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)

Distinct proteins complexed with somatostatin and the somatostatin analogue BIM-23014C were revealed in human breast cancer cells using the cross-linking assay. One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer, nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM-23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr 27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was visible in HBL-100. No correlation was found between receptors for BIM-23014C and epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr 27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000), two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and one had just the Mr 42,000 complex. The presence of the three BIM-23014C receptors was positively correlated (P less than 0.05) to the low amount of sex steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor negative, progesterone receptor negative) versus four of 14 (estrogen receptor positive, progesterone receptor positive)]. Another positive correlation was established between the absence of progesterone receptors and the presence of these three complexes [12 of 16 (progesterone receptor negative) versus four of 14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor-positive biopsies and its inhibitory activity would support its clinical potential for the treatment of breast cancer.
Cancer Res 1992 Feb 15
PMID:Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay. 134 85

Protein kinase C (PKC) activity and expression were measured in 54 adenomas (prolactin (PRL)-, growth hormone (GH)- and non-secreting), 1 of them obtained from a patient treated with the dopamine agonist bromocriptine and 2 from patients treated with the somatostatin analog octreotide. They were also measured in normal human and rat pituitaries. Total PKC activity was measured by incorporation of 32P into histones, and PKC expression by dot blot immunoquantification using purified PKC as a standard. Both enzyme activity and expression were higher in adenomatous pituitaries than in normal human or rat pituitaries. PKC expression in GH-secreting and non-secreting tumors was significantly higher than that in PRL-secreting tumors. Furthermore, it was significantly higher invasive tumors than in non-invasive tumors. In the 3 adenomas which were obtained from patients treated with bromocriptine or octreotide and which were used for PKC-activity measurement, particulate- and soluble-PKC activities were significantly lower than those measured in non-treated adenomas.
Int J Cancer 1992 Mar 12
PMID:Protein kinase C activity and expression in normal and adenomatous human pituitaries. 134 14

AR4-2J, a rat pancreatic acinar-tumor cell line, was used to investigate long-term effects of basic fibroblast growth factor (bFGF) and somatostatin on pancreatic cancer cells. We observed that bFGF stimulated cell proliferation when cells were cultured in serum-free medium. The effect was dose-dependent with half-maximal and maximal effects at 25 pM and I nM bFGF, respectively. The somatostatin analog SMS 201-995 (SMS) decreased the growth-promoting effect of bFGF. The maximal effect was observed at I nM SMS and the half-maximal effect at 20 pM SMS. Characterization of bFGF receptor-binding properties with [125I]bFGF revealed that AR4-2J cells exhibited 2 classes of bFGF binding site with respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9 pmol/10(6) cells. High-affinity receptors correlated with bFGF stimulation of AR4-2J cell growth, suggesting that the effects of bFGF are receptor-mediated.
Int J Cancer 1992 Mar 12
PMID:Basic fibroblast growth factor induces proliferation of a rat pancreatic cancer cell line. Inhibition by somatostatin. 134 15

A wide variety of primary and metastatic human neoplasms express somatostatin receptors (SS-Rs). We evaluated the SS-R status of malignant lymphomas that had been surgically removed from 31 patients by use of in vitro SS-R autoradiography with the SS analog 125I-[Tyr3]-octreotide as radioligand. Of 11 low-grade-malignancy B-cell non-Hodgkin's lymphomas, 10 were SS-R-positive, with a high receptor density restricted to the neoplastic follicles. All of the 8 intermediate-grade lymphomas were SS-R-positive. Of the B-cell lymphomas of high-grade malignancy, 7 out of 10 were SS-R-positive, often with a high density of receptors. One T-cell lymphoma and one Hodgkin's lymphoma were also positive. SS-Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In 4 patients, the lymphomas were localized in vivo by use of gamma-camera scintigraphy after i.v. injection of the SS analog 111In-[DTPA-D-Phe1]-octreotide. Hot spots, identified in all 4 patients, corresponded to SS-R-positive malignant-lymphoma tissue, as confirmed by receptor autoradiography of the surgically removed tumors. Our data show that SS-Rs are valuable pathobiochemical tissue markers and potentially useful in vivo diagnostic tools for human malignant lymphomas.
Int J Cancer 1992 Apr 01
PMID:In vitro and in vivo detection of somatostatin receptors in human malignant lymphomas. 134 40

