69 results on '"Wenchu Lin"'
Search Results
2. Hydrophobic Carbon Dots Derived from Organic Pollutants and Applications in NIR Anticounterfeiting and Bioimaging
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Xinyi Shi, Xingyu Wang, Shaobo Zhang, Zonghui Zhang, Xiangfu Meng, Hongji Liu, Yong Qian, Yefeng Lin, Yanyan Yu, Wenchu Lin, and Hui Wang
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Electrochemistry ,General Materials Science ,Surfaces and Interfaces ,Condensed Matter Physics ,Spectroscopy - Published
- 2023
3. Mitochondrial temperature-responsive drug delivery reverses drug resistance in lung cancer
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Wenchu Lin, Zhifang Chai, Lifo Ruan, Guangjun Nie, Huiru Lu, Yi Hu, Jun Chen, Xiaomeng Cai, Rui Dou, Jia-yu Zhang, and Chuanchao Du
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Mitochondrial temperature ,QH301-705.5 ,Biomedical Engineering ,Drug resistance ,Biomaterials ,medicine ,polycyclic compounds ,Doxorubicin ,Biology (General) ,Cytotoxicity ,Lung cancer ,Materials of engineering and construction. Mechanics of materials ,Thermoresponsive ,business.industry ,Cancer ,medicine.disease ,Nanomedicines ,carbohydrates (lipids) ,Drug delivery ,Cancer research ,TA401-492 ,Efflux ,Nanocarriers ,business ,Biotechnology ,medicine.drug - Abstract
Reversal of cancer drug resistance remains a critical challenge in chemotherapy. Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer. To overcome the intrinsic limitations in conventional mitochondrial targeting strategies, we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin (DOX) resistance in lung cancer. Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors. As a consequence, thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice. This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.
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- 2022
4. Corrigendum: The MYC paralog-PARP1 axis as a potential therapeutic target in MYC paralog-activated small cell lung cancer
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Xing Bian, Xiaolin Wang, Qiuyan Zhang, Liying Ma, Guozhen Cao, Ao Xu, Jinhua Han, Jun Huang, and Wenchu Lin
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Cancer Research ,Oncology - Published
- 2023
5. Supplementary Fig. S2 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Supplementary Fig. S2. Histone mark profiles in known menin targets
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- 2023
6. Interview with Dr. Meyerson from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
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Matthew Meyerson, Roman K. Thomas, Eric B. Haura, Kwok-Kin Wong, Nathanael S. Gray, Daniel Rauh, Jeonghee Cho, Adam J. Bass, Heidi Greulich, Wendy Winckler, Bruce E. Johnson, Pasi A. Janne, Michael J. Eck, Charles Hatton, Megan Hanna, Ming Sound Tsao, David G. Beer, Jürgen Wolf, Erich Stoelben, Hannie Sietsma, Wim Timens, Harry Groen, Joachim H. Clement, Iver Petersen, Åslaug Helland, Odd Terje Brustugun, Philippe Lorimier, Christian Brambilla, Elisabeth Brambilla, Sascha Ansén, Silvia Querings, Franziska Gabler, Frauke Leenders, Mirjam Koker, Holger Moch, Alex Soltermann, Johannes M. Heuckmann, Thomas Zander, Danila Seidel, Helga B. Salvesen, Robert C. Onofrio, Michael S. Lawrence, Jeffrey R. Simard, Martin Peifer, Stefanie Heynck, Sang Min Lim, Xianming Deng, Jianming Zhang, Wenchu Lin, Brittany A. Woods, Lear E. Brace, Wenjun Zhou, Amit Dutt, Chunxiao Xu, Alex H. Ramos, Martin L. Sos, and Peter S. Hammerman
- Abstract
mp3 file (6.8 MB). In the inaugural edition of the Cancer Discovery podcast, Executive Editor Mark Landis talks with Matthew Meyerson about his paper, which describes the identification of the DDR2 kinase as a therapeutic target in squamous cell lung cancer.
