GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (22)
Material
Publisher
  • American Association for Cancer Research (AACR)  (22)
Person/Organisation
Language
Years
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Development of Autoantibody Signatures as Novel Diagnostic Biomarkers of Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2010
    In:  Clinical Cancer Research Vol. 16, No. 14 ( 2010-07-15), p. 3760-3768
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 16, No. 14 ( 2010-07-15), p. 3760-3768
    Abstract: Purpose: To select autoantibody signatures as noninvasive biomarkers of non–small cell lung cancer (NSCLC). Experimental Design: A phage cDNA expression library was constructed with fresh samples from 30 lung cancer patients and biopanned using serum pools of 10 NSCLC patients and 10 healthy controls. A six–phage peptide detector was discovered by two-step immunoscreenings and was validated in an independent set of 90 NSCLC patients and 90 matched healthy controls, 30 NSCLC patients with chemotherapy, and 12 chronic obstructive pulmonary disease (COPD) patients. The expression of a peptide target was validated by using immunohistochemistry. Factors affecting NSCLC-related death were evaluated by Cox regression analysis. Results: Six phage peptide clones showing higher seroreactivity than others in 30 NSCLC patients were selected for diagnostic validation. The six–phage peptide detector was able to discriminate between NSCLC patients and healthy controls with a sensitivity and specificity of & gt;92%, and had similar validity for indicating NSCLC at early stage. The seroreactivity of the six phage peptides was significantly higher in the NSCLC patients than in those with chemotherapy and the COPD patients, respectively. Of the six phage peptides, one encoded a peptide showing 100% homology to olfactomedin 1. Expression of olfactomedin 1 protein was significantly higher in lung adenocarcinoma than in lung cancer of other histologic types and normal lung tissues. The autoantibody signature was not associated with the prognosis of the NSCLC patients. Conclusions: The six–phage peptide detector stands out as promising diagnostic biomarkers for NSCLC, unlikely for NSCLC relapse after chemotherapy. Olfactomedin 1 may be a novel target of lung adenocarcinoma. Clin Cancer Res; 16(14); 3760–8. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-10-0193
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract LB-288: An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. LB-288-LB-288
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. LB-288-LB-288
    Abstract: Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12 and plays pivotal roles in transcriptional regulation through its histone H3K27 methyltransferase activity. Dysregulation of PRC2 is observed in multiple human cancers, for example, the catalytic subunit EZH2 is overexpressed in a wide range of human cancers and gain-of-function mutations of EZH2 within its catalytic site have been reported in human B-cell lymphoma, parathyroid carcinoma and melanoma. Small molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported and showed anti-lymphoma efficacy in pre-clinical studies. EED within the PRC2 complex allosterically activate the enzymatic activity by binding to tri-methylated H3K27 (H3K27me3). Here we report the discovery of EED226, a potent and selective PRC2 inhibitor directly binding to the H3K27me3 binding pocket of EED. EED226 induces conformational change upon binding EED leading to loss of PRC2 activity. EED226 shows similar activity as SAM-competitive inhibitors in blocking H3K27 methylation of PRC2 target genes and inducing regression of human lymphoma xenograft tumors. Interestingly, EED226 also effectively inhibits PRC2 containing mutant EZH2 protein resistant to SAM-competitive inhibitors. Together, we show EED226 inhibits PRC2 activity via an allosteric mechanism and offers opportunity for treatment of PRC2-dependent cancers. Citation Format: Wei Qi, Kehao Zhao, Justin Gu, Ying Huang, Youzhen Wang, Hailong Zhang, Man Zhang, Jeff Zhang, Zhengtian Yu, Ling Li, Lin Teng, Shannon Chuai, Chao Zhang, Mengxi Zhao, HoMan Chan, Zijun Chen, Douglas Fang, Fei Qi, Leying Feng, Lijian Feng, Yuan Gao, Hui Ge, Xinjian Ge, Andreas Lingel, Guobin Li, Ying Lin, Yueqin Liu, Fangjun Luo, Minlong Shi, Long Wang, Zhaofu Wang, Yanyan Yu, Jue Zeng, Chenhui Zeng, Lijun Zhang, Qiong Zhang, Shaolian Zhou, Counde Oyang, Peter Atadja, En Li. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED [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 LB-288. doi:10.1158/1538-7445.AM2017-LB-288
