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

The available somatostatin analogs for subcutaneous administration lower growth hormone (GH) levels in more than 90% of patients and Insulin-like growth factor-I (IGF-I) levels in up to 60%. They are also capable of reducing tumor size in up to 50%. Recently long-acting somatostatin analogs were introduced. The use of these application forms can result in normalization of IGF-1 in 60% of patients after 1 year and in 75% after 3 years. The development of selective analogs for the somatostatin receptor subtype-5 potentially will enhance the potency and the spectrum of the medical treatment of acromegaly with somatostatin analogs. The new generation of dopaminergic drugs also form a potentially effective and well tolerated therapy that should be considered in the management of those acromegalic patients, which have relative low serum IGF-I concentrations, along with high serum prolactine levels. Finally, growth hormone receptor (GHR) antagonists are under development for the use in humans. Preliminary results look promising, when biochemical parameters are concerned. Interim analysis of a phase 3 study with B2036-PEG in 38 patients does show that normalization of IGF-I concentrations is reached in at least 92% of the treated patients.
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PMID:New medical treatment for acromegaly. 1108 Nov 77

Conventional treatments for acromegaly include surgery, radiotherapy, dopamine agonists and somatostatin (SMS) analogues, which effect disease control by lowering circulating growth hormone (GH). Due to variability in tumour characteristics, combinations of these treatment modalities leave a significant number of patients with sub-optimal serum GH and insulin-like growth factor-I (IGF-I) levels, which have been linked to increased morbidity and mortality. The GH receptor antagonist pegvisomant is a genetically engineered analogue of GH that prevents functional dimerisation of the growth hormone receptor (GHR); a process that is critical to GH action at the cellular level. A crucial amino acid substitution at Gly(120) to Arg(120) within the third alpha helix of the antagonist prevents functional GHR dimerisation. Pegvisomant represents a novel treatment for acromegaly as, unlike existing treatment modalities, the effectiveness of pegvisomant is independent of pituitary tumour characteristics. Initial clinical studies in patients with active acromegaly have demonstrated serum IGF-I normalisation in over 90% of patients receiving 20 mg per day, such that, in terms of serum IGF-I normalisation, pegvisomant now represents the most effective medical treatment for acromegaly. Although there are limited long-term data on the use of pegvisomant and questions regarding pituitary tumour growth and altered liver function remain, this therapy offers the prospect of serum IGF-I normalisation in the vast majority of patients with active acromegaly.
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PMID:The place of pegvisomant in the management of acromegaly. 1177 81

The primary aim of therapy should be to remove symptoms, reduce tumor bulk, prevent relapse, and improve long-term outcome. Surgery, radiotherapy and medical therapies are used to achieve these aims. Post-treatment mean "safe" serum growth hormone values of < 2.5 ng/ml should be the therapeutic goal. Transsphenoidal surgery remains the first line treatment for acromegaly. Patients with microadenoma can expect 85%, while those with macroadenoma 50% chance to achieve safe serum growth hormone levels. Less than 20% of acromegalics respond to treatment with bromocriptine, while quinagolide and cabergoline may show better clinical response; the success rate is higher for tumors secreting both growth hormone and prolactin. Dopamine agonists may be considered either in combination with somatostatin-analogues or as monotherapy in selected patients, and in those with co-secretion of prolactin. Octreotide (Sandostatin, Novartis) is a synthetic somatostatin-analogue, which is administered subcutaneously in doses between 100 and 250 micrograms 3 times daily. Long-acting octreotide (Sandostatin LAR, Novartis) contains octreotide incorporated into microspheres of biodegradable polymer. To effectively lower serum growth hormone levels, monthly injections of 10-30 mg of long-acting octreotide are needed, serum growth hormone falls to 2.5 ng/ml in 70% of cases, and serum insulin-like growth factor I normalizes in 67%. Slow release lanreotide (Somatuline SR, Ipsen) is an alternative depot long-acting somatostatin-analogue, which is administered in a dose of 30 mg intramuscularly every 14, 10 or 7 days. Both compounds are equally, if not more, effective than subcutaneous octreotide, and significantly improve patient compliance. Pegvisomant (Sensus Drug Development Corporation) is a genetically engineered growth hormone receptor antagonist, which inhibits growth hormone action. When given subcutaneously in a dose of 20 mg/day, serum insulin-like growth factor I levels return to normal in 90% of patients. Theoretical concerns of tumor expansion have not been a problem to date, but long term studies are needed. Primary medical--somatostatin-analogue--therapy is recommended if surgery fails, if the patient refuses or unsuited for surgery and it may be also considered in patients with macroadenoma with extra--but not suprasellar extension, since the surgical "cure" rates of these tumors are low.
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PMID:[Novel pharmacologic therapies in acromegaly]. 1206 60

