| 1. |
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| 2. |
- Kristiansson, A., et al.
(author)
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Correction to: Protection of Kidney Function with Human Antioxidation Protein α1-Microglobulin in a Mouse 177Lu-DOTATATE Radiation Therapy Model by Kristiansson A, Ahlstedt J, Holmqvist B, Brinte A, Tran TA, Forssell-Aronsson E, Strand S-E, Gram M, and Åkerström B. Antioxidants & Redox Signaling 30: 1746-1759, 2019. DOI: 10.1089/ars.2018.7517.
- 2020
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In: Antioxidants & redox signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 32:9
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Journal article (peer-reviewed)
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| 3. |
- 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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| 4. |
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| 5. |
- Kristiansson, Amanda, et al.
(author)
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Protection of Kidney Function with Human Antioxidation Protein α 1 -Microglobulin in a Mouse 177 Lu-DOTATATE Radiation Therapy Model
- 2019
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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 30:14, s. 1746-1759
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Journal article (peer-reviewed)abstract
- Aims: Peptide receptor radionuclide therapy (PRRT) is in clinical use today to treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin analog peptides target tumors that are killed by irradiation damage. The peptides, however, are also retained in kidneys due to glomerular filtration, and the administered doses must be limited to avoid kidney damage. The human radical scavenger and antioxidant, α 1 -microglobulin (A1M), has previously been shown to protect bystander tissue against irradiation damage and has pharmacokinetic and biodistribution properties similar to somatostatin analogs. In this study, we have investigated if A1M can be used as a renal protective agent in PRRT. Results: We describe nephroprotective effects of human recombinant A1M on the short- and long-term renal damage observed following lutetium 177 ( 177 Lu)-DOTATATE (150 MBq) exposure in BALB/c mice. After 1, 4, and 8 days (short term), 177 Lu-DOTATATE injections resulted in increased formation of DNA double-strand breaks in the renal cortex, upregulated expression of apoptosis and stress response-related genes, and proteinuria (albumin in urine), all of which were significantly suppressed by coadministration of A1M (7 mg/kg). After 6, 12, and 24 weeks (long term), 177 Lu-DOTATATE injections resulted in increased animal death, kidney lesions, glomerular loss, upregulation of stress genes, proteinuria, and plasma markers of reduced kidney function, all of which were suppressed by coadministration of A1M. Innovation and Conclusion: This study demonstrates that A1M effectively inhibits radiation-induced renal damage. The findings suggest that A1M may be used as a radioprotector during clinical PRRT, potentially facilitating improved tumor control and enabling more patients to receive treatment. © Amanda Kristiansson et al. 2018; Published by Mary Ann Liebert, Inc.
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| 7. |
- Benjegård, S A, et al.
(author)
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Evaluation of three gamma detectors for intraoperative detection of tumors using 111In-labeled radiopharmaceuticals.
- 1999
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In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 40:12, s. 2094-101
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Journal article (peer-reviewed)abstract
- Attempts to detect tumors with intraoperative scintillation using tumor-binding radiopharmaceuticals have intensified recently. In some cases previously unknown lesions were found, but in most cases no additional lesions were detected. In this study the physical characteristics of three detector systems and their ability to detect tumors through accumulation of an 111In-labeled radiopharmaceutical were investigated. The first was a sodium iodide (NaI[TI]) detector; the second, a cesium iodide (CsI[TI]) detector; and the third, a cadmium telluride (CdTe) detector.
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| 8. |
- Benjegård, S A, et al.
(author)
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Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.
- 2001
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In: European journal of nuclear medicine. - : Springer Science and Business Media LLC. - 0340-6997 .- 1619-7070 .- 1619-7089. ; 28:10, s. 1456-62
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Journal article (peer-reviewed)abstract
- Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(T1) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(T1) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(T1) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.
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| 9. |
- Fjälling, M, et al.
(author)
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Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.
- 1996
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In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:9, s. 1519-21
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Journal article (peer-reviewed)abstract
- A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.
