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  • American Association for Cancer Research (AACR)  (8)
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  • American Association for Cancer Research (AACR)  (8)
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  • 1
    Online Resource
    Online Resource
    Abstract 785: Application of CRISPR/Cas9 gene editing to primary T cells
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 785-785
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 785-785
    Abstract: T cells mediate a broad range of immune responses, especially generation of adaptive immunity for cancer cell clearance. Identification of genetic components that modulate T cell proliferation, differentiation, migration and cytotoxicity would facilitate development of more effective cancer immunotherapy. CRISPR/Cas9, as a tool, could generate gene knockout with high specificity and efficiency and has been widely used in genome-wide screening for therapeutic targets in many tumor cell models. However, its application to primary cells especially T cell has not been extensively investigated. Here, we described how to employ the CRISPR/Cas9 tools for immune-oncology target identification in primary mouse T cells. Cas9/sgRNA could be transduced into T cells with high efficiency and low toxicity using a lentivirus based delivery system. The transduced T cells acquired Cas9 expression but no DNA editing was observed. However, we achieved gene editing in primary T cells isolated from a Cas9 transgenic mouse strain after lentiviral delivery of guide RNA's. In summary, we provide a new method to generate DNA editing in primary T cell using CRISPR/Cas9 technology. It could be used for gene knockout, knockin and even genome-wide screening in primary T cell for immune checkpoint regulators. Citation Format: Xi Li, Wanbing Tang, Chenjie Zhou, Yulin Yang, Zhengang Peng, Wenrong Zhou, Qunsheng Ji, Yong Cang. Application of CRISPR/Cas9 gene editing to primary T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 785.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-785
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 2
    Online Resource
    Online Resource
    Abstract 1842: The safety assessment and the pharmacodynamics evaluation of therapeutic cytokine in non-human primates
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1842-1842
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1842-1842
    Abstract: Cytokines are indispensable regulators of innate and adaptive immunity that transfer signals between cells over short distances. Given their abilities to initiate and activate immune responses, cytokines have long been utilized in cancer therapy, whereas there are limitations, short half-life, pleiotropism, functional redundancy, and side effects, slow down the wide application of cytokine therapy. Thus, evaluating the pharmaceutical properties of cytokines or their translated forms, such as supercytokines, immunocytokines, engager cytokines, and synthetic cytokines, in non-human primates shall be a substantial approach to guide and define clinical trial strategies of cytokine-based therapies. In this study, Interleukin-15 (IL-15) is preferably focused due to its potential in proliferating natural killer cells and cytotoxic T lymphocytes by which host’s immunity was boosted to fight against tumor progression. To evaluate the safety and pharmacodynamics of IL-15 in vivo, rhesus macaques were administered intravenously with recombinant human IL-15 (rhIL-15). We revealed that intravenous administration of rhIL-15 to rhesus macaques caused a slightly weight loss and neutropenia, while no other abnormalities were observed during the whole study. Moreover, the level of C-reactive protein (CRP) was found significantly elevated which was consistent with the increased abundance of MCP1, CCL4, and IL-RA chemokines in serum, suggesting that IL-15 treatment induces acute inflammatory response. Furthermore, flow cytometry analysis showed the activation, proliferation and expansion of memory T and NK cells after receiving IL-15. In conclusion, our study deepens the understanding of T and NK cell homeostasis after IL-15 administration in NHPs and may offer critical clinical strategies for human trials. Citation Format: Wei Li, Yixuan Xu, Xin Zhou, Dan Zhu, Meng Xiao, Yulin Zhou, Zhijie Yang, Haodong Li, Bo Pang, Xinghai Song, Yan Xiao, Wenting Shi, Qian Qian, Qingyang Gu. The safety assessment and the pharmacodynamics evaluation of therapeutic cytokine in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1842.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-1842
