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 efficacy of tamoxifen and ovariectomy in the management of breast cancer is limited by the resistance of many neoplasms to these endocrine therapies and by the fact that initially responding tumors often escape from control during long-term treatment. We evaluated the effect of coadministration of the somatostatin analogue octreotide, which has single agent activity in several in vivo and in vitro breast cancer models, on the antineoplastic actions of tamoxifen and ovariectomy on 7,12-dimethylbenz(alpha)anthracene-induced mammary tumors. Rats received tamoxifen (0.5 mg/kg twice weekly s.c.), octreotide (10 micrograms/kg/h for 6 weeks by osmotic minipump), or the combination 7 weeks following 7,12-dimethylbenz(alpha)anthracene administration. The number of tumors per animal and the sum of the volumes of palpable tumors per animal were significantly less in the combination treatment than in the others. In ovariectomized rats the marked regression of established tumors in the initial 4 weeks after ovariectomy was frequently followed by tumor regrowth. However, continuous infusion of octreotide (50 micrograms/kg/h for 6 weeks postovariectomy) significantly (P < 0.01) suppressed this regrowth. Our data suggest that octreotide enhances the antitumor effects of tamoxifen or ovariectomy in the 7,12-dimethylbenz(alpha)anthracene mammary cancer model.
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PMID:Somatostatin analogue octreotide enhances the antineoplastic effects of tamoxifen and ovariectomy on 7,12-dimethylbenz(alpha)anthracene-induced rat mammary carcinomas. 798 24

Various tumors of neuroendocrine origin that have amine precursor and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous injection of the somatostatin analogue [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks in its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]-octreotide) was developed. This analogue is excreted mainly via the kidneys, 90% of the dose being present in the urine 24 h after injection. Using 111In-octreotide scintigraphy, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, 3 out of 3 unclassified apudomas, but none out of 18 exocrine pancreatic carcinomas were visualized. Also, 19 out of 19 carcinoids, 15 out of 15 glomus tumors, 8 out of 12 medullary thyroid carcinomas, 6 out of 6 small cell lung carcinomas, 4 out of 4 growth hormone-producing and 6 out of 9 clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD-cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied to visualize breast cancer, lymphomas and granulomas. In 39 out of 50 patients with breast carcinoma, 10 out of 11 patients with non-Hodgkin lymphomas, 3 out of 3 patients with Hodgkin's disease, and 8 out of 8 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:111In-octreotide scintigraphy in oncology. 835 73

The binding characteristics of several cytotoxic analogs of luteinizing hormone-releasing hormone (LH-RH) developed in our laboratory were examined in membranes from human breast cancer and estrogen independent MXT mammary cancer. Specific binding of [125I]D-Trp6-LH-RH and the cytotoxic LH-RH analog [125I]T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (HMAQG) was demonstrated in membrane preparations from human breast and MXT mammary tumor cells. Ligand binding of T-98 was specific, saturable, and dependent on temperature, time, and plasma membrane concentration. Analysis of the binding data showed that in human breast cancer, interaction of [125I]T-98 was consistent with the presence of two classes of LH-RH receptors, one class showing high affinity and low capacity, and the other class showing low affinity and high capacity binding. In membranes from MXT mammary cancer, T-98 bound to one class of saturable, specific, noncooperative binding sites with high affinity and low capacity. The rates of association and dissociation for [125I]T-98 were calculated to be 4.757 x 10(8) M-1 min-1 and 0.016 min-1 (t1/2 = 38.7) in membranes from MXT mammary cancer. In human breast cancer, association rate constants (K1a and K1b) were 2.3 x 10(6) M-1 min-1 for binding to high affinity and 1.8 x 10(4) M-1 min-1 for binding to low affinity binding sites. Dissociation rate constants were K-1a = 0.0801 min-1 (t1/2a = 63.4 min) and K-1b = 0.0467 min-1 (t1/2b = 23.5 min), respectively. [125I]T-98 was not displaced by either unlabeled somatostatin or epidermal growth factor, but was displaced completely by unlabeled T-98 or [D-Trp6]LH-RH. The analysis of displacement curves of [D-Trp6]LH-RH by cytotoxic agonists and antagonists of LH-RH synthesized in our laboratory showed that T-121, AJ-11, T-120, T-133, and T-98 were the most potent in displacing [125I]D-Trp6-LH-RH from breast and MXT cancer membranes. Binding kinetics and analyses of displacement curves of [125I]D-Trp6-LH-RH and [125I]T-98 in membranes of human breast cancer and estrogen independent MXT mouse mammary cancer suggest that binding of the cytotoxic analog T-98 to the LH-RH receptor proceeds reversibly like that of its congeners without cytotoxic radicals. Our findings may provide a stimulus for further studies with LH-RH analogs carrying cytotoxic radicals.(ABSTRACT TRUNCATED AT 400 WORDS)
Breast Cancer Res Treat 1992
PMID:Evaluation of binding of cytotoxic analogs of luteinizing hormone-releasing hormone to human breast cancer and mouse MXT mammary tumor. 844 2

