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)

Although various types of treatment of hepatocellular carcinoma (HCC) have been tried, the prognosis remains dismal, especially in patients with advanced stage of the disease. Somatostatin analogues exert antitumor effects. HCC have been shown to exhibit somatostatin receptors. The present randomized placebo-controlled study aimed at examining the efficacy of long-acting octreotide (Sandostatin LAR) for the treatment of advanced HCC. Seventy patients were randomized to receive a 2-week course of 250 microg short-acting octreotide twice daily followed by Sandostatin LAR 30 mg injection once every 4 weeks for 6 doses (n = 35) or placebo (control group) (n = 35). The clinical and laboratory parameters were monitored. There was no difference in the cumulative survival between the Sandostatin LAR-treated group compared with the control group [median survival 1.93 months vs. 1.97 months, respectively, P = NS (log-rank test)]. There was no tumor regression and no reduction of alpha-fetoprotein (AFP) levels in patients receiving Sandostatin LAR treatment. There was no improvement of quality of life assessed by Karnofsky performance score. In conclusion, Sandostatin LAR monotherapy did not have survival benefit in our selected group of patients with advanced HCC. Further studies should be performed in patients with less advanced disease and/or different etiology to evaluate its benefit.
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PMID:A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma. 1257 12

Depot somatostatin analogs are now increasingly being prescribed as adjuvant and primary therapy for the treatment of acromegaly. Previous studies have shown them to be both effective and safe, suppressing GH levels to less than 2 micro g/liter in 50-65% of cases and normalizing serum IGF-I levels in 65%. However, published data on their long-term efficacy and safety is scanty. We analyzed data from 22 patients (16 female and 6 male) treated with Sandostatin LAR or Lanreotide for an average of 41 months (range 12-89). Three patients had previously been treated with surgery, two with radiotherapy, and seven with both. Ten patients had received primary medical therapy. Mean pretreatment GH levels were 13.1 +/- 3.4 micro g/liter, and IGF-I levels were 592.9 +/- 53.9 micro g/liter. Results after 12 months of therapy indicated reduction in GH (3.2 +/- 0.7 micro g/liter; P < 0.0001) and IGF-I (321.9 +/- 33.9 micro g/liter; P < 0.001) concentrations, and this was sustained at latest follow-up. Using GH criteria (serum GH < 2 micro g/liter), 46% of subjects achieved a cure at 12 months, and 36% achieved a cure long-term. Fifty-two percent achieved normal IGF-I values at 12 months, and 67% long-term. Mean fasting and 2-h plasma glucose concentrations were similar at latest follow-up and at 12 months to baseline values. Three patients developed impaired glucose tolerance within 12 months of treatment, one going on to develop frank diabetes mellitus. However, glucose tolerance improved in five patients. Five patients developed gallstones while on treatment. In summary, this study reports the long-term efficacy of the depot somatostatin analogs as either adjuvant or primary therapy. Although overall glucose tolerance did not change, the development of impaired glucose tolerance in three patients at a time when GH levels were not changing highlights the ongoing need to monitor the long-term safety of these preparations.
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PMID:Long-term safety and efficacy of depot long-acting somatostatin analogs for the treatment of acromegaly. 1221 62

