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)

We have assessed the possible interaction between the microtubular component of the cytoskeleton and signal transducing GTP-binding (G) proteins by examining the ability of colchicine and vinblastine (two microtubule disrupters) to alter Gs and Gi protein activity in S49 lymphoma cells. Treatment of wild type S49 cells with cholchicine and vinblastine increased beta-adrenergic agonist- and prostaglandin (PG) E1-stimulated formation of cAMP. The microtubular inhibitor nocodazole also enhanced isoproterenol-stimulated cAMP accumulation, whereas the inactive analog of colchicine, beta-lumicolchicine, did not have this action. Based on data obtained with wild type, cyc-, and UNC S49 cells, we determined that enhancement in cyclic AMP accumulation is proximal to the catalytic (C) unit of adenylylcyclase, distal to hormone receptors, and seems to be located on Gs. Treatment with colchicine increased guanosine 5'-(gamma-thio)triphosphate-stimulated accumulation of cAMP in permeabilized wild type cells. The increase in activity of Gs appeared not to result from a change in the intracellular concentration of GTP. Treatment of cells with colchicine or vinblastine also increased the amount of the alpha s-C complex, as assessed by the binding of [3H]forskolin to intact cells at 37 degrees C. In contrast to the observed effect on Gs, treatment of wild type S49 cells with colchicine failed to modify the degree of inhibition of cAMP formation produced by somatostatin, which acts via the activation of Gi. These data suggest that microtubules regulate the ability of Gs to interact with and activate the catalyst of adenylylcyclase.
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PMID:Alteration in Gs-mediated signal transduction in S49 lymphoma cells treated with inhibitors of microtubules. 809 44

Somatostatin receptor scintigraphy with 111In-labeled octreotide was performed in 22 patients with suspected or known malignant lymphoma. The majority of extra-abdominal lesions (21/24 = 87.5%) were correctly localized, however, only one of nine intraabdominal lymphomas could be detected. No significant correlation was found between scintigraphic results and histological type of lymphoma. Metabolic imaging by positron-emission tomography with 18F-labeled deoxyglucose yielded a higher rate of detection of lymphoma manifestations (92% vs 64%) and better tumor contrast. Further prospective studies are needed to establish the clinical relevance of somatostatin receptor scintigraphy in malignant lymphoma.
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PMID:Somatostatin receptor scintigraphy in malignant lymphoma: first results and comparison with glucose metabolism measured by positron-emission tomography. 833 Aug 73

The regulation and function of CREB was examined in B cells to begin to elucidate the role of cAMP-derived signals in B cell activation. CRE-binding activity detected by the electrophoretic mobility shift assay was found to be constitutively expressed in nuclear extracts of primary murine splenic B cells and was unchanged in nuclear extracts obtained from B cells stimulated in a variety of ways. This activity was shown to be specific by competition analysis and to represent CREB or a closely related molecule on the basis of a "supershift" in the mobility of the nucleoprotein complex induced by anti-CREB antiserum. The function of B cell CREB was assessed by transient transfection of the murine B lymphoma cell line, BAL-17, with a CRE-dependent chloramphenicol acetyl-transferase (CAT) construct that contains a portion of the somatostatin promoter. Cross-linking of the surface Ig receptors of transfected BAL-17 B cells produced a threefold induction of CAT activity. Forskolin, which markedly induced CAT expression in PC12 cells transfected with the CRE-dependent construct, failed to stimulate CAT activity in transfected BAL-17 B cells despite an increase in cAMP. However, anti-Ig was found to act in synergy with forskolin to produce enhanced CAT activity. A phosphoprotein of appropriate molecular size for CREB was immunoprecipitated from anti-Ig plus forskolin treated BAL-17 B cells. These results suggest that CREB is present in primary B cells and that CRE-dependent gene expression is regulated by surface Ig either alone or in synergy with cAMP; the latter implies cross-talk between intracellular signaling pathways acting at the level of CREB.
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PMID:Induction of CREB activity via the surface Ig receptor of B cells. 839 39

