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)

High-performance liquid chromatography-purified 125I-vasoactive intestinal peptide (VIP) bound to T-47D human breast cancer cells in a specific, saturable, and reversible manner. Scatchard plots were compatible with the presence of one class of VIP receptors with high affinity (Kd = 4.5 X 10(-10) M VIP, and Bmax = 293 fmol/mg protein). The neuropeptide and its natural analogues inhibited the binding of 125I-VIP and stimulated cyclic AMP (cAMP) generation in T-47D cells 96-fold (EC50 = 7 X 10(-10) M VIP), in the following order of potency: VIP greater than helodermin greater than human peptide with N-terminal histidine and C-terminal methionine greater than human pancreatic growth hormone-releasing factor greater than human secretin. In contrast, 125I-VIP binding was not displaced by pancreatic glucagon, human oxyntomodulin, truncated glucagon-like peptide-1, glucagon-like peptide-2, the somatostatin analogue SMS 201-995, gastric inhibitory peptide, and a series of steroid hormones or peptides unrelated to VIP. VIP also increased cAMP generation in seven other human breast cancer cell lines: H4-66B, HSL 53, HSL 78, MCF 7, MDA-MB231, T-47D2, and ZR75-1. Adenylate cyclase activity rose from 72.2 +/- 14 to 1069 +/- 66 pmol cAMP/min mg protein after the addition of 10(-7) M VIP to T-47D plasma membranes. In agreement with our pharmacological results and the Scatchard analysis of the binding data, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized receptor in the T-47D membranes permitted identification of one autoradiographic band with a molecular weight of 69,000. The sensitivity of the Mr 69,000 binding site to GTP and low doses of VIP implies that in T-47D cells, this component constitutes the membrane domain involved in the functional regulation of adenylate cyclase by VIP receptors. Our results indicate a role for the VIP receptor-cAMP system in human breast cancer cells.
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PMID:Pharmacology, molecular identification and functional characteristics of vasoactive intestinal peptide receptors in human breast cancer cells. 284 44

Various hormones and growth factors are involved in the growth regulation of breast (tumor) cells. In this report we show for the first time that an analogue of the neuropeptide somatostatin (Sandostatin) can also influence the proliferation of human breast cancer cells (MCF-7), namely, in an inhibitory fashion. With respect to dose-response relationship a bell-shaped curve was observed with the maximal inhibition of tumor cell growth at a sharply defined amount of Sandostatin (10 nM). The same effects were found with the natural hormone somatostatin-14 and another analogue (CGP 15-425). These results, together with the observation that high affinity binding sites for an iodinated derivative of Sandostatin are present in MCF-7 cells, support the conclusion that somatostatin and analogues act directly on breast cancer cells.
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PMID:Direct inhibitory effects of somatostatin (analogues) on the growth of human breast cancer cells. 288 Jun 60

The antiproliferative effect of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines (CG5, T 47 D, and ZR 75-1) is reported. Both peptides markedly inhibited CG5 cell growth with a maximal inhibition of about 40% as compared with control cells. The antiproliferative effect of somatostatin on T 47 D and ZR 75-1 cells was much less evident. These results suggest that somatostatin is a peptide inhibitory factor for human breast cancer cells. Possible therapeutic implications of these findings are still to be investigated.
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PMID:Antiproliferative effects of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines. 289 76

A new approach to the treatment of endocrine-dependent tumors based on analogs of hypothalamic hormones is in the early stages of development, but appears promising and significant. Administration of hypothalamic hormones can mimic hypophysectomy and gonadectomy, and is essentially devoid of side effects. A successful use of agonistic analogs of LH-RH for treatment of endocrine-dependent prostate cancer has been documented in several hundred patients. Experimental studies suggest that agonists and/or antagonists of LH-RH might be useful for treatment of breast cancer and pituitary tumors. Our work in animal models also indicates that analogs of somatostatin, alone or combined with LH-RH agonists, could be considered for therapy of chondrosarcomas, osteosarcomas, and pancreatic cancer. Experiments are in progress on the use of LH-RH analogs for treatment of ovarian cancer, neoplasms of the female genital tract, and for protection against gonadal damage during chemotherapy. These investigations should extend the concepts of endocrine treatment of cancers.
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PMID:Antitumor effects of analogs of hypothalamic hormones in endocrine-dependent cancers. 614 69