Somatostatin analogues are potent growth hormone and glucagon inhibitors and are commonly used in the treatment of several endocrine and non-endocrine disorders. We report severe and longstanding hypoglycemia triggered by long-acting octreotide (Sandostatin LAR) in a 62-year-old women with malignant mesenchymal tumor. Hypoglycemia developed after 6 hours of octreotide injection and she was admitted to the emergency unit with sweating, tremor, palpitation and confusion. On admission, her plasma glucose level was: 17 mg/dl (normal: 65-110), cortisol: 31 microg/dl (normal: 5-25), insulin: 4.32 microIU/ml (normal: 6-27), C-peptide: 2.64 ng/ml (normal: 0.9-4.0), growth hormone: 0.06 ng/ml (normal: 0.06-5.0), insulin-like growth factor-I: 8.5 ng/ml (normal: 101-303), insulin-like growth factor binding protein-3: 1715 ng/ml (normal: 2020-3990). Intravenous dextrose infusion was given for a month to sustain normoglycemia since hypoglycemia recurred following cessation of infusion. Therefore, prednisolone, 35 mg/day was added and the parenteral dextrose infusion rate was decreased gradually and finally stopped. Normoglycemia could be maintained with prednisolone 20 mg/day. In patients prone to tumor hypoglycemia, long-acting octreotide may trigger severe and prolonged hypoglycemia due to suppression of counter-regulatory hormones; clinical trial with short-acting octreotide may be warranted to predict and prevent this life-threating complication.
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PMID:Severe and prolonged hypoglycemia triggered by long-acting octreotide in a patient with malignant mesenchymal tumor: case report. 1267 21

Octreotide is a potent somatostatin analog that inhibits growth hormone (GH) release and restricts somatotrope cell growth. The long-acting octreotide formulation Sandostatin LAR is effective clinically in approximately 60% of patients with acromegaly. Tumoral GH secretion in this disorder is characterized by increases in pulse amplitude and frequency, nonpulsatile (basal) release, and irregularity. Whether sustained blockade by octreotide can restore physiological secretion patterns in this setting is unknown. To address this question, we studied seven patients with GH-secreting tumors during chronic receptor agonism. Responses were monitored by sampling blood at 10-min intervals for 24 h, followed by analyses of secretion and regularity by multiparameter deconvolution and approximate entropy (ApEn). The somatostatin agonist suppressed GH secretory-burst mass, nonpulsatile (basal) GH release, and pulsatile secretion, thereby decreasing total GH secretion by 86% (range 70-96%). ApEn decreased from 1.203 +/- 0.129 to 0.804 +/- 0.141 (P = 0.032), denoting greater regularity. None of GH pulse frequency, basal GH secretion rates, or ApEn normalized. In summary, chronic somatostatin agonism is able to repress amplitude-dependent measures of excessive GH secretion in acromegaly. Presumptive tumoral autonomy is inferred by continued elevations of event frequency, overall pattern disruption (irregularity), and nonsuppressible basal GH secretion.
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PMID:Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly. 1450 78

Previous studies have shown that the growth hormone (GH) axis is important for timing the later stages of puberty in female monkeys. However, it is not clear whether these growth-related signals are important for the initiation of puberty and early pubertal events. The present study, using female rhesus monkeys, used two approaches to answer this question. Experiment 1 tested the hypothesis that reduced GH secretion would blunt the rise in nocturnal LH secretion in young (17 mo; n = 7) but not older adolescent ovariectomized females (29 mo; n = 6). Reduced GH secretion was induced by treating females with the sustained release somatostatin analogue formulation, Sandostatin LAR (625 microg/kg). Morning (0900-0930 h) and evening (2200-2230 h) concentrations of bioactive LH were higher in older adolescent compared to young adolescent females. However, diurnal concentrations were not affected by the inhibition of GH secretion in either age group when compared to the placebo-treated, control condition. Experiment 2 tested the hypothesis that reduced GH secretion induced in young juvenile females would delay the initial increase in nocturnal LH secretion and subsequent early signs of puberty. In order to examine this hypothesis, puberty in control females (n = 7) was compared to those in which puberty had been experimentally arrested until a late adolescent age (29 mo) by the use of a depot GnRH analogue, Lupron (750 microg kg(-1) mo(-1); n = 7). Once the analogue treatment was discontinued, the progression of puberty was compared to a group treated in a similar fashion but made GH deficient by continuous treatment with Sandostatin LAR (n = 6). Puberty occurred as expected in control females with the initial rise in evening LH at 21 mo, menarche at 22 mo, and first ovulation at 30 mo. As expected, Lupron arrested reproductive maturation, but elevations in morning and evening LH and menarche occurred within 2 mo of the cessation of Lupron in both Lupron and Lupron-GH-suppressed females. In contrast, first ovulation was delayed significantly in the Lupron-GH-suppressed females (41 mo) compared to the Lupron-only females (36 mo). These data indicate that within this experimental model, reduced GH secretion does not perturb the early stages of puberty but supports previous observations that the GH axis is important for timing the later stages of puberty and attainment of fertility. Taken together, the data indicate that factors that reduce GH secretion may have a deleterious effect on the completion of puberty.
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PMID:Reduced growth hormone secretion prolongs puberty but does not delay the developmental increase in luteinizing hormone in the absence of gonadal negative feedback. 1511 27

