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  • Open Access

    ARTICLE

    NOTCH3 Overexpression and Posttranscriptional Regulation by miR-150 Were Associated With EGFR–TKI Resistance in Lung Adenocarcinoma

    Youwei Zhang*, Bi Chen, Yongsheng Wang, Qi Zhao, Weijun Wu§, Peiying Zhang*, Liyun Miao, Sanyuan Sun*

    Oncology Research, Vol.27, No.7, pp. 751-761, 2019, DOI:10.3727/096504018X15372657298381

    Abstract Acquired resistance remains a key challenge in epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) therapy in lung adenocarcinoma (LUAD). Recent studies have shown that Notch signaling is associated with drug resistance. However, its role and possible mechanisms in EGFR-TKI resistance are not yet clear. In our study, we found that among four members of NOTCH1–4, only NOTCH3 was upregulated in LUAD tissues and TKI-resistant cell line (HCC827GR6). Knockdown of NOTCH3 by siRNA significantly inhibited proliferative ability, and decreased colony and sphere formation in HCC827GR6 cells. Then miR-150 was identified as a posttranscriptional regulator of NOTCH3. Its expression was downregulated… More >

  • Open Access

    ARTICLE

    Apatinib Plus Chemotherapy Shows Clinical Activity in Advanced NSCLC: A Retrospective Study

    Jing Tang*1, Xu Yong Li†1, Jing Bo Liang, De Wu§, Li Peng, Xiaobing Li

    Oncology Research, Vol.27, No.6, pp. 635-641, 2019, DOI:10.3727/096504018X15288447760357

    Abstract Apatinib is an oral TKI with antiangiogenic properties, and it is currently approved for the treatment of advanced gastric cancer in China. This agent has also been tested in other human solid tumors, including non-small cell lung cancer (NSCLC). Since the combination of chemotherapy and an antiangiogenic agent has been shown to be a feasible strategy in NSCLC, it is conceivable that a similar approach combining apatinib with chemotherapy may yield clinical activity. With this in mind, we investigated the efficiency of apatinib in combination with pemetrexed or docetaxel in advanced NSCLC. We treated a total of 20 patients with… More >

  • Open Access

    ARTICLE

    Hsa_circ_0003998 Promotes Chemoresistance via Modulation of miR-326 in Lung Adenocarcinoma Cells

    Wanjun Yu*, Weidong Peng*, Hanyun Sha, Jipeng Li

    Oncology Research, Vol.27, No.5, pp. 623-628, 2019, DOI:10.3727/096504018X15420734828058

    Abstract Circular RNAs (circRNAs) represent a new class of noncoding RNAs that is involved in the development of cancer. However, little is known about their role in chemoresistance. In the present study, we found that hsa_circ_0003998 expression levels in lung adenocarcinoma (LAD) tissues and docetaxel-resistant cell lines (A549/DTX and H1299/DTX) were upregulated. Knockdown of hsa_circ_0003998 decreased chemoresistance, inhibited proliferation, and enhanced apoptosis in docetaxel-resistant LAD cells. Moreover, by using bioinformatics and luciferase reporter assays, we found that miR-326 was a direct target of hsa_circ_0003998. Functional analysis revealed that miR-326 mediated the effect of hsa_circ_0003998 on chemosensitivity. Our findings provide a molecular… More >

  • Open Access

    ARTICLE

    Clinical Characteristics and Molecular Patterns of RET-Rearranged Lung Cancer in Chinese Patients

    Kai Zhang*, Huajun Chen, Ye Wang, Lin Yang§, Chengzhi Zhou, Weiqiang Yin#, Guangsuo Wang§, Xinru Mao**, Jianxing Xiang**, Bing Li**, Tengfei Zhang**, Shihong Fei*

    Oncology Research, Vol.27, No.5, pp. 575-582, 2019, DOI:10.3727/096504018X15344979253618

    Abstract RET rearrangement has been proven as an oncogenic driver in patients with lung cancer. However, the prevalence, clinical characteristics, molecular features, and therapeutic options in RET-rearranged patients remain unclear, especially in Chinese lung cancer patients. We retrospectively collected 6,125 Chinese lung cancer patients who have been profiled using next-generation sequencing (NGS). The clinical demographics and molecular features of RET rearrangement-positive patients were analyzed. RET rearrangements were identified in 84 patients with a proportion of 1.4% in our cohort. The median age at diagnosis was 58 years, and it mainly occurred in females with adenocarcinoma histology. KIF5B-RET was the most frequent… More >

  • Open Access

    ARTICLE

    Microenvironment Analysis of Prognosis and Molecular Signature of Immune-Related Genes in Lung Adenocarcinoma

    Bo Ling, Zuliang Huang, Suoyi Huang, Li Qian, Genliang Li, Qianli Tang

    Oncology Research, Vol.28, No.6, pp. 561-578, 2020, DOI:10.3727/096504020X15907428281601

    Abstract There is growing evidence on the clinical significance of tumor microenvironment (TME) cells in predicting prognosis and therapeutic effects. However, cell interactions in tumor microenvironments have not been thoroughly studied or systematically analyzed so far. In this study, 22 immune cell components in the lung adenocarcinoma (LUAD) TME were analyzed using gene expression profile from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The TME-based molecular subtypes of LUAD were defined to evaluate further the relationship between molecular subtypes, prognosis, and clinical characteristics. A TME risk score model was constructed by using the differentially expressed genes (DEGs) of… More >

