| 1. |
- Nilsson, Eva, 1963-
(author)
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Barn i rättens gränsland. : Om barnperspektiv vid prövning om uppehållstillstånd.
- 2007
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Doctoral thesis (other academic/artistic)abstract
- The aim of this study is to highlight problems regarding the status of children in determining the granting of residence permits. Central to the study are the rules contained in the Swedish Aliens Act (2005:716) about hearing children in the course of proceedings and the child’s best interests. The rules are based on Articles 3 and 12 respectively, in the United Nations Convention on the Rights of the Child (CRC). They were introduced into the Swedish legislation in 1997, after an intense debate questioning whether Sweden was meeting its obligations under the Convention. The application in aliens matters has, however, continued to be criticized after the revision of 1997, especially in matters concerning children. In 2006 a new Aliens Act came into force, involving a shift in the handling of such matters from administrative authorities and the Government to a system where appeals are tried in administrative courts. The legislation also involves comprehensive changes concerning the material legislation. The question has been raised, however, as to whether these changes have had any vital impact concerning the general construction of the material regulation. The apparent gap between the legislator’s intentions and the application of the law raises questions about the limitations of law and how the spirit and intentions of the CRC have been implemented in the Aliens Act, and, in view of this, the limits of law. The study involves an analysis of the fundamental premises that the legislation and application rest on, the general provisions of the proceedings and the technical formulation and also the material content of these rules. There is also an analysis of the impact and function of the legislation in practical applications. The conclusion is that the legislation allows extensive scope for assessing the circumstances in each case. This is the case, particularly in matters concerning children. Nevertheless, in practical applications, children often become irrelevant; children are simply not the real focus of the laws that affect them. Key words: Children’s rights, residence permit, asylum, immigration, equality, feminist perspectives. Eva Nilsson, Juridiska institutionen, Umeå universitet, 901 87 Umeå.
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| 2. |
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| 3. |
- Ahlman, Håkan, 1947, et al.
(author)
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The relevance of somatostatin receptors in thyroid neoplasia.
- 1997
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In: The Yale journal of biology and medicine. - 0044-0086. ; 70:5-6, s. 523-33
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Journal article (other academic/artistic)abstract
- 111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).
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| 4. |
- Amiri-Mosavi, A, et al.
(author)
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Expression of cholecystokinin-B/gastrin receptors in medullary thyroid cancer.
- 1999
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In: The European journal of surgery = Acta chirurgica. - : Oxford University Press (OUP). - 1102-4151. ; 165:7, s. 628-31
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Journal article (peer-reviewed)abstract
- To characterise the cholecystokinin (CCK) receptor subtypes in medullary thyroid cancer by measuring the expression of CCK-A and CCK-B/gastrin receptor mRNA.
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| 5. |
- Andersson, Maria Eva, et al.
(author)
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Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar.
- 2017
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 65:8, s. 1371-1377
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Journal article (peer-reviewed)abstract
- Background: Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure.Methods: Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens.Results: At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children.Conclusions: Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.
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| 6. |
- Bernhardt, Peter, 1966, et al.
(author)
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Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice.
- 2007
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In: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:5, s. 644-53
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Journal article (peer-reviewed)abstract
- PURPOSE: The aim of this study was to analyze the effect therapeutic injections of (177)Lu-DOTA(0)-Tyr(3)]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with (111)In-DOTATATE in GOT1-bearing nude mice. METHODS AND MATERIALS: Nude mice, xenografted with the human midgut carcinoid, GOT1, were first intravenously injected with a curative (30 MBq) or a suboptimal (7.5 MBq) amount of (177)Lu-DOTATATE. At various intervals thereafter (4-13 days), a second injection with (111)In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor (111)In and (177)Lu activity concentration determined, and tumor regression/cell density was recorded. RESULTS: In animals given curative amounts, the uptake of (111)In was lower than in untreated animals. On the other hand, a second late injection (3-13 days) after suboptimal amounts resulted in a twofold higher tumor activity concentration versus untreated animals. When the uptake of the curative injection was corrected for tumor cell density, which decreased from 66% to 4% over 2 weeks, an enhanced uptake per tumor cell was observed. The curative and suboptimal amounts resulted in a different uptake and retention of (177)Lu in tumors. The suboptimal amount resulted in a constant activity concentration, while the curative amount resulted in an increased activity concentration over time. CONCLUSIONS: Our results, as presented in this paper, describe how the second injection in a fractionation protocol will be affected by the first therapeutic amount. This new information might be useful in the optimization of radionuclide therapy.
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| 7. |
- Dunér, Pontus, et al.
