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Article: [Research Progress in Hepatocyte Growth Factor/Mesenchymal-epithelial Transition Factor Signaling Pathway:Effects and Mechanisms on Resistance to Targeted Therapy for Non-small Cell Lung Cancer].

Chen, Heng Yi / He, Yong

Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae

2021 Volume 43, Issue 2, Page(s) 259–264

Abstract: Targeted therapy is an important therapeutic method for advanced non-small cell lung cancer with driver gene alteration.However,resistance to targeted therapy will inevitably happen in clinical practice,which has become a major issue demanding prompt ... ...

Abstract	Targeted therapy is an important therapeutic method for advanced non-small cell lung cancer with driver gene alteration.However,resistance to targeted therapy will inevitably happen in clinical practice,which has become a major issue demanding prompt solution.Studies have demonstrated that bypass resistance mediated by the activation of hepatocyte growth factor(HGF)/mesenchymal-epithelial transition factor(MET)signaling pathway is a common cause of resistance to targeted therapy.Presently,relevant studies have accumulated rich experience in the specific mechanisms.To be brief,HGF/MET is an important target for overcoming the resistance to targeted therapy and promises to be a leading biomarker for judging and observing the occurrence of resistance.This paper introduces the recent studies concerning the effects and mechanisms of HGF/MET signaling pathway on resistance to targeted therapy.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Epithelial-Mesenchymal Transition ; Hepatocyte Growth Factor ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Proto-Oncogene Proteins c-met/genetics ; Proto-Oncogene Proteins c-met/metabolism ; Signal Transduction
Chemical Substances	Hepatocyte Growth Factor (67256-21-7) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	Chinese
Publishing date	2021-05-09
Publishing country	China
Document type	Journal Article
ZDB-ID	604853-5
ISSN	1000-503X
ISSN	1000-503X
DOI	10.3881/j.issn.1000-503X.11968
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Article ; Online: Micro but mighty-Micronutrients in the epigenetic regulation of adaptive immune responses.

Chen, Heng-Yi / Hsu, Michael / Lio, Chan-Wang Jerry

Immunological reviews

2021 Volume 305, Issue 1, Page(s) 152–164

Abstract: Micronutrients are essential small molecules required by organisms in minute quantity for survival. For instance, vitamins and minerals, the two major categories of micronutrients, are central for biological processes such as metabolism, cell replication, ...

Abstract	Micronutrients are essential small molecules required by organisms in minute quantity for survival. For instance, vitamins and minerals, the two major categories of micronutrients, are central for biological processes such as metabolism, cell replication, differentiation, and immune response. Studies estimated that around two billion humans worldwide suffer from micronutrient deficiencies, also known as "hidden hunger," linked to weakened immune responses. While micronutrients affect the immune system at multiple levels, recent studies showed that micronutrients potentially impact the differentiation and function of immune cells as cofactors for epigenetic enzymes, including the 2-oxoglutarate-dependent dioxygenase (2OGDD) family involved in histone and DNA demethylation. Here, we will first provide an overview of the role of DNA methylation in T cells and B cells, followed by the micronutrients ascorbate (vitamin C) and iron, two critical cofactors for 2OGDD. We will discuss the emerging evidence of these micronutrients could regulate adaptive immune response by influencing epigenetic remodeling.
MeSH term(s)	Epigenesis, Genetic ; Humans ; Immunity/genetics ; Micronutrients/metabolism ; Minerals/metabolism ; Vitamins
Chemical Substances	Micronutrients ; Minerals ; Vitamins
Language	English
Publishing date	2021-11-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13045
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Article: Update two-dimensional SAR offset tracking deformation time series with complex sequential least squares estimation

Wang, Bao-Hang / Zhao, Chao-Ying / Zhang, Qin / Chen, Li-Quan / Chen, Heng-Yi

Remote sensing letters. 2021 Mar. 04, v. 12, no. 3

2021

Abstract: Unlike synthetic aperture radar (SAR) interferometry, SAR offset tracking method can measure two-dimensional (2-D) large-gradient deformation with precision as 1/10 to 1/30 pixels size. In terms of 2-D deformation time series estimation, the pixel-offset ...

