two fundamental steps of KS initiation and progression: new blood vessel formation (angiogenesis) and KS tumour cell invasion. This is because indinavir or saquinavir inhibit the activation of matrix metalloproteinase-2 (MMP-2), a basement membrane-degrading enzyme, which is required for the progression of most tumours. Based on these results, a multicentre clinical trial is now starting in Italy, which will assess PI effects on the progression of KS in HIV-uninfected individuals (classical KS)
Immune activation, rather than immune deficiency, cooperates with HIV infection in the development of AIDS-associated Kaposi’s sarcoma.
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