Somatostatin analogues have been shown to suppress some hormones and growth factors involved in breast tumour growth and a direct in vivo and clinical antimumour effect has recently been reported. In our study the effects of tamoxifen, combined with a depot somatostatin analogue in 33 postmenopausal untreated breast cancer patients, have been evaluated. Blood samples were obtained before treatment, after 14 days and then monthly, in order to evaluate the behaviour of serum IGF-I, GH and somatuline levels. The drug combination resulted in a significant and synergistic reduction of plasma IGF-I concentration. No significant changes of serum GH were observed. 12.5% of patients exhibited a complete response and 37.5% a partial response for an overall objective response rate of 50% (95% CL 35-69%). The high remission rate reported, the absence of overlapping side effects between tamoxifen and somatuline and the synergistic activity on IGF-I suppression justify a further evaluation of the drug-combination.
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PMID:Somatuline (BIM 23014) and tamoxifen treatment of postmenopausal breast cancer patients: clinical activity and effect on insulin-like growth factor-I (IGF-I) levels. 866 48

We describe the successful treatment with octreotide, a somatostatin analogue, of a patient with malignant hypercalcemia associated with advanced breast cancer. A 70-year-old female with advanced breast cancer was admitted to our department for treatment of hypercalcemia. The administration of pamidronate disodium was effective to decrease serum calcium from 6.2 mEq/l to 4.0 mEq/l for the first time, but her hypercalcemia later responded less to pamidronate, and her serum calcium remained raised in spite of the administration of pamidronate and elcatonin. Then, her condition deteriorated with hypercalcemic symptoms, such as nausea vomiting and drowsiness. After octreotide treatment (100 microg/body/day, s.c.) with a combination of prednisolone, her serum calcium level improved from 6.7 mEq/l to 5.0-5.5 mEq/l, Leading to a dramatic improvement in her symptoms. During these treatments, anti-cancer therapy, hydration and the administration of diuretics have been continued. We think octreotide is very useful for the treatment of malignant hypercalcemia associated with advanced breast cancer.
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PMID:[Somatostatin analogue treatment for malignant hypercalcemia associated with advanced breast cancer]. 871 28

Somatostatin receptor scintigraphy (SRS) with the diethylenetriaminopentaacetic-acid-conjugated somatostatin analogue [111In-DTPA-D-Phe1] octreotide, also known as 111In-pentetreotide, is a new non-invasive modality for the evaluation of tumours that express receptors for somatostatin. These receptors are present on neuroendocrine and other tumours, including lymphomas and some breast cancers. In oncology SRS is a promising diagnostic tool for localizing primary tumours, staging, control and follow-up after therapy, and for identification of patients who may benefit from therapy with unlabelled octreotide or, in the future, with radiolabelled octreotide. In the past few years many small and large studies investigating various aspects of SRS have been reported. In this review the value of SRS in the management of individual tumour types is explored. For many tumours the best sensitivity in lesion detection is only achieved by very careful imaging after the administration of at least 200 MBq 111In-pentetreotide. On the basis of the current experience the main value of SRS in oncology is in the staging and evaluation of gastroenteropancreatic tumours, paragangliomas, small-cell lung cancer and lymphomas. Promising areas for SRS are the evaluation of breast cancer, non-medullary thyroid cancer and melanoma, and initial results with targeted radionuclide therapy using radiolabelled octreotide have been reported.
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PMID:The diagnostic utility of somatostatin receptor scintigraphy in oncology. 878 66

Tamoxifen is useful in the treatment of breast cancer, but its effects in metastatic disease are rarely long term, and development of resistance to the drug is common. In vitro and in vivo data demonstrate anti-neoplastic (anti-proliferative) effects of somatostatin analogues, which may occur via binding to somatostatin receptors on the neoplastic cells, and/or via reductions in insulin-like growth factor-1 bioactivity. Moreover, several lines of evidence from in vitro and in vivo studies indicate that the long-acting somatostatin analogue octreotide enhances the anti-neoplastic effects of anti-oestrogenic agents such as tamoxifen. The anti-oestrogen-somatostatin approach appears to have a favourable long-term toxicity profile. Large-scale clinical trials are currently being planned to investigate the efficacy of combined tamoxifen plus octreotide therapy compared to tamoxifen alone in patients with breast cancer.
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PMID:Enhancement of the anti-neoplastic effects of tamoxifen by somatostatin analogues. 881 63

