METTL14 enhances the m6A modification level of lncRNA MSTRG.292666.16 to promote the progression of non-small cell lung cancer.

Background: m6A modification has close connection with the occurrence, development, and prognosis of tumors. This study aimed to explore the roles of m6A modification and its related mechanisms in non-small cell lung cancer (NSCLC).

Methods: NSCLC tissues and their corresponding para-cancerous tissues were collected to determine the m6A levels of total RNA/lncRNAs and the expression of m6A modification-related genes/lncRNAs.

DNMT3A governs tyrosine kinase inhibitors responses through IAPs and in a cell senescence-dependent manner in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis.

Temporal genomic heterogeneity guiding individualized therapy in recurrent non-small cell lung cancer.

Introduction: Despite the benefit of adjuvant systemic therapy for patients with resected non-small cell lung cancer (NSCLC), the risk of postoperative recurrence remains high. Our objective was to characterize temporal genetic heterogeneity between primary resected and recurrent tumors, and its impact on treatment outcomes.

Methods: In this study, next-generation sequencing (NGS) testing was performed on tissue specimens and circulating tumor DNA (ctDNA) collected at postoperative recurrence, and results were compared to the genotypes of initial surgical specimens.

Exosomes derived from M2 type tumor-associated macrophages promote osimertinib resistance in non-small cell lung cancer through MSTRG.292666.16-miR-6836-5p-MAPK8IP3 axis.

Background: Osimertinib resistance limits the treatment of epidermal growth factor receptor-(EGFR)-mutated non-small-cell lung carcinoma (NSCLC). The mechanisms of osimertinib resistance need to be elucidated to determine alternative treatment strategies. This study explores the role of M2 type tumor-associated macrophage (TAM)-derived exosomal MSTRG.

Exosomal long non-coding RNA MSTRG.292666.16 is associated with osimertinib (AZD9291) resistance in non-small cell lung cancer.

Acquired resistance of osimertinib is encountered in clinic treatment of non-small cell lung cancer (NSCLC). However, the molecular mechanisms of osimertinib resistance are not fully revealed. This study aimed to investigate the roles of exosomes in delivering osimertinib resistance in NSCLC.

Cyclooxygenase-2 mediates gefitinib resistance in non-small cell lung cancer through the EGFR/PI3K/AKT axis.

Gefitinib is a potent inhibitor of EGFR and represents the front-line treatment for non-small cell lung cancer (NSCLC) therapeutics. However, NSCLC patients are prone to develop acquired resistance through as yet, undefined mechanisms of resistance. Here, we investigated the role of COX-2 during gefitinib resistance in NSCLC cells and revealed its underlying mechanism(s) of action.

A novel virtual barcode strategy for accurate panel-wide variant calling in circulating tumor DNA.

Background: Hybrid capture-based next-generation sequencing of DNA has been widely applied in the detection of circulating tumor DNA (ctDNA). Various methods have been proposed for ctDNA detection, but low-allelic-fraction (AF) variants are still a great challenge. In addition, no panel-wide calling algorithm is available, which hiders the full usage of ctDNA based 'liquid biopsy'.

Detection of plasma EGFR mutations for personalized treatment of lung cancer patients without pathologic diagnosis.

Introduction: Next-generation sequencing (NGS) and digital polymerase chain reaction (PCR) based platforms have been used to detect EGFR mutations in plasma circulating tumor DNA (ctDNA) with high accuracy. Generally, molecular testing is performed after histopathological analysis. However, many patients with suspected advanced nonsmall cell lung cancer are unable to undergo biopsy thus forgoing potential treatment with highly effective tyrosine kinase inhibitors (TKIs) in patients with sensitizing EGFR mutations.

Predictive value of unmethylated RASSF1A on disease progression in non-small cell lung cancer patients receiving pemetrexed-based chemotherapy.

Background And Objective: Chemotherapy remains the basis of the treatment of lung cancer, and screening biomarkers with predictive value for chemotherapy is of great interest. The present study focused on status of genes methylation in NSCLC patients receiving pemetrexed- or gemcitabine-based chemotherapy.

