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  1. Article: Cell-free DNA methylation profiles enable early detection of colorectal and gastric cancer.

    Lei, Xiaotian / Zhou, Dongxun / Wen, Ying / Sha, Weihong / Ma, Juan / Tu, Xixiang / Zhai, Kewei / Li, Caixia / Wang, Hong / Tao, Jinsheng / Chen, Zhiwei / Ruan, Weimei / Fan, Jian-Bing / Wang, Bin / Cui, Chunhui

    American journal of cancer research

    2024  Volume 14, Issue 2, Page(s) 744–761

    Abstract: Colorectal cancer (CRC) and gastric cancer (GC) rank the top five common and lethal cancers worldwide. Early detection can significantly reduce the mortality of CRC and GC. However, current clinical screening methods including invasive endoscopic ... ...

    Abstract Colorectal cancer (CRC) and gastric cancer (GC) rank the top five common and lethal cancers worldwide. Early detection can significantly reduce the mortality of CRC and GC. However, current clinical screening methods including invasive endoscopic techniques and noninvasive fecal occult blood test screening tests/fecal immunochemical test have shown low sensitivity or unsatisfactory patient's compliance. Aberrant DNA methylation occurs frequently in tumorigenesis and cell-free DNA (cfDNA) methylation has shown the potential in multi-cancer detection. Herein, we aimed to explore the value of cfDNA methylation in the gastrointestinal cancer detection and develop a noninvasive method for CRC and GC detection. We applied targeted methylation sequencing on a total of 407 plasma samples from patients diagnosed with CRC, GC, and noncancerous gastrointestinal benign diseases (Non-Ca). By analyzing the methylation profiles of 34 CRC, 62 GC and 107 Non-Ca plasma samples in the training set (n=203), we identified 40,110 gastrointestinal cancer-specific markers and 63 tissue of origin (TOO) prediction markers. A new integrated model composed of gastrointestinal cancer detection and TOO prediction for three types of classification of CRC, GC and Non-Ca patients was further developed through logistic regression algorithm and validated in an independent validation set (n=103). The model achieved overall sensitivities of 83% and 81.3% at specificities of 81.5% and 80% for identifying gastrointestinal cancers in the test set and validation set, respectively. The detection sensitivities for GC and CRC were respectively 81.4% and 83.3% in the cohort of the test and validation sets. Among these true positive cancer samples, further TOO prediction showed accuracies of 95.8% and 95.8% for GC patients and accuracies of 86.7% and 93.3% for CRC patients, in test set and validation set, respectively. Collectively, we have identified novel cfDNA methylation biomarkers for CRC and GC detection and shown the promising potential of cfDNA as a noninvasive gastrointestinal cancer detection tool.
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2589522-9
    ISSN 2156-6976
    ISSN 2156-6976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Prediction of competing endogenous RNA coexpression network as prognostic markers in AML.

    Wang, Jun-Dan / Zhou, Hong-Sheng / Tu, Xi-Xiang / He, Yi / Liu, Qi-Fa / Liu, Quentin / Long, Zi-Jie

    Aging

    2019  Volume 11, Issue 10, Page(s) 3333–3347

    Abstract: Recently, competing endogenous RNAs (ceRNAs) hypothesis has gained a great interest in the study of molecular biological mechanisms of cancer occurrence and progression. However, studies on leukemia are limited, and there is still a lack of comprehensive ...

