الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 191 |  |  |
| | | from | 191 | | |
Abstract
Angiogenesis is the process of new blood vessel development from pre-existing vasculature. Although vascular endothelium is usually quiescent in the adult, active angiogenesis has been shown to be an important process for new vessel formation, tumor growth, progression, and spread.
The angiogenic phenotype depends on the balance of proangiogenic growth factors such as vascular endothelial growth factor (VEGF) and inhibitors, as well as interactions with the extracellular matrix, allowing for endothelial migration. In healthy individual, angiogenesis is a feature of a limited number of physiological processes such as, during ovulation, development of the corpus luteum, embryogenesis, lactating breast, during immune response, and during Inflammation and wound repair. Also development of kidney and in the maintenance of glomerular structures and glomerular filtration barrier function.
Imbalance of an angiogenic response either because of the over production of normal forms of angiogenic mediators or of a relative deficiency in inhibitors results in a large number of pathologic conditions such as heart and brain ischemia, hypertension, osteoporosis, respiratory diseases, and many other diseases.
Endocrine glands are typically vascular organs, and their blood supply is essential for normal function and tight control of hormone feedback loops. In addition to metabolic factors such as hypoxia, the process of angiogenesis is also regulated by hormonal changes such as increased estrogen, IGF-I, and TSH levels.
By measuring microvascular density, differences in angiogenesis have been related to differences in tumor behavior, and similar techniques have been applied to both benign and malignant endocrine tumors with the aim of identification of tumors that subsequently behave in an aggressive fashion. In contrast to other tumor types, pituitary tumors are less vascular than normal pituitary tissue, although the mechanism for this observation is not known. A relationship between angiogenesis and tumor size, tumor invasiveness, and aggressiveness has been shown in some pituitary tumor types, but not in others.
There are few reports on the role of microvascular density or angiogenic factors in adrenal tumors. The mechanism of the vascular tumors, which include adrenomedullary tumors, found in patients with Von Hippel Lindau disease has been well characterized, and clinical trials of antiangiogenic therapy are currently being performed in patients with Von Hippel Lindau disease.
Thyroid tumors are more vascular than normal thyroid tissue, and there is a clear correlation between increased VEGF expression and more aggressive thyroid tumor behavior and metastasis.
Although parathyroid tissue induces angiogenesis when autotransplanted and PTH regulates both VEGF and MMP expression, there are few studies of angiogenesis and angiogenic factors in parathyroid tumors.
An understanding of the balance of angiogenesis in these vascular tumors and mechanisms of vascular control may assist in therapeutic decisions and allow appropriately targeted treatment.
The tumour-generated aggregation of many biological mediators has been found to result in the formation of a physical
barrier protecting the tumour from exogenous anti-cancer agents. Thus, pro-angiogenesis drugs should be used to stimulate physiological angiogenesis in aging, healthy patients; as drug-resistance and drug-delivery issues are to be overcome on existing drugs, more research is needed to find target specific anti-angiogenesis agents, which should be used to prevent and treat pathological angiogenesis.
Despite the enormous progress made in terms of prevention and early intervention, a pressing need remains to develop innovative therapeutic strategies for ischemic cardiovascular disorders, including acute myocardial infarction, chronic cardiac ischemia, peripheral artery disease and stroke. The induction of new blood vessel formation by delivering angiogenic genes to ischemic tissues continues to appear as a promising, alternative strategy to currently available therapies. In aspiring to induce therapeutic angiogenesis, the members of the vascular endothelial growth factor (VEGF) family have long been recognized as major molecular tools.
In diabetic retinopathy, the balance between VEGF and angiogenic inhibitors may determine the proliferation of angiogenesis in diabetic retinopathy. Since VEGF-A is a powerful angiogenic inducer, utilizing anti-VEGF treatments has proved to be a successful protocol in the treatment of proliferative diabetic retinopathy.
Dopamine agonists (already in clinical use for prolactinomas) have potent inhibitory actions on VEGF signaling, and thus may be a new tool in antiangiogenic therapy. Secretion of VEGF in the great majority of human pituitary adenomas is inhibited by dexamethasone. This suggests that glucocorticoids can be considered in the treatment of certain pituitary tumors. The cyclic nature of angiogenesis in the
female reproductive tract indicates that stimulation or inhibition of paracrine angiogenic factors may lead to new approaches for being able to influence reproductive endocrine disorders.
The use of angiogenesis inhibitors is not without risk. Sorafenib [anti-angiogenic agent] cause a unique combination of acute thrombotic microangiopathy and minimal change disease [MCD] resulting in renal failure and nephrotic syndrome.