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)

Lung cancer is nowadays one of the most common malignancies and the leading cause of cancer mortality worldwide. Its early diagnosis and treatment is therefore the target of extensive research. Although radiologic imaging methods, especially CT, are the most widely used, they have well known constraints, including solitary pulmonary nodule characterisation, mediastinal lymph node staging, characterisation of the remaining tissue after chemo- or radiotherapy and early diagnosis of relapse. The main reason for these drawbacks is that radiologic methods primarily rely upon morphologic and anatomic criteria, which usually have little relevance to the biological status of a pulmonary lesion. The radiopharmaceuticals used in nuclear medicine, exploit special pathophysiologic localization mechanisms and provide unique functional information for their target tissues. Thus, many of the above mentioned problems can be elucidated. This is obvious in the published figures of sensitivity and specificity of the radionuclidic methods, which are often superior to those of CT [Table 1: see text]. In this article the main nuclear medicine procedures in the field of lung cancer imaging are reviewed. Emphasis is given in newer developments such as (99m)Tc-sestamibi, labeled somatostatin analogues and positron emission tomography with (18)F-FDG. We especially describe the "weaknesses" of the anatomic-radiologic imaging modalities and how the attending physicians, i.e. the pneumonologists, oncologists and thoracic surgeons can overcome them, by using the functional imaging methods of nuclear medicine.
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PMID:[Nuclear medicine procedures in lung cancer imaging]. 1584 Dec 89

There has been an exponential growth in the development of radiolabeled peptides for diagnostic and therapeutic applications in the last decade. The automated means of synthesizing these compounds in large quantities and the simplified methods of purifying, characterizing, and optimizing them have kindled attention to peptides as carrier molecules. These new techniques have accelerated the commercial development of radiolabelled peptides, which has provided additional radiopharmaceuticals for the nuclear medicine community. Peptides have many key properties including fast clearance, rapid tissue penetration, and low antigenicity, and can be produced easily and inexpensively. However, there may be problems with in vivo catabolism, unwanted physiologic effects, and chelate attachment. Radiolabeled peptides have made their greatest impact in the management of relatively rare neuroendocrine malignancies. Indeed, Indium-111 ((111)In)-pentetreotide ((111)In-DTPA-octreotide, Octreoscan), which binds to somatostatin receptors (SSTRs), has become the diagnostic 'gold standard' in these diseases. However, (111)In-pentetreotide has been less successful in the diagnosis of other more prevalent diseases in which SSTRs are upregulated. Technetium-99m (99mTc)-depreotide (NeoTect), a 99mTc-labeled SSTR-analog, could have wider impact since it has high sensitivity and specificity for lung cancer lesion detection. However, this impact may be minimized by the increased availability of positron emission tomography imaging with Fluorine-18 (18F)-flourodeoxyglucose, which has similar sensitivity and specificity for lesion identification in this disease, and is currently more widely used. The receptors for bombesin, alpha-melanocyte-stimulating hormone, neurotensin, and the integrin alpha(v)beta3, are under active investigation as targets for radiolabelled peptides, but are still in the pre-clinical stage. Compounds directed at the cholecystokinin-B/gastrin receptor have shown promising results in clinical trials in humans. Radiolabelled peptide therapy is usually indicated for patients with widespread disease that is not amenable to focused radiation therapy or is refractory to chemotherapy. Phase I/II studies using various radiolabelled peptides (including (111)In-pentetreotide, Yttrium-90 [90Y]-DOTA-Phe1-Tyr3-octreotide, 90Y-DOTA-lanreotide, and Lutetium-177 [177Lu]-DOTA-octreotate) for the treatment of patients with neuroendocrine malignancy are in progress. Over 400 patients have been treated, and the response rate has ranged from 60% to 75%, although few patients have had a complete response. Patients have been given individual doses ranging from 2 to 11 GBq with a slow infusion every 4-8 weeks (up to 12 times). The kidney is the dose-limiting organ and most patients experience a transient decline in blood cell counts. A concomitant infusion of an amino acid mixture can reduce kidney toxicity and increase the effective tumor dose. Other peptides currently under investigation, some of which have shown promising results, include Rhenium-188 (188Re)-P2045 and 90Y-alpha(v)beta3 antagonist.
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PMID:Radiolabeled peptides in oncology: role in diagnosis and treatment. 1598

