Co-delivery of cisplatin and paclitaxel by folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles for the treatment of non-small lung cancer

Objectives: Video assisted thoracoscopic surgery (VATS) can currently be used to diagnose and treat pulmonary nodules. However, intraoperative location of pulmonary nodules in VATS is challenging due to their small diameter and deep location in the pulmonary parenchyma. The purpose of this study was to report the clinical safety and effectiveness of CT-guided hook-wire for preoperative localization of malignant pulmonary nodules smaller than 1 cm in diameter. Methods: From February 2017 to January 2018, we collected the data of 80 patients with malignant pulmonary nodules less than 1 cm in diameter who underwent CT-guided hook-wire preoperative localization and VATS surgery. The effectiveness of preoperative localization was evaluated based on surgical duration, success rate of VATS surgery, and localization-related complications. Results: The diameter of pulmonary nodules were 0.85 ± 0.17 mm with a distance to the pleural surface of 19.66 ± 14.10 mm. The length of the hook-wire in the lung parenchyma was 29.17 ± 13.14 mm and hook-wire dislodgement occurred in 2 patients. Complications included 27 cases of minor pneumothorax and 18 cases of mild parenchymal hemorrhage. A significant correlation was observed between the length of the hook-wire in the lung parenchyma and mild parenchymal hemorrhage (P = 0.044). The average time of hook-wire localization was 9.0 ± 2.6 min and the average operation time for VATS was 89.02 ± 23.35 min without conversion thoracotomy. Conclusions: CT-guided hook-wire localization of the lesion during VATS resection is safe for malignant pulmonary nodules with diameter less than 1 cm.

Introduction: Cranial radiotherapy (CRT) is the main treatment for non-small cell lung cancer (NSCLC) with brain metastasis (BM) and non-EGFR/ALK/ROS1-TKIs indication, and anlotinib can improve overall prognosis. However, the clinical effects of CRT combined with anlotinib for the treatment of NSCLC with BM remain unclear. Methods: We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone in NSCLC patients with BM and non-EGFR/ALK/ROS1-TKIs indication from September 2016 to June 2020. The progression-free survival (PFS) and overall survival (OS) of anlotinib + CRT versus CRT alone were analyzed. After evaluation of the clinical characteristics to generate a baseline, the independent prognostic factors for intracranial PFS (iPFS) and OS were subjected to univariate and multivariate analysis. Finally, subgroup analysis for iPFS and OS was performed to assess treatment effects using randomized stratification factors and stratified Cox proportional hazards models. Results: This study included data for 73 patients with BM at baseline. Of the 73 patients, 45 patients received CRT alone, and 28 patients received CRT + anlotinib. There was no significant difference in clinical features between the two groups (P > 0.05). Compared with the CRT group, the combined group had longer iPFS (median iPFS [miPFS]: 3.0 months vs 11.0 months, P = 0.048). However, there were no significant differences in OS, extracranial PFS, and systemic PFS. For clinical features, univariate and multivariate analysis showed that the plus anlotinib treatment was an independent advantage predictor of iPFS (hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.27– 0.95; P = 0.04), and age ≥ 57 years (HR 1.04, 95% CI 1.01– 1.08, P = 0.014) and KPS score ≤ 80 (HR 1.04, 95% CI 1.01– 1.08, P = 0.014) were independent disadvantage predictors of OS (P < 0.05). In addition, although this difference was not statistically significant (p > 0.05), the patients with the anlotinib + local CRT (LCRT) treatment had the longest iPFS (miPFS: 27.0 months) and OS (median OS [mOS]: 36 months). The miPFS and mOS values for the LCRT group were 11 months and 18 months, respectively, with shorter values for whole-brain RT (WBRT) + anlotinib group, WBRT + LCRT + anlotinib group, WBRT, and WBRT + LCRT. Conclusion: Anlotinib can improve the intracranial lesion control and survival prognosis of NSCLC patients with CRT.