    Abstract Recently, competing endogenous RNAs (ceRNAs) hypothesis has gained a great interest in the study of molecular biological mechanisms of cancer occurrence and progression. However, studies on leukemia are limited, and there is still a lack of comprehensive analysis of lncRNA-miRNA-mRNA ceRNA regulatory network of AML based on high-throughput sequencing and large-scale sample size. We obtained RNA-Seq data and compared the expression profiles between 407 normal whole blood (GTEx) and 151 bone marrows of AML (TCGA). The similarity between two sets of genes with trait in the network was analyzed by weighted correlation network analysis (WGCNA). MiRcode, starBase, miRTarBase, miRDB and TargetScan was used to predict interactions between lncRNAs, miRNAs and target mRNAs. At last, we identified 108 lncRNAs, 10 miRNAs and 8 mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network, which might act as prognostic biomarkers of AML. Among the network, a survival model with 8 target mRNAs (HOXA9+INSR+KRIT1+MYB+SPRY2+UBE2V1+WEE1+ZNF711) was set up by univariate and multivariate cox proportional hazard regression analysis, of which the AUC was 0.831, indicating its sensitivity and specificity in AML prognostic prediction. CeRNA networks could provide further insight into the study on gene regulation and AML prognosis.
    MeSH term(s) Adult ; Aged ; Bone Marrow/metabolism ; Case-Control Studies ; Female ; Gene Expression Profiling ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; Leukemia, Myeloid, Acute/mortality ; Male ; MicroRNAs/metabolism ; Middle Aged ; Proportional Hazards Models ; RNA, Long Noncoding/metabolism ; RNA, Messenger/metabolism
    Chemical Substances MicroRNAs ; RNA, Long Noncoding ; RNA, Messenger
    Language English
    Publishing date 2019-02-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.101985
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Accurate diagnosis of pulmonary nodules using a noninvasive DNA methylation test.

    Liang, Wenhua / Chen, Zhiwei / Li, Caichen / Liu, Jun / Tao, Jinsheng / Liu, Xin / Zhao, Dezhi / Yin, Weiqiang / Chen, Hanzhang / Cheng, Chao / Yu, Fenglei / Zhang, Chunfang / Liu, Luxu / Tian, Hui / Cai, Kaican / Liu, Xiang / Wang, Zheng / Xu, Ning / Dong, Qing /
    Chen, Liang / Yang, Yue / Zhi, Xiuyi / Li, Hui / Tu, Xixiang / Cai, Xiangrui / Jiang, Zeyu / Ji, Hua / Mo, Lili / Wang, Jiaxuan / Fan, Jian-Bing / He, Jianxing

    The Journal of clinical investigation

    2021  Volume 131, Issue 10

    Abstract: BACKGROUNDCurrent clinical management of patients with pulmonary nodules involves either repeated low-dose CT (LDCT)/CT scans or invasive procedures, yet causes significant patient misclassification. An accurate noninvasive test is needed to identify ... ...

    Abstract BACKGROUNDCurrent clinical management of patients with pulmonary nodules involves either repeated low-dose CT (LDCT)/CT scans or invasive procedures, yet causes significant patient misclassification. An accurate noninvasive test is needed to identify malignant nodules and reduce unnecessary invasive tests.METHODWe developed a diagnostic model based on targeted DNA methylation sequencing of 389 pulmonary nodule patients' plasma samples and then validation in 140 plasma samples independently. We tested the model in different stages and subtypes of pulmonary nodules.RESULTSA 100-feature model was developed and validated for pulmonary nodule diagnosis; the model achieved a receiver operating characteristic curve-AUC (ROC-AUC) of 0.843 on 140 independent validation samples, with an accuracy of 0.800. The performance was well maintained in (a) a 6 to 20 mm size subgroup (n = 100), with a sensitivity of 1.000 and adjusted negative predictive value (NPV) of 1.000 at 10% prevalence; (b) stage I malignancy (n = 90), with a sensitivity of 0.971; (c) different nodule types: solid nodules (n = 78) with a sensitivity of 1.000 and adjusted NPV of 1.000, part-solid nodules (n = 75) with a sensitivity of 0.947 and adjusted NPV of 0.983, and ground-glass nodules (n = 67) with a sensitivity of 0.964 and adjusted NPV of 0.989 at 10% prevalence. This methylation test, called PulmoSeek, outperformed PET-CT and 2 clinical prediction models (Mayo Clinic and Veterans Affairs) in discriminating malignant pulmonary nodules from benign ones.CONCLUSIONThis study suggests that the blood-based DNA methylation model may provide a better test for classifying pulmonary nodules, which could help facilitate the accurate diagnosis of early stage lung cancer from pulmonary nodule patients and guide clinical decisions.FUNDINGThe National Key Research and Development Program of China; Science and Technology Planning Project of Guangdong Province; The National Natural Science Foundation of China National.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; DNA Methylation ; DNA, Neoplasm/metabolism ; Female ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/metabolism ; Male ; Middle Aged ; Multiple Pulmonary Nodules/diagnosis ; Multiple Pulmonary Nodules/diagnostic imaging ; Multiple Pulmonary Nodules/metabolism ; Retrospective Studies ; Tomography, X-Ray Computed
    Chemical Substances DNA, Neoplasm
    Language English
    Publishing date 2021-04-01
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI145973
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation.

