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32.
The resistance of cancer cells to the anti-cancer drugs is the most important reason that affecting the efficacy of the non-small cell lung cancer (NSCLC) chemotherapy; thus, to explore the underlying mechanism of drug resistance of NSCLC medications is urgently needed for improving the therapeutic efficacy of current anti-NSCLC chemotherapies. The aim of the present study is to explore the roles of exosomes in the chemosensitivity of A549 cells and the related mechanism. A549 cells and cisplatin resistant cell line A549/DDP derived exosomes were isolated, and the expressions of CXCR4 were compared. Then, after cisplatin treatment, A549 cells were treated with exosomes, and the proliferation, apoptosis, migration, and invasion of the cells were examined. Finally, the tumorigenic effect of A549/DDP derived exosomes were also evaluated by cisplatin treated xenograft tumor mice models in vivo. We found that A549/DDP derived exosomes increased the proliferation, migration, and invasion, and inhibited the apoptosis and cisplatin sensitivity of A549 cells. CXCR4 was also significantly increased in cells treated with A549/DDP derived exosomes. Furthermore, A549/DDP derived exosomes may also decrease the chemosensitivity of NSCLC cells to cisplatin in vivo. Our data suggested that A549/DDP derived exosomes can affect the chemosensitivity of A549 cells to cisplatin, possibly by transporting CXCR4 to A549 cells. Our data may provide novel evidence for the investigation of drug resistance of NSCLC. 相似文献
33.
目的研究鸦胆子油乳联合GP方案治疗晚期非小细胞肺癌的临床效果。方法对2007年6月至2009年6月我院入院治疗的36例患者进行研究,随机分为2组,治疗组采用GP化疗联合使用药鸦胆子油乳,3周为1个疗程,共治疗4个疗程。对照组单独使用GP方案进行化疗。结果治疗组有效率为55.6%,对照组有效率为33.3%,2组差异具有统计学意义(P<0.05)。实验组发生血液性毒性不良反应的发生率为27.8%,低于对照组50%,有显著性差异(P<0.05),并且治疗组治疗后的生活质量要好于对照组。结论鸦胆子油乳联合GP治疗非小细胞肺癌疗效显著,好于GP单独化疗,并且骨髓抑制副作用小,能够显著提高患者生活质量,值得临床推广应用。 相似文献
34.
Shu-Lin Chen Ning Xue Mian-Tao Wu Hao Chen Xia He Jian-Pei Li Wan-Li Liu Shu-Qin Dai 《International journal of molecular sciences》2016,17(9)
The purpose of this work is to analyze preoperative serum aspartate aminotransferase (AST) levels and their effect on the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical operation. These analyses were performed retrospectively in patients with NSCLC followed by surgery; participants were recruited between January 2004 and January 2008. All clinical information and laboratory results were collected from medical records. We explored the association between preoperative serum AST and recurrence-free survival (RFS), and the overall survival (OS) of NSCLC patients. Kaplan–Meier analysis and Cox multivariate analysis, stratified by the AST median value, were used to evaluate the prognostic effect. A chi-squared test was performed to compare clinical characteristics in different subgroups. A p-value of ≤0.05 was considered to be statistically significant. A total of 231 patients were enrolled. The median RFS and OS were 22 and 59 months, respectively. The AST levels were divided into two groups, using a cut-off value of 19 U/L: High AST (>19 U/L), n = 113 vs. low AST (≤19 U/L), n = 118. Multivariate analysis indicated that preoperative serum AST > 19 U/L (hazard ratio (HR) = 0.685, 95% confidence interval (CI): 0.493–0.994, p = 0.046 for RFS, HR = 0.646, 95% CI: 0.438–0.954, p = 0.028 for OS) was an independent prognostic factor for both RFS and OS. High preoperative serum AST levels may serve as a valuable marker to predict the prognosis of NSCLC after operation. 相似文献
35.
