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)

Familial occurrence of malignant carcinoid is rare (about 3%). Authors describe occurrence of the malignant carcinoid in two brothers. In the older one the diagnosis was estimated in 1991. He had multiple intestinal carcinoid tumor with multiple liver metastases histological type III by Soga classification. Patient is intermittently treated with somatostatin analogue--lanreotid and with interferon alfa. By this therapy the disease is stabile. In the younger of brothers the diagnosis was estimated in 1999. The disease had rapid progression and in ten months patient died despite of the therapy. Definitive diagnosis was a malignant neuroendocrine tumor of pancreas-mixed low differentiated carcinoid with calcitonin overproduction. (Fig. 4, Ref. 15.)
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PMID:Malignant carcinoid in two brothers. 1172 74

Surgery is the only therapy able to cure patients with digestive neuroendocrine tumor. However, due to the presence of diffuse metastases, radical surgery is often not feasible. In these cases, medical treatment plays a critical role, because of its ability to control symptoms in functioning tumors and to inhibit tumor growth. Different therapeutic approaches, such as chemotherapy, hepatic artery chemoembolization and targeted radio-nuclide therapy can be used alone or combined to the biologic treatment with somatostatin analogues and interferon. However, an accurate staging by imaging procedures plus a histological, immunohistochemical and biomolecular examination must be performed before planning an optimal medical treatment.
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PMID:[Medical treatment of digestive neuroendocrine tumours]. 1175 37

The authors briefly review radiopeptides currently approved for use in the United States. They present a short review of the peptide somatostatin's actions and also note the five somatostatin receptors (SSTRs) to which the peptide and its synthetic analogs octreotide, lanreotide, and vapreotide bind. The many conditions besides neuroendocrine tumors having SSTRs are listed. Labeled octreotide and the other two analogues have a strong affinity for SSTR2 and SSTR5, which thereby produce positive imaging. The various neuroendocrine tumors best imaged by somatostatin receptor scintigraphy (SRS) are discussed, and the exceptions (insulinoma and medullary thyroid carcinoma) are noted to be seen better with labeled VIP and (99m)Tc-dimethylsuccinic acid (DMSA), respectively. SRS and VIP receptor scintigraphy are also noted to image many nonneuroendocrine tumors, which often have appropriate receptors. Several of the currently emerging and very effective new imaging techniques are described. These include (99m)Tc-DMSA for medullary thyroid carcinoma, (18)F dihydroxyphenylalanine positron emission tomography, and C(11) 5-hydroxytryptophan positron emission tomography scanning for all neuroendocrine tumor, but especially carcinoid tumor, metastases. The special role of SRS in identifying gastric carcinoid tumors in hypergastrinemic patients is reviewed. Various pitfalls in interpreting SRS are presented and receptor-enhancing techniques described. Besides use of SRS (mainly Octreoscan, Mallinckrodt Medical, St. Louis, MO) only for detecting and localizing primary tumors and metastases for staging, there are many additional special uses for clinical management of SRS-positive tumors. These include the intraoperative use of the handheld gamma-detecting probe. A brief enumeration is given of the most promising of other non-SST G-protein-coupled receptors and ligands currently under development. Finally, we have posed a number of questions for which answers are needed in the immediate future to facilitate better imaging. Extrapolations of current knowledge and experience with radiolabeled peptide pharmaceutical imaging are converted to reasonable speculations of anticipated future developments in this field.
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PMID:Radiolabeled peptides in diagnosis and tumor imaging: clinical overview. 1196 2

[(111)In-DTPA(0)]octreotide is a radiopharmaceutical with a great potential for the visualization of somatostatin receptor-positive tumors. The overall sensitivity of Somatostatin Receptor Imaging (SRI) to localize neuroendocrine tumors is high. In a number of neuroendocrine tumor types, as well as in Hodgkin's disease, inclusion of SRI in the localization or staging procedure may be very rewarding, either in terms of cost-effectiveness, patient management, or quality of life. The value of SRI in patients with other tumors, like breast cancer, or in patients with granulomatous diseases, has to be established. The development of Peptide Receptor Radionuclide Therapy (PRRT) is expected to stimulate peptide receptor imaging.
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PMID:Somatostatin receptor imaging. 1196 3

