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991.
The synthesis of ten tris-sydnone imine derivatives, unknown up to now, is described. All compounds are alkyl or arylalkyl substituted in 3-position of the sydnone imine. The most powerful agent was the 3-propyl derivative 6c . It inhibits the aggregation of human platelets induced by collagen in a concentration of 1 γmol/L half maximally. Its N-ethoxycarbonyl derivative 7c , which was designed as a prodrug, showed only small antithrombotic effects in rats. The reason for this low degree of activity is discussed. 相似文献
992.
Klaus Rehse Klaus-Jürgen Schleifer Antje Martens Michael Kmpfe 《Archiv der Pharmazie》1994,327(6):393-397
Nine 4,4′-bis- and four 4,4′-tris-N-nitroso sydnone imines were synthesized. The sydnone imine moiety is connected either by aromatic 1,3-phenylene or 1,3,5-benzene or aliphatic methylene or propylene bridges. Compared to the corresponding sydnone imines the collagen induced platelet aggregation inhibiting activity is increased by several orders of magnitude by the nitroso derivatives. The most potent compound bears a hexyl substituent in 3-position ( 1d : IC50 = 0.05 μmol/L). These data show that aromatic bridges ( 1d, 2d ) are more favourable than aliphatic ones ( 4b ). This indicates the mutual influence of the nitroso-imino moieties via the aromatic bridges. In the series of 3,3′-bis-nitrososydnone imines (13 compounds) mostly additive effects of the nitroso groups are seen. The activities range from IC50 = 0.2 μmol/L ( 5i ; 1,3-xylene bridge) to IC50 = 8 μmol/L ( 5b ; trimethylene bridge). The differences suggest different affinities to the platelet membrane. 相似文献
993.
Florian Kollert Sophie Christoph Corina Probst Stephan Budweiser Bettina Bannert Moritz Binder Bettina Sehnert Reinhard E. Voll Gernot Zissel Ulrich A. Walker Antje Prasse Anja Saalbach 《Arthritis care & research》2013,65(2):281-287
Objective
Vascular injury and endothelial cell (EC) activation are pathogenic hallmarks of systemic sclerosis (SSc; scleroderma). Human CD90 is highly expressed on activated ECs and can be shed from the cell surface. This study was conducted to examine whether soluble CD90 (sCD90) is elevated in the sera of patients with SSc and linked to pulmonary involvement and in particular, pulmonary arterial hypertension (PAH).Methods
sCD90 serum concentrations were assessed in 76 patients with SSc and related to clinical data, lung function, 6‐minute walk distance, echocardiography, bronchoalveolar lavage fluid, and laboratory parameters. Thirty‐one healthy volunteers and 29 patients with idiopathic retroperitoneal fibrosis (IRF) served as controls.Results
sCD90 serum concentrations were elevated in patients with SSc compared to healthy volunteers (P = 0.001) and patients with IRF (P = 0.01). SSc patients with pulmonary fibrosis (P = 0.006) and patients with PAH (P < 0.001) had increased sCD90 serum concentrations compared to patients without the respective pulmonary manifestation of SSc. sCD90 levels correlated with diffusing capacity for carbon monoxide (n = 65; r = ?0.348, P = 0.005) and systolic pulmonary artery pressure (n = 53; r = 0.469, P < 0.001). Receiver operating characteristic curve testing determined an optimal cutoff value of ≥626 ng/ml with a sensitivity of 68% and a specificity of 83% for PAH (area under the curve 0.773, 95% confidence interval 0.648–0.898; P < 0.001).Conclusion
sCD90 concentrations were increased in the sera of SSc patients, particularly in patients with vascular involvement of the lungs. These data suggest that sCD90 should be further evaluated as a marker for diagnosis of PAH in SSc.994.
995.
The aim of the study was to analyze the morphology of the viscerocranium in patients with unilatertal or bilateral cleft lip and palate (CLP) who had undergone no surgical intervention of the alveolous meaning that no bone grafting was conducted. In this cross-sectional study 47 patients with complete unilateral (UCLP) or bilateral clefts (BCLP) were examined, and compared to a group of 42 patients without facial clefts. Each group was subdivided into two age groups (ca. 8 and ca. 15 years) approximately before and after the pubertal growth maximum. All patients with CLP received a complete palate closure by means of velopharyngoplasty at age of three, without any alveolar ridge osteoplasty. The craniofacial morphology of all patients was analysed in three planes (sagittal, coronal, horizontal) with help of model analysis and cephalometric analysis. The craniofacial morphology of all groups of CLP patient differed from that of the control groups. On average, more markedly impaired growth was observed in the older age group. Moderate retrognathic maxilla and slight mandible, a coronal skeletal excess, and a remarkable retrusion of the upper and lower anterior teeth were characteristic. Horizontal restriction of width could only be identified in the region of maxillary canines. CLP patients who had no bone grafting showed that the craniofacial developmental impairment was reasonably slight compared to patients without CLP, although it became more pronounced in the older age groups. 相似文献
996.
