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)

Binding of [125I]monoiodoinsulin to human astrocytoma cells (U-373 MG) was time dependent, reaching equilibrium after 1 h at 22 degrees C with equilibrium binding corresponding to 2.2 fmol/mg protein: this represents approximately 2,000 occupied binding sites per cell. The t1/2 of 125I-insulin dissociation at 22 degrees C was 10 min; the dissociation rate constant of 1.1 X 10(-2) s-1 was unaffected by a high concentration of unlabeled insulin (16.7 microM). Porcine insulin competed for specific 125I-insulin binding in a dose-dependent manner and Scatchard analysis suggested multiple affinity binding sites (higher affinity Ka = 4.4 X 10(8) M-1 and lower affinity Ka = 7.4 X 10(6) M-1). Glucagon and somatostatin did not compete for specific insulin binding. Incubation of cells with insulin (0.5 microM) for 2 h at 37 degrees C increased [2-14C]uridine incorporation into nucleic acid by 62 +/- 2% (n = 3) above basal. Cyclic AMP, in the absence of insulin, also stimulated nucleoside incorporation into nucleic acid [65 +/- 1% (n = 3)] above basal. Preincubation with cyclic AMP followed by insulin had an additive effect on nucleoside incorporation [160 +/- 4% (n = 3) above basal]. Dipyridamole (50 microM), a nucleoside transport inhibitor, blocked both basal and stimulated uridine incorporation. These studies confirm that human astrocytoma cells possess specific insulin receptors with a demonstrable effect of ligand binding on uridine incorporation into nucleic acid.
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PMID:Insulin binding to human astrocytoma cells and its effect on uridine incorporation into nucleic acid. 256 7

Forty nine gliomas were analysed for the following neuropeptides: somatostatin (SS), substance P (SP), neurotensin (NT) and vasoactive intestinal polypeptide (VIP) and the pituitary peptide, adrenocorticotrophin (ACTH). A significant amount of authentic SS was found in a medulloblastoma, and low concentrations of SP and NT immunoreactivity in an ependymoma and cerebellar astrocytoma respectively. The majority of the other gliomas did not contain detectable levels of these five neuropeptides. Low levels of neuropeptides were found in some specimens probably due to contamination with cerebral cortex.
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PMID:Neuropeptides in gliomas: identification of somatostatin 14 in a medulloblastoma. 287 61

The concentration of somatostatin-like immunoreactivity (SLI) was determined by specific radioimmunoassay in the cerebroventricular fluid of patients with tumours of the basal midline and compared to findings in patients with multiple sclerosis. Mean SLI levels of the two groups were not significantly different. In patients with basal tumours (astrocytoma, craniopharyngioma, etc.) SLI levels varied widely and tended to increase with increased intracranial pressure. Lateral ventricular SLI levels decreased in patients with blockade of foramen Monro and in patients with communicating hydrocephalus or post-radiation encephalopathy. There was no apparent correlation with dysfunction of the hypothalamohypophyseal axis.
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PMID:Somatostatin-like immunoreactivity in cerebroventricular fluid of patients with basal midline tumours. 289 Oct 71

A selection of 90 mainly endocrine but nonpituitary tumors have been tested for their content of specific somatostatin receptors using receptor autoradiography. Somatostatin receptors were detected in the following tumors: in all 5 meningiomas tested; in 3 of 39 malignant breast tumors; and in 3 growth hormone releasing factor-producing tumors, i.e., one mediastinal carcinoid, one intestinal carcinoma, and its liver metastasis. Receptor density varied greatly among individual tumors. Some of the positive tumors were biochemically characterized using in vitro binding assay and were shown to have saturable and high affinity receptors with pharmacological specificity for somatostatin. The following tumors did not contain somatostatin receptors: prostate carcinomas (n = 17); prostate hyperplasia (n = 2); ovarian carcinomas (n = 6); endometrial carcinomas (n = 4); primary liver cell carcinomas (n = 3); pheochromocytomas (n = 3); aldosteronomas (n = 2); medullary thyroid carcinomas (n = 2); one adrenocorticotropic hormone-secreting pulmonary carcinoid; one astrocytoma; one neurofibroma; one lung tumor; and one bladder tumor. Somatostatin receptors can be found in benign or malignant tumors, originating in part from tissue not primarily known as a somatostatin target. The biological function of such receptors is, therefore, partly unknown. If they can mediate antiproliferative properties, as has been suggested to be the case for somatostatin receptors in selected endocrine tumors in rats and humans, the present data could be of potential therapeutic interest.
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PMID:Somatostatin receptors in human endocrine tumors. 302 22

The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were subjected to immunoelectron microscopic study for glial fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III beta-tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III beta-tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 5-hydroxytryptamine (33%), beta-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter ("heterotopias"), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.
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PMID:Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study. 854 29

Paediatric oncology continues to search for improved methods for the early detection and effective treatment of solid tumours, especially those of the nervous system, which constitute 50% of all solid tumours in children and adolescents. These tumours, including neuroblastoma, meningioma, low-grade astrocytoma and medulloblastoma express somatostatin receptors and can be imaged effectively using 111In-octreotide. In addition to improved imaging techniques, somatostatin analogues are being developed for use in radioreceptor-guided surgery, as a component of adjuvant chemotherapy and for supportive treatment. Radioreceptor-guided surgery utilises 125I-Tyr3-octreotide or 125I-lanreotide to detect tumour foci within minutes of injection. It allows the detection of 0.1-1.0 mg tumour (1 x 10(5) to 1 x 10(6) tumour cells). This technique has successfully located foci of occult tumour in children with neuroblastoma. Somatostatin analogues are also currently being studied as tumour growth inhibitors between regular chemotherapy cycles and for the treatment of chemotherapy-induced pancreatitis in children with leukaemia. Research on somatostatin receptor subtype expression in paediatric tumours suggests that further investigation of analogue effects on growth inhibition and induction of differentiation will contribute to improved therapy for children with solid tumours.
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PMID:Clinical use of somatostatin analogues in paediatric oncology. 881 66

Somatostatin (somatotropin release-inhibiting hormone; SRIH) has been demonstrated in neurons of the central nervous system (CNS) as well as in endocrine cells of the pancreas and gastrointestinal tract and can suppress various immune functions including lymphocyte proliferation, immunoglobulin synthesis, and cytokine production. Since astrocytes possess antigen-presenting activity and can secrete a wide array of immunoregulatory and inflammatory cytokines, we studied SRIH gene expression in both astrocyte cell lines and mitogen-stimulated peripheral blood mononuclear leukocytes from healthy donors. We now report by means of a complementary DNA-based reverse transcription PCR that differential levels of SRIH mRNA were expressed in 9 of 11 human astrocytoma cell lines tested but were undetectable in activated peripheral blood mononuclear leukocytes as well as in a variety of human lymphocyte and monocyte cell lines. The synthesis and secretion of SRIH protein by astrocytoma cells that expressed SRIH transcripts were confirmed by specific radioimmunoassay of cell culture fluids. These findings support the notion that SRIH gene expression occurs in human astrocytoma cells but not in mature lymphoid cells of the immune system.
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PMID:Expression of the somatostatin gene in human astrocytoma cell lines. 899 28

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

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

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.
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PMID:Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas. 1035 35


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