To study somatostatin/dopamine (SS/D) synergy in a human cell system constitutively expressing SS and D receptors (SSR and DR, respectively), we characterized the expression of SSR and DR subtypes in the non-small-cell lung cancer line Calu-6, and then we evaluated the effect on cell proliferation of SS/D chimeric molecules (BIM-23A387 and BIM-23A370), which bind with high affinity both sst(2) and D(2)R, and compared the results with those obtained by using SS-14 and subtype-selective SS analogs (SSA) and D agonists (DA). Because Calu-6 cells produce insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) peptides, which play a role in the autocrine/paracrine control of cell growth, we also investigated the effects of chimeric compounds on secretion and expression of IGF system components. Relative high levels of sst(2) and the long isoform of the D(2)R were detected by real-time RT-PCR and Western blot in Calu-6, together with sst(5) and to a lesser extent sst(3) and D(4)R. BIM-23A387 and BIM-23A370 significantly inhibited growth of Calu-6, whereas IGF-IGFBP secretion or expression was unaffected, suggesting a direct inhibitory effect. The inhibition of cell growth, measured by both [(3)H]thymidine incorporation and cell count, was significantly lower when individual SSA and DA control peptides or subtype-specific SSA and DA were tested. BIM-23A370 was more potent than BIM-23A387 (P < 0.001). These findings show that SS/D chimeras can inhibit Calu-6 proliferation in an IGF-independent manner and suggest that this enhanced potency might be because of the induction of SSR/DR dimerization. The Calu-6 cell line, constitutively expressing SSR and DR, provides a suitable model to elucidate the mechanism of action of SSA and DA on regulation of cell growth and to characterize the interaction between SSR and DR.
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PMID:Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation. 1604 58

Early, accurate detection of small-cell lung cancer (SCLC), before it becomes systemic, is essential for successful treatment. Fluorescence-based imaging provides safe, sensitive detection of malignancies. Targeted delivery of fluorophores increases sensitivity of endoscopic imaging. We synthesized novel somatostatin analogs, based on backbone cyclic peptides, and conjugated them with fluorescent agents. Nineteen conjugates differing in core peptide, length of alkyl linker and fluorescence moiety (rhodamine and fluorescein) were tested in vitro, using a receptor binding assay, and nine of the more promising conjugates were tested in vivo by fiber-optic spectrofluorimetry and quantitative spectral imaging, on an H69 human SCLC tumor mouse xenograft model. The lead compound showed exceptional tumor/normal tissue ratios, ranging from 9 to 90, and has potential for targeting SCLC overexpressing somatostatin receptors.
Lung Cancer 2005 Dec
PMID:Targeting small-cell lung cancer with novel fluorescent analogs of somatostatin. 1615 81

The solitary pulmonary nodule (SPN) is a relatively common imaging finding, often representing a diagnostic challenge. Radiological appearance, growth rate calculation during follow up and probability of malignancy assessment by the Bayes' theorem are widely used for identifying the nature of a SPN. Molecular imaging by fluoro-18 deoxy glucose positron emission tomography has revolutionised non-invasive diagnosis of lung cancer, but the low-cost, widely available conventional nuclear imaging modalities still remain valid in the field. We present a case of a growing SPN in a middle-aged male smoker. Growth rate assessment by sequential computed tomography scans, over a follow up period of five years, was suggestive of benign histology, while Bayesian analysis warranted histological confirmation of the nodule's nature. Imaging by both labelled somatostatin analogue technetium 99m-depreotide ((99m)Tc-depreotide) and thallium 201-chloride was almost exclusive of malignancy. The nodule was excised and histology showed a pulmonary hamartoma. We briefly discuss the relative role of invasive and non-invasive methods, with emphasis in conventional radionuclide molecular imaging, for the identification of the nature of SPN.
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PMID:The contribution of conventional nuclear molecular imaging in characterising the nature of a growing solitary pulmonary nodule. Report of a case. 1745 Feb 48

Tumours of the thymus are uncommon and are generally regarded as being indolent. Whilst this is often true of thymomas; thymic adenocarcinoma and thymic neuroendocrine cancer can be aggressive and have a poor prognosis. Understanding the biology of these tumours is important for prognosis and management. The pathological features of these tumours are examined in detail. Imaging modalities for aiding in diagnosis and staging of these tumours are described; this includes CT and MRI, plus more recent advances including the use of FDG-PET and Indium-111 Octreotide scintigraphy. The treatment options available including curative surgery, debulking surgery, chemotherapy, somatostatin analogues and peptide receptor radionuclide therapy are discussed. The optimal chemotherapy regimens are still unclear, although promising results have been obtained with platinum-based chemotherapy. The role for adjuvant therapy in both thymic carcinoma and thymoma is unclear except, in patients with stage I thymomas. There is a high expression of somatostatin receptors in thymic tumours and anti-tumour benefit has been reported in patients treated with somatostatin analogues. A new development is the role of peptide receptor radionuclide therapy. This has become an established therapy in management of gastroenteropancreatic neuroendocrine tumours and its use has been recently described in case reports in both thymoma and thymic carcinoma.
Lung Cancer 2008 Apr
PMID:A review of thymic tumours. 1834 28

