[Impact of Smoking on the Histological Subtype and Outcome of the Primary Lung Adenocarcinoma].
Sichuan Da Xue Xue Bao Yi Xue Ban. 2019 Dec;50(6):867-871
Authors: Xu Y, Tan WW, Fan P, Yang ZZ, Zhang S, Xi JL, Wang YX, Hu X
OBJECTIVE: To explore the effect of smoking on the histological subtype and prognosis of patients with lung adenocarcinoma (LAC) in China.
METHODS: According to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society(IASLC/ATS/ERS)classification, 266 donors with primary LAC were reclassified. The correlation between clinicopathological factors including smoking status and the histological subtype was analyzed, and survival analysis was used to analyze the prognosis of primary LAC.
RESULTS: There were four main histological subtypes including acinar predominant adenocarcinoma (APA) 30.1%, papillary predominant adenocarcinoma (PPA) 26.7%, solid predominant adenocarcinoma (SPA) 25.9%, and lepidic predominant adenocarcinoma (LPA) 11.7%.Smoking was associated with the histological subtype.The proportion of smokers was significantly higher than non-smokers in the SPA group, and the proportion of non-smokers was higher in other subtypes group. Cox regression model showed that the histological subtype and TNM stage were the independent predictors of prognostic in all patients.TNM stage was the predictor of postoperative survival in both smokers and non-smokers, and histological subtypes was the predictor only in smokers (β=0.898, RR=2.455). Compared with the non-SPA group, the prognosis of the SPA group was significantly worse.
CONCLUSION: Smoking is associated with SPA subtype, which affect the prognosis of primary LAC.
PMID: 31880119 [PubMed - indexed for MEDLINE]
[Role of microRNA-155 in Brain Metastasis of Hypoxic Lung Cancer].
Sichuan Da Xue Xue Bao Yi Xue Ban. 2019 Dec;50(6):835-839
Authors: Liu Y, Jia YS, Qin LJ
OBJECTIVE: To clarify the relationship between hypoxia stress and the microRNA-155 released from lung cancer cells, to reveal the possible mechanism of brain metastases of lung cancer.
METHODS: The hypoxia model of A549 lung cancer cells was established. Lung cancer cells were cultured under the hypoxia condition or normal oxygen condition as control for 0.5, 2, 4, 8, 12 and 24 h immunofluorescence and Western blot methods were used to determine the expression level of heat shock protein 70 (hsp70) in lung cancer cells. Hsp70 overexpressed lung cancer cell line was established, the levels of microRNA-155 in A549 and hsp70 overexpressed A549 cell culture medium were determined by qRT-PCR.An in vitro blood-brain barrier model was established, and was treated with A549 cell culture medium collected at different hypoxia time points. Horseradish peroxidase (HRP) was used to detect the changes of permeability of the in vitro blood-brain barrier model, automatic cell technical instrument was used to count A549 lung cancer cells in the culture medium in under Transwell room. Culture mediums of A549 lung cancer cells collected at different hypoxia time points were injected into rats via tail vein, Western blot was used to analyze the expression of occludin in brain tissue, Evans blue was used to detect the change of blood-brain barrier permeability in animals.
RESULTS: When lung cancer cells were hypoxic cultured for 8 h, both the expression level of hsp70 in lung cancer cells and microRNA-155 in culture medium reached the highest level (P < 0.05). Compared with A549 cells, the enhancement of microRNA-155 level in culture medium of hsp70 overexpressed cell was more notably under hypoxia condition. At the same time, the permeability of blood-brain barrier was the highest, and the number of lung cancer cells crossed the blood-brain barrier model was the most. In animal experiment, after injection the lung cancer cell culture fluid with hypoxia 8 h, the tight junction protein occludin expression in blood-brain barrier was lowest, and the permeability of blood-brain barrier was the largest.
CONCLUSION: Hypoxia can cause the increase of hsp70 production in lung cancer cells. Increased hsp70 promotes the synthesis and release of microRNA-155, which in turn leads to reduced expression of occludin protein in the blood-brain barrier, resulting in increased permeability of the blood-brain barrier and eventually causing lung cancer cells to metastasize into the brain.
PMID: 31880114 [PubMed - indexed for MEDLINE]
Development and characterization of octreotide-modified curcumin plus docetaxel micelles for potential treatment of non-small-cell lung cancer.
Pharm Dev Technol. 2019 Nov;24(9):1164-1174
Authors: An Q, Shi CX, Guo H, Xie SM, Yang YY, Liu YN, Liu ZH, Zhou CZ, Niu FJ
We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated in vitro using A549 cells, and in vivo antitumor effects were evaluated using xenograft tumor-bearing mice. In vitro assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. In vivo assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.
PMID: 31340709 [PubMed - indexed for MEDLINE]
Intratumoral delivery and therapeutic efficacy of nanoparticle-encapsulated anti-tumor siRNA following intrapulmonary administration for potential treatment of lung cancer.
Pharm Dev Technol. 2019 Nov;24(9):1095-1103
Authors: Kanehira Y, Togami K, Ishizawa K, Sato S, Tada H, Chono S
This study evaluated the delivery efficiency and antitumor effects of the intrapulmonary administration of antitumor small interfering ribonucleic acid (siRNA)-containing nanoparticles to mice with metastatic lung tumor. Fluorescence-labeled, siRNA-containing nanoparticles were administered using Liquid MicroSprayer® to mice with metastatic lung tumors induced by the murine melanoma cell line B16F10. Fluorescent signals in the whole lung and in the tumor region following the intrapulmonary administration of siRNA-containing nanoparticles were stronger than those following intravenous administration. The intrapulmonary administration of nanoparticles containing a mixture of siRNA against MDM2, c-Myc, and vascular endothelial growth factor (VEGF) significantly improved survival and prolonged the survival of mice with metastatic lung tumor. In addition, after the intrapulmonary or intravenous administration of the mixture, the activity levels of interleukin-6 and -12, markers of systemic toxicity, were similar to those of nontreatment. These results indicate that the antitumor siRNA-containing nanoparticles were delivered efficiently and specifically to tumor cells, effectively silencing the oncogenes in the lung metastasis without any significant systemic toxicity.
PMID: 31204552 [PubMed - indexed for MEDLINE]