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| 3. |
- Benjegård, S A, et al.
(författare)
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Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.
- 2001
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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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| 4. |
- Carlsson, J, et al.
(författare)
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Therapy with radiopharmaceuticals
- 2002
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Ingår i: Acta Oncologica. - 1651-226X. ; 41:7-8, s. 623-628
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Tidskriftsartikel (refereegranskat)abstract
- In an investigation by the Swedish Cancer Society, an expert group described the present status, critical issues and future aspects and potentials for each of nine major areas of radiation therapy research. The present report deals with therapy with radiopharmaceuticals.
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| 6. |
- Fjälling, M, et al.
(författare)
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Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.
- 1996
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 37:9, s. 1519-21
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Tidskriftsartikel (refereegranskat)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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| 11. |
- Gunnarsson, H, et al.
(författare)
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Heterogeneity of colon cancer patients reported as emergencies
- 2014
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 38:7, s. 1819-1826
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Hendil-Forssell, Peter, 1983-
(författare)
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Rational engineering of esterases for improved amidase specificity in amide synthesis and hydrolysis
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biocatalysis is an ever evolving field that uses enzymes or microorganisms for chemical synthesis. By utilizing enzymes that generally have evolved for specific reactions under mild conditions and temperatures, biocatalysis can be a more environmentally friendly option compared to traditional chemistry.Amide-type chemistries are important and bond formation avoiding poor atom economy is of high priority in organic chemistry. Biocatalysis could potentially be a solution but restricted substrate scope is a limitation. Esterases/lipases usually display broad substrate scope and catalytic promiscuity but are poor at hydrolyzing amides compared to amidases/proteases. The difference between the two enzyme classes is hypothesized to reside in one key hydrogen bond present in amidases, which facilitates the transition state for nitrogen inversion during catalysis.In this thesis the work has been focused on introducing a stabilizing hydrogen bond acceptor in esterases, mimicking that found in amidases, to develop better enzymatic catalysts for amide-based chemistries.By two strategies, side-chain or water interaction, variants were created in three esterases that displayed up to 210-times increased relative amidase specificity compared to the wild type. The best variant displayed reduced activation enthalpy corresponding to a weak hydrogen bond. The results show an estimated lower limit on how much the hydrogen bond can be worth to catalysis.MsAcT catalyze kinetically controlled N-acylations in water. An enzymatic one-pot one-step cascade was developed for the formation of amides from aldehydes in water that gave 97% conversion. In addition, engineered variants of MsAcT with increased substrate scope could synthesize an amide in water with 81% conversion, where the wild type gave no conversion. Moreover, variants of MsAcT displayed up to 32-fold change in specificity towards amide synthesis and a switch in reaction preference favoring amide over ester synthesis.
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| 13. |
- Jakobsen, A M, et al.
(författare)
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Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.
- 2001
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Ingår i: The Journal of pathology. - : Wiley. - 0022-3417. ; 195:4, s. 463-72
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Tidskriftsartikel (refereegranskat)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. |
- Koppal, Sandeep, et al.
(författare)
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Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis
- 2017
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Ingår i: Magnetic Resonance in Medicine. - : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 78:1, s. 285-296
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. Methods: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60×0.60×0.70mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH. Results: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64±0.2737% versus 9.294±0.1762% (mean±standard error of the mean [SEM]; P<0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81±1.276 s-1 versus 56.94±0.9095 s-1 (mean±SEM; P<0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2=0.92) as well as between cumulative R2* and IPH (R2=0.94). Conclusion: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH.
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| 15. |
- Kristiansson, A., et al.
(författare)
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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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Ingår i: Antioxidants & redox signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 32:9
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Tidskriftsartikel (refereegranskat)
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| 16. |
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| 17. |
- Kölby, Lars, 1963, et al.
(författare)
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Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors.
- 1998
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Ingår i: Digestion. - 0012-2823. ; 59:2, s. 160-6
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Tidskriftsartikel (refereegranskat)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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| 18. |
- Langen, Britta, et al.
(författare)
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Age and sex effects across the blood proteome after ionizing radiation exposure can bias biomarker screening and risk assessment
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular biomarkers of ionizing radiation (IR) exposure are a promising new tool in various disciplines: they can give necessary information for adaptive treatment planning in cancer radiotherapy, enable risk projection for radiation-induced survivorship diseases, or facilitate triage and intervention in radiation hazard events. However, radiation biomarker discovery has not yet resolved the most basic features of personalized medicine: age and sex. To overcome this critical bias in biomarker identification, we quantitated age and sex effects and assessed their relevance in the radiation response across the blood proteome. We used high-throughput mass spectrometry on blood plasma collected 24 h after 0.5 Gy total body irradiation (15 MV nominal photon energy) from male and female C57BL/6 N mice at juvenile (7-weeks-old) or adult (18-weeks-old) age. We also assessed sex and strain effects using juvenile male and female BALB/c nude mice. We showed that age and sex created significant effects in the proteomic response regarding both extent and functional quality of IR-induced responses. Furthermore, we found that age and sex effects appeared non-linear and were often end-point specific. Overall, age contributed more to differences in the proteomic response than sex, most notably in immune responses, oxidative stress, and apoptotic cell death. Interestingly, sex effects were pronounced for DNA damage and repair pathways and associated cellular outcome (pro-survival vs. pro-apoptotic). Only one protein (AHSP) was identified as a potential general biomarker candidate across age and sex, while GMNN, REG3B, and SNCA indicated some response similarity across age. This low yield advocated that unisex or uniage biomarker screening approaches are not feasible. In conclusion, age- and sex-specific screening approaches should be implemented as standard protocol to ensure robustness and diagnostic power of biomarker candidates. Bias-free molecular biomarkers are a necessary progression towards personalized medicine and integral for advanced adaptive cancer radiotherapy and risk assessment.
