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J. IDN-6556 order Med. Invest. 67 351-354, August, 2020.Drug-tolerant cells are mediators of acquired resistance. BIM-intron2 deletion polymorphism (BIM-del) is one of the mechanisms underlying the resistance to epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI)-mediated apoptosis that induces drug tolerance. Here, we investigated whether resminostat, a histone deacetylase inhibitor, circumvents BIM-del-associated apoptosis resistance. The human EGFR-mutated non-small cell lung cancer (NSCLC) cell line PC-9 and its homozygous BIM-del-positive variant (PC-9 BIMi2- / -), established by editing with zinc finger nuclease, were used. In comparison with PC-9 cells, PC-9 BIMi2- / - cells were less sensitive to apoptosis mediated by EGFR-TKIs such as gefitinib and osimertinib. The combined use of resminostat and an EGFR-TKI preferentially induced the expression of the pro-apoptotic BIM transcript containing exon 4 rather than that containing exon 3, increased the level of pro-apoptotic BIM protein (BIMEL), and stimulated apoptosis in vitro. In a subcutaneous tumor model derived from PC-9 BIMi2- / - cells, gefitinib monotherapy decreased tumor size but retained residual lesions, indicative of the presence of tolerant cells in tumors. The combined use of resminostat and gefitinib increased BIMEL protein level and induced apoptosis, subsequently leading to the remarkable shrinkage of tumor. These findings suggest the potential of resminostat to circumvent tolerance to EGFR-TKIs associated with BIM deletion polymorphism. J. Med. Invest. 67 343-350, August, 2020.Background  The aim of this study was to investigate quality of life (QOL) and night-time sleep disturbance in colon cancer patients with middle risk chemotherapy for proper antiemetic therapy. Methods  The study enrolled 139 patients with colorectal cancer. All patients received oxaliplatin or irinotecan-based chemotherapy. Patients completed a questionnaire about chemotherapy-induced nausea and vomiting and sleep disturbance. Sleep disturbance was checked, and the relationship between sleep disturbance and nausea was analyzed. Results  The prevalence of nausea was 48.9% (68 / 139). The degree of the nausea was slight / moderate / severe in 51 / 11 / 6 patients, and 12 patients had vomiting. Appetite showed no change / slightly decreased / half / one-fourth / none in 51 / 34 / 33 / 6 / 7 patients. There were significant differences in the mental component summary (MCS) score and the role-social component score (RCS). (MCS  nausea(+) vs nausea(-) 46.4 ± 1.1 vs 54.1 ± 1.1 p  less then  0.01 RCS  nausea(+) vs nausea(-) 33.1 ± 2.1 vs 41.6 ± 2.1 p  less then  0.01). Using the MCS with a cut-off score of 50, patients were divided into two groups, and nausea was significantly correlated with a low MCS score. Furthermore, patients were divided into two groups using a Pittsburgh Sleep Quality Index cut-off score of 6, and sleep disturbance was correlated with old age and second-line chemotherapy. Conclusions  Nausea affects QOL and night-time sleep of colon cancer patients with middle risk chemotherapy. J. Med. Invest. 67 338-342, August, 2020.Background  Since diaphragm passivity induces oxidative stress that leads to rapid atrophy of diaphragm, we investigated the effect of controlled ventilation on diaphragm thickness during assist-control ventilation (ACV). Methods  Previously, we measured end-expiratory diaphragm thickness (Tdiee) of patients mechanically ventilated for more than 48 hours on days 1, 3, 5 and 7 after the start of ventilation. We retrospectively investigated the proportion of controlled ventilation during the initial 48-hour ACV (CV48%). Patients were classified according to CV48%  Low group, less than 25% ; High group, higher than 25%. Results  Of 56 patients under pressure-control ACV, Tdiee increased more than 10% in 6 patients (11%), unchanged in 8 patients (14%) and decreased more than 10% in 42 patients (75%). During the first week of ventilation, Tdiee decreased in both groups  Low (difference, -7.4% ; 95% confidence interval [CI], -10.1% to -4.6% ; p  less then  0.001) and High group (difference, -5.2% ; 95% CI, -8.5% to -2.0% ; p = 0.049). Maximum Tdiee variation from baseline did not differ between Low (-15.8% ; interquartile range [IQR], -22.3 to -1.5) and High group (-16.7% ; IQR, -22.6 to -11.1, p = 0.676). Conclusions  During ACV, maximum variation in Tdiee was not associated with proportion of controlled ventilation higher than 25%. J. Med. Invest. 67 332-337, August, 2020.Purpose  Antiresorptive agents, such as bisphosphonates, are useful for the prevention of the recurrence of hip fractures. However, their administration has a risk of antiresorptive agent-related osteonecrosis of the jaw (ARONJ), and risk factors include poor oral hygiene. It is difficult for an orthopedic surgeon to examine a patient's oral condition thoroughly. This study evaluated the relationship between risk factors for ARONJ and intraoral findings in hip fracture patients. Materials and Methods  We evaluated 79 patients (average age of 82.2 years) with hip fracture surgery who underwent an oral assessment by dentists. The risk assessments of the intraoral findings were classified into four levels (levels 0-3), with levels 2 and 3 requiring dental treatment intervention. Data that could be extracted as risk factors of ARONJ were also examined. Results  Level 1 was found most frequently (54.4%), followed by level 0 (35.4%), level 2 (8.9%), level 3 (1.3%). The area under the receiver operating characteristic curve for the number of risk factors for the two groups (dental treatment intervention required and unnecessary) and oral findings were 0.732. When the cut-off value was set to two risk factors, the specificity and sensitivity was 53.5% and 87.5%. Conclusions  For hip fracture patients with a more than 2 risk factors, dental visits are recommended to prevent ARONJ. This is a useful evaluation method that can be used to screen for ONJ from data obtained from other risk factors, even if it is difficult to evaluate the oral condition in hospitals where dentists are absent. J. Med. Invest. 67 328-331, August, 2020.