Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide (SMS), a somatostatin analogue, is an established antigrowth peptide, but it does not effectively inhibit the growth of insulinoma cells. In order to study the mechanisms that underlie this apparent lack of an antiproliferative effect on insulinoma tumor cells we established the rat insulinoma cell line, RINm5F, in culture. Cells in culture were tested by incubation in media with and without SMS. To study tritiated [3H]-thymidine incorporation into extracted DNA (TTID), 2 muCi/well of 3H was added for 24 hr, and cells were harvested and assayed for TTID (cpm/microgram DNA). Insulin (IRI) and intracellular cAMP (cAMPi) were measured by RIA. To study the effects of SMS on insulin secretion, conditioned media were sampled after 24 hr. To study the effects of cAMPi, conditioned medium was used to extract cAMPi following incubation with SMS for 15 min. Increasing concentrations of SMS had no significant effect on TTID in the presence of 1% FBS. Trypan blue exclusion tests showed > 90% viable cells throughout all stages of these experiments. There were no significant differences in cell numbers and protein content in the presence of SMS. There was a significant decrease in the secretion of insulin and intracellular cAMP levels in response to 50 nM SMS. However, SMS significantly inhibited TTID in RINm5F cells following a 4-hr pretreatment with pertussis toxin (PT) (23553 +/- 1747 vs 20635 [cpm/microgram DNA] +/- 1983 [SEM], P < 0.01). We conclude that the inhibition of insulin secretion by SMS is associated with an attenuation of cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of somatostatin action in RINm5F cells in culture: preliminary evidence for possible altered G protein function. 135 94

The possible risk factors for failure of medical therapy were examined in 23 patients with pancreatic ascites or effusion. The ascites or effusion resolved completely in 10 patients after a mean (+/- SEM) of 30 +/- 2 days of conventional medical treatment. In five patients in whom conventional medical therapy failed, the addition of an octreotide (SMS 201-995) analogue to the medical therapy led to a resolution of the ascites (three patients) or effusion (two patients). Six patients underwent surgery after failed medical therapy, one patient died while receiving conservative therapy, and one patient refused hospital treatment. Serum sodium and albumin levels were significantly lower, and the ratio of total fluid protein to total serum protein was significantly higher in the group that failed to heal in response to conventional medical therapy. Nine of 11 patients with mild to moderately severe chronic pancreatitis healed in response to conservative therapy. Only one of 10 patients with advanced pancreatitis healed in response to conventional medical therapy. Our results suggest that a selective surgical approach is warranted to treat pancreatic ascites and effusion. In patients with mild or moderately severe pancreatitis, medical therapy is recommended. Patients with advanced pancreatic disease should be selected for early surgery. Octreotide may be useful in the patient in whom surgery may be associated with a prohibitive morbidity or mortality.
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PMID:Pancreatic ascites and effusion. Risk factors for failure of conservative therapy and the role of octreotide. 159 72

The influence exerted by somatostatin on the secretion of ACTH and opioid peptides has still to be clarified. To gain further information on this issue, we performed in 10 normal volunteers two CRF tests (100 micrograms i.v.) one of which was preceded by s.c. injection of 100 micrograms of the long-acting somatostatin analogue SMS 201-995 (Sandostatin, Sandoz) (SMS), given 30 minutes before CRF. Premedication with SMS markedly inhibited the response of beta-EP to CRF, leaving unchanged the response of beta-LPH, ACTH and cortisol; mean incremental areas of beta-EP were 199.8 +/- 49.31 (SEM) vs 532.9 +/- 95.91 pmol 120 min (P less than 0.01) in the CRF test with and without SMS, respectively. To interpret the selective inhibitory effect of SMS on CRF-stimulated beta-EP secretion, it can be hypothesized that: a) the action of SMS was confined to a population of pituicytes preferentially secreting beta-EP; b) SMS interfered with the processing of POMC inhibiting the formation of beta-EP; c) SMS acted on extrapituitary, possibly peripheral, sources of beta-EP. In conclusion, this study indicates that, in man, somatostatin selectively inhibits the CRF-induced secretion of beta-EP, but not that of ACTH and beta-LPH, by an action that may be exerted at pituitary or extrapituitary level. This is a further example of dissociated secretion of POMC-derived peptides.
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PMID:Effect of sandostatin on CRF-stimulated secretion of ACTH, beta-lipotropin and beta-endorphin. 165 95

Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201-995 (octreotide) in active acromegaly. Twenty-four-hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 micrograms three times a day throughout the first month. The dose was increased by 300 micrograms/day at monthly intervals to a maximum of 1500 micrograms/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24-h GH fell from a basal level of 34.3 +/- SEM 7.6 mU/l to 8.0 +/- 1.3 mU/l (P less than 0.05) after 6 months. At 1 month (300 micrograms/day) mean GH was 13.6 +/- 2.2 mU/l and at 2 months (600 micrograms/day) 10.8 +/- 2.2 mU/l (P less than 0.05 vs 300 micrograms/day dose), and at 5 months (1500 micrograms/day) 11.3 +/- 2.0 mU/l (all P less than 0.05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 micrograms/day. After 1 year the mean GH of the group (n = 8) was 7.5 +/- 1.3 mU/l (P less than 0.05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1-year period. We found no evidence that routinely increasing the dose beyond 600 micrograms/day was helpful.
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PMID:A long-term dose-response study of somatostatin analogue (SMS 201-995, octreotide) in resistant acromegaly. 190 8

Somatostatin receptors (SS-R) were measured with in vitro receptor autoradiography using the SS analog 125I-[Tyr3]-SMS 201-995 as radioligand in 342 breast-tumor samples. In a group of 158 "small" tumor samples (mean section surface: 14 mm2 +/- 0.4; mean +/- SEM), 34 tumors (21%) were SS-R positive. In a group of 72 "large" tumor samples (mean size: 180 mm2 +/- 8; mean +/- SEM), 33 tumors (46%) were SS-R positive. In this second group, more than half of the tumors had a non-homogeneous distribution of SS-R, i.e., tumor regions within SS-R positive tumors were SS-R negative. In a group of 48 additional patients, we could show that primaries and their metastases, or double primaries from right and left breasts, or 2 primaries resected consecutively, could both occasionally be SS-R positive. Finally, in 71 SS-R-positive primary tumors, 18 tumor samples were found to have simultaneously Epidermal Growth Factor receptors (EGF-R); in 12 of these 18 cases, the 2 receptor types were not topographically overlapping. Whereas SS-R were located on tumor tissue, EGF-R were often seen on adjacent normal lobules and ducts. These results show that a subgroup of breast tumors contain SS-R, in several cases non-homogeneously distributed. Their location does not coincide with that of EGF-R. Metastasis of SS-R-positive primaries may be SS-R-positive, as are sometimes second primaries. For evaluation of SS-R incidence and distribution, autoradiography is of advantage, specially if it is performed on large tumor samples, since it allows precise identification of the tissue elements containing these receptors.
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PMID:Somatostatin receptor incidence and distribution in breast cancer using receptor autoradiography: relationship to EGF receptors. 216 44

Twenty-six acromegalic patients were randomized to treatment with either SMS 201-995 or bromocriptine in increasing doses and were investigated before treatment, after 2, 4, and 8 weeks of treatment, and 2 weeks after discontinuation of treatment. There were two dropouts from the bromocriptine group and one from the SMS 201-995 group. Amelioration of clinical signs and symptoms was seen in both groups during treatment. After 8 weeks mean 12-h GH concentrations had declined from 13.8 +/- 5.2 to 2.9 +/- 4.4 (mean +/- SEM) in SMS 201-995-treated and from 18.8 +/- 7.5 to 5.4 +/- 1.2 micrograms/L in bromocriptine-treated patients. Somatomedin-C concentrations fell from 3.04 +/- 0.36 to 1.43 +/- 0.36 in SMS 201-995-treated and from 2.93 +/- 0.40 to 2.13 +/- 0.27 U/mL in bromocriptine-treated patients. Size reduction of the pituitary tumor was seen in one patient receiving bromocriptine. Gastrointestinal glucose absorption was delayed, and insulin secretion suppressed during treatment with SMS 201-995. Hemoglobin-A1 concentrations remained unchanged in SMS 201-995-treated patients, but declined in the bromocriptine group. Side-effects were common, but usually tolerable, with both treatments. It is concluded that both drugs are of benefit in the treatment of acromegaly.
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PMID:A randomized study of SMS 201-995 versus bromocriptine treatment in acromegaly: clinical and biochemical effects. 218 55

