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| 53. |
- Edfeldt, Katarina, 1979-, et al.
(författare)
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DcR3, TFF3 and Midkine are Novel Serum Biomarkers in Small Intestinal Neuroendocrine Tumors
- 2017
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 105:2, s. 170-181
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Tidskriftsartikel (refereegranskat)abstract
- Small intestinal neuroendocrine tumors (SI-NETs) are amine- and peptide producing neoplasms. Most patients display metastases at the time of diagnosis, they have an unpredictable individual disease course and the tumors are often therapy resistant. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are the clinically most used biomarkers today, but there is a great need for novel diagnostic and prognostic biomarkers and new therapeutic targets. Sixty-nine biomarkers were screened in serum from 23 SI-NET patients and 23 healthy controls using multiplex PLA (proximity ligation assay). A refined method, PEA (proximity extension assay), was used to analyze 76 additional biomarkers. Statistical testing and multivariate classification were performed. Immunohistochemistry and ELISA assays were performed in an extended cohort. Using PLA, 19 biomarkers showed a significant difference in serum concentrations between patients and controls, and PEA revealed difference in concentrations in 13 proteins. Multivariate classification analysis revealed decoy receptor 3 (DcR3), trefoil factor 3 (TFF3) and Midkine to be good biomarkers for disease, which was confirmed by ELISA analysis. All three biomarkers were expressed in tumor tissue. DcR3 concentrations were elevated in patients with stage IV disease. High concentrations of DcR3 and TFF3 were correlated to poor survival. DcR3, TFF3 and Midkine exhibited elevated serum concentrations in SI-NET patients compared to healthy controls, and DcR3 and TFF3 were associated with poor survival. DcR3 seems to be a marker for liver metastases while TFF3 and Midkine may be new diagnostic biomarkers for SI-NETs.
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| 54. |
- Ekström, Peter, et al.
(författare)
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Localization of 2-[125I]lodomelatonin binding sites in the brain of the atlantic salmon, salmo salar L.
- 1992
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 55:5, s. 529-537
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Tidskriftsartikel (refereegranskat)abstract
- The photosensory pineal organ of teleost fish shows a circadian rhythm in melatonin synthesis, and melatonin is known to influence a number of physiological functions. However, the target sites for melatonin are not known. We have investigated the distribution of melatonin binding sites in the brain of the salmon, Salmo salar. Brains were collected for receptor binding assay and autoradiography at each of three time points; just after lights on, just before lights off, and in the dark at midnight (photoperiod light-dark 12: 12, lights on at 08.00 h, lights off at 20.00 h). Specific binding of 2-[125I]iodomelatonin was observed in several brain areas. High densities were associated with (1) the optic tectum, (2) the preoptic area, (3) an area encompassing the magnocellu-lar superficial pretectal nucleus ('nucleus rotundus') and the glomerular complex, (4) the inferior lobes of the hypothalamus, (5) the lateral mesencephalic tegmentum including the torus semicircularis, and (6) the molecular layer of the cerebellum. No binding was observed in the pineal organ or in the pituitary. We observed no differences in labeling between brains collected at different time points, except in the preoptic area where binding was high at 20.00 and 24.00 h, but low at 08.00 h, and in the corpus cerebelli, where labeling in the molecular laver was higher at 24.00 and 08.00 h than at 20.00 h. Saturation experiments with crude brain membranes indicated the presence of a single binding site with no significant differences related to the time of day, with Kd values ranging from 30 to 54 pM, and Bmax values from 7.0 to 10.8 fmol/mg protein. Nonspecific binding, determined with 0.1 μM melatonin, was < 20%. The Kd and Bmax, values are in the same range as those reported for the so-called high-affinity binding site in mammalian neural tissue.
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| 55. |
- Elvebakken, Hege, et al.
