Adrenergic Control of Serotonin Release From a Midgut Carcinoid Tumour

Nilsson, Ola; Ko, Grönstad; Goldstein, Menek; Skolnik, G.; Dahlström, Annica; Ahlman, Håkan

doi:10.1002/ijc.1985.36.3.307

Cited by 22 publications

(13 citation statements)

References 19 publications

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“…PG has previously been shown not to cause release of 5-HT from human midgut carcinoid tumour cells in vitro (Nilsson et al, 1985). In vivo there is strong experimental evidence that PG acts via an indirect mechanism causing release of catecholamines from the adrenals, in turn activating P-adrenoceptors located on enterochromaffin cells (or carcinoid tumour cells) (Gronstad et al, 1987).…”

Section: Discussionmentioning

confidence: 96%

The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells

Wängberg

Nilsson²,

Theodorsson³

et al. 1991

Br J Cancer

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Summary The use of a somatostatin analogue has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we Moattari, 1989;Gorden et al., 1989). In clinical studies the somatostatin analogue has been shown to reduce the levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), in peripheral blood under basal conditions and after pentagastrin (PG) provocation (Ahlmann et al., 1988a;Oberg et al., 1989). Hemodynamic studies have demonstrated that octreotide rapidly stabilises arterial blood pressure during carcinoid crisis despite high circulating levels of 5-HT, indicating a peripheral site of action as well (Kvols et al., 1985;Ahlman et al., 1988a). Using a model with intraocular heterotransplants of human midgut carcinoid tumours to immunosuppressed rats we have previously demonstrated a significant reduction of the P-adrenoceptor mediated release of 5-HT from these tumours after systemic treatment of the host animals with octreotide (Ahlund et al., 1989b). However, in those studies the effect of the drug may theoretically have been conveyed via receptors on tumour vessels and/or on the tumour cell surface. In order to investigate the effects of the somatostatin analogue on isolated tumour cells, we have studied growth and secretion of 5-HT and NPK from cultured human midgut carcinoid tumour cells subjected to octreotide treatment. The biochemical response to treatment with octreotide, studied by urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) and by levels of 5-HT in peripheral whole blood during PG provocation, were also monitored in the clinical situation. Material and methodsClinical provocation with pentagastrin A provocation test using PG (0.6 jg kg-' i.v.) was used Oberg et al., 1989 The urinary 5-HIAA levels at referral were 300 tsmol 24 h-' and the peak/basal ratio of 5-HT levels in peripheral whole blood at PG provocation were 1.50 (basal level 590 ng ml-'). After treatment with SMS (100 fig x 2 Case II Male, age 59, had mesenteric lymph node metastases and localised retroperitoneal tumour masses, but no demonstrable hepatic spread. The 5-HIAA levels at referral were 117 jsmol 24 h-' and the peak/basal ratio of 5-HT levels in peripheral blood at PG provocation were 1.63 (basal level 204 ng ml-'). Under protection with SMS he underwent radical surgical removal of the lesions. After surgery, SMS treatment was cessated and the postoperative 5-HIAA levels were then normal (51 Lmol 24 h-') and so was the PG test with a peak/basal ratio of 1.19 (basal level 115 ng ml-'). Two years after surgery this patient still has normal radiological and biochemical findings.

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Section: Discussionmentioning

confidence: 96%

The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells

Wängberg

Nilsson²,

Theodorsson³

et al. 1991

Br J Cancer

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“…The results indicate that endocrine tumours can be studied either in in vitro systems, i.e. in cell suspensions (NILSSON et al, 1985(NILSSON et al, , 1986aGRONSTAD et al, 1987), and in tissue culture (AHLMAN et al, 1988) or in in vivo systems, i. e., tumour transplants to the anterior eye-chamber of immunosuppressed rats (NILSSON et al, 1986a, b). In these experimental situations, we have been able to demonstrate that the tumour retains most of its endocrine characteristics and can be made to synthesize and secrete the same hormonal products as in the patient.…”

Section: Discussionmentioning

confidence: 99%

“…OLSON, 1970;NILSSON et al, 1984NILSSON et al, , 1985 of , immunosuppressed during the period of study by daily injections of cyclosporin A (20mg/kg s.c., Sandoz AG, Switzerland). Generally bilateral transplantations were carried out.…”

Section: In Oculo Transplantsmentioning

confidence: 99%

Expression of gastrointestinal endocrine tumours in culture systems.

Ahlman

Ahlund

Dahlström

et al. 1989

Archives of Histology and Cytology

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“…Thus regional or general anaesthesia, invasive radiological procedures including embolisation or radiofrequency ablation, and all forms of surgery can precipitate such a crisis. Although it is by no means clear what the mechanisms are which prompt the release of peptide mediators from tumour tissue, catecholamines are considered contributory (Nilsson et al 1985), usually elevated following sympathetic nervous system responses to hypotension. Midgut carcinoid tumour cells possess β-receptors, stimulation of which by circulating catecholamines may initiate release of serotonin and other vasoactive amines (Nilsson et al 1985).…”

Section: Carcinoid Crisismentioning

confidence: 99%

Surgery for midgut carcinoid.

Doran¹,

Williams²,

Vora³

et al. 2003

Endocrine-Related Cancer

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Many clinicians prefer to avoid surgery in patients with carcinoid neoplasia, because of its slow growth and relatively favourable prognosis. Nevertheless, the commonest cause of death in patients with carcinoid is advanced metastatic disease, and both clinical and epidemiological data indicate that the more effectively the disease is ablated, the more long-lasting the benefit. Multidisciplinary management of patients with carcinoid must consider inherited risk, possible multiple carcinoids and/ or synchronous non-carcinoid cancer, and the use of a range of investigations that also evaluate the 10% of patients with carcinoid syndrome with or without valvular heart disease. Although primary size is correlated with the presence of nodal with or without liver metastases, carcinoid tumours < 1 cm in diameter may be metastatic at presentation, particularly those arising within the small intestine. In the jejunum and ileum, resection of all sizes of carcinoid with local and regional nodes is preferred, to prevent nodal dissemination causing mesenteric ischaemia with or without infarction. Resection of nodal metastases should be undertaken in those with persistent or recurrent nodal disease if possible. Appendiceal and right colonic carcinoids are most effectively treated by right hemicolectomy with local and regional nodal clearance, as for adenocarcinoma. However, for most appendiceal carcinoids which are < 1 cm in diameter and non-invasive, appendicectomy alone is sufficient. For appendiceal carcinoids 1-2 cm in diameter, histopathological assessment helps to determine the need for hemicolectomy. Liver resection has been followed by prolonged 5 year survival in several series and is recommended in appropriate patients to attempt cure or to debulk metastatic disease. Liver transplantation has had only qualified success in highly selected patients without extra-hepatic disease in whom other therapies have failed.

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Adrenergic Control of Serotonin Release From a Midgut Carcinoid Tumour

Cited by 22 publications

References 19 publications

The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells

The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells

Expression of gastrointestinal endocrine tumours in culture systems.

Surgery for midgut carcinoid.

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