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Background: Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by irreversible scarring of the lung parenchyma. Despite various interventions aimed at mitigating several different molecular aspects of the disease, only two drugs with limited clinical efficacy have so far been approved for IPF therapy. Objective: We investigated the therapeutic efficacy of amifostine, a detoxifying drug clinically used for radiation-caused cytotoxicity, in bleomycin-induced murine pulmonary fibrosis. Methods: C57BL6/J mice were intratracheally instilled with 3 U/kg of bleomycin. Three doses of amifostine (WR-2721, 200 mg/kg) were administered intraperitoneally on days 1, 3, and 5 after the bleomycin challenge. Bronchoalveolar lavage fluid (BALF) was collected on day 7 and day 21 for the assessment of lung inflammation, metabolites, and fibrotic injury. Human fibroblasts were treated in vitro with transforming growth factor beta 1 (TGF-β1), followed by amifostine (WR-1065, 1–4 µg/mL) treatment. The effects of TGF-β1 and amifostine on the mitochondrial production of reactive oxygen species (ROS) were assessed by live cell imaging of MitoSOX. Cellular metabolism was assessed by the extracellular acidification rate (ECAR), the oxygen consumption rate (OCR), and the concentrations of various energy-related metabolites as measured by mass spectrum (MS). Western blot analysis was performed to investigate the effect of amifostine on sirtuin 1 (SIRT1) and adenosine monophosphate activated kinase (AMPK). Results: Three doses of amifostine significantly attenuated lung inflammation and pulmonary fibrosis. Pretreatment and post-treatment of human fibroblast cells with amifostine blocked TGF-β1-induced mitochondrial ROS production and mitochondrial dysfunction in human fibroblast cells. Further, treatment of fibroblasts with TGF-β1 shifted energy metabolism away from mitochondrial oxidative phosphorylation (OXPHOS) and towards glycolysis, as observed by an altered metabolite profile including a decreased ratio of NAD + /NADH and increased lactate concentration. Treatment with amifostine significantly restored energy metabolism and activated SIRT1, which in turn activated AMPK. The activation of AMPK was required to mediate the effects of amifostine on mitochondrial homeostasis and pulmonary fibrosis. This study provides evidence that repurposing of the clinically used drug amifostine may have therapeutic applications for IPF treatment. Conclusion: Amifostine inhibits bleomycin-induced pulmonary fibrosis by restoring mitochondrial function and cellular metabolism. [ABSTRACT FROM AUTHOR]

Background: Tumor heterogeneity and clonal evolution are related to the treatment resistance and disease progression in metastatic breast cancer (MBC). However, the process of clonal evolution and their relationship to prognosis remain unclear. This study aimed to elucidate the evolution of MBC through circulating tumor DNA (ctDNA) analysis and to develop a novel indicator for predicting treatment efficacy and prognosis., Methods: This multicenter retrospective study enrolled MBC patients who underwent next-generation sequencing between April 2016 and October 2022. The clonal evolution of tumors was inferred using PyClone and CITUP software., Results: The study included 406 MBC patients. A cohort of 139 patients from the National Cancer Center served as the training cohort, while 267 patients from other centers comprised the validation cohort. In the training cohort, clonal analysis revealed that most MBCs exhibited branched clonal evolution, while a minority showed linear evolution. The branched evolution pattern was associated with slower disease progression (HR, 0.53; 95% CI, 0.32-0.87; P = 0.012). We introduced tumor clonal evolution rate (TER) as a novel concept to reflect the speed of clonal evolution. Survival analysis demonstrated that compared to the TER-high group, patients in the TER-low group had better progression-free survival (PFS) (HR, 0.62; 95% CI, 0.40-0.96; P = 0.033) and overall survival (OS) (HR, 0.45; 95% CI, 0.24-0.85; P = 0.013). Similarly, in the validation cohort, although the median OS was not reached, patients in the TER-low group had better prognosis compared to those in the TER-high group (HR, 0.41; 95% CI, 0.21-0.83; P < 0.001)., Conclusions: Patients with branched evolution have better treatment efficacy than those with linear evolution. The TER shows potential as a biomarker for treatment efficacy and prognosis, providing new evidence that ctDNA is a valuable molecular indicator for predicting treatment outcomes in metastatic breast cancer., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Review Board of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital (Approval No.16–038/1117). All patients provided written informed consent to participate in the biomarker analysis study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: The aim of this article was to determine outcomes in patients with squamous cell carcinoma of the hypopharynx (SCCHP) in whom the free posterior tibial flap was used for primary reconstruction of hypopharynx defects after cancer resection., Subjects and Methods: Between August 2009 and February 2012, 10 patients with SCCHP underwent posterior tibial flap reconstruction for hypopharynx defects. The corresponding clinical data were retrospectively collected and analyzed., Results: Despite the multistep and time-consuming procedure, the posterior tibial flap survival rate was 100%. Operation-induced complications did not occur in four patients. Six patients developed postoperative hypoproteinemia, four patients developed postoperative pulmonary infections, and four patients developed pharyngeal fistula. The pharyngeal and laryngeal functions of all patients were preserved., Conclusion: Our experience demonstrates that the posterior tibial flap is a safe and reliable choice for the reconstruction of hypopharynx defects.