Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm.Conclusions: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC.Clinical Trial number: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index. htm), number UMIN000010667.

Prostatic cancer in 1885 autopsy cases was classified according to the number of organs involved in metastasis, and a comparison was made concerning the frequency of metastasis to the various organs. The frequencies of metastasis to the lungs and para‐aortic lymph nodes were low in cases with single‐organ involvement (4.6% and 2.3%, respectively), but increased rectilinearly in accordance with the number of organs involved and became high in cases with metastasis to three or more organs (49.1% and 21.8% in total, respectively). On the other hand, the frequencies of local extension to the bladder and invasion of the pelvic lymph nodes were high even in cases with single‐organ involvement (34.5% and 9.2%, respectively) and were not significantly changed regardless of the number of organs involved. No significant correlation was seen between pelvic and para‐aortic lymph node involvement. In cases with single‐organ involvement, metastasis to the lumbar spine occurred frequently, but those to the ribs, sternum, and ilium occurred less frequently. There may be multiple metastases in cases with metastases to the para‐aortic lymph nodes, sternum, and ilium. The number of metastatically involved organs is useful in analyzing the mode of metastasis.

In an analysis of the autopsy records of 1,828 patients with renal adenocarcinoma 424 nephrectomized and 1,404 nonnephrectomized cases were compared to explore the effect of nephrectomy on metastasis. Over-all, no significant difference was observed except for a high incidence of metastases to the brain and femur, and a low incidence of metastases to the ipsilateral adrenal and renal hilar lymph nodes in nephrectomized cases. No significant difference was seen between the nephrectomized and nonnephrectomized cases with metastatic involvement of 1 organ, with respect to the frequency with which any given organ was involved. There were 5 patients with metastasis in whom survival was 10 years or longer after nephrectomy. Lung metastasis was present in 4 cases and lymph node metastasis in 1. Of these 5 patients 3 had undergone nephrectomy only. The results failed to show any evidence of the effectiveness of nephrectomy or adjuvant therapy. It was inferred that the mode of metastasis and the clinical progress of patients after nephrectomy for renal adenocarcinoma are influenced more profoundly by characteristics of the tumor itself than by nephrectomy.

L-type amino acid transporter 1 (LAT1) plays a role in transporting essential amino acids including leucine, which regulates the mTOR signaling pathway. Here, we studied the expression profile and functional role of LAT1 in bladder cancer. Furthermore, the pharmacological activity of JPH203, a specific inhibitor of LAT1, was studied in bladder cancer. LAT1 expression in bladder cancer cells was higher than that in normal cells. SiLAT1 and JPH203 suppressed cell proliferative and migratory and invasive abilities in bladder cancer cells. JPH203 inhibited leucine uptake by > 90%. RNA-seq analysis identified insulin-like growth factor-binding protein-5 (IGFBP-5) as a downstream target of JPH203. JPH203 inhibited phosphorylation of MAPK / Erk, AKT, p70S6K and 4EBP-1. Multivariate analysis revealed that high LAT1 expression was found as an independent prognostic factor for overall survival (HR3.46 P = 0.0204). Patients with high LAT1 and IGFBP-5 expression had significantly shorter overall survival periods than those with low expression (P = 0.0005). High LAT1 was related to the high Grade, pathological T stage, LDH, and NLR. Collectively, LAT1 significantly contributed to bladder cancer progression. Targeting LAT1 by JPH203 may represent a novel therapeutic option in bladder cancer treatment.Bladder cancer (BC) is the ninth most common malignant tumour worldwide, with 430 000 patients newly diagnosed and 165 000 deaths annually 1 . The pathological type of BC is mainly urothelial cancer ( > 90%) and approximately 70% of patients had non-muscle-invasive BC at diagnosis 2 . These patients have a favorable prognosis with transurethral resection and subsequent intravesical injection therapy, whereas the survival rate of patients with locally advanced and metastatic BC is poor 3 . For metastatic BC patients, platinum-based systematic chemotherapy is the classical treatment, while immunotherapy targeting programmed cell death ligand 1 (PD-L1) blocking antibody was recently approved in Japan 4 . However, drug resistance will occur, and the survival benefit of these agents is not adequate. Their limited efficacy is due to side effects and challenges of drug resistance, leading to treatment failure and require additional treatment options 5 . Therefore, more effective and less toxic therapeutic strategies are needed for the treatment of metastatic BC. Additionally, there are presently no useful diagnostic markers for BC. The urine cytology test is a non-invasive examination, but its sensitivity remains low. Cystoscopy is an essential diagnostic tool but is invasive for patients 5 . Thus, a novel therapeutic approach and biomarker candidates for BC remain a major issue.

Normal and reverse vesicle systems with nonionic surfactants were investigated. The solvent self-diffusion coefficient was measured using the 1H-NMR Fourier transform pulsed gradient spin-echo technique. In the case of normal vesicles, the water solvent is found to exchange rapidly between the inside and outside of the vesicles on the experimental time scale (≈0.1 s). Here, only an average self-diffusion coefficient can be measured from which the fraction of entrapped water can be determined. In the reverse vesicle case, we observe either a fast or a slow exchange, depending, on the oil and the bilayer composition. In particular we have investigated a semipermeable membrane system, where with a solvent mixture, one of the two types of solvent molecules exchanges fast while the other exchanges slowly on the experimental time scale. Here, the lifetime of a solvent molecule inside the reverse vesicles was found to depend on the composition of the mixed reverse bilayers, leading to an observed transition from fast to slow exchange conditions when varying the bilayer composition. In the slow exchange case, the self-diffusion coefficients of solvent molecules on the outside and inside of the vesicles, where the latter reports on the vesicle self-diffusion coefficient, are in principal resolved. From the bimodal type of decay of the spin-echo amplitude, it is also possible to determine directly the fraction of solvent molecules entrapped inside the vesicles.