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    Abstract 1565: Magnetic bead-based serum peptidome profiling for identifying potential biomarkers in esophageal squamous cell carcinoma
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 1565-1565
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 1565-1565
    Abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide, especially in China. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Therefore, there is an urgent need to develop novel serological biomarkers for ESCC. Here, we performed a two-stage serum peptide profiling in 477 unique samples using weak cationic exchange magnetic beads coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The three significantly differentially expressed peaks were used to establish a genetic algorithm model for ESCC. The sensitivity and specificity were 97% and 95.92% in the training set, and 97.03% and 100% in the validation set, respectively. It was significantly better than the other well studied serum proteins such as squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragment 21-1 (Cyfra 21-1). Notably, the diagnostic capability of this model was superior for early stage ESCC with a sensitivity of 96.94% and a specificity of 100%. Furthermore, the three diagnostic peptides were identified as fragments of alpha-2-HS-glycoprotein, thrombospondin-1, and fibrinogen alpha, respectively. The immunohistochemical staining assay showed that TSP1 was significantly overexpressed in tumor tissues and associated with lymph node metastasis and poor prognosis. Overall, we constructed a novel diagnostic model which will benefit the screening, early detection and diagnosis of ESCC. And the identified proteins and their derivative peptides will deepen our understanding of tumorigenesis and serve as potential serological biomarkers for ESCC. Note: This abstract was not presented at the meeting. Citation Format: Kun Jia, Wei Li, Feng Wang, Fang Liu, Xiaofei Liu, Yuanyuan Qiao, Yang Xu, Lanping Zhou, Yulin Sun, Qingwei Ma, Xiaohang Zhao. Magnetic bead-based serum peptidome profiling for identifying potential biomarkers in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1565. doi:10.1158/1538-7445.AM2015-1565
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-1565
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    Abstract 5298: Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5298-5298
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5298-5298
    Abstract: The successful predictively treatment of metastatic breast cancer (MBC) remains a major challenge. Until now there is no definite marker to distinguish responder from non-responder and more and more important, metastasis occurred within different organs lead to serious variations of overall survival. In this study, paclitaxel and anthracyclines pretreated153 patients with MBC received 606 cycles of docetaxel plus thiotepa. 65 of 153 patients were concurrently diagnosed as MBC involved liver metastasis (LM). Among 153 patients, the response were 1 complete response (CR) (0.7%), 25 partial responses (PR) (16.3%), 73 stable diseases (SD) (47.7%), 46 progressive diseases (PD) (30.1%) and 8 unevaluable(5.2%). For LM patients, the localized liver response were 2 CR (3.1%), 20 PR (30.8%), 16 SD (24.6%), 22 PD (33.8%),5 unevaluable (7.7%). Median PFS and OS for both entire and LM subgroup were 6.5 (95% CI, 5.6 to 7.4) versus 4.2 (95%CI, 2.3-6.1), and 20.0 (95% CI, 15.6 to 24.4) versus 14.2 (95%CI, 9.5-18.9) months respectively. 79 SNPs in CYP450, whose minor allele frequency were ≥ 10% were genotyped. There was no significant difference of SNPs in therapeutic responses, PFS or OS. Of importance, there were two distinctive SNPs, rs2277119 and rs4646487 *2/*3 alleles, which tended to have the better liver metastases response than *1 when choosing a false discovery rate as 12%. It seemed that docetaxel plus thiotepa might be regarded as an active specific regimen for MBC with liver metastasis. The generation of conceptually specific chemotherapy targeting the organ with cancer metastasis should be considered in the future. Citation Format: Jing Yu, Ningning Dong, Ying Yan, Bin Shao, Lijun Di, Guohong Song, Li Che, Jun Jia, Hanfang Jiang, Xu Liang, Yulin Zhu, Chaoying Wang, Jie Zahng, Budong Zhu, Xinna Zhou, Xiaoli Wang, Huabing Yang, Jun Ren, Herbert Kim Lyerly. Two distinctive single nucleotide polymorphisms determine liver metastases responses to docetaxel plus thiotepa for metastatic breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5298. doi:10.1158/1538-7445.AM2013-5298 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-5298