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-LB-288
    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
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    FDA Approval: Ceritinib for the Treatment of Metastatic Anaplastic Lymphoma Kinase–Positive Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Clinical Cancer Research Vol. 21, No. 11 ( 2015-06-01), p. 2436-2439
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 11 ( 2015-06-01), p. 2436-2439
    Abstract: On April 29, 2014, the FDA granted accelerated approval to ceritinib (ZYKADIA; Novartis Pharmaceuticals Corporation), a breakthrough therapy-designated drug, for the treatment of patients with anaplastic lymphoma kinase (ALK)–positive, metastatic non–small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. The approval was based on a single-arm multicenter trial enrolling 163 patients with metastatic ALK-positive NSCLC who had disease progression on (91%) or intolerance to crizotinib. Patients received ceritinib at a starting dose of 750 mg orally once daily. The objective response rate (ORR) by a blinded independent review committee was 44% (95% CI, 36–52), and the median duration of response (DOR) was 7.1 months. The ORR by investigator assessment was similar. Safety was evaluated in 255 patients. The most common adverse reactions and laboratory abnormalities included diarrhea (86%), nausea (80%), increased alanine transaminase (80%), increased aspartate transaminase (75%), vomiting (60%), increased glucose (49%), and increased lipase (28%). Although 74% of patients required at least one dose reduction or interruption due to adverse reactions, the discontinuation rate due to adverse reactions was low (10%). With this safety profile, the benefit–risk analysis was considered favorable because of the clinically meaningful ORR and DOR. Clin Cancer Res; 21(11); 2436–9. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-14-3157
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract LB211: Discovery of RenNano®-derived human heavy-chain-only antibodies that cross the blood-brain barrier
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 8_Supplement ( 2023-04-14), p. LB211-LB211
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 8_Supplement ( 2023-04-14), p. LB211-LB211
    Abstract: Therapeutic antibodies have been successfully used to treat several diseases, such as cancers and autoimmune diseases. However, the utility of conventional antibodies for neurological conditions is limited by the blood-brain barrier (BBB). Several strategies to address this issue have been reported, including receptor-mediated transcytosis (RMT) of antibodies using transferrin receptors. We hypothesize that this strategy could be further improved by the use of single-domain antibodies (sdAbs), such as the variable domain of heavy-chain-only antibodies (HCAbs), or variable new antigen receptors (VNARs), which are significantly smaller, and therefore could be used to more efficiently transport drugs of interest across the BBB. To this end, we developed anti-transferrin receptor 1 (TFR1) HCAbs utilizing our fully human heavy-chain-only antibody mice (RenNano®). We immunized RenNano® mice with recombinant TFR1 proteins, isolated the B cells from spleen and lymph nodes, and performed single B cell antibody screening using the Beacon® Optofluidic system. Most of the antibodies tested were cross-reactive to human and monkey TFR1. Furthermore, even though the antigen specificity relies on the VHH domain instead of a conventional antibody variable domain, the affinity of these HCAbs can reach 10−8-10−9 (KD). Of the 7 HCAbs tested, 6 were internalized into the human brain microvascular endothelial cell line, hCMEC/D3. To assess brain penetration of these antibodies in vivo, mice expressing human TFR1 (hTFR1 mice) received a tail vein injection with either isotype control, positive control pabinafusp alfa (a BBB penetrating anti-TFR1 monoclonal antibody enzyme conjugate) analog or RenNano®-derived HCAbs. After 0.5, 6, 24, and 72 h of exposure, mice brains were dissected for the quantification of HCAbs and for immunohistochemical analyses. The levels of anti-TFR1 HCAbs in the parenchyma was significantly higher than isotype controls and pabinafusp alfa analog. In brain sections, HCAbs were clearly observed in the parenchyma, and were colocalized with TFR1-expressing cells. These results demonstrate that HCAbs developed from RenNano® mice are able to penetrate the BBB. Taken together, these data highlight the tremendous potential for HCAbs and its variable domain sdAbs for transporting cargo across the BBB. Due to their smaller size and simpler structure, sdAbs could ultimately provide therapeutic benefit for neurodegenerative diseases, and offer promising potential for tumor penetration. Citation Format: Yiqing Hu, Lijun Zhang, Wenying Wang, Huizhen Zhao, Jiawei Yao, Chunhui Lv, Yunsheng Yao, Li Hui, Qingcong Lin, Taolin Liu, Yuelei Shen. Discovery of RenNano®-derived human heavy-chain-only antibodies that cross the blood-brain barrier [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB211.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-LB211
