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Anti-angiogenic Molecules (anti-angiogenic + molecule)
Selected AbstractsCritical overexpression of thrombospondin 1 in chronic leg ischaemiaTHE JOURNAL OF PATHOLOGY, Issue 3 2005Judith Favier Abstract The aim of this study was to identify gene expression governing the balance of angiogenic and angiostatic factors in human ischaemic leg tissues. In situ hybridization was used to screen for the expression of angiogenesis-related genes in tissues from 13 amputated limbs from patients suffering from critical leg ischaemia. The authors tested for mRNA of hypoxia-inducible transcription factors 1, and 2,, vascular endothelial growth factor, and its receptors VEGFR-1 and -2, the angiopoietin receptor Tie2, and the anti-angiogenic molecule thrombospondin 1. The expression levels of the genes in proximal, healthy muscles were compared with those in the distal, ischaemic counterparts. Surprisingly, only thrombospondin 1 was overexpressed in the ischaemic part of the leg of all patients studied. Thrombospondin 1 mRNA was assayed by real-time RT-PCR and the gene was overexpressed 20-fold. The presence of its encoded protein was confirmed by western blotting. The overproduction of this anti-angiogenic molecule was associated with a decrease in capillary density in the affected muscles. Thrombospondin 1 is thus a marker of chronic ischaemia and may affect angiogenesis in ischaemic tissues. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2008Ian Buysschaert ,,Introduction ,,Angiogenesis is genetically pre-determined ,,Mutations causing vascular anomalies -,Venous anomalies -,Haemangiomas -,The transforming growth factor-ß in vascular anomalies -,Cerebral cavernous malformations ,,Translocations reveal novel angiogenic genes ,,Single nucleotide polymorphisms shape the angio-genome -,SNPs in VEGF and their association with cancer -,SNPs in VEGF pathway genes associated with other diseases -,Genetic variability in VEGFR-2 -,Genetic variability in HIF-1, -,SNPs in VEGFR-1 integrate angiogenesis within the P53 pathway -,Variations in angiogenic genes are linked with neurodegeneration -,Angiogenic factors in genome-wide association studies ,,Copy number variability affects angiogenesis ,,Epigenetic regulation of angiogenesis -,Methylation of anti-angiogenic factors -,Methylation as a second hit event in cancer -,Histone modifications determine angiogenesis ,,Micromanagers of angiogenesis ,,Perspectives Abstract Angiogenesis is controlled by a balance between pro- and anti-angiogenic factors. Studies in mice and human beings have shown that this balance, as well as the general sensitivity of the endothelium to these factors, is genetically pre-determined. In an effort to dissect this genetic basis, different types of genetic variability have emerged: mutations and translocations in angiogenic factors have been linked to several vascular malformations and haemangiomas, whereas SNPs have been associated with complex genetic disorders, such as cancer, neurodegeneration and diabetes. In addition, copy number alterations of angiogenic factors have been reported in several tumours. More recently, epigenetic changes caused by aberrant DNA methylation or histone acetylation of anti-angiogenic molecules have been shown to determine angiogenesis as well. Initial studies also revealed a crucial role for microRNAs in stimulating or reducing angiogenesis. So far, most of these genetic studies have focused on tumour angiogenesis, but future research is expected to improve our understanding of how genetic variants determine angiogenesis in other diseases. Importantly, these genetic insights might also be of important clinical relevance for the use of anti-angiogenic strategies in cancer or macular degeneration. [source] Concept, mechanisms and therapeutics of angiogenesis in cancer and other diseasesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2003Tayade Pralhad Angiogenesis supports normal physiology as well as contributing to the progression of various diseases including cancer. Determination of the key role of angiogenesis in cancer has led to much optimism for the development of targeted drugs without cytotoxic side-effects. Currently, research in angiogenesis therapy is robust, with the discovery of a growing number of pro- and anti-angiogenic molecules. More time, however, is required to be able to elucidate the complex interactions among these molecules, how they affect vasculature and their functions in different environments. As we learn more about the molecular mechanisms of angiogenesis, a number of effective methods to treat cancer and other diseases will be developed. [source] Angiomyolipomata: challenges, solutions, and future prospects based on over 100 cases treatedBJU INTERNATIONAL, Issue 1 2010Prasanna Sooriakumaran Study Type , Therapy (case series) Level of Evidence 4 OBJECTIVE To examine the presentation, management and outcomes of patients with renal angiomyolipoma (AML) over a period of 10 years, at St George's Hospital, London, UK. PATIENTS AND METHODS We assessed retrospectively 102 patients (median follow-up 4 years) at our centre; 70 had tuberous sclerosis complex (TSC; median tumour size 3.5 cm) and the other 32 were sporadic (median tumour size 1.2 cm). Data were gathered from several sources, including radiology and clinical genetics databases. The 77 patients with stable disease were followed up with surveillance imaging, and 25 received interventions, some more than one. Indications for intervention included spontaneous life-threatening haemorrhage, large AML (10,20 cm), pain and visceral compressive symptoms. RESULTS Selective arterial embolization (SAE) was performed in 19 patients; 10 received operative management and four had a radiofrequency ablation (RFA). SAE was effective in controlling haemorrhage from AMLs in the acute setting (six) but some patients required further intervention (four) and there was a significant complication rate. The reduction in tumour volume was only modest (28%). No complications occurred after surgery (median follow-up 5.5 years) or RFA (median follow-up 9 months). One patient was entered into a trial and treated with sirolimus (rapamycin). CONCLUSIONS The management of AML is both complex and challenging, especially in those with TSC, where tumours are usually larger and multiple. Although SAE was effective at controlling haemorrhage in the acute setting it was deemed to be of limited value in the longer term management of these tumours. Thus novel techniques such as focused ablation and pharmacological therapies including the use of anti-angiogenic molecules and mTOR inhibitors, which might prove to be safer and equally effective, should be further explored. [source] | ||||||||||