(author)
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Antibodies against apoB100 peptide 210 inhibit atherosclerosis in apoE(-/-) mice
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Atherosclerotic plaques are characterized by an accumulation and subsequent oxidation of LDL, resulting in adaptive immune responses against formed or exposed neoepitopes of the LDL particle. Autoantibodies against native p210, the 3136-3155 amino acid sequence of the LDL protein apolipoprotein B-100 (apoB100) are common in humans and have been associated with less severe atherosclerosis and decreased risk for cardiovascular events in clinical studies. However, whether apoB100 native p210 autoantibodies play a functional role in atherosclerosis is not known. In the present study we immunized apoE(-/-) mice with p210-PADRE peptide to induce an antibody response against native p210. We also injected mice with murine monoclonal IgG against native p210. Control groups were immunized with PADRE peptide alone or with control murine monoclonal IgG. Immunization with p210-PADRE induced an IgG1 antibody response against p210 that was associated with reduced atherosclerotic plaque formation in the aorta and reduced MDA-LDL content in the lesions. Treatment with monoclonal p210 IgG produced a similar reduction in atherosclerosis as immunization with p210-PADRE. Our findings support an atheroprotective role of antibodies against the apoB100 native p210 and suggest that vaccines that induce the expression of native p210 IgG represent a potential therapeutic strategy for lowering cardiovascular risk.
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| 8. |
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| 9. |
- Forssell-Aronsson, Eva, 1961, et al.
(author)
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Aspects on radionuclide therapy in malignant pheochromocytomas.
- 2006
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In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 498-504
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Journal article (peer-reviewed)abstract
- Malignant pheochromocytomas/paragangliomas (PCs/PGs) often have distant metastases to the skeleton, liver, and lungs. Radionuclide therapy is valuable for treatment of disseminated tumor disease and could be used as adjuvant therapy after surgery. Patients with local and/or distant metastases of PC/PG should be investigated preoperatively by scintigraphy using both 123I-MIBG and 111In-DTPA-D-Phe1-octreotide, to evaluate the possibilities for radionuclide therapy (i.e., a dosimetric estimation of radiation dose to the tumor tissue versus critical normal tissues). Individual patient dose-planning should be performed. For patients in whom positive therapeutic effects are anticipated radionuclide therapy can be applied. Therapy with both 131I-MIBG and 177Lu-octreotate might be favorable in individual patients with lesions visualized by both metaiodobenzylguanidine (MIBG) and octreotide scintigraphy with enhanced therapeutic effects and reduced side effects.
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| 10. |
- Grenegård, Magnus, 1963-, et al.
(author)
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The cardioprotective, anti-inflammatory and antithrombotic piperazinyl-purine analogue MK177 is a bifunctional drug with promising therapeutic potential
- 2023
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In: British Journal of Pharmacology. - : Macmillan Publishers Ltd.. - 0007-1188 .- 1476-5381. ; 180:Suppl. 1, s. 158-159
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Journal article (other academic/artistic)abstract
- Introduction: Nitrate ester bearing 6-piperazinyl-purine analogues (denoted MK drugs) are cardioprotective in infarction animal models and act as inhibitors of Janus kinase (JAK) and Rho-associated kinase (ROCK) [1-3]. Despite the presence of nitrate ester moiety, the MK drugs do not release nitric oxide (NO).Methods: We utilized organic chemistry platforms to design a dinitrate ester derivative denoted MK177, cell-free and cellular assays to elucidate antithrom-botic and anti-ischemic mechanisms. Furthermore, we also used tissue models to analyze vasodilation, and animal models to evaluate drug activities in vivo.Results: In anesthetized pigs, intravenous infusion of MK177 produced“nitroglycerin-like”effects on vital parameters. Analysis of exhaled air confirmed release of NO. MK177 caused concentration-dependent relaxation of iliac arteries (87±6.8 % relaxation of precontracted arteries, mean value ±SD, n=5) and this effect was mediated by activation of the NO/cyclic GMP signaling pathway. It is noteworthy that other mononitrate or non-nitrate MKs did not cause NO-induced vasodilation. In cellular model systems, MK177 evoked antithrombotic effects by targeting ROCK in a NO-independent manner. Specifically, MK177 inhibited platelet aggregation induced by collagen (72±12.6 % inhibition of aggregation, mean value±SD, n=7). Western blot analyses confirmed that MK177 reduced ROCK-dependent phosphorylation of myosin phosphatase sub-unit (MYPT-1) in platelets. Finally, kinase screening assay revealed that MK177 concentration-dependently inhibited ROCK and JAK (Kd values around 5μM).Conclusion: We have developed a bifunctional drug molecule, MK177, that acts by NO-dependent and NO-independent mechanisms. MK 177 induced car-diovascular NO effects in vivo and relaxed vessels in vitro. MK177 also prevented blood platelet activation via NO-independent ROCK inhibition. The bifunctional nature of MK177 can be of significance in future management of thrombotic and ischemic disease. Collectively, the novel cardio-protective and bifunctional drug MK177 has promising therapeutic potential.References:1. Koufaki M, Fotopoulou T, Iliodromitis EK, Bibli SI, Zoga A, Kremastinos DT, Andreadou I. Discovery of 6-[4-(6-nitroxyhexanoyl)(piperazin-1-yl)]-9H-purine, as pharmacological post-conditioning agent. Bioorg Med Chem. 2012;20(19):5948-5956. https://doi.org/10.1016/j.bmc.2012.07.0372. Kardeby C, Paramel GV, Pournara D, Fotopoulou T, Sirsjö A, Koufaki M, Fransén K, Grenegård M. A novel purine analogue bearing nitrate ester prevents platelet activation by ROCK activity inhibition. Eur J Pharmacol. 2019;15(857):172428-172434. https://doi.org/10.1016/j.ejphar.2019.1724283. Paramel GV, Lindkvist M, Idosa BA, Sebina LS, Kardeby C, Fotopoulou T, Pournara D, Kritsi E, Ifanti E, Zervou M, Koufaki M, Grenegård M, Fransén K. Novel purine analogues regulate IL-1βrelease via inhibition of JAK activity in human aortic smooth muscle cells. Eur J Pharmacol. 2022;15(929):175128-175135. https://doi.org/10.1016/j.ejphar.2022.175128
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| 11. |
- Gunnlaugsson, Adalsteinn, et al.
