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 investigated the effects of our synthetic bombesin/gastrin-releasing peptide (GRP) antagonists and somatostatin analogue RC-160 on the growth of human small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (non-SCLC) lines in nude mice. Athymic nude mice bearing xenografts of the SCLC NCl-H69 line or non-SCLC NCl-H157 line were treated for 5 and 4 weeks, respectively, with somatostatin analogue RC-160 or various bombesin/GRP antagonists. RC-160, administered s.c. peritumorally at a dose of 100 micrograms per animal per day, inhibited the growth of H69 SCLC xenografts as shown by more than 70% reduction in tumour volumes and weights, as compared with the control group. Bombesin/GRP antagonists, RC-3440, RC-3095 and RC-3950-II, given s.c. peritumorally at a dose of 20 micrograms per animal per day, also inhibited the growth of H69 SCLC tumours. RC-3950-II had the greatest inhibitory effect and decreased tumour volume and weights by more than 80%. The growth of H-157 non-SCLC xenografts was significantly reduced by treatment with RC-160, but not with bombesin/GRP antagonist RC-3095. In mice bearing either tumour model, administration of RC-160 significantly decreased serum growth hormone and gastrin levels. Specific high-affinity receptors for bombesin and somatostatin were found on membranes of SCLC H69 tumours, but not on non-SCLC H157 tumours. Receptor analyses demonstrated high-affinity binding sites for epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on the membranes of H69 and H157 tumours. EGF receptors were down-regulated on H69 tumours after treatment with RC-160 and bombesin/GRP antagonists. The concentration of binding sites for EGF and IGF-I on the H157 tumours was decreased after treatment with RC-160, but bombesin/GRP antagonist RC-3095 had no effect. These results demonstrate that bombesin/GRP antagonists inhibit the growth of H-69 SCLC, but not of H-157 non-SCLC xenografts in nude mice, whereas somatostatin analogue RC-160 is effective in both tumour models. This raises the possibility that these peptide analogues could be used selectively in the treatment of various subclasses of lung cancer.
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PMID:Effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonists on the growth of human small-cell and non-small-cell lung carcinomas in nude mice. 794 94

Somatostatin (SS) acts as a universal endocrine off-swich, and also inhibits the growth of neuroendocrine tumors through its specific receptors. Small cell lung cancer (SCLC) demonstrates some neuroendocrine characteristics and has been proposed as a candidate for treatment with SS and its analogues. In the present study, we investigated the expression of somatostatin receptor (SSTR) subtype (SSTR1 and SSTR2) mRNA in various human lung cancer cell lines by the sensitive reverse-transcription-PCR method and Southern blotting. The levels of expression of SSTR1 mRNA were higher in both SCLC and squamous cell carcinoma than in adenocarcinoma cell lines. Interestingly, SSTR1 gene expression was independent of that of SSTR2 in each SCLC cell line, although the expression of both genes showed a positive correlation in non-SCLC cells. Membranes from a cell line exhibiting highest expression of SSTR2 gene bound SS and its analogue, octreotide, with moderate affinity. These findings may provide useful information for the future clinical application of SS and its analogues for the treatment of lung cancer.
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PMID:Gene expression of somatostatin receptor subtypes, SSTR1 and SSTR2, in human lung cancer cell lines. 796 60

Somatostatin receptor scintigraphy (SRS) with the diethylenetriaminopentaacetic-acid-conjugated somatostatin analogue [111In-DTPA-D-Phe1] octreotide, also known as 111In-pentetreotide, is a new non-invasive modality for the evaluation of tumours that express receptors for somatostatin. These receptors are present on neuroendocrine and other tumours, including lymphomas and some breast cancers. In oncology SRS is a promising diagnostic tool for localizing primary tumours, staging, control and follow-up after therapy, and for identification of patients who may benefit from therapy with unlabelled octreotide or, in the future, with radiolabelled octreotide. In the past few years many small and large studies investigating various aspects of SRS have been reported. In this review the value of SRS in the management of individual tumour types is explored. For many tumours the best sensitivity in lesion detection is only achieved by very careful imaging after the administration of at least 200 MBq 111In-pentetreotide. On the basis of the current experience the main value of SRS in oncology is in the staging and evaluation of gastroenteropancreatic tumours, paragangliomas, small-cell lung cancer and lymphomas. Promising areas for SRS are the evaluation of breast cancer, non-medullary thyroid cancer and melanoma, and initial results with targeted radionuclide therapy using radiolabelled octreotide have been reported.
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PMID:The diagnostic utility of somatostatin receptor scintigraphy in oncology. 878 66

