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      Imbalance of Angiogenesis in Diabetic Complications: The Mechanisms

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          Abstract

          Type 2 diabetes mellitus is a complex disease and a chronic health-care problem. Nowadays, because of alteration of lifestyle such as lack of exercise, intake of high fat diet subsequently obesity and aging population, the prevalence of diabetes mellitus is increasing quickly in around the world. The international diabetes federation estimated in 2008, that 246 million adults in worldwide suffered from diabetes mellitus and the prevalence of disease is expected to reach to 380 million by 2025. Although, mainly in management of diabetes focused on hyperglycemia, however, it is documented that abnormalities of angiogenesis may contribute in the pathogenesis of diabetes complications. Angiogenesis is the generation of new blood vessels from pre-existing ones. Normal angiogenesis depends on the intricate balance between angiogenic factors (such as VEGF, FGF 2, TGF-β, angiopoietins) and angiostatic factors (angiostatin, endostatin, thrombospondins). Vascular abnormalities in different tissues including retina and kidney can play a role in pathogenesis of micro-vascular complications of diabetes; also vascular impairment contributes in macrovascular complications e.g., diabetic neuropathy and impaired formation of coronary collaterals. Therefore, identifying of different mechanisms of the diabetic complications can give us an opportunity to prevent and/or treat the following complications and improves quality of life for patients and society. In this review, we studied the mechanisms of angiogenesis in micro-vascular and macro-vascular complications of diabetes mellitus.

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          Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis.

          Diabetes mellitus appears to be a risk factor for some cancers, but the effect of preexisting diabetes on all-cause mortality in newly diagnosed cancer patients is less clear. To perform a systematic review and meta-analysis comparing overall survival in cancer patients with and without preexisting diabetes. We searched MEDLINE and EMBASE through May 15, 2008, including references of qualifying articles. English-language, original investigations in humans with at least 3 months of follow-up were included. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Of 7858 titles identified in our original search, 48 articles met our criteria. One reviewer performed a full abstraction and other reviewers verified accuracy. We contacted authors and obtained additional information for 3 articles with insufficient reported data. Studies reporting cumulative survival rates were summarized qualitatively. Studies reporting Cox proportional hazard ratios (HRs) or Poisson relative risks were combined in a meta-analysis. A random-effects model meta-analysis of 23 articles showed that diabetes was associated with an increased mortality HR of 1.41 (95% confidence interval [CI], 1.28-1.55) compared with normoglycemic individuals across all cancer types. Subgroup analyses by type of cancer showed increased risk for cancers of the endometrium (HR, 1.76; 95% CI, 1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95% CI, 1.24-1.41). Patients diagnosed with cancer who have preexisting diabetes are at increased risk for long-term, all-cause mortality compared with those without diabetes.
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            Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing

            Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia due to lack of or resistance to insulin. Patients with DM are frequently afflicted with ischemic vascular disease or wound healing defect. It is well known that type 2 DM causes amplification of the atherosclerotic process, endothelial cell dysfunction, glycosylation of extracellular matrix proteins, and vascular denervation. These complications ultimately lead to impairment of neovascularization and diabetic wound healing. Therapeutic angiogenesis remains an attractive treatment modality for chronic ischemic disorders including PAD and/or diabetic wound healing. Many experimental studies have identified better approaches for diabetic cardiovascular complications, however, successful clinical translation has been limited possibly due to the narrow therapeutic targets of these agents or the lack of rigorous evaluation of pathology and therapeutic mechanisms in experimental models of disease. This paper discusses the current body of evidence identifying endothelial dysfunction and impaired angiogenesis during diabetes.
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              Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer.

              The matrix metalloproteinase (MMP) family of enzymes is comprised of critically important extracellular matrix remodeling proteases whose activity has been implicated in a number of key normal and pathologic processes. The latter include tumor growth, progression, and metastasis as well as the dysregulated angiogenesis that is associated with these events. As a result, these proteases have come to represent important therapeutic and diagnostic targets for the treatment and detection of human cancers. In this review, we summarize the literature that establishes these enzymes as important clinical targets, discuss the complexity surrounding their choice as such, and chronicle the development strategies and outcomes of their clinical testing to date. The status of the MMP inhibitors currently in US Food and Drug Administration approved clinical trials is presented and reviewed. We also discuss the more recent and successful targeting of this enzyme family as diagnostic and prognostic predictors of human cancer, its status, and its stage. This analysis includes a wide variety of human cancers and a number of human sample types including tissue, plasma, serum, and urine.
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                Author and article information

                Journal
                Int J Prev Med
                Int J Prev Med
                IJPVM
                International Journal of Preventive Medicine
                Medknow Publications & Media Pvt Ltd (India )
                2008-7802
                2008-8213
                December 2012
                : 3
                : 12
                : 827-838
                Affiliations
                [1]Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran
                Author notes
                Correspondence to: Asso. Prof. Majid Khazaei, Department of Physiology, Faculty of Medicine and Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. E-mail: khazaei@ 123456med.mui.ac.ir
                Article
                IJPVM-3-827
                10.4103/2008-7802.104853
                3530300
                23272281
                939e0521-78bf-4025-b6a7-921b24b68875
                Copyright: © International Journal of Preventive Medicine

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 May 2012
                : 07 October 2012
                Categories
                Review Article

                Health & Social care
                angiogenesis,diabetes mellitus,diabetic complications,macro-vascular,micro-vascular

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