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991.
992.
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
993.
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
994.
John R. Davies Rosalyn Jewell Paul Affleck Gabriella M. Anic Juliette Randerson‐Moor Aija Ozola Kathleen M. Egan Faye Elliott Zaida García‐Casado Johan Hansson Mark Harland Veronica Höiom Guan Jian Göran Jönsson Rajiv Kumar Eduardo Nagore Judith Wendt Håkan Olsson Jong Y. Park Poulam Patel Dace Pjanova Susana Puig Dirk Schadendorf P. Sivaramakrishna Rachakonda Helen Snowden Alexander J. Stratigos Dimitrios Bafaloukos Zighereda Ogbah Antje Sucker Joost J. Van den Oord Remco Van Doorn Christy Walker Ichiro Okamoto Pascal Wolter Jennifer H. Barrett D. Timothy Bishop Julia Newton‐Bishop 《International journal of cancer. Journal international du cancer》2014,135(7):1625-1633
We report the association of an inherited variant located upstream of the poly(adenosine diphosphate‐ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single‐strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma‐specific survival (MSS). Results were combined using random effects meta‐analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin‐fixed paraffin‐embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04–1.28, p = 0.005, eleven cohorts) and MSS (HR = 1.20 per allele, 95% CI 1.01–1.39, p = 0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS. 相似文献
995.
Peripheral blood sCD3− CD4+ T cells: a useful diagnostic tool in angioimmunoblastic T cell lymphoma
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Anju Singh Richard Schabath Richard Ratei Andrea Stroux Claus‐Detlev Klemke Thomas Nebe Anne Flörcken Antje van Lessen Ioannis Anagnostopoulos Bernd Dörken Wolf‐Dieter Ludwig Antonio Pezzutto Jörg Westermann 《Hematological oncology》2014,32(1):16-21
Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important information for the differential diagnosis of AITL. sCD3? CD4+ T cells are a typical feature of AILT in flow cytometry of peripheral blood. In this retrospective study, the diagnostic value of flow cytometry for the diagnosis ‘AITL’ was assessed by comparing the frequency of sCD3? CD4+ T cells in leukemic AITL patients and in patients with other leukemic CD4+ T cell lymphomas. Immunophenotyping of peripheral blood by flow cytometry was performed in a lymphocyte gate using fluorochrome‐labelled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD10, CD14, CD16, CD19, CD56, CD57 and T cell receptor. In 17/17 leukemic AITL patients, a small but distinct population of sCD3? CD4+ T cells was detected (mean percentage of sCD3? CD4+ T cells in the lymphocyte gate: 11.9 ± 15.4%, range 0.1–51.8%). In contrast, sCD3? CD4+ T cells were found in only 1/40 patients with other leukemic CD4+ T cell lymphomas (one patient with mycosis fungoides). sCD3? CD4+ T cells have a high positive predictive value (94%) for the diagnosis ‘AITL’. Flow cytometry is particularly useful in the differential diagnosis of AITL, even if the aberrant T cell population has a very low frequency. Further biological characterization of this subfraction of lymphoma cells is warranted. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
996.
Sandra Pinkert Meike Kespohl Nicolas Kelm Ziya Kaya Arnd Heuser Karin Klingel Antje Beling 《Viruses》2021,13(7)
Infection of mice with Coxsackievirus B3 (CVB3) triggers inflammation of the heart and this mouse model is commonly used to investigate underlying mechanisms and therapeutic aspects for viral myocarditis. Virus-triggered cytotoxicity and the activity of infiltrating immune cells contribute to cardiac tissue injury. In addition to cardiac manifestation, CVB3 causes cell death and inflammation in the pancreas. The resulting pancreatitis represents a severe burden and under such experimental conditions, analgesics may be supportive to improve the animals’ well-being. Notably, several known mechanisms exist by which analgesics can interfere with the immune system and thereby compromise the feasibility of the model. We set up a study aiming to improve animal welfare while ensuring model integrity and investigated how tramadol, an opioid, affects virus-induced pathogenicity and immune response in the heart. Tramadol was administered seven days prior to a CVB3 infection in C57BL/6 mice and treatment was continued until the day of analysis. Tramadol had no effect on the virus titer or viral pathogenicity in the heart tissue and the inflammatory response, a hallmark of myocardial injury, was maintained. Our results show that tramadol exerts no disruptive effects on the CVB3 myocarditis mouse model and, therefore, the demonstrated protocol should be considered as a general analgesic strategy for CVB3 infection. 相似文献
997.
Andrej Khandoga Michael Thomas Axel Kleespies Lennart Kühnke Joachim Andrassy Antje Habicht Manfred Stangl Markus Guba Martin Angele Jens Werner Markus Rentsch 《The surgeon》2019,17(2):63-72
Background
Surgical complications following kidney transplantation compromise immediate graft survival. However, the role of early surgical complications in the impairment of long-term survival is not completely established due to various other influences, such as patient comorbidities. The purpose of this study was to characterize the impact of surgical complications and overlapping patient comorbidities on graft function and survival after living donor kidney transplantation (LDKT).Methods
Two groups of patients following LDKT between 1995 and 2014 with (n = 65) or without (n = 294) Clavien–Dindo grade 3 and 4 complications were analyzed. Type of surgical revision, graft and patient survival, general patient characteristics, pre-transplant renal function, immunosuppression, and immunological characteristics (HLA mismatch, panel-reactive antibodies, rejections) were determined. Post-transplant graft function as well as long-term graft and patient survival were quantified.Results
Graft survival was 84.4/97.6% (1y), 75.2/92.7% (3y), and 62.1/87.6% (5y) with/without surgical revision, patient survival was 95.3/99.3%, 90.0/97.5%, and 84.7/93.7%, respectively. Surgical revision was required in 18%, which affected graft survival (p = 0.008) to a comparable extent as pre-existing cardiopulmonary/-vascular disease. Initially impaired graft function recovered to an equal level without complications following surgical revision. Whereas pre-existing cardiopulmonary/-vascular disease affected graft loss and patient survival, surgical revision had no particular impact on patient survival. These observations were confirmed by Cox regression.Conclusion
Long-term graft survival following LDKT is independently impaired by both postoperative complications and cardiovascular comorbidities. Although both factors may interact, a complication-free postsurgical course may improve graft survival, thereby reducing the need for dialysis restart and enhancing long-term recipient survival. 相似文献998.
999.
1000.
Stefanie Schlichtherle Afschin Gandjour Antje Neugebauer Walter Rüssmann Karl Wilhelm Lauterbach 《Strabismus》2013,21(4):291-295
Five screening strategies for amblyopia in different age groups were compared according to a decision-analytical model from the perspective of the health insurance funds. Our findings indicate that the costs per detected case of amblyopia range from about 1200 DM to 3000 DM (613 Euro to 1534 Euro). The two most cost-effective screening strategies were to screen high-risk children up to the age of one by ophthalmologists and to screen all children up to the age of one by ophthalmologists. The screening of high-risk children identifies only about a third of all affected children in this age group, when compared with the number of cases detected by screening all children up to the age of one. However, the average cost per detected case of amblyopia among high-risk children is lower than the cost of screening all children in this age range. 相似文献