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    Abstract 4578: Comparative subcellular proteomics study of hepatocellular carcinoma cell lines differentially expressed alpha fetoprotein: Annexin A2 could serve as a potential histological and serological biomarker
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4578-4578
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4578-4578
    Abstract: Hepatocellular carcinoma (HCC) is a common tumor worldwide with an extremely poor prognosis. Alpha-fetoprotein (AFP) is the only available HCC serological biomarker and has limited effect at early stages. Previous work has proven that AFP-producing and -nonproducing HCC cells have different gene/protein expression profiles. To identify additional candidates that might aid in HCC diagnosis, in addition to giving a better understanding of the mechanisms underlying hepatocarcinogenesis, subcellular fraction proteins from multiple liver cancer (HepG2, Hep3B and SK-HEP-1) and normal cells (HL-7702) were separated and identified using a 2-DE/MALDI-TOF-TOF approach. In total, 50 differentially-expressed proteins between liver cancer and normal liver cells were identified from different fractions including the cytosol, membrane/organelles and nuclear proteins. Among them, the tumor-related protein Annexin A2, was verified to be significantly upregulated in HCC tissues (63.5%, 80/126) especially in AFP-normal cases based on large-scale clinical specimens. Serum levels of Annexin A2 measured by an established ELISA assay were found to be significantly elevated in HCC patients compared with healthy individuals. The serum concentration was also correlated with histological grade. Combined use of AFP and Annexin A2 could increase the diagnostic performance of HCC. These data suggest that Annexin A2 may serve as a novel serological/histological candidate involved in HCC, especially among individuals with normal levels of serum AFP. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4578.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-4578
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 410466-3
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  • 6
    Online Resource
    Online Resource
    Matrix stiffness triggers lipid metabolic crosstalk between tumor and stromal cells to mediate bevacizumab resistance in colorectal cancer liver metastases
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research ( 2023-08-23)
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), ( 2023-08-23)
    Abstract: Bevacizumab is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody that plays an important role in the combination treatment of advanced colorectal cancer (CRC). However, resistance remains a major hurdle limiting bevacizumab efficacy, highlighting the importance of identifying mechanism of anti-angiogenic therapy resistance. Here, we investigated biophysical properties of the extracellular matrix (ECM) related to metabolic processes and acquired resistance to bevacizumab. Evaluation of paired pre- and post-treatment samples of liver metastases from 20 CRC patients treated with combination bevacizumab therapy, including 10 responders and 10 non-responders, indicated that ECM deposition in liver metastases and a highly activated fatty acid oxidation (FAO) pathway were elevated in non-responders after anti-angiogenic therapy compared to responders. In mouse models of liver metastatic CRC, anti-VEGF increased ECM deposition and FAO in CRC cells, and treatment with the FAO inhibitor etomoxir enhanced the efficacy of antiangiogenic therapy. Hepatic stellate cells (HSCs) were essential for matrix stiffness-mediated FAO in colon cancer cells. Matrix stiffness activated lipolysis in HSCs via the focal adhesion kinase (FAK)/yes-associated protein (YAP) pathway, and free fatty acids secreted by HSCs were absorbed as metabolic substrates and activated FAO in colon cancer cells. Suppressing HSC lipolysis using FAK and YAP inhibition enhanced the efficacy of anti-VEGF therapy. Together, these results indicate that bevacizumab-induced ECM remodeling triggers lipid metabolic crosstalk between colon cancer cells and HSCs. This metabolic mechanism of bevacizumab resistance mediated by the physical tumor microenvironment represents a potential therapeutic target for reversing drug resistance.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-23-0025
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    Online Resource
    Online Resource
    Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Immunology Research Vol. 7, No. 5 ( 2019-05-01), p. 737-750
