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排序方式: 共有384条查询结果,搜索用时 15 毫秒
41.
Natalie Falkenberg Nata?a Anastasov Annalisa Schaub Vanja Radulovic Manfred Schmitt Viktor Magdolen Michaela Aubele 《Oncotarget》2015,6(10):8103-8114
miR-221/-222 and components of the urokinase-type plasminogen activator system (uPAS) are associated with metastasis and poor prognosis in breast cancer, including the triple-negative subtype (TNBC). Modification of components of uPAS and involved miRNAs may contribute to targeted therapy for breast cancer patients. miR-221−/−222-overexpressing or miR-221-depleted cells were employed for qRT-PCR and Western blots to show associations of uPAR with miR-221/-222. To substantiate direct targeting of miR-221/-222 within 3′ UTR of the uPAR isoform 2, in silico analysesand in vitro assays were conducted. Significant associations between miR-221 and uPAR isoform 2 expressions were observed at the mRNA and protein levels in breast cancer cells representing TNBC. For the first time, the uPAR isoform 2 was demonstrated as direct target for miR-221/-222. Inhibition of miR-221 reduced uPAR protein expression and expression of the tumor cell invasion markers vimentin and RHOC. These results demonstrate a direct and positive regulation of the secreted uPAR isoform 2 by miR-221, increasing its protein expression, a prerequisite for malignancy, while the other uPAR isoforms (1, 3 and 4) are indirectly regulated through miR-10b and miR-221/-222. By targeting uPAR isoforms and/or miRNA-221/-222, the diagnosis and therapy of breast cancer, in particular in TNBC, could be significantly improved. 相似文献
42.
Faltynek CR; Princler GL; Rossio JL; Ruscetti FW; Maluish AE; Abrams PG; Foon KA 《Blood》1986,67(4):1077-1082
Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor. 相似文献
43.
Nonhomogeneous distribution of leukemia in the bone marrow during minimal residual disease 总被引:2,自引:0,他引:2
In a rat model (BNML) for human acute myelocytic leukemia the distribution of leukemic cells in bone marrow samples from various sites was investigated, using monoclonal antibodies (MoAbs) and flow cytometry. Rats were studied before chemotherapy as well as thereafter, ie, in the "minimal residual disease" (MRD) phase. Bone marrow from different types of bones was analyzed from each animal. Before treatment, the ratio of the measured extreme values (ie, highest/lowest value) for leukemic cell frequencies in bones from individual rats ranged from 3.7 to 11.7. During the MRD phase the ratios of the extremes ranged from a factor of 36 to more than 13,000 from one rat to another. The variability between bones of comparable size was estimated by studying the ribs from each individual animal. Within individuals the extremes differed by a factor of 1.2 to 4.0 before chemotherapy and from 2.4 to greater than 320 after chemotherapy. The variability within the marrow cavity of a single bone was determined by analyzing multiple samples from femoral bones cut into slices. The leukemic cell frequency appeared to vary considerably, ie, before treatment from 1.7 to 7.3 and during MRD from 4 to 28,000. The presented data may contribute to understanding the sometimes conflicting observations in leukemic patients. Improvement of methods for detecting MRD will not automatically lead to a more accurate estimation of the total tumor burden. The reliability of diagnoses based on the analysis of single bone marrow aspirates appears to be highly questionable. 相似文献
44.
High-level expression and purification of a recombinant human erythropoietin produced using a baculovirus vector 总被引:1,自引:0,他引:1
Conditions presently have been established for the high-level expression and simplified purification of recombinant human erythropoietin produced in Spodoptera frugiperda cells. Expression, as mediated by infection with a recombinant baculovirus, was accomplished in suspension culture using reduced levels of serum and media supplements experimentally determined to provide optimum levels of factor production (500,000 U/L). Purification of this recombinant human erythropoietin to virtual homogeneity (greater than or equal to 99%) was accomplished via a simple three-step procedure involving isocratic elution from DEAE-Sephacel, reverse-phase high performance liquid chromatography (HPLC) on a C4 medium, and the single-step elution of purified hormone from concanavalin A agarose. Overall, an 890-fold purification was accomplished with a recovery of 80% as assayed in vitro. Biologically, this purified erythropoietin is highly active, possessing a specific activity in vitro of 200,000 U/mg protein. Chemically, this erythropoietin (molecular weight [mol wt] 26,200) appears exceptionally uniform in its oligosaccharide constitution (30%) as contrasted with heterogeneously glycosylated erythropoietins derived from mammalian cells (mol wt 30,000 to 38,000; 40% to 50% complex-type oligosaccharide). Thus, human erythropoietin as presently produced in an insect cell line comprises not only an abundant source of highly active, readily purified hormone for studies of its mechanism of action and cell surface receptor, but also represents a uniquely homogeneous form that should prove advantageous for direct structural analyses. 相似文献
45.
