KLF3 is a crucial regulator of metastasis by controlling STAT3 expression in lung cancer.

Lung cancer is one of the most common causes of cancer-related mortality worldwide, which is partially due to its metastasis. However, the mechanism underlying its metastasis remains elusive. In this study, we showed that a low Krüppel-like factor 3 (KLF3) expression level is correlated with a poor prognosis and TNM stages in clinical patients with lung cancer and further demonstrated that KLF3 expression is downregulated in lung cancer tissues compared with adjacent normal samples. In addition, bioinformatics analysis results showed that KLF3 expression is related to lung cancer epithelial-mesenchymal transition (EMT). In vitro and in vivo experiments also showed that KLF3 silencing promotes lung cancer EMT and enhances lung cancer metastasis. More importantly, bioinformatics analysis and in vitro experiments indicated that the role of KLF3 in lung cancer metastasis is dependent on the STAT3 signaling pathway. Overall, our data indicated the crucial function of KLF3 in lung cancer metastasis and suggested opportunities to improve the therapy of patients with lung cancer.

miR-202 Enhances the Anti-Tumor Effect of Cisplatin on Non-Small Cell Lung Cancer by Targeting the Ras/MAPK Pathway.

BACKGROUND/AIMS: KRas is usually mutated in non-small cell lung cancer (NSCLC). The mutated KRas gene is a negative prognostic indicator that promotes tumor proliferation, metastasis, and drug resistance in NSCLC, and thus has become a target for cancer therapy. This study is focused on the effects of the microRNA (miR)-202/KRas axis in regulating chemosensitivity in NSCLC. METHODS: Quantitative reverse transcriptase real-time PCR analysis was performed to examine the expression of miR-202. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays were performed to evaluate the sensitivity of cisplatin against NSCLC cells. The miR-202/KRas axis was confirmed by western blot and luciferase reporter assays. Cell apoptosis was measured by flow cytometry. KRas expression, MEK1/2 and ERK1/2 phosphorylation, and activation of caspase-9 and caspase-3 were detected by western blot. RESULTS: A significant decrease in miR-202 expression was observed in NSCLC cells both in vivo and in vitro. In addition, miR-202 expression was associated with drug resistance. Recovery of miR-202 expression levels was found to increase the sensitivity of both NCI-H441 and A549 NSCLC cells to cisplatin treatment. Mechanically, as the Ras/mitogen-activated protein kinase (MAPK) pathway was aberrantly activated in NCI-H441 and A549 NSCLC cells, the overexpression of miR-202 was found to inhibit the Ras/MAPK pathway by targeting the KRas gene. As a result, increased miR-202 expression expanded apoptosis signaling induced by cisplatin in NSCLC cells. CONCLUSION: The miR-202/KRas axis controlled the chemosensitivity of NSCLC by mediating the Ras/MAPK pathway. Thus, the combination of platinum-based drugs with miR-202 may represent a novel strategy to enhance the anti-tumor effect against NSCLC.

Lipopolysaccharide-induced toll-like receptor 4 signaling in esophageal squamous cell carcinoma promotes tumor proliferation and regulates inflammatory cytokines expression.

Emerging evidence suggests toll-like receptor 4 (TLR4) signaling contributes to cancer development and progression. However, the consequences of signaling via the TLR4 pathway in esophageal squamous cell carcinoma (ESCC) are still unclear. Here, we investigated the impact of Lipopolysaccharide (LPS)-induced TLR4 signaling on ESCC cell proliferation, inflammatory cytokines expression, and downstream molecular mechanisms. Seventy-eight ESCC and 26 normal esophageal specimens were analyzed by immunohistochemistry, and two cell lines (Eca-109 and TE-1) were used for in vitro studies. LPS, a natural agonist of TLR4, was used to activate TLR4 signaling. The effects of LPS-TLR4 signaling on cell proliferation and inflammatory cytokines regulation were examined. Specific inhibitors of mitogen-activated protein kinase (MAPK) (extracellular regulated protein kinase [ERK] and p38) signaling pathways were used to investigate the role of each pathway in LPS-TLR4 signaling. TLR4 protein was increased in ESCC tumor tissues compared with the adjacent normal tissues. TLR4 over-expression was significantly correlated with tumor differentiation grade, lymph node metastasis, and UICC stage. LPS-induced activation of TLR4 signaling promoted cancer cell proliferation, increased production of proinflammatory or immunosuppressive cytokines TNF-α, TGF-ß and inhibited the anti-inflammatory cytokine IL-10. LPS-TLR4 signaling was associated with the activation of ERK and p38 MAPK signaling pathways. Further inactivation of the two pathways by specific inhibitors attenuated cell proliferation and inflammatory cytokines expression induced by LPS. Our results indicate that LPS-TLR4 signaling in cancer cells contributes to the progression of human ESCC.

