Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Octreotide is a synthetic somatostatin analogue which has shown inhibitory activity against human breast cancer cells in culture. Ten patients with metastatic breast cancer and no prior hormonal therapy exposure received octreotide at 150 micrograms subcutaneously thrice daily. No objective responses were observed and the median time to treatment failure was short at 57 days.
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PMID:Octreotide as first-line treatment for women with metastatic breast cancer. 891 47

A new casomorphin pentapeptide (alpha S1-casomorphin) has been isolated from the sequence of human alpha S1-casein [alpha S1-casein-(158-162)], with the sequence Tyr-Val-Pro-Phe-Pro. This peptide was found to bind with high affinity to all three subtypes of the kappa-opioid receptor (kappa 1-kappa 2). When amidated at the C-terminus, alpha S1-casomorphin amide binds to the delta- and kappa 3-opioid sites. Both alpha S1-casomorphin and its amide inhibit in a dose-dependent and reversible manner the proliferation of T47D human breast cancer cells. This anti-proliferative activity was greater for alpha S1-casomorphin, which was the most potent opioid in inhibiting T47D cell proliferation. In T47D breast cancer cells, other casomorphins have been found to bind to somatostatin receptors in addition to opioid sites. In contrast, alpha S1-casomorphin and its amide do not interact with somatostatin receptors in our system.
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PMID:Identification of a novel opioid peptide (Tyr-Val-Pro-Phe-Pro) derived from human alpha S1 casein (alpha S1-casomorphin, and alpha S1-casomorphin amide). 892 Sep 97

Somatostatin (SRIF) and its analogs exhibit antiproliferative effects that are mediated by SRIF receptors (sst) present in responsive normal and neoplastic tissue including breast cancer. However, information regarding regulation of sst gene expression in cancer cells and modulation of SRIF binding is limited. In the present study we have determined the pattern of sst subtype messenger RNA (mRNA) expression in human breast cancer cells. Furthermore, we investigated the effect of 17beta-Estradiol (E2) treatment on steady state levels of sst mRNA by solution hybridization/nuclease protection analysis and on SRIF binding to membranes of treated cells by receptor binding assay. sst2 mRNA was highly expressed in T47D, ZR75-1, and MDA MB231 cells. Transcripts for sst1 were also detected at very low levels in ZR75-1 cells, whereas sst5 mRNA was expressed at low levels in MCF-7 cells. No sst subtype was detected in MDA MB 435s cells. When the estrogen receptor (ER)(+) cell lines T47D and ZR75-1 were cultured in phenol red-free media plus CS-FCS, sst2 mRNA levels decreased by 60-80% compared with complete serum controls. Adding E2 restored sst2 mRNA levels to control in both cell lines. Moreover, the effect of E2 on sst2 gene expression in T47D and ZR75-1 cells was dose- and time-dependent. In contrast, neither culturing in phenol red-free media plus CS-FCS nor E2 influenced sst2 expression in the ER(-) cell line MDA MB231. E2-induced regulation of SRIF binding and sst2 mRNA expression occurred in a parallel manner in T47D cells but were dissociated in ZR75-1 cells. The pure antiestrogen ICI 182 780 inhibited E2-induced sst2 expression in both cell lines. The antiestrogen 4OH tamoxifen showed strong estrogen-like effects on sst2 mRNA expression in T47D cells, while acting as a potent antiestrogen in ZR75-1 cells. Thus, these data suggest that E2 regulates sst2 expression in human breast cancer cell lines through the ER. The human breast cancer cell lines provide a useful model to examine the molecular mechanisms involved in E2 regulation of sst2 expression.
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PMID:Estrogen regulates somatostatin receptor subtype 2 messenger ribonucleic acid expression in human breast cancer cells. 894 Mar 94