We examined the potential of radiolabeled somatostatin analogs, 125I-Tyr-3-octreotide (125I-octreotide), (111)In-DTPA(diethylenetriaminepentaacetatic acid)-D-Phe-1-octreotide (111In-octreotide), and 188Re-octreotide for targeting small-cell lung cancer (SCLC) in a mouse model. Tyr-3-octreotide was labeled with 125I by the chloramine T method, and (111)In-octreotide was obtained as a kit, while 188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled with 188Re by reducing disulfide bonds. The 125I-, 111In-, and 188Re-octreotides were injected i.v. into athymic mice bearing NCI-H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5+/-0.2, 0.3+/-0.1, 0.3+/-0.1 %ID/g, and tumor-to-blood ratios were 1.8, 11.9, 1.2 at 8 h for 125I-, 111In-, and 188Re-octreotides, respectively. Accumulations of 111In-octreotide in normal tissues were lower than those of 125I- and 188Re-octreotides. 188Re-octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111In-octreotide was the most suitable agent to obtain high tumor-to-normal tissue contrast for localizing SCLC.
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PMID:Localization of small-cell lung cancer xenografts with iodine-125-, indium-111-, and rhenium-188-somatostatin analogs. 887 64

We investigated the role of radiolabeled somatostatin analogs (SAs) in adrenal imaging. We evaluated 15 patients (6 men and 9 women, mean age 47 +/- 17 years) with imaging-detected adrenal tumors. Patient population was divided into two groups on the basis of the nature of adrenal lesions. Group 1 consisted of patients with benign adrenal lesions (n = 10). Group 2 consisted of patients with malignant adrenal lesions (n = 5). Pathology examinations were obtained in 13 cases: 7 pheochromocytomas, 2 adenomas, 2 cysts, 1 carcinoma, and 1 fibro-histiocytoma. One patient had a proven diagnosis of non-small-cell lung cancer associated with the presence of a right adrenal mass. The last patient had a clinical diagnosis of Werner syndrome associated with the presence of a large left adrenal mass. All patients underwent scientigraphic studies using radiolabeled SAs, of which indium-111 (In-111) pentetreotide was used in 11 cases and technetium-99m (Tc-99m)-labeled peptides (P-587 or P-829) were used in the remaining four cases. No significant labeled SAs uptake was observed in the majority (8 of 10, 80%) of the benign adrenal lesions (Group 1); however, increased uptake was found in two benign pheochromocytomas. Conversely, significant labeled SAs uptake was observed in the majority (4 of 5, 80%) of the malignant adrenal lesions (Group 2); however, the last lesion (carcinoma) did not show abnormal uptake. Results of this study show that the majority of benign adrenal tumors do not concentrate radiolabeled SAs; conversely, the majority of malignant adrenal lesions show significant SAs uptake, suggesting the presence of somatostatin receptors. This finding may allow the use of somatostatin as a treatment agent in malignant adrenal tumors. Thus, the main role of labeled SAs in adrenal imaging consists of lesion characterization rather than tumor detection and localization.
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PMID:The role of radiolabeled somatostatin analogs in adrenal imaging. 894 Jul 9

Somatostatin receptors have been identified on the cellular surface of a subset of patients with small cell lung cancer (SCLC) and may be associated with a less aggressive evolution of the tumor. Moreover, medical therapy with somatostatin analogues holds promise for neoplastic growth control. We performed planar imaging in 22 patients with histologically proven SCLC at 2-4 and 24 hours after the injection of 111-185 MBq of 111In-DTPA-octreotide (Octreoscan, Byk-Gulden). Tumor uptake was observed in 19 patients in both early and late scans, while 2 patients previously treated with chemotherapy showed negative early and late scans. One patient had a positive early scan and a negative late scan. All the scintigraphic studies showed more extensive disease than expected by CT. No significant modification in tumor uptake of radiooctreotide was observed in three patients studied before and after chemotherapy. In conclusion, 111In-octreotide is a suitable radiopharmaceutical for the in vivo evaluation of the somatostatin receptors of small lung cancer. The prognostic and therapeutical implications of this nuclear technique must be further investigated, however.
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PMID:111In-octreotide scintigraphy in small cell lung cancer. 900 64