    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
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract LB131: Genome-wide CRISPR-Cas9 screen parallel with transcriptome RNAseq to identify synthetic lethal drug targets to cisplatin/doxorubicin in triple-negative breast cancer
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. LB131-LB131
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. LB131-LB131
    Abstract: Triple-negative breast cancer (TNBC) accounts for 15-20% of cases yet disproportional accounts for 35% of breast cancer deaths. Chemotherapy remains the first-line treatment for TNBC. Despite the great research efforts, above half of TNBC patients have developed drug resistance after chemotherapies. Thus, the study of chemo-resistance and identification of novel targets are critical to improving TNBC treatment. In our study, we compared genomic profiles between TNBC cell lines and patients' samples and selected the most representative one, MDA-MB-231,for TNBC chemotherapy-poor responders. Then, Genome-wide CRISPR-Cas9 screen and RNAseq were performed in MDA-MB-231 to identify potential synthetic lethal targets to Cisplatin/Doxorubicin. To identify cell lines that correspond to poor responder patients, we selected genomic profiles of 17 good responders, 36 poor responders, and 21 TNBC cell lines from GEO database. We used Hierarchical clustering analysis, Spearman's rank correlation, and GSEA analysis to determine the representative cell lines in gene expression level and pathway level. With the results from our analysis, MDA-MB-231 is most representative among 21 TNBC cell lines. To identify essential genes and pathways for cell survival under Cisplatin/Doxorubicin treatment, we performed genome-wide CRISPR-Cas9 knockout screens in MDA-MB-231 and introduced CRISPR library TKOV3 into cells by lentivirus. After puromycin selection, the surviving cells were treated with Cisplatin/Doxorubicin for 21 days and sgRNAs were sequenced at ~80 million reads per sample to achieve a 600x coverage over the TKOV3 library. To accurate the CRISPR-Cas9 screen results and capture the transcriptomic changes during the Cisplatin/Doxorubicin treatment, we performed RNAseq from MDA-MD-231 after treating in same drug conditions matched with the CRISPR screen. By the MAGeCK algorithm, we generated the list of candidate genes that can form a synthetic lethal partnership with Cisplatin/Doxorubicin. Our negative selection screen confirmed that loss of essential genes from DNA damage repair and regulation of DNA replication pathways, such as BCL2L1, ATM, CDC25B, NBN, sensitizes cells to Cisplatin/Doxorubicin, which has been reported in DNA damage drug synthetic lethal studies. Meanwhile, our analysis also revealed hundreds of unrecognized genes involved in the G2/M DNA damage checkpoint, AMPK signaling pathway, mTOR signaling pathway, and Hsp90-mediated pathways. In addition, the pathways related to transcriptomic response to Cisplatin/Doxorubicin from RNAseq data show many differences with essential pathways shown in the CRISPR screen, which proposed a complex regulation system in cell response to DNA damage drug. In general, Genome-wide CRISPR-Cas9 screen along with transcriptome RNAseq is efficient to identify essential genes that have potential synthetic lethal interaction with Cisplatin/Doxorubicin. This provides new opportunities for combination therapies in TNBC chemo-resistant patients. Citation Format: Shuai Shao, Shan Tang, Xue Wu, Yue Zhao, Huo Yang, Lijun Cheng, Lang Li. Genome-wide CRISPR-Cas9 screen parallel with transcriptome RNAseq to identify synthetic lethal drug targets to cisplatin/doxorubicin in triple-negative breast cancer [abstract] . In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB131.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-LB131