Abstract	Unlike synthetic aperture radar (SAR) interferometry, SAR offset tracking method can measure two-dimensional (2-D) large-gradient deformation with precision as 1/10 to 1/30 pixels size. In terms of 2-D deformation time series estimation, the pixel-offset small baseline subset (PO-SBAS) method was proposed. However, little research has been conducted on the dynamic estimation of 2-D deformation time series for new SAR acquisitions, which has increasing demand with the availability of SAR data. In this letter, we introduced a novel method to update 2-D deformation time series dynamically under the frame of PO-SBAS. Firstly, complex least squares (CLS) method is derived to solve the complex linear function model, and the difference between the CLS estimation in complex value and the LS estimation in real value for the real and imaginary parts, respectively, are compared. Secondly, complex sequential least squares (CSLS) estimation is proposed to update 2-D deformation time series dynamically and efficiently. Finally, both simulated and real SAR data verified the performance of the proposed method. It can be taken as a promising SAR tool for dynamic 2-D deformation estimation for the scenarios of glacier movement, mining-induced displacement, and co-seismic deformation, etc.
Keywords	deformation ; glaciers ; interferometry ; models ; synthetic aperture radar ; time series analysis
Language	English
Dates of publication	2021-0304
Size	p. 249-258.
Publishing place	Taylor & Francis
Document type	Article
Note	NAL-AP-2-clean
ISSN	2150-7058
DOI	10.1080/2150704X.2020.1864055
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Article ; Online: Role of Galectins in Tumors and in Clinical Immunotherapy.

Chou, Feng-Cheng / Chen, Heng-Yi / Kuo, Chih-Chi / Sytwu, Huey-Kang

International journal of molecular sciences

2018 Volume 19, Issue 2

Abstract: Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins is known to be linked to the development, progression ... ...

Abstract	Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins is known to be linked to the development, progression and metastasis of cancers. Galectins also have diverse functions on different immune cells that either promote inflammation or dampen T cell-mediated immune responses, depending on cognate receptors on target cells. Thus, tumor-derived galectins can have bifunctional effects on tumor and immune cells. This review focuses on the biological effects of galectin-1, galectin-3 and galectin-9 in various cancers and discusses anticancer therapies that target these molecules.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Galectin 1/antagonists & inhibitors ; Galectin 1/genetics ; Galectin 1/metabolism ; Galectin 3/antagonists & inhibitors ; Galectin 3/genetics ; Galectin 3/metabolism ; Galectins/antagonists & inhibitors ; Galectins/genetics ; Galectins/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Molecular Targeted Therapy/methods ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism
Chemical Substances	Antineoplastic Agents ; Galectin 1 ; Galectin 3 ; Galectins ; LGALS3 protein, human ; LGALS9 protein, human
Language	English
Publishing date	2018-02-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms19020430
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Article ; Online: Epigenetic remodeling by vitamin C potentiates plasma cell differentiation.

Chen, Heng-Yi / Almonte-Loya, Ana / Lay, Fang-Yun / Hsu, Michael / Johnson, Eric / González-Avalos, Edahí / Yin, Jieyun / Bruno, Richard S / Ma, Qin / Ghoneim, Hazem E / Wozniak, Daniel J / Harrison, Fiona E / Lio, Chan-Wang Jerry

eLife

2022 Volume 11

Abstract: Ascorbate (vitamin C) is an essential micronutrient in humans. The severe chronic deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and ... ...

Abstract	Ascorbate (vitamin C) is an essential micronutrient in humans. The severe chronic deficiency of ascorbate, termed scurvy, has long been associated with increased susceptibility to infections. How ascorbate affects the immune system at the cellular and molecular levels remained unclear. From a micronutrient analysis, we identified ascorbate as a potent enhancer for antibody response by facilitating the IL-21/STAT3-dependent plasma cell differentiation in mouse and human B cells. The effect of ascorbate is unique as other antioxidants failed to promote plasma cell differentiation. Ascorbate is especially critical during early B cell activation by poising the cells to plasma cell lineage without affecting the proximal IL-21/STAT3 signaling and the overall transcriptome. As a cofactor for epigenetic enzymes, ascorbate facilitates TET2/3-mediated DNA modification and demethylation of multiple elements at the
MeSH term(s)	Animals ; Ascorbic Acid/pharmacology ; Cell Differentiation ; Epigenesis, Genetic ; Epigenomics ; Humans ; Mice ; Vitamins
Chemical Substances	Vitamins ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2022-09-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.73754
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Article ; Online: Intracellular Galectin-9 Enhances Proximal TCR Signaling and Potentiates Autoimmune Diseases.