    Wang, Le-Xun / Wang, Jun-Dan / Chen, Jia-Jie / Long, Bing / Liu, Ling-Ling / Tu, Xi-Xiang / Luo, Yu / Hu, Yuan / Lin, Dong-Jun / Lu, Gui / Long, Zi-Jie / Liu, Quentin

    Scientific reports

    2016  Volume 6, Page(s) 35533

    Abstract: The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In ... ...

    Abstract The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. Our results showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. Surprisingly, inhibition of AurA by AKI603 induced leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells. Furthermore, the induction of senescence was associated with enhancing reactive oxygen species (ROS) level. Moreover, the anti-tumor effect of AKI603 was proved in the BALB/c nude mice KBM5-T315I xenograft model. Taken together, our data demonstrate that the small molecule AurA inhibitor AKI603 may be used to overcome drug resistance induced by BCR-ABL-T315I mutation in CML.
    Language English
    Publishing date 2016-11-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep35533
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells.

    Long, Zi-Jie / Wang, Le-Xun / Zheng, Fei-Meng / Chen, Jia-Jie / Luo, Yu / Tu, Xi-Xiang / Lin, Dong-Jun / Lu, Gui / Liu, Quentin

    International journal of oncology

    2015  Volume 46, Issue 6, Page(s) 2488–2496

    Abstract: Drug resistance still represents a major obstacle to successful chronic myeloid leukemia (CML) treatment and novel compounds or strategies to override this challenging problem are urgently required. Here, we evaluated a novel compound AKI603 against ... ...

    Abstract Drug resistance still represents a major obstacle to successful chronic myeloid leukemia (CML) treatment and novel compounds or strategies to override this challenging problem are urgently required. Here, we evaluated a novel compound AKI603 against oncogenic Aurora kinase A (Aur-A) in imatinib-resistant CML cells. We found that Aur-A was highly activated in imatinib-resistant KBM5-T315I cells. AKI603 significantly inhibited the phosphorylation of Aur-A kinase at Thr288, while had little inhibitory effect on BCR-ABL kinase in both KBM5 and KBM5-T315I cells. AKI603 inhibited cell viability, and induced cell cycle arrest with polyploidy accumulation in KBM5 and KBM5-T315I cells. Moreover, inhibition of Aur-A kinase by AKI603 suppressed colony formation capacity without promoting obvious apoptosis. Importantly, AKI603 promoted cell differentiation in both CML cell types. Thus, our study suggested the potential clinical use of small molecule Aurora kinase inhibitor AKI603 to overcome imatinib resistance in CML treatment.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Aurora Kinase A/antagonists & inhibitors ; Aurora Kinase A/metabolism ; Cell Cycle/drug effects ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Drug Resistance, Neoplasm/drug effects ; Humans ; Imatinib Mesylate/pharmacology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism ; Phosphorylation/drug effects ; Polyploidy ; Pyrazoles/pharmacology ; Pyrimidines/pharmacology
    Chemical Substances AKI603 ; Antineoplastic Agents ; Pyrazoles ; Pyrimidines ; Imatinib Mesylate (8A1O1M485B) ; AURKA protein, human (EC 2.7.11.1) ; Aurora Kinase A (EC 2.7.11.1)
    Language English
    Publishing date 2015
    Publishing country Greece
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1154403-x
    ISSN 1791-2423 ; 1019-6439
    ISSN (online) 1791-2423
    ISSN 1019-6439
    DOI 10.3892/ijo.2015.2960
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3690: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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