Lim S, et al. Yonsei Med J. 2019 Oct;60(10):898-904. https://doi.org/10.3349/ymj.2019.60.10.898

Dalyong Kim, M.D., Hyun Jung Lee, Ph.D., Soo-Young Yu, Ph.D., M.P.H., Jung Hye Kwon, Ph.D., Hee Kyung Ahn, Ph.D., Jee Hyun Kim, Ph.D., Seyoung Seo, Ph.D., Chi Hoon Maeng, Ph.D., Seungtaek Lim, M.D., Do Yeun Kim, Ph.D. and Sung Joon Shin, Ph.D.. J Hosp Palliat Care 2021;24:204-13. https://doi.org/10.14475/jhpc.2021.24.4.204

Background: Modulating ethanol metabolism and attenuating alcohol-induced oxidative stress are promising therapeutic strategies for reducing the severity of hangovers and alleviating their associated physiological burden. Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effects of the probiotic strain Leuconostoc mesenteroides VITA-PB2 on ethanol metabolism, oxidative stress, and hangover-related symptoms in 28 healthy adults. The participants consumed either VITA-PB2 or a placebo before standardized alcohol intake, with a 7-day washout period and subsequent crossover. Primary outcomes included blood ethanol, acetaldehyde levels, and aldehyde dehydrogenase (ALDH) activity. Secondary outcomes measured hangover severity assessed by the Acute Hangover Scale (AHS), liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT), oxidative stress indicators reactive oxygen species (ROS) and nitric oxide (NO), and antioxidant responses measured by glutathione peroxidase (GPx), catalase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity. Results: VITA-PB2 supplementation led to a sustained reduction in blood ethanol concentrations beginning at 0.5 h post-ingestion compared with the placebo group, indicating more efficient ethanol clearance. Additionally, VITA-PB2 significantly reduced acetaldehyde levels at 1 h post-ingestion (p < 0.05) and increased ALDH activity by 42.15% at 30 min (p < 0.05). It also markedly reduced ROS levels at 1 h (p < 0.05), enhanced glutathione peroxidase (GPx) activity at 2 h (p < 0.01), and significantly improved the subjective hangover symptoms, particularly thirst (p < 0.05). Conclusions: No adverse effects were reported during the trial, indicating that Leuconostoc mesenteroides VITA-PB2 is a safe probiotic. These findings suggest its efficacy in mitigating alcohol-induced oxidative stress and alleviating hangover-related symptoms.

Introduction: Small cell lung cancer (SCLC) is known for its high proliferative rate and poor prognosis. Although Delta‐like ligand 3 (DLL3) is specifically expressed on the surface of SCLC, the association of DLL3 with prognosis in SCLC remains uncertain. Hence, we aimed to evaluate prognostic role of DLL3 in extensive stage of SCLC treated with first‐line chemotherapy.Materials and Methods: A total of 54 patients with extensive stage of SCLC (ES‐SCLC) who were treated with first‐line chemotherapy were included for our analysis. In addition, tissue specimen should be available for immuno‐histochemical staining for DLL3, and their clinico‐pathologic data, including progression‐free survival (PFS) and overall survival (OS), were obtained. DLL3 expression and the percentage of tumor cells with DLL3 positive among total cancer cells were analyzed microscopically and DLL3 high and DLL3 low were defined as the percentage of DLL3 positive tumor cells versus total cancer cells ≧ 75% and < 75%, respectively.Results: DLL3 expression was not associated with any of the clinico‐pathological characteristics such as age at diagnosis, sex, response to first‐line chemotherapy, second‐line chemotherapy (Yes or No), and number of metastatic sites. However, response to first‐line chemotherapy and number of metastatic sites were correlated to PFS, while DLL3 expression and number of metastatic sites were correlated to OS.Conclusion: DLL3 was highly expressed in SCLC, and not associated with any clinico‐pathological characteristics. In survival outcome, DLL3 was correlated with worse OS, which suggests the prognostic role of DLL3 in ES‐SCLC.

Purpose: Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) are implicated in tumor angiogenesis. Although erdafitinib showed efficacy in urothelial carcinoma (UC) patients harboring FGFR pathway alteration, the anti-angiogenic activity of this compound remains uncertain. Here, we investigated the suppression of UC growth by inhibiting angiogenesis with erdafitinib both in vitro and in vivo. Materials and Methods: The inhibitory effect of erdafitinib on UC cells was evaluated by wound healing assay, transwell invasion assay, and zymography assay. Tubule formation assay and transwell migration assay was conducted to assess inhibitory effect of erdafitinib on endothelial cells (EC). Transwell migration assay to assess crosstalk of EC co-cultured with UC cell was also performed. For in vivo study, athymic nude mice bearing RT4 cells were randomly divided into a control group, and erdafitinib group. Tumors were then extracted for analysis such as immunohistochemistry. Results: The results of wound healing assay and transwell invasion assay demonstrated that erdafitinib has inhibitory actions on the migratory and invasive potential of UC cells. Erdafitinib also suppressed tube formation and migratory potential of ECs. Transwell migration assay using EC co-cultured with RT4 showed that migration of EC was significantly inhibited by erdafitinib. For in vivo experiments, immuno-deficient mice (N=14) bearing RT4 xenografts were treated with or without erdafitinib (40mg/kg) orally three times a week for three weeks, and erdafitinib significantly suppressed tumor volumes and weight by 60.0% and 24.4%, respectively. The decrease of both CD31-positive and Ki-67-positive cells indicated that erdafitinib exerted anti-angiogenic activity. Conclusion: This study demonstrated that erdafitinib has anti-angiogenic activities both in vitro and in vivo. It warrants further investigation for development of new therapeutic strategy. Citation Format: Seungtaek Lim, Sun Young Rha, Hyun Joo Bae, Sang Woo Cho, Jii Bum Lee, Tae Soo Kim, Sun Kyung Kang, Woo Sun Kwon, Nam Hoon Cho, Young Deuk Choi, Kunhong Kim, Hoi Young Lee. Antiangiogenic activity of FGFR inhibitor erdafitinib in urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5972.