Opioids and somatostatin analogs have been implicated in the modulation of renal water handling, but whether their action is accomplished through central and/or peripheral mechanisms remains controversial. In different cell systems, on the other hand, opioids and somatostatin inhibit cell proliferation. In the present study, we have used an established cell line, derived from opossum kidney (OK) proximal tubules, in order to characterize opioid and somatostatin receptors and to investigate the action of opioids and somatostatin on tubular epithelial tissue. Our results show the presence of one class of opioid binding sites with kappa, selectivity (KD 4.6 +/- 0.9 nM, 57,250 sites/cell), whereas delta, mu, or other subtypes of the kappa site were absent. Somatostatin presents also a high affinity site on these cells (KD 24.5 nM, 330,000 sites/cell). No effect of either opioids or somatostatin on the activity of the NA+/Pi cotransporter was observed, indicating that these agents do not affect ion transport mechanisms. However, opioid agonists and somatostatin analogs decrease OK cell proliferation in a dose-dependent manner; in the same nanomolar concentration range, they displayed reversible specific binding for these agents. The addition of diprenorphine, a general opioid antagonist, reversed the effects of opioids, with the exception of morphine. Furthermore, morphine interacts with the somatostatin receptor in this cell line too, as was the case in the breast cancer T47D cell line. Our results indicate that in the proximal tubule opioids and somatostatin do not affect transport, but they might have a role in the modulation of renal cell proliferation either during ontogenesis or in kidney repair.
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PMID:Identification and characterization of opioid and somatostatin binding sites in the opossum kidney (OK) cell line and their effect on growth. 897 57

Somatostatin is a widely distributed inhibitory peptide with growth-inhibitory effects in several human tumours, including breast cancer, raising the possibility that it may have therapeutic potential. The effects of somatostatin are mediated via a family of cell-surface receptors that differ in their tissue distribution, pharmacological properties and intracellular response mediators, suggesting that they mediate different functions of the peptide. We have analysed the expression of somatostatin receptor subtype (SSTR1-5) mRNA in normal and malignant breast tissue. Receptor expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) using receptor subtype-specific primers and by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR products. A total of 51 breast carcinomas, 36 samples of matched normal tissue, two axillary node metastases and eight normal/benign breast tissue samples were analysed. SSTR2 expression was ubiquitous in both normal and malignant breast tissue. Expression of SSTR5 was detected in approximately one-third of tumour and normal tissue, but fewer than 13% of all tissues expressed SSTR1, 3 and 4. These data suggest that SSTR2 gene expression is ubiquitous in breast cancer. Although this is unlikely to have diagnostic or prognostic significance, SSTR2-specific somatostatin analogues may have therapeutic potential in breast cancer.
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PMID:Analysis of somatostatin receptor subtype mRNA expression in human breast cancer. 906 98

Somatostatin receptors (SR) are surface markers characterizing not only APUDomas associated with neuroendocrine identities but also malignancies without neuroendocrine expression. Recently, the somatostatin analog pentetreotide was labeled with In-111 (OctreoScan 111, Mallinckrodt Medical BV, Petten, Holland) and introduced for the in vivo visualization in man of SR-positive tissues. In the present report, SR-specific scintigraphy is evaluated as a clinical tool for tissue characterization in correlation with histological and radiological examinations. Scintigraphy was focused and performed in cancer types without neuroendocrine tissue expression such as brain (n = 6) and breast tumors (n = 9) and lymphomas (n = 5). Scintigraphy was performed for comparison at 6 and 22 h after i.v. application of 111 MBq (3 mCi) of In-111-Pentetreotide. In the breast cancer group, the primary tumor was visualized in all 9 women as well as in all 4 cases with palpable axillary lymph nodes. Three women with a negative axillary node scan and impalpable nodes had positive biopsy. In two cases, mediastinal lymph node involvement was observed. So far the role of SR-positive breast cancer (BC) scans remains unknown. It is tempting to speculate that in resected women who are histologically and scintigraphically SR positive, it might be of value in the early detection of symptom-free recurrences. High densities of SR were present within both meningiomas, the high-grade astrocytoma and the craniopharyngioma. Differentiation of low- and high-grade astrocytomas could not be successfully achieved because both grades showed intense radioactivity uptake, even though high-grade tumors lack SR. The latter might be due to the damaged blood-brain barrier and the poor radioactivity washout observed in high-grade astrocytomas. All five lymphomas could be detected due to the presence of activated lymphocytes and macrophages that express SR at a sufficient density. In conclusion, SR scintigraphy in non-neuroendocrine malignancies does not seem to be reliable for an initial tumor staging but rather more suitable for a tissue characterization and extremely useful for monitoring changes of SR expression after treatment.
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PMID:Receptor scintigraphy of non-neuroendocrine cancers with In-111 pentetreotide. 908 40