ZHAO Ying-hao MA Tong-hui ZHENG Yong-chen ZHANG Kun YANG Jing-bo YANG Long-fei YANG Zhi-guang SHAO Guo-guang 《Canadian Metallurgical Quarterly》2011,27(1)
Matrix metalloproteinase-9(MMP-9)and p53 genes play an essential role in the multi-step process of tumorigenesis in lung cancer.Single nucleotide polymorphisms(SNPs)of MMP-9 and p53 genes are associated with the risk and progression of many cancers.In this study,we evaluated the association of the R279Q polymorphism of MMP-9 or the A1/A2 polymorphism of p53 gene with the risk of no-small-cell lung cancer(NSCLC)in Hart population of Northeast China.We examined the frequency of SNPs in the two kinds of genes of 50 patients with NSCLC and 50 cancer-free controls frequency-matched by age and sex.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique was used to determine the genotypes.The results indicate that the 279RR genotype in MMP-9 gene and the A1/A2 genotype in p53 gene show a significantly increased risk of NSCLC.Therefore,the MMP-9 279RR and p53 A1/A2 genotypes may be used as markers for susceptibility to NSCLC in Han population of Northeast China. 相似文献
36.
ZONG Min-ru ZHAO Ying-hao ZHANG Kun YANG Long-fei ZHENG Yong-chen HE Cheng-yan 《Canadian Metallurgical Quarterly》2011,27(2)
Alantolactone is a natural compound identified from the roots of Inula helenium L. that has multiple bio-activities. We examined its inhibitory effects on human non-small cell lung cancer(NSCLC) A549 cells. The antiproliferative effect of alantolactone on A549 ceils was investigated via MTT[3'-(4,5dimethylthiazol-2-yl)-2,5diphenyl tetrazolium bromide] assay and its apoptosis-inducing effect was determined by Hoechst staining and flow cytometry. We found that alantolactone significantly inhibited the proliferation of A549 cells and induced morphological changes typical for apoptosis. Flow cytometry analysis indicates dose-dependent cell cycle retardation at G0/G1 and S stages. The results indicate that alantolactone could be an attractive small-molecular natural compound for further development as a therapeutic drug against NSCLC. 相似文献
37.
Qing Kay Li Ed Gabrielson Frederic Askin Daniel W. Chan Hui Zhang 《Proteomics. Clinical applications》2013,7(1-2):55-69
Lung cancer is the leading cancer in the United States and worldwide. In spite of the rapid progression in personalized treatments, the overall survival rate of lung cancer patients is still suboptimal. Over the past decade, tremendous efforts have been focused on the discovery of protein biomarkers to facilitate the early detection and monitoring of lung cancer progression during treatment. In addition to tumor tissues and cancer cell lines, a variety of biological material has been studied. Particularly in recent years, studies using fluid-based specimen or so-called “fluid-biopsy” specimens have progressed rapidly. Fluid specimens are relatively easier to collect than tumor tissue, and they can be repeatedly sampled during the disease progression. Glycoproteins are the major content of fluid specimens and have long been recognized to play fundamental roles in many physiological and pathological processes. In this review, we focus the discussion on recent advances of glycoproteomics, particularly in the identification of potential glyco protein biomarkers using fluid-based specimens in lung cancer. The purpose of this review is to summarize current strategies, achievements, and perspectives in the field. This insight will highlight the discovery of tumor-associated glycoprotein biomarkers in lung cancer and their potential clinical applications. 相似文献
39.
