Low-molecular-weight glutenin subunits (LMW-GS), encoded by Glu-3 complex loci in hexaploid wheat, play important roles in the processing quality of wheat flour. To date, the molecular characteristics and effects on dough quality of individual Glu-3 alleles and their encoding proteins have been poorly studied. We used a Glu-A3 deletion line of the Chinese Spring (CS-n) wheat variety to conduct the first comprehensive study on the molecular characteristics and functional properties of the LMW-GS allele Glu-A3a.

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P < 0.001). In patients who received second-line crizotinib therapy, the median PFS was 9.9 months (95% CI: 6.4-13.4 months). The difference between first-line and second-line crizotinib treatment was not statistically significant (adjusted hazard ratio for progression, 0.56; 95% CI: 0.29-1.11; P = 0.092). Thus, there was a significant PFS benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy.

MicroRNAs (miRNAs) are involved in human cancer including non-small cell lung cancer (NSCLC). In this study, we compared miRNA expression microarray of SPC-A-1sci (high metastatic) and SPC-A-1 (weakly metastatic) cells. We found that miRNA-10a was up-regulated in NSCLC compared with corresponding normal tissues. High expression of miR-10a was associated with tumor node metastasis and lymph node metastasis. Furthermore, overexpression of miR-10a promoted NSCLC cell proliferation, migration and invasion in vitro. We found that PTEN was a direct target of miR-10a in NSCLC. Also miR-10a activated the PTEN/AKT/ERK pathway. We suggest that miR-10a contributes to NSCLC by targeting PTEN.

The malignancy of non-small cell lung cancer (NSCLC) is largely due to its invasion. Hence, prevention of the cancer cell invasion, which is essentially regulated by vascular endothelial growth factor A (VEGF-A), is substantially critical for a successful treatment for NSCLC. Here, we showed that compared to other cancers, NSCLC had a significant higher ratio of VEGF-A protein vs mRNA, and significantly lower levels of miR-497, suggesting presence of a post-transcriptional control of VEGF-A in NSCLC different from other cancers. Compared with paired normal lung tissue, NSCLC expressed lower levels of miR-497 and higher levels of VEGF-A. Moreover, the levels of miR-497 and VEGF-A were inversely correlated in NSCLC specimen. Bioinformatics analyses showed that miR-497 bound to 3'-UTR of VEGF-A mRNA in NSCLC lines to inhibit its translation. Overexpression of miR-497 in NSCLC lines decreased VEGF-A protein, while depletion of miR-497 in NSCLC lines increased VEGF-A protein. However, modification of miR-497 levels in NSCLC lines did not alter VEGF-A mRNA levels. Overexpression of miR-497 in NSCLC lines inhibited cell growth and invasion, while depletion of miR-497 in NSCLC lines increased cell growth and invasion. Together, our data demonstrate a previously unappreciated role for miR-497 in suppression of VEGF-A-mediated NSCLC cancer cell growth and invasion.

As a member of the N-myc down-regulated gene family, N-Myc downstream-regulated gene 2 (NDRG2) contributes to the tumorigenesis of various types of cancers. However, the correlation between NDRG2 expression and the prognosis of solid tumor remains to be elucidated because of small sample sizes and inconsistent results in previous studies. In the present study, we conducted a systematic review and meta-analysis to explore the prognostic significance of NDRG2 in human solid tumors.

The optimal neoadjuvant regimen for locally advanced resectable non-small cell lung cancer (NSCLC) remains controversial. EGFR inhibitors have significantly improved survival in patients with EGFR-mutant advanced NSCLC. However, their efficacy in neoadjuvant settings, particularly for treating locally advanced NSCLC, remains unclear. We compared the clinical benefits of chemotherapy and erlotinib as neoadjuvant therapy for stage IIIA NSCLC.

Objectives: To study whether ongoing clinical benefits of continuing anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibition are achieved by crizotinib treatment post progressive disease (PD) in advanced non-small cell lung cancer (NSCLC) patients harboring ALK/ROS1 mutations. Materials and methods: Demographic and clinicopathologic parameters were collected from 38 patients who continued crizotinib therapy beyond Response Evaluation Criteria in Solid Tumors (RECIST)-defined PD and analyzed. After adjusting for potential confounding factors, factors influencing the time from RECIST-PD to crizotinib discontinuation (progress-free survival 2, PFS2) were analyzed. Results: The median time from first dose treatment to RECIST-PD (PFS1) was 9.6 months (95% CI 5.6-13.6 months). The estimated median PFS2 was 5.9 months (95% CI 0.1-11.7 months). Six- and twelve-month crizotinib treatment probabilities after initial PD were 42.1% (95% CI 25.7-58.6%) and 21.1% (95% CI 7.5-34.6%), respectively. Patients who demonstrated RECIST-PD due to new lesions had a longer median PFS2 compared to patients who were attested to enlargement of original lesions (10.0 versus 2.4 months, p = 0.009). The median PFS2 was numerically longer among patients who received local therapy compared to those who did not receive local therapy, however the difference was not significant (9.9 versus 4.2 months, p = 0.094). Multivariable Cox regression analysis showed that only the progression pattern [new lesions versus enlargement of original lesions, HR = 0.329 (95% CI 0.138-0.782), p = 0.012] remained an independent prognostic factor of PFS2. Conclusion: Continuation of crizotinib therapy after RECIST-PD in Chinese NSCLC patients with positive ALK/ROS1 mutations is feasible in clinical practice.

Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated.

Anlotinib is a multitargeted antiangiogenic drug, and its clinical predictor for responsive non-small cell lung cancer (NSCLC) patients is still elusive. Here, tumor-specific target capture is used to profile the circulating DNA of ALTER0303 (evaluating NSCLC clinical antitumor efficacy through anlotinib therapy) study participants. The results indicate that patients receiving no benefit can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. For patients with no durable benefit and durable clinical benefit patients, three predictors: germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB), and unfavorable mutation score of circulating DNA profiling are identified. Through integrating the advantages and disadvantages of three independent predictors, the tumor mutation index (TMI) is established as a prediction model and the patients who are very likely to benefit more from anlotinib therapy are identified. Furthermore, the IDH1 exon 4 mutation is identified as an unfavorable factor for anlotinib therapy under TMI-based stratification, and the TMI plus IDH1 exon 4 mutation status potentially predicts response to anlotinib. Collectively, this study provides a circulating DNA sequencing-based stratification method for identifying anlotinib responders via a noninvasive approach, and thus potentially improves the clinical outcome of NSCLC patients receiving third-line therapy.

The findings of this prospective, single-arm, phase II study showed that neoadjuvant erlotinib was well tolerated and might improve the radical resection rate in patients with stage IIIA-N2 epidermal growth factor receptor mutation-positive non-small cell lung cancer (NSCLC).Erlotinib shows promise as a neoadjuvant therapy option in this patient population.Next-generation sequencing may be useful for predicting outcomes with preoperative tyrosine kinase inhibitors (TKIs) in patients with NSCLC.Large-scale randomized controlled trials investigating the role of TKIs in perioperative therapy, combining neoadjuvant and adjuvant treatments to enhance personalized therapy for patients in this precision medicine era, are warranted.

50%-70% of patients with advanced lung cancer will develop bone metastases. The aim of this study is to establish the nude mice bone metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all of which own different invasion and migration abilities in vitro and supervise the bone metastases by MicroCT.

Circulating tumor cells (CTCs) have important applications in clinical practice on early tumor diagnosis, prognostic prediction, and treatment evaluation. Platinum-based chemotherapy is a fundamental treatment for non-small cell lung cancer (NSCLC) patients who are not suitable for targeted drug therapies. However, most patients progressed after a period of treatment. Therefore, revealing the genetic information contributing to drug resistance and tumor metastasis in CTCs is valuable for treatment adjustment. In this study, we enrolled nine NSCLC patients with platinum-based chemotherapy resistance. For each patient, 10 CTCs were isolated when progression occurred to perform single cell-level whole-exome sequencing (WES). Meanwhile the patients' paired primary-diagnosed formalin-fixed and paraffin-embedded samples and progressive biopsy specimens were also selected to perform WES. Comparisons of distinct mutation profiles between primary and progressive specimens as well as CTCs reflected different evolutionary mechanisms between CTC and lymph node metastasis, embodied in a higher proportion of mutations in CTCs shared with paired progressive lung tumor and hydrothorax specimens (4.4-33.3%) than with progressive lymphatic node samples (0.6-11.8%). Functional annotation showed that CTCs not only harbored cancer-driver gene mutations, including frequent mutations of EGFR and TP53 shared with primary and/or progressive tumors, but also particularly harbored cell cycle-regulated or stem cell-related gene mutations, including SHKBP1, NUMA1, ZNF143, MUC16, ORC1, PON1, PELP1, etc., most of which derived from primary tumor samples and played crucial roles in chemo-drug resistance and metastasis for NSCLCs. Thus, detection of genetic information in CTCs is a feasible strategy for studying drug resistance and discovering new drug targets when progressive tumor specimens were unavailable.

Chimeric antigen receptor (CAR)-T cell therapy is a powerful adoptive immunotherapy against both B-cell malignancies and some types of solid tumors. Interleukin (IL) -15 is an important immune stimulator that may provide ideal long-term persistent CAR-T cells. However, higher base line or peak serum IL-15 levels are also related to severe toxicity, such as cytokine release syndrome (CRS), graft-versus-host disease (GVHD), and neurotoxicity.

Afatinib 30 mg has been proved to be with comparable efficacy but more tolerable than the dose of 40 mg for Asian patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical outcomes of afatinib at 30 mg/d in the treatment of advanced lung adenocarcinomas (LAD) with common and uncommon epidermal growth factor receptor (EGFR) mutations.