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| 19. |
- Leskinen, J., et al.
(författare)
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Diagnostic criteria for temporomandibular disorders (DC/TMD) : interexaminer reliability of the Finnish version of Axis I clinical diagnoses
- 2017
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 44:7, s. 493-499
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Tidskriftsartikel (refereegranskat)abstract
- Recently, updated diagnostic criteria for temporomandibular disorders (DC/TMD) were published to assess TMD in a standardised way in clinical and research settings. The DC/TMD protocol has been translated into Finnish using specific cultural equivalency procedures. To assess the interexaminer reliability using the Finnish translations of the DC/TMD-FIN Axis I clinical diagnostic assessment instruments. Reliability assessment data were collected during a 1-day DC/TMD Examiner Training Course at the University of Turku, Finland, in collaboration with the International DC/TMD Training and Calibration Center in Malmo University. Clinical TMD examinations according to the Finnish pre-final version of the DC/TMD Axis I assessment protocol were performed by four experienced TMD specialists on altogether 16 models. Kappa coefficient, overall percentage agreement (%A) as well as positive (PA) and negative (NA) agreements were used to define the reliability. Myofascial pain with referral, headache attributed to TMD and disc displacement (DD) without reduction without limited opening showed excellent kappa values (range 087-100). Fair-to-good reliability was observed for diagnoses of myalgia (k = 067), arthralgia (k = 071) and DD with reduction (k = 064). The PA was high for all pain-related diagnoses and DD without reduction without limited opening (medians 83%), and acceptable for DD with reduction (median 67%). The NA was high (medians 87%) for all DC/TMD diagnoses, except for myalgia which showed acceptable NA (median 75%). The %A was high for all assessed diagnoses (medians >85%). The findings of this study showed DC/TMD-FIN Axis I to demonstrate sufficiently high reliability for pain-related TMD diagnoses.
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| 20. |
- Li, Wei, et al.
(författare)
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Overexpression of transferrin receptor and ferritin related to clinical symptoms and destabilization of human carotid plaques
- 2008
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Ingår i: Experimental biology and medicine. - 1535-3702 .- 1535-3699. ; 233:7, s. 818-826
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of tissue iron has been implicated in development of atherosclerotic lesions mainly because of increased iron-catalyzed oxidative injury. However, it remains unknown whether cellular iron import and storage in human atheroma are related to human atheroma development. We found that transferrin receptor 1 (TfR1), a major iron importer, is highly expressed in foamy macrophages and some smooth muscle cells in intimal lesions of human carotid atheroma, mainly in cytoplasmic accumulation patterns. In 52 human carotid atherosclerotic lesions, TfR1 expression was positively correlated with macrophage infiltration, ectopic lysosomal cathepsin L, and ferritin expression. Highly expressed TfR1 and ferritin in CD68-positive macrophages were significantly associated with development and severity of human carotid plaques, smoking, and patient's symptoms. The findings suggest that pathologic macrophage iron metabolism may contribute to vulnerability of human atheroma, established risk factors, and their clinical symptoms. The cytoplasmic overexpression of TfR1 may be the result of lysosomal dysfunction and ectopic accumulation of lysosomal cathepsin I caused by atheroma-relevant lipids in atherogenesis. Copyright © 2008 by the Society for Experimental Biology and Medicine.
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| 23. |
- Saadati, Sofia, 1992, et al.
(författare)
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Early indications on UVC-related carcinogenesis: premutagenic DNA damage in mice following 222-nm light exposure
- 2016
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Ingår i: 4th Swedish Cancer Research Meeting, Gothenburg, Sweden, November 7-8, 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Surgical site infections, caused by air borne bacteria and viruses, can have lethal consequences. The use of conventional germicidal UV lamps, emitting primarily 254-nm light, at the surgical site has been prevented by being cancerogenic. Far-UVC light (200-222 nm) has been shown to be equieffective without being as damaging to human cells in vitro. In mammalian skin, it is DNA-damage in the basal cells that contributes to the major risk of cancer induction. The aim was to test the hypothesis that 222-nm light is less premutagenic than 254-nm light in vivo. SKH1 mice were exposed to different doses of 222-nm light and compared with positive (254-nm light) and negative (sham irradiated) controls. The mice were killed after 48h and dorsal skin samples were excised. UV specific DNA-damage cyclobutane pyrimidine dimer (CPD) was assessed by immunohistochemical analysis and a damage depth profile was determined. Loss of light intensity was also determined using phantoms with different protein concentrations, simulating various depths in skin. While the amount of CPD was significantly lower following 222-nm light in comparison with 254-nm light at all epidermal depths, no difference was seen in comparison with negative controls. Absorption of 222-nm light was much higher than 254-nm light. Results show that 222-nm light, for the investigated doses, does not appear to be premutagenic. These promising results indicate the potentials of far-UVC lamps as a disinfecting tool without patient and staff being subject to hazardous exposure.
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| 26. |
- Zou, Zhiyuan V., et al.
(författare)
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Genomic profiling of the transcription factor Zfp148 and its impact on the p53 pathway
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)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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