Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was performed to investigate HIF-1alpha (hypoxia-inducible factor-1alpha) expression in a large number of immunohistochemically and ultrastructurally characterized surgically removed pituitary tumours. The potential relation of HIF-1alpha with outcome variables as well as the presence of HIF-1alpha expression in the tumours treated with dopamine agonists and octreotide, a long-acting somatostatin analogue was also investigated. HIF-1alpha immunoreactivity was confined to the nucleoplasm whereas the nucleoli were unconspicuous. The distribution of HIF-1alpha was evident in the tumours whereas normal adenohypophysial cells showed no HIF-1alpha staining. HIF-1alpha expression was detected not only in the tumour cells but also in endothelial cells lining the blood vessels within the tumour. ACTH producing adenomas showed the lowest level of HIF-1alpha expression whereas pituitary carcinomas and GH producing adenomas had the highest counts. The statistical study demonstrated no significant correlation between HIF-1alpha expression, patient age, gender, tumour, size, invasiveness, cell proliferation rate and vascularity. These results suggest that the behaviour of pituitary tumours does not primarily depend of HIF-1alpha expression. Our study demonstrated an increase HIF-1alpha expression in bromocriptine treated PRL producing pituitary adenomas compared with untreated tumours but no increase in octreotide treated tumours.
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PMID:Expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in pituitary tumours. 1279 78

Pathological angiogenesis in the retina and underlying choroid is a major cause of visual impairment in all age groups. The last decade has seen an explosion in the clinical availability of antiangiogenic compounds. Emphasis has been placed on inhibitors of the VEGF signaling pathway and considerable success has been achieved with aptamers and antibodies that bind VEGF. However, regression of neovascularization is rarely permanent and the regrowth of new vessels, often within a few months, requires multiple applications of drug. A number of antiangiogenic factors such as IGFBP3, SDF-1 blockers, PEDF, gamma-secretase, Delta-like ligand 4, and integrin antagonists have been identified, which act either indirectly on the VEGF system or independent of it. The importance of other candidates such as HIF-1alpha and protein kinase CK2, which act as "master" regulators of angiogenesis, offer realistic alternative targets for pharmacological intervention. The concept of combination therapy is rapidly gaining interest in the eye field and co-administration of two angiogenic agents (e.g., a CK2 inhibitor with a somatostatin analog, octreotide) are often significantly more effective at inhibiting retinal angiogenesis than either drug alone. The following review will discuss the current therapies available for aberrant ocular angiogenesis, consider new candidate targets for development of antiangiogenic compounds and emphasize the importance of combinatorial pharmacological agents in the treatment of such a dynamic cellular event as angiogenesis.
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PMID:Retinal and choroidal microangiopathies: therapeutic opportunities. 1758 51

Gastroenteropancreatic (GEP) endocrine tumors are hypervascular tumors able to synthesize and secrete high amounts of VEGF. We aimed to study the regulation of VEGF production in GEP endocrine tumors and to test whether some of the drugs currently used in their treatment, such as somatostatin analogues and mTOR inhibitors, may interfere with VEGF secretion. We therefore analyzed the effects of the somatostatin analogue octreotide, the mTOR inhibitor rapamycin, the PI3K inhibitor LY294002, the MEK1 inhibitor PD98059 and the p38 inhibitor SB203850 on VEGF secretion, assessed by ELISA and Western blotting, in three murine endocrine cell lines, STC-1, INS-r3 and INS-r9. Octreotide and rapamycin induced a significant decrease in VEGF production by all three cell lines; LY294002 significantly inhibited VEGF production by STC-1 and INS-r3 only. We detected no effect of PD98059 whereas SB203850 significantly inhibited VEGF secretion in INS-r3 and INS-r9 cells only. By Western blotting analysis, we observed decreased intracellular levels of VEGF and HIF-1alpha under octreotide, rapamycin and LY294002. For rapamycin and LY294002, this effect was likely mediated by the inhibition of the mTOR/HIF-1/VEGF pathway. In addition to its well-known anti-secretory effects, octreotide may also act through the inhibition of the PI3K/Akt pathway, as suggested by the decrease in Akt phosphorylation detected in all three cell lines. In conclusion, our study points out to the complex regulation of VEGF synthesis and secretion in neoplastic GEP endocrine cells and suggests that the inhibition of VEGF production by octreotide and rapamycin may contribute to their therapeutic effects.
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PMID:VEGF secretion by neuroendocrine tumor cells is inhibited by octreotide and by inhibitors of the PI3K/AKT/mTOR pathway. 2038 30