scholarly journals D-Limonene Inhibits the Occurrence and Progression of LUAD by Suppressing Lipid Metabolism Dysregulation Induced by PM2.5 Exposure

2021 ◽  
Author(s):  
Tengteng Zhu ◽  
Yangyang Li ◽  
Tienan Feng ◽  
Yuqing Yang ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lipid Metabolism ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Preventive Intervention ◽  
Lung Epithelial Cells ◽  
Normal Lung ◽  
Lung Cancer Patients ◽  
Potential Intervention ◽  
Lipid Metabolism Disorders

Abstract Background: PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions.Methods: PM2.5 was collected near South-North elevated way in Shanghai city. Lung adenocarcinoma cells, pulmonary epithelial cell and mice were exposed to PM2.5 or D-limonene for 48h and two month separately. Cell morphology, abilities of invasion, migration and proliferation, pulmonary fibrosis level were assessed. Lipid metabolism changes were also studied in 11,564 lung cancer patients.Results: PM2.5 exposure induced accumulation of lipid droplets in LUAD cells which was accompanied by increased malignant cellular behaviors and disrupted lipid metabolism. PM2.5 exposure of LUAD led to cleaved N-SREBP1 translocation from the cytoplasm to nucleus, which upregulated the expression of FASN and ACACA. These changes increased lipid accumulation in LUAD. D-limonene, a natural monoterpene, was found to inhibit the changes in lipid metabolism through upregulating the expression of miR-195, a reported tumor suppressor that inhibited the expression of SREBP1, FASN and ACACA specifically induced by PM2.5 exposure. Same changes were also observed in normal lung epithelial cells and normal lung tissue from mice after PM2.5 exposure, and the changes were inhibited by D-limonene treatment. Furthermore, in a cohort of 11,564 lung cancer patients, significant lipid metabolism disorders were observed in high, compared to low, PM2.5 polluted areas, and a small human intervention trial showed that serum miR-195 was upregulated after oral intake of D-limonene.Conclusion: Our study reveals a potential intervention target for LUAD that is related to PM2.5 exposure-induced lipid metabolism disturbance and that D-limonene may inhibit the disruption through the upregulation of miR-195, which suggests a novel low-cost preventive intervention for people living in PM2.5 polluted regions.

scholarly journals The M1/M2 spectrum and plasticity of malignant pleural effusion-macrophage in advanced lung cancer

2020 ◽  
Author(s):  
Ming-Fang Wu ◽  
Chih-An Lin ◽  
Tzu-Hang Yuan ◽  
Hsiang-Yuan Yeh ◽  
Sheng-Fang Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Patient Outcomes ◽  
Malignant Pleural Effusion ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Anti Cancer ◽  
Cancer Activity

Abstract Background Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. Methods Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. Results We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p < 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity. Conclusions We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that “re-education” of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies.

scholarly journals Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

2020 ◽  
Vol 13 (2) ◽  
pp. 896-903
Author(s):  
Brendan Seng Hup Chia ◽  
Wen Long Nei ◽  
Sabanayagam Charumathi ◽  
Kam Weng Fong ◽  
Min-Han Tan
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Early Stage ◽  
Early Stage Disease ◽  
Lung Cancer Patients ◽  
Limited Stage ◽  
Potential Biomarker ◽  
Egfr Mutant

The use of circulating cell-free tumour DNA (ctDNA) is established in metastatic lung adenocarcinoma to detect and monitor sensitising EGFR mutations. In early-stage disease, there is very little data supporting its role as a potential biomarker. We report on a prospective cohort of 9 limited-stage EGFR mutant lung cancer patients who were treated with radical radiotherapy. We looked at baseline plasma EGFR ctDNA and noted the detection rates to be higher in locally advanced disease. At a median follow-up of 13.5 months, an association between a detectable pre-radiotherapy plasma EGFR ctDNA and early tumour relapse (155 days vs. NR, p = 0.004) was noted. One patient with persistent plasma EGFR ctDNA predated radiological progression. The role of ctDNA in early-stage lung cancer is developing. Plasma EGFR ctDNA could be a useful biomarker in lung cancer patients undergoing radical treatments for staging, prognostication, and follow-up. These preliminary findings should be explored in larger studies.

scholarly journals EP-1167 FDG-PET response in the normal lung for lung cancer patients receiving fractionated radiotherapy and erlotinib

2015 ◽  
Vol 115 ◽  
pp. S634-S635
Author(s):  
A. Abravan ◽  
I. Knudtsen ◽  
H. Eide ◽  
O. Brustugun ◽  
A. Helland ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Fdg Pet ◽  
Normal Lung ◽  
Fractionated Radiotherapy ◽  
Lung Cancer Patients

scholarly journals Overexpression of BZW1 is an independent poor prognosis marker and its down-regulation suppresses lung adenocarcinoma metastasis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jean Chiou ◽  
Yu-Chan Chang ◽  
Yi-Hua Jan ◽  
Hsing-Fang Tsai ◽  
Chih-Jen Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Leucine Zipper ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Nsclc Patient ◽  
Basic Leucine Zipper ◽  
Lung Cancer Patients

Abstract The basic leucine zipper and the W2 domain-containing protein 1 (BZW1) plays a key role in the cell cycle and transcriptionally control the histone H4 gene during G1/S phase. Since cellular proliferation rates are frequently dysregulated in human cancers, we identified the characteristics of BZW1 in cancer cells and analyzed its prognostic value in lung cancer patients. By searching public databases, we found that high BZW1 expression was significantly correlated with poor survival rate in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma. Similar trends were also shown in an array comprising NSCLC patient tissue. Knockdown of BZW1 inhibited cell metastatic ability, but did not affect the cell proliferation rate of NSCLC cells. From transcriptomics data mining, we found that coordination between BZW1 and EGFR overexpression was correlated with a worse outcome for lung cancer patients. In summary, BZW1 expression serves as an independent prognostic factor of NSCLC, especially in lung adenocarcinoma. Overexpression of BZW1 in lung cancer cells revealed a novel pathway underlying the induction of lung cancer metastasis.

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