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract 549: Genome-wide CRISPR-Cas9 screen and RNAseq analysis identify new candidate synthetic lethality partners to PARP inhibitor in triple-negative breast cancer
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 549-549
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 549-549
    Abstract: As monotherapy, Poly (ADP-ribose) polymerase inhibitors (PARPi) have achieved remarkable success in treating tumors with germline BRCA1/2 mutation due to the synthetic lethality in DNA damage response. The efficacy of PARPi in combination with other therapeutic agents is still under investigation. However, BRCA mutant tumors constitute only 5-10% of total breast cancer diagnoses. Therefore, to extend the benefit of PARPi beyond BRCA mutant tumors, it is imperative to identify other genetic determinants that also contribute to PARPi sensitivity. Such knowledge also provides valuable insight into the development of combination therapies involving PARPi. To identify genes and pathways that are essential for cell survival under PARPi treatment, we performed genome-wide CRISPR-Cas9 knockout screens in a BRCA-functional, triple-negative breast cancer cell line MDA-MB-231 treated with talazoparib at a low dose (IC20, 20nM). Toronto CRISPR human knockout library TKOV3 was introduced into cells using lentivirus at MOI of 0.3~0.4. After puromycin selection, the surviving cells were treated with talazoparib or DMSO for 20 days before harvesting. The sgRNAs were sequenced at ~30 million reads per sample to achieve a 300x coverage over the TKOV3 library. To increase the accuracy of the CRISPR-Cas9 screen result, and to capture the transcriptomic changes during a relative long-term PARPi treatment as used in the screening process, we also did RNAseq profiling in MDA-MD-231 cells cultured in the conditions matched with the CRISPR-Cas9 screen. Using mRNA level as a filter to remove non-expressed genes, we were able to generate a list of candidate genes that have the potential to form synthetic lethal partnership with talazoparib. Our negative selection screen confirmed that loss of key components of DNA damage repair and DNA replication pathways such as ATM, RNASEH2C, ESCO2, EME1, and several components of Fanconi Anemia (FA) core complex sensitizes cells to talazoparib, as has been reported in similar screens using other PARP inhibitors. Meanwhile, our analysis also revealed several previously unrecognized partner genes involved in subcellular trafficking, RNA splicing, and microRNA biogenesis. In addition, the RNAseq profile depicted a transcriptomic response to long-term talazoparib treatment that has many distinctions from the essential pathways shown in the CRISPR-Cas9 screen, suggesting a complex, multi-layer regulation system in cell response to PARP inhibition. Our study identified a set of genes that have potential synthetic lethal interaction with PARPi. The status of these genes can be used to identify subset of triple-negative breast cancer patients who could potentially benefit from PARPi treatment. Strategies targeting these genes represent new opportunities for PARPi combination therapies. Citation Format: Xue Wu, Yue Zhao, Xiaoyu Xie, Xiaoling Xuei, Yunlong Liu, Lijun Cheng, Lang Li. Genome-wide CRISPR-Cas9 screen and RNAseq analysis identify new candidate synthetic lethality partners to PARP inhibitor in triple-negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 549.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-549
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract 830: New bioinformatics workflow of genome-wide CRISPR-Cas9 knockout screens
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 16_Supplement ( 2020-08-15), p. 830-830
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 830-830
    Abstract: Introduction: Genome-wide CRISPR-Cas9 based loss-of-function screens can be used to find essential genes for proliferation and survival of cancer cells. While recent studies have focused on establishing reference sets of essential and non-essential genes, correcting copy number effect and characterizing off-target effect, it lacks in-depth studies of the effects of gene abundance and sgRNAs that targeting multi-genomic loci. To fill this gap timely, we here present a bioinformatics workflow to reduce false positives in CRISPR-Cas9 screens. Description: Gastric adenocarcinoma cell line AGS was infected with CRISPR knockout library (TKOv3) at a multiplicity of infection of 0.3~0.4. We used the cells right after puromycin selection as the baseline sample, and the cells cultured for 14 days or 20 days as the negative selection