| 1. |
- Andersson, Eva, et al.
(författare)
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Evaluation of OAE-recording as a complementary test method for adults with moderate to profound mental retardation
- 2000
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Ingår i: Scandinavian Audiology. - : Taylor & Francis. - 0105-0397 .- 1940-2872. ; 29:2, s. 120-126
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Tidskriftsartikel (refereegranskat)abstract
- The recording of otoacoustic emissions (OAE) was evaluated as a complementary test method for adults with moderate to profound mental retardation (MR). A portable apparatus, ILO 288 Echoport linked to a Compaq LTE 5100 notebook with software ILO 88 V 4.2, was used. Otoscopy and tympanometry were also performed. Criteria for emissions were S/N 3 dB or more and reproducibility 60% or more for at least three frequency-bands. The criteria for partial emissions were the same, but for only one or two frequencies. Two examiners were needed: one to keep the tested person calm and quiet and the other to handle the keyboard. Thirty-eight people with different degrees of MR in connection with other disabilities were included. They had all exhibited incomplete results in a previous hearing screening of more than 1000 adults with MR. Reproducible transiently evoked OAEs (TEOAE) were recorded from II ears (7 people), partial TEOAEs from 6 ears (4 people) and no emissions from 15 ears (10 people). Registration from 24 ears (13 people) could not be evaluated because of too much external and internal noise. Eight people rejected the examination. Only four people showed emissions in both ears. Accordingly, 34 people (89.5%) had to be re-tested or referred for further investigation, 21 of them (55%) because of noisy recordings or no co-operation. It is concluded that the TEOAE-test in its present form cannot fulfil the demands for a functioning test method for this population. In single cases, however, TEOAE-recording can complement other audiological tests.
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| 2. |
- Andersson, Håkan, 1944, et al.
(författare)
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Astatine-211-labeled antibodies for treatment of disseminated ovarian cancer: an overview of results in an ovarian tumor model
- 2003
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Ingår i: Clin Cancer Res. - 1078-0432. ; 9:10 Pt 2
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of the study was to establish and refine a preclinical model to alpha-immunoradiotherapy of ovarian cancer. EXPERIMENTAL DESIGN: At-211 was produced by cyclotron irradiation of a bismuth-209 target and isolated using a novel dry distillation procedure. Monoclonal antibodies were radiohalogenated with the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate and characterized in terms of radiochemical yield and in vitro binding properties. In vitro OVCAR-3 cells were irradiated using an external Cobalt-60 beam, as reference, or At-211-albumin and labeled antibody. Growth assays were used to establish cell survival. A Monte Carlo program was developed to simulate the energy imparted and the track length distribution. Nude mice were used for studies of WBC depression, with various activities of Tc-99m antibodies, as reference, and At-211 antibodies. In efficacy studies, OVCAR-3 cells were inoculated i.p., and animals were treated 2 weeks later. The animals were either dissected 6 weeks later or followed-up for long-term survival. RESULTS: A rapid distillation procedure, as well as a rapid and high-yield, single-pot labeling procedure, was achieved. From growth inhibition data, the relative biological effectiveness of the alpha-emission for OVCAR-3 cells was estimated to be approximately 5, which is in the same range as found in vivo for hematological toxicity. At-211 MOv18 was found to effectively inhibit the development of tumors and ascites, also resulting in long-term survival without significant toxic effect. CONCLUSIONS: Use of the short-range, high-linear energy transfer alpha-emitter At-211 conjugated to a surface epitope-recognizing monoclonal antibody appears to be highly efficient without significant toxicity in a mouse peritoneal tumor model, urging a Phase I clinical trial.
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| 3. |
- Andersson, Håkan, 1944, et al.
(författare)
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Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer.
- 2001
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Ingår i: Anticancer research. - 0250-7005. ; 21:1A, s. 409-12
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to compare the therapeutic efficacy of the alpha-emitter Astatine-211 with the beta-emitter Iodine-131 bound to the specific monoclonal antibody MOv18. The measurements were performed in an ovarian cancer cell line (NIH:OVCAR 3) growing intraperitoneally in nude mice. Two weeks after the intraperitoneal inoculation of 1 x 10(7) cells of the human ovarian cancer cell line NIH:OVCAR-3 twenty mice were treated intraperitoneally with the specific monoclonal antibody MOv-18 labelled with either 211At (310-400 kBq) or 131I (5100-6200 kBq). The pharmacokinetics and biodistribution of labelled antibody in tumour-free animals were studied and the resulting bone marrow dose was estimated. When the mice were treated with 211At-labelled antibody 9 out of 10 mice were free of macro- and microscopic tumour compared to 3 out of 10 when Iodine-131 was used. The equivalent dose to the bone marrow was 2.4-3.1 Sv from 211At- and 3.4-4.1 Sv from 131I-irradiation. The therapeutic efficacy of 211At-labelled specific antibody is very good and, at approximately equivalent bone marrow doses, better than that of 131I.
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| 4. |
- Andersson, Håkan, 1944, et al.
(författare)
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Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study.