Neuroendocrine (NE) cells are involved in gastro-enteropancreatic (GEP) neoplasms. Biological markers, such as peptides hypersecreted by biologically active NE tumours, aid in the evaluation of response to treatment. For surgically untreatable NE neoplasms, the therapeutic approach remains undefined. Somatostatin analogues, particularly octreotide, can control the clinical effects of hormone overproduction in NE neoplasms and they have revolutionised individualised treatment, particularly for biologically active tumours. So far, like interferon, octreotide used at standard dosages has failed to control neoplastic growth per se. We gave the somatostatin analogue lanreotide to women with advanced breast cancer and to colorectal carcinoma patients. Results confirmed that inhibition of the production of insulin-like growth factor-1, which plays an important role in neoplastic proliferation, could be obtained using the highest doses. Considering these data, we started a clinical trial of 58 patients affected by NE tumours, treated with two sequential doses (500 and 1,000 micrograms subcutaneously t.i.d.) of octreotide. Long-term disease stabilisation (> 6 months) was achieved in 43% of patients but an objective response in only 3%. Good control of clinical symptoms and markers was obtained in 73 and 77% of cases, respectively. Toxicity was negligible. Somatostatin analogues should be carefully evaluated at high doses for possible anti-proliferative effects. Studies are currently investigating their promising association with interferon.
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PMID:The role of somatostatin analogues in the treatment of gastro-enteropancreatic endocrine tumours. 881 75

In previous studies, we have shown that opioid agonists ([D-Ala2, D-Leu5]enkephalin (DADLE), [D-Ser2, Leu5]enkephalin-Thr6 (DSLET), ethylketocyclazocine and etorphine) bind to opioid binding sites and decrease cell proliferation of human T47D breast cancer cells. Furthermore, we provided evidence about a cross-reaction, also in the T47D human breast cancer cell line, of mu-acting opioids with type-II somatostatin receptors. Since a potential source of opioid activity in the breast might be casomorphin peptides (produced by the enzymatic degradation of alpha-casein and beta-casein), we investigated the antiproliferative action of five different casomorphin peptides: alpha-casein-(90-95), alpha-casein-(90-96), beta-casomorphin, beta-casomorphin-(1-5) and morphiceptin. We show that all five peptides decreased, in a dose-dependent manner, cell proliferation. The general antagonist diprenorphine produced only a partial reversal of their action. Furthermore, we provide evidence that all peptides (except for morphiceptin) bind to delta- and kappa-opioid binding sites of T47D cells with different selectivity. Finally, we show that these peptides are also partial competitors at the somatostatin receptors present in the same cell line.
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PMID:Antiproliferative and receptor binding properties of alpha- and beta-casomorphins in the T47D human breast cancer cell line. 888 20

We report a series of new in vitro and in vivo data proving the selective antitumor activity of our somatostatin structural derivative, TT-232. In vitro, it inhibited the proliferation of 20 different human tumor cell lines in the range of 50-95% and induced a very strong apoptosis. In vivo TT-232 was effective on transplanted animal tumors (Colon 26, B16 melanoma, and S180 sarcoma) and on human tumor xenografts. Treatment of MDA-MB-231 human breast cancer xenografted in mice with low submaximal doses of TT-232 [0.25 and 0.5 mg/kg of body weight (b.w.)] caused an average 80% decrease in the tumor volume resulting in 30% tumor-free animals surviving for longer than 200 days. Treatment of prostate tumor (PC-3) xenografted animals with 20 mg/kg of b.w. of TT-232 for 3 weeks resulted in 60% decrease in tumor volume and 100% survival even after 60 days, while 80% of nontreated animals perished. We have demonstrated that TT-232 did not bind to the membrane preparation of rat pituitary and cortex and had no antisecretory activity. TT-232 was not toxic at a dose of 120 mg/kg of b.w. in mice. Long-term incubation (24 h) of tumor cells with TT-232 caused significant inhibition of tyrosine kinases in good correlation with the apoptosis-inducing effect. The level of p53 or KU86 did not change following TT-232 treatment, suggesting a p53-independent apoptotic effect. Preincubation of human breast cancer cells (MDA-MB-453) with TT-232 for 2 h decreased the growth factor receptor autophosphorylation. All of these data suggest that TT-232 is a promising and selective antitumor agent.
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PMID:A tumor-selective somatostatin analog (TT-232) with strong in vitro and in vivo antitumor activity. 890 13


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