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991.
Nils D. Arvold Matthew Cefalu Yun Wang Corwin Zigler Deborah Schrag Francesca Dominici 《Journal of neuro-oncology》2017,131(2):301-311
It is unknown whether the addition of temozolomide (TMZ) to radiotherapy (RT) is associated with improved overall survival (OS) among older glioblastoma patients. We performed a retrospective cohort SEER-Medicare analysis of 1652 patients aged ≥65 years with glioblastoma who received ≥10 fractions of RT from 2005 to 2009, or from 1995 to 1999 before TMZ was available. Three cohorts were assembled based on diagnosis year and treatment initiated within 60 days of diagnosis: (1) 2005–2009 and TMZ/RT, (2) 2005–2009 and RT only, or (3) 1995–1999 and RT only. Associations with OS were estimated using Cox proportional hazards models and propensity score analyses; OS was calculated starting 60 days after diagnosis. Pre-specified sensitivity analyses were performed among patients who received long-course RT (≥27 fractions). Median survival estimates were 7.4 (IQR, 3.3–14.7) months for TMZ/RT, 5.9 (IQR, 2.6–12.1) months for RT alone in 2005–2009, and 5.6 (IQR, 2.7–9.6) months for RT alone in 1995–1999. OS at 2 years was 10.1?% for TMZ/RT, 7.1?% for RT in 2005–2009, and 4.7?% for RT in 1995–1999. Adjusted models suggested decreased mortality risk for TMZ/RT compared to RT in 2005–2009 (AHR, 0.86; 95?% CI, 0.76–0.98) and RT in 1995–1999 (AHR, 0.71; 95?% CI, 0.57–0.90). Among patients from 2005 to 2009 who received long-course RT, however, the addition of TMZ did not significantly improve survival (AHR, 0.91; 95?% CI, 0.80–1.04). In summary, among a large cohort of older glioblastoma patients treated in a real-world setting, the addition of TMZ to RT was associated with a small survival gain. 相似文献
992.
993.
Stefan Esser Alexander Kreuter Mark Oette Andrea Gingelmaier Franz Mosthaf Marie‐Luise Sautter‐Bihl Johannes Jongen Norbert H. Brockmeyer Gerd Eldering Jochen Swoboda Nils Postel Olaf Degen Horst Schalk Arne Jessen Heribert Knechten Jan Thoden Hans‐Jürgen Stellbrink Armin Schafberger Ulrike Wieland 《Journal der Deutschen Dermatologischen Gesellschaft》2015,13(12):1302-1319
994.
995.
996.
An extract of Carthamus oxyacantha (wild safflower) was investigated using two approaches: a traditional, nontarget fractionation by VLC and HPLC, and the hyphenated technique HPLC-PDA-HRMS-SPE-NMR followed by targeted isolation of selected constituents for inclusion in a screening library of pure natural products. While the nontarget fractionation involved considerable time spent on pursuing fractions containing well-known or undesired compounds, the hyphenated analysis was considerably faster and required less solvent and other consumables. The results were used to design and execute an optimized, HPLC-HRMS-guided, targeted isolation scheme aiming exclusively at a series of identified spiro compounds. Thus, HPLC-PDA-HRMS-SPE-NMR is a dereplication technique of choice, allowing economical acquisition of comprehensive data about compounds in crude extracts, which can be used for rational, prospective decisions about further isolation efforts. A total of 15 compounds were identified in the extract. Six spiro compounds, of which four have not previously been characterized, and tracheloside (a lignin glucoside) are presented with assigned 1H and 13C chemical shifts. 相似文献
997.
Fredrik Mertens Emely Möller Nils Mandahl Piero Picci Antonio R. Perez‐Atayde Ignace Samson Raf Sciot Maria Debiec‐Rychter 《International journal of cancer. Journal international du cancer》2011,128(2):487-491
Subungual exostosis is a benign bone‐ and cartilage‐forming tumor known to harbor a pathognomonic t(X;6)(q22;q13‐14). Using global gene expression analysis and quantitative real‐time PCR, we could show that this translocation results in increased expression of the IRS4 gene, presumably due to disruption and/or exchange of regulatory sequences with the translocation partner, the COL12A1 gene. A corresponding deregulation at the protein level could be demonstrated in primary cell cultures using a combination of fluorescence in situ hybridization and immunostaining. As the t(X;6) usually is the sole cytogenetic aberration in subungual exostosis, the deregulated expression of IRS4 is likely to be pathogenetically essential. The exact role of IRS4 is still poorly investigated, but IRS proteins are known to act as mediators of signaling from receptors, such as the insulin and insulin‐like growth factor 1 receptors, and thus have an important effect on cell growth and survival. 相似文献
998.