Endocrine therapy of breast cancer consists of a variety of both medical and surgical ablative treatment modalities, but ablative therapy is increasingly replaced by medical treatment. Most endocrine therapies have more than one endocrine effect, frequently together with direct growth inhibitory actions via receptors. Endocrine therapy can be effective in all phases of the disease, but curative only in early disease while in advanced cancer it can only prolong survival. In the past decade the number of available endocrine agents has been drastically increased. Novel approaches in the endocrine therapy of breast cancer are application of new antiestrogens, antiprogestins, new potent aromatase inhibitors, analogues of luteinizing hormone-releasing hormone (LHRH-A) and somatostatin, inhibitors of prolactin secretion, vitamin A and D analogues, bisphosphonates, growth factor antagonists, tyrosine protein kinase inhibitors, protease inhibitors, inhibitors of angiogenesis, radiolabeled hormones and monoclonal antibodies. New cell biological factors such as oncogenes and suppressorgenes, secretory proteins and membrane receptors can be used not only as prognostic factors but also for prediction of type of response to endocrine and chemotherapy. Thus, these cell biological parameters can be used to select high and low risk patients, type of systemic treatment, and can also be used as targets for new treatment modalities. Future studies on treatment of all stages of disease will increasingly focus on promising combined treatment modalities.
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PMID:Novel endocrine therapies in breast cancer. 914 62

In-111 pentetreotide is a new radiolabelled [OctreoScan 111, Mallinckrodt Medical BV, Petten] somatostatin analog with high affinity to somatostatin receptors (SR). introduced for the in vivo imaging of SR positive tissues. In an attempt to evaluate its clinical usefulness for tissue characterization in malignancies without neuroendocrine expression in parallel with histological and radiological examinations, specific scintigraphy was performed on brain (6 cases), thyroid (6 cases) and breast (9 cases) tumors, and in lymphomas (9 cases) and melanomas (6 cases). A dose of 111MBq of In-111 pentetreotide was injected i.v. to each patient and scintimages at 6 and 22 hours (for comparison) p.i. were obtained. The primary lesion of the breast cancer population was imaged in all 9 cases as well as all the palpable axillary nodes in 4 cases. Three women with impalpable axillary lymph nodes scanned negative but had a positive biopsy. Both meningiomas were positive for SR scans: positive results were also obtained for the high grade astrocytoma and the craniopharyngioma: Two out of 6 patients with papillary thyroid cancer showed a marked radiotracer accumulation. Scintigraphy in all 5 lymphomas was positive for SR but did not detect the Tc-99m sulphur microcolloid [Lymphoscint, Solco, Basel, Suitzerland] imaged lymph nodes in 5 melanomectomized patients. When judging the imaging results of these non-neuroendocrine malignancies definite conclusions should not be drawn since the number of studied cases polymorph, was small for every cancer histotype; nevertheless SR scintigraphy does not seem to be reliable for tumor staging in non-neuroendocrine malignancies, but is more suitable for a tissue characterization and monitoring changes of SR expression during and after therapy.
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PMID:Somatostatin receptor scintigraphy of non-neuroendocrine malignancies with 111In-pentetreotide. 917