Clinicopathological and prognostic significance of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma: a meta-analysis.

Published literatures on the prognostic value of hypoxia-inducible factor-1α (HIF-1α) overexpression in esophageal squamous cell carcinoma (ESCC) are conflicting and heterogeneous. We performed a meta-analysis to more precisely evaluate the clinicopathological and prognostic value of HIF-1α in patients with ESCC. Searches were applied to MEDLINE, Pubmed, Embase, Cochrane Library, Web of Science, and Chinese BioMedical Literature Databases until September 10, 2013, without language restrictions. The pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to estimate the effects. Twelve studies with 942 ESCC patients were selected to evaluate the correlation between HIF-1α and overall survival (OS), disease-free survival (DFS), response to chemoradiation (RC), and clinicopathological features. HIF-1α overexpression was significantly associated with poor OS (HR 1.78, 95% CI 1.41-2.24), DFS (HR 1.91, 95% CI 1.15-3.18), and RC (HR 3.56, 95% CI 1.68-7.53). Besides, HIF-1α overexpression was significantly associated with stage (OR 2.90, 95% CI 1.97-4.27), lymph node metastasis (OR 1.86, 95% CI 1.39-2.49), depth of invasion (OR 2.45, 95% CI 1.24-4.86), lymphatic invasion (OR 2.28, 95% CI 1.46-3.56), distant metastasis (OR 2.04, 95% CI 1.19-3.50), and vascular endothelial growth factor (OR 3.67, 95% CI 1.81-7.46). Our results indicate that HIF-1α overexpression can potently predict the poor prognosis and chemoradiation resistance for ESCC. Large prospective studies with multivariable survival analyses are now needed to confirm the clinical utility of HIF-1α as an independent prognostic marker.

Perinatal exposure to Di-(2-ethylhexyl)-Phthalate leads to cognitive dysfunction and phospho-tau level increase in aged rats.

Di-(2-ethylhexyl)-Phthalate (DEHP) can affect glucose and insulin homeostasis in periphery and lead to insulin resistance, especially exposure of DEHP during critical developmental period. Given the potential relationship between insulin resistance and pathogenesis of Alzheimer's disease (AD) in elderly life, we investigated the relationship between perinatal DEHP exposure and AD pathogenesis. Our results suggested that perinatal exposure to DEHP can affect the expression of insulin and insulin-Akt- GSK-3ß signal pathway in hippocampus. Furthermore, impaired cognitive ability and increased level of phospho-Tau was observed in DEHP-exposed rat offspring (1.25 ± 0.11 vs. 0.47 ± 0.07, P < 0.05). The present study demonstrates that perinatal exposure to DEHP may be a potential risk factor for AD pathogenesis associated with insulin resistance and insulin metabolism disorder in the hippocampus.

Genetic variation in a miR-335 binding site in BIRC5 alters susceptibility to lung cancer in Chinese Han populations.

Polymorphisms in 3' untranslated region (UTR) of cancer-related genes might affect their regulation by microRNAs (miRNAs) and thereby contribute to carcinogenesis. In this study, we screened single nucleotide polymorphisms (SNPs) in 3' UTR of cancer-related genes and investigated their effects on risk of lung cancer. First, we genotyped seven SNPs in a Chinese Han population with 600 lung cancer patients and 600 matched healthy controls and found that compared with the TT genotype of rs2239680 in 3' UTR of baculoviral IAP repeat containing 5 (BIRC5), C allele was associated with a significantly increased risk of lung cancer and advanced pathologic stage, with the odds ratio for participants carrying the CT or CC genotype being 1.50 [95% confidence interval (CI) 1.20-1.89, P<0.01] and 2.29 (95% CI 1.64-3.18, P<0.01), respectively. These results were further replicated and confirmed in another independent population with 1000 lung cancer cases and 1000 matched healthy controls. In support of the postulation that the 3' UTR SNP may directly affect miRNA-binding site, reporter gene assays indicated BIRC5 was a direct target of miR-335, and the rs2239680 T>C change resulted in altered regulation of BIRC5 expression. Moreover, BIRC5 was over expressed in lung cancer tissues compared with the normal lung tissues, and the protein levels of BIRC5 correlated with SNP genotypes in normal lung tissues. Our findings defined a 3' UTR SNP in human BIRC5 oncogene that may increase individual susceptibility to lung cancer probably by attenuating the interaction between miR-335 and BIRC5.