Jesper Kolenda Stine Skov Jensen Charlotte Aaberg-Jessen Karina Christensen Claus Andersen Nils Brünner Bjarne Winther Kristensen 《Journal of neuro-oncology》2011,103(1):43-58
Tumor hypoxia has been attributed to play a crucial role in tumorigenesis and therapeutic resistance. Recently, it has been
suggested that hypoxia leads to and maintains the undifferentiated state of tumor stem cells, thereby contributing to chemoresistance.
The aim of the present study is to investigate the influence of hypoxia on the protein expression of a panel of stem cell
and chemoresistance markers using in vivo-like multicellular tumor spheroids derived from a glioblastoma short-term culture
with tumor stem cell properties (SJ-1) as well as a conventional glioblastoma cell line (U87). Spheroids were formed in 21%
and 1% O2 in serum-free medium. The immunohistochemical panel included hypoxia (HIF-1α, HIF-2α), proliferation (Ki-67), and stem cell
markers (CD133, podoplanin, Bmi-1, nestin, Sox-2) as well as markers related to chemoresistance (MGMT, TIMP-1, Lamp-1, MRP1,
MDR-1). As spheroids derived in hypoxia were smaller than in normoxia, a set of experiments was included in which the culturing
time of hypoxic spheroids was extended to obtain equally sized spheroids. The results showed that expression of HIF-1α and
HIF-2α was increased in hypoxia, whereas Ki-67 was reduced. Expression of stem cell markers CD133, podoplanin, Bmi-1, and
nestin was increased in hypoxia, whereas Sox-2 was increased in SJ-1 only. TIMP-1 and Lamp-1 were increased in both SJ-1 and
U87. In conclusion, the tumor cell phenotype related to stemness, and thereby potentially to chemoresistance, seems to depend
on the oxygen tension, suggesting that development of therapeutic strategies targeting tumor stem cells should take oxygen
tension into account. 相似文献
999.
Huber L Lachmann N Dürr M Matz M Liefeldt L Neumayer HH Schönemann C Budde K 《Drugs》2012,72(10):1335-1354
Sensitization is generally referred to as the development of alloantibodies, specifically anti-human leukocyte antigen (HLA) immunoglobulin G (IgG) antibodies, most commonly caused by pregnancy, blood transfusion or a previous transplant. Despite being a well known phenomenon, there has not been a general consensus on its definition, monitoring or management. Today, 25% of the patients waitlisted for kidney transplant in the US have a panel reactive antibody (PRA) of >10% while, in the Eurotransplant zone, 14% have a PRA of >5%. Sensitized patients have more difficulty in finding a well HLA-matched donor, and have a higher risk of experiencing longer waiting times, more rejection episodes and eventually inferior long-term graft or patient survival. We review the currently available strategies in identifying and managing highly sensitized patients undergoing renal transplantation. We discuss the progress and limitations in laboratory techniques to elaborate on challenges in defining sensitized patients. The main management options (i.e. the Acceptable Mismatch Program, donor exchange programmes and the desensitization approach) and their mechanisms, related policies, advantages and outcomes, as well as medications and methods being investigated, are updated. In addition, particular emphasis is given to sensitization prevention, a practice that is neglected with our increasing ability to suppress the immune system. 相似文献
1000.
Vardya I Hoestgaard-Jensen K Nieto-Gonzalez JL Dósa Z Boddum K Holm MM Wolinsky TD Jones KA Dalby NO Ebert B Jensen K 《Neuropharmacology》2012,63(3):469-479
δ-subunit containing extrasynaptic GABAA receptors are potential targets for modifying neuronal activity in a range of brain disorders. With the aim of gaining more insight in synaptic and extrasynaptic inhibition, we used a new positive modulator, AA29504, of δ-subunit containing GABAA receptors in mouse neurons in vitro and in vivo. Whole-cell patch-clamp recordings were carried out in the dentate gyrus in mouse brain slices. In granule cells, AA29504 (1 μM) caused a 4.2-fold potentiation of a tonic current induced by THIP (1 μM), while interneurons showed a potentiation of 2.6-fold. Moreover, AA29504 (1 μM) increased the amplitude and prolonged the decay of miniature inhibitory postsynaptic currents (mIPSCs) in granule cells, and this effect was abolished by Zn2+ (15 μM). AA29504 (1 μM) also induced a small tonic current (12.7 ± 3.2 pA) per se, and when evaluated in a nominally GABA-free environment using Ca2+ imaging in cultured neurons, AA29504 showed GABAA receptor agonism in the absence of agonist. Finally, AA29504 exerted dose-dependent stress-reducing and anxiolytic effects in mice in vivo. We propose that AA29504 potentiates δ-containing GABAA receptors to enhance tonic inhibition, and possibly recruits perisynaptic δ-containing receptors to participate in synaptic phasic inhibition in dentate gyrus. 相似文献