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Glycosphingolipids (GSLs), mainly located in the cell membrane, play various roles in cancer cell function. GSLs have potential as renal cell carcinoma (RCC) biomarkers; however, their analysis in body fluids is challenging because of the complexity of numerous glycans and ceramides. Therefore, we applied wide-targeted lipidomics using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with selected reaction monitoring (SRM) based on theoretical mass to perform a comprehensive measurement of GSLs and evaluate their potency as urinary biomarkers. In semi-quantitative lipidomics, 240 SRM transitions were set based on the reported/speculated structures. We verified the feasibility of measuring GSLs in cells and medium and found that disialosyl globopentaosylceramide (DSGb5 (d18:1/16:0)) increased GSL in the ACHN medium. LC–MS/MS analysis of urine samples from clear cell RCC (ccRCC) patients and healthy controls showed a significant increase in the peak intensity of urinary DSGb5 (d18:1/16:0) in the ccRCC group compared with that in the control group. Receiver operating characteristic analysis indicated that urinary DSGb5 could serve as a sensitive and specific marker for RCC screening, with an AUC of 0.89. This study demonstrated the possibility of urinary screening using DSGb5 (d18:1/16:0). In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of intravenous administration of human multilineage‐differentiating stress‐enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. Materials and Methods: Male Sprague–Dawley rats were randomised into three groups after CN crush injury. Either human‐Muse cells, non‐Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non‐Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C‐X‐C motif chemokine ligand (Cxcl12) and glial cell line‐derived neurotrophic factor (Gdnf) in the MPG were examined by real‐time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one‐way analysis of variance followed by the Tukey test for parametric data and Kruskal–Wallis test followed by the Dunn–Bonferroni test for non‐parametric data. Results: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non‐Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non‐Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non‐Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. Conclusion: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy of pharmacotherapy for metastatic non‐clear cell renal cell carcinoma (nccRCC) in Japanese population. Methods: In this retrospective analysis, we compared the time to treatment failure (TTF) for molecular‐targeted agents as first‐line therapy, or nivolumab therapy as sequential therapy between ccRCC and nccRCC using the data of Japanese metastatic RCC patients registered in the Michinoku Japan Urological Cancer Study Group database. Results: In total, 511 cases of ccRCC and 77 cases of nccRCC were treated with pharmacotherapy. After excluding the patients who received cytokine therapy, chemotherapy, or others, there were 391 ccRCC patients and 60 nccRCC patients who were treated with tyrosine kinase inhibitors (TKIs), and 7 ccRCC patients and 7 nccRCC patients who were treated with mammalian‐target of rapamycin inhibitors (mTORIs). In addition, 132 ccRCC patients and 16 nccRCC patients received nivolumab. There was no significant difference in IMDC risk classification before first‐line therapy between ccRCC and nccRCC groups, or in each subgroup within the nccRCC group. TTF for TKIs (161 days, 95% CI: 75‐212 days) and mTORIs (21 days, 95% CI: 9‐31 days) didn't differ significantly between nccRCC and ccRCC groups (205 days, 95% CI: 174‐243 days and 33 days, 95% CI: 8‐113 days, respectively). TTF for TKIs was significantly longer than that for mTORIs in nccRCC group (p<0.01). There was no significant difference in TTF between the different TKIs in nccRCC group. In addition, no significant difference in TTF for nivolumab was seen between ccRCC and nccRCC groups. Conclusions: The results showed that the efficacy of molecular‐targeted agents as first‐line therapy was similar oncological outcomes between metastatic nccRCC and ccRCC in Japanese patients. TKIs may be more effective than mTORIs in metastatic nccRCC patients. Nivolumab administration might also be as effective in nccRCC patients as in ccRCC patients in Japanese population. [ABSTRACT FROM AUTHOR]

It remains unknown whether the early response to vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR‐TKI) management in malignancies links to long‐term survival. The objective of this study was to investigate the survival rates and predictive factors of early response in patients with metastatic renal cell carcinoma (mRCC) managed by VEGFR‐TKIs. From Jan. 2008 to Oct. 2018, 496 patients were treated with VEGFR‐TKIs as first‐line treatment at the eight Japanese hospitals (Michinoku RCC). Early cessation was defined as VEGFR‐TKIs being given up within 3 months after their initiation. The number of patients in early cessation VEGFR‐TKIs (Cohort I) was 173 (34.9%), and in long‐term use (Cohort II) was 323 (65.1%). The cancer‐specific survival (CSS) and overall survival (OS) were better in Cohort II. IMDC Poor‐risk was at risk of early cessation of a first‐line VEGFR‐TKI. Axitinib was the most preferred drug for long‐term treatment. On closer examination, both Cohort I and II were divided into two groups, the patients ceased VEGFR‐TKI due to adverse events (Group A [67 from Cohort I] and Group C [51 from Cohort II]) and disease progression (Group B [106 from Cohort I] and Group D [272 from Cohort II]). Despite that the cessation was adverse events, CSS and OS in Group A were worse than both Group C and D. Axitinib was administered with the safer profile. IMDC Poor risk was the risk factor for the early disease progression. Managing early adverse events may contribute to a better prognosis in mRCC patients treated VEGFR‐TKIs. [ABSTRACT FROM AUTHOR]

Objective: Laparoscopic adrenalectomy (LADX) improves hypertension in patients with primary aldosteronism (PA). However, the antihypertensive impact of LADX appears restricted in older patients with PA. In this study, we evaluated the impact of LADX in older patients focusing on the health-related quality of life (HRQoL). Methods: A total of 156 patients with PA who underwent LADX in a single institution were enrolled in this prospective cohort study. The patients were divided into 2 groups, with a boundary of 60 years. The HRQoL was evaluated using the Medical Outcomes Study's 36-Item Short-Form Health Survey version 2 (SF-36v2) questionnaire before and after LADX. Demographics, clinical features, antihypertensive drugs before and after surgery, and perioperative evaluation were recorded. We compared all scale scores and summed scores between groups. Multivariate regression models were used to determine the associations between various covariables and the HRQoL. Results: In the older PA patients, most subscales of HRQoL at baseline were lower than the national standard values. The antihypertensive drug-free rate by LADX was only 21% in older patients, compared to 58% in younger patients. However, a significant improvement in mental HRQoL was observed after LADX (p = 0.002). The much preoperative antihypertensive drugs, lower preoperative potassium level, and smaller degree of comorbidities were predictors of improved mental HRQoL by LADX on multivariate analyses. Conclusion: The older PA patients showed lower mental HRQOL than the national standard populations. Although antihypertensive effects were limited for these patients, LADX was beneficial as PA treatment via improvement of mental HRQoL. [ABSTRACT FROM AUTHOR]