| 1. |
- Ahlstedt, Jonas, et al.
(författare)
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Non-invasive imaging methodologies for assessment of radiation damage to bone marrow and kidneys from peptide receptor radionuclide therapy. : -
- 2019
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 1423-0194 .- 0028-3835. ; 110:1-2, s. 130-138
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: 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. Methods: Mice treated with [177Lu]Lu-DOTA-TATE PRRT or vehicle were examined at baseline and following treatment with [18F]fluorothymidine (FLT) positron emission tomography (PET) and technetium-99m-mercapto-acetyl-tri-glycine ([99mTc]Tc-Mag3) single-photon emission tomography (SPECT) to assess dynamic changes in bone marrow proliferation and renal function, respectively. Results: Bone marrow proliferation as assessed by [18F]FLT was decreased 2 days after PRRT treatment, but not vehicle, compared to baseline (target-to-background ratio [TBRmax] baseline:1.69 ± 0.29 vs. TBRmax PRRT: 0.91 ± 0.02, p < 0.01). Renal function as assessed by [99mTc]Tc-Mag3 SPECT was similarly decreased 2 days following PRRT compared to vehicle (fractional uptake rate [FUR] vehicle: 0.030 ± 0.014 s–1 vs. FUR PRRT: 0.0051 ± 0.0028 s–1, p < 0.01). Conclusion: [18F]FLT PET and [99mTc]Tc-Mag3 SPECT are promising techniques for assessing bone marrow and renal injury from [177Lu]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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| 2. |
- Ahrén, K, et al.
(författare)
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Histamine stimulates progesterone synthesis and cyclic adenosine 3',5'-monophosphate accumulation in isolated preovulatory rat follicles
- 1987
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 46:1, s. 69-74
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Tidskriftsartikel (refereegranskat)abstract
- The effect of histamine on progesterone synthesis and cyclic adenosine 3',5'-monophosphate (cAMP) accumulation was studied in superfused and incubated follicles dissected free from immature rats treated with pregnant mare serum gonadotrophin (PMSG). Histamine, like LH, increased the progesterone synthesis, but to a smaller extent. The H2-antagonist, cimetidine, inhibited completely the histamine-induced progesterone increase while the H1-antagonist, pyrilamine, as well as propranolol and atropine did not affect the initial response but modified its duration. The specific H2-agonist, 4-methylhistamine, but not the H1-agonist, 2-methylhistamine, mimicked the effect of histamine on progesterone synthesis. In the presence of the phosphodiesterase inhibitor, IBMX, histamine increased tissue levels of cAMP. These results suggest that histamine stimulates progesterone synthesis via the H2-receptor with cAMP acting as secondary intracellular messenger.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Järhult, Johannes, et al.
(författare)
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First Report on Metastasizing Small Bowel Carcinoids in First-Degree Relatives in Three Generations
- 2010
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 91:4, s. 318-323
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: There is an established association between the multiple endocrine neoplasia type 1 (MEN 1) syndrome and foregut carcinoids. Some registry studies also indicate that offspring to carcinoid patients run an increased risk of developing a carcinoid tumor themselves. However, there are only scattered reports of gastrointestinal carcinoids in two generations. The aim of this study was to describe the clinical characteristics as well as the histopathological, immunohistochemical (IHC) and genetic data of metastasizing ileal carcinoids in three consecutive first-degree relatives. Methods: The histopathological and IHC analyses were performed on newly cut sections of the tumor specimens and included growth pattern, proliferation index (Ki67) as well as expression of established neuroendocrine markers and recently introduced cocaine-amphetamine-regulated transcript (CART). The genetic analyses were focused on establishing whether a connection with the MEN 1 syndrome existed in this family, by means of mutation screening using polymerase chain reaction, multiple ligation-dependent probe amplification, and genotyping using fluorescent-labeled microsatellite markers. Results: Histopathology and IHC revealed that the tumors were virtually identical, with only minor differences in proliferation index and expression of CART. Genetic analyses indicated that the inheritance of the small bowel carcinoids in the family was not linked to the MEN1 gene. Conclusion: Metastasizing small bowel carcinoids have been found in first-degree relatives in three consecutive generations. All three tumors were very similar when characterized by histopathology and IHC. Based on clinical findings and genetic analyses, it seems unlikely, although not completely excluded, that inheritance was linked to the MEN 1 syndrome. Copyright (c) 2010 S. Karger AG, Basel
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| 6. |
- Landerholm, Kalle, et al.
