Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care

An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib) and TARCEVA (Erlotinib) treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care

Half-Metallic Heusler Alloy/GaN Heterostructure for Semiconductor Spintronics Devices

Because spin-orbit coupling in wurtzite semiconductors is relatively weak compared with that in zincblende ones, the III-nitride semiconductor GaN is a promising material for high-performance optical semiconductor spintronic devices such as spin lasers. For the purpose of reducing the operating power of spin lasers, it is necessary to demonstrate highly efficient electrical spin injection from a ferromagnetic material into GaN with a low-resistance contact. Here, an epitaxial half-metallic Heusler alloy Co2FeAlxSi1−x(CFAS)/GaN heterostructure is developed by inserting an ultrathin Co layer between the CFAS and GaN. The CFAS/n+-GaN heterojunctions clearly show tunnel conduction with very small rectification and a low resistance-area product of ≈3.8 kΩµm2, which is several orders of magnitude smaller than those reported in previous work, at room temperature. Nonlocal spin signals and a Hanle effect curve are observed at low temperatures using lateral spin-valve devices with the CFAS/n+-GaN contacts, suggesting pure spin current transport in bulk GaN. The spin transport is observed at temperatures as high as room temperature, with a high spin polarization of 0.2 at a low bias voltage less than 2.0 V. This study is expected to open a path to GaN-based spintronic devices with highly spin-polarized and low-resistance contacts.Yamada S., Kato M., Ichikawa S., et al. Half-Metallic Heusler Alloy/GaN Heterostructure for Semiconductor Spintronics Devices. Advanced Electronic Materials 9, 2300045 (2023); https://doi.org/10.1002/aelm.202300045

Kick velocity induced by magnetic dipole and quadrupole radiation

We examine the recoil velocity induced by the superposition of the magnetic dipole and quadrupole radiation from a pulsar/magnetar born with rapid rotation. The resultant velocity depends on not the magnitude, but rather the ratio of the two moments and their geometrical configuration. The model does not necessarily lead to high spatial velocity for a magnetar with a strong magnetic field, which is consistent with the recent observational upper bound. The maximum velocity predicted with this model is slightly smaller than that of observed fast-moving pulsars.Comment: 10 pages, 3 color figure

Prognostic Impact of Number of Resected and Involved Lymph Nodes at Complete Resection on Survival in Non-small Cell Lung Cancer

BackgroundLymph node (LN) status is a major determinant of stage and survival in patients with lung cancer. In the 7th edition of the TNM Classification of Malignant Tumors, the number of involved LNs is included in the definition of pN factors in breast, stomach, esophageal, and colorectal cancer, and the pN status significantly correlates with prognosis.MethodsWe retrospectively investigated the prognostic impact of the number of resected LNs (RLNs) and involved LNs in the context of other established clinical prognostic factors, in a series of 928 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete resection at our institution between 2000 and 2007.ResultsThe mean number of RLNs was 15. There was a significant difference in the total number of RLNs categorized between less than 10 and ≥10 (p = 0.0129). Although the incidence of LN involvement was statistically associated with poor prognosis, the largest statistically significant increase in overall survival was observed between 0 to 3 and ≥4 involved LNs (hazard ratio = 7.680; 95% confidence interval = 5.051–11.655, p < 0.0001). On multivariate analysis, we used the ratio between the number of involved LNs and RLNs. The number of RLNs was found to be a strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95% confidence interval = 4.137–11.186, p < 0.0001).ConclusionComplete resection including 10 or more LNs influenced survival at complete NSCLC resection. Four involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved LNs is a strong independent prognostic factor in NSCLC, and the results of this study may provide new information for determining the N category in the next tumor, node, metastasis classification

