Hospital burden of long-term genitourinary and gastrointestinal toxicity after radical radiotherapy for prostate cancer

Introduction

Treatment options for prostate cancer (PCa) include radical radiotherapy (RT) and radical prostatectomy, both of which have comparable oncological outcomes. The aim of this study was to investigate the hospital burden of long-term genitourinary and gastrointestinal toxicity among patients with PCa who were treated with radiotherapy at our institution.

Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations

Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing.     

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study, we aimed to determine the incidence of adverse drug reactions (ADRs) of atezolizumab, identify ADR signals that are significantly related to atezolizumab, and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events (ADEs) reported in the American Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Methods In total, 4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed. Results The top three ADEs were febrile neutropenia (3.7％), anemia (2.9％), and acute renal failure (2.3％). In addition, the incidence rates of some ADEs were significantly different according to sex and age. The systematic organ classification of atezolizumab ADEs involved 32 systems, among which the top three were blood and lymphatic system disorders (585 cases, 12.2％), gastrointestinal disorders (433 cases, 9.0％), and infections and infestations (401 cases, 8.4％). The reporting odds ratio (ROR) method was used to detect the ADR signals of atezolizumab. The ROR (95％ confidence interval) of the top ADE, febrile neutropenia, was 39.236 (33.757–45.604). In addition, we found 121 cases of complications associated with immune-related ADEs. Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use, suggesting that atezolizumab has an acceptable and controllable drug effect.     

Simple in vitro migration assay for neural crest cells and the opposite effects of all‐trans‐retinoic acid on cephalic‐ and trunk‐derived cells

Here, we describe a simple in vitro neural crest cell (NCC) migration assay and the effects of all‐trans‐retinoic acid (RA) on NCCs. Neural tubes excised from the rhombencephalic or trunk region of day 10.5 rat embryos were cultured for 48 h to allow emigration and migration of NCCs. Migration of NCCs was measured as the change in the radius (radius ratio) calculated from the circular spread of NCCs between 24 and 48 h of culture. RA was added to the culture medium after 24 h at embryotoxic concentrations determined by rat whole embryo culture. RA (10 μM) reduced the migration of cephalic NCCs, whereas it enhanced the migration of trunk NCCs, indicating that RA has opposite effects on these two types of NCCs.     

Toxic effects arising from selenium and deferasirox interaction in the biological system

This investigation was conducted to evaluate the effect of deferasirox on selenium toxicity in male rat organs. After 50 days of selenium administration, all the rats showed toxicity symptoms. After poisoning, deferasirox was given orally to rats during 10 days. The results show that toxicity symptoms were unexpectedly increased. The new symptoms of toxicity after deferasirox administration were including loss of body hairs, yellowish discoloration of hair, weakness, brown spot on their skin, enlargement of the spleen and shrinking of sex organs. Selenium and iron concentrations were determined by GFAAS and FAAS, respectively. The results indicate the poisoned rats with selenium that received deferasirox as a drug, shown serious symptoms such as exacerbate toxicity, reduction in iron concentration, anemia and even death after a few days of deferasirox administration.