(författare)
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Cocaine- and Amphetamine-Regulated Transcript in Neuroendocrine Tumors
- 2011
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 94:3, s. 228-236
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Cocaine-and amphetamine-regulated transcript (CART) is an anorexigenic regulatory peptide highly expressed in the brain's appetite control centers, but also in peripheral neurons and in endocrine cells in the adrenal medulla, thyroid, pancreatic islets, and in the gastrointestinal tract. Plasma levels of CART were recently shown to be elevated in patients with neuroendocrine tumors (NETs), but the cellular sources of CART in NETs have remained unknown. The aim of the study was to establish whether CART is expressed in various types of NETs and, if so, to examine the frequency, distribution and phenotype of CART-expressing cells. Methods: Tumor specimens from 133 NETs originating in the stomach, ileum, rectum, pancreas and thyroid were examined with immunohistochemistry and in situ hybridization. The expression of CART was quantified and the CART-expressing cells were phenotyped by double staining for established markers and hormones. Results: CART-expressing tumor cells were found in the majority of the examined NETs. The expression pattern of CART was highly heterogeneous not only between tumors, but also within individual tumors. In 14% of the NETs, CART was found in a major population of the tumor cells. Conclusion: CART is produced in the majority of NETs, regardless of tumor origin. This likely explains the elevated levels of circulating CART in certain NETs patients, as recently described. CART could therefore prove to be a useful tool in the diagnostics of NETs not only in blood samples, but also in histopathological specimens. Copyright (C) 2011 S. Karger AG, Basel
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| 7. |
- Möller, C A, et al.
(författare)
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Distribution of cystatin C (gamma-trace), an inhibitor of lysosomal cysteine proteinases, in the anterior lobe of simian and human pituitary glands
- 1985
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 41:5, s. 400-404
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Tidskriftsartikel (refereegranskat)abstract
- Cystatin C, a protein inhibitor of lysosomal cysteine proteinases, was demonstrated by immunohistochemical techniques to be present in most luteinizing hormone- (LH-)containing cells in simian and human adenohypophyses. Immunoreactivity of cystatin C was also found in simian adrenocorticotrophic hormone- (ACTH-)containing cells localized to an area corresponding to the pars intermedia but not in the ACTH-containing cells of the anterior pituitary lobe of monkey. No immunoreactivity of cystatin C was detected in the growth hormone- (GH-) and prolactin-containing cells of monkey and man.
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| 8. |
- Sundlöv, Anna, et al.
(författare)
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Pituitary function after high-dose 177Lu-DOTATATE therapy and long-term follow-up.
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:4, s. 344-353
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Tidskriftsartikel (refereegranskat)abstract
- The pituitary gland has a high expression of somatostatin receptors (SSTRs) and is therefore a potential organ at risk for radiation-induced toxicity after 177Lu-DOTATATE treatment.To study changes in pituitary function in patients with neuroendocrine tumors (NETs) treated with dosimetry-based 177Lu-DOTATATE to detect possible late toxicity.68 patients from a phase II clinical trial of dosimetry-based, individualized 177Lu-DOTATATE-therapy were included in this analysis. Patients had received a median of 5 (range 3-9) treatment cycles of 7.4 GBq/cycle. Median follow-up was 30 months (range 11-89). The GH/IGF1-axis, gonadotropins, adrenal and thyroid axes were analyzed from baseline and on a yearly basis thereafter. Percent changes in hormonal levels over time were analyzed statistically using a linear mixed model and described graphically using boxplots. The absorbed radiation dose to the pituitary was estimated based on post-therapeutic imaging, and the results analyzed vs % change in IGF1-levels over time.A statistically significant decrease in the levels of IGF1 was found (p<0.005), which was correlated to the number of treatment cycles (p=0.008) and absorbed radiation dose (p=0.03). A similar decrease, although non-significant, was seen in the gonadotropins in post-menopausal women, while in men there was an increase during the first years post-therapy, after which the levels returned to baseline. No change was observed in the adrenal nor thyroid axes.No signs of severe endocrine disorder were detected, although a significant decrease in the GH/IGF1-axis was found, where dosimetric analyses indicate radiation-induced damage to the pituitary gland as a probable cause.
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| 9. |
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| 10. |
- Karam, Elias, et al.
(författare)
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Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia : A Multi-Institutional Pancreas2000/EPC Study
- 2023
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Ingår i: Neuroendocrinology. - 0028-3835. ; 113:10, s. 1024-1034
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. Methods: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. Results: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. Conclusion: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.
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