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排序方式: 共有114条查询结果,搜索用时 62 毫秒
1.
S B Wieslander B T Mortensen L Binderup N I Nissen 《European journal of haematology》1987,39(1):35-38
10 patients with CLL and 2 with CML were treated with gradually increasing doses of 1 alpha(OH)D3, up to 4 micrograms daily during 6 wk. 3 patients with preleukemia and 1 with myelofibrosis were treated with 2 micrograms daily of 1 alpha(OH)D3 for a prolonged period up to 17 wk. The treatment with 1 alpha (OH)D3 did not result in changes of disease parameters in any of the patients under study. Receptor studies for 1,25(OH)2D3 were performed in 8 CLL patients and revealed only 1 patient with increased specific receptor binding capacity. The maximum tolerable dose of 1 alpha(OH)D3 varied individually, but was in the range of 2-4 micrograms daily. 相似文献
2.
Cecilia Johnsson Gunnar Tufveson Lise Binderup Alex Karlsson-Parra 《Xenotransplantation》1997,4(3):186-193
Abstract: The vitamin D analogue MC 1288 (20-epi-1α,25-dihydroxycholecalciferol) effectively postpones rejection of cardiac, intestinal, skin, and aortic allografts. MC 1288 binds to the vitamin D receptor and is thus assumed to exert its immunosuppressive effects via the same mechanisms as 1α,25-dihydroxycholecalciferol, the active form of vitamin D. 1α,25-Dihydroxycholecalciferol has been demonstrated to inhibit the production of various cytokines (interleukin-2, interferon-γ, granulocyte macrophage colony-stimulating factor, and interleukin-12) and to prevent B lymphocyte secretion of immunoglobulins. In the present study MC 1288 was evaluated for its ability to prevent rejection of mouse-to-rat cardiac xenografts, alone and in combination with 15-deoxyspergualin (DSG). Combined treatment with MC 1288 (given days -1 to 9) and DSG (given day -1 and onward) postponed rejection from day 3.0 (untreated recipients) until day 19.5. In rats treated with MC 1288 or DSG as monotherapy, rejection occurred after 3.0 and 7.5 days, respectively. Functioning grafts, obtained on day 9 from recipients treated with MC 1288 and DSG in combination, displayed an almost normal morphology without any obvious deposition of immunoglobulins in the vessels of the grafts and with just a few infiltrating cells. Thus, we have demonstrated synergistic actions of MC 1288 and DSG in delaying rejection of xenografts. Analysis of cellular infiltration, immunoglobulin deposition and graft survival times in the various treatment groups indicate a combined inhibitory effect of these two drugs on the level of macrophage effector function, direct or indirect via T lymphocytes, as well as on antibody production. 相似文献
3.
Anncatrine Luisa Petersen Jonas Rosager Henriksen Tina Binderup Dennis Ringkjøbing Elema Palle Hedengran Rasmussen Anne Mette Hag Andreas Kjær Thomas Lars Andresen 《European journal of nuclear medicine and molecular imaging》2016,43(5):941-952
Purpose
The objective of this study was to evaluate the potential of PEGylated 64Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated 177Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model.Methods
Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and 64Cu- and 177Lu-loading efficiency. The tumor imaging potential of 64Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The 64Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of 177Lu-liposomes.Results
High remote loading efficiency (>95 %) was obtained for both 64Cu and 177Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 °C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2?±?0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the 64Cu-liposomes estimated an acceptable total effective dose of 3.3·10?2 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177Lu-liposomes.Conclusion
The overall preclinical profile of PEGylated 64Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of 64Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated 64Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for 177Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of 177Lu-liposomes in animals before potential testing in man.4.
J E Severinsen T D Als H Binderup T A Kruse A G Wang M Vang W J Muir D H R Blackwood O Mors A D B?rglum 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(5):524-533
Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ). In a study of a sample from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13. The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Nine SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: an extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ, and 200 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall P-values of 0.0009, 0.0054, and 0.0023 were found for haplotypes in BPD, SZ, and combined cases, respectively, and in the Scottish sample overall P-values of 0.0003, 0.0005, and 0.016 were observed for similar groupings. Specific haplotypes showed associations with lowest P-values of 7 x 10(-5) and 0.0006 in the combined group of cases from the Faeroe Islands and Scotland, respectively. The G protein-coupled receptor 24 encoded by GPR24 binds melanin-concentrating hormone (MCH) and has been implicated with feeding behavior, energy metabolism, and regulation of stress and mood. To our knowledge this is the first study reporting association between GPR24 and BPD and SZ, suggesting that GPR24 variants may confer susceptibility to both disorders. 相似文献
5.