(author)
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A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and Ga-68-PSMA-PET for biochemical relapse after radical prostatectomy-The PROPER 1 trial
- 2022
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In: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 36, s. 77-82
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Journal article (peer-reviewed)abstract
- Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still >= 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy. Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders. Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.
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| 12. |
- Jacobsson, Maritha, 1960-, et al.
(author)
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Barnrätten som kunskapsregim och social praktik
- 2012
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In: Rätt, social utsatthet och samhälleligt ansvar. - Stockholm : Norstedts Juridik AB. - 9789139016649 ; , s. 53-71
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Book chapter (other academic/artistic)
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| 13. |
- Jakobsen, A M, et al.
(author)
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Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.
- 2001
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In: The Journal of pathology. - : Wiley. - 0022-3417. ; 195:4, s. 463-72
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Journal article (peer-reviewed)abstract
- Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.
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| 14. |
- Kalra, Hina, et al.
(author)
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Vesiclepedia : a compendium for extracellular vesicles with continuous community annotation
- 2012
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In: PLoS biology. - : Public library of science. - 1544-9173 .- 1545-7885. ; 10:12, s. e1001450-
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Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
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| 15. |
- Kölby, Lars, 1963, et al.
(author)
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A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.
- 2001
-
In: The American journal of pathology. - 0002-9440. ; 158:2, s. 745-55
-
Journal article (peer-reviewed)abstract
- A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
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| 16. |
- Kölby, Lars, 1963, et al.
(author)
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Can quantification of VMAT and SSTR expression be helpful for planning radionuclide therapy of malignant pheochromocytomas?
- 2006
-
In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 491-7
-
Journal article (peer-reviewed)abstract
- Tumor-specific uptake of the radio-iodinated norepinephrine analogue meta-iodobenzylguanidine (MIBG) or uptake of radiolabeled somatostatin analogues via somatostatin receptors (SSTRs) are possibilities to diagnose and treat malignant pheochromocytomas/paragangliomas (PCs/PGs). The aims of this study were to investigate the quantitative expression of vesicular monoamine transporters (VMAT 1, 2) and all five SSTRs in malignant pheochromocytoma/paraganglioma (PC/PG) to evaluate the possibilities for tumor-specific radionuclide therapy. High scintigraphic 123I-MIBG uptake was found in two malignant PGs with high VMAT expression (500-730 copies of VMAT 1, 1,500-1,700 copies of VMAT 2 per 1,000 beta-actin), while no 123I-MIBG uptake was found in the malignant PG with low VMAT expression (330 copies of VMAT 1, 350 copies of VMAT 2 per 1,000 beta-actin). The two patients with high VMAT expression and high 123I-MIBG uptake were treated with 131I-MIBG (2-3x8 GBq). In vitro, the VMAT antagonist, reserpine, and the membrane pump inhibitor, clomipramine, inhibited the uptake of 123I-MIBG into tumor cells equally well (48% and 53% reduction respectively, P<0.001). SSTR2 was the most abundant receptor subtype, but in the two malignant PGs its expression was only 110-260 copies/1,000 beta-actin. The transporters at the cell membrane and in the vesicular membrane both appear to be of importance for the uptake of 123I-MIBG into malignant PC/PG. Quantitative determination of VMAT expression may be helpful in selecting patients suitable for radionuclide therapy with 131I-MIBG. The present data indicate that SSTR-mediated radionuclide therapy will not be effective treatment of malignant PC/PG.
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| 17. |
- Kölby, Lars, 1963, et al.