The surface characteristics of intravenously administered particulate drug carriers decisively influence the protein adsorption that is regarded as a key factor for the in vivo fate of the carriers. We labeled surface-modified polymer particles with the gamma-emitting radioisotope 99mTc in order to test their properties in blood and follow their in vivo fate. The biodistribution was different in various types of polymer particles. As expected, labeled particles were found in the mononuclear phagocyte system in a large scale but markedly different biodistribution for some particles were also shown. 相似文献
997.
Markus Hutterer Martha Nowosielski Johannes Haybaeck Sabine Embacher Florian Stockhammer Thadd?us Gotwald Bernhard Holzner David Capper Matthias Preusser Christine Marosi Stefan Oberndorfer Martin Moik Johanna Buchroithner Marcel Seiz Jochen Tuettenberg Ulrich Herrlinger Antje Wick Peter Vajkoczy Günther Stockhammer 《Neuro-oncology》2014,16(1):92-102
Background
Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing.Methods
This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules.Results
Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5%, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed prolonged stable disease ≥6 months with a median PFS of 16.0 months (range, 6.4–41.4 mo) and a median OS of 46.9 months (range, 21.2–49.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n = 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated treatment due to toxicity.Conclusion
Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS.ClinicalTrials.gov Identifier: . NCT00535379相似文献998.
999.
Cytokine-suppressive anti-inflammatory drugs (CSAIDs) inhibit invasion and MMP-1 production of ovarian carcinoma cells 总被引:1,自引:0,他引:1
The development of therapeutic strategies for inhibition of peritoneal dissemination and invasion would be central for the treatment of ovarian carcinoma. In the microenvironment of ovarian carcinomas, various inflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) are present. In this study we investigated the role of inflammatory cytokines in the regulation of invasion of SKOV-3 ovarian carcinoma cells in-vitro. Treatment of cells with TNF-alpha or interleukin 1beta (IL-1beta) lead to increased phosphorylation of the stress-activated p38 mitogen-activated protein kinase (p38MAPK). Furthermore, TNF-alpha as well as IL-1beta stimulated matrigel invasion of tumor cells. An inhibitor of stress-activated protein kinase pathways, the cytokine-suppressive anti-inflammatory drug (CSAID) SB203580 inhibited invasion of cytokine-stimulated SKOV-3 cells. The MEK-1 inhibitor PD98059 similarly inhibited invasion of cytokine-stimulated cells, but to a lesser extent. Expression of mRNA and protein levels of matrix metalloproteinase-1 (MMP-1) by SKOV-3 cells could be stimulated by inflammatory cytokines and inhibited by SB203580, and partially also by PD98059. Our results show that CSAIDs reduce invasion and MMP expression of ovarian carcinoma cells. Further studies are required to investigate whether inhibition of cytokine-induced signal transduction may be of value in therapy of ovarian carcinomas in-vivo. 相似文献
1000.
Günter Eisele Antje Wick Anna-Carina Eisele Paul M. Clément Jörg Tonn Ghazaleh Tabatabai Adrian Ochsenbein Uwe Schlegel Bart Neyns Dietmar Krex Matthias Simon Guido Nikkhah Martin Picard Roger Stupp Wolfgang Wick Michael Weller 《Journal of neuro-oncology》2014,117(1):141-145
The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT → TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ/RT → TMZ in newly diagnosed glioblastoma. Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial served as a reference. MRIcro software was used to map location and extent of initial preoperative and recurrent tumors on MRI of both groups into the same stereotaxic space which were then analyzed using an automated tool of image analysis. Clinical and outcome data of the cilengitide-treated patients were similar to those of the EORTC/NCIC trial except for a higher proportion of patients with a methylated O6-methylguanyl-DNA-methyltransferase gene promoter. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location between groups. Overall frequencies of distant recurrences were 20 % in the reference group and 19 % (4/21 patients) in the cilengitide group. Compared with TMZ/RT → TMZ alone, the addition of cilengitide does not alter patterns of progression. This analysis does not support concerns that integrin antagonism by cilengitide may induce a more aggressive phenotype at progression, but also provides no evidence for an anti-invasive activity of cilengitide in patients with newly diagnosed glioblastoma. 相似文献