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| 10. |
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| 12. |
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| 13. |
- Forssell-Aronsson, Eva, 1961, et al.
(author)
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THE IMPACT OF CIRCADIAN RHYTHMS ON MEDICAL IMAGING AND RADIOTHERAPY REGIMES FOR THE PAEDIATRIC PATIENT
- 2017
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In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 173:1-3, s. 16-20
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Journal article (peer-reviewed)abstract
- Daily rhythmic changes are found in cellular events in cell cycle, DNA repair, apoptosis and angiogenesis in both normal and tumour tissue, as well as in enzymatic activity and drug metabolism. In this paper, we hypothesize that circadian rhythms need to be considered in radiation protection and optimization in personalized medicine, especially for paediatric care. The sensitivity of the eye lens to ionizing radiation makes the case for limiting damage to the lens epithelium by planning medical radio-imaging procedures for the afternoon, rather than the morning. Equally, the tumour and normal tissue response to radiotherapy is also subject to diurnal variation enabling optimization of time of treatment.
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| 14. |
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| 15. |
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| 16. |
- Gunnarsson, H, et al.
(author)
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Heterogeneity of colon cancer patients reported as emergencies
- 2014
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 38:7, s. 1819-1826
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Journal article (peer-reviewed)abstract
- BACKGROUND:Up to one-fourth of all colon cancer patients are reported as emergencies, and the aim of the present study was to scrutinize mode of presentation in this group.MATERIALS AND METHODS:All reported cases of emergency (n = 263) and randomly selected elective controls (1:2) of colon cancer in four Swedish counties 2006-2008 were eligible (n = 854). Symptoms and aspects of management were retrieved from surgery and primary care records. Outcomes were compared using Kaplan-Meier estimates and Cox regression.RESULTS:Among patients reported as emergencies, 158/263 (60 %) underwent operation within three days (acute), and 105 (40 %) after more than 3 days (subacute). In the latter group, 20/94 (21 %) had reported two symptoms, and 31/94 (33 %) had reported three or more symptoms associated with colon cancer to primary care during the last 12 months prior to surgery. In total, 46/105 (44 %) had already had an examination of the large bowel, and 52/105 (50 %) were stage IV, as opposed to 36/158 (23 %) in the acute group and 83/577 (15 %) in the elective group (p < 0.001). Mortality at 30 and 90 days was 15.2 and 35.6 % in the subacute group, 8.2 and 14.9 % in the acute group (p = 0.001), and 1.9 and 4.3 % in the elective group (p < 0.001); 5-year survival was 28.3, 40.1, and 57.8 %, respectively, in the three groups (p < 0.001). The hazard ratio, adjusted for age, sex, and stage, was 1.88 95 % confidence interval (CI) 1.5-2.4) for the acute group and 2.29 (95 % CI 1.7-3.1) for the subacute group.CONCLUSIONS:Colon cancer patients reported as emergencies but operated upon more than three days after admission had the worst outcome. Efforts to decrease the interval between admission and surgery is one important aspect of care, but wider attention must also be paid to this group of patients.
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| 17. |
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| 18. |
- 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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| 19. |
- 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
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In: The American journal of pathology. - 0002-9440. ; 158:2, s. 745-55
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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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| 20. |
- 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
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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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| 21. |
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| 22. |
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| 23. |
- Nilsson, Ola, 1957, et al.
(author)
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Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.
- 1998
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In: British journal of cancer. - 0007-0920. ; 77:4, s. 632-7
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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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| 24. |
- Nyström, Elisabeth, et al.
(author)
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Combined use of bone grafts and implants in the severely resorbed maxilla. Postoperative evaluation by computed tomography.