(author)
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Chromogranin A as a determinant of midgut carcinoid tumour volume
- 2004
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In: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 120:1-3, s. 269-73
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Journal article (peer-reviewed)abstract
- Neuroendocrine (NE) tumours are characterized by their capacity to synthesize, store and release hormonal products. These substances are stored in neurosecretory vesicles together with chromogranin A (CgA). The concentration of plasma CgA in patients with NE tumours is thought to reflect the degree of NE differentiation, total tumour burden and effect of medical treatment. The aim of this study was to analyse the correlation between tumour weight and plasma CgA levels as well as the influence of treatment with a long-acting somatostatin analogue (octreotide) using nude mice with xenografted human ileal carcinoid tumours. There was a correlation between tumour weight and plasma CgA levels in all animals (p < 0.00001). In octreotide-treated mice, plasma CgA levels were significantly reduced versus untreated animals (p = 0.037). In conclusion, this study demonstrates that plasma CgA levels are closely correlated to tumour burden, and that plasma CgA is well suited for monitoring the clinical course and outcome of treatment in patients with NE tumours.
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| 18. |
- Kölby, Lars, 1963, et al.
(author)
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Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors.
- 1998
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In: Digestion. - 0012-2823. ; 59:2, s. 160-6
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Journal article (peer-reviewed)abstract
- A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MelmAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.
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| 19. |
- Kölby, Lars, 1963, et al.
(author)
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Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors.
- 1998
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In: World journal of surgery. - 0364-2313. ; 22:7, s. 679-83
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Journal article (peer-reviewed)abstract
- Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28-71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.
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| 20. |
- Kölby, Lars, 1963, et al.
(author)
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Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour
- 2005
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In: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 93:10, s. 1144-51
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Journal article (peer-reviewed)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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| 21. |
- Kölby, Lars, 1963, et al.
(author)
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Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters.
- 2003
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In: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1383-8
-
Journal article (peer-reviewed)abstract
- The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of (123)I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated (123)I after i.v. injection of (123)I-MIBG. A high concentration of (123)I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n=4 and pheochromocytomas, n=4), reserpine significantly reduced the uptake of (123)I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of (123)I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of (123)I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.
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| 22. |
- Magnusson, Petra, 1963-, et al.
(author)
-
"Nu sätter vi ord på det, ryggraden har flyttat till huvudet" : kollegialt lärande och ett språkutvecklande förhållningssätt som beprövad erfarenhet i fritidshemsverksamheten
- 2016
-
In: Skolportens nättidskrift Undervisning & Lärande. ; :13
-
Journal article (other academic/artistic)abstract
- Artikeln beskriver ett utvecklingsarbete bedrivet i fritidshemsverksamhet. Syftet var att genom kollegialt lärande utveckla ett språkutvecklande förhållningssätt i verksamheten. Arbetet genomfördes under tre terminer och dokumentationen utgörs av anteckningar från observationer och samtalsträffar samt ljudinspelning från ett återkopplande samtal inspirerat av ”stimulated recall”. Resultatet bekräftar tidigare forsknings beskrivningar av fritidsverksamhet som en verksamhet som under senare år påverkats av organisatoriska förändringar och som en miljö för informellt lärande och processinriktad didaktik. Resultatet visar också på möjligheter att utveckla fritidshemsverksamhetens särskilda karaktär genom kollegialt lärande och strävan efter vetenskaplig grund. Utvecklingsarbetet bidrog till att stärka fritidslärarnas yrkesroll och öka deras medvetenhet om språkets betydelse för lärande.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Nilsson, Eva, 1963-
(author)
-
Children crossing borders : on child perspectives in the Swedish aliens act and the limits of law
- 2007
-
In: Exploiting the limits of law. - Aldershot : Ashgate. - 9780754649359 - 9781315581569 ; , s. 105-126
-
Book chapter (peer-reviewed)abstract
- This chapter discusses two questions regarding this comprehensive issue that is what are the legal premises for the rules in question and what are their implications for a legal study about children in matters concerning residence permits. It is based on findings from an ongoing doctoral study concerning the status of children in the determination of residence permit. The chapter aims to discuss the implications the legal premises that have been described might have for a legal study and why it is important to conduct studies in this field of law. In the middle of 1990s, there was an intense debate in Sweden questioning whether Sweden was fulfilling its obligations under the United Nations Convention on the Rights of the Child (CRC). In 2006, a new Aliens Act came into force in Sweden, which introduced new rules relating to the circumstances in which judicial review would be available as well as a new process for dealing with such reviews.
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| 27. |
- Nilsson, Eva, 1963-
(author)
-
Persecution on account of one’s gender : refugee status or status quo?
