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BACKGROUND/AIM To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC). PATIENTS AND METHODS This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated. RESULTS Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR

Objective Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100 ng/mL and chemokine (CC motif) ligand 2 ≥ 320 pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. Methods Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. Results Patients with chemokine (CC motif) ligand 2 ≥ 320 pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2 Conclusions This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.

Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.The study included 97 patients with advanced UC whose lesions were classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median age was 73 years. Nineteen patients (20%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The efficacy, safety, and risk factors for prognosis were evaluated for patients with and without measurable lesions.The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8-4.7) and 11.8 months (95% CI: 6.7-17.0), respectively. Twenty-one (22%) patients had no measurable lesions per RECIST. In univariate and multivariate analysis, PS 2-4 and lesions by RECIST were identified as factors associated with short overall survival (OS). The median OS of 18.3 months in patients without lesions by RECIST was significantly longer than the median OS of 6.7 months in patients with lesions by RECIST (p = .012).We demonstrated that good PS 0-1 and no measurable lesions, especially small lesions, by RECIST were favorable prognostic factors in patients with advanced UC treated by pembrolizumab.

This study evaluated the effects of three types of hybrid iterative reconstruction (IR) on image quality of pediatric body computed tomography images. The image quality components evaluated were noise power spectrum (NPS), task-based modulation transfer function (TTF), and system performance function (SPF). As the IR strength was increased while reducing the radiation dose, the NPS increased in a low-frequency range and the TTF decreased in low-contrast regions. In the low-contrast regions, the calculated SPF decreased over the entire frequency range. Alternatively, in the high-contrast regions, the SPF decreased in the low-frequency regions and increased in the high-frequency regions. The radiation dose reduction using the hybrid IR resulted in the deterioration of the image quality in the low-contrast regions and changes in the spatial frequency characteristics in the high-contrast regions.

Autophagy is a mechanism of bulk protein degradation that plays an important role in regulating homeostasis in many organisms. Among several methods for evaluating its activity, a fluorescent reporter GFP-LC3-RFP-LC3ΔG, in which GFP-LC3 is cleaved by ATG4 following autophagic induction and degraded in lysosome, has been used for monitoring autophagic flux, which is the amount of lysosomal protein degradation. In this study, we modified this reporter by exchanging GFP for pHluorin, which is more sensitive to low pH, and RFP to mCherry, to construct pHluorin-LC3-mCherry reporter. Following starvation or mTOR inhibition, the increase of autophagic flux was detected by a decrease of the fluorescent ratio of pHluorin to mCherry; our reporter was also more sensitive to autophagy-inducing stimuli than the previous one. To establish monitoring cells for mouse genome-wide screening of regulators of autophagic flux based on CRISPR/Cas9 system, after evaluating knockout efficiency of clones of Cas9-expressing MEFs, we co-expressed our reporter and confirmed that autophagic flux was impaired in gRNA-mediated knockout of canonical autophagy genes. Finally, we performed genome-wide gRNA screening for genes inhibiting starvation-mediated autophagic flux and identified previously reported genes such as Atgs. Thus, we have successfully established a system for screening of genes regulating autophagic flux with our pHluorin-LC3-mCherry reporter in mice.

Although various types of on-site immunoassay platforms have been developed, facile and reliable sample-to-answer immunoassay systems are still under development. In this study, we proposed a lateral-flow immunoassay system utilizing a polymer sheet with microcone array structures fabricated by thermal imprinting. By adding a surfactant to the running/washing buffer, we were able to dispense with complicated chemical modification protocols, which are usually necessary to enhance antibody adsorption. We investigated three types of polymeric materials and confirmed that polycarbonate is most suitable as an imprinted polymer substrate. Experiments using microcone arrays with different distances revealed that the increased surface area with nanometer-scale surface roughness was key to achieving stable immobilization of antibodies. To assess the applicability of this assay to clinical diagnosis, C-reactive protein in a pure buffer and in a serum sample was analyzed as a model, with a ∼0.1 μg mL−1 lower limit of detection. The presented approach would open a new path to the development of immunoassay-based on-site point-of-care testing by virtue of its simplicity of operation, high sensitivity, and versatility.

Purpose To assess the efficacy of a combined regimen of levofloxacin (LVFX) plus isepamicin (ISP) as prophylaxis for transrectal ultrasound-guided needle biopsy of the prostate (TRUSP-Bx). Materials and methods Overall, 562 patients undergoing TRUSP-Bx were included in the present study. All patients were administered a single-dose of oral LVFX (500 mg) in the morning and intravenous ISP (400 mg) 60 min before biopsy. All biopsies were performed via TRUSP-Bx with an 18-gauge needle, and 12-core specimens were routinely obtained. Before initiating antibiotic treatment, urine and blood bacterial cultures were tested to determine the causative microorganisms in the patients with acute bacterial prostatitis. Results Acute bacterial prostatitis developed in three (0.53%) participants. The incidence rates of acute bacterial prostatitis in the low- and high-risk groups were 0.79% and 0.46%, respectively. These patients showed clinical symptoms of acute bacterial prostatitis 12–24 h after their biopsy. Escherichia coli (E. coli) was isolated in the urine or bladder cultures of all of patients. All three isolates were determined to be LVFX-resistant E. coli, although they had good sensitivity to aminoglycosides, cephalosporins, and carbapenems. All patients were administered antibiotic treatment (cephalosporin or carbapenem) immediately and were treated successfully with no evidence of further disease progression. Conclusion Antibiotic prophylaxis with LVFX plus ISP was effective, resulting in a lower incidence of acute bacterial prostatitis after TRUSP-Bx in both low- and high-risk patients.