Targeted chemotherapy is a novel approach to cancer therapies. This study evaluated the anti-tumor effects of conjugates made by coupling cytotoxic paclitaxel to the somatostatin analog octreotide in A549 human non-small-cell lung cancer (NSCLC) cells xenografted into nude mice. Two cytotoxic somatostatin analogs, paclitaxel-octreotide and 2paclitaxel-octreotide, were prepared by the coupling of one or two paclitaxel molecules with an octreotide molecule. A549 xenografts expressed mRNAs for type 1, 2, 4, and 5 somatostatin receptors. Immunohistology revealed that type 2 somatostatin receptors were mainly located in tumor cell membrane but type 5 somatostatin receptors were found in tumor cell membrane and cytoplasm. Significant tumor growth inhibition was achieved by 2paclitaxel-octreotide at 150 nM/kg and 300 nM/kg. 2paclitaxel-octreotide also significantly extended the tumor doubling time and significantly reduced tumor microvessel density at these doses. Moreover, there was more fragmented DNA in the 2paclitaxel-octreotide single and double dose groups than in the controls. Paclitaxel was ineffective and more toxic than the conjugate as shown by the significant decline of body weight in Paclitaxel group on Days 6, 12, and 26 compared to those treated with 2paclitaxel-octreotide (P<0.05). White blood cell counts in the paclitaxel single and double dose groups were also significantly less than in the controls (P<0.05). In conclusion, the targeting conjugate 2paclitaxel-octreotide made by coupling two molecules of cytotoxic paclitaxel to one somatostatin analog octreotide could enhance tumor growth inhibition and reduce toxicity in comparison to using the cytotoxic paclitaxel alone.
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PMID:Paclitaxel-octreotide conjugates in tumor growth inhibition of A549 human non-small cell lung cancer xenografted into nude mice. 1898 39

Bronchial neuroendocrine tumours account for 1-2% of all lung cancers; they are thought to arise from the neuroendocrine cells located in the bronchial mucosa. The majority of the literature available comprises surgical series and there is a scarcity of data available for the management of patients with inoperable disease. We present a series of 45 patients referred to our institution from 1998 to 2006, with a mean follow-up of 54 months. Histological diagnosis from our department was available for 39 patients, with the remainder having had histological assessment performed previously. Typical carcinoid was present in 25 cases, atypical in 9 cases, large cell neuroendocrine carcinoma in 4 and 1 case of small cell lung carcinoma. All patients were staged at time of initial diagnosis with CT scan, in addition Octreoscans were performed when appropriate. Twenty-six of these 45 cases had unresectable disease, whilst the remainder were treated with surgical resection. Initial therapy with surgical resection was performed in 19 patients, 2 of whom had undergone neo-adjuvant chemotherapy. Recurrence occurred in 7 (36.8%), average duration of disease-free survival post-surgery was 61 months. Chemotherapy was first line therapy in five cases, four achieved disease stabilization and one case had progressive disease. Somatostatin analogues were used as first line therapy in six patients, for symptom control and anti-tumour effect. Peptide receptor radionuclide therapy, with Yttrium-90 DOTA-Octreotate, was given in two cases, both of whom achieved disease stabilization for 9-12 months respectively. There was a significant difference between Stage 4 and Stage 1 disease at presentation and survival. In conclusion curative surgical resection is treatment of choice, however, chemotherapy, somatostatin analogues and peptide receptor radionuclide therapy offers palliation improving both symptoms and mortality.
Lung Cancer 2009 Jul
PMID:Surgical management and palliative treatment in bronchial neuroendocrine tumours: a clinical study of 45 patients. 1907 Mar 98

The use of somatostatin (SS) analogues in humans takes advantage by the availability of many related chemical forms that can be used for receptor therapy and, after radiolabelling, for diagnostic imaging and radionuclide therapy. The first proposed radiocompound, yet clinically widely diffuse, has been (111)In-octreotide (OCT), followed by positron emission tomography (PET) and beta emitter tracers. The main field of clinical applications is in neuroendocrine tumours (NET), starting by the demonstration of SS receptors (SSR) on the majority of NET, particularly on gastroenteropancreatic (GEP) tumours. Uptake of SS analogues can also be due to a SSR expression on non malignant cells when activated, as lymphocytes, macrophages, fibroblasts , vascular cells. Because of this uptake clinical indications can be found also in active benign diseases, as Grave's ophthalmopathy, rheumatoid arthritis, histiocitosis, sarcoidosis, idiopatic pulmonary fibrosis. Moreover, these cells can also determine the OCT in vivo uptake in tumours non expressing in vitro SSR, as non-snall cell lung cancer (NSCLC). Because of a different kinetic respect to SCLC a differential histotype diagnosis could be obtained. Starting from this premise OCT can also allows radioguided surgery in tumours non expressing SSR. Finally a relevant clinical role can be defined in the a priori recruitment and as marker of therapeutic efficacy in all the therapeutic strategies utilizing SSR, both in malignant and benign diseases.
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PMID:The non tumour uptake of (111)In-octreotide creates new clinical indications in benign diseases, but also in oncology. 2016 84

Post operative chylothorax occurs in less than a few percentages of pulmonary resection and lymph node dissection for lung cancer and is a serious complication. The management of post operative chylothorax is both conservative and surgical treatment and generally the former is used. In our hospital during 1992-2005, almost patients responded to conservative treatment. Surgical interventions with video-assisted thoracoscopic surgery (VATS) is considered that it is low invasive method and can prevent the demerits of conservative therapy such as infection of long-term drain detention and lymphocyte loss, malnutrition and so on. Early detection of surgical interventions might be one of strategies in the management of post operative chylothorax for the patients with much quantity of drainage. We consider that administration of somatostatin and lymphangiography are effective treatments and are recommended as the previous step of surgical interventions.
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PMID:[The management of post operative chylothorax]. 2071 13


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