Prussian Blue/Calcium Peroxide Nanocomposites-Mediated Tumor Cell Iron Mineralization for Treatment of Experimental Lung Adenocarcinoma

ACS Nano ◽  
2021 ◽  
Author(s):  
Kaixin Zhang ◽  
Jicheng Wu ◽  
Xiaoxiong Zhao ◽  
Jiale Qin ◽  
Yi Xue ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Lung Adenocarcinoma ◽  
Prussian Blue ◽  
Calcium Peroxide

Identification of the signature genes and network of Reactive Oxygen Species (ROS) related genes and DNA repair genes in Lung Adenocarcinoma (LUAD)

2021 ◽  
Author(s):  
Ye Zhao ◽  
Hai-Ming Feng ◽  
Xiao-Ping Wei ◽  
Wei-Jian Yan ◽  
Bin Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Repair ◽  
Tumor Cell ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Patient Survival ◽  
Reactive Oxygen ◽  
Dna Repair Genes ◽  
Oxygen Species ◽  
Repair Genes

Abstract Reactive Oxygen Species (ROS) are present in high amount in patients with tumors, and these ROS can kill and destroy tumor cells. Thus, tumor cells upregulate ROS-related genes to protect themselves and reduce their destruction. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. In this work, lung adenocarcinoma (LUAD) transcriptome data in the TCGA database was analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related genes and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related genes and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby increasing the growth of tumor cells and balancing the level of ROS, leading to tumor cell death and constant damage to the tumor cell repair system, thus prolonging patient survival. Thus, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX and PFKP), the risk score might be used as an independent prognostic factor in LUAD patients.

scholarly journals PPARG Drives Molecular Networks as an Inhibitor for the Pathologic Development and Progression of Lung Adenocarcinoma

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Min Zhao ◽  
Xiaoyang Li ◽  
Yunxiang Zhang ◽  
Hongming Zhu ◽  
Zhaoqing Han ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Lung Adenocarcinoma ◽  
Large Scale ◽  
Enrichment Analysis ◽  
Molecular Networks ◽  
Pathway Enrichment Analysis ◽  
Molecular Pathways ◽  
Functional Connection ◽  
Regulatory Pathways ◽  
Protein Protein Interaction

Previous studies showed that low PPARG expression was associated with poor prognosis of lung adenocarcinoma (LA) with limited mechanisms identified. We first conducted a large-scale literature-based data mining to identify potential molecular pathways where PPARG could exert influence on the pathological development of LA. Then a mega-analysis using 13 independent LA expression datasets and a Pathway Enrichment Analysis (PEA) was conducted to study the gene expression levels and the functionalities of PPARG and the PPARG-driven triggers within the molecular pathways. Finally, a protein-protein interaction (PPI) network was established to reveal the functional connection between PPARG and its driven molecules. We identified 25 PPARG-driven molecule triggers forming multiple LA-regulatory pathways. Mega-analysis using 13 LA datasets supported these pathways and confirmed the downregulation of PPARG in the case of LA (p=1.07e−05). Results from the PEA and PPI analysis suggested that PPARG might inhibit the development of LA through the regulation of tumor cell proliferation and transmission-related molecules, including an LA tumor cell suppressor MIR145. Our results suggested that increased expression of PPARG could drive multiple molecular triggers against the pathologic development and prognosis of LA, indicating PPARG as a valuable therapeutic target for LA treatment.

scholarly journals Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Coaltered Lung Adenocarcinoma

2015 ◽  
Vol 33 (32) ◽  
pp. 3701-3709 ◽  
Author(s):  
Weijing Cai ◽  
Dongmei Lin ◽  
Chunyan Wu ◽  
Xuefei Li ◽  
Chao Zhao ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Lung Adenocarcinoma ◽  
Treatment Strategies ◽  
Potential Effect ◽  
Growth Patterns ◽  
Intratumoral Heterogeneity ◽  
Egfr Mutations ◽  
Histologic Heterogeneity ◽  
Oncogenic Driver ◽  
Cell Subpopulations