Carlos M Perez-Stable Gary G Schwartz Adan Farinas Milton Finegold Lise Binderup Guy A Howard Bernard A Roos 《Cancer epidemiology, biomarkers & prevention》2002,11(6):555-563
Transgenic mouse models of prostate cancer provide unique opportunities to understand the molecular events in prostate carcinogenesis and for the preclinical testing of new therapies. We studied the G gamma T-15 transgenic mouse line, which contains the human fetal globin promoter linked to SV40 T antigen (Tag) and which develops androgen-independent prostate cancer. Using the immunohistochemistry of normal mouse prostates before tumor formation, we showed that the target cells of carcinogenesis in G gamma T-15 mice are located in the basal epithelial layer. We tested the efficacy of the 1,25(OH)(2)D(3) analogue, EB 1089, to chemoprevent prostate cancer in these transgenic mice. Compared with treatment with placebo, treatment with EB 1089 at three different time points before the onset of prostate tumors in mice did not prevent or delay tumor onset. However, EB 1089 significantly inhibited prostate tumor growth. At the highest dose, EB 1089 inhibited prostate tumor growth by 60% (P = 0.0003) and the growth in the number of metastases, although this dose also caused significant hypercalcemia and weight loss. We conducted several in vitro experiments to explore why EB 1089 did not prevent the occurrence of the primary tumors. EB 1089 significantly inhibited the growth of a Tag-expressing human prostate epithelial cell line, BPH-1, and an androgen-insensitive subline of LNCaP cells [which was not inhibited by 1,25(OH)(2)D(3)]. Thus, neither Tag expression nor androgen insensitivity explain the absence of chemopreventive effect. Conversely, neither 1,25(OH)(2)D(3) nor EB 1089 inhibited the growth of the normal rat prostate basal epithelial cell line NRP-152. It is likely that EB 1089 was not effective in delaying the growth of the primary tumor in G gamma T-15 transgenic mice because the target cells of carcinogenesis in these mice are located in the basal epithelial layer. We conclude that G gamma T-15 transgenic mice are a useful model for testing vitamin D-based therapies in androgen-insensitive prostate cancer but are not suitable for studies of vitamin D-based chemoprevention. The superiority of EB 1089 over 1,25(OH)(2)D(3) in the growth suppression of androgen-insensitive prostate cancer cells supports the use of EB 1089 in androgen-insensitive prostate cancer. 相似文献
6.
K. W. Colston S. Y. James E. A. Ofori-Kuragu L. Binderup A. G. Grant 《British journal of cancer》1997,76(8):1017-1020
The GER human pancreatic carcinoma cell line possesses receptors for 1,25-dihydroxyvitamin D3. We report that the vitamin D analogue EB 1089 inhibits the growth of these cells in vitro and when grown as tumour xenografts in immunodeficient mice. Tumour-bearing mice were given EB 1089 at a dose of 5 microg kg(-1) body weight i.p. thrice weekly for 4-6 weeks. Tumour growth was significantly inhibited in treated animals compared with controls in the absence of hypercalcaemia. These findings may have therapeutic implications in pancreatic cancer. 相似文献
7.
Kragh M Binderup L Vig Hjarnaa PJ Bramm E Johansen KB Frimundt Petersen C 《Oncology reports》2005,14(1):99-104
Experimental and clinical studies indicate that low molecular weight heparins (LMWH) may inhibit cancer and/or metastasis. The purpose of this study was to investigate whether it is possible to design non-anti-coagulant, anti-metastatic compounds based on heparin. The LMWH Tinzaparin and a series of non-anti-coagulant (NAC) heparin derivatives, varying in size from 2,500 to 10,000 Da, were tested for their anti-metastatic activity in an experimental B16F10 metastasis model. The most promising NAC heparin drug candidate and Tinzaparin were further evaluated in B16F10 model with spontaneous metastasis from a primary subcutaneous tumor. In the experimental model, Tinzaparin, NAC2500, and NAC6000 were inactive whereas both NAC8000 and NAC10000 significantly inhibited the number of induced experimental metastases by 69 and 73%, respectively. NAC8000 was chosen over NAC10000 for further studies because of its lower molecular weight with an expected better bioavailability. In the spontaneous model, Tinzaparin had no inhibitory effect on metastatic activity. In contrast, NAC8000 significantly inhibited the number of metastases by 58%. Neither Tinzaparin nor NAC8000 inhibited primary subcutaneous tumor growth. Together, these results indicate that the anti-metastatic effect of heparin derivatives is not a result of anti-coagulant activity. The non-anti-coagulant NAC8000 specifically inhibits early establishment of tumor cells, but not primary tumor growth. Therefore, NAC8000 is a promising non-anti-coagulant compound for preventing tumor metastasis. 相似文献
8.