Rhenium-188 (beta- = 2.2 MeV; gamma = 155 keV; T1/2 16.9 hours) is an attractive therapeutic radioisotope which is produced from decay of the reactor-produced tungsten-188 parent (T1/2 69 days) and thus conveniently obtained on demand by elution from the alumina-based tungsten-188 /rhenium-188 generator system. The rhenium-188 is obtained as sodium perrhenate by elution of the generator with 0.9% saline. The post elution use of disposable tandem, ion-exchange columns is a simple method for the concentration of rhenium-188 saline solutions with specific volumes > 500 mCi/ml. This method can also extend the useful shelf-life of the generator, which can be as long as one year. The long useful shelf-life of the generator is expected to provide rhenium-188 at very reasonable costs for routine preparation of a variety of radiopharmaceuticals for the treatment of a variety of cancers including breast cancer. We are evaluating two types of Re-188-labeled agents under investigation which have potential for the treatment of breast cancer. Rhenium-188-labeled hydroxyethylidenediphosphonate (HEDP) and Re-188-dimercaptosuccinic acid (DMSA) are being applied for palliative treatment of pain associated with skeletal metastases, and the Re-188-RC-160 somatostatin analogue [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Lys-Val-Cys-Trp-NH2] for somatostatin-receptor-positive tumors. The results of initial clinical studies with the two bone pain agents demonstrate good targeting to skeletal metastases, and use of Re-188-HEDP has resulted in pain palliation with minimal bone marrow suppression in the initial patient studies. While these initial studies have been conducted in patients with prostate cancer, similar results are expected in planned studies in breast cancer patients. In animal studies, Re-188-RC-160 has been successfully used for the local/regional treatment of experimental breast cancer and other cancers. Re-188-RC-160 binds to somatostatin-receptor-positive cells both in vitro and in vivo, including breast cancer cells (ZR-75-1 breast carcinoma and NCI-H69 human small cell ling carcinoma), but not to binding-negative cells (Raji, Burkitt's lymphoma). A structurally similar Re-188-cyclic peptide with different binding specificity (CTOP [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Orn-Thr-Pen-Thr-ol]; an opiate-receptor antagonist) did not bind to target cells. Both gentisic acid and ascorbic acid are present in the Re-188-HEDP and Re-188-RC-160 formulations, and have been found to also significantly reduce radiolytic degradation of the somatostatin peptide analogues, and may have general application in the stabilization of Re-188-labeled radio-pharmaceuticals.
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PMID:Availability of rhenium-188 from the alumina-based tungsten-188/rhenium-188 generator for preparation of rhenium-188-labeled radiopharmaceuticals for cancer treatment. 917 35

Over the past decade, impressive antineoplastic activity of somatostatin analogs has been demonstrated in many tumor models. More recent research has provided information regarding mechanisms underlying the antiproliferative and apoptosis-inducing actions of these compounds. These include both 'direct' mechanisms that are sequellae of binding of somatostatin analogs to somatostatin receptors present on neoplastic cells and 'indirect' mechanisms related to effects of somatostatin analogs on the host. The upregulation of intracellular tyrosine phosphatase activity triggered by binding of ligands to the type II somatostatin receptor has received considerable attention as a direct mechanism, not only because this activity is the converse of the tyrosine kinase activity associated with many peptide mitogen receptors, but also because the type II somatostatin receptor is frequently expressed by common human neoplasms, including breast cancer. The potential importance of indirect mechanisms of action of somatostatin analogs, such as alterations in host insulin-like growth factor physiology, is emphasized by the in vivo antineoplastic activity of these compounds against somatostatin receptor-negative neoplasms. Clinical efficacy and a favorable toxicity profile of somatostatin analogs in the treatment of relatively uncommon conditions such as acromegaly and neuroendocrine tumors have already been demonstrated. Preclinical data now are sufficient to justify controlled clinical trials in breast, prostate, and pancreatic cancer. The development of monthly depot formulations will facilitate the clinical evaluation of somatostatin analogs for these and other indications.
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PMID:Mechanisms of antineoplastic action of somatostatin analogs. 945 37


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