Setd1A-mediated methylation of h3k4me3 inhibits ferroptosis in non-small cell lung cancer by regulating the WTAPP1/WTAP axis.

INTRODUCTION: SETD1A is upregulated in non-small cell lung cancer (NSCLC) tissues. This study investigated the molecular mechanism of the SETD1A/WTAPP1/WTAP axis in NSCLC. METHODS: Ferroptosis is a unique cell death mode driven by iron-reliant phospholipid peroxidation, which is regulated by multiple cellular metabolic pathways, including REDOX homeostasis, iron metabolism, mitochondrial activity and metabolism of amino acids, lipids and sugars. Thus, the levels of ferroptosis markers (MDA, SOD, GSH) were measured in vitro, and NSCLC cell behaviors were assessed. SETD1A-mediated H3K4me3 methylation was analyzed. SETD1A-exerted effects on ferroptosis and tumor growth in vivo were verified in nude mouse models. RESULTS: SETD1A was highly expressed in NSCLC cells. Silencing SETD1A suppressed NSCLC cell proliferation and migration, inhibited MDA, and enhanced GPX4, SOD, and GSH levels. SETD1A elevated WTAP expression through WTAPP1 upregulation by mediating H3K4me3 methylation in the WTAPP1 promoter region. WTAPP1 overexpression partly averted the promotional effect of silencing SETD1A on NSCLC cell ferroptosis. WTAP interference abrogated the inhibitory effects of WTAPP1 on NSCLC cell ferroptosis. Silencing SETD1A facilitated ferroptosis and accelerated tumor growth in nude mice through the WTAPP1/WTAP axis. CONCLUSION: SETD1A amplified WTAP expression through WTAPP1 upregulation by mediating H3K4me3 modification in the WTAPP1 promoter region, thus promoting NSCLC cell proliferation and migration and inhibiting ferroptosis.

The roles of CPSF6 in proliferation, apoptosis and tumorigenicity of lung adenocarcinoma.

Cleavage and polyadenylation specific factor 6 (CPSF6), a member of serine/arginine-rich protein family, is implicated in HIV-1-infection and replication. Overexpression of CPSF6 predicts poor prognostic outcomes of breast cancer. However, the expression and possible function of CPSF6 in lung adenocarcinoma (LUAD) still needs to be explored. Here, we found that CPSF6 is significantly higher expressed in tumor tissues than normal tissues in multiple cancer types. Besides, CPSF6 plays a significant risky role in LUAD that is associated with overall survival (HR=1.337, P=0.051) and disease-specific survival (HR=1.4739, P=0.042). CPSF6 mRNA was up-regulated in LUAD tissues by analyzing publicly available datasets from Gene Expression Omnibus (GEO). Further survival analysis on The Cancer Genome Atlas (TCGA) dataset suggested a close correlation between CPSF6 expression and overall survival, and disease-free survival of LUAD patients. Inhibition of CPSF6 expression by lentivirus-mediated RNA interference (RNAi) in two LUAD cell lines (A549 and NCH-H1299) caused a significant reduction in cell proliferation, colony formation and a notable induction in apoptotic rate. CPSF6 knockdown in xenograft tumors inhibited LUAD cell growth in vivo. Moreover, we identified differentially expressed genes with CPSF6 inhibition by Microarray analysis, and pathway analyses revealed that CPSF6 knockdown resulted in the dysregulation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. Collectively, our results are the first to demonstrate that CPSF6 functions as an oncoprotein by regulating cancer-related pathways in LUAD.

Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification.

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%-3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups. Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared. Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort. Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.