  • Open Access

    ARTICLE

    lncCRLA Enhanced Chemoresistance in Lung Adenocarcinoma That Underwent Epithelial–Mesenchymal Transition

    Weili Min*1, Liangzhang Sun†1, Burong Li, Xiao Gao*, Shuqun Zhang*, Yang Zhao*

    Oncology Research, Vol.28, No.9, pp. 857-872, 2020, DOI:10.3727/096504021X16203818567367

    Abstract EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated caspase 8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel in patients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of caspase 8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of caspase 8, during which FADD interacted with RIPK1 to activate the RIPK1/RIPK3/MLKL signaling axis. Accompanied… More >

  • Open Access

    ARTICLE

    Identification of a Novel Cancer Stemness-Associated ceRNA Axis in Lung Adenocarcinoma via Stemness Indices Analysis

    Pihua Han*†1, Haiming Yang‡1, Xiang Li*1, Jie Wu*, Peili Wang§, Dapeng Liu*, Guodong Xiao, Xin Sun*, Hong Ren*

    Oncology Research, Vol.28, No.7-8, pp. 715-729, 2020, DOI:10.3727/096504020X16037124605559

    Abstract The aim of this study was to identify a novel cancer stemness-related ceRNA regulatory axis in lung adenocarcinoma (LUAD) via weighted gene coexpression network analysis of a stemness index. The RNA sequencing expression profiles of 513 cancer samples and 60 normal samples were obtained from the TCGA database. Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) were identified with R software. Functional enrichment analysis was conducted using DAVID 6.8. The ceRNA network was constructed via multiple bioinformatics analyses, and the correlations between possible ceRNAs and prognosis were analyzed using Kaplan–Meier plots. WGCNA was then applied to distinguish key genes… More >

  • Open Access

    ARTICLE

    Curcumol Inhibits Lung Adenocarcinoma Growth and Metastasis via Inactivation of PI3K/AKT and Wnt/β-Catenin Pathway

    Sheng Li*1, Guoren Zhou*1, Wei Liu, Jinjun Ye, Fangliang Yuan, Zhi Zhang

    Oncology Research, Vol.28, No.7-8, pp. 685-700, 2020, DOI:10.3727/096504020X15917007265498

    Abstract Curcumol (Cur), isolated from the Traditional Chinese Medical plant Rhizoma Curcumae, is the bioactive component of sesquiterpene reported to possess antitumor activity. However, its bioactivity and mechanisms against lung adenocarcinoma are still unclear. We investigated its effect on lung adenocarcinoma and elucidated its underlying molecular mechanisms. In vitro, Cur effectively suppressed proliferation, migration, and invasion of lung adenocarcinoma cells A549 and H460, which were associated with the altered expressions of signaling molecules, including p-AKT, p-PI3K, p-LRP5/6, AXIN, APC, GSK3 and p- -catenin, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, Cur significantly induced cell apoptosis of A549 and H460 by promoting the… More >

  • Open Access

    ARTICLE

    Comprehensive analysis reveals an arachidonic acid metabolism-related gene signature in patients with pancreatic ductal adenocarcinoma

    HUILI ZHU1, LINA XIAO1, XIA YIN1, SHIBING XIANG1, CHUNHUI WANG2,*

    BIOCELL, Vol.46, No.10, pp. 2241-2256, 2022, DOI:10.32604/biocell.2022.020389

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous, making its prognosis prediction difficult. The arachidonic acid (AA) cascade is involved in carcinogenesis. Therefore, the metabolic enzymes of the AA cascade consist of lipoxygenases (LOXs), phospholipase A2s (PLA2s), and cyclooxygenases (COXs) along with their metabolic products, including leukotrienes. Nevertheless, the prognostic potential of AA metabolism-associated PDAC has not been explored. Herein, the mRNA expression patterns and the matching clinical information of individuals with PDAC were abstracted from online data resources. We employed the LASSO Cox regression model to develop a multigene clinical signature in the TCGA queue. The GEO queue and the… More >

  • Open Access

    ARTICLE

    Clinical Significance of PD-L1 Expression and CD8-Positive Tumor-Infiltrating Lymphocytes in Patients with Cavitary Lung Adenocarcinoma

    Jiangyong Liu1,#,*, Mingming Gu2,#, Yang Xue1, Qiong Wang3, Yong Ren3, Wencai Huang1,*

    Oncologie, Vol.23, No.3, pp. 439-452, 2021, DOI:10.32604/oncologie.2021.017220

    Abstract Cavitary lung cancer is a rare type of lung cancer. Generally, the relationship between cavitary lung adenocarcinoma (LUAD) and specific immune checkpoints remains unknown. In this study, we aimed to detect the expression of programmed cell death ligand-1(PD-L1) and the density of CD8-positive (CD8+) tumor-infiltrating lymphocytes (TILs) to evaluate their clinicopathological significance in the case of patients with cavitary LUAD. This study included 65 patients with cavitary LUAD. Patient specimens were obtained from surgery. The expression of PD-L1 protein and CD8+ TIL status was detected by traditional immunohistochemistry and multiplex quantitative immunofluorescence technology. The correlation of PD-L1 expression and CD8+More >

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