Franco Pandolfi1, Laura Franza2, Simona Altamura2, Claudia Mandolini2, Rossella Cianci2, Aftab Ansari3, James T Kurnick4. 1. Institute of Internal Medicine, Catholic University, Rome, Italy. Electronic address: franco.pandolfi@unicatt.it. 2. Institute of Internal Medicine, Catholic University, Rome, Italy. 3. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia. 4. CytoCure LLC, Beverly, Massachusetts; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Abstract
PURPOSE: Although the role of integrins has been described in a variety of diseases, these roles seem to be distinct. To date, no study has attempted to provide links to the various pathways by which such integrins can be involved in these diverse disease settings. The purpose of this review was to address this gap in our knowledge with the hypothesis that there is, in fact, a common pathway by which integrins may function. METHODS: This article provides an in-depth perspective on the discovery, development, and design of therapeutics that modulate cellular function by targeting integrin:ligand interactions by reviewing the literature on this subject; the review included the most recent results of clinical and subclinical studies. A MEDLINE search was conducted for articles pertaining to the various issues related to integrins, and the most relevant articles are discussed (ie, not only those published in journals with a higher impact factor). FINDINGS: It seems that the ligation of the integrins with their cognate ligands plays a major role in translating membrane dialogue into biological function. In addition, they also seem to play a major regulatory role that can enhance or inhibit biological function depending on the context within which such receptor:ligand interactions occur and the organ and tissues at which interactions occurs and is manipulated. Those studies that used statistical analyses have been included where appropriate. IMPLICATIONS: Our findings show that anti-integrin treatment has the potential to become a valid coadjuvant in the treatment of several diseases including cancer, inflammatory diseases, HIv infection and cardiovascular diseases.
PURPOSE: Although the role of integrins has been described in a variety of diseases, these roles seem to be distinct. To date, no study has attempted to provide links to the various pathways by which such integrins can be involved in these diverse disease settings. The purpose of this review was to address this gap in our knowledge with the hypothesis that there is, in fact, a common pathway by which integrins may function. METHODS: This article provides an in-depth perspective on the discovery, development, and design of therapeutics that modulate cellular function by targeting integrin:ligand interactions by reviewing the literature on this subject; the review included the most recent results of clinical and subclinical studies. A MEDLINE search was conducted for articles pertaining to the various issues related to integrins, and the most relevant articles are discussed (ie, not only those published in journals with a higher impact factor). FINDINGS: It seems that the ligation of the integrins with their cognate ligands plays a major role in translating membrane dialogue into biological function. In addition, they also seem to play a major regulatory role that can enhance or inhibit biological function depending on the context within which such receptor:ligand interactions occur and the organ and tissues at which interactions occurs and is manipulated. Those studies that used statistical analyses have been included where appropriate. IMPLICATIONS: Our findings show that anti-integrin treatment has the potential to become a valid coadjuvant in the treatment of several diseases including cancer, inflammatory diseases, HIv infection and cardiovascular diseases.
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