samples. The sgRNA inserts were amplified by PCR and the corresponding libraries were sequenced on NextSeq 500 with a single-end 75 bp run, followed by analysis by MAGeCK. The read counts of sgRNAs were normalized by non-essential genes to reduce false positives. The RNA-seq data and copy number data were obtained by CCLE portal. To characterize sgRNAs targeting multiple-genomic loci, Bowtie was used to align sgRNA to the reference human genome (GRCh38) with no mismatch, and only the alignments followed by NGG PAM site were remained for downstream analysis. Summary: Integration of RNA-seq data with CRISPR negative screen results showed that the selection signal was noisy for the lowly expressed genes. The fraction of selected essential genes (overall FDR & lt;0.05, absolute value of beta score & gt;1) was as low as 0.11% among the genes with the bottom 10% expression level, while 27% among the genes with the top 10% expression level. After filtering out the lowly expressed genes ( & lt;0.06 RPKM), the selected essential genes had an FDR much closer to 0. Out of the 40 essential genes selected without filtering out lowly expressed genes, none of them was reported oncogenes in literature. To study the influences of multiple alignments of sgRNAs, we only considered the ones with perfect alignments (i.e., no mismatch) so that we can prevent it from being confounding with off-target effects caused by mismatch tolerance. Log fold changes in read counts were calculated for each sgRNA between a later time point (day 14 or 20) vs. baseline (day 0). The median log fold change significantly decreased as a function of the number of perfect alignments (p = 0.0001, Jonckheere trend test). This supports the hypothesis that a sgRNA aligned to several DNA targets will introduce multiple double stranded cuts, and thus will result in biased essentiality scores. Conclusions: Filtering out lowly-expressed genes prior to CRISPR screen data analysis can reduce false positives. In addition, multiple-target sgRNAs can lead to false positives but the effect needs further analysis in a case by case manner. Citation Format: Yue Zhao, Xue Wu, Yuru Wang, Kin Fai Au, Lijun Cheng, Lang Li. New bioinformatics workflow of genome-wide CRISPR-Cas9 knockout screens [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 830.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2020-830
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Abstract 610: Dynamic immune landscape of the peripheral blood mononuclear cells from recurrent hepatocellular carcinoma patients undergoing radiofrequency ablation treatment
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 610-610
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 610-610
    Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third most lethal malignancy worldwide. Radiofrequency ablation (RFA) is the most commonly used curative treatment for the patients not suitable for surgical resection or liver transplantation. It can cause regional and global anti-tumor immune response, but is insufficient to prevent HCC recurrence in many patients. Peripheral blood mononuclear cells (PBMC) are considered to be the best target for the study of the global immune status after RFA. Previous studies on PBMC were mainly based on traditional flow cytometry, which could not differentiate the complicated immune cell subtypes. In this study, we used mass cytometry to comprehensively characterize the phenotypic and functional alterations of the PBMC in recurrent HCC patients who had received RFA treatment. Fifty-four (54) blood samples from 13 patients were analyzed. Manual gating, SPADE analysis and viSNE analysis were used to interpret the mass cytometry data. The percentage of monocytes showed a fast increase after RFA, and reduced to the normal level before the HCC recurrence (P=0.026). A long-lasting reduction of B cells count were also found after the first RFA (P=0.021), and the B cell count remained at a low level before and after the secondary RFA. The percentage of CD4+ T cells in CD45+ cells was significantly reduced after the first RFA, then restored to the pretreatment level at the time of recurrence, and reduced again after the second RFA(P=0.024). CD8+ T cells showed the same alteration trend as CD4+ cells (P=0.03). We also examined the expression of functional markers in T cells and Tregs. Alterations of CD28 expression were most frequently found in T cells. The Treg population showed a large heterogeneity among the patients with TIM3, LAG3 or CTLA4 positive Tregs being the largest populations. These results suggest a more specific treating modality should be used in combination with the RFA treatment. Citation Format: Dexi Chen, Yang Zhao, Yabo Ouyang, Kai Liu, Wei Rao, Feili Wei, Xiaoni Liu, Ying Shi, Shanshan Wang, Lijun Pang, Luxin Qiao, Yunjin Zang, Xiaoming Yin. Dynamic immune landscape of the peripheral blood mononuclear cells from recurrent hepatocellular carcinoma patients undergoing radiofrequency ablation treatment [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 610.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-610
