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- Hashemi, S H, et al.
(författare)
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111In-labelled octreotide binding by the somatostatin receptor subtype 2 in neuroendocrine tumours.
- 2003
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 90:5, s. 549-54
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the importance of somatostatin receptor subtype 2 (SSTR2) expression for 111In-labelled diethylenetriamine-pentaacetic acid (DTPA)-D-Phe1-octreotide binding and uptake of 111In in neuroendocrine tumours.
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- Kölby, Lars, 1963, et al.
(författare)
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Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour
- 2005
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 93:10, s. 1144-51
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Tidskriftsartikel (refereegranskat)abstract
- Somatostatin receptor (sstr)-mediated radiation therapy is a new therapeutic modality for neuroendocrine (NE) tumours. High expression of sstr in NE tumours leads to tumour-specific uptake of radiolabelled somatostatin analogues and high absorbed doses. In this study, we present the first optimised radiation therapy via sstr using [(177)Lu-DOTA(0)-Tyr(3)]-octreotate given to nude mice xenografted with the human midgut carcinoid GOT1. The tumours in 22 out of 23 animals given therapeutic amounts showed dose-dependent, rapid complete remission. The diagnostic amount (0.5 MBq [(177)Lu-DOTA(0)-Tyr(3)]-octreotate) did not influence tumour growth and was rapidly excreted. In contrast, the therapeutic amount (30 MBq [(177)Lu-DOTA(0)-Tyr(3)]-octreotate) induced rapid tumour regression and entrapment of (177)Lu so that the activity concentration of (177)Lu remained high, 7 and 13 days after injection. The entrapment phenomenon increased the absorbed dose to tumours from 1.6 to 4.0 Gy MBq(-1) and the tumours in animals treated with 30 MBq received 120 Gy. Therapeutic amounts of [(177)Lu-DOTA(0)-Tyr(3)]-octreotate rapidly induced apoptosis and gradual development of fibrosis in grafted tumours. In conclusion, human midgut carcinoid xenografts can be cured by receptor-mediated radiation therapy by optimising the uptake of radioligand and taking advantage of the favourable change in biokinetics induced by entrapment of radionuclide in the tumours.
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- Lerner, Ulf H, et al.
(författare)
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Serotonin: budbärare mellan hjärna/tunntarm och skelett. Djurmodeller styrker hypotes om serotoninets roll för bildning av benmassa : [Serotinin: a messenger between the brain/small intestine and the skeleton. Animal models strengthen the hypothesis about the role of serotonin in bone formation]
- 2011
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Ingår i: Läkartidningen. - : Svergies läkarförbund. - 0023-7205 .- 1652-7518. ; 108:11, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies by Karsenty and co-workers at Columbia University, New York, have demonstrated the importance in skeletal remodeling in mice of serotonin in the brain and in the periphery. Leptin activates receptors in the brain stem which inhibit tryptophane hydroxylase 2 (Tph2), decreasing serotonin biosynthesis. As a consequence, fewer hypothalamic serotonin receptors are activated, sympathetic outflow increases, and there is enhanced activation of ?-adrenergic receptors on osteoblasts. This leads to decreased bone formation, and increased expression of RANKL, which stimulates bone resorption. In contrast, peripheral serotonin is produced in enterochromaffine cells in the dudenum by the enzyme Tph1. Activation of osteoblastic receptors by peripheral serotonin decreases bone formation without affecting RANKL or resorption. Interstingly, pharmacological inhibition of Tph1 in the duodenum can prevent bone loss after ovariectomy in both mice and rats. These preclinical data need to be confirmed in humans and the feedback loops between the skeleton and serontonin releasing cells in brain and gut to be elucidated.
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- Lindskog, Stefan, et al.
(författare)
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[Phenotypic expression of a mutation in MEN 2A documented in a family in the western part of Sweden]. : Fenotypiskt uttryck av mutation vid MEN 2A kartlagd i västsvensk familj.