The high-level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled peptide analogues as tumor tracers in nuclear medicine. The vast majority of human tumors seem to overexpress one or the other of 5 distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress human(h) SSTR2, intestinal adenocarcinomas frequently express hSSTR3 or hSSTR4, or both of these hSSTRs. In contrast to (111)In-diethylenetriamine pentaacetic acid (DTPA)-(D)he(1)-octreotide (OctreoScan; Mallinckrodt, Petten, NL), which binds to hSSTR2 and 5 with high affinity (K(d)0.1-5 nmol/L), to hSSTR3 with moderate affinity (K(d)10-100 nmol/L), and does not bind to hSSTR1 and hSSTR4, (111)In /(90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d)200 nmol/L). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. When directly compared with (111)In-DTPA-(D)he(1)-octreotide and (111)In-DOTA-(D)he(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic imaging pattern are seen in about one third of tumor patients concerning both the tumor uptake as well as the detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a higher high-affinity binding affinity of (111)In-DOTA-(D)he(1)-Tyr(3)-octreotide for hSSTR2 (K(d)0.1-1 nmol/L). Beneficial results of receptor-mediated experimental radionuclide therapy were first reported for high-dose treatment with (111)In-DTPA-(D)he(1)-octreotide, based on the emission of Auger electrons. Phase IIa of the Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a European Study (MAURITIUS), shows in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy/GBq (90)Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the MAURITIUS study, cumulative treatment doses up to 232 mCi (90)Y-DOTA-lanreotide were given as short-term intravenous infusion. Preliminary treatment results in 154 patients indicate stable tumor disease in 41% (63 of 154) of patients and regressive tumor disease in 14% (22 of 154) of tumor patients with different tumor entities expressing hSSTR. No severe acute or chronic hematologic toxicity, change in renal or liver function parameters caused by (90)Y-DOTA-lanreotide treatment were reported for patients in the MAURITIUS trial. In two thirds of patients with neuroendocrine tumor lesions, (90)Y-DOTA-(D)he(1)-Tyr(3)-octreotide showed a higher tumor uptake and should therefore be considered the first choice for experimental receptor-based therapy. Potential indications for (90)Y-DOTA-lanreotide treatment are radioiodine-negative thyroid cancer, hepatocellular cancer, lung cancer, some brain tumors, and possibly melanomas. In conclusion, preclinical data and clinical studies confirm the potential usefulness of radiolabeled lanreotide for tumor diagnosis and therapy. However, careful consideration of the type of radiotracer used for receptor-mediated therapy should be made for the individual patient. Whole-body dosimetry should always be performed to predict doses for tumors and the critical organs, which are kidney and bone marrow.
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PMID:In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial. 1196 10

The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to overexpress more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to In-DTPA-DPhe(1)-octreotide (OctreoScan(R)) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (K(d) 10-100 nM) and does not bind to hSSTR1 and hSSTR4, (111)In / (90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d) 200 nM). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to (111)In-DTPA-DPhe(1)-octreotide and (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higherrdquuo; high-affinity binding of (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide to hSSTR2 (K(d) 0.1-1 nM). Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, such as (99m)Tc-depreotide (NeoSpect(R); NeoTect(R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or nonsmall cell lung cancer ((99m)Tc-depreotide), indicating high diagnostic cabability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. Beneficial results were reported for high-dose treatment with (111)In-DTPA-DPhe(1)-octreotide, based on the emission of Auger electrons. The Phase IIa study "MAURITIUS" (Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study) showed in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy / GBq (90)Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the "MAURITIUS" study, cummulative treatment doses up to 200 mCi (90)Y-DOTA-lanreotide were given as short-term infusion. Overall treatment results in 70 patients indicated stable tumor disease in 35% of patients and regressive tumor disease in 10% of tumor patients with different tumor entities expressing hSSTR. No acute or chronic severe hematological toxicity, change in renal or liver function parameters due to (90)Y-DOTA-lanreotide treatment, were reported. (90)Y-DOTA-DPhe(1)-Tyr(3)-octreotide may show a higher tumor uptake in neuroendocrine tumor lesions and may therefore be superior for treatment in patients with neuroendocrine tumors. However, there is only limited excess to long-term and survival data at present. Potential indications for (90Y-DOTA-lanreotide are radioiodine-negative thyroid cancer, hepatocellular cancer and lung cancer. Besides newer approaches and recent developments of 188)Re-labeled radioligands, no clinical results on the treatment response are yet available. In conclusion, several radioligands have been implemented on the basis of peptide receptor recognition throughout the last decade. A plentitude of preclinical data and clinical studies confirm their potential use in diagnosis as well as "proof-of-principle" for therapy of cancer patients. However, an optimal radiopeptide formulatioents. However, an optimal radiopeptide formulation does not yet exist for receptor-targeted radionuclide therapy. Ongoing developments may result in peptides more suitable for this kind of receptor-targeted radionuclide therapy.
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PMID:Experience with indium-111 and yttrium-90-labeled somatostatin analogs. 1217 31

