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Simple Summary: Androgen receptor signaling is an important target to investigate in urothelial carcinoma of the bladder because basic and clinical evidence strongly suggests that the androgen receptor is involved in bladder carcinogenesis. Moreover, androgen receptor signaling may suppress anti-tumor immunity. These factors may also be important contributors to the strong male sex bias in urothelial carcinoma of the bladder. Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development. The roles of the androgen receptor in bladder carcinogenesis have obvious implications for understanding the strong male sex bias in this disease and for potential therapeutic strategies as well. In this review, we summarize what is known about androgen receptor signaling in urothelial carcinoma as well as in tumor-infiltrating immune cells, reviewing preclinical and clinical data. We also highlight clinical trial efforts in this area. [ABSTRACT FROM AUTHOR]

The suggested study adheres to a particular protocol to ensure that the process is environmentally friendly and sustainable. It is worth mentioning that several tools have been adopted as prospective measures of the method greenness. Fortunately, the established analytical method is identified as white by the white analytical chemistry (WAC) concept, which uses the red/ green/blue color scheme (RGB 12 tool) to combine ecological and functional factors for the first time in studying of the cited drug. Amlodipine (AMD), a cardiovascular treating agent, belongs to the dihydropyridine class of oral calcium channel‐blocking agents. This article presents a novel, simple, green, one‐pot‐processed, fast, and ultrasensitive fluorimetric approach for monitoring and assessment of AMD using molecular‐size‐dependent fluorescence augmentation of the light scattering‐driven signal of eosin, a biological stain at a wavelength of 415 nm. This enhancement was directly proportional to the size of the produced complex. The linearity range was from 30 to 900 ng mL−1, with corresponding sensitivity limits (detection and quantitation levels) of 9.2 and 28 ng mL−1, respectively. The planned approach was also successfully used to track AMD content in bulk, dosage forms, and bio‐fluids (human plasma and urine). The developed method's eco‐friendliness was established by different eco‐rating metric tools. [ABSTRACT FROM AUTHOR]

Purpose : To describe early results of two cohorts of patients with low and intermediate risk of early breast cancer treated with accelerated partial breast irradiation (APBI) using different schedules of multicatheter brachytherapy. Material and methods: Patients with early stage breast cancer after breast conserving surgery were enrolled for a prospective analysis. The APBI, using multicatheter brachytherapy, was delivered either eight times 4 Gy in five days with a planned total dose of 32 Gy, or seven times 5 Gy in four days with a planned total dose of 35 Gy. Primary endpoints were side effects. Results : Forty-eight patients were enrolled between 2012 and 2014. Patients characteristics were as follow: median age of patients was 55 years, early breast cancer was defined according GEC-ESTRO recommendations. With a median follow-up period of 37 months, no significant differences regarding late side effects and cosmesis between two cohorts of patients were documented. In total, cosmesis was excellent in 13/48 (27.1%) patients, good in 34/48 (70.8%) patients, and moderate in 1/48 patient (2.1%). Conclusions : Accelerated partial breast irradiation using multicatheter brachytherapy with 32 Gy/8 fractions and 35 Gy/7 fractions for early breast cancer seems to be similar in terms of late side effects. According to our findings, APBI was also feasible for intermediate-risk of early breast cancer patients.

Abstract Background UroVysion fluorescence in situ hybridization (uFISH) was reported to have superior sensitivity to urine cytology. However uFISH studies are limited by varying definitions of what is considered a positive result, absence of histopathology and small sample size. The aim of our study was to better determine the performance characteristics of uFISH and urine cytology by overcoming some of the deficiencies of the current literature. Methods Intraoperative bladder wash cytology and uFISH were collected prospectively on all patients. Strict definitions for positivity of uFISH and cytology were determined before initiating the study. A re-review of false-negative uFISH specimens was performed to analyze potential sources of error. Sixteen bladder tumors embedded in paraffin were analyzed by uFISH and compared with the result in the urine. Results One hundred and twenty-nine specimens were analyzed. Sensitivity was 67% and 69% (p = 0.54); specificity was 72% and 76% (p = 1.0), for uFISH and cytology, respectively. Thirty-two false negative uFISH samples were re-reviewed. Low grade tumors often showed cells with abnormal morphology and patchy DAPI staining but diploid chromosomal counts and a few high grade tumors had tetraploid counts but less than needed to interpret uFISH as positive. uFISH study of the tumors revealed three categories; positive in both tumor and urine (9), negative in both tumor and urine (5) and positive in tumor but negative in urine (2). Conclusion In a pathologically-confirmed analysis of bladder washed urine specimens, uFISH does not outperform urine cytology in cancer detection.

