693 research outputs found

    Chlorpromazine cooperatively induces apoptosis with tyrosine kinase inhibitors in EGFR-mutated lung cancer cell lines and restores the sensitivity to gefitinib in T790M-harboring resistant cells

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    主査:西尾和人 教授  学内授与番号:医第1394号 Ryosuke Fujiwara, Yasuhiro Taniguchi, Shinya Rai, Yoshio Iwata, Aki Fujii, Ko Fujimoto, Takahiro Kumode, Kentaro Serizawa, Yasuyoshi Morita, J. Luis Espinoza , Hirokazu Tanaka, Hitoshi Hanamoto, Itaru Matsumura "Chlorpromazine cooperatively induces apoptosis with tyrosine kinase inhibitors in EGFR-mutated lung cancer cell lines and restores the sensitivity to gefitinib in T790M-harboring resistant cells"Biochemical and Biophysical Research Communications, Volume 626, 20 October 2022, Pages 156-166 https://doi.org/10.1016/j.bbrc.2022.08.010 掲

    Chlorpromazine cooperatively induces apoptosis with tyrosine kinase inhibitors in EGFR-mutated lung cancer cell lines and restores the sensitivity to gefitinib in T790M-harboring resistant cells

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    近畿大学Kindai University博士(医学)主査:西尾和人 教授  学内授与番号:医第1394号 Ryosuke Fujiwara, Yasuhiro Taniguchi, Shinya Rai, Yoshio Iwata, Aki Fujii, Ko Fujimoto, Takahiro Kumode, Kentaro Serizawa, Yasuyoshi Morita, J. Luis Espinoza , Hirokazu Tanaka, Hitoshi Hanamoto, Itaru Matsumura "Chlorpromazine cooperatively induces apoptosis with tyrosine kinase inhibitors in EGFR-mutated lung cancer cell lines and restores the sensitivity to gefitinib in T790M-harboring resistant cells"Biochemical and Biophysical Research Communications, Volume 626, 20 October 2022, Pages 156-166 https://doi.org/10.1016/j.bbrc.2022.08.010 掲載doctoral thesi

    Structural equation modeling (SEM) of kidney function markers and longitudinal CVD risk assessment.

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    Lower kidney function is known to enhance cardiovascular disease (CVD) risk. It is unclear which estimated glomerular filtration rate (eGFR) equation best predict an increased CVD risk and if prediction can be improved by integration of multiple kidney function markers. We performed structural equation modeling (SEM) of kidney markers and compared the performance of the resulting pooled indexes with established eGFR equations to predict CVD risk in a 10-year longitudinal population-based design. We split the study sample into a set of participants with only baseline data (n = 647; model-building set) and a set with longitudinal data (n = 670; longitudinal set). In the model-building set, we fitted five SEM models based on serum creatinine or creatinine-based eGFR (eGFRcre), cystatin C or cystatin-based eGFR (eGFRcys), uric acid (UA), and blood urea nitrogen (BUN). In the longitudinal set, 10-year incident CVD risk was defined as a Framingham risk score (FRS)>5% and a pooled cohort equation (PCE)>5%. Predictive performances of the different kidney function indexes were compared using the C-statistic and the DeLong test. In the longitudinal set, a SEM-based estimate of latent kidney function based on eGFRcre, eGFRcys, UA, and BUN showed better prediction performance for both FRS>5% (C-statistic: 0.70; 95% CI: 0.65-0.74) and PCE>5% (C-statistic: 0.75; 95%CI: 0.71-0.79) than other SEM models and different eGFR formulas (DeLong test p-values5% and 5%, respectively). However, the new derived marker could not outperform eGFRcys (DeLong test p-values = 0.88 for FRS>5% and 0.20 for PCE>5%, respectively). SEM is a promising approach to identify latent kidney function signatures. However, for incident CVD risk prediction, eGFRcys could still be preferrable given its simpler derivation

    From the 'Rescue of the Nation State' to the Emergence of European Spaces. EUIJ-Kansai Workshop on "New Research Horizons of the History of European Integration", May 10, 2008, Toyonaka (Osaka)