Fifty-one adrenal pheochromocytomas and 14 paragangliomas were evaluated for somatostatin (SRIH) receptor content with in vitro autoradiography on tissue sections from surgically removed tumors, using iodinated 125I[Tyr]3 octreotide as radioligand. Thirty-seven of 51 pheochromocytomas were SRIH receptor positive (73%), as well as 13 of 14 paragangliomas (93%). These SRIH receptors were of high affinity, pharmacologically specific for SRIH and localized on the tumor tissue. Using in vivo imaging techniques with radiolabeled SRIH analogs, paragangliomas could be visualized in five patients, as well as pheochromocytomas in two of three patients. All tumors tested subsequently in vitro (n = 7) were shown to contain SRIH receptors. A majority of pheochromocytomas were also shown to have a high tumoral SRIH content as measured by immunohistochemical techniques. Detection of SRIH messenger RNA in pheochromocytomas by in situ hybridization indicated that the SRIH was produced in the tumors. A weak inverse correlation was observed between SRIH receptor status and tumoral SRIH content, suggesting that SRIH receptors may be down-regulated by high levels of endogenous SRIH in some tumors. There was no correlation between the SRIH receptor status and sex, age, tumor size, benign vs. malignant tumor, or urinary metanephrine excretion. These tumors were also analyzed for allelic losses on various chromosomes and showed significant loss of heterozygosity (LOH) on chromosomes 1p, 3p, 17p, and 22q. All eight tumors with LOH on chromosome 1p were SRIH receptor positive (100%), whereas only 6 of 11 tumors without LOH on 1p (55%) were SRIH receptor positive, suggesting a correlation between LOH on 1p and SRIH receptor positive status. SRIH receptors thus represent a consistent pathobiochemical marker for most of these adrenal and extra-adrenal tumors. In addition, these receptors may be of potential interest for the in vivo localization of these tumors.
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PMID:In vitro and in vivo detection of somatostatin receptors in pheochromocytomas and paragangliomas. 134 24

Fifty exocrine pancreatic adenocarcinomas and 57 benign tumors induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) were examined for the presence of argyrophil cells antiinsulin, -glucagon, -somatostatin, -pancreatic polypeptide (PP), -gastrin/CCK, -vasoactive intestinal polypeptide (VIP), and - neuron-specific enolase (NSE) reactive cells. Argyrophil - and antihormone-reactive cells were found in the normal pancreatic ducts and in the acini, as well as in hyperplastic and atypical ducts/ductules, tubular complexes, benign lesions, and in 80% of ductal adenocarcinomas. Insulin and antiNSE-reactive cells were the most common, followed in decreasing frequency by glucagon, somatostatin, and PP cells. Antigastrin-/CCK-and -VIP-reactive cells were found in two cases. Argyrophil cells were present in about 60% of the tumors with Grimelius staining and in 55% of those with Churukian-Schenk staining. Insulin cells were seen in ductal cancer that had grown into a lymph node and in the lymph node metastases of another cancer. A novel finding was the presence of argyrophil and insulin cells within the lumen of some malignant glandular structures. Coexistence of several peptide cells was found in 52% of the cancers. The presence of argyrophil and hormone-producing cells in induced pancreatic ductal/ductular lesions further strengthens the existence of a close developmental relationship between exocrine and endocrine cells of the pancreas.
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PMID:Immunohistochemical characterization of endocrine cells in experimental exocrine pancreatic cancer in the Syrian golden hamster. 135 11