- 2012
-
In: feminists@law. - 2046-9551. ; 2:1
-
Journal article (peer-reviewed)abstract
- The subject of this paper is women experiencing male partner violence and the determination of refugee status. My central point of departure is the changes that were made in the Swedish Aliens Act in 2006 concerning the definition of ‘refugee’, which inter alia states that persecution on account of a person’s gender should be included within the definition. The changes came into force at the same time as the new Aliens Act which was introduced in order to strengthen the ‘rule of law’ in migration matters. The objective of this article is to analyse the premises for these changes. The conclusion is that the changes are gender biased and marked by ‘othering’ mechanisms and underlying racism. The conclusion is also that many of these women, as a consequence of the constructions in the legislation, are exposed by the Swedish migration authorities to such institutionalized violence ‘on account of gender’ that would have been a basis for refugee status if it had been the authorities in their homeland that had exposed them to it. The reason for this is that the ‘special’ character of migration law rests upon demands other than those usually required by the ‘rule of law’, limiting the possibilities for change. However, maintaining the ‘rule of law’ also means exclusion for women seeking asylum. With or without the rule of law, it seems ongoing exclusion is the keyword for women in this branch of law.
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| 28. |
- Nilsson, Eva, 1963-
(author)
-
The 'Refugee' and the 'Nexus' Requirement : The Relation between Subject and Persecution
in the United Nations Refugee Convention
- 2014
-
In: Women's Studies. - : Elsevier. - 0277-5395 .- 1879-243X. ; 46, s. 123-131
-
Journal article (peer-reviewed)abstract
- The challenge that my paper deals with is the complexities of gender and violence within international refugee law, taking women exposed to male partner violence as a starting point. The focus is the definition of ‘refugee’ in the United Nations Refugee Convention and the requirement that the persecution must be based on specific grounds, the ‘nexus’ requirement. My analysis shows that the Convention is grounded in an essentialist understanding of the subject and that the preservation of its structure and integrity also means preserving the power structures in society. The argumentation suggests that it is time to abolish the ‘nexus’ requirement and the limitation of the grounds, but my conclusion is rather that we must continue to work with our frame of thought focusing on the ‘refugee situation’ and the discursive constitution of the subject in time and space.
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| 29. |
- Nilsson, Gill, et al.
(author)
-
Neurodevelopmental problems should be considered in children with febrile seizures
- 2019
-
In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:8, s. 1507-1514
-
Journal article (peer-reviewed)abstract
- Aim: Clinical developmental phenotyping of four- to five-year-old children with febrile seizures (FSs).Methods: Children with FS (n = 157, corresponding to 3.7% of the targeted general population of four-five-year-olds) had been identified at child healthcare centres in Gothenburg. Parents of 73 children (41 boys, 32 girls) accepted participation in the present study. The assessments included a neuropaediatric assessment, Movement ABC, Wechsler Preschool and Primary Scale of Intelligence-III and parent questionnaires (Five-to-Fifteen (FTF) and Strengths and Difficulties Questionnaire (SDQ)). Hospital records were reviewed, when applicable.Results: One-third of the children had at least one DSM-5 neurodevelopmental disorder diagnosis or marked developmental problems within areas of attention, activity regulation, behaviour, speech and language, general cognition or motor functioning. No differences were found between children with single vs recurrent or simple vs complex FS.Conclusion: Febrile seizure are relatively often associated with Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations (ESSENCEs). We found no indications that ESSENCE might be caused by FS per se. However, the results suggest that child healthcare professionals should consider the possibility of ESSENCE in children with a history of FS.
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| 30. |
- Nilsson, Jan, 1963-, et al.
(author)
-
Development and validation of a new tool measuring nurses self-reported professional competence — The nurse professional competence (NPC) Scale
- 2014
-
In: Nurse Education Today. - Midlothian, Scotland : Elsevier BV. - 0260-6917 .- 1532-2793. ; 34:4, s. 574-580
-
Journal article (peer-reviewed)abstract
- Objectives: To develop and validate a new tool intended for measuring self-reported professional competence among both nurse students prior to graduation and among practicing nurses. The new tool is based on formal competence requirements from the Swedish Board of Health and Welfare, which in turn are based on WHO guidelines. Design: A methodological study including construction of a new scale and evaluation of its psychometric properties. Participants and settings: 1086 newly graduated nurse students from 11 universities/university colleges. Results: The analyses resulted in a scale named the NPC (Nurse Professional Competence) Scale, consisting of 88 items and covering eight factors: “Nursing care”, “Value-based nursing care”, “Medical/technical care”, “Teaching/ learning and support”, “Documentation and information technology”, “Legislation in nursing and safety planning”, “Leadership in and development of nursing care” and “Education and supervision of staff/students”. All factors achieved Cronbach's alpha values greater than 0.70. A second-order exploratory analysis resulted in two main themes: “Patient-related nursing” and “Nursing care organisation and development”. In addition, evidence of known-group validity for the NPC Scale was obtained.
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| 31. |
- Nilsson, Jan, 1963-, et al.