- 2009
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505. ; 50:7, s. 1153-60
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Tidskriftsartikel (refereegranskat)abstract
- The alpha-emitter (211)At labeled to a monoclonal antibody has proven safe and effective in treating microscopic ovarian cancer in the abdominal cavity of mice. Women in complete clinical remission after second-line chemotherapy for recurrent ovarian carcinoma were enrolled in a phase I study. The aim was to determine the pharmacokinetics for assessing absorbed dose to normal tissues and investigating toxicity. METHODS: Nine patients underwent laparoscopy 2-5 d before the therapy; a peritoneal catheter was inserted, and the abdominal cavity was inspected to exclude the presence of macroscopic tumor growth or major adhesions. (211)At was labeled to MX35 F(ab')(2) using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with (211)At-MX35 F(ab')(2) (22.4-101 MBq/L) in dialysis solution via the peritoneal catheter. gamma-Camera scans were acquired on 3-5 occasions after infusion, and a SPECT scan was acquired at 6 h. Samples of blood, urine, and peritoneal fluid were collected at 1-48 h. Hematology and renal and thyroid function were followed for a median of 23 mo. RESULTS: Pharmacokinetics and dosimetric results were related to the initial activity concentration (IC) of the infused solution. The decay-corrected activity concentration decreased with time in the peritoneal fluid to 50% IC at 24 h, increased in serum to 6% IC at 45 h, and increased in the thyroid to 127% +/- 63% IC at 20 h without blocking and less than 20% IC with blocking. No other organ uptakes could be detected. The cumulative urinary excretion was 40 kBq/(MBq/L) at 24 h. The estimated absorbed dose to the peritoneum was 15.6 +/- 1.0 mGy/(MBq/L), to red bone marrow it was 0.14 +/- 0.04 mGy/(MBq/L), to the urinary bladder wall it was 0.77 +/- 0.19 mGy/(MBq/L), to the unblocked thyroid it was 24.7 +/- 11.1 mGy/(MBq/L), and to the blocked thyroid it was 1.4 +/- 1.6 mGy/(MBq/L) (mean +/- SD). No adverse effects were observed either subjectively or in laboratory parameters. CONCLUSION: This study indicates that by intraperitoneal administration of (211)At-MX35 F(ab')(2) it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity.
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| 5. |
- Andersson, Leif, et al.
(författare)
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Inventering av violgubbe (Gomphus clavatus) och rödlistade fjälltaggsvampar (Sarcodon spp.) i Västmanlands län 2008.
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna inventering av violgubbe (Gomphus clavatus) och rödlistade fjälltaggsvampar (Sarcodon spp.) har utförts på uppdrag av Länsstyrelsen i Västmanlands län. Syftet har varit att öka kunskapen om arternas förekomst i länet samt behovet av skydd och andra åtgärder på de olika lokalerna. Inventeringen har genomförts inom ramen för åtgärdsprogrammen (ÅGP) för bevarande av violgubbe och rödlistade fjälltaggsvampar. Inventeringen har genomförts under september 2008 av Leif Andersson, Kurt- Anders Johansson, Rolf-Göran Carlsson, Stig Jacobsson och Tomas Fasth. Alla kända lokaler för violgubbe och rödlistade fjälltaggsvampar besöktes. Även lokaler för arter med likartade miljökrav har besökts och områden kända för kalkrik berggrund. Under inventeringen har mycel för de eftersökta arterna noterats och koordinater för dessa tagits. Även andra svampar har noterats om än i olika omfattning. Totalt har ett hundratal lokaler besökts varav svampar har noterats på 80 lokaler. Säsongen var mycket god för fjälltaggsvampar, möjligen med undantag för brödtaggsvamp (Sarcodon versipellis). För violgubbe var säsongen något sämre. Totalt noterades violgubbe och/eller rödlistade fjälltaggsvampar på 17 lokaler. Av de 19 kända lokalerna för violgubbe noterades den på sex och en ny lokal upptäcktes. Tidigare var 20 lokaler kända för de olika rödlistade fjälltaggsvamparna varav återfynd gjordes på sex av dessa. Dessutom gjordes 14 nya fynd av rödlistade fjälltaggvampar. Nya för Västmanlands län är blåfotad taggsvamp (Sarcodon glaucopus), sammetstaggsvamp (Sarcodon martioflavus) och den ännu obeskrivna Sarcodon ”modestum”. Den goda svamptillgången 2008 gjorde att särskilt många rödlistade spindelskivlingar noterades. Flera arter är nya för Västmanlands län. Även andra nyfynd av rödlistade svampar för Västmanlands län gjordes t. ex. narrvaxskivlingen (Hygrophorus subviscifer) som noterades på två platser. Totalt gjordes 146 fynd av 42 rödlistade svampar inklusive violgubbe och rödlistade fjälltaggsvampar. Ett antal lokaler och områden har kristalliserats ut som särskilt intressanta för de eftersökta svamparna. I Sala kommun finns många värdefulla områden, särskilt nära tätorten, ofta i närheten av där gruvdrift bedrivits. Särskilt Snarpsätraskogen norr om staden samt områden söder och sydväst om staden hyste många hotade arter. Områdena söder om staden ingår i Salakalkens Natura 2000-område, men skogsnaturtyperna är i dagsläget inte anmälda som naturtyp. I Fagersta och Norberg finns också värdefulla stråk för violgubbe och rödlistade fjälltaggsvampar. Särskilt ska här framhållas Jättåsarna i Fagersta kommun. Flera områdena är inte utpekade som naturvärden eller nyckelbiotoper och saknar också formellt områdesskydd. Ett antal lokaler för de eftersökta svamparna finns i naturreservat och biotopskydd.
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| 6. |
- Björklund, Emmelie, et al.
(författare)
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Ketoconazole Inhibits the Cellular Uptake of Anandamide via Inhibition of FAAH at Pharmacologically Relevant Concentrations
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e87542-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA). Methodology/Principal Findings: The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH) activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 mu M, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component) of 34 mu M. Conclusions/Significance: The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer.
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| 7. |
- Brodin, Ola, et al.
(författare)
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Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study
- 2015
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 7:6, s. 4978-4994
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. Materials and Methods: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. Results and Conclusion: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.
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| 8. |
- Bäck, Tom, 1964, et al.
(författare)
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211At radioimmunotherapy of subcutaneous human ovarian cancer xenografts: evaluation of relative biologic effectiveness of an alpha-emitter in vivo
- 2005
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Ingår i: J Nucl Med. - 0161-5505. ; 46:12, s. 2061-7
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Tidskriftsartikel (refereegranskat)abstract
- The use of alpha-particle emitters in radioimmunotherapy (RIT) appears to be promising. We previously obtained convincing results in the treatment of microscopic intraperitoneal ovarian cancer in nude mice by using the alpha-emitter 211At. This study was performed to evaluate the relative biological effectiveness (RBE) of 211At compared with that of 60Co gamma-irradiation in an RIT model. Our endpoint was growth inhibition (GI) of subcutaneous xenografts. METHODS: GI after irradiation was studied with subcutaneous xenografts of the human ovarian cancer cell line NIH:OVCAR-3 implanted in nude mice. The animals received an intravenous injection of 211At-labeled monoclonal antibody MX35 F(ab')2 at different levels of radioactivity (0.33, 0.65, and 0.90 MBq). Control mice received unlabeled MX35 F(ab')2 only. To calculate the mean absorbed dose to tumor, a separate biodistribution study established the uptake of 211At in tumors and organs at different times after injection. External irradiation of the tumors was performed with 60Co. Tumor growth was monitored, and the normalized tumor volume (NTV) was calculated for each tumor. GI was defined by dividing the NTV values by the fitted NTV curve obtained from the corresponding control mice. To compare the biologic effects of the 2 radiation qualities, the mean value for GI (from day 8 to day 23) was plotted for each tumor as a function of its corresponding absorbed dose. From exponential fits of these curves, the doses required for a GI of 0.37 (D37) were derived, and the RBE of 211At was calculated. RESULTS: The biodistribution study showed the uptake of the immunoconjugate by the tumor (amount of injected radioactivity per gram) to be 14% after 7 h. At 40 h, the ratio of uptake in tumors to uptake in blood reached a maximum value of 6.2. The administered activities of 211At corresponded to doses absorbed by tumors of 1.35, 2.65, and 3.70 Gy. The value (mean+/-SEM) for D37 was 1.59+/-0.08 Gy. Tumor growth after 60Co external irradiation showed a value for D37 of 7.65+/-1.0 Gy. The corresponding RBE of 211At irradiation was 4.8+/-0.7. CONCLUSION: Using a tumor GI model in nude mice, we were able to derive an RBE of alpha-particle RIT with 211At. The RBE was found to be 4.8+/-0.7.
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| 9. |
- Bäck, Tom, 1964, et al.
(författare)
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A Novel Method for Real-Time Quantification of Radioligand Binding to Living Tumor Cells In Vitro
- 2024
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Ingår i: CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS. - 1084-9785 .- 1557-8852. ; 39:1, s. 75-81
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Tidskriftsartikel (refereegranskat)abstract
- Background: Real-time quantification of radioligand binding to cells under in vivo-like conditions improves evaluation of clinical potential.Materials and Methods: SKOV-3 tumor cells were grown in a monolayer on a thin glass plate placed in a sealable shallow chamber with a continuous flow of 125I-trastuzumab solution. The time-dependent cell binding was measured using a NaI detector, and the binding parameters were derived by computational analysis.Results: The detection efficiency of 125I was 65 cps/kBq for radioligand bound to the cells. Experiments were analyzed to find the values of kon and koff. The resulting kon was 3.2-7.9 x 10(4) M-1 s(-1) and koff was 0.11-4.2 x 10(-5) s(-1).Conclusions: Radioligands can be rapidly evaluated by binding to living cells for selection and optimization of radioconjugates for diagnostic and therapeutic purposes.
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| 10. |
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