Somatostatin receptor imaging (SRI) was carried out as part of the initial staging of 26 patients with histologically proven Hodgkin's (3) and non-Hodgkin's (23) lymphoma, and in the assessment of the first treatment's efficacy in seven of these patients. Static acquisitions over the whole body were performed 4 and 24 h after intravenous administration of 150 MBq of indium-111 pentetreotide. SRI data were compared with the results of conventional methods (clinical data, abdominal and thoracic computed tomography, bone marrow biopsy). Only 50 of the 86 (58%) confirmed extra-medullary tumour sites were detected by SRI. Twelve previously unknown localizations were visualized in seven patients. The Ann Arbor clinical stage was modified in only one of them. When tumoral tracer uptake was present, a tumour uptake index (TUI) was calculated using two regions of interest (one over the tumoral hot spot and one over the shoulder) on 24-h planar images. The patients were classified into three groups: high tumour uptake (TUI > 2.5 in all tumour sites, group A, six patients), low tumour uptake (1.5 < TUI < 2.5 in all tumour sites, group B, 18 patients), and no tumour uptake (group C, two patients). The sensitivity of SRI detection was higher in group A (90%) than in group B (52%) (P < 0.001). Six weeks after the fourth chemotherapy cycle, conventional methods and SRI were concordant in five of seven investigated cases (four complete remissions and one residual active thoracic mass showing tracer uptake), and discordant in two. SRI demonstrated residual tumoral tracer uptake in these two patients, who had previously been considered to be in complete remission. In conclusion, SRI does not seem to be reliable for the initial staging of lymphomas because of the highly variable and usually low tumoral tracer uptake. It may be more useful in the diagnosis of residual masses after treatment. However, further studies are needed to assess its specificity.
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PMID:Indium-111 pentetreotide scintigraphy in malignant lymphomas. 854 92

Somatostatin receptor (SS-R) scintigraphy has been successfully used in the visualization of a variety of neuroendocrine tumours. In vitro studies have shown that SS-Rs are present in human malignant lymphomas. We conducted a prospective study in 56 consecutive untreated patients with histologically proven Hodgkin's disease (HD) and compared the results of SS-R scintigraphy with physical and radiological examinations as initial evaluation. SS-R scintigraphy was positive in 55/56 (98%) patients at sites of documented disease. In 20 patients SS-R scintigraphy disclosed lymphoma localizations not revealed following procedures of conventional staging. As a result in 12 patients (21%) SS-R scintigraphy produced a change of stage and in seven patients (13%) the additional information obtained from SS-R scintigraphy led to a change of treatment. SS-R scintigraphy failed to visualize sites of HD in four patients, mainly in the abdominal area. In three patients a false-positive result was obtained. These data show that SS-R scintigraphy provides an imaging technique that appears to visualize tumours in most patients with HD and may be clinically useful in the management of these patients.
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PMID:Somatostatin receptor scintigraphy in the initial staging of Hodgkin's disease. 861 82

Somatostatin (SRIF) receptor (sst) expression on lymphoid cells may be related to activation or proliferation of these cells. We investigated the effectiveness of sst scintigraphy in the staging of malignant lymphomas compared with conventional methods. One hundred twenty-six patients with newly diagnosed, histologically proven malignant lymphoma (54 with Hodgkin's disease [HD] and 72 with non-Hodgkin's lymphoma [NHL]) received 111In-labeled DTPA-octreotide (> 200 MBq 111In) and were assessed by planar total-body scintigraphy and single-photon emission computed tomography (SPECT) images of the upper abdomen. The sst scintigraphy was positive in 98% of HD patients. Compared with conventional methods, additional lymphomas were detected in 37%, while lesions escaped detection in 7% (all located in the abdomen); 10 HD patients were downgraded and one was upgraded. The sst scintigraphy was positive in 85% of NHL patients, but positivity did not correlate with the degree of malignancy. Additional lesions were detected in 21% of NHL patients, with false-negatives in 7% and upgrading in 13 NHL patients. The results indicate that sst scintigraphy is sensitive in patients with HD and NHL and may reveal sites of active disease undetected by conventional methods, making it a useful diagnostic tool for malignant lymphomas. Further studies should define its value in clinical management.
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PMID:The relevance of somatostatin receptor expression in malignant lymphomas. 876 95

A variety of new diagnostic imaging methods have been developed in recent years for patients with Hodgkin's disease in an attempt to improve the detection of spleen and bone marrow involvement within the scope of staging and to discriminate between fibrosis and vital lymphoma after treatment. Somatostatin receptor scintigraphy has been performed only in a small number of patients to date and further studies must be conducted. Magnetic resonance imaging (MRI), as the established method, has shown its potential in several studies in detecting both spleen and bone marrow involvement; MRI investigations, however, only visualize a limited portion of the body and therefore must be performed in areas of clinically suspected disease. Immunoscintigraphy with radiolabeled antibodies is still in a preclinical or at most early clinical stage of evaluation and first results have to be confirmed in a controlled trial. Positron emission tomography (PET) with [18F]fluorodeoxy-glucose (FDG) is a technique which is still not a routine clinical procedure. However, whole-body FDG-PET seems to be a promising method in staging and follow-up of lymphoma, because it offers the unique capability of visualising metabolic activity throughout the entire body. Long-term multicenter studies are necessary to confirm these promising initial data. In the future, wholebody FDG-PET will probably be the technique of choice for immunoscintigraphic studies with radiolabeled monoclonal antibodies and studies on the pharmacokinetics of cytostatic compounds.
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PMID:New diagnostic imaging procedures in Hodgkin's disease. 883 11

