Recently, artificial cells have been attracted much attention as a model of living cells.The living cells are non-equilibrium chemically open systems and transport molecules in and out through their cell membrane in a controlled manner.However, artificial cells with a chemically open feature and a controlled transport of molecules have never been achieved yet.Here, we propose a chemically open artificial cell with a feedback control over molecular permeability of the cell membrane.To implement this feedback control system, diffusion coefficient inside the artificial cell is changed according to the concentration of inside chemicals.We believe that this numerical analysis will promote the understanding of dynamic chemical systems in artificial cells.
Caveolae are invagination structures in plasma membrane, size of about 100 nm.The main function of caveolae is still under debate.Recently it is proposed that the caveolae become flattened as buffers of plasma membrane at hypo-osmotic shock.We performed theoretical analysis and computer simulation to test this hypothesis.In the theoretical analysis, we calculated force acted on the caveolae and found that, the direction of force depends on the shape of caveolae: the expanding force and constriction force are both expected.The constriction force may give the opposite result; constricted caveolae.Then we performed coarse-grained membrane (polygon membrane) simulation and confirmed the existence of constricted caveolae, which is a novel membrane structures.
Abstract Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.
To evaluate the efficacy of low dose tamsulosin for facilitating spontaneous passage of ureteral stones in Japanese male patients.A total of 71 patients with symptomatic ureteral stones, 10 mm or smaller in size, were randomly allocated into groups 1 and 2. Group 1 received tamsulosin (0.2 mg/day) for a maximum of 4 weeks and group 2 received no medication. The primary endpoint was the stone expulsion rate and the secondary endpoints were stone expulsion time and analgesic use.There were no significant differences between the groups in terms of age, stone size and location. The stone expulsion rate was significantly higher in group 1 than in group 2 (77% vs 50%, P = 0.002). No significant differences were noted in the stone expulsion time and analgesic use between the groups.Low dose tamsulosin can significantly facilitate spontaneous passage of ureteral stones without significant side-effects in Japanese male patients.
Abstract Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.
Abstract Background While the occurrence of immune‐related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment‐related adverse events (trAEs) in patients undergoing antibody–drug conjugates such as enfortumab vedotin (EV) is controversial. Methods We reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression‐free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias. Results Of 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow‐up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into “physical trAEs” such as skin disorders and “laboratory trAEs” such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival. Conclusions Physical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody–drug conjugates such as EV.