(author)
-
Nursing in a globalized world : Nursing students with international study experience report higher competence at graduation
- 2014
-
In: Open Journal of Nursing. - : Scientific Research Publishing, Inc.. - 2162-5336 .- 2162-5344. ; :4, s. 848-858
-
Journal article (peer-reviewed)abstract
- Due to globalization, there is a need for nurses with skills and competence in providing safe, competent and culturally appropriate care. The aim of the study was to investigate whether International Study Experiences (ISE) in other countries during basic nursing education had an impact on newly graduated nurses as regards to self-reported competence. Moreover, a second aim was to explore what background factors that facilitated or constituted a hindrance for nursing students to choose to conduct part of their basic nursing education abroad. At 11 Universities/University Colleges (henceforth called Higher Education Institutions [HEIs]) in Sweden, 565 nursing students responded to the Nurse Professional Competence (NPC) Scale. Students with ISE rated their competence significantly higher on three NPC competence areas; “Legislation in nursing and safety planning”, “Leadership and development of nursing” and “Education and supervision of staff/students”. Background factors that significantly seemed to enhance ISE were; living alone, not having children or other commitments, international focus at the HEI and previous international experience. Lack of financial means was reported to prevent students from choosing ISE. The study implies that several background factors are of importance whether students choose ISE or not. ISE during basic nursing education might result in better self-reported competence in leading and developing nursing care, including education of future nurses, and in providing safe care.
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| 32. |
- Nilsson, Ola, 1957, et al.
(author)
-
Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.
- 1998
-
In: British journal of cancer. - 0007-0920. ; 77:4, s. 632-7
-
Journal article (peer-reviewed)abstract
- We have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [111In]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The 111In activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 111In activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction). Incubation of midgut carcinoid tumours in primary culture with octreotide (10 microM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.
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| 33. |
- Nilsson, Ola, 1957, et al.
(author)
-
GOT1 xenografted to nude mice: a unique model for in vivo studies on SSTR-mediated radiation therapy of carcinoid tumors
- 2004
-
In: Annals of the New York Academy of Sciences. - 0077-8923. ; 1014, s. 275-9
-
Journal article (peer-reviewed)abstract
- Malignant carcinoid tumors express high numbers of somatostatin receptors. Radiation therapy using labeled somatostatin analogs is a novel treatment modality for these tumors. We have analyzed the biokinetics and therapeutic effect of radiolabeled somatostatin analog on a human midgut carcinoid grafted to nude mice. A transplantable human midgut carcinoid (GOT1) was grafted to the back of nude mice. Tumor-bearing mice were injected with (111)In-DTPA-D-Phe(1)-octreotide, followed by measurement of (111)In activity concentration ratios in tumor tissues. Tumor-bearing mice were also injected with (177)Lu-DOTA-Tyr(3)-octreotate and followed for 7 days. The concentration of (111)In-DTPA-D-Phe(1)-octreotide in tumor tissues was very high 4 hours postinjection with 0.4-13% of injected activity per gram. Injection of 30-120 MBq (177)Lu-DOTA-Tyr(3)-octreotate reduced tumor volume to 7-14% of the original tumor volume 7 days postinjection. Microscopic analysis of treated tumors revealed widespread areas of tumor cell necrosis and fibrosis. It was found that grafted GOT1 cells to nude mice represent an authentic model for studying human midgut carcinoids. Radiolabeled somatostatin analogs have a high selectivity for tumor tissue and can induce tumor cell necrosis. Radiotherapy of carcinoid tumors with (177)Lu-DOTA-Tyr(3)-octreotate appears to be a promising treatment modality for either palliative treatment or completion therapy after attempted surgical cure.
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| 34. |
- Nilsson, Ola, 1957, et al.
(author)
-
Importance of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors.
- 2004
-
In: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1014, s. 280-3
-
Journal article (peer-reviewed)abstract
- We have analyzed the expression of synaptic vesicle proteins in human neuroendocrine tumors and the potential use of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. Biopsies from endocrine and nonendocrine tumors of the gastrointestinal tract, pancreas, and adrenals were examined by immunocytochemistry using antibodies against synaptic vesicle protein 2 (SV2), vesicular monoamine transporter 1 and 2 (VMAT1 and 2), and neuroendocrine secretory protein 55 (NESP55). SV2 was expressed in all endocrine tumors of the gastrointestinal tract and pancreas as well as in gastrointestinal stromal tumors (GISTs). None of the adenocarcinomas expressed SV2. VMAT1 and 2 were expressed in amine-producing tumors of the gastrointestinal tract (ECL cell and EC cell carcinoids) and in a small number of peptide-producing pancreatic endocrine tumors. NESP55 was expressed in neuroblastomas and adrenal pheochromocytomas as well as in a subgroup of pancreatic endocrine tumors. The importance of VMAT1 and 2 for the uptake of 123I-MIBG in tumor cells was demonstrated. It was concluded that neuroendocrine tumors express multiple synaptic vesicle proteins that are useful in the histopathological diagnosis and classification of tumors. Vesicle proteins may prove to be useful for targeting tumor therapy.
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| 35. |
- Oddstig, Jenny, 1978, et al.