Patients And Methods: Promoter methylation of Ras association domain family (RASSF1A) and short stature homeobox 2 (SHOX2) was examined in bronchoalveolar lavage (BAL) from 117 NSCLC patients treated with chemotherapy.

Competitive evolution of NSCLC tumor clones and the drug resistance mechanism of first-generation EGFR-TKIs in Chinese NSCLC patients.

Purpose: Although many studies have reported on the resistance mechanism of first-generation EGFR TKIs (1 EGFR TKIs) treatment, large-scale dynamic ctDNA mutation analysis based on liquid biopsy for non-small cell lung cancer (NSCLC) in the Chinese population is rare. Using in-depth integration and analysis of ctDNA genomic mutation data and clinical data at multiple time points during the treatment of 53 NSCLC patients, we described the resistance mechanisms of 1 EGFR TKIs treatment more comprehensively and dynamically. The resulting profile of the polyclonal competitive evolution of the tumor provides some new insights into the precise treatment of NSCLC.

Engineering docetaxel-loaded micelles for non-small cell lung cancer: a comparative study of microfluidic and bulk nanoparticle preparation.

Bulk preparation of micelles has the drawbacks of facile formation of large aggregates and heterogeneous particle size distribution. Microfluidic technology has shown clear potential to address these challenges for robust nanomedicine applications. In this study, docetaxel-loaded PLGA-PEG-Mal-based micelles were prepared by microfluidics and dialysis methods and their physicochemical properties were analyzed.

The Evolution and Expression Pattern of Human Overlapping lncRNA and Protein-coding Gene Pairs.

Long non-coding RNA overlapping with protein-coding gene (lncRNA-coding pair) is a special type of overlapping genes. Protein-coding overlapping genes have been well studied and increasing attention has been paid to lncRNAs. By studying lncRNA-coding pairs in human genome, we showed that lncRNA-coding pairs were more likely to be generated by overprinting and retaining genes in lncRNA-coding pairs were given higher priority than non-overlapping genes.

Cancer-Related Triplets of mRNA-lncRNA-miRNA Revealed by Integrative Network in Uterine Corpus Endometrial Carcinoma.

The regulation of transcriptome expression level is a complex process involving multiple-level interactions among molecules such as protein coding RNA (mRNA), long noncoding RNA (lncRNA), and microRNA (miRNA), which are essential for the transcriptome stability and maintenance and regulation of body homeostasis. The availability of multilevel expression data enables a comprehensive view of the regulatory network. In this study, we analyzed the coding and noncoding gene expression profiles of 301 patients with uterine corpus endometrial carcinoma (UCEC).

SPOP promotes SIRT2 degradation and suppresses non-small cell lung cancer cell growth.

SIRT2 is a NAD-dependent deacetylase and inhibition of SIRT2 has a broad anticancer activity. Here we report that SPOP binds to SIRT2 and mediates its degradation by the 26S proteasome, which can be blocked by MG132 treatment. We also found that the levels of SPOP significantly decreased, while the levels of SIRT2 significantly increased in non-small cell lung cancer (NSCLC) cell lines, compared to normal bronchial epithelial cell line and NSCLC specimens, compared to the paired non-tumor lung tissue.

[Relationship between ID1 and EGFR-TKI Resistance in Non-small Cell Lung Cancer].

Background: Non-small cell lung cancer (NSCLC) presents the highest morbidity and mortality among malignant tumors worldwide. The overall effective rate of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is 30% to 40%, and PFS (progression-free sruvival) is 12 months. However, EGFR-TKI resistance is typical in clinical observations, and this phenomenon significantly affects tumor suppression.

Shorter EGFR Dinucleotide Repeat Length Predicts Better Response of Patients with Advanced Non-small Cell Lung Cancer to EGFR Tyrosine Kinase Inhibitor.

The purpose of this study is to evaluate the association between intron 1 CA-repeat polymorphisms of the epidermal growth factor receptor gene (EGFR) and the clinical outcome of Chinese patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). We genotyped the intron 1 CA-repeat genetic polymorphisms of EGFR in 84 Chinese patients with NSCLC. The relationship between the length of the CA repeats and EGFR mutations in exons 18-21 in the 84 patients was elucidated.