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- 2023
7. Table S5 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Table S5. Primer list
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- 2023
8. Table S4 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Table S4. Biological annotation for the top 25 genes
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- 2023
9. Supplementary Fig. S5 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Supplementary Fig. S5. Time-dependent epigenetic changes at the promoters of Men1-dependent targets
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- 2023
10. Table S3 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Table S3. Differential H3k4me3 signal in Men1 KO pancreatic islet compared with RIP-Cre control
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- 2023
11. Supplementary Table 1 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
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Matthew Meyerson, Roman K. Thomas, Eric B. Haura, Kwok-Kin Wong, Nathanael S. Gray, Daniel Rauh, Jeonghee Cho, Adam J. Bass, Heidi Greulich, Wendy Winckler, Bruce E. Johnson, Pasi A. Janne, Michael J. Eck, Charles Hatton, Megan Hanna, Ming Sound Tsao, David G. Beer, Jürgen Wolf, Erich Stoelben, Hannie Sietsma, Wim Timens, Harry Groen, Joachim H. Clement, Iver Petersen, Åslaug Helland, Odd Terje Brustugun, Philippe Lorimier, Christian Brambilla, Elisabeth Brambilla, Sascha Ansén, Silvia Querings, Franziska Gabler, Frauke Leenders, Mirjam Koker, Holger Moch, Alex Soltermann, Johannes M. Heuckmann, Thomas Zander, Danila Seidel, Helga B. Salvesen, Robert C. Onofrio, Michael S. Lawrence, Jeffrey R. Simard, Martin Peifer, Stefanie Heynck, Sang Min Lim, Xianming Deng, Jianming Zhang, Wenchu Lin, Brittany A. Woods, Lear E. Brace, Wenjun Zhou, Amit Dutt, Chunxiao Xu, Alex H. Ramos, Martin L. Sos, and Peter S. Hammerman
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Supplementary Table 1 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
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- 2023
12. Supplementary material from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Supplementary material.
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- 2023
13. Supplementary Figures 1-7 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
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Matthew Meyerson, Roman K. Thomas, Eric B. Haura, Kwok-Kin Wong, Nathanael S. Gray, Daniel Rauh, Jeonghee Cho, Adam J. Bass, Heidi Greulich, Wendy Winckler, Bruce E. Johnson, Pasi A. Janne, Michael J. Eck, Charles Hatton, Megan Hanna, Ming Sound Tsao, David G. Beer, Jürgen Wolf, Erich Stoelben, Hannie Sietsma, Wim Timens, Harry Groen, Joachim H. Clement, Iver Petersen, Åslaug Helland, Odd Terje Brustugun, Philippe Lorimier, Christian Brambilla, Elisabeth Brambilla, Sascha Ansén, Silvia Querings, Franziska Gabler, Frauke Leenders, Mirjam Koker, Holger Moch, Alex Soltermann, Johannes M. Heuckmann, Thomas Zander, Danila Seidel, Helga B. Salvesen, Robert C. Onofrio, Michael S. Lawrence, Jeffrey R. Simard, Martin Peifer, Stefanie Heynck, Sang Min Lim, Xianming Deng, Jianming Zhang, Wenchu Lin, Brittany A. Woods, Lear E. Brace, Wenjun Zhou, Amit Dutt, Chunxiao Xu, Alex H. Ramos, Martin L. Sos, and Peter S. Hammerman
- Abstract
Supplementary Figures 1-7 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
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- 2023
14. Table S1 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Table S1. H3K4me3 Peaks in RIP-Cre control
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- 2023
15. Supplementary Fig. S3 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Supplementary Fig. S3. Histone mark profiles in Hox genes
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- 2023
16. Supplementary Fig. S1 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Supplementary Fig. S1. Intersection of genes showing enhanced H3K4me3 with upregulated genes, in Men1 KO islets
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- 2023