- 1995
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In: International Journal of Oral and Maxillofacial Surgery. - 0901-5027 .- 1399-0020. ; 24:1 Pt 1, s. 20-25
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Journal article (peer-reviewed)abstract
- Combined horseshoe-shaped iliac bone grafts and Brånemark fixtures were used to rehabilitate patients with severely resorbed maxillae. Twenty patients were followed-up by computed tomography (CT) examination with axial slices to assess the fixture sites and to study the changes in height and width of the bone graft 3 weeks and 3, 6, 12, and 24 months postoperatively. The mean height of the bone graft at the 3-week postoperative examination was 8.2 mm; after 2 years the mean value had decreased to 6.2 mm. The height reduction occurred mainly between the 3-month and 1-year examinations. The mean width of the bone graft at the 3-week postoperative examination was 12.2 mm, and it decreased to 8.6 mm after 2 years. Most of the width reduction took place during postoperative months 1-3. From 1 year after the grafting procedure, the rate of reduction of both height and width was very low.
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| 25. |
- Odeberg, Jacob, et al.
(author)
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Influence of pre-existing inflammation on the outcome of acute coronary syndrome: a cross-sectional study
- 2016
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In: Bmj Open. - : BMJ. - 2044-6055. ; 6:1
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Journal article (peer-reviewed)abstract
- Objectives: Inflammation is a well-established risk factor for the development of coronary artery disease (CAD) and acute coronary syndrome (ACS). However, less is known about its influence on the outcome of ACS. The aim of this study was to determine if blood biomarkers of inflammation were associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with ACS. Setting: Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992-1996). Participants: In a substudy of Carlscrona Heart Attack Prognosis Study (CHAPS) of 5292 patients admitted to the coronary care unit, we identified 908 patients aged 30-74 years, who at discharge had received the diagnosis of either MI (527) or UA (381). Main outcome measures: MI or UA, based on the diagnosis set at discharge from hospital. Results: When adjusted for smoking, age, sex and duration of chest pain, concentrations of plasma biomarkers of inflammation (high-sensitivity C reactive protein >2 mg/L (OR=1.40 (1.00 to 1.96) and fibrinogen (p for trend=0.035)) analysed at admission were found to be associated with MI over UA, in an event of ACS. A strong significant association with MI over UA was found for blood cell markers of inflammation, that is, counts of neutrophils (p for trend <0.001), monocytes (p for trend <0.001) and thrombocytes (p for trend=0.021), while lymphocyte count showed no association. Interestingly, eosinophil count (p for trend=0.003) was found to be significantly lower in patients with MI compared to those with UA. Conclusions: Our results show that, in patients with ACS, the blood cell profile and degree of inflammation at admission was associated with the outcome. Furthermore, our data suggest that a pre-existing low-grade inflammation may dispose towards MI over UA.
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| 33. |
- Zou, Zhiyuan V., et al.
(author)
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Genomic profiling of the transcription factor Zfp148 and its impact on the p53 pathway
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Recent data suggest that the transcription factor Zfp148 represses activation of the tumor suppressor p53 in mice and that therapeutic targeting of the human orthologue ZNF148 could activate the p53 pathway without causing detrimental side effects. We have previously shown that Zfp148 deficiency promotes p53-dependent proliferation arrest of mouse embryonic fibroblasts (MEFs), but the underlying mechanism is not clear. Here, we showed that Zfp148 deficiency downregulated cell cycle genes in MEFs in a p53-dependent manner. Proliferation arrest of Zfp148-deficient cells required increased expression of ARF, a potent activator of the p53 pathway. Chromatin immunoprecipitation showed that Zfp148 bound to the ARF promoter, suggesting that Zfp148 represses ARF transcription. However, Zfp148 preferentially bound to promoters of other transcription factors, indicating that deletion of Zfp148 may have pleiotropic effects that activate ARF and p53 indirectly. In line with this, we found no evidence of genetic interaction between TP53 and ZNF148 in CRISPR and siRNA screen data from hundreds of human cancer cell lines. We conclude that Zfp148 deficiency, by increasing ARF transcription, downregulates cell cycle genes and cell proliferation in a p53-dependent manner. However, the lack of genetic interaction between ZNF148 and TP53 in human cancer cells suggests that therapeutic targeting of ZNF148 may not increase p53 activity in humans.
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