We have studied prospectively 47 patients with CNS tumours including 16 meningiomas and 33 other tumours using combined 111In-octreotide and 99mTc-DTPA brain scintigraphy. 111In-octreotide scintigraphy was used to image somatostatin receptors (SSR) and 99mTc-DTPA scintigraphy was used to assess the integrity of the blood-brain barrier (BBB). A total of 32 tumours (65%) were detected. All SSR positive tumours also had positive 99mTc-DTPA scans and all SSR negative tumours were negative on 99mTc-DTPA scans. Among the tumours located outside the BBB, all meningiomas and two out of six schwannomas were positive on combined SSR/99mTc-DTPA scintigraphy. Among the tumours located inside the BBB, seven out of nine gliomas grade I-III were negative, whereas all glioblastomas were positive. Other positive tumours included one malignant non-Hodgkin lymphoma and two cerebral metastases. SSR scintigraphy alone was non-specific in the diagnosis of meningiomas, as 16 non-meningiomatous tumours also had positive SSR scans probably due to a breakdown of the BBB (excluding the malignant lymphoma). Measuring the tumour-to-background ratio on SSR scans improved specificity, but sensitivity was decreased below 70% because some meningiomas were only slightly positive. Only the ratio of SSR scintigraphy to conventional 99mTc-DTPA brain scintigraphy (SSR-to-BS index) allowed a reliable differentiation of meningiomas from other CNS tumours, most notable from schwannomas (sensitivity: 94%; specificity: 100%). Our results support the usefulness of combined SSR and conventional brain scintigraphy in the noninvasive pre-operative diagnosis of meningiomas.
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PMID:Noninvasive differentiation of meningiomas from other brain tumours using combined 111Indium-octreotide/99mtechnetium-DTPA brain scintigraphy. 895 37

Small-cell lung cancer (SCLC) cells may express somatostatin receptors [14]. Receptor-positive tissue can be visualised in vivo by scintigraphy with radiolabelled somatostatin analogues. In a prospective study we examined 18 patients with histologically proven SCLC for the diagnostic value of somatostatin receptor scintigraphy using indium-111 pentetreotide. Planar whole body scanning was performed 4 and 24 hours after administration. Additional SPECT imaging of the thorax and the abdomen was done at 24 hours. The results were compared with conventional staging procedures: ultrasound, x-ray, computed tomography and bone scintigraphy. In all 18 patients the primary tumour was correctly identified. Out of 13 patients with mediastinal lymphoma formation 10 patients showed positive SRS. In 2 more patients SRS showed mediastinal uptake while CT scanning was negative. The detection of distant metastases in patients with extensive disease was true positive in 8 cases (OSS, HEP, BRA), false negative in 4 cases (PLE, ADR, HEP), corresponding to a sensitivity of 67%. In 2 patients cerebral metastases were no longer detectable by SRS after previous local irradiation. Even though the method is limited in respect of revealing distant metastases in the upper abdominal area due to physiological uptake in liver, spleen and kidneys, differentiation between limited disease (LD) and extensive disease (ED) was possible in all cases. We conclude that [111In]pentetreotide scintigraphy is a suitable method for the detection of SCLC primary tumours and a substantial tool for differentiation between LD and ED if combined with ultrasonography of the upper abdomen.
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PMID:[Diagnostic value of somatostatin receptor scintigraphy with indium-111 pentetreotide in small-cell bronchial carcinoma]. 955 59

Primary lymphoma of the central nervous system, until recently representing about 1% of all brain tumours, shows a dramatically increased incidence in the general population as well as in high-risk groups (immunocompromised, AIDS), and may rise up to 6% in a population of AIDS patients. The clinical presentation is variable and cannot reliably be distinguished from other intracerebral tumours. At present, CT and MRI are the methods of choice for diagnosing cerebral lymphomas. However, their characteristics are not specific. The radiological picture may suggest glioma, meningioma, metastatic carcinoma or even a cerebrovascular accident. A labelled somatostatin analogue (pentetreotide) has been proposed as a new tracer for the imaging of somatostatin receptors, which have been identified by immunocytochemical or radioimmunoassay techniques in several organ systems. Somatostatin receptors were also identified in surgical biopsy samples from patients with Hodgkin and non-Hodgkin lymphoma and extracerebral lymphoma has already been visualised in vivo by means of In-111-labelled pentetreotide. While CT images of the brain showed a regression of the tumour after radiotherapeutic treatment, the scintigraphic images showed persistence of the tumoural tissue, corresponding with the clinical evolution and outcome. Furthermore, the absence of extra-cerebral lymphoma tissue, seen on the whole body images, was confirmed by post-mortem examination. To our knowledge, this is the first report of a primary intracerebral lymphoma visualised by means In-111-pentetreotide.
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PMID:Primary cerebral lymphoma visualised by means of In-111-pentetreotide scintigraphy. 992 25


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