High-absorption curcumin reduces BNP in hypertensive heart disease

Aims Hypertension is a strong risk factor for heart failure with preserved ejection fraction. Curcumin has p300-specific histone acetyltransferase inhibitory activity, suppresses cardiomyocyte hypertrophy and fibrosis, and significantly reduces myocardial brain natriuretic peptide (BNP) expression without altering blood pressure in a rat model of hypertensive heart disease. This double-blind, placebo-controlled, randomized study, for the first time, aimed to examine the efficacy of a high-absorption curcumin for the prevention of hypertensive heart disease in humans. Methods and results Patients exhibiting initial signs of hypertensive heart disease with left ventricular ejection fraction ≥60% and stable blood pressure <140/90 mmHg orally took a double-blinded capsule (either a 90 mg curcumin capsule or placebo) twice daily for 24 weeks. The primary endpoint was per cent changes in left ventricular diastolic function (E/E′) from baseline to 6 months after administration. The secondary endpoint was the per cent change in plasma BNP levels. The E/E′ ratio per cent change from baseline to 6 months after administration was similar between the placebo (n = 69) and the curcumin (n = 73) groups. The per cent change in plasma BNP levels was significantly lower in the curcumin group than in the placebo group. In patients <65 years, BNP per cent changes were significantly lower in the curcumin group than in the placebo group, but similar between groups in ≥65 years (<65 vs. ≥65 years: P for interaction = 0.011). Conclusions A high-absorption curcumin agent did not affect the E/E′ ratio, rather it significantly inhibited the increase in plasma BNP levels in patients with initial signs of hypertensive heart disease

Measurement of Erythrocyte Deformability by Uniaxial Stretching : Mesurement of Apparent Young\u27s Modulus and Time Constant of Shape Recovering

An erythrocyte can be deformed very easily by even small amounts of stress, enabling it to flow smoothly through approximately 3μm diameter microvessels despite its larger size of 8μm in diameter and 2μm in thickness. Reduction of erythrocyte deformability leads to poor circulation particularly in microvessels, which may result in hypertension and various circulatory diseases. To clarify blood microcirculatory properties, it is very important to understand the deformability of erythrocytes. However, a standard method for quantitative evaluation of erythrocyte deformability has not yet been established. In this study, an apparent Young\u27s modulus and a time constant for the recovery of erythrocyte shape following uniaxial stretching are proposed as deformability indices. When an erythrocyte was pulled horizontally on opposite ends using two micropipettes, tensile stress and strain were measured, and an apparent Young\u27s modulus was calculated based on Hooke\u27s law. On returning to its initial shape after the erythrocyte was released from stretching, the elapsed time and strain were measured, and a time constant for shape recovery was calculated based on the Kelvin model. The average apparent Young\u27s modulus was 16.0 Pa, and the average time constant was 113.4 ms, with a slight tendency toward an inverse relation between the two physical quantities

Unhealthy food intake restriction awareness and mortality

Background: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. Methods: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35–69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. Results: The mean follow-up period was 11 years and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR=0.73; 95% CI, 0.55 to 0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. Conclusion: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk

Association of perceived stress and coping strategies with the renal function in middle-aged and older Japanese men and women

Elucidating the risk factors for chronic kidney disease is important for preventing end-stage renal disease and reducing mortality. However, little is known about the roles of psychosocial stress and stress coping behaviors in deterioration of the renal function, as measured by the estimated glomerular filtration rate (eGFR). This cross-sectional study of middle-aged and older Japanese men (n = 31,703) and women (n = 38,939) investigated whether perceived stress and coping strategies (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were related to the eGFR, with mutual interactions. In multiple linear regression analyses adjusted for age, area, lifestyle factors, and psychosocial variables, we found a significant inverse association between perceived stress and the eGFR in men (Ptrend = 0.02), but not women. This male-specific inverse association was slightly attenuated after adjustment for the history of hypertension and diabetes and was more evident in lower levels of emotional expression (Pinteraction = 0.003). Unexpectedly, problem solving in men (Ptrend < 0.001) and positive reappraisal in women (Ptrend = 0.002) also showed an inverse association with the eGFR. Perceived stress may affect the eGFR, partly through the development of hypertension and diabetes. The unexpected findings regarding coping strategies require the clarification of the underlying mechanisms, including the hormonal and immunological aspects