Background: Preoperative localization is challenging due to the small diameter of pulmonary nodules or their deep location in the lung parenchyma during VATS surgery. The purpose of this study was to compare the efficacy and safety of both hook-wire and medical glue for pre-operative localization of pulmonary nodules.Methods: In the current study, 158 patients were retrospectively analyzed (January 2019 and January 2020). The patients underwent hook-wire or medical glue for pre-operative localization of pulmonary nodules. Among them, 74 patients in the hook-wire group and 84 patients in the medical glue group underwent VATS anatomic segmentectomy or wedge resection after localization of pulmonary nodules. Pre-operative localization data from all patients were compiled. Moreover, the efficacy and safety of the two methods were evaluated according to localization success rates and localization-related complications.Results: The success rate of localization in the medical glue group was 100% while 97.3% in the hook-wire group. After localization of the pulmonary nodules, the incidence of minor pneumothorax in the medical glue group (11.9%) was lower than that in the hook-wire group (37.8%) (p=0.01). The incidence of mild pulmonary parenchymal hemorrhage in the medical glue group (13.1%) was also lower than that in the hook-wire group (24.3%) (p=0.000). The mean time from the completion of localization to the start of surgery was also longer in the medical glue group than in the hook-wire group (p=0.000). The mean visual analog scale (VAS) scores after localization were higher in the hook-wire group than in the medical glue group (p=0.02). In both groups, parenchymal hemorrhage was significantly associated with the needle length in hook-wire localization and the depth of the medical glue in the lung parenchyma (p = 0.009 and 0.001, respectively).Conclusion: These two localization methods are safe and effective in pre-operative pulmonary nodule localization. The medical glue localization method had a lower risk of complications, a higher localization success rate, less pain after localization and more flexibility in the arrangement of operation time.

Metastasis of cancer is the main cause of death in many types of cancer. Acute shear stress (ASS) is an important part of tumor micro-environment, it plays a crucial role in tumor invasion and spread. However, less is known about the role of ASS in tumorigenesis and metastasis of NSCLC. In this study, NSCLC cells were exposed to ASS (10 dyn/cm²) to explore the effect of ASS in regulation of autophagy and exosome mediated cell survival. Finally, the influence of SIRT2 on NSCLC cell metastasis was verified in vivo. Our data demonstrates that ASS promotes exosome and autophagy components releasing in a time dependent manner, inhibition of exosome release exacerbates ASS induced NSCLC cell apoptosis. Furthermore, we identified that this function was regulated by sirtuin 2 (SIRT2). And, RNA immunoprecipitation (RIP) assay suggested SIRT2 directly bound to the 3′UTR of transcription factor EB (TFEB) and facilitated its mRNA stability. TFEB is a key transcription factor involved in the regulation of many lysosome related genes and plays a critical role in the fusion of autophagosome and lysosome. Altogether, this data revealed that SIRT2 is a mechanical sensitive protein, and it regulates ASS induced cell apoptosis by modulating the release of exosomes and autophagy components, which provides a promising strategy for the treatment of NSCLCs.

Thymosin beta 4 (Tβ4), a pleiotropic actin-sequestering polypeptide that is involved in wound healing and developmental processes, has been reported to be strongly associated with tumorigenesis. A recent tissue microarray analysis showed that Tβ4 was highly expressed in certain tumor cells, including lung cancer. However, the exact expression pattern and the role of Tβ4 in non-small cell lung cancer (NSCLC) have not to our knowledge been investigated. In the present study, we confirmed that Tβ4 expression was increased in NSCLC tissues and cell lines. Tβ4 gene silencing in A549 and H1299 cells inhibited cell proliferation, migration, and invasion in vitro and decreased tumor growth in vivo. Mechanistic investigations revealed a significant decrease in Notch1 activation in Tβ4 gene-silenced cells. Moreover, restoring the Notch1 expression attenuated the function of Tβ4 silencing in NSCLC cells. Taken together, these findings suggest that Tβ4 may play an oncogenic role in NSCLC progression and may be a novel molecular target for anti-NSCLC therapy.