Pituitary tumours are benign but cause significant problems, both because of their compressive effects on brain structures and also because of the syndromes of hormone excess or deficiency that they can cause. Endocrine therapy has become increasingly successful, with the development of dopamine agonists and somatostatin analogues. Recently growth hormone receptor antagonists have been developed by modification of the GH molecule. It is likely that further advances based on our understanding of the biology will dramatically improve the treatment of these tumours.
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PMID:Pituitary tumour therapy: using the biology. 1252 Oct 30

Medical therapy plays an important role in the management of acromegaly. Dopamine agonists and somatostatin analogs are two classes of drugs approved for this purpose worldwide. Pegvisomant, a growth hormone receptor antagonist, has recently been evaluated in clinical trials. Somatostatin analogs have been the mainstay of medical treatment during the last 10 yr with their acceptability enhanced by the development of depot preparations. Somatostatin analogs improve symptoms and signs of acromegaly in the majority, normalize IGF- 1 in up to 60%, and result in tumor shrinkage in up to half of patients. Dopamine agonists have modest efficacy and limited tolerability. They are more effective in mixed GH/prolactin-secreting tumors. Newer agonists with D2 receptor specificity have fewer side effects but are less efficacious than somatostatin analogs. The addition of a dopamine agonist to somatostatin analog therapy can result in greater biochemical control than with individual agents. Pegvisomant is the most effective drug treatment for acromegaly, but it is likely to have a major adjuvant role as its mechanism of action is not directed at the tumor. The availability of more effective and better tolerated drug therapies offers greater flexibility and individualization of therapy that will lead to improved patient care and disease control.
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PMID:Comparison of efficacy and tolerability of somatostatin analogs and other therapies for acromegaly. 1272 11

Pegvisomant is a pegylated analogue of growth hormone (GH) that functions as a growth hormone receptor antagonist. Clinical trials of its use in acromegaly commenced in 1997; the drug was approved in the US in March 2003 and in Europe in November 2003. In the same year, it was made available on prescription in several European countries, with further launches due in 2004. Pegvisomant is capable of normalising serum insulin-like growth factor-I concentrations (the chief mediator of disease activity in acromegaly) in 97% of patients with active acromegaly, and therapy is associated with a significant improvement in the symptoms and signs of GH excess. Disease control is achievable with pegvisomant in patients who are wholly or partially resistant or do not tolerate somatostatin analogues; preliminary data suggest that the drug may be particularly suitable for patients with acromegaly and co-existent diabetes mellitus.
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PMID:Pegvisomant: a novel pharmacotherapy for the treatment of acromegaly. 1500 35

Acromegaly is a rare but disabling condition associated with reduced life expectancy. It is caused almost invariably by a growth hormone-secreting pituitary adenoma. Transsphenoidal surgery and/or radiotherapy are still considered to be the treatment of choice, but despite recent advances in both these forms of treatment, the overall surgical cure rate remains approximately 60%, and radiotherapy is characterised by delayed effect and a high incidence of hypopituitarism. Medical therapy in the form of dopamine agonists and somatostatin analogues has traditionally been used as an adjunct to surgery and/or radiotherapy, but is increasingly being used as first line therapy in the treatment of acromegaly. Recently, a third form of medical therapy, the growth hormone receptor antagonist, pegvisomant, has been licensed for use in acromegaly. This article examines the design, properties, clinical efficacy and safety of pegvisomant.
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PMID:The role of growth hormone-receptor antagonism in relation to acromegaly. 1550 Mar 74

