A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide Uptake

Kölby, Lars; Bernhardt, Peter; Ahlman, Håkan; Wängberg, Bo; Johanson, Viktor; Wigander, A.; Forssell-Aronsson, Eva; Karlsson, Sven; Åhrén, Bo; Stenman, Göran; Nilsson, Ola

doi:10.1016/s0002-9440(10)64017-5

Cited by 88 publications

(78 citation statements)

References 23 publications

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“…26 These cells were treated with 0-10 μM cabozantinib, MK-2206, P276-00, regorafenib, sorafenib, sunitinib, veliparib, vorinostat or 0-5 μM alvespimycin (Selleck Chemicals) for 4 days. All drugs were dissolved in DMSO.…”

Section: In Vitro Experiments With Got1 Cellsmentioning

confidence: 99%

Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets

et al. 2016

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Section: In Vitro Experiments With Got1 Cellsmentioning

confidence: 99%

Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets

et al. 2016

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“…The xenograft model with the human small intestinal NET cell line GOT1 in nude mice has been described previously (7). In brief, small pieces (;1 mm) of excised tumor were transplanted subcutaneously to female BALB/c nude mice.…”

Section: Animal Model and Xenograftingmentioning

confidence: 99%

NAMPT Inhibitor GMX1778 Enhances the Efficacy of¹⁷⁷Lu-DOTATATE Treatment of Neuroendocrine Tumors

et al. 2016

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Neuroendocrine tumors (NETs) can be treated by peptide receptor radionuclide therapy using radiolabeled somatostatin analogs. However, the efficacy of such treatment is low and needs to be optimized. Our study evaluated the potential radiosensitizing effects of inhibition of nicotineamide phosphoribosyltransferase on 177 Lu-DOTATATE treatment in a NET model. Methods: Nude mice xenografted with the human NET cell line GOT1 were treated with semiefficient doses of 177 Lu-DOTATATE (7.5 MBq, intravenously) or the nicotineamide phosphoribosyltransferase inhibitor GMX1778 (100 mg/kg/wk, orally). Results: Median time to tumor progression (tumor volume larger than at day 0) was 3 d for controls, 7 d for single-dose GMX1778, 28 d for single-dose 177 Lu-DOTATATE, 35 d for 3 weekly doses of GMX1778, and 98 d for combined treatment with 177 Lu-DOTATATE and GMX1778 · 1. After 177 Lu-DOTATATE and 3 weekly doses of GMX1778, none of the tumors progressed within 120 d. Conclusion: GMX1778 enhances the efficacy of 177 Lu-DOTATATE treatment and induces a prolonged antitumor response.

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“…The GOT1 cell line was established from a liver metastasis of a small intestinal carcinoid (Kölby et al 2001) and the BON cell line was derived from a metastasis of a malignant pancreatic carcinoid (Evers et al 1991). The GOT1 cell line was cultured in RPMI-1640 medium with 5 mg/ml transferrin and 5 mg/ml insulin, and the BON cell line was grown in Dulbecco's Modified Eagle's Medium (DMEM)/F-12 medium, both supplemented with 10% bovine serum, 200 IU/ ml penicillin and 200 mg/ml streptomycin, and incubated in a 5% CO 2 humidified atmosphere at 37 8C.…”

Section: Cell Culturementioning

confidence: 99%

Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract

Arvidsson¹,

Andersson²,

Bergström³

et al. 2008

Endocrine Related Cancer

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We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor-like protein 1 (APLP1). Quantitative real-time PCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of APLP2 expression in neuroendocrine (NE) tumours when compared with non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed a correlation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence tumour cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.

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A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide Uptake

Cited by 88 publications

References 23 publications

Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets

Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets

NAMPT Inhibitor GMX1778 Enhances the Efficacy of¹⁷⁷Lu-DOTATATE Treatment of Neuroendocrine Tumors

Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract

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A Transplantable Human Carcinoid as Model for Somatostatin Receptor-Mediated and Amine Transporter-Mediated Radionuclide Uptake

Cited by 88 publications

References 23 publications

Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets

Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets

NAMPT Inhibitor GMX1778 Enhances the Efficacy of177Lu-DOTATATE Treatment of Neuroendocrine Tumors

Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract

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NAMPT Inhibitor GMX1778 Enhances the Efficacy of¹⁷⁷Lu-DOTATATE Treatment of Neuroendocrine Tumors