Visual improvement following octreotide for growth hormone secreting pituitary macroadenomas is uncommon without tumour shrinkage. A 45-year old lady presented with blurred vision for 12 months. Visual assessment revealed a bitemporal hemianopia and CT scan demonstrated a large pituitary tumour with lateral and suprasellar extension. Acromegaly was confirmed by 75 g glucose tolerance testing. Primary transsphenoidal surgery was performed with normalisation of visual acuity and fields of vision. Post-operatively she had anterior pituitary hormone deficiency. As GH and IGF-1 levels remained elevated she underwent external pituitary irradiation. CT scanning demonstrated tumour shrinkage associated with a modest fall in GH levels. IGF-1 levels remained elevated falling to the age-related upper limit of normal after 5 years. At regular review she had stable visual acuity and fields of vision. She presented as an emergency 7 years from presentation with reduced vision and recurrence of bitemporal hemianopia. An MRI demonstrated a large pituitary adenoma. We therefore undertook a carefully monitored trial of octreotide with great caution with daily reassessment of acuity and fields. A decision was made to proceed to surgery in the event of deterioration or lack of improvement after a short trial over 5-7 days. We observed normalisation of visual acuity and perimetry within 3 days. She then commenced long-acting octreotide (Sandostatin LAR) 20 mg every 28 days. MRI after 1 week showed shrinkage of the tumour by a few millimetres. Five months later repeat MRI failed to show any further improvement in tumour size. However she remains well 29 months from treatment with normal vision and is being monitored carefully as her chosen form of therapy. Somatostatin analogues may be effective as therapy in a selected group of patients with acromegaly and visual loss who are not suitable for pituitary surgery. If used in this way the drug must be given cautiously with frequent detailed ongoing visual assessments. In this present case there has been a restoration of vision but the long-term outlook remains guarded without significant tumor shrinkage.
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PMID:Sustained improvement in vision in a recurrent growth hormone secreting macroadenoma during treatment with octreotide in the absence of marked tumour shrinkage. 1523 32

Adiponectin, an adipocyte-derived hormone, possesses insulin-sensitizing, antiinflammatory, and antiatherogenic properties. We hypothesized that hypoadiponectinemia was present in acromegaly, as in other conditions with increased insulin resistance and cardiovascular risk. Using an in-house RIA, serum adiponectin was determined in 35 patients with active acromegaly and 35 age-, sex-, and body mass index-matched healthy controls. Twenty-five patients were restudied after GH-lowering therapies. Serum adiponectin was significantly reduced in the acromegalic patients (4.3 +/- 1.8 vs. 6.7 +/- 1.8 microg/ml in controls; P < 0.001), but was increased after treatment with Sandostatin LAR, a long-acting somatostatin analog (5.8 +/- 2.6 vs. 3.8 +/- 1.6 microg/ml pretreatment; P < 0.001; n = 15) or transsphenoidal surgery (6.5 +/- 2.7 vs. 3.9 +/- 1.5 microg/ml preoperation; P < 0.01; n = 10). Fasting insulin was an independent determinant of serum adiponectin levels (P < 0.01) in control subjects, contributing to 11.7% of the variance in circulating adiponectin. In cultured 3T3-L1 adipocytes, adiponectin mRNA levels were decreased by insulin (1.5 microm; P < 0.005) or IGF-I (1 microg/ml; P < 0.05), but not by GH (1 microm) or somatostatin (1 microm). In conclusion, hypoadiponectinemia is present in active acromegaly, probably secondary to the inhibitory effect of high circulating insulin levels. Hypoadiponectinemia, reversible with GH-lowering therapies, may contribute to the increased insulin resistance and cardiovascular risk in patients with acromegaly.
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PMID:Serum adiponectin is reduced in acromegaly and normalized after correction of growth hormone excess. 1553 96