- 2001
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Ingår i: Lakartidningen. - 0023-7205. ; 98:35
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A missense mutation at codon 618 of the RET proto-oncogene is a rather unusual cause of multiple endocrine neoplasia 2A. We report the phenotypic expression of this specific RET mutation in a large Swedish family. The family was mapped back to the 18th century. Since 1971 the family has been included in a biochemical screening program, and since 1994 has undergone genetic screening. Twenty-seven individuals were found to have medullary thyroid carcinoma (MTC). Eighteen were detected by screening. The incidence of pheochromocytoma (4%) and hyperparathyroidism (7%) was low. Five individuals died of MTC, but of these none had been included in the screening program. One patient underwent prophylactic thyroidectomy after positive genetic screening. MTC tumor aggressivity differed markedly between gene carriers. The screening program shows that the clinical aggressivity of MTC can be mitigated by early and adequate surgical intervention.
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- Schmitt, Anneli, 1971, et al.
(författare)
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Radiation therapy of small cell lung cancer with 177Lu-DOTA-Tyr3-octreotate in an animal model
- 2004
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Ingår i: Journal of nuclear medicine. - 0161-5505. ; 45:9, s. 1542-8
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Tidskriftsartikel (refereegranskat)abstract
- Small cell lung cancer (SCLC) is a tumor of neuroendocrine (NE) origin with very low survival rate. Somatostatin receptor scintigraphy using 111In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) is a well-established method for the visualization of somatostatin receptor-expressing NE tumors. Recently, new combinations of radionuclides and somatostatin analogs have been investigated for therapeutic purposes. In this study, the somatostatin analog DOTA-Tyr3-octreotate (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid), labeled with the medium-energy electron emitter 177Lu (maximal electron energy = 498 keV, half-life = 6.6 d), was used for radiation therapy of human SCLC in an animal model. METHODS: Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were injected intravenously with 177Lu-DOTA-Tyr3-octreotate. Groups of animals (n = 5 or 6) were injected with 45-, 60-, and 120-MBq fractions and two 45-MBq fractions 48 h apart. Furthermore, 1 control group was treated with unlabeled DOTA-Tyr3-octreotate and another control group was not treated. RESULTS: In both control groups, the tumor volumes were increased 2-fold in approximately 5 d. Treatment with 177Lu-DOTA-Tyr3-octreotate resulted in marked tumor regression with statistically significant tumor volume reduction after 1 wk (P < 0.001). The tumor growth delay time was dependent on the amount of injected activity for the groups with single injections, 26 d for 60 MBq and 40 d for 120 MBq. The best therapeutic effect was obtained in mice injected with 2 fractions of 45 MBq. The relative tumor volume after 1 mo was 0.004 +/- 0.004. CONCLUSION: Radiation therapy with 177Lu-DOTA-Tyr3-octreotate on SCLC-bearing mice was successful. Since the experiments were performed on a human SCLC cell line xenografted to nude mice, the results may be clinically relevant and treatment with 177Lu-DOTA-Tyr3-octreotate could be a treatment alternative in this tumor disease that normally has a dismal prognosis.
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- Tisell, L E, et al.
(författare)
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The Ki67 index a prognostic marker in medullary thyroid carcinoma.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:11, s. 2093-7
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to examine the usefulness of the Ki67 proliferation index as a prognostic marker in patients with medullary thyroid carcinoma (MTC). It is difficult to predict the prognosis of MTC by using conventional prognostic factors. Immunocytochemical analysis of tumour proliferation has been used as a prognostic tool in some tumours, but only rarely in MTC. In all, 71 tumours from 36 patients were investigated, by using a semiautomatic image analysis programme. On average 10,000 nuclear profiles were counted per tumour, and the percentage of tumour cells expressing the proliferation marker, Ki67, was calculated. Primary tumours that had metastasised had higher Ki67 indices than primary tumours that had not metastasised. Recurrent lymph node metastasis had higher Ki67 indices than the primary tumours. By using a Poisson model, it was possible to estimate the median survival time for individual patients if the Ki67 index for the primary tumour and the age at surgery were known. The higher the Ki67 index and the age at operation were, the shorter was the survival. Estimating the median survival of individual patients will be of help for planning the patients' life and postoperative follow-up and treatment.
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