Erratum: Histone demethylase KDM4C activates HIF1α/VEGFA signaling through the costimulatory factor STAT3 in NSCLC.

[This corrects the article on p. 491 in vol. 10, PMID: 32195022.].

Long noncoding RNA CASC7 is a novel regulator of glycolysis in oesophageal cancer via a miR-143-3p-mediated HK2 signalling pathway.

Long noncoding RNAs have been proven to play a crucial role in many tumours. Here, we explored the role of the lncRNA cancer susceptibility candidate 7 (CASC7) in oesophageal cancer. LncRNA CASC7 was identified in our database analysis, and we found that it was significantly higher in oesophageal tumour tissue than in normal tissue and that high expression of lncRNA CASC7 predicted a poor prognosis. Furthermore, we verified through cell experiments that low expression of lncRNA CASC7 in oesophageal cancer cells significantly inhibited tumour proliferation, which could be explained by the effect of lncRNA CASC7 on aerobic glycolysis. Next, we found that the expression of CASC7 and hexokinase 2 (HK2) in oesophageal cancer was positively correlated in database analysis, and this conclusion was further verified in cell experiments. To determine the mechanism, we found that miR-143-3p can bind to both lncRNA CASC7 and HK2. In clinical specimens, we also found high expression of lncRNA CASC7 in tumours, and the expression levels of lncRNA CASC7 and HK2 were positively correlated. In conclusion, downregulating lncRNA CASC7 could inhibit tumour proliferation by reducing glycolysis through the miR-143-3p/HK2 axis.

Study on metabonomic characteristics of human lung cancer using high resolution magic-angle spinning 1H NMR spectroscopy and multivariate data analysis.

Lung cancer causes serious health problems. Clinical diagnosis of lung cancer relies on histopathological evalution of tissue specimen. However, extensive knowledge of the metabolic biochemistry of tumors can potentially provide important information for accurate diagnosis of lung cancer. High resolution magic-angle spinning NMR spectroscopy has emerged and be widely acknowledged as an excellent tool in investigating tissue metabolism. Moreover, the combination of high resolution magic-angle spinning NMR technique and multivariate data analysis has become an important metabonomics platform for studying the intact biological tissues. This study reported the metabonomic characteristics of 51 lung tissues from 17 patients with lung cancer using the high resolution magic-angle spinning 1H NMR spectroscopy and the multivariate data analysis methods including principal component analysis and orthogonal partial least squares-discriminant analysis. Clear differences among the metabonomic characteristics of lung cancer tissues at various sites were disclosed. Compared with the adjacent noninvolved tissues, the lung cancer tissues had significantly high levels of aspartate, phosphocholine, glycerophosphocholine and lactate but significantly low levels of glucose and valine. Furthermore, significantly positive (or negative) correlations were observed between the levels of some metabolites such as lactate, fatty acids, valine, phosphocholine, and glycerophosphocholine.

Histone demethylase KDM4C activates HIF1α/VEGFA signaling through the costimulatory factor STAT3 in NSCLC.

Tumor development is accompanied by high hypoxia and a dense network of immature vessels. The hypoxia-inducible factor/vascular endothelial growth factor (HIF/VEGF) signaling pathway is activated in various solid tumors. It is thought that HIF/VEGF signaling activation results from intratumoral hypoxia partly. Multiple studies have reported that VEGF is a common target gene for both transcription factors STAT3 and HIF1. KDM4C has also been reported to function as a co-activation factor for HIF-1ß/VEGF signaling activation. In this manuscript. Our results demonstrate that KDM4C promotes NSCLC tumor angiogenesis by transcriptionally activating HIF1α/VEGFA signaling pathway. We also find that STAT3 functions as a costimulatory factor in this process. This pathway opens a potential therapeutic window for the treatment of NSCLC.

A case report with COVID-19 during perioperative period of lobectomy.