(author)
-
Inhomogeneous activity distribution of (177)Lu-DOTA (0)-Tyr (3)-octreotate and effects on somatostatin receptor expression in human carcinoid GOT1 tumors in nude mice.
- 2012
-
In: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1423-0380. ; 33:1, s. 229-239
-
Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the activity distribution in neouroendocrine tumors after diagnostic, or therapeutic, amounts of [(177)Lu-DOTA(0)-Tyr(3)]-octreotate and to investigate how the activity distribution influences the absorbed dose. Furthermore, the activity distribution of a second administration of radiolabeled octreotate was studied. Nude mice with subcutaneously grown human midgut carcinoid (GOT1) were injected intravenously with different amounts of (177)Lu-octreotate. At different time points thereafter (4h to 13days), a second injection of [(111)In-DOTA(0)-Tyr(3)]-octreotate was given to estimate the somatostatin receptor (sstr) expression. The activity distribution in the tumors was then determined. Monte Carlo simulations with PENELOPE were performed for dosimetry. Fifty-one out of 58 investigated tumors showed a lower activity concentration in the peripheral part than in the central part of the tumor. The amount of activity injected, or time after administration, did neither influence the relative activity nor the sstr distribution in the tumor. After an initial down-regulation (at 4-24h), there was an up-regulation of sstr (1.5-2 times, at 7-14days). Monte Carlo simulations demonstrated an inhomogeneous absorbed dose distribution in the tumor using (177)Lu, with twice as high absorbed dose centrally than peripherally. The high activity concentration centrally and the up-regulation of sstr demonstrated will facilitate fractionated therapy using radiolabeled somatostatin analogues if similar results will be obtained also in patients. The inhomogeneous activity distribution in the tumor has to be taken into account when the absorbed dose distribution in tumor is calculated.
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| 36. |
- Olsson, Karin H., 1979, et al.
(author)
-
Dark eyes in female sand gobies indicate readiness to spawn
- 2017
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
-
Journal article (peer-reviewed)abstract
- In animals, colorful and conspicuous ornaments enhance individual attractiveness to potential mates, but are typically tempered by natural selection for crypsis and predator protection. In species where males compete for females, this can lead to highly ornamented males competing for mating opportunities with choosy females, and vice versa. However, even where males compete for mating opportunities, females may exhibit conspicuous displays. These female displays are often poorly understood and it may be unclear whether they declare mating intent, signal intrasexual aggression or form a target for male mate preference. We examined the function of the conspicuous dark eyes that female sand gobies temporarily display during courtship by experimentally testing if males preferred to associate with females with artificially darkened eyes and if dark eyes are displayed during female aggression. By observing interactions between a male and two females freely associating in an aquarium we also investigated in which context females naturally displayed dark eyes. We found that dark eyes were more likely to be displayed by more gravid females than less gravid females and possibly ahead of spawning, but that males did not respond behaviorally to dark eyes or prefer dark-eyed females. Females behaving aggressively did not display dark eyes. We suggest that dark eyes are not a signal per se but may be an aspect of female mate choice, possibly related to vision.
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| 37. |
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| 38. |
- Schmitt, Anneli, 1971, et al.
(author)
-
Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide, and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model
- 2005
-
In: Cancer biotherapy & radiopharmaceuticals. - 1084-9785. ; 20:2, s. 231-6
-
Journal article (peer-reviewed)abstract
- AIM: (177)Lu-DOTA-Tyr(3)-octreotate is a candidate radiopharmaceutical for the therapy of somatostatin receptor (sstr)-positive small cell lung cancer (SCLC). Scintigraphy of lung tumors is made with 2 alternative somatostatin analogs, (111)In-DTPA-octreotide or (99m)Tc-depreotide. The aim of this study was to compare the biodistribution of these 3 radiopharmaceuticals in SCLC xenografted to nude mice. METHODS: Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were intravenously injected with 10 MBq (2.4 microg) (99m)Tc-depreotide and 2 MBq (0.5 microg) (111)In-DTPA-octreotide simultaneously. The activity concentration (%IA/g) was measured in tumor and normal tissue at 2, 4, and 24 hours postinjection (hpi). The results were compared with earlier published biodistribution data of 3 MBq (0.7 microg) (177)Lu-DOTA-Tyr(3)-octreotate in the same animal model. RESULTS: The activity concentration of (111)In-DTPAoctreotide in tumor was higher than the activity concentration of (99m)Tc-depreotide at 2-24 hpi, p < 0.05. The highest tumor uptake at 24 hpi was, however, found for (177)Lu-DOTA-Tyr(3)-octreotate. The activity concentration of (99m)Tc-depreotide was significantly higher in the heart, lungs, liver, the salivary glands, spleen, and bone marrow than for (111)In-DTPA-octreotide at 2-24 hpi. Saturation of the somatostatin receptors may have influenced the uptake in tumor and sstr-positive normal tissues. CONCLUSION: The low tumor-to-lung and tumor-to-liver activity concentration ratios for (99m)Tc-depreotide could result in a lower detection rate of SCLC with this compound versus (111)In-DTPA-octreotide. (177)Lu-DOTA-Tyr(3)-octreotate gave the highest tumor-activity concentration, and has, thus, the best properties for therapy.