Purpose Genetic intratumoral heterogeneity has a profound influence on the selection of clinical treatment strategies and on addressing resistance to targeted therapy. The purpose of this study was to explore the potential effect of intratumoral heterogeneity on both genetic and pathologic characteristics of ALK-rearranged lung adenocarcinoma (LADC). Methods We tested ALK fusions and EGFR mutations in 629 patients with LADC by using laser-capture microdissection to capture spatially separated tumor cell subpopulations in various adenocarcinoma subtypes and to test for ALK fusions and EGFR mutations in ALK-rearranged, EGFR-mutated, and ALK/EGFR coaltered LADCs to compare the oncogenic driver status between different tumor cell subpopulations in the same primary tumor. Results Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%) had EGFR mutations, and two had ALK fusions that coexisted with EGFR mutations. Intratumoral heterogeneity of ALK fusions were identified in nine patients by reverse-transcriptase polymerase chain reaction. In the two patients with an ALK/EGFR coaltered status, genetic intratumoral heterogeneity was observed both between different growth patterns and within the same growth pattern. The relative abundance of ALK and EGFR alterations was different in the same captured area. ALK fusions were positively associated with a micropapillary pattern (P = .002) and were negatively associated with a lepidic pattern (P = .008) in an expanded statistical analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients. Conclusion Intratumoral genetic heterogeneity was demonstrated to coexist with histologic heterogeneity in both single-driver and ALK/EGFR coaltered LADCs. Altered oncogenic drivers in spatially separated subclones of the same tumor may be different.

A phase I/II randomized trial using GM-CSF-producing and CD40L-expressing bystander cell line (GM.CD40L) vaccine in combination with CCL21 in stage IV lung adenocarcinoma: Preliminary results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3091-3091
Author(s):  
Jhanelle Elaine Gray ◽  
Alberto Chiappori ◽  
Charles C. Williams ◽  
Mary Colleen Pinder ◽  
Eric B. Haura ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cell ◽  
Phase I ◽  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Phase Ii ◽  
Elispot Assay ◽  
T Cell Responses ◽  
Bystander Cell ◽  
Cell Responses

3091 Background: Our GM.CD40L vaccine (an allogeneic tumor cell-based vaccine generated from human bystander cell line) recruits and activates dendritic cells, which then migrate to regional lymph nodes, where T cell activation occurs, leading to systemic tumor cell killing. The CCL21 chemokine helps to recruit T cells and leads to enhanced T cell responses. The GM.CD40L.CCL21 combination has demonstrated additive effects in NSCLC mouse models. Methods: We initiated a phase I/II randomized study to evaluate GM.CD40L (Arm A) vs. GM.CD40L.CCL21 (Arm B) in patients with lung adenocarcinoma who had failed first-line therapy. Primary endpoints were safety and tolerability of Arm B in phase I and progression-free survival (PFS) in phase II; secondary endpoints included anti-tumor immune responses/T-cell responses by ELISpot assay on PBMC. Immune-related response criteria as determined by the investigator served to determine discontinuation from study treatment. Intradermal vaccines were administered every 14 days for 3 doses and then monthly X3. A two-stage minimax design was used. Results: In phase I, 3 patients received GM.CD40L.CCL21; no dose-limiting toxicities occurred. Between 4/2012 and 12/2012, Arm A enrolled 11 and Arm B enrolled 16 patients, including those in phase I (median age: 70/67.5 years, females: 45.5%/37.5%, PS1: 54.5%/75%, median prior regimens: 3/5 for Arm A vs. Arm B, respectively). Most common toxicities for Arm A vs. Arm B were injection site reaction (45.5%/43.8%), fatigue (9.1%/37.5%), anorexia (0%/12.5%), and pain in extremity (0%/12.5%). Median PFS for Arm A vs. B was 4.4 vs. 4.4 months (p=0.37). Of the 6 patients who remained on study post RECIST v1.1 progression, all demonstrated further progression on subsequent scans and were removed from the study. Of patients evaluable for efficacy, stable disease was 3/7 and progressive disease was 6/7 for Arm A vs. Arm B, respectively. Analyses of ELISpot assay on the PBMC are underway. Conclusions: GM.CD40L.CCL21 vaccine is well tolerated; thus far, median PFS results are similar to GM.CD40L vaccine. Updated results of the phase II trial will be presented. Clinical trial information: NCT01433172.

scholarly journals A novel BMX variant promotes tumor cell growth and migration in lung adenocarcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (20) ◽  
pp. 33405-33415 ◽  
Author(s):  
Ye Wang ◽  
Jufeng Xia ◽  
Zhaoyuan Fang ◽  
Fei Li ◽  
Duo Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Lung Adenocarcinoma ◽  
Tumor Cell Growth ◽  
Cell Growth And Migration ◽  
And Migration
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