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    The aim of this paper is to make some contribution to the discussion on the future direction of the historical research on the European integration processes. What I intend to do here is, broadly, to link the contemporary European studies to the Historical studies, and concretely, to emphasise the transnational dimension of European integration. This exercise should be read as presenting my "wish list" to the Integration Historians

    Associations between dietary patterns and kidney health assessed in the population-based CHRIS study using reduced rank regression

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    Objective: While diet plays a key role in CKD management, the potential for diet to impact CKD prevention in the general population is less clear. Using a priori knowledge, we derived disease-related dietary patterns (DPs) through reduced rank regression (RRR) and investigated associations with kidney function, separately focusing on generally healthy individuals and those with self-reported kidney diseases, hypertension or diabetes mellitus. Methods: 8,686 participants from the population-based Cooperative Health Research in South Tyrol (CHRIS) study were split into a group free of kidney disease, hypertension and diabetes (n=6,133) and a group with any of the three conditions (n=2,553). Diet was assessed through the self-administered GA2LEN food frequency questionnaire (FFQ) and DPs were derived through RRR selecting FFQ-derived sodium, potassium, phosphorus and protein intake as mediators. Outcomes were creatinine-based estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), CKD and microalbuminuria. Multiple linear and logistic models were used to assess associations between RRR-based DPs and kidney outcomes separately in the two analytic groups. Results: We identified three DPs, where high adherence reflected high levels of all nutrients (DP1), high potassium-phosphorus and low protein-sodium levels (DP2), and low potassium-sodium and high protein-phosphorus levels (DP3), respectively. We observed heterogeneous associations with kidney outcomes, varying by analytic group and sex. Kidney outcomes were much more strongly associated with DPs than with single nutrients. Conclusion: RRR is a feasible approach to estimate disease-related DPs and explore the combined effects of nutrients on kidney health. Heterogeneous associations across kidney outcomes suggest possible specificity to kidney function or damage. In individuals reporting kidney disease, hypertension or diabetes, specific dietary habits were associated with better kidney health, indicating that disease-specific dietary interventions can be effective for disease control

    SimpleBounce: A simple package for the false vacuum decay

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    We present SimpleBounce, a C++ package for finding the bounce solution for the false vacuum decay. This package is based on a flow equation which is proposed by the author R. Sato (2020) and solves Coleman–Glaser–Martin’s reduced problem (S. R. Coleman et al. 1978): the minimization problem of the kinetic energy while fixing the potential energy. The bounce configuration is obtained by a scale transformation of the solution of this problem. For models with 1–8 scalar field(s), the bounce action can be calculated with O(0.1) % accuracy in O(0.1) s. This package is available at http://github.com/rsato64/SimpleBounce

    APPLICATION OF A MARKOV PROCESS TO A MECHANICAL MODEL OF GRANULAR MATERIALS (2)

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    In the previous paper the author proposed a mechanical model of particulate materials as aMarkov process and explained the concepts of the potential barrier and the potential slip planewhich are introduced in the proposed model. Furthermore, the strain of particulate materialswas defined by using the change of contact angles at the contact points of particles and the dis-continuous motion of particles.In this paper the results of shearing tests obtained by the modified triaxial apparatus whichis designed and constructed, and can generate three different principal stresses are presented.The results of numerical experiments which are carried out by using the proposed model arealso presented. From both results it is shown that the proposed model can versatilely follow themechanical behaviours of particulate materials such as sands with complicated stress paths include-ing the stress reverse and repeated loading.In the previous paper the author proposed a mechanical model of particulate materials as aMarkov process and explained the concepts of the potential barrier and the potential slip planewhich are introduced in the proposed model. Furthermore, the strain of particulate materialswas defined by using the change of contact angles at the contact points of particles and the dis-continuous motion of particles.In this paper the results of shearing tests obtained by the modified triaxial apparatus whichis designed and constructed, and can generate three different principal stresses are presented.The results of numerical experiments which are carried out by using the proposed model arealso presented. From both results it is shown that the proposed model can versatilely follow themechanical behaviours of particulate materials such as sands with complicated stress paths include-ing the stress reverse and repeated loading

    Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing

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    SummarySpinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations
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