Chen, Heng-Yi / Wu, Yen-Fei / Chou, Feng-Cheng / Wu, Yu-Hsuan / Yeh, Li-Tzu / Lin, Kuo-I / Liu, Fu-Tong / Sytwu, Huey-Kang

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 204, Issue 5, Page(s) 1158–1172

Abstract: Galectin-9 is a risk gene in inflammatory bowel disease. By transcriptomic analyses of ileal biopsies and PBMCs from inflammatory bowel disease patients, we identified a positive correlation between galectin-9 expression and colitis severity. We observed ...

Abstract	Galectin-9 is a risk gene in inflammatory bowel disease. By transcriptomic analyses of ileal biopsies and PBMCs from inflammatory bowel disease patients, we identified a positive correlation between galectin-9 expression and colitis severity. We observed that galectin-9-deficient T cells were less able to induce T cell-mediated colitis. However, several mouse-based studies reported that galectin-9 treatment induces T cell apoptosis and ameliorates autoimmune diseases in an exogenously modulated manner, indicating a complicated regulation of galectin-9 in T cells. We found that galectin-9 is expressed mainly inside T cells, and its secreted form is barely detected under physiological conditions. Endogenous galectin-9 was recruited to immune synapses upon T cell activation. Moreover, proximal TCR signaling was impaired in galectin-9-deficient T cells, and proliferation of these cells was decreased through an intracellularly modulated manner. Th17 cell differentiation was downregulated in galectin-9-deficient T cells, and this impairment can be rescued by strong TCR signaling. Taken together, these findings suggest that intracellular galectin-9 is a positive regulator of T cell activation and modulates the pathogenesis of autoimmune diseases.
MeSH term(s)	Animals ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; Autoimmune Diseases/pathology ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Galectins/genetics ; Galectins/immunology ; Mice ; Mice, Knockout ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Th17 Cells/immunology ; Th17 Cells/pathology
Chemical Substances	Galectins ; Receptors, Antigen, T-Cell ; galectin 9, mouse
Language	English
Publishing date	2020-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1901114
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Article ; Online: PERK is a critical metabolic hub for immunosuppressive function in macrophages.

Raines, Lydia N / Zhao, Haoxin / Wang, Yuzhu / Chen, Heng-Yi / Gallart-Ayala, Hector / Hsueh, Pei-Chun / Cao, Wei / Koh, Yeojung / Alamonte-Loya, Ana / Liu, Pu-Ste / Ivanisevic, Julijana / Lio, Chan-Wang Jerry / Ho, Ping-Chih / Huang, Stanley Ching-Cheng

Nature immunology

2022 Volume 23, Issue 3, Page(s) 431–445

Abstract: Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular ... ...

Abstract	Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation. Loss of PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. PERK activation mediated the upregulation of phosphoserine aminotransferase 1 (PSAT1) and serine biosynthesis via the downstream transcription factor ATF-4. Increased serine biosynthesis resulted in enhanced mitochondrial function and α-ketoglutarate production required for JMJD3-dependent epigenetic modification. Inhibition of PERK suppressed macrophage immunosuppressive activity and could enhance the efficacy of immune checkpoint programmed cell death protein 1 inhibition in melanoma. Our findings delineate a previously undescribed connection between PERK signaling and PSAT1-mediated serine metabolism critical for promoting immunosuppressive function in M2 macrophages.
MeSH term(s)	Endoplasmic Reticulum Stress/genetics ; Macrophages/metabolism ; Signal Transduction ; Unfolded Protein Response ; eIF-2 Kinase/genetics ; eIF-2 Kinase/metabolism
Chemical Substances	eIF-2 Kinase (EC 2.7.11.1)
Language	English
Publishing date	2022-02-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-022-01145-x
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Article ; Online: Diagnostic possibility of the combination of exhaled nitric oxide and blood eosinophil count for eosinophilic asthma.