(författare)
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A Consensus-Developed Morphological Re-Evaluation of 196 High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Its Clinical Correlations
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:9, s. 883-894
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Tidskriftsartikel (refereegranskat)abstract
- High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are classified according to morphology as well-differentiated neuroendocrine tumours (NETs) G3 or poorly differentiated neuroendocrine carcinomas (NECs). Little data exist concerning which morphological criteria this subdivision should be based on. Uncertainty exists if the NEC group should be further subdivided according to proliferation rate. Clinical data on NET G3 and NEC with a lower Ki-67 range are limited. A total of 213 patients with high-grade GEP-NEN (Ki-67 >20%) were included from the Nordic NEC Registries. Four experienced NET pathologists re-evaluated the cases to develop the best morphological criteria to separate NET G3 from NEC, assuming longer survival in NET G3. Organoid growth pattern, capillary network in direct contact to tumour cells, and absence of desmoplastic stroma were found to best separate NET G3 from NEC. Of 196 patients with metastatic disease, NET G3 was found in 12.3%, NEC with a Ki-67 <55% (NEC < 55) in 29.6%, and NEC with a Ki-67 >= 55% (NEC >= 55) in 56.6%. Only in 1.5%, the morphology was ambiguous. Of 164 patients receiving first-line chemotherapy, 88% received platinum/etoposide treatment. Response rate was higher for NEC >= 55 (44%) than that of NEC < 55 (25%) and NET G3 (24%) (p = 0.025 and p = 0.026). Median progression-free survival was 5 months for all groups. Median overall survival was 33 months for NET G3 compared to 11 months for both NEC < 55 and NEC >= 55 (p = 0.004 and 0.003). Specific morphological criteria can separate NET G3 from NECs and show prognostic significance. High-grade GEP-NEN patients stratified by morphology and proliferation rate demonstrate significant differences in response to chemotherapy and survival.
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| 56. |
- Erfurth, Eva Marie
(författare)
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Diagnosis, Background, and Treatment of Hypothalamic Damage in Craniopharyngioma
- 2020
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:9-10, s. 767-779
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Forskningsöversikt (refereegranskat)abstract
- Craniopharyngiomas (CP) are rare brain tumors managed primarily with surgery and radiotherapy. There are 2 phenotypes of CP, i.e., one with a rather good outcome without hypothalamic damage and another with hypothalamic damage. With hypothalamic damage, progressive disease with recurrent operations and additional cranial radiotherapy often result in hypothalamic obesity, an affected psychosocial life, and cognitive dysfunction. The morbidity and mortality are increased for particularly cerebrovascular diseases. Preoperative hypothalamic involvement to predict hypothalamic damage is important for decision making for hypothalamus-sparing surgery. Also a postoperative hypothalamic damage evaluation with the use of hypothalamus volume measurement can predict hypothalamic obesity, which is important for early treatment options. The morbidity of CP includes cognitive dysfunction with attention deficits and impaired episodic memory and processing speed. Again patients with hypothalamic damage are more affected. Treatment options of hypothalamic obesity in the chronic phase are scarce and not convincingly successful. The most optimal situation is to try to hinder or stop the evolution of hypothalamic obesity. Prevention of hypothalamic damage is recommended, with special regard to hypothalamus-sparing therapeutic approaches that respect the integrity of essential nuclei located in both the medial and the posterior hypothalamic areas.
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| 57. |
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| 60. |
- Eriksson, Olof
(författare)
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Non-invasive imaging methodologies for assessment of Peptide Receptor Radiotherapy damage to bone marrow and kidney
- 2020
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194.
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Peptide receptor radionuclide therapy (PRRT) is becoming clinical routine for management of neuroendocrine tumours. The number of PRRT cycles is correlated with treatment effect but theoretically limited by off-target radiation damage to kidneys and bone marrow. New imaging biomarkers for assessment of PRRT tissue damage would enable evaluation of novel renal and bone marrow protective agents, as well as personalised PRRT treatment regiments. <b><i>Methods:</i></b> Mice treated with [<sup>177</sup>Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [<sup>18</sup>F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([<sup>99m</sup>Tc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. <b><i>Results:</i></b> Bone marrow proliferation as assessed by [<sup>18</sup>F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBR<sub>max</sub>] baseline:1.69 ± 0.29 vs. TBR<sub>max</sub> PRRT: 0.91 ± 0.02, <i>p</i> < 0.01). Renal function as assessed by [<sup>99m</sup>Tc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s<sup>–1</sup> vs. FUR PRRT: 0.0051 ± 0.0028 s<sup>–1</sup>, <i>p</i> < 0.01). <b><i>Conclusion:</i></b> [<sup>18</sup>F]FLT PET and [<sup>99m</sup>Tc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [<sup>177</sup>Lu]Lu-DOTA-TATE PRRT and may potentially improve patient management by allowing evaluation of protective interventions as well as enabling personalised PRRT treatments.
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