Somatostatin is a regulatory peptide implicated in the control of cellular proliferation in epithelial tissues and this regulation may occur directly via membrane bound receptor activation. The aim of this study was to investigate somatostatin binding in human gastrointestinal cancer and normal mucosa. Plasma membranes were prepared from specimens of tumour and normal mucosa from 51 patients undergoing surgical resection for malignancy (28 gastric, 23 colorectal). Using a competitive displacement assay, specific 125I-tyrosine-11-somatostatin-14 binding to plasma membranes was assessed and and characterised in terms of receptor affinity (Kd) and maximum binding capacity (Bmax) as determined by Scatchard analysis. Specific low affinity (Kd = 166 nM), high capacity (Bmax = 1.2 pmol mg-1 protein) somatostatin binding was demonstrated in 22 of the gastric cancers and 17 of the colorectal cancers (Kd = 140 nM, Bmax = 1.8 pmol mg-1 protein). Similar affinity and binding capacity was demonstrable in normal mucosal samples. High affinity receptors for somatostatin were expressed by one gastric carcinoma (Kd = 0.9 nM; Bmax = 0.23 pmol mg-1 protein). Thus, low affinity, high capacity binding is a common feature of gastrointestinal tumours and normal mucosa, and high affinity receptors may occasionally be demonstrated. The functional significance of these low affinity binding sites requires elucidation to determine whether long-acting somatostatin analogues may have therapeutic benefit in gastrointestinal malignancy.
Br J Cancer 1992 Aug
PMID:Somatostatin binding in normal and malignant human gastrointestinal mucosa. 135 73

The rat pancreatic cell line, AR42J possessed high-affinity gastrin and somatostatin receptors and its growth was stimulated by physiological gastrin-17 concentrations between 5 x 10(-11) mol/l and 10(-9) mol/l as measured by [75Se]selenomethionine uptake. The somatostatin analogue, octreotide (2 x 10(-7) to 2 x 10(-11) mol/l), reduced this stimulated growth. Gastrin-stimulated AR42J growth was also inhibited by proglumide (3 x 10(-4) mol/l) and lorglumide (3 x 10(-5) mol/l) at maximal G17 concentrations of 5 x 10(-11) and 10(-10) mol/l, respectively, and the analogues competed with [125I] gastrin-17 (5 x 10(-10) mol/l) for binding to gastrin receptors on AR42J (50% inhibitory concentrations, less than or equal to 10(-3) mol/l and 4 x 10(-6) mol/l, respectively. Octreotide reduced the basal growth of the human gastric cell line, MKN45G, (which is associated with intracellular gastrin immunoreactivity) in serum-free medium to 73% of control at a concentration of 2 x 10(-8) mol/l, which was reversed by gastrin-17 (10(-10) mol/l). Lorglumide (3 x 10(-5) mol/l) also reduced the basal growth to 30% of control, which was reversed to 78% by 10(-5) mol/l gastrin. Proglumide had no effect on the basal growth of MKN45G.
Eur J Cancer 1992
PMID:Inhibition of gastrin-stimulated growth of gastrointestinal tumour cells by octreotide and the gastrin/cholecystokinin receptor antagonists, proglumide and lorglumide. 135 50

The in vivo administration of somatostatin (SS) or its analogues is capable of suppressing the growth of pancreatic cancer in experimental animals. We examined the effects of SS-14 and its analogue RC-160 on the in vitro growth of two human pancreatic cancer cell lines MiaPaCa-2 and Panc-1 stimulated with epidermal growth factor (EGF) or insulin-like growth factor 1 (IGF-1). Neither SS-14 nor RC-160 inhibited the growth of either cell line. In contrast RC-160 did inhibit the EGF-stimulated growth of a rat pancreatic cancer cell line AR42J. Binding studies with 125I-Tyr11 somatostatin revealed the presence of a single class of high affinity binding sites with a Kd of 0.20 +/- 0.05 nM and a Bmax of 2.1 +/- 0.26 pmoles mg-1 protein on AR42J but not displaceable binding was observed on MiaPaCa-2 or Panc-1. We conclude that lack of receptors accounts for the failure of SS-14 and RC-160 to influence the growth of human pancreatic cancer in vitro. These results, taken together with other findings, lead us to question the therapeutic efficacy of somatostatin and its analogues as mono-therapy in the treatment of human pancreatic cancer.
Br J Cancer 1992 Sep
PMID:Human pancreatic cancer cell lines do not express receptors for somatostatin. 135 59

Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radioactive isotope-labelled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 30/31 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, 5/7 small cell lung cancers, 6/7 neuroblastomas, 38/49 primary breast cancers, and 0/18 pancreatic adenocarcinomas. Also 11/11 meningiomas, 4/4 astrocytomas and 0/3 glioblastomas could be visualized. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It is an in vivo method for the recognition of neuroendocrine cancers. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers.
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PMID:Somatostatin receptor imaging in the diagnosis and treatment of neuroendocrine tumors. 135 13


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