Li, Jiang-Hua / Han, Rui / Wang, Yu-Bo / Cheng, Min / Chen, Heng-Yi / Lei, Wen-Hui / Li, Li / Gao, Chen / Zhao, Na-Na / Nie, Nai-Fu / Li, Zhong-Yan / Yin, Guo-Qing / Huang, Shuai / He, Yong

BMC pulmonary medicine

2021 Volume 21, Issue 1, Page(s) 259

Abstract: Background: Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide ...

Abstract	Background: Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests. Methods: We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis. Results: In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P < 0.001). The odds ratio for having asthma increased progressively with a gradual increase in FeNO or B-Eos count (both P < 0.001; assessed using the Cochran-Armitage trend test). Further analysis of in-series combinations of different threshold values for these biomarkers indicated that moderately elevated biomarker levels (FeNO > 40 ppb and B-Eos > 300 cells/μl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017-2019 data as the internal validation dataset. Conclusion: FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/μl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.
MeSH term(s)	Adult ; Asthma/blood ; Asthma/complications ; Asthma/diagnosis ; Cohort Studies ; Eosinophils ; Female ; Fractional Exhaled Nitric Oxide Testing ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Pulmonary Eosinophilia/complications ; Retrospective Studies
Language	English
Publishing date	2021-08-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2059871-3
ISSN	1471-2466 ; 1471-2466
ISSN (online)	1471-2466
ISSN	1471-2466
DOI	10.1186/s12890-021-01626-z
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Article: Combined treatment with metformin and gefitinib overcomes primary resistance to EGFR-TKIs with EGFR mutation via targeting IGF-1R signaling pathway.

Pan, Yong-Hong / Jiao, Lin / Lin, Cai-Yu / Lu, Cong-Hua / Li, Li / Chen, Heng-Yi / Wang, Yu-Bo / He, Yong

Biologics : targets & therapy

2018 Volume 12, Page(s) 75–86

Abstract: Aim: Although EGFR tyrosine kinase inhibitors (TKIs) have shown dramatic effects against sensitizing EGFR mutations in non-small cell lung cancer (NSCLC), ~20%-30% of NSCLC patients with EGFR-sensitive mutation exhibit intrinsic resistance to EGFR-TKIs. ...

Abstract	Aim: Although EGFR tyrosine kinase inhibitors (TKIs) have shown dramatic effects against sensitizing EGFR mutations in non-small cell lung cancer (NSCLC), ~20%-30% of NSCLC patients with EGFR-sensitive mutation exhibit intrinsic resistance to EGFR-TKIs. The purpose of the current study was to investigate the enhanced antitumor effect of metformin (Met), a biguanide drug, in combination with gefitinib (Gef) in primary resistant human lung cancer cells and the associated molecular mechanism. Experimental design: H1975 cell line was treated with Met and/or Gef to examine the inhibition of cell growth and potential mechanism of action by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Ki67 incorporation assay, flow cytometry analysis, small interfering RNA technology, Western blot analysis and xenograft implantation. Results: Insulin-like growth factor-1 receptor (IGF-1R) signaling pathway was markedly activated in EGFR-TKI primary resistant H1975 cells as compared to EGFR-TKI acquired resistance cells (PC-9GR, H1650-M3) and EGFR-TKI sensitivity cells (PC-9, HCC827). Inhibition of IGF-1R activity by AG-1024 (a small molecule of IGF-1R inhibitor), as well as downregulation of IGF-1R by siRNA, significantly enhanced the ability of Gef to suppress proliferation and induce apoptosis in H1975 cells via the inhibition of AKT activation and subsequent upregulation of Bcl-2-interacting mediator of cell death (BIM). Interestingly, the observation showed that Met combined with Gef treatment had similar tumor growth suppression effects in comparison with the addition of AG-1024 to therapy with Gef. A clear synergistic antiproliferative interaction between Met and Gef was observed with a combination index (CI) value of 0.65. Notably, IGF-1R silencing mediated by RNA interference (RNAi) attenuated anticancer effects of Met without obviously resensitizing H1975 cells to Gef. Finally, Met-based combinatorial therapy effectively blocked tumor growth in the xenograft with TKI primary resistant lung cancer cells. Conclusion: Our findings demonstrated that Met combined with Gef would be a promising strategy to overcome EGFR-TKI primary resistance via suppressing IGF-1R signaling pathway in NSCLC.
Language	English
Publishing date	2018-08-20
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2415708-9
ISSN	1177-5491 ; 1177-5475
ISSN (online)	1177-5491
ISSN	1177-5475
DOI	10.2147/BTT.S166867
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Article ; Online: Metformin synergistically enhances the antitumor activity of the third-generation EGFR-TKI CO-1686 in lung cancer cells through suppressing NF-κB signaling.