Our objective was to report the outcome in patients with liver metastasis from endocrine tumors who underwent transarterial chemoembolization (TACE) as first-line non-surgical treatment. From January 1990 to December 2000, 14 patients with progressive unresectable liver metastases from digestive neuroendocrine tumor were treated with TACE (mean of 3.6 sessions) before any non-surgical treatment (somatostatin analogue, chemotherapy or interferon). Liver involvement was less than 50% in 11 patients. Size of the largest lesion ranged from 1.5 to 10 cm. Ten patients presented with carcinoid symptoms. The TACE was performed with Doxorubicin emulsified in Lipiodol and gelatin sponge particles. Symptomatic response upon flushes and/or diarrhea was complete in 7 of 10 cases and partial in 2 of 10 cases. An objective morphologic response was noted in 12 of 14 cases. The 5- and 10-year survival rate from diagnosis was 83 and 56%, respectively. Six patients were alive at the end of the study after 27-100 months from first TACE and 38-142 months from diagnosis. Three of them were successfully palliated for 55, 69, and 100 months with only TACE as treatment. Long-term palliation is possible in unresectable liver metastases from digestive neuroendocrine tumors with a few sessions of TACE as first-line and eventually exclusive treatment.
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PMID:Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. 1254 Nov 21

Neuropeptides can function as autocrine growth factors in cancer cells. High levels of bombesin (BB) and neurotensin (NT)-like immunoreactivity are present in small cell lung cancer (SCLC), a neuroendocrine tumor. Vasoactive intestinal peptide (VIP) stimulates and somatostatin (SST) inhibits the release of BB-like peptides from SCLC cells. BB-like peptides bind to BB(2) receptors, which are present on the cell surface. BB-like peptides stimulate the mitogen activated protein kinase (MAPK) cascade leading to increased expression of nuclear oncogenes and growth factors in SCLC cells. Due to the high density of neuropeptide receptors present on the cell surface, SST analogs have been radiolabeled to image neuroendocrine tumors. VIP receptors are present in many epithelial cancers including breast, colon, non-small cell lung cancer (NSCLC), pancreatic and prostate cancers. Due to the high density of VIP receptors on lung cancer cells, radiolabeled VIP agonists may be used to image these tumors. VIP receptor antagonists, such as VIPhybrid, inhibit the growth of cancer cell lines in vitro and in vivo. VIPhybrid and SR48692, a NT receptor antagonist, potentiate the cytotoxicity of chemotherapeutic drugs. These results suggest that neuropeptide receptor antagonists may be useful in the treatment of cancer.
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PMID:Neuropeptides as autocrine growth factors in cancer cells. 1257 Aug 13

Somatostatin (SS) is an inhibitory regulator of secretory and proliferative responses that activates a group of receptors in the plasma membrane termed SSR1-5. SSR2 is one of the most abundant SSR, which also is expressed in high numbers in many neuroendocrine tumor types. Here, we describe a study of the presence and intracellular localization of the spliced variant SSR2(a) and its endogenous ligand SS in the cultured human neuroblastoma (NB) cell line, SH-SY5Y, by immunohistochemistry and confocal laser scanning. The integral neuronal synaptic vesicle membrane proteins synaptophysin (p38) and SV2 were studied, as well as the IR of catecholaminergic and cholinergic markers. RA treatment was used as an inducer of neuronal-like differentiation in our SH-SY5Y cell line. After the treatment, the presence of catecholaminergic markers (including NPY) decreased while the cholinergic markers (including VIP) increased. p38 and SV2 as well as VIP were shifted into the rather long neuritic processes, indicating efficient intracellular transport. The SSR2(a) protein was significantly increased by RA treatment, but only minor increases in mRNA for this receptor protein could be seen. No subcellular co-localization between p38/SV2 and the cytoplasmic granular receptor material was demonstrated. The SSR2(a) receptor ligand SS was found to be present not only in the cytoplasm but also in the nucleus, and more strongly so after RA treatment. The possible reason for this may be that this peptide, like other small peptides, may serve as transcription factor, or cofactor.
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PMID:SSR2(a) receptor expression and adrenergic/cholinergic characteristics in differentiated SH-SY5Y cells. 1267 30

With the in vivo demonstration of somatostatin-receptor- positive tumors in patients using a radiolabeled somatostatin analog, peptide receptor scintigraphy became available some 15 yr ago. Octreoscan is a radiopharmaceutical with proven clinical importance in the visualization of somatostatin-receptor-positive tumors, and the overall sensitivity of somatostatin receptor imaging is high. In a number of neuroendocrine tumor types, as well as in Hodgkin's disease, inclusion of somatostatin receptor imaging in the localization or staging procedure may be very rewarding. The value of somatostatin receptor imaging in patients with other tumors, like breast cancer, or in patients with granulomatous diseases, has to be established.
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PMID:Octreoscan radioreceptor imaging. 1272 12


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