Suppression of RAF/MEK or PI3K synergizes cytotoxicity of receptor tyrosine kinase inhibitors in glioma tumor-initiating cells

Additional file 5. Data of RPPA analysis

統合失調症患者に対する作業療法における主観経験尺度の作成 : OT治療要素経験尺度の信頼性・妥当性の検討

研究報告Original Paper背景:筆者は、先行研究において統合失調症患者の作業療法における主観経験を調査するために、37項目からなるOT治療要素経験尺度(RSOTE)を作成した。この尺度は、精神科作業療法における作業活動と集団に関する項目で構成されている。本研究では、この尺度の信頼性・妥当性を検討することを目的とした。方法:精神科病院に入院中の統合失調症患者(各54名)の協力を待て、RSOTEによる評価を実施した。得られたデータについて因子分析を行い、先行研究との因子構造を比較した。さらに信頼性を検討するために、Cronbachのα信頼性係数を算出した。全ての統計処理にはStatistical Package for the Social Sciences(SPSS)12.0Jを用いた。結果:各データの因子分析の結果、因子。『試行探索と成功体験』(4項目)、因子「『身体感覚の自覚』(4項目)、因子」『生活の構成』(4項目)の12項目3因子構造が一致し、0.69～0.77のCronbachのα信頼性係数が得られた。結論:以上のことから本尺度の信頼性と妥当性が確認され、競合失調症者を村象とした作業療法において、対象者の主観経験を確認する評価法として利用できることが示された。Background: In our previous study, a rating scale for occupational therapy experiences (RSOTE), which consists of 37 items, was developed and administered to schizophrenic inpatients. This scale consists of items related to activities and group dynamics for occupational therapy in mental health. In this study, we attempted to examine the reliability and validity of the rating scale for occupational therapy experiences (RSOTE). Methods: 54 schizophrenic inpatients consented to participate in writing, and completed the 37-item RSOTE. To assess the validity, we carried out a factor analysis about the provided data, and compared the factor structure with that on our previous study. The reliability of the RSOTE was measured by the Cronbach\u27s alpha coefficient. All of the statistical analyses were performed with the Statistical Package for the Social Sciences (SPSS) ver. 12.0J for Windows. Results: A factor analysis showed three factors: Factor I- trial search and success experience (4items), Factor II-awareness of a physical sense (4items), Factor III-constitution of life (4items). This factor structure accorded with that on our previous study. The Cronbach\u27s alpha showed 0.69-0.77. Conclusions: These results suggest that the RSOTE is a reliable and valid scale and can be used as an evaluation method to confirm subjectivity experience in occupational therapy for schizophrenic inpatients

Decreased gene expression of fatty acid binding protein 3 in the atrium of patients with new onset of atrial fibrillation in cardiac perioperative phase

Background: Post-operative atrial fibrillation (POAF) frequently occurs after cardiac surgery. However, the mechanisms of POAF have not been fully elucidated. We aimed to examine whether pre-operative atrial gene expression related to cardiac metabolism is changed in patients with POAF. Methods: Right atrial tissue was obtained during surgery from 38 patients who underwent cardiac surgery from 2013 to 2015. Atrial expression levels were determined by reverse transcription polymerase chain reaction for the following genes: glucose transporter type 4, peroxisome proliferator-activated receptor-α, fatty acid translocase, carnitine palmitoyltransferase 1B, and fatty acid binding protein 3 (FABP3). To investigate fatty acid β-oxidation and tricarboxylic acid cycle capacities in the mitochondria, β-hydroxyacyl CoA dehydrogenase and citrate synthase activity levels were spectrophotometrically determined. Results: POAF within 7 days after surgery was observed in 18 (47%) patients. POAF patients were significantly older, had a larger left atrial diameter, and had reduced expression of FABP3, a fatty acids transport gene in the cytosol, compared to those in the non-POAF group. Reduced FABP3 expression predicted POAF independent of age and atrial size. In contrast, fatty acid β-oxidation enzymatic activity was comparable between the groups. Conclusions: FABP3 gene expression in the atrium was reduced in patients with POAF. These findings suggest a potential link between altered fatty acid transport in the atrium and increased AF onset after cardiac surgery