RATIONALE: Currently, COVID-19 has made a significant impact on many countries in the world. However, there have been no reported cases of pulmonary lobectomy with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection. We are the first to report such a case. PATIENT CONCERNS: We report a 63-year-old Wuhan male patient with smoking history of 40 cigarettes per day for 40 years. He sought medical consultation for right lower lung nodules found by CT scan. DIAGNOSES AND INTERVENTIONS: The patient's postoperative pathological diagnosis was squamous cell carcinoma of the right lower lung. On the fourth day after the operation, the real-time reverse transcription polymerase chain reaction test showed a positive result. After the operation, we routinely give symptomatic treatments such as anti-infection, nebulization and oxygen inhalation. We also change antibiotics several times depending on the patient's condition. OUTCOMES: The patient's condition continued to deteriorate. On the fifth day after surgery, the patient died despite medical treatment. LESSONS: We are the first to report the diagnosis and treatment process of patients with COVID-19 during perioperative period of lobectomy. It provides a case for the postoperative management of such patients.

LncRNA-NBAT-1 modulates esophageal cancer proliferation via PKM2.

Esophageal cancer is one of the most common malignant cancers worldwide. Long non-coding RNAs (lncRNAs) have been reported to be associated with different types of cancer; however, the precise function of lncRNAs in tumorigenesis remains largely unknown. Herein, we found that lncRNA NBAT-1 levels were lower in EC clinic tissues than in normal samples, and lncRNA NBAT-1 expression was negatively associated with prognosis and TNM stage in EC patients. More importantly, in EC cancer cells, lncRNA NBAT-1 overexpression strongly inhibited cell proliferation, cell growth and tumor glycolysis. Furthermore, a series of rescue experiments were performed to demonstrate that the role of lncRNA NBAT-1 in EC cell proliferation, cell growth and tumor glycolysis was partially dependent on the PKM2 protein, which is a key metabolic enzyme in tumor development. Taken together, our data illustrate a functional role for lncRNA NBAT-1 in metabolic reprogramming in EC cancer; thus, lncRNA NBAT-1 might be a potential clinical therapeutic target in EC patients.

MicroRNA-503 Inhibits Non-Small Cell Lung Cancer Progression By Targeting PDK1/PI3K/AKT Pathway.

OBJECTIVES: The aim of the study was to study the role of dysregulated expression of a microRNA (miRNA), miR-503, in non-small-cell lung cancer (NSCLC) and investigate the underlying mechanism. METHODS: Quantitative real-time PCR (qRT-PCR) and in situ hybridization staining (ISH) were used to evaluate the expression level of miR-503 in NSCLC tissues and paired adjacent tissues. CCK-8, colony formation and flow cytometry were performed to explore the effects of miR-503 overexpression on cell proliferation, colony formation and apoptosis. Cells with miR-503 overexpression were used to initiate xenograft models. Dual luciferase reporter assay, qRT-PCR, immunohistochemistry and Western blotting were conducted to investigate the interaction of miR-503 and its potential target. RESULTS: Significantly downregulated miR-503 was found in NSCLC tumor tissues and cell lines. miR-503 overexpression significantly inhibited NSCLC cell proliferation, migration and invasion. PDK1 was predicted as the direct targets of miR-503. PDK1 overexpression reversed the inhibitory effects of miR-503 on biological functions, while PDK1 silencing significantly counteracted miR-503 inhibitor-induced pro-tumor effects in A549 cells. Mechanistically, upregulation of miR-503 inhibited PDK1 expression and subsequently caused the inactivation of PI3K/AKT pathway. CONCLUSION: Our results suggest that miR-503 inhibits NSCLC progression by targeting PDK1/PI3K/AKT pathway, potentiating the use of miR-503 as a biomarker and therapeutic target for NSCLC.

Tan IIA inhibits H1299 cell viability through the MDM4­IAP3 signaling pathway.

Tanshinone IIA (Tan IIA), as a bioactive compound extracted from the dried roots of Salvia miltiorrhiza (also known as Danshen), is known to inhibit cancer cell proliferation and induce apoptosis. However, the mechanisms underlying the function of Tan IIA in cancer cell apoptosis remain to be elucidated The aim of the present study was to identify the molecular mechanisms underlying the anti­cancer effects of Tan IIA in p53­deficient H1299 cells. Tan IIA was demonstrated to suppress murine double minute 4 (MDM4) expression in a time­ and dose­dependent manner through the inhibition of MDM4 mRNA synthesis. Tan IIA­induced downregulation of MDM4 resulted in an increase of P73α and a decrease of inhibitor of apoptosis 3 (IAP3). However, P73α was not activated as two P73α target genes, BCL2 binding component 3 and phorbol­12­myristate­13­acetate­induced protein 1, were not significantly induced. Tan IIA­induced inhibition of IAP3 expression may be involved in Tan IIA­induced apoptosis and inhibition of H1299 cell viability. Notably, a combination of Tan IIA and doxorubicin (DOX) exposure resulted in further MDM4 overexpression in H1299 cells, indicating that Tan IIA sensitized p53­deficient and MDM4­overexpressing H1299 cells to DOX­induced apoptosis.

