scholarly journals A Preclinical Evaluation of Antimycin A as a Potential Antilung Cancer Stem Cell Agent

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Chi-Tai Yeh ◽  
Chun-Li Su ◽  
Chi-Ying F. Huang ◽  
Justin Kung-Yi Lin ◽  
Wei-Hwa Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Side Population ◽  
A549 Cells ◽  
Antimycin A ◽  
Lung Cancer Patients ◽  
Tumor Sphere ◽  
Lung Cancer Stem Cells ◽  
Sphere Formation

Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs) as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP) method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs), was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA), was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog,β-catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppressβ-catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulateβ-catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.

scholarly journals Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

Oncotarget ◽  
2017 ◽  
Vol 8 (40) ◽  
pp. 67056-67081 ◽  
Author(s):  
Leonel Armas-López ◽  
Patricia Piña-Sánchez ◽  
Oscar Arrieta ◽  
Enrique Guzman de Alba ◽  
Blanca Ortiz-Quintero ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Cancer Drug ◽  
Lung Cancer Patients ◽  
Cancer Drug Resistance

Detecting ultra low-frequency variants and gene fusions in lung cancer patients using an amplicon-based Firefly NGS method.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23062-e23062
Author(s):  
Li Weng ◽  
Lin Wang ◽  
Xiao Chen ◽  
Jacey Zhang ◽  
Chiahui Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Cancer Patients ◽  
Allele Frequency ◽  
Sensitivity And Specificity ◽  
Low Frequency ◽  
Analytical Sensitivity ◽  
Gene Fusions ◽  
Lung Cancer Patients

e23062 Background: The analysis of EGFR, KRAS, and BRAF mutations and Alk fusion is critical for guiding targeted therapy selection, detecting drug resistance, and monitoring residual disease in patients with NSCLC. Designing next-generation sequencing (NGS) assays for detecting low-frequency variants, however, is an ongoing challenge. The limited availability of cfDNA combined with the breadth of coverage necessary to create meaningful, clinically-actionable results requires a solution with multiplex capacity which, in turn, requires greater technological sensitivity and specificity. Here we aim to develop such a solution: an ultra-accurate NGS technology using concatmer-based error correction with amplicon workflow for fast detection of rare mutations including SNV and fusion. Methods: We developed an amplicon-based panel covering variants of EGFR, BRAF, and KRAS, as well as a panel to detect Alk fusion. CfDNA simulate and cfDNA from healthy individuals were used to test assay sensitivity and specificity. Further validation was performed via a comparative analysis of 64 late-stage lung cancer patients using both Firefly -Comet and ddPCR. Results: Analytical sensitivity of the EGFR-TKI 3-gene panel was 100% detection at an allele frequency of 0.1% for 20ng of cfDNA input. Similarly, analytical sensitivity of the Alk fusion panel was 75% detection at an allele frequency of 0.1% and 100% at an allele frequency of 0.25% for the same input. Among our patient cohort, 5 EGFR variants (19del, T790M, L858R, G719X, L861X) and 2 KRAS variant (G12X) were detected. Firefly-Comet demonstrated strong per-variant detection-rate concordance ( > 99%) compared to ddPCR results. The PPV is 100% and the NPV is 98.7%. Statistical analysis of reported allele frequency concordance between Firefly-Comet and ddPCR reveals R-Sq > 0.9. Conclusions: In summary, we have developed Firefly-Comet, an easy-to-use amplicon-based NGS assay capable of detecting single-digit copies of somatic mutants and gene fusions in cfDNA. The multiplex capacity of Firefly-Comet makes it well-suited for supporting targeted therapy selection, drug resistance detection, and treatment monitoring.

scholarly journals Gene expression profile of A549 cells from tissue of 4D model predicts poor prognosis in lung cancer patients

2013 ◽  
Vol 134 (4) ◽  
pp. 789-798 ◽  
Author(s):  
Dhruva K. Mishra ◽  
Chad J. Creighton ◽  
Yiqun Zhang ◽  
Don L. Gibbons ◽  
Jonathan M. Kurie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cancer Patients ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Poor Prognosis ◽  
A549 Cells ◽  
Lung Cancer Patients

Analysis of Flora Distribution and Drug Resistance in Sputum Culture from Patients with Lung Cancer

2013 ◽  
Vol 641-642 ◽  
pp. 625-629
Author(s):  
Feng Hao ◽  
Rui Ze Ma ◽  
Xue Yan Wang ◽  
Hui Jing Xu ◽  
Fang Fang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Culture Method ◽  
Sputum Culture ◽  
High Drug ◽  
Lung Cancer Patients ◽  
Resistance To Penicillin ◽  
And Control

Abstract. Lung cancer takes the first place among all the cancer mortality and then it becomes important to study how to use antibiotics reasonably during clinical treating. Now we analyze lung cancer patients’ sputum samples Flora distribution and drug resistance and results are as follows. According to retrospective study, we analyzed lung cancer patients and identify the bacterial with routine sputum culture method strictly. At the same time, we use SPSS 19.0 soft to take a statistical analysis and judge flora drug resistance with CLSI. In the sputum culture , the rate of G- bacillus is 69.1% and it has high drug-resistance to cephalosporin, ampicillin and piperacillin, and it is sensitive to imipenem fairly.The rate of G+ coccus is 10.1% and it is resistance to penicillin, ampicillin , oxacillin and erythromycin ,and is sensitive to vancomycin . The rate of fungi is 20.8% and has obvious resistance to Pyrroles. The clinic should care more about the quality of the sputum samples, use targeted and reasonable antibiotics and control the flora drug-resistance .

scholarly journals Upregulation of SPP1 Is a Marker for Poor Lung Cancer Prognosis and Contributes to Cancer Progression and Cisplatin Resistance

2021 ◽  
Vol 9 ◽  
Author(s):  
Huaping Tang ◽  
Jianyou Chen ◽  
Xiaolei Han ◽  
Yan Feng ◽  
Fang Wang
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Cancer Patients ◽  
A549 Cells ◽  
High Expression ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Tumor Growth Rate ◽  
Clinical Prognosis ◽  
Lung Cancer Patients

The chemoresistance of lung cancer is a significant contributor to its high mortality and morbidity rate. There is an urgent need to identify differentially expressed genes in lung cancer patients with a poor prognosis to develop effective means to overcome drug resistance in subsequent treatment. In this study, we identified the secreted phosphoprotein 1 (SPP1) as a potential gene associated with a poor diagnosis of lung cancer patients using the Cancer Genome Atlas analysis, which suggested that the expression of SPP1 in tumor tissues was significantly higher than normal tissues. The high expression of SPP1 was also correlated with tumor grade and poor clinical prognosis. To understand the roles of SPP1 and the DNA methyltransferase 1 (DNMT1), which regulated SPP1 expression, in affecting cell viability, migration and invasion, SPP1 and DNMT1 were overexpressed in the human lung cancer A549 and NCI-446 cells, followed by analyzing cell viability, migration and invasion. We showed that SPP1 promoted the proliferation, migration and invasion of lung cancer cells, and increased the resistance of lung cancer to the chemotherapeutic drug cisplatin. Knocking down SPP1 in cells restored sensitivity to cisplatin. Further, A549 cells without SPP1 overexpression demonstrated lower tumor growth rate than SPP1 overexpression cells using the xenograft tumor mouse model. High expression of SPP1 in lung cancer tumor tissue was caused by the reduced methylation level of its promoter region mediated by DNMT1. Our data suggested that SPP1 can be used as a marker for highly malignant lung cancer and targeting SPP1 may be a potential lung cancer treatment strategy.

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