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1.
Michels Guido Horn Rudolf Helfen Andreas Hagendorff Andreas Jung Christian Hoffmann Beatrice Jaspers Natalie Kinkel Horst Greim Clemens-Alexander Knebel Fabian Bauersachs Johann Busch Hans-Jörg Kiefl Daniel Spiel Alexander O. Marx Gernot Dietrich Christoph F. 《Der Anaesthesist》2022,71(4):307-310
Die Anaesthesiologie - 相似文献
2.
Theresa M. Thole Joern Toedling Annika Sprüssel Sebastian Pfeil Larissa Savelyeva David Capper Clemens Messerschmidt Dieter Beule Stefanie Groeneveld-Krentz Cornelia Eckert Guido Gambara Anton G. Henssen Sabine Finkler Johannes H. Schulte Anja Sieber Nils Bluethgen Christian R. A. Regenbrecht Annette Künkele Marco Lodrini Angelika Eggert Hedwig E. Deubzer 《International journal of cancer. Journal international du cancer》2020,146(4):1031-1041
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
3.
Leonie Konczalla Daniel R. Perez Nadine Wenzel Gerrit Wolters-Eisfeld Clarissa Klemp Johanna Lüddeke Annika Wolski Dirk Landschulze Chris Meier Anika Buchholz Dichao Yao Bianca T. Hofmann Julia K. Graß Sarah L. Spriestersbach Katharina Grupp Udo Schumacher Christian Betzel Svetlana Kapis Theresa Nuguid Pablo Steinberg Klaus Püschel Guido Sauter Maximillian Bockhorn Faik G. Uzunoglu Jakob R. Izbicki Cenap Güngör Alexander T. El Gammal 《International journal of cancer. Journal international du cancer》2020,146(6):1618-1630
MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms. 相似文献
4.
Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability.Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy;however,many infants still experience lifelong disabilities to movement,sensation and cognition.Clinical guidelines,based on strong clinical and preclinical evidence,recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours,with a target brain temperature of 33.5 ±0.5℃ for infants with moderate to severe hypoxic-ischemic encephalopathy.The clinical guidelines also recommend that infants be re warmed at a rate of 0.5℃ per hour,but this is not based on strong evidence.There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy.Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia.In this review,we evaluate the evidence for the optimal start time,duration and depth of hypothermia,and whether the rate of rewarming after treatment affects brain injury and neurological outcomes. 相似文献
5.
Andrew X. Zhu Richard S. Finn Yoon-Koo Kang Chia-Jui Yen Peter R. Galle Josep M. Llovet Eric Assenat Giovanni Brandi Kenta Motomura Izumi Ohno Bruno Daniele Arndt Vogel Tatsuya Yamashita Chih-Hung Hsu Guido Gerken John Bilbruck Yanzhi Hsu Kun Liang Ryan C. Widau Chunxiao Wang Paolo Abada Masatoshi Kudo 《British journal of cancer》2021,124(8):1388
Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH () and REACH-2 ( NCT01140347).Subject terms: NCT02435433Oncology, Biomarkers 相似文献
6.
F. Javier Moreno-Martínez Davide Quaranta Guido Gainotti 《Journal of clinical and experimental neuropsychology》2019,41(6):634-643
Introduction: Both the neuropsychological study of patients with category-specific semantic disorders (CSSD) and the experimental research on categorical processing in healthy subjects (HSs) have shown that men are mainly impaired with fruits and vegetables and women with animals and artifacts. Since this difference is more striking in patients with CSSD than in HSs, we hypothesized that the lack of power of some investigations conducted with HSs and the different methods used in studies conducted with HSs and patients with CSSD could explain some of these inconsistencies and that a study conducted with a very large number of HSs using visual naming tasks should strongly confirm the role of gender in categorical tasks.
Methods: Picture naming data gathered during the last ten years with our category-specificity paradigm from a large number (702) of HSs were reanalyzed.
Results: As predicted, men named significantly more animals and artifacts, while women named more plant life items.
Discussion: These data confirm that, if different domains of knowledge are studied in a very large sample of HSs using a picture naming task equivalent to the naming tasks used in most anatomo-clinical studies on CSSD, then the gender effects are highly significant. 相似文献
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9.
Esther Diana Rossi MD PhD MIAC Guido Fadda MD Antonino Mule MD Gian Franco Zannoni MD Guido Rindi MD 《Cancer cytopathology》2020,128(5):317-320
The 2019 coronavirus pandemic, which started in Wuhan, China, spread around the globe with dramatic and lethal effects. From the initial Chinese epicenter, the European diaspora taxed the resources of several countries and especially those of Italy, which was forced into a complete social and economic shutdown. Infection by droplets contaminating hands and surfaces represents the main vehicle of diffusion of the virus. The common and strong efforts to contain the pandemic have relevant effects on the management of samples from histopathology laboratories. The current commentary reports and focuses on the protocols and guidelines in use at a large tertiary Italian hospital that accordingly are proposed for adoption in Italian laboratories as a potential model for national guidelines for the coronavirus emergency. 相似文献
10.
Henrieke W. Schutte MD Guido B. van den Broek MD PhD Stefan C. A. Steens MD PhD Rosella P. M. G. Hermens PhD Jimmie Honings MD PhD Henri A. M. Marres MD PhD Matthias A. W. Merkx MD PhD Willem L. J. Weijs MD Anne I. J. Arens MD Adriana C. H. van Engen–van Grunsven MD PhD Carla M. L. van Herpen MD PhD Johannes H. A. M. Kaanders MD PhD Frank J. A. van den Hoogen MD PhD Robert P. Takes MD PhD 《Cancer》2020,126(17):3982-3990