Nuclear medicine plays a major role in the diagnosis of pulmonary embolism as well as in other lung diseases. Important innovations have concerned in recent years the equipment and radiopharmaceuticals. In ventilation studies the use of technegas, a monodisperse aerosol able to supply images of the same quality or even superior to gas images, is widespread in the clinical practice. Significant clinical results in the evaluation of acute thromboembolism have been achieved with antifibrin monoclonal antibodies and radioactive peptides specific for activated platelet receptors. Primary lung cancer and its metastases can now be visualized with tracers used for the study of myocardial perfusion (sestaMIBI, tetrofosmin) or labeled ocreotide, a molecule able to recognize lung tumors with somatostatin receptors. 99mTc-NR-LU-10 Fab immunoscintigraphy was shown to be very sensitive for tumors, while the major role of PET in the differential diagnosis of solitary pulmonary nodule, in the initial staging and in the response assessment to lung cancer therapy, is confirmed. SPECT is widespread in the clinical field with the use of 2-3 head gamma cameras and the possible combined imaging with CT or MRI. The use of PET with common gamma cameras with appropriate collimation systems or coincident recording without collimation is being studied. PET is used in the study of tumor metabolism as well as in the evaluation of intra-and extravascular lung water, regional blood flow and pulmonary vascular permeability. PET studies of vascular lung physiology as well as of receptor physiology, amine accumulation and clearance and drug transport to the areas of healthy or impaired lung, were also shown to be fundamental.
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PMID:Advances in pulmonary nuclear medicine. 914 15

Small cell lung cancer (SCLC) expresses somatostatin receptors that can be traced with 111In-DTPA-octreotide scintigraphy. Although this technique is currently employed for staging and follow-up of neuroendocrine tumors of the gastrointestinal tract, its role in the clinical work-up of SCLC is at present under discussion. A better imaging contrast is desirable and recent reports suggest that this aim could be achieved by pretreatment with cold octreotide. Here we report on the results of 111In-DTPA-octreotide scintigraphy in 12 SCLC patients carried out before and after octreotide treatment. The patients were treated for 7 days with octreotide 200 micrograms three times a day s.c. Uptake was studied at 5 h with whole body planar and SPET imagings. In all cases studied, pretreatment with octreotide was followed by enhancement of tumor imaging. In one patient a better contrast of the lesions was found at the parenchymal and mediastinal levels as well as at brain level, allowing a clear definition of otherwise questionable metastases. After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was observed in most cases, allowing a better imaging of liver metastases. The enhancement effect was confirmed by semiquantitative analysis of scintigraphic uptake. Taken together, our results seem to indicate that cold octreotide enhancement can improve 111In-DTPA-octreotide imaging and optimize its clinical role in SCLC.
Lung Cancer 1997 Jul
PMID:Intensification of 111In-DTPA-octreotide scintigraphy by means of pretreatment with cold octreotide in small cell lung cancer. 923 58

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

Several authors proposed the stage at diagnosis and some histopathological features as prognostic factors of bronchial carcinoids. However, since large tumour diameters or nodal metastases are frequently associated to aggressive histology, their prognostic role is unclear. To investigate the relationships between the clinicopathological parameters at diagnosis and outcome, 21 patients were analysed. Overall 26% of the radically resected patients recurred. Recurrences and disease-specific mortality were related to atypical histology and, only in cases with typical histology, to the presence of hilar or mediastinal lymph node metastases. These prognostic factors were valuable independently of the size of the primary tumour, that was remarkably homogeneous, always less than 3 cm, thus not predictive of recurrence. Moreover we evaluated the role of somatostatin receptor scintigraphy, a diagnostic tool only preliminary studied in this field. Scintigraphy with 111In-octreotide revealed the primary tumours at diagnosis (8/8), the increase in tumour size in two unresected patients, and all the cases of recurrent or metastatic disease (5/11), sometimes before the appearance of symptoms. These results suggest the usefulness of histology and nodal status as prognostic factors in clinical practice. Somatostatin receptor scintigraphy turns out to be a powerful diagnostic tool, for an accurate staging and an early diagnosis of recurrence in bronchial carcinoids.
Lung Cancer 1998 Nov
PMID:Bronchial carcinoid tumours: a study on clinicopathological features and role of octreotide scintigraphy. 1002 17


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