Mafee MF; Peyman GA; Grisolano JE; Fletcher ME; Spigos DG; Wehrli FW; Rasouli F; Capek V 《Radiology》1986,160(3):773-780
Twenty-one patients with intraocular disease were studied by magnetic resonance (MR) imaging and computed tomography (CT). In 13 cases, malignant uveal melanoma was considered the likely diagnosis. Both imaging methods were accurate in determining the location and size of uveal melanomas. MR imaging was superior for the assessment of possible associated retinal detachment, for assessment of vitreous change, and for differentiating uveal melanoma from choroidal hemangioma and choroidal detachment. A case of retinal gliosis could not be differentiated from uveal melanoma by either technique. Uveal melanomas appeared as hyperintense lesions on T1-weighted images and as hypointense lesions on T2-weighted images. High signal intensity of the vitreous was observed in patients with vitritis and in those who were thought to have protein leaking into the vitreous as a result of impairment of the retinal-blood barrier. 相似文献
46.
Greenlee MW; Koessler M; Cornelissen FW; Mergner T 《Cerebral cortex (New York, N.Y. : 1991)》1997,7(3):253-267
Visual discrimination and short-term recognition memory for computer-
generated random patterns were explored in 23 patients with a postsurgical
lesion in one of the cortical hemispheres. Their results are compared with
those of 23 age-matched volunteers. In a same- different forced-choice
discrimination task, d' and log beta (measures of sensitivity and bias), as
well as reaction time (RT) were determined. All participants viewed
patterns defined either by luminance contrast or isoluminant red-green
color contrast, the amplitude of which was adjusted to be 10 times the
respective detection threshold level. Block patterns consisting of a 6 x 6
matrix of light and dark (red and green) checks were randomly configured on
each presentation. They were presented in pairs, randomly in two visual
quadrants for a duration of 200 msec. Three presentation conditions were
used: simultaneous presentation of reference and test stimulus, sequential
presentation with a short delay (interstimulus interval, ISI = 3 s), and
sequential presentation with a long delay (ISI = 6 s). The results indicate
that patients with a lesion in the occipitotemporal cortex, the superior
temporal cortex and the frontal cortex were significantly impaired on both
luminance-contrast and color-contrast pattern discrimination. Patients with
damage in the anterior inferotemporal cortex showed no overall impairment.
The results suggest that performance in visual discrimination and
recognition memory tasks rely on distributed neural processes with more
than one neocortical location.
相似文献
47.
48.
B Schwahn U Wendel P Schadewaldt N Falkenberg E Mönch 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(12):1245-1246
Protein turnover is a cyclic process with a net loss of protein in the (catabolic) fasted state and a net gain in the (anabolic) fed state. In maple syrup urine disease (MSUD) the early block of degradation of the branched-chain amino acids (BCAA) brings about the opportunity for evaluation of the diurnal variation in net protein anabolism and catabolism by studying cyclic changes in the plasma concentrations of BCAA. The alterations in plasma BCAA in a 3-y-old boy with classical MSUD were studied in the fed and fasted state over a period of 19 months. For each amino acid a total of 34 data pairs was calculated. The plasma concentrations of the BCAA leucine, valine and isoleucine were constantly higher in the fasted than in the fed state. Plasma concentrations of alloisoleucine, being a non-protein amino acid, did not participate in cyclic changes. In contrast, the essential amino acid pair tyrosine and phenylalanine increased after meals. The fasting concentration of alanine increased after feeding, while glycine did not change significantly. Healthy subjects show a decrease in all amino acids in the fasted (mild catabolic) state and an increase in the fed state. These findings in MSUD suggest a net decrease in non-BCAA as result of a greater rate of amino acid oxidation rate than of protein breakdown and a net entry of BCAA into plasma in the fasted state due to the specific metabolic block. Such changes in amino acid plasma pools have to be taken into account during monitoring of treatment and especially when in vivo leucine oxidation is assessed. 相似文献
49.
Harald Walach Torkel Falkenberg Vinjar Fønnebø George Lewith Wayne B Jonas 《BMC medical research methodology》2006,6(1):29-9
Background
The reasoning behind evaluating medical interventions is that a hierarchy of methods exists which successively produce improved and therefore more rigorous evidence based medicine upon which to make clinical decisions. At the foundation of this hierarchy are case studies, retrospective and prospective case series, followed by cohort studies with historical and concomitant non-randomized controls. Open-label randomized controlled studies (RCTs), and finally blinded, placebo-controlled RCTs, which offer most internal validity are considered the most reliable evidence. Rigorous RCTs remove bias. Evidence from RCTs forms the basis of meta-analyses and systematic reviews. This hierarchy, founded on a pharmacological model of therapy, is generalized to other interventions which may be complex and non-pharmacological (healing, acupuncture and surgery). 相似文献50.