Search results for "genetics [Transcriptome]"
showing 10 items of 3033 documents
Fetal neurogenesis: breathe HIF you can.
2016
Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, s…
The Volatilomic Footprints of Human HGC-27 and CLS-145 Gastric Cancer Cell Lines
2021
The presence of certain volatile biomarkers in the breath of patients with gastric cancer has been reported by several studies; however, the origin of these compounds remains controversial. In vitro studies, involving gastric cancer cells may address this problem and aid in revealing the biochemical pathways underlying the production and metabolism of gastric cancer volatile indicators. Gas chromatography with mass spectrometric detection, coupled with headspace needle trap extraction as the pre-concentration technique, has been applied to map the volatilomic footprints of human HGC-27 and CLS-145 gastric cancer cell lines and normal Human Stomach Epithelial Cells (HSEC). In total, 27 volat…
Meta-analysis of exome array data identifies six novel genetic loci for lung function
2018
Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associatio…
Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo
2016
Summary - The realization that nuclear distribution of DNA, RNA, and proteins differs between cell types and developmental stages suggests that nuclear organization serves regulatory functions. Understanding the logic of nuclear architecture and how it contributes to differentiation and cell fate commitment remains challenging. Here, we use soft X-ray tomography (SXT) to image chromatin organization, distribution, and biophysical properties during neurogenesis in vivo. Our analyses reveal that chromatin with similar biophysical properties forms an elaborate connected network throughout the entire nucleus. Although this interconnectivity is present in every developmental stage, differentiati…
mRCC Outcome in the Treatment of Metastatic Renal Cell Carcinoma - A German Single-center Real-world Experience.
2018
Background/Aim: Since the advent of targeted therapeutics, paradigms in metastatic renal cell carcinoma (mRCC) treatment have changed. We investigated if efficacy and safety data from randomized controlled trials can be transferred into real-world settings. Patients and Methods: All patients with mRCC treated from 2006-2015 at the Department of Urology (Marburg-Germany) were retrospectively analyzed. Collected data include: Patient demographics, tumor characteristics, efficacy, safety, and used therapy sequences. Results: In total, 197 patients with mRCC were identified. About one third of patients reached third-line therapy. Median overall survival in real-world amounted to 25.8 months wit…
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
2018
Current treatment options for advanced and recurrent head and neck squamous cell carcinoma (HNSCC) enclose radiation and chemo-radiation approaches with or without surgery. While platinum-based chemotherapy regimens currently represent the gold standard in terms of efficacy and are given in the vast majority of cases, new chemotherapy regimens, namely immunotherapy are emerging. However, the response rates and therapy resistance mechanisms for either chemo regimen are hard to predict and remain insufficiently understood. Broad variations of chemo and radiation resistance mechanisms are known to date. This study describes the development of a standardized, high-throughput in vitro assay to a…
Combinaisons de chimiothérapie ou de radiothérapie et d’inhibiteurs de checkpoints
2018
Les progrès récents de l’immunothérapie en oncologie dus au développement des anticorps anti-PD1/PDL1 révolutionnent la prise en charge des patients. Malgré tout, l’efficacité de ces traitements en monothérapie est limitée à une sous-population représentant environ 25 à 30 % des patients dans la plupart des indications. Le développement de nouvelles stratégies se base sur les combinaisons entre les traitements standards (chimiothérapie cytotoxique et radiothérapie) et l’immunothérapie afin de trouver des combinaisons synergiques.
Involvement of non-coding RNAs in chemo- and radioresistance of colorectal cancer
2016
Despite recent progress in understanding the cancer signaling pathways and in developing new therapeutic strategies, however, the resistance of colorectal cancer (CRC) cells to chemo- and radiotherapy represents the main hurdle to the successful treatment, leading to tumor recurrence and, consequently, a poor prognosis. Therefore, overcoming drug and radiation resistance, enhancing drug and radiation sensitivity of CRC cells, and improving the effi cacy of chemo- and radiotherapy have an important signifi cance in the treatment of CRC. The identifi cation of new molecular biomarkers which can predict therapy response and prognosis is one of the most signifi cant aims in pharmacogenomics and…
Oxidative stress and frailty : a systematic review and synthesis of the best evidence
2017
Objective Oxidative stress (OS) is associated with accelerated aging. Previous studies have suggested a possible relationship between OS and frailty but this association remains unclear. We conducted a systematic review to investigate potential interactions between OS and frailty. Methods A systematic literature search of original reports providing data on ‘OS and antioxidant’ parameters and frailty was carried out across major electronic databases from inception until May 2016. Cross-sectional/case control and longitudinal studies reporting data on the association between frailty and anti-oxidants-OS biomarkers were considered for inclusion. Results were summarized with a synthesis based o…
Distinct Activities of Glycolytic Enzymes Identify Chronic Lymphocytic Leukemia Patients with a more Aggressive Course and Resistance to Chemo-Immuno…
2018
A higher capacity to grow under hypoxic conditions can lead to a more aggressive behavior of tumor cells. Determining tumor activity under hypoxia may identify chronic lymphocytic leukemia (CLL) with aggressive clinical course and predict response to chemo-immunotherapy (CIT). A metabolic score was generated by determining pyruvate kinase and lactate dehydrogenase, key enzymes of glycolysis, ex vivo in primary CLL samples under normoxic and hypoxic conditions. This score was further correlated with clinical endpoints and response to CIT in 96 CLL patients. 45 patients were classified as metabolic high risk (HR), 51 as low risk (LR). Treatment-free survival (TFS) was significantly shorter in…