scholarly journals Lobaplatin Enhances Radioactive 125I Seed-Induced Apoptosis and Anti-Proliferative Effect in Non-Small Cell Lung Cancer by Suppressing the AKT/mTOR Pathway

2021 ◽  
Vol Volume 14 ◽  
pp. 289-300
Author(s):  
Jia-hui Rong ◽  
Dong Li ◽  
Yu-liang Li
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Mtor Pathway ◽  
125I Seed ◽  
Small Cell Lung ◽  
Proliferative Effect ◽  
Induced Apoptosis

Effectiveness and safety of CT-guided 125I seed brachytherapy for postoperative locoregional recurrence in patients with non–small cell lung cancer

Brachytherapy ◽  
2016 ◽  
Vol 15 (3) ◽  
pp. 370-380 ◽  
Author(s):  
Xiaodong Huo ◽  
Huixing Wang ◽  
Jingkui Yang ◽  
Xiaodong Li ◽  
Weiliang Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locoregional Recurrence ◽  
Small Cell ◽  
125I Seed ◽  
Small Cell Lung ◽  
Ct Guided

scholarly journals 921 Comparison of PI3K/AKT/mTOR pathway profiles amongst three immune phenotypes classified by artificial intelligence-powered H&E analyzer in non-small cell lung cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A966-A966
Author(s):  
Hyung-Gyo Cho ◽  
Grace Lee ◽  
Hye Sung Kim ◽  
Sanghoon Song ◽  
Kyunghyun Paeng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Mtor Pathway ◽  
Small Cell Lung ◽  
Gene Set ◽  
Mtorc1 Signaling ◽  
Immune Phenotypes

BackgroundThe phosphatidylinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway plays a significant role in both tumorigenesis and progression of disease in non-small cell lung cancer (NSCLC).1 Increased activation of the pathway, whether in tumor or immune cells, results in an immunosuppressive tumor microenvironment.2 Therefore, we looked into how this pathway differs in three distinct NSCLC immune phenotypes.MethodsLunit SCOPE IO (Lunit, Seoul, Republic of Korea), a deep learning-based hematoxylin and eosin (H&E) image analytics tool, identifies lymphocytes and quantifies lymphocyte density within the cancer epithelium (CE-Lym), stroma (CS-Lym), and combined area (C-Lym). We applied Lunit-SCOPE IO to H&E-stained tissue images of 965 NSCLC samples from The Cancer Genome Atlas (TCGA). Tumors in the lowest tertile of C-Lym were labeled as immune-desert, and the remaining tumors were classified as inflamed and immune-excluded according to the median of the ratio of CE-Lym to CS-Lym.Utilizing RNA-sequencing data from TCGA, gene set enrichment analysis (GSEA) was conducted to analyze the differences in mTORC1 and PI3K/Akt/mTOR signaling between the subtypes.3 We obtained mutational data related to the PI3K/Akt/mTOR pathway from cBioPortal to compare the ratio of functional mutations between the immune phenotypes.4ResultsThe mTORC1 signaling gene set was consistently enriched in immune-excluded, whether compared to inflamed (padj < 0.01, normalized enrichment score [NES]: 2.3) or immune-desert (padj < 0.01, NES: 1.6). However, PI3K/Akt/mTOR signaling gene set enrichment did not show statistically significant differences between the immune phenotypes.Within the three immune phenotypes, we analyzed three functional mutations: PIK3CA, PTEN, and Akt1 (figure 1). Of the total 112 samples showing the functional mutations of the PI3K/Akt/mTOR pathway, 53 were immune-excluded, 31 inflamed, and 28 immune-desert. The relation between mutation frequency and the immune subtypes was significant (X2 (2) = 11.1979, p < .01). The immune-excluded was more likely than the other subtypes to have functional PI3K/Akt/mTOR mutations.Abstract 921 Figure 1The landscape of functional mutation and immune phenotypes regarding PI3K/Akt/mTOR pathwayConclusionsThe three tissue phenomic subtypes showed different PI3K/Akt/mTOR pathway profiles, with immune-excluded having the most mutation samples and the greatest enhancement of mTORC1 signaling gene set. Likewise, tissue H&E based tumor microenvironment classification by Lunit SCOPE IO can be applied to other hallmark pathways and tumor types, and such further investigation of the tumor microenvironment can provide insights into novel therapeutic avenues.ReferencesTan AC. Targeting the PI3K/Akt/mTOR pathway in non-small cell lung cancer (NSCLC). Thorac Cancer 2020;11(3):511–8.O’Donnell JS, Massi D, Teng MWL, Mandala M. PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux. Semin Cancer Biol 2018;48:91–103.Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database hallmark gene set collection. Cell Systems 2015;1(6):417–25.Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012;2(5):401–4.

scholarly journals N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5

2018 ◽  
Vol 45 (5) ◽  
pp. 2054-2070 ◽  
Author(s):  
Ye Liang ◽  
Wenhua Xu ◽  
Shihai Liu ◽  
Jingwei Chi ◽  
Jisheng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Sodium Dodecyl ◽  
Death Receptor ◽  
Small Cell ◽  
Clinical Samples ◽  
Small Cell Lung ◽  
Induced Apoptosis

Background/Aims: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL. Methods: In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo. Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5. After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting. Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope. Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC). O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown. Results: We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis. Furthermore, GlcNAc promoted DR5 clustering by improving its O-glycosylation. Conclusion: These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.

scholarly journals Trifolium Flavonoids Overcome Gefitinib Resistance of Non-Small-Cell Lung Cancer Cell by Suppressing ERK and STAT3 Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zhiqiang Wu ◽  
Bin Xu ◽  
Zhiyi Yu ◽  
Qin He ◽  
Zhuyuan Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathways ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stat3 Signaling ◽  
Induced Apoptosis ◽  
Gefitinib Resistance

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.

Proteasome Inhibition Sensitizes Non–Small-Cell Lung Cancer to Gemcitabine-Induced Apoptosis

2004 ◽  
Vol 78 (4) ◽  
pp. 1207-1214 ◽  
Author(s):  
Chadrick E. Denlinger ◽  
Brian K. Rundall ◽  
Michael D. Keller ◽  
David R. Jones
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proteasome Inhibition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Induced Apoptosis
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