We studied the sequential changes of plasma levels of immunoreactive '7B2' (IR-7B2), a neuroendocrine polypeptide, after a subcutaneous injection of 50 micrograms of synthetic octapeptide somatostatin analogue (SMS 201-995) in seven patients with acromegaly due to GH-producing pituitary adenoma. Compared to the basal levels, mean plasma IR-7B2 and GH levels significantly decreased, until 5 and 10 h respectively after the administration of SMS 201-995. The mean (+/- SEM) nadir levels of plasma IR-7B2 and GH were 68.1 +/- 10.1 and 13.1 +/- 6.9%, respectively, compared to mean plasma levels before treatment (100%). Plasma IR-7B2 as well as GH levels did not change significantly when saline was administered subcutaneously to three acromegalic patients. In addition, plasma IR-7B2 levels did not change significantly after the administration of SMS 201-995 in normal subjects or in patients with primary hypothyroidism in whom SMS 201-995 induced a decrease of plasma TSH levels. These results strongly suggest that SMS 201-995 has an unequivocal suppressive effect on the synthesis and/or the secretion of 7B2 in human somatotroph adenoma cells.
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PMID:Effect of octapeptide somatostatin analogue (SMS 201-995) on plasma 7B2 (a neuroendocrine polypeptide) levels in patients with acromegaly. 233 11

Somatostatin is known to inhibit hormone release and gastrointestinal secretion and hence may be useful in the treatment of amine precursor uptake, decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural hormone. Our study evaluated the effect of a synthetic analog of somatostatin, SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated gastrin release and gastric acid secretion in 10 patients with the Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours; SMS 201-995, 1 microgram/kg, was given subcutaneously; gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a secretin (2 U/kg) or a calcium stimulation test (2 mg/kg) with or without pretreatment with SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in gastrin (ng X 60 min/ml) without SMS 201-995, 36.8 +/- 11 (secretin), and 129 +/- 30 (calcium) were reduced with SMS 201-995 to -1.1 +/- 0.76 (secretin) and -29 +/- 28 (calcium) (p less than 0.05). In the Zollinger-Ellison syndrome, SMS 201-995 caused significant and long-lasting inhibition of both tumor gastrin release and gastric acid secretion, probably by direct action on both the gastrinoma and the stomach. SMS 201-995 blocks acid secretion and secretin- and calcium-stimulated gastrin release, indicating that SMS 201-995 inhibits peptide secretion by postreceptor mechanisms. SMS 201-995 will be useful in the palliative treatment of apudomas.
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PMID:Observations on the effect of a somatostatin analog in the Zollinger-Ellison syndrome: implications for the treatment of apudomas. 242 19

Eight patients with postprandial hypotension and orthostatic hypotension were treated with the somatostatin analogue SMS-201-995. Low doses of this drug (0.2-0.4 microgram/kg) raised the blood pressure after breakfast in all six patients with postprandial hypotension. 60 min after breakfast the mean sitting blood pressure was 35 +/- 10 (SEM) mm Hg higher after administration of SMS-201-995 0.4 microgram/kg than after placebo (p less than 0.001). Larger doses (up to 1.6 micrograms/kg) raised upright blood pressure during the postprandial period in five of seven patients. Before therapy three patients were unable to stand after eating; after an injection of SMS-201-995 0.8 microgram/kg at the beginning of breakfast they were able to walk for 35-100 min. The duration of therapeutic effect of each injection was 3-6 h. Treatment was followed by abdominal cramps and nausea in two patients with gastroparesis diabeticorum. SMS-201-995 holds promise as a treatment for postprandial hypotension and orthostatic hypotension.
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PMID:Treatment of autonomic neuropathy with a somatostatin analogue SMS-201-995. 287 21

Serum type III procollagen propeptide (PIIIP) is a reliable index of tissue collagen synthesis. Since in acromegaly there is increased collagen production, we measured serum PIIIP in acromegalic patients before any treatment (basal), during medical treatment with the somatostatin analog SMS 201-995, and after pituitary adenomectomy. In all patients, serum GH and plasma somatomedin-C (SmC) levels were also measured. Basal serum PIIIP levels were significantly (P less than 0.01) higher in acromegalic patients (mean +/- SEM, 22.7 +/- 2.1 ng/ml) than in normal subjects (n = 30; 9.7 +/- 0.5 ng/ml), and they were significantly correlated with plasma SmC values (r = 0.31; P less than 0.05). A significant (P less than 0.01) reduction in PIIIP levels occurred in patients treated with SMS 201-995 or surgery (from 24.3 +/- 2.7 to 12.4 +/- 1 ng/ml) as well as in GH and SmC levels. The maximum percent decrease in serum PIIIP was significantly correlated with those in GH (r = 0.65; P less than 0.01) and SmC (r = 0.60; P less than 0.01). Serum PIIIP levels did not change in those patients in whom neither GH nor SmC were decreased by treatment. In conclusion, serum PIIIP levels are elevated in acromegalic patients, and they decline in parallel with GH and SmC during medical or surgical treatment. Serum PIIIP measurements may be useful in the evaluation of acromegalic patients to gain information on the biological activity of GH and in monitoring the course of the disease.
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PMID:Serum type III procollagen propeptide levels in acromegalic patients. 287 8


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