Somatostatin peptide analogs have revolutionized the medical treatment of patients with acromegaly. More recent deep intramuscular depot preparations have further improved control, with consistent suppression of growth hormone secretion and optimal lowering of insulin-like growth factor-1. Effective control of growth hormone should, with long-term use, reduce morbidity and mortality from acromegaly and has been shown to result in partial involution of the pituitary adenoma in the majority of treated patients. The currently available depot formulations allow for an injection frequency of 14 days (lanreotide LA 30mg) to 28 days (octreotide LAR 20mg) according to the manufacturers' recommendations. In clinical practice, dose titration by evaluating a growth hormone day profile prior to the next injection can extend the interval between injection (to 6 or even 8 weeks in certain individuals). This is especially true for octreotide LAR, which also has increased flexibility regarding dosage with a 10 and 30mg preparation. The annual 'drug cost' is broadly similar between the two formulations though the additional expenditure on nurse time and clinic visits incurred by an increased injection frequency is a significant consideration. Decreased injection frequency improves acceptability for the patient without a loss in treatment efficacy. A subjective return of typical acromegalic symptoms, such as sweating and headache, also seem to be useful in predicting the timing of the next injection. Other formulations and doses of lanreotide are currently being evaluated, but more interestingly, newer analogs with greater efficacy at the type 5 somatostatin receptor subtype, and pan-receptor analogs, are being developed. These peptides, in conjunction with the likely availability of a growth hormone receptor blocking agent (pegvisomant), will further expand the medical therapy options for patients with acromegaly.
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PMID:Optimizing somatostatin analog therapy in acromegaly: long-acting formulations. 1579 7

The genes that are part of the somatotropic axis play a crucial role in the regulation of growth and development of chickens. The identification of genetic polymorphisms in these genes will enable the scientist to evaluate the biological relevance of such polymorphisms and to gain a better understanding of quantitative traits like growth. In the present study, 75 pairs of primers were designed and four chicken breeds, significantly differing in growth and reproduction characteristics, were used to identify single nucleotide polymorphisms (SNP) using the denaturing high performance liquid chromatography (DHPLC) technology. A total of 283 SNP were discovered in 31 897 base pairs (bp) from 12 genes of the growth hormone (GH), growth hormone receptor (GHR), ghrelin, growth hormone secretagogue receptor (GHSR), insulin-like growth factor I and II (IGF-I and -II), insulin-like growth factor binding protein 2 (IGFBP-2), insulin, leptin receptor (LEPR), pituitary-specific transcription factor-1 (PIT-1), somatostatin (SS), thyroid-stimulating hormone beta subunit (TSH-beta). The observed average distances in bp between the SNP in the 5'UTR, coding regions (non- and synonymous), introns and 3'UTR were 172, 151 (473 and 222), 89 and 141 respectively. Fifteen non-synonymous SNP altered the translated precursors or mature proteins of GH, GHR, ghrelin, IGFBP-2, PIT-1 and SS. Fifteen indels of no less than 2 bps and 2 poly (A) polymorphisms were also observed in 9 genes. Fifty-nine PCR-RFLP markers were found in 11 genes. The SNP discovered in this study provided suitable markers for association studies of candidate genes for growth related traits in chickens.
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PMID:Identification and characterization of single nucleotide polymorphisms in 12 chicken growth-correlated genes by denaturing high performance liquid chromatography. 1582 39

Pegvisomant is a pegylated analog of growth that functions as a growth hormone receptor antagonist. The drug is capable of normalizing serum IGF-I concentrations (the chief mediator of disease activity in acromegaly) in 97% of patients, and therapy is associated with significant improvements in the symptoms and signs of GH excess. Biochemical control may be achieved with pegvisomant in patients wholly or partially resistant to somatostatin analogs, and there are emerging data to suggest that the drug may be particularly suitable for patients with acromegaly and co-existent diabetes mellitus.
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PMID:Treatment of pituitary tumors: pegvisomant. 1631 17


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