In the present study we have investigated the role of human breast-cancer-derived fibroblasts in the proliferation of primary cultures of epithelial cells derived from the same tumor. For this purpose, a co-culture system, using Transwell tissue-culture inserts with microporous membranes was employed. Fibroblasts and epithelial cells were enriched according to differences in their density on Percoll density gradients. The co-culture system was first established using MCF-7 breast cancer cells and a human fibroblast line (HF cells). Insulin, 17 beta-estradiol, EGF and HF cells all significantly stimulated the growth of MCF-7 breast cancer cells. The stimulatory effects of insulin, E2 and EGF were additive to the stimulatory effect of HF cells. These data suggest that (unique) factor(s), other than the above-mentioned growth-promoting compounds, are responsible for the growth-promoting effects of fibroblasts. In half of the human breast cancers investigated, tumor-derived fibroblasts stimulated tumor-derived epithelial cell proliferation. EGF significantly stimulated epithelial cell proliferation in 4 out of 6 cultures. The stimulatory effects of fibroblasts and EGF were additive or synergistic, and were observed in the additional presence of FCS, again suggesting production of unique factor(s) by the fibroblasts. In one culture the fibroblasts significantly inhibited epithelial tumor-cell proliferation. Conversely, the epithelial cells significantly stimulated proliferation of fibroblasts in 3 out of 3 cultures. The somatostatin analogue octreotide significantly inhibited epithelial cell proliferation by 46% in one tumor-cell culture in the absence, but not in the presence, of fibroblasts. In one culture, octreotide significantly inhibited the proliferation of fibroblasts co-cultured with epithelial cells.
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PMID:Role of tumor-derived fibroblasts in the growth of primary cultures of human breast-cancer cells: effects of epidermal growth factor and the somatostatin analogue octreotide. 752 13

Tamoxifen is a commonly used chemotherapeutic agent in human breast cancer, although some tumours develop resistance. Somatostatin is also being introduced as an anti-tumour agent. Here we show that the action of these drugs is, at least partly, due to their induction of apoptosis. Both 50 nM somatostatin, and 60 nM tamoxifen significantly enhanced the percentage of cells undergoing apoptosis, when compared to untreated or oestrogen treated control cells. This effect was observed in SK-N-BE(2) human neuroblastoma cells and in MCF-7G human breast cancer cells but not in their drug-resistant counterpart MCF-7A which showed a very low rate of spontaneous programmed cell death. Finally, we propose a simple test of the sensitivity and resistance of individual tumours to these agents by assessing their ability to induce apoptosis in vitro as measured by flow cytometry.
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PMID:Tamoxifen and somatostatin affect tumours by inducing apoptosis. 755 2

Biological data support the development of clinical trials designed to evaluate the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC). Although previous clinical trials have failed to show antitumor activity, various factors may have biased their results. In an attempt to improve our understanding of the role of SMS analogues in ABC, 10 patients with favourable prognostic factors and who had not been heavily pretreated for advanced disease were treated with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were periodically taken to evaluate the effect of the drug on growth hormone (GH) and insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although the drug was well tolerated, no clinical activity was observed. Serum GH and IGF-1 levels were not properly suppressed over time and drug serum concentrations fluctuated widely. In conclusion, SMS analogues cannot be recommended even as palliative treatment of ABC. Further studies should be undertaken to investigate the effect of higher drug doses, given subcutaneously or by means of continuous infusion, in suppressing GH and IGF-1 serum levels.
Breast Cancer Res Treat 1995 Jun
PMID:Biological and clinical evaluation of lanreotide (BIM 23014), a somatostatin analogue, in the treatment of advanced breast cancer. A pilot study by the I.T.M.O. Group. Italian Trials in Medical Oncology. 757 88