    Details
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 7, No. 5 ( 2019-05-01), p. 737-750
    Abstract: Tumor microenvironment (TME) cells constitute a vital element of tumor tissue. Increasing evidence has elucidated their clinicopathologic significance in predicting outcomes and therapeutic efficacy. Nonetheless, no studies have reported a systematic analysis of cellular interactions in the TME. In this study, we comprehensively estimated the TME infiltration patterns of 1,524 gastric cancer patients and systematically correlated the TME phenotypes with genomic characteristics and clinicopathologic features of gastric cancer using two proposed computational algorithms. Three TME phenotypes were defined, and the TMEscore was constructed using principal component analysis algorithms. The high TMEscore subtype was characterized by immune activation and response to virus and IFNγ. Activation of transforming growth factor β, epithelial–mesenchymal transition, and angiogenesis pathways were observed in the low TMEscore subtype, which are considered T-cell suppressive and may be responsible for significantly worse prognosis in gastric cancer [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.33–0.54; P & lt; 0.001]. Multivariate analysis revealed that the TMEscore was an independent prognostic biomarker, and its value in predicting immunotherapeutic outcomes was also confirmed (IMvigor210 cohort: HR, 0.63; 95% CI, 0.46–0.89; P = 0.008; GSE78220 cohort: HR, 0.25; 95% CI, 0.07–0.89; P = 0.021). Depicting a comprehensive landscape of the TME characteristics of gastric cancer may, therefore, help to interpret the responses of gastric tumors to immunotherapies and provide new strategies for the treatment of cancers.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    URL: Article
    DOI: 10.1158/2326-6066.CIR-18-0436
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2732517-9
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  • 8
    Online Resource
    Online Resource
    Abstract 2846: Identify urinary biomarkers for colorectal carcinoma liver metastasis
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2846-2846
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2846-2846
    Abstract: Colorectal cancer (CRC) is the third leading prevalent cause of death from cancer in adults, and more than one third of CRC patients are accompanied by liver metastasis. The disease begins as a benign adenomatous polyp, and it subsequently develops into an advanced adenoma and gradually progresses to an invasive cancer. The driving factors behind CRC comprise a series of successive accumulated gene mutations that follow the order “APC-KRAS-TP53-DCC”. Moreover, urine is an important display window for tumor-derived exosomes. Here, to explore the roles of TP53 in CRC and identify novel urinary biomarkers for colorectal cancer metastatic to the liver, a comprehensive proteomic analysis of exosomal proteins from HCT116 TP53-wild type (WT), TP53-knockout (KO) and constructed TP53 (R273H)-mutant (MT) cells, as well as urine samples from CRC patients with and without liver metastasis was performed using the isobaric tag for relative and absolute quantitation (iTRAQ)-2D-LC-MS/MS strategy. The exosomes from the MT and KO cells exhibited significantly reduced sizes compared with the WT cells. A total of 3437 protein groups with ≥2 matched peptides were identified. Specifically, hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) was consistently down-regulated in the exosomes from the MT and KO cells. Functional studies demonstrated that low HGS levels were responsible for the decreased exosome size. TP53 regulated HGS expression and thus HGS-dependent exosome formation. Furthermore, the HGS expression was gradually increased concomitant with CRC carcinogenesis and was an independent poor prognostic factor. In addition, HGS was one of the differentially expressed urine proteins between CRC liver metastasis and healthy individuals. In conclusion, HGS mediates TP53-regulated exosome formation. HGS may serve as a novel histological and urinary prognostic biomarker and a candidate target for therapeutic interventions in CRC. Citation Format: Meng Cai, Yulin Sun, Jiajia Gao, Lina Zhao, Fang Liu, Wei Sun, Zhixiang Zhou, Xiaohang Zhao. Identify urinary biomarkers for colorectal carcinoma liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2846. doi:10.1158/1538-7445.AM2017-2846
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-2846
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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