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- Ludvigsen, Eva, et al.
(author)
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Regulation of insulin and glucagon secretion from rat pancreatic islets in vitro by somatostatin analogues
- 2007
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In: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 138:1, s. 1-9
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Journal article (peer-reviewed)abstract
- Somatostatin is an inhibitor of hormone secretion through specific receptors (sst1-5). The aim of this study was to investigate the putative regulatory role of somatostatin analogues on the secretion of insulin and glucagon by rat pancreatic islets. After 48 h exposure only the non-selective agonists (somatostatin, octreotide and SOM-230) inhibited insulin accumulation. The inhibition of insulin secretion was accompanied by increased islet insulin contents. None of the analogues showed a consistent effect on the glucagon accumulation in the medium after 48 h. Since we observed a difference in the regulatory effect between the non-selective and selective analogues, combinations of selective analogues were studied. Combination of sst2 + sst5 agonists inhibited the medium insulin accumulation, while combination of sst1 + sst2 analogues caused a decrease in glucagon accumulation. After removal of somatostatin a rebound effect with increased insulin secretion were observed. This effect was reversed after 6 h. For SOM-230 insulin secretion continued to be suppressed even after the analogue was removed and returned to control values after 3 h. As for glucagon secretion there was an initial decline after culture with octreotide, while the other substances failed to induce any changes. In summary, non-selective somatostatin analogues or combinations of receptor selective analogues may cause inhibition of hormone secretion from rat pancreatic islets. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively may exert this effects. Thus, our data suggest that more than one sst must be involved to down-regulate islet glucagon and insulin secretion.
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| 4. |
- Saras, Jan, et al.
(author)
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Somatostatin induces rapid contraction of neuroendocrine cells
- 2007
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In: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 581:10, s. 1957-1962
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Journal article (peer-reviewed)abstract
- The peptide hormone somatostatin, as well as the somatostatin analog octreotide, induces rapid morphological changes in neuroendocrine cells. The effect can be detected in less than 2min: retraction fibers are formed, cells round up and cell–cell contacts are broken. Somatostatin-dependent cell contraction is inhibited by Y-27632, indicating that this effect is dependent on Rho kinase. In BON1 cells, the somatostatin-induced inhibition of forskolin-induced secretion of chromogranin A is not blocked by Y-27632. It is therefore concluded that the inhibitory effect of somatostatin in forskolin-stimulated cells is not dependent on cell contraction.
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| 5. |
- Tiensuu Janson, Eva, et al.
(author)
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Carcinoid tumors : analysis of prognostic factors and survival in 301 patients from a referral center
- 1997
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In: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 8:7, s. 685-690
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Journal article (peer-reviewed)abstract
- BACKGROUND:Little is known about factors related to prognosis in patients with carcinoid disease. In this study we have tried to identify such factors.PATIENTS AND METHODS:We have evaluated 301 consecutive carcinoid patients (256 midgut, 39 foregut and six hindgut) referred during 15 years for medical treatment with respect to tumor distribution, hormone production, prognostic factors and survival.RESULTS:Survival was significantly shorter in midgut carcinoid patients with > or = 5 liver metastases or with high levels of urinary 5-hydroxyindoleacetic acid, plasma chromogranin A or neuropeptide K. By univariate analysis, these variables together with the presence of carcinoid syndrome were related to a higher risk of dying. In multivariate analyses, performed in the 71 patients with full information on all variables, advanced age and plasma chromogranin A > 5000 micrograms/l were independent predictors of overall survival.CONCLUSIONS:Poor prognostic factors for midgut carcinoid patients were multiple liver metastases, presence of carcinoid syndrome and high levels of the tumor markers studied. In this study the only independent predictors of bad prognosis in midgut, carcinoid patients were advanced age, which however is inherently related to overall survival, and plasma chromogranin A > 5000 micrograms/l. Thus, chromogranin A may prove to be an important prognostic marker for patients with carcinoid tumors.
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| 7. |
- Welin, Staffan, et al.
(author)
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Elevated Plasma Chromogranin A is the First Indication of Recurrence in Radically Operated Midgut Carcinoid Tumours
- 2009
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 89:3, s. 302-307
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Journal article (peer-reviewed)abstract
- Background:Patients with malignant midgut carcinoids are occasionally diagnosed with limited tumor spread, and surgery with radical intention is performed. Despite curative intent, recurrences occur frequently, motivating long-term biochemical and radiological follow-up. This study aimed to compare the usefulness of various methods in detecting such recurrences.Methods:This retrospective study included 56 patients with radically operated midgut carcinoids referred to our University Hospital for evaluation and follow-up between 1985 and 2004. Patients were monitored 1-3 times per year using plasma-chromogranin A (P-CgA), urinary 5-hydroxyindoleacetic acid (U-5HIAA) concentrations as well as radiological examinations, including ultrasonography, computerized tomography or magnetic resonance investigation. In a subset of cases, somatostatin receptor scintigraphy and/or positron emission tomography with 5-hydroxytryptophan was performed. Time from operation until established recurrence was recorded.Results:Tumor recurrence was established in 33 of 56 patients after a median of 32 months (range 6-217). Elevated P-CgA was the first marker to become pathologically elevated in 28 of these 33 patients (85%). In 3 of these 28 patients, radiology was simultaneously positive for a recurrence.Conclusion:P-CgA was the first marker to indicate tumor recurrence in the majority of radically operated midgut carcinoid patients. To avoid unnecessary and costly examinations in asymptomatic patients, we suggest that follow-up should comprise measurements of P-CgA twice a year and annual ultrasonography until P-CgA is elevated or clinical symptoms occur, at which time all efforts should be made to identify recurrent tumor lesions in order to give the patient the best possible treatment which, if possible, should be surgical removal of the recurrence.
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| 8. |
- Welin, Staffan, et al.
(author)
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High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours
- 2004
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 151:1, s. 107-112
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Journal article (peer-reviewed)abstract
- OBJECTIVE:High-dose somatostatin analogue treatment has shown an antiproliferative effect in one study including patients with neuroendocrine tumours. To explore this therapeutic strategy further, we have studied the effect of a high-dose formula of octreotide, octreotide pamoate, in midgut carcinoid patients.DESIGN AND METHODS:Twelve patients with advanced midgut carcinoid tumours with a median duration of disease of more than 5 years were included. All were in a progressive state despite several previous treatment modalities. Octreotide pamoate (160 mg) was given as an intramuscular injection every 2 weeks for 2 months and then monthly. Radiological and biochemical responses were monitored.RESULTS:Tumour size and biochemical markers were stabilised for a median of 12 months in 75% of the patients. Ten patients had symptomatic improvement of flush and diarrhoea.CONCLUSION:In this group of patients with advanced midgut carcinoid tumours and progressive disease, octreotide pamoate managed to improve symptoms, and stabilise hormone production and tumour growth in 75% of the patients. We believe that high-dose treatment with somatostatin analogues can be an important addition to the therapeutic arsenal for patients with advanced progressive midgut carcinoid tumours.
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