The large-conductance Ca2+-activated K+ channel KCa1.1 plays an important role in the promotion of breast cancer cell proliferation and metastasis. The androgen receptor (AR) is proposed as a therapeutic target for AR-positive advanced triple-negative breast cancer. We herein investigated the effects of a treatment with antiandrogens on the functional activity, activation kinetics, transcriptional expression, and protein degradation of KCa1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, voltage-sensitive dye imaging, and whole-cell patch clamp recording. A treatment with the antiandrogen bicalutamide or enzalutamide for 48 h significantly suppressed (1) depolarization responses induced by paxilline (PAX), a specific KCa1.1 blocker and (2) PAX-sensitive outward currents induced by the depolarizing voltage step. The expression levels of KCa1.1 transcripts and proteins were significantly decreased in MDA-MB-453 cells, and the protein degradation of KCa1.1 mainly contributed to reductions in KCa1.1 activity. Among the eight regulatory β and γ subunits, LRRC26 alone was expressed at high levels in MDA-MB-453 cells and primary and metastatic breast cancer tissues, whereas no significant changes were observed in the expression levels of LRRC26 and activation kinetics of PAX-sensitive outward currents in MDA-MB-453 cells by the treatment with antiandrogens. The treatment with antiandrogens up-regulated the expression of the ubiquitin E3 ligases, FBW7, MDM2, and MDM4 in MDA-MB-453 cells, and the protein degradation of KCa1.1 was significantly inhibited by the respective siRNA-mediated blockade of FBW7 and MDM2. Based on these results, we concluded that KCa1.1 is an androgen-responsive gene in AR-positive breast cancer cells, and its down-regulation through enhancements in its protein degradation by FBW7 and/or MDM2 may contribute, at least in part, to the antiproliferative and antimetastatic effects of antiandrogens in breast cancer cells.

N,N-diethyl-3-toluamide (DEET) is one of the most widely used insect repellents in the world. It was reported that a solution containing 6–30% cyclodextrin (CD) as a solvent instead of ethanol (EtOH) provided an enhancement of the repellent action time duration of the DEET formulation, although the high-dose CD caused stickiness. In order to overcome this shortcoming, we attempted to prepare a 10% DEET formulation using EtOH containing low-dose CDs (β-CD, 2-hydroxypropyl-β-CD (HPβCD), methyl-β-CD, and sulfobutylether-β-CD) as solvents (DEET/EtOH/CD formulations). We determined the CD concentration to be 0.1% in the DEET/EtOH/CD formulations, since the stickiness of 0.1% CDs was not felt (approximately 8 × 10−3 N). The DEET residue on the skin superficial layers was prolonged, and the drug penetration into the skin tissue was decreased by the addition of 0.1% CD. In particular, the retention time and attenuated penetration of DEET on the rat skin treated with the DEET/EtOH/HPβCD formulation was significantly higher in comparison with that of the DEET/EtOH formulation without CD. Moreover, the repellent effect of DEET was more sustained by the addition of 0.1% HPβCD in the study using Aedes albopictus. In conclusion, we found that the DEET/EtOH/HPβCD formulations reduced the skin penetration of DEET and prolonged the repellent action without stickiness.

Background Tisagenlecleucel yielded a high durable response rate in patients with relapsed/refractory (r/r) follicular lymphoma (FL) in the global phase 2 ELARA trial. Here, we report the efficacy, safety, and cellular kinetics of tisagenlecleucel in a subgroup of Japanese patients with r/r FL from ELARA. Methods ELARA (NCT03568461) is a global single-arm trial of tisagenlecleucel in patients with r/r FL who received ≥ 2 prior lines of therapy. The primary endpoint was the complete response rate (CRR), and the secondary endpoints were the overall response rate, duration of response, progression-free survival, overall survival, safety, and cellular kinetics. Results As of March 29, 2021, nine Japanese patients were enrolled and received tisagenlecleucel with a median follow-up of 13.6 months (range, 10.5‒19.3). Per independent review committee, CRR was 100% (95% CI 63.1‒100). Within 8 weeks of infusion, cytokine release syndrome (CRS) of any grade was reported in 6 patients (66.7%); however, no grade ≥ 3 CRS or any grade serious neurological events or treatment-related deaths were observed. Conclusion Tisagenlecleucel showed high efficacy and manageable safety in adult Japanese patients with r/r FL. Moreover, the clinical outcomes were similar to the global population, which supports the potential of tisagenlecleucel in Japanese patients with r/r FL.

Only a few evaluation has been reported on both design impression and usability of commodity containers. In this survey, we evaluated both the design impression and usability of an insect repellent spray container. In the design impression, the spray containers were evaluated on a 7-point scale with adjective pairs. As a result of factor analysis, three factors were extracted: factor 1 favorability, factor 2 trustworthy and friendliness, and factor 3 softness and gentleness. In the usability, the grip comfort were evaluated on a 5-point scale using the Likert scale, along with measurement of the pressure applied to the hand when gripping the spray container. As a result of the correlation analysis of grip comfort and grip pressure, we found that the thumb and the upper part of the palm affects the grip comfortability. By evaluating both design impression and usability, it can lead to a better container assessment.

Objectives This study aimed to adapt the meaning-centered psychotherapy (MCP) to treat post-bereavement grief in Japanese bereaved families who lost their loved ones to cancer and to examine the feasibility of the intervention using both quantitative and qualitative methods. Methods A modified version of MCP was developed with cultural consideration. Bereaved individuals aged ≥18 years who had lost their family members to cancer at least 6 months before and had severe or persistent grief with a score of ≥26 on the Inventory of Complicated Grief (ICG-19) were included in the study. The participants received the modified version of MCP, which was provided in a 5-session monthly format. The levels of grief (ICG-19), depression (Center for Epidemiologic Studies Depression Scale [CES-D]), general health (General Health Questionnaire-12), and post-traumatic growth (Post-traumatic Growth Inventory -Short Form) were compared before and after the intervention. Results Five bereaved individuals were enrolled, and all the participants completed the program. The mean scores of the ICG-19. The participants’ sense of regret, guilt, and being separated from the deceased person gradually shifted to the reappraisal of the experience, leading to a broadened view of the relationship with the deceased, and rediscovery of the core values, identity, and roles of the participants through the process of rediscovery of the meaning of life. Significance of results A modified version of the MCP was well accepted by Japanese bereaved families. The intervention appears to promote the rediscovery of the meaning of life and appears to have the potential to alleviate the bereaved individuals’ depression and grief-related symptoms and to facilitate their post-traumatic growth.