Background: Although immunotherapy has revolutionized the treatment paradigm of many cancers including HNSCC, only a subset of patients derives meaningful clinical benefit from immune checkpoint inhibitors (ICIs). Currently, PD-L1 protein expression remains the only predictive biomarker for ICI response studied in prospective first line immunotherapy clinical trials in HNSCC. PD-L1 expression level, however, is an imperfect biomarker for ICI response due to several limitations such as the variability in expression level cut-offs defined as positive vs. negative between assays, subjective interobserver variability and clinical sampling bias in acquiring specimens. Research efforts are ongoing to develop other biomarkers that can precisely identify patients who will derive benefits from ICIs. Our objective was to assess the results of comprehensive genomic and immune profiling (CGIP) in patients with HNSCC and describe the immune microenvironment of tumors with different levels of PD-L1 expression. Methods: A retrospective analysis of 409 patients with HNSCC tested by CGIP during standard-of-care was performed to compare the immune microenvironment of tumors with high (N=168), moderate-low (N=183), or negative (N=58) PD-L1 expression. Patient tumors were categorized into PD-L1 expression groups using combined positive score (CPS) thresholds of ≥20 (high), 1 to 19 (moderate-low), and <1 (negative). These CPS scores were selected according to the cut-offs used in the Phase III Keynote-048 study that led to the approval of pembrolizumab in HNSCC. DNA-seq of 523 genes analyzed tumor mutational burden (TMB). RNA expression analysis was performed for 395 immune genes. Gene expression-based signatures for tumor immunogenicity score (TIGS), cellular proliferation (CP) and cancer testis antigen burden (CTAB) were calculated from percentile ranks of normalized gene expression values. Expressions of three emerging biomarkers linked to an immune checkpoint mechanism (LAG3, TIGIT and TIM3) were also determined by RNA-seq. PD-L1 expression was assessed using immunohistochemistry. Wilcoxon rank-sum tests were used to detect significant differences between PD-L1 groups in TMB, gene expression signatures, and gene expressions of TIM-3, TIGIT and LAG-3. Results: Tumors with high PD-L1 demonstrated increased expression of genes associated with tumor immunogenicity compared to moderate-low (median TIGS of 54 vs 41; p<1E-4) and negative (median TIGS of 54 vs 43; p<1E-4) tumors (Fig 1B). PD-L1 high tumors also showed increased expression of other emerging biomarkers involved in immune checkpoint pathways such as LAG-3, TIGIT and TIM-3, compared to moderate-low and negative tumors (Fig 1E-G). We found no significant differences between PD-L1 groups in TMB and the remaining composite gene expression signatures (p>0.05; Fig 1A,C,D). Conclusion: Our findings highlight the complex interplay of diverse immune cells and checkpoint markers in the tumor microenvironment (TME) beyond PD-L1 in HNSCC. Tumors with high PD-L1 expression harbored a greater degree of immune infiltration, demonstrating a higher TIGS score as well as other checkpoint markers of emerging clinical importance such as LAG-3, TIGIT and TIM-3. Interestingly, tumors with PD-L1 moderate-low expression did not exhibit significant differences in TIGS, TIGIT and TIM-3, compared to PD-L1 negative tumors. These results suggest that HNSCC tumors with PD-L1 CPS ≥ 20 have the most robust immunogenic profile. Understanding the different components of TME can aid in implementing innovative therapeutic strategies to enhance the immune responses and potentially overcome resistance to ICIs in HNSCC. [ABSTRACT FROM AUTHOR]