Octreotide acetate was developed as a pharmacologically stable, long-acting analogue of the hormone somatostatin. Mimicking the actions of somatostatin, octreotide has been used for its antisecretory effects. Randomized control trials have established the efficacy of octreotide for malignant bowel obstruction and for chemotherapy-induced diarrhea. Octreotide has proven to be an effective agent for symptoms of carcinoid syndrome. Newer uses include for bone marrow transplantation, infectious diarrheal syndromes, and management of hepatic metastases. More evidence is needed for the establishment of its efficacy for hypercalcemia, pain, pleural effusions, diarrhea after celiac plexus block, and malignant ascites.
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PMID:Established and potential therapeutic applications of octreotide in palliative care. 1825 59

Gastrinomas may occur in the pancreas, duodenum or peripancreatic lymph nodes. The gastrin overproduction leads to the Zollinger-Ellison syndrome with multiple gastric and duodenal ulcers and diarrhea. About two thirds of gastrinomas are malignant. Diagnosis is made by clinical history, gastroscopy, and measurement of serum gastrin, gastric juice pH, CT scan, endoscopic ultrasonography and somatostatin receptor scintigraphy. Surgery should always be considered if the liver is not involved. Proton pump inhibitors offer symptomatic relief. Medical therapy for tumor control includes biotherapy with alpha-interferon and somatostatin analogs yielding a response rate of about 10-15%, chemotherapy or targeted radiotherapy. We describe a patient with almost complete response on treatment with Sandostatin LAR, a long-acting somatostatin analog. In patients with metastatic gastrinomas not suitable for chemotherapy, interferon or targeted radiotherapy, single therapy with somatostatin analogs may be an alternative.
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PMID:Regression of a large malignant gastrinoma on treatment with Sandostatin LAR: a case report. 1837 30

We report on the efficacy of octreotide acetate in two patients with intestinal phlebectasia and no evidence of portal hypertension or mesenteric thrombosis. Patient 1 was a 46-year-old woman with primary pulmonary arterial hypertension. She required repeated transfusions for recurrent episodes of gastrointestinal bleeding (GIB). Intraoperative enteroscopy revealed wide-spread small bowel phlebectasia and intestinal resection was not performed. Blue rubber-bleb syndrome, portal hypertension and mesenteric thrombosis were ruled out. Octreotide acetate long-acting release was started. A transient interruption in treatment was followed by severe overt GIB. This was effectively controlled with continuous infusion of octreotide acetate. After this episode, octreotide acetate long-acting release was resumed and no further episodes of GIB have been reported until the most recent follow up (total duration of 74 months). Patient 2 was a 51-year-old woman with a history of recurrent GIB requiring multiple blood transfusions since young adulthood with negative endoscopic investigations. An enteroscopy showed numerous submucosal serpiginous varices in the colon and the terminal ileum. All putative causes including portal hypertension or mesenteric thrombosis were ruled out. Monthly intramuscular injections of long-acting octreotide acetate were initiated, and no GIB occurred since then (27 months of follow up). Somatostatin analogues are known to reduce splanchnic blood flow, to increase vascular resistance, to enhance platelet aggregation; and are thus efficacious in preventing GIB secondary to various vascular lesions (portal hypertension, intestinal angiodysplasia and blue rubber-bleb syndrome). These case reports suggest that they are also effective in preventing GIB in intestinal phlebactasia without portal hypertension.
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PMID:Octreotide for recurrent intestinal variceal bleeding in patients without portal hypertension. 1938 Oct 96


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