Po-Wen Shen Chun-Te Ho Shih-Hsin Hsiao Yu-Ting Chou Yi-Cheng Chang Jun-Jen Liu 《International journal of molecular sciences》2021,22(16)
Patients with advanced-stage non-small-cell lung cancer (NSCLC) are susceptible to malnutrition and develop folate deficiency (FD). We previously found that folate deprivation induces drug resistance in hepatocellular carcinoma; here, we assessed whether disrupted cytoplasmic folate metabolism could mimic FD-induced metastasis and affect the sensitivity of NSCLC cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We examined whether cytosolic folate metabolism in NSCLC cells was disrupted by FD or the folate metabolism blocker pemetrexed for 1–4 weeks. Our results revealed an increase in NF-κB overexpression–mediated epithelial-mesenchymal transition biomarkers: N-cadherin, vimentin, matrix metalloproteinases (MMPs), SOX9, and SLUG. This finding suggests that the disruption of folate metabolism can drastically enhance the metastatic properties of NSCLC cells. Cytosolic FD also affected EGFR-TKI cytotoxicity toward NSCLC cells. Because SLUG and N-cadherin are resistance effectors against gefitinib, the effects of SLUG knockdown in folate antagonist–treated CL1-0 cells were evaluated. SLUG knockdown prevented SLUG/NF-κB/SOX9-mediated invasiveness and erlotinib resistance acquisition and significantly reduced pemetrexed-induced gelatinase activity and MMP gene expression. To summarize, our data reveal two unprecedented adverse effects of folate metabolism disruption in NSCLC cells. Thus, the folic acid status of patients with NSCLC under treatment can considerably influence their prognosis. 相似文献
40.
Renato Jos da Silva-Oliveira Izabela Natalia Faria Gomes Luciane Sussuchi da Silva Andr van Helvoort Lengert Ana Carolina Laus Matias Eliseo Melendez Carla Carolina Munari Fernanda de Paula Cury Giovanna Barbarini Longato Rui Manuel Reis 《International journal of molecular sciences》2022,23(14)
Background: EGFR mutations are present in approximately 15–50% of non-small cell lung cancer (NSCLC), which are predictive of anti-EGFR therapies. At variance, NSCLC patients harboring KRAS mutations are resistant to those anti-EGFR approaches. Afatinib and allitinib are second-generation pan-EGFR drugs, yet no predictive biomarkers are known in the NSCLC context. In the present study, we evaluated the efficacy of pan-EGFR inhibitors in a panel of 15 lung cancer cell lines associated with the KRAS mutations phenotype. Methods: KRAS wild-type sensitive NCI-H292 cell line was further transfected with KRAS mutations (p.G12D and p.G12S). The pan-EGFR inhibitors’ activity and biologic effect of KRAS mutations were evaluated by cytotoxicity, MAPK phospho-protein array, colony formation, migration, invasion, and adhesion. In addition, in vivo chicken chorioallantoic membrane assay was performed in KRAS mutant cell lines. The gene expression profile was evaluated by NanoString. Lastly, everolimus and pan-EGFR combinations were performed to determine the combination index. Results: The GI50 score classified two cell lines treated with afatinib and seven treated with allitinib as high-sensitive phenotypes. All KRAS mutant cell lines demonstrated a resistant profile for both therapies (GI50 < 30%). The protein array of KRAS edited cells indicated a significant increase in AKT, CREB, HSP27, JNK, and, importantly, mTOR protein levels compared with KRAS wild-type cells. The colony formation, migration, invasion, adhesion, tumor perimeter, and mesenchymal phenotype were increased in the H292 KRAS mutated cells. Gene expression analysis showed 18 dysregulated genes associated with the focal adhesion-PI3K-Akt-mTOR-signaling correlated in KRAS mutant cell lines. Moreover, mTOR overexpression in KRAS mutant H292 cells was inhibited after everolimus exposure, and sensitivity to afatinib and allitinib was restored. Conclusions: Our results indicate that allitinib was more effective than afatinib in NSCLC cell lines. KRAS mutations increased aggressive behavior through upregulation of the focal adhesion-PI3K-Akt-mTOR-signaling in NSCLC cells. Significantly, everolimus restored sensibility and improved cytotoxicity of EGFR inhibitors in the KRAS mutant NSCLC cell lines. 相似文献