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| 39. |
- Schmitt, Anneli, 1971, et al.
(author)
-
Radiation therapy of small cell lung cancer with 177Lu-DOTA-Tyr3-octreotate in an animal model
- 2004
-
In: Journal of nuclear medicine. - 0161-5505. ; 45:9, s. 1542-8
-
Journal article (peer-reviewed)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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| 40. |
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| 41. |
- Swärd, Christina, 1967, et al.
(author)
-
Comparison of [177Lu-DOTA0,Tyr3]-octreotate and [177Lu-DOTA0,Tyr3]-octreotide for receptor-mediated radiation therapy of the xenografted human midgut carcinoid tumor GOT1.
- 2008
-
In: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 23:1, s. 114-20
-
Journal article (peer-reviewed)abstract
- The aim of this study was to compare the tumor uptake versus time and the tumor response in nude mice transplanted with a human midgut carcinoid (GOT1), when treated with either [(177)Lu-DOTA(0),Tyr(3)]-octreotide or [(177)Lu-DOTA(0),Tyr(3)]-octreotate and to evaluate if plasma chromogranin A (P-CgA) was a reliable marker of tumor response. The tumor uptake and retention of activity of a single intravenous (i.v.) dose (15 MBq) of [(177)Lu-DOTA(0),Tyr(3)]-octreotate or [(177)Lu-DOTA(0),Tyr(3)]-octreotide were compared in nude mice xenografted with GOT1. The activity concentration 24 hours after injection was significantly higher in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate versus [(177)Lu-DOTA(0),Tyr(3)]-octreotide (16%+/-1.4% of injected activity per gram [%IA/g] vs. 8.1%+/-2.1% IA/g, mean +/- standard error of the mean) (p=0.00061). The mean absorbed dose was higher in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate (46+/-4.3 vs. 17 +/- 3.4 Gy). The reduction of tumor volume was accordingly more prominent in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate than in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotide (p=0.003). The mean tumor volume for animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate was reduced to 3% of its initial value. P-CgA values were strongly correlated with tumor volume. Octreotate seems to be a more suitable somatostatin analog than octreotide for receptor-mediated radiation therapy. P-CgA is a simple, accurate method for the estimation of tumor response in this animal model.
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| 42. |
- Tisell, Lars-Eric, 1931, et al.
(author)
-
Expression of somatostatin receptors in oncocytic (Hürthle cell) neoplasia of the thyroid.
- 1999
-
In: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 79:9-10, s. 1579-82
-
Journal article (peer-reviewed)abstract
- Ten consecutive patients with Hürthle cell lesions of the thyroid (nodule/adenoma/carcinoma) were studied by (111)In-DTPA-D-Phe1-octreotide scintigraphy. Octreotide scintigraphy localized the primary Hürthle cell tumour in eight patients as distinct areas of increased uptake of radionuclide. Two patients with Hürthle cell carcinoma, previously thyroidectomized, had their metastases visualized by octreotide scintigraphy. Northern analyses showed expression of multiple somatostain receptor subtypes. Visualization of the Hürthle cell tumour may be due to a higher expression of somatostatin receptors in the lesions than in surrounding normal thyroid tissue. The tissue/blood (111)In concentration ratios for tumour samples from five patients showed clearly higher values than observed for normal connective tissue, muscle or lymph nodes. A relatively high uptake of (111)In was also observed in goiter tissue, which may lead to misinterpretations. The main indication for octreotide scintigraphy in patients with Hürthle cell carcinoma is suspicion of metastatic disease.
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| 43. |
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| 44. |
- Wängberg, Bo, 1953, et al.
(author)
-
Somatostatin Receptors in the Diagnosis and Therapy of Neuroendocrine Tumor.
- 1997
-
In: The oncologist. - 1549-490X. ; 2:1, s. 50-58
-
Journal article (peer-reviewed)abstract
- The expression of somatostatin receptors in neuroendocrine tumors has facilitated the diagnosis and surgical treatment of patients with these tumors. After injection of a radiolabeled long-acting somatostatin analog, (111)In-octreotide, scintigraphic tumor imaging can ben performed as well as intraoperative tumor localization. During localization studies very high (111)In concentration values were found in tumor tissues versus normal tissues, especially in carcinoid tumors and endocrine pancreatic tumors. Studies on such tumors in cell culture further indicated internalization of (111)In into tumor cells, which is a prerequisite for a radiobiological effect from short range Auger and conversion electrons. Attempts to systemic radionuclide therapy via somatostatin receptors in patients with neuroendocrine tumors have been initiated.
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