Overexpression of miR-100 inhibits cancer growth, migration, and chemosensitivity in human NSCLC cells through fibroblast growth factor receptor 3.

Nonsmall cell lung cancer (NSCLC) is a commonly occurring lung cancer. A combination of molecular biological treatments with regular chemotherapy may result in improved therapeutic outcome. Here, we reported significantly higher levels of fibroblast growth factor receptor 3 (FGFR3) and significantly lower levels of miR-100 in the NSCLC specimen, compared to the paired NSCLC-adjacent normal lung tissues.

Rapamycin Enhances the Anti-Cancer Effect of Dasatinib by Suppressing Src/PI3K/mTOR Pathway in NSCLC Cells.

Src and the mammalian target of rapamycin (mTOR) signaling are commonly activated in non-small cell lung cancer (NSCLC) and hence potential targets for chemotherapy. Although the combined use of Src inhibitor Dasatinib with other chemotherapeutic agents has shown superior efficacy for cancer treatment, the mechanisms that lead to enhanced sensitivity of Dasatinib are not completely understood. In this study, we found that Rapamycin dramatically enhanced Dasatinib-induced cell growth inhibition and cell cycle G1 arrest in human lung adenocarcinoma A549 cells without affecting apoptosis.

Mechanisms behind the inhibition of lung adenocarcinoma cell by shikonin.

Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, can exert inhibitory effect on tumor cell growth. However, little has been known concerning the effect of shikonin on lung adenocarcinoma cell and underlying mechanisms. In the present study, we investigated the effect of shikonin on the proliferation, cell cycle arrest, and apoptosis in human lung adenocarcinoma cells.

MiR-21 overexpression is associated with acquired resistance of EGFR-TKI in non-small cell lung cancer.

Background And Purpose: With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) in patients with advanced non-small cell lung cancer (NSCLC), its acquired resistance has become a major clinical problem. Recent studies revealed that miR-21 was involved into the resistance of cytotoxic agents. The aim of this study was to investigate its role in the acquired resistance of NSCLC to EGFR-TKI.

[Interventional therapy for lung cancer patients with superior vena cava syndrome].

Objective: To investigate the method, therapeutic effect and safety of interventional therapy for lung cancer patients with superior vena cava syndrome (SVCS).

Methods: Fifty-two cases of lung cancer with SVCS who received interventional therapy in our hospital between Jan to Dec 2011 were included in this study. Of the 52 cases, 50 cases had successfully carried out superior vena cava stent implantation.

Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway.

Integrin β1 facilitates cancer cell adhesion, migration and metastasis by activating intracellular signaling pathways including the ERK and PI3K signaling pathways. In previous studies, shikonin, an active naphthoquinone isolated from the Chinese medicine Zi Cao (gromwell), showed effective anticancer activity both in vivo and in vitro. However, the mechanisms underlying shikonin's anticancer activity are not fully elucidated.

Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1.

Objective: Experimental evidence suggests that the overexpression of breast cancer-specific tumor suppressor protein 1 (BRCA1) gene enhances sensitivity to docetaxel and resistance to cisplatin and ribonucleotide reductase M1 (RRM1) gene overexpression enhances resistance to gemcitabine. To further examine the effect of BRCA1 and RRM1 mRNA levels on outcome in advanced non-small cell lung cancer (NSCLC), we performed this non-randomized phase II clinical trial which tested the hypothesis that customized therapy would confer improved outcome over non-customized therapy.

Methods: RNA was isolated from fresh tumor tissue.

Gefitinib-resistance is related to BIM expression in non-small cell lung cancer cell lines.

Recent evidence indicates that both the phosphatidylinositol 3-kinase (PI3K)/AKT and the MEK/ERK pathways are strictly regulated by epidermal growth factor receptor in non-small cell lung cancer (NSCLC) that responds to Gefitinib. Gefitinib resistance is partly owing to the activation of two major downstream signaling pathways PI3K/AKT or MEK/ERK. In this study, we found that in Gefitinib-sensitive cell lines, Gefitinib could induce tumor cell apoptosis via upregulation of a proapoptotic protein BIM.