    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
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Abstract 2025: Spatial transcriptomic profiling of progression markers in clear cell renal cell carcinoma
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 2025-2025
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 2025-2025
    Abstract: Next-generation sequencing enabled molecular landscaping and the discovery of novel tumor markers in ccRCC. However, the spatial relationships and histological features of the tumor microenvironment were lost during this process. Combining snRNA-seq, snATAC-seq, Spatial Transcriptomics (ST) technology, and immunofluorescence labeling, we discovered novel ccRCC progression tumor markers, and uncovered their spatial dependent expression pattern in both human ccRCC tumors and patient-derived xenograft (PDX). Using snRNA-seq and snATAC-seq, novel tumor progression markers such as NDRG1, MGST1, ABCC3 and PCSK6 were discovered, and their expressions were validated in ST. We found that one of the key novel tumor markers, CP, exhibited specific spatial expression patterns on tissue slides. The elevation of CP expression region is associated with a higher degree of hyalinization in ccRCC human tumor samples. Similarly, using immunofluorescence labeling, we validated the co-expression of CP and PCSK6 canonical ccRCC marker CA9. Overall, this study revealed novel ccRCC progression markers and linked their spatial expression pattern with histological features. Citation Format: Chia-Kuei Mo, Yige Wu, Terekhanova Nadezhda, Caravan Wagma, Preet Lal, Siqi Chen, Nataly Naser AL Deen, Ruiyang Liu, Yanyan Zhao, Kazuhito Sato, Lijun Yao, Mamatha Serasanambati, Andrew Shinkle, Reyka G. Jayasinghe, Li Ding, Feng Chen. Spatial transcriptomic profiling of progression markers in clear cell renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2025.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-2025
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Neddylation Inhibition Activates the Extrinsic Apoptosis Pathway through ATF4–CHOP–DR5 Axis in Human Esophageal Cancer Cells
    American Association for Cancer Research (AACR) ; 2016
    In:  Clinical Cancer Research Vol. 22, No. 16 ( 2016-08-15), p. 4145-4157
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 22, No. 16 ( 2016-08-15), p. 4145-4157
    Abstract: Purpose: Targeting the protein neddylation pathway has become an attractive anticancer strategy; however, the role of death receptor–mediated extrinsic apoptosis during treatment remained to be determined. Experimental Design: The activation of extrinsic apoptosis and its role in MLN4924 treatment of human esophageal squamous cell carcinoma (ESCC) were evaluated both in vitro and in vivo. The expression of the components of extrinsic apoptotic pathway was determined by immunoblotting analysis and downregulated by siRNA silencing for mechanistic studies. Results: Pharmaceutical or genetic inactivation of neddylation pathway induced death receptor 5 (DR5)–mediated apoptosis and led to the suppression of ESCC in murine models. Mechanistically, neddylation inhibition stabilized activating transcription factor 4 (ATF4), a Cullin-Ring E3 ubiquitin ligases (CRL) substrate. Transcription factor CHOP was subsequently transactivated by ATF4 and further induced the expression of DR5 to activate caspase-8 and induce extrinsic apoptosis. Moreover, the entire neddylation pathway was hyperactivated in ESCC and was negatively associated with patient overall survival. Conclusions: Our findings highlight a critical role of ATF4–CHOP–DR5 axis-mediated extrinsic apoptosis in neddylation-targeted cancer therapy and support the clinical investigation of neddylation inhibitors (e.g., MLN4924) for the treatment of ESCC, a currently treatment-resistant disease with neddylation hyperactivation. Clin Cancer Res; 22(16); 4145–57. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-15-2254
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...