In a previous study, we found that morphine decreases, in a dose-dependent manner, the cell growth of T47D human breast cancer cells, despite the lack of mu opioid receptors and an interaction of morphine with other opioid sites. We have therefore examined a possible interaction of morphine with other membrane receptor systems of the cell. The present study describes for the first time an interaction between mu-acting opioid drugs and the somatostatinergic system. We have found that [125I]Tyr11-somatostatin binds with high affinity to T47D cells. Analysis of the binding data showed the presence of two components: one with high affinity but low capacity (Kd, 0.145 nM; 1450 sites/cell), and another of lower affinity but higher capacity (Kd, 1.192 nM; 11920 sites/cell). Somatostatin-14 and somatostatin-28 showed multiphasic displacement curves, indicating heterogeneity of binding sites. The latter was confirmed by reverse transcription-PCR, which revealed the existence of the somatostatin receptor subtypes 2 and 3 (SSTR2 and SSTR3), with a relative mRNA concentration of 85 and 15%, respectively. Morphine and the morphinomimetic peptide morphiceptine (Tyr-Pro-Phe-Pro-NH2) displace somatostatin from its binding sites. Further analysis indicated that mu-acting opioids interact with the SSTR2 receptor subtype.
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PMID:Morphine cross-reacts with somatostatin receptor SSTR2 in the T47D human breast cancer cell line and decreases cell growth. 758 46

Somatostatin-receptor (SS-R) scintigraphy successfully shows primary cancers and distant metastases in most patients with carcinoids, islet cells tumours, and paragangliomas. Previous in-vitro studies indicated that somatostatin receptors are present in human breast cancers. We report positive scintigraphy with [111In-DTPA-D-Phe1]-octreotide in 39 of 52 primary breast cancers (75%). Parallel in-vitro autoradiography with [125I-Tyr3]-octreotide of 30 of these showed a corresponding somatostatin-receptor status in 28. Significantly more invasive ductal cancers could be shown than invasive lobular carcinomas (85% vs 56%; p < 0.05). Also the number of T2 cancers which were shown was higher than T1 (86% vs 61%; p < 0.05). Imaging of the axillae showed non-palpable cancer-containing lymph nodes in 4 of 13 patients with subsequently histologically-proven metastases. In the follow-up after a mean of 2.5 yr, SS-R scintigraphy in 28 of the 37 patients with an originally SS-R-positive cancer, was positive in the 2 patients with clinically-recognised metastases, as well as in 6 of the remaining 26 patients who were symptom-free. Raised carcinoembryonic antigen (CEA) and CA 15-3 values were observed in only 2 and 1, respectively, of these patients. Most primary breast cancers can be shown by SS-R scintigraphy, especially invasive ductal cancers. This technique may be of value in selecting patients for clinical trials with somatostatin analogues or other medical treatments. Furthermore, SS-R scintigraphy is more sensitive than measurements of the usual serum cancer markers for detecting recurrences of SS-R-positive breast cancer.
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PMID:Somatostatin-receptor scintigraphy in primary breast cancer. 790 7

The use of agonistic analogues of luteinizing hormone releasing hormone (LHRH) is an established therapy for hormone-dependent metastatic pre-menopausal breast cancer. Their mechanism of action in this disease is the suppression of ovarian oestrogen production (medical castration). In the treatment of post-menopausal metastatic breast cancer, LHRH agonists also have some effect, although minor, probably through a suppression of ovarian androgen production. Convincing evidence has been accumulated that LHRH analogues can directly inhibit the proliferation of breast cancer cells in vitro. The clinical impact of these findings, however, is still controversial. Experimental data and several pilot clinical trials suggest that in epithelial ovarian cancer and sex-cord-stromal tumours of the ovary, LHRH agonists might have antitumour activity through the suppression of gonadotrophin secretion (selective medical hypophysectomy). Phase III clinical trials, evaluating this hypothesis, are in progress. Direct antiproliferative effects of LHRH analogues on epithelial ovarian cancer cells have been demonstrated in vitro. In endometrial cancer, experimental and early clinical results support the concept of a direct antiproliferative activity of LHRH analogues. Recently, potent antagonistic analogues of LHRH, devoid of relevant side-effects have become available for clinical testing. These new antagonists might be superior to agonistic LHRH analogues with respect to the rapidity and efficacy of selective medical hypophysectomy and medical castration. Modern LHRH antagonists might also permit a better exploitation of direct antitumour effects. A further therapeutic improvement in gynaecological oncology might result from a combination of LHRH agonists or antagonists with other peptide hormone analogues such as agonists of somatostatin or antagonists of bombesin/gastrin releasing peptide which have antitumour activity. Since 50% of breast cancers and 80% of epithelial ovarian cancers and endometrial cancers have high affinity binding sites for LHRH, cytotoxic LHRH analogues might provide a targeted chemotherapy, which would be more efficacious and less toxic than conventional regimens.
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PMID:The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers. 1096 15


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