Melatonin and verteporfin synergistically suppress the growth and stemness of head and neck squamous cell carcinoma through the regulation of mitochondrial dynamics

The prevalence of head and neck squamous cell carcinoma (HNSCC) has continued to rise for decades. However, drug resistance to chemotherapeutics and relapse, mediated by cancer stem cells (CSCs), remains a significant impediment in clinical oncology to achieve successful treatment. Therefore, we focused on analyzing CSCs in HNSCC and demonstrated the effect of melatonin (Mel) and verteporfin (VP) on SCC-25 cells. HNSCC CSCs were enriched in the reactive oxygen species-low state and in sphere-forming cultures. Combination treatment with Mel and VP decreased HNSCC viability and increased apoptosis without causing significant damage to normal cells. Sphere-forming ability and stem cell population were reduced by co-treatment with Mel and VP, while mitochondrial ROS level was increased by the treatment. Furthermore, the expression of mitophagy markers, parkin and PINK1, was significantly decreased in the co-treated cells. Mel and VP induced mitochondrial depolarization and inhibited mitochondrial function. Parkin/TOM20 was localized near the nucleus and formed clusters of mitochondria in the cells after treatment. Moreover, Mel and VP downregulated the expression of markers involved in epithelial-mesenchymal transition and metastasis. The migration capacity of cells was significantly decreased by co-treatment with Mel and VP, accompanied by the down-regulation of MMP-2 and MMP-9 expression. Taken together, these results indicate that co-treatment with Mel and VP induces mitochondrial dysfunction, resulting in the apoptosis of CSCs. Mel and VP could thus be further investigated as potential therapies for HNSCC through their action on CSCs.     

Role of Elective Nodal Irradiation in Patients With ypN0 After Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery (KROG 16-16)

Background

Given the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status.

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Blood lead level and Helicobacter pylori infection in a healthy population: A cross-sectional study

Abstract

The aim of this study was to investigate whether elevated blood lead level (BLL) is a risk factor for Helicobacter pylori infection. Upper gastrointestinal endoscopy was performed on 2,625 subjects who visited a university hospital for general health examination. H. pylori infection was detected using histologic examination with Giemsa staining, and BLLs were measured. The mean BLL was 2.83?±?1.31?μg/dL. The prevalence of H. pylori infection was 27.8%. The BLL was significantly higher in the H. pylori infection-positive group compared to the non-infected group (2.96?±?1.33?μg/dL vs. 2.78?±?1.30?μg/dL, p?<?0.001), which remained significant after adjusting for other confounders. H. pylori infection significantly increased as the BLL increased (OR: 1.143, 95% CI 1.068–1.223). We found a relationship between BLL elevation and H. pylori infection rate.     

Decorin‐expressing adenovirus decreases collagen synthesis and upregulates MMP expression in keloid fibroblasts and keloid spheroids

Decorin is a natural transforming growth factor‐β1 (TGF‐β1) antagonist. Reduced decorin synthesis is associated with dermal scarring, and increased decorin expression appears to reduce scar tissue formation. To investigate the therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and keloid‐derived fibroblasts (KFs) were transduced with decorin‐expressing adenovirus (dE1‐RGD/GFP/DCN), and we examined the therapeutic potential of decorin‐expressing Ad for treating pathologic skin fibrosis. Decorin expression was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were transduced with dE1‐RGD/GFP/DCN or control virus, and protein levels of decorin, epidermal growth factor receptor (EGFR) and secreted TGF‐β1 were assessed by Western blotting and ELISA. And type I and III collagen, and matrix metalloproteinase‐1 (MMP‐1) and matrix metalloproteinase‐3 (MMP‐3) mRNA levels were measured by real‐time RT‐PCR. Additionally, we immunohistochemically investigated the expression levels of the major extracellular matrix (ECM) proteins in keloid spheroids transduced with dE1‐RGD/GFP/DCN. Lower decorin expression was observed in the keloid region compared to adjacent normal tissues. After treatment with dE1‐RGD/GFP/DCN, secreted TGF‐β1 and EGFR protein expressions were decreased in TGF‐β1‐treated HDFs and KFs. Also, type I and III collagen mRNA levels were decreased, and the expression of MMP‐1 and MMP‐3 mRNA was strongly upregulated. In addition, the expression of type I and III collagen, fibronectin and elastin was significantly reduced in dE1‐RGD/GFP/DCN‐transduced keloid spheroids. These results support the utility of decorin‐expressing adenovirus to reduce collagen synthesis in KFs and keloid spheroid, which may be highly beneficial in treating keloids.     

Improved treatment outcome of pembrolizumab in patients with nonsmall cell lung cancer and chronic obstructive pulmonary disease

Emerging immune profiling data suggest a higher sensitivity to immune checkpoint inhibitors (ICIs) in nonsmall cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), compared to those without COPD. This study aimed to investigate the clinical impact of COPD on the treatment response to ICIs in a large number of patients with NSCLC. In total, 133 patients with spirometry test results were retrospectively identified among those who received palliative pembrolizumab for NSCLC. COPD was defined as pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.7. Overall survival (OS), progression-free survival (PFS), and objective response rate were analyzed according to the presence of COPD. Spirometry-based COPD was present in 59 (44%) patients. Patients with COPD had better OS (hazard ratio [HR] for death, 0.45; 95% confidence interval [CI], 0.26–0.78) and PFS (HR for disease progression or death, 0.50; 95% CI, 0.31–0.79) than those without COPD. These associations persisted after adjusting for potential confounders including smoking history. The response rate was also higher in patients with COPD than in those without COPD (38.2% vs. 20.5%, p = 0.028). Spirometry-defined COPD was associated with a significantly longer OS and PFS in patients with NSCLC treated with palliative pembrolizumab. Identifying coexisting COPD could predict favorable treatment outcomes in patients with NSCLC treated with pembrolizumab.