Pan, Yong-Hong / Lin, Cai-Yu / Lu, Cong-Hua / Li, Li / Wang, Yu-Bo / Chen, Heng-Yi / He, Yong

The clinical respiratory journal

2018 Volume 12, Issue 12, Page(s) 2642–2652

Abstract: Purpose: Third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), rociletinib (CO-1686), is great efficacy against EGFR-mutated patients bearing the T790M resistance mutation. However, acquired resistance may ... ...

Abstract	Purpose: Third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), rociletinib (CO-1686), is great efficacy against EGFR-mutated patients bearing the T790M resistance mutation. However, acquired resistance may emerge. There is a need to characterize acquired resistance mechanism(s) and to devise ways to overcome CO-1686 resistance. Experimental design: MTT assay, ki67 incorporation assay, transwell assay and TUNEL assay were employed to analyze the effects of metformin to reverse CO-1686 resistance in vitro. The NF-κB activity was measured by the antibody of p50, p65, p-IKBɑ, and p-IKKɑ/β. Western blotting was used to analyze the proteins in cells. Results: We have established CO-1686-resistant cell lines of PC-9GRCOR and H1975COR from two parental cell lines of PC-9GR and H1975 by long-term exposure to increasing doses of CO-1686. Compared with the parental cells, PC-9GRCOR cells and H1975COR cells showed 90-folds and 20-folds higher resistance to CO-1686, respectively. Critically, we showed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecular proteins subunits of p50, p65 and its inhibitor proteins of IKBɑ, IKKɑ/β in phosphorylation levels in resistant cells were higher than parental cells. Accordingly, inhibition of NF-κB activity used TPCA-1 effective in decreasing viability and inducing apoptosis of resistant cells. Moreover, metformin overcame the acquired resistance to CO-1686 by reducing cell proliferation and invasion. Metformin combined with CO-1686 synergistically inhibited the p-IKBɑ, p-IKKɑ/β, p50, and p65. Conclusions: NF-κB signaling activation induced acquired resistance to CO-1686. Metformin sensitized resistant cells to CO-1686 via inhibiting NF-κB signaling.
MeSH term(s)	Acrylamides/administration & dosage ; Acrylamides/therapeutic use ; Apoptosis ; Cell Line, Tumor/drug effects ; Cell Proliferation/drug effects ; China/epidemiology ; Drug Resistance/drug effects ; Drug Synergism ; ErbB Receptors/drug effects ; ErbB Receptors/genetics ; Humans ; Hypoglycemic Agents/adverse effects ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Metformin/adverse effects ; Metformin/pharmacology ; NF-kappa B/drug effects ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/administration & dosage ; Pyrimidines/therapeutic use ; Signal Transduction/drug effects ; Signal Transduction/genetics
Chemical Substances	Acrylamides ; Hypoglycemic Agents ; NF-kappa B ; Protein Kinase Inhibitors ; Pyrimidines ; rociletinib (72AH61702G) ; Metformin (9100L32L2N) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2018-11-09
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2442214-9
ISSN	1752-699X ; 1752-6981
ISSN (online)	1752-699X
ISSN	1752-6981
DOI	10.1111/crj.12970
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