17. Supplementary Figure Legends 1-7 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
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Matthew Meyerson, Roman K. Thomas, Eric B. Haura, Kwok-Kin Wong, Nathanael S. Gray, Daniel Rauh, Jeonghee Cho, Adam J. Bass, Heidi Greulich, Wendy Winckler, Bruce E. Johnson, Pasi A. Janne, Michael J. Eck, Charles Hatton, Megan Hanna, Ming Sound Tsao, David G. Beer, Jürgen Wolf, Erich Stoelben, Hannie Sietsma, Wim Timens, Harry Groen, Joachim H. Clement, Iver Petersen, Åslaug Helland, Odd Terje Brustugun, Philippe Lorimier, Christian Brambilla, Elisabeth Brambilla, Sascha Ansén, Silvia Querings, Franziska Gabler, Frauke Leenders, Mirjam Koker, Holger Moch, Alex Soltermann, Johannes M. Heuckmann, Thomas Zander, Danila Seidel, Helga B. Salvesen, Robert C. Onofrio, Michael S. Lawrence, Jeffrey R. Simard, Martin Peifer, Stefanie Heynck, Sang Min Lim, Xianming Deng, Jianming Zhang, Wenchu Lin, Brittany A. Woods, Lear E. Brace, Wenjun Zhou, Amit Dutt, Chunxiao Xu, Alex H. Ramos, Martin L. Sos, and Peter S. Hammerman
- Abstract
Supplementary Figure Legends 1-7 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer
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- 2023
18. Supplementary Fig. S4 from Dynamic Epigenetic Regulation by Menin During Pancreatic Islet Tumor Formation
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Matthew Meyerson, Adam J. Bass, Agoston Agoston, Aruna Ramachandran, Chandra Sekhar Pedamallu, Nathan Kaplan, Joshua M. Francis, Shouyong Peng, Hideo Watanabe, and Wenchu Lin
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Supplementary Fig. S4. Relationship between H3K4me3 and H3K27me3 levels in Men1 target genes
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- 2023
19. 具有NIR-II吸收的碳包覆磁铁矿纳米团簇用于成像引导的光热-化学动力学协同治疗
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Yefeng Lin, Ke Zhou, Shaobo Zhang, Yijun Lu, Yuan He, Hongji Liu, Xiangfu Meng, Yong Qian, Xingyu Wang, Xinyi Shi, Wenchu Lin, Junchao Qian, and Hui Wang
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General Materials Science - Published
- 2023
20. Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance
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Xiaolin Wang, Jiahui Zhang, Guozhen Cao, Jinghan Hua, Ge Shan, and Wenchu Lin
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Cancer Research ,Oncology ,Stomach Neoplasms ,Biomarkers, Tumor ,Drug Resistance ,Humans ,RNA, Circular - Abstract
Gastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis, primarily caused by metastatic lesions. Improved understanding of GC metastasis at the molecular level yields meaningful insights into potential biomarkers and therapeutic targets. Covalently closed circular RNAs (circRNAs) have emerged as crucial regulators in diverse human cancers including GC. Furthermore, accumulating evidence has demonstrated that circRNAs exhibit the dysregulated patterns in GC and have emerged as crucial regulators in GC invasion and metastasis. However, systematic knowledge regarding the involvement of circRNAs in metastatic GC remains obscure. In this review, we outline the functional circRNAs related to GC metastasis and drug resistance and discuss their underlying mechanisms, providing a comprehensive delineation of circRNA functions on metastatic GC and shedding new light on future therapeutic interventions for GC metastases.
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- 2022
21. CircVAPA promotes small cell lung cancer progression by modulating the miR-377-3p and miR-494-3p/IGF1R/AKT axis
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Jinghan Hua, Xiaolin Wang, Liying Ma, Jingxin Li, Guozhen Cao, Shaobo Zhang, and Wenchu Lin
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Cancer Research ,Lung Neoplasms ,RNA, Circular ,Small Cell Lung Carcinoma ,Receptor, IGF Type 1 ,Mice ,MicroRNAs ,Phosphatidylinositol 3-Kinases ,Oncology ,Cell Line, Tumor ,Animals ,Humans ,Molecular Medicine ,Proto-Oncogene Proteins c-akt ,Cell Proliferation - Abstract
Background Multiple lines of evidence have demonstrated that circular RNAs (circRNAs) play oncogenic or tumor-