Knockdown of lncRNA-XIST enhances the chemosensitivity of NSCLC cells via suppression of autophagy.

Drug resistance is the major factor contributing to the failure of chemotherapy in non-small cell lung cancer (NSCLC) patients. Emerging evidence suggests that autophagy plays a vital role in the chemoresistance of many types of tumors. However, the exact mechanism underlying the chemoresistance of NSCLC is still elusive, and it is unclear whether lncRNA-XIST is involved in autophagy and chemoresistance of NSCLC. In the present study, we demonstrated that lncRNA-XIST was overexpressed in NSCLC tumor samples, and knockdown of lncRNA-XIST significantly decreased autophagy by regulation of ATG7 as determined by qPCR and by western blotting. Furthermore, we found that miR-17 was upregulated following knockdown of lncRNA-XIST, and miR-17 mimics decreased the protein levels of ATG7 by directly targeting the 3'-untranslated region of ATG7 mRNA as determined by RT-qPCR and by western blotting. Furthermore, we found that the expression level of lncRNA-XIST was markedly increased in cisplatin-resistant A549 cells as determined by q-PCR. Knockdown of lncRNA-XIST restored the chemosensitivity of cisplatin-resistant A549 cells to cisplatin, which was reversed by miR-17 inhibitor and overexpression of ATG7 as determined by CCK8 assays. This study provides evidence that lncRNA-XIST may be a potential marker of poor response to cisplatin chemotherapy in NSCLC patients and the pathway 'lncRNA-XIST/miR-17/autophagy' may be a promising target for patients with chemoresistant NSCLC.

Inhibitory effect of pulmonary carcinoma by adenovirus-mediated CD/UPRT gene.

The cell killing effects and bystander effects of double suicide gene on pulmonary carcinoma cells were explored. Lung adenocarcinoma cells (A549) were transfected with different titers of adenovirus vector and followed with different concentrations of 5-FC after a recombinant adenovirus vector carrying CD/UPRT gene (Ad-CD/UPRT) was constructed. The cell viability was measured by MTT assay 4 days later. The cell viability was dropped to 30.57 %-8.62 % after 10 MOI of Ad-CD/UPRT transfected and 5-FC (10-1000 microg/mL) administration. Furthermore, Ad-CD/UPRT-infected A549 cells showed a profound neighbor cell killing effect in the same methods. These results suggested that Ad-CD/UPRT/5-FC system can effectively suppress growth of lung adenocarcinoma cells, which may provide a novel and powerful candidate for lung cancer gene therapy strategies.

Metabonomic characteristics and biomarker research of human lung cancer tissues by HR1H NMR spectroscopy.

BACKGROUND: The combination of NMR spectroscopy and multivariate data analysis (MVDA), such as orthogonal partial least squares-discriminant analysis (OPLS-DA), has been collectively acknowledged as an excellent tool to investigate tissue metabolism and provide metabolite information for the diagnosis of disease, and become an important metabonomic platform for studies in biological tissues so far. METHODS: Both ex vivo high resolution magic-angle spinning1H NMR and in vitro1H NMR spectroscopy technique were synchronously employed to analyze the metabonomic characteristics of 102 lung tissues from 34 patients with lung cancer in hope to identify potential diagnostic biomarkers for malignancy detection in lung tissues. RESULTS: Significant elevations in the levels of lipids and lactate and significant reductions in the levels of myo-inositol and valine in the cancer tissues had been identified when compared with the adjacent non-involved tissues. Furthermore, the OPLSDA models calculated by two1H NMR spectra provided for relatively high sensitivity, specificity and good prediction accuracy in the identification of class membership regardless of the number of metabolites involved. CONCLUSIONS: MVDA in combination with1H NMR spectra highlighted the potential of metabonomics in clinical settings so that the techniques might be further exploited for future lung cancer biomarker research or identification.