Ottosen ER Sørensen MD Björkling F Skak-Nielsen T Fjording MS Aaes H Binderup L 《Journal of medicinal chemistry》2003,46(26):5651-5662
We wish to report the synthesis and structure-activity relationship (SAR) of a series of 4-aminobenzophenones, as a novel compound class with high antiinflammatory activity. Our initial lead, (4-[(2-aminophenyl)amino]phenyl)(phenyl)methanone (3), was systematically optimized and resulted in compounds that potently inhibited the release of the proinflammatory cytokines IL-1beta and TNF-alpha in human peripheral blood mononuclear cells stimulated by LPS. One of the most potent compounds, among others, was (4-[(2-aminophenyl)amino]-2-chlorophenyl)(2-methylphenyl)methanone (45) with IC(50) values of 14 and 6 nM for the inhibition of IL-1beta and TNF-alpha, respectively. Furthermore, we found these types of compounds to be potent and selective p38 MAP kinase inhibitors, e.g. 45 had an IC(50) value of 10 nM. Molecular modeling was used to rationalize our SAR data and to propose a model for the interaction of compound 45 with the p38 MAP kinase. The model involved a favorable hydrogen bond between the carbonyl group of the benzophenone and the NH of Met-109, positioning ring A in the hydrophobic pocket I of the enzyme. Good antiinflammatory effects were demonstrated in two murine models of dermatitis after topical application (oxazolone and TPA model). 相似文献
9.
Petersen AL Binderup T Rasmussen P Henriksen JR Elema DR Kjær A Andresen TL 《Biomaterials》2011,32(9):2334-2341
We have developed a highly efficient method for utilizing liposomes as imaging agents for positron emission tomography (PET) giving high resolution images and allowing direct quantification of tissue distribution and blood clearance. Our approach is based on remote loading of a copper-radionuclide ((64)Cu) using a new ionophore, 2-hydroxyquinoline, to carry (64)Cu(II) across the membrane of preformed liposomes and deliver it to an encapsulated copper-chelator. Using this ionophore we achieved very efficient loading (95.5?±?1.6%) and retention stability (>99%), which makes the (64)Cu-liposomes highly applicable as PET imaging agents. We show the utility of the (64)Cu-liposomes for quantitative in vivo imaging of healthy and tumor-bearing mice using PET. This remote loading method is a powerful tool for characterizing the in vivo performance of liposome based nanomedicine, and has great potential in diagnostic and therapeutic applications. 相似文献
10.
L Binderup 《International journal of immunopharmacology》1985,7(1):93-101
Isoprinosine--a new drug possessing immunostimulating properties--was investigated for its ability to influence cell-mediated immune responsiveness in animal models of deficient T-cell function. In vitro isoprinosine strongly increased T-cell mitogenesis in spleen cells from normal rats, with only modest increases in B-cell mitogenesis and no effects on unstimulated cells. In vivo isoprinosine (50 mg kg-1 day-1 orally) had no effects on spleen cell responsiveness when administered to normal rats for 4 or 14 days. However, when the same dose of isoprinosine was administered to rats immunosuppressed with cyclophosphamide (5 mg kg-1 day-1 orally) a partial restoration of T-cell mitogenesis was observed after 14 days of treatment. In rats with adjuvant arthritis treated with isoprinosine for 14 days, depressed T-cell responsiveness was completely restored to the level of the nonarthritic animals. The involvement of different cell types in the observed effects of isoprinosine was further studied in arthritic rats. Removal of monocytes/macrophages from the cell suspensions prior to culture did not affect the increased T-cell response in isoprinosine-treated rats, suggesting a direct stimulatory effect of isoprinosine on T-cell functions. T-suppressor cell function, impaired in arthritic rats, was not restored by treatment with isoprinosine. These results suggest that isoprinosine may exert selective effects on specific T-cell subsets, a finding that may increase the therapeutic interest of the drug. 相似文献