| 1. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
-
Indium-111 activity concentration in tissue samples after intravenous injection of indium-111-DTPA-D-Phe-1-octreotide.
- 1995
-
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 36:1, s. 7-12
-
Tidskriftsartikel (refereegranskat)abstract
- Indium-111 activity concentrations in human tumor and normal tissue samples were determined at 24, 48 and 120 hr after i.v. injection of 111In-DTPA-D-Phe-1-octreotide. Fourteen patients were included in the study. Seven patients had medullary thyroid carcinoma, four had midgut carcinoid tumors, two had endocrine pancreatic tumors and one had chronic pancreatitis.
|
|
| 2. |
- Wängberg, Bo, 1953, et al.
(författare)
-
Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.
- 1996
-
Ingår i: British journal of cancer. - 0007-0920. ; 73:6, s. 770-5
-
Tidskriftsartikel (refereegranskat)abstract
- After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors.
|
|
| 3. |
- Hofving, Tobias, 1989, et al.
(författare)
-
177 Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition
- 2019
-
Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 26:4, s. 437-449
-
Tidskriftsartikel (refereegranskat)abstract
- Lu-177-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The Lu-177-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the Lu-177-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate < 3.2 x 10(-11)). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of Lu-177-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of Lu-177-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of Lu-177-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated.
|
|
| 4. |
- Tisell, Lars-Eric, 1931, et al.
(författare)
-
Somatostatin receptor scintigraphy in medullary thyroid carcinoma.
- 1997
-
Ingår i: The British journal of surgery. - 0007-1323. ; 84:4, s. 543-7
-
Tidskriftsartikel (refereegranskat)abstract
- 111In-radiolabelled (DTPA-D-Phe1)-octreotide scintigraphy can be used to localize neuroendocrine tumours expressing somatostatin receptors (SSTRs). The aim of this paper was to analyse the importance of tumour volume and growth for the visualization by SSTR scintigraphy of metastases from medullary thyroid carcinoma (MTC).
|
|
| 5. |
- Ahlman, Håkan, 1947, et al.
(författare)
-
Somatostatin receptors on neuroendocrine tumors--a way to intraoperative diagnosis and localization.
- 1994
-
Ingår i: The Yale journal of biology and medicine. - 0044-0086. ; 67:3-4, s. 215-21
-
Tidskriftsartikel (refereegranskat)abstract
- Intraoperative radionuclide detection using 111In-DTPA-D-Phe1-octreotide was evaluated in five patients with midgut carcinoids and in three patients with recurrent medullary thyroid carcinoma. Three different time intervals (24, 48 and 120 hr) from injection of the radiopharmaceutical to surgery were used. At surgery, suspect tumors were measured by probe in situ and ex vivo after excision. All tissue specimens and blood samples withdrawn during surgery were measured for 111In activity, and tissue/blood activity concentration ratios were calculated. In situ measurements were valuable especially in neck surgery, where the probe was helpful not only in localization of tumors but also in the control of tumor clearance. Ex vivo measurements were helpful in diagnosing tumor tissue. All five patients with midgut carcinoids were somatostatin receptor-positive, while only three out of seven patients with medullary thyroid carcinoma were receptor-positive. The tissue/blood activity concentration ratios and probe measurement ratios were in general higher in patients with midgut carcinoid than in patients with medullary thyroid carcinoma. Of particular interest were the high tissue/blood concentration ratios in all receptor-positive patients at all time intervals studied. This fact suggests a potential role for radiolabelled octreotide in radiotherapy of these tumor types.
|
|
| 6. |
- Andersson, P, et al.
(författare)
-
Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide.
- 1996
-
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:12, s. 2002-6
-
Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine tumor cells frequently overexpress somatostatin receptors at their cell surfaces. To evaluate the possibility of using the somatostatin analog 111In-DTPA-D-Phe1-octreotide for radiation therapy, we studied the binding and subsequent internalization of 111In into three types of cultured human neuroendocrine tumor cells.
|
|
| 7. |
- Kölby, Lars, 1963, et al.
(författare)
-
Histidine decarboxylase expression and histamine metabolism in gastric oxyntic mucosa during hypergastrinemia and carcinoid tumor formation.
- 1996
-
Ingår i: Endocrinology. - 0013-7227. ; 137:10, s. 4435-42
-
Tidskriftsartikel (refereegranskat)abstract
- Histamine is an important stimulator of gastric acid secretion. In experimental animals, inhibition of acid secretion by long term histamine2 receptor blockade causes hypergastrinemia, proliferation of enterochromaffin-like (ECL) cells, and formation of histamine-producing gastric carcinoids. The aim of this study was to examine the role of gastrin in histamine synthesis and metabolism of the oxyntic mucosa of normal, hyperplastic, and carcinoid-bearing Mastomys natalensis. Administration of exogenous gastrin to normal animals increased histidine decarboxylase (HDC) messenger RNA (mRNA) expression in the oxyntic mucosa within 30 min, indicating that gastrin stimulates histamine synthesis by regulating HDC mRNA abundance. Endogenous hypergastrinemia, induced by short term histamine2 receptor blockade (loxtidine) for 3-29 days, did not induce tumors, but enhanced the expression of HDC mRNA (2- to 4-fold elevated) and histamine contents (2-fold elevated) in the oxyntic mucosa. Long term histamine2 receptor blockade (7-21 months) resulted in sustained hypergastrinemia and ECL tumor formation. Tumor-bearing animals had a 4-fold increase in HDC mRNA expression and histamine contents of the oxyntic mucosa. Urinary excretion of the histamine metabolite methyl-imidazole-acetic acid was 2-fold elevated. Tumor-bearing animals recovering from histamine2 receptor blockade were normogastrinemic and had normal levels of HDC mRNA and histamine in the oxyntic mucosa as well as normal excretion of methyl-imidazole-acetic acid. The results indicate that ECL cell carcinoids developing during hypergastrinemia are well differentiated tumors that respond to high gastrin levels with increased histamine synthesis and secretion.
|
|
| 8. |
- Nilsson, Ola, 1957, et al.
(författare)
-
Growth factors and carcinoid tumours.
- 1993
-
Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 32:2, s. 115-24
-
Tidskriftsartikel (refereegranskat)abstract
- The presence of growth factors and their receptors in human midgut carcinoids and in gastric carcinoids of Mastomys have been investigated. Human midgut carcinoid tumours produce IGF-I as demonstrated by immunocytochemistry and radioimmunoassay. IGF-I receptors were detectable in half of the tumours and stimulation of cultured tumour cells with IGF-I enhanced DNA synthesis. IGF-I may therefore act as an autocrine stimulator of carcinoid tumour growth. Expression of TGF-alpha and EGF-receptors could also be demonstrated in midgut carcinoids by immunocytochemistry and Northern analysis, suggesting that TGF-alpha participates in the autocrine modulation of carcinoid growth. Co-culture of human midgut carcinoid tumours and rat fetal cholinergic neurons demonstrated secretion of a potent neuronotrophic factor by cultured tumour cells. IGF-I and TGF-alpha may account for these neuronotrophic effects, but carcinoid tumours may also secrete an as yet unidentified growth factor. Gastric (ECL cell) carcinoids developed rapidly in Mastomys during hypergastrinemia due to histamine2-receptor blockade, suggesting that gastrin is an essential growth factor for these carcinoids.
|
|
| 9. |
|
|
| 10. |
- Nilsson, Ola, 1957, et al.
(författare)
-
Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.
- 1992
-
Ingår i: The Yale journal of biology and medicine. - 0044-0086. ; 65:6
-
Tidskriftsartikel (refereegranskat)abstract
- The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied.
|
|