Glioma Stem Cells: Signaling, Microenvironment, and Therapy

Glioblastoma remains the most common and devastating primary brain tumor despite maximal therapy with surgery, chemotherapy, and radiation. The glioma stem cell (GSC) subpopulation has been identified in glioblastoma and likely plays a key role in resistance of these tumors to conventional therapies as well as recurrent disease. GSCs are capable of self-renewal and differentiation; glioblastoma-derived GSCs are capable of de novo tumor formation when implanted in xenograft models. Further, GSCs possess unique surface markers, modulate characteristic signaling pathways to promote tumorigenesis, and play key roles in glioma vascular formation. These features, in addition to microenvironmental factors, present possible targets for specifically directing therapy against the GSC population within glioblastoma. In this review, the authors summarize the current knowledge of GSC biology and function and the role of GSCs in new vascular formation within glioblastoma and discuss potential therapeutic approaches to target GSCs

Utilizing murine inducible telomerase alleles in the studies of tissue degeneration/regeneration and cancer.

Telomere dysfunction-induced loss of genome integrity and its associated DNA damage signaling and checkpoint responses are well-established drivers that cause tissue degeneration during ageing. Cancer, with incidence rates greatly increasing with age, is characterized by short telomere lengths and high telomerase activity. To study the roles of telomere dysfunction and telomerase reactivation in ageing and cancer, the protocol shows how to generate two murine inducible telomerase knock-in alleles 4-Hydroxytamoxifen (4-OHT)-inducible TERT-Estrogen Receptor (mTERT-ER) and Lox-Stopper-Lox TERT (LSL-mTERT). The protocol describes the procedures to induce telomere dysfunction and reactivate telomerase activity in mTERT-ER and LSL-mTERT mice in vivo. The representative data show that reactivation of telomerase activity can ameliorate the tissue degenerative phenotypes induced by telomere dysfunction. In order to determine the impact of telomerase reactivation on tumorigenesis, we generated prostate tumor model G4 PB-Cre4 PtenL/L p53L/L LSL-mTERTL/L and thymic T-cell lymphoma model G4 Atm-/- mTERTER/ER. The representative data show that telomerase reactivation in the backdrop of genomic instability induced by telomere dysfunction can greatly enhance tumorigenesis. The protocol also describes the procedures to isolate neural stem cells (NSCs) from mTERT-ER and LSL-mTERT mice and reactivate telomerase activity in NSCs in vitro. The representative data show that reactivation of telomerase can enhance the self-renewal capability and neurogenesis in vitro. Finally, the protocol describes the procedures of performing telomere FISH (Fluorescence In Situ Hybridization) on both mouse FFPE (Formalin Fixed and Paraffin Embedded) brain tissues and metaphase chromosomes of cultured cells

Impaired mitochondrial oxidative phosphorylation capacity in epicardial adipose tissue is associated with decreased concentration of adiponectin and severity of coronary atherosclerosis

Epicardial adipose tissue (EAT), a source of adipokines, is metabolically active, but the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between EAT mitochondrial respiratory capacity, adiponectin concentration in the EAT, and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. Based on the coronary angiographycal findings, the patients were divided into two groups; coronary artery disease (CAD; n= 14) and non-CAD (n = 11) groups. The mitochondrial respiratory capacities including oxidative phosphorylation (OXPHOS) capacity with non-fatty acid (complex I and complex I + II-linked) substrates and fatty acids in the EAT were significantly lowered in CAD patients. The EAT mitochondrial OXPHOS capacities had a close and inverse correlation with the severity of coronary artery stenosis evaluated by the Gensini score. Intriguingly, the protein level of adiponectin, an anti-atherogenic adipokine, in the EAT was significantly reduced in CAD patients, and it was positively correlated with the mitochondrial OXPHOS capacities in the EAT and inversely correlated with the Gensini score. Our study showed that impaired mitochondrial OXPHOS capacity in the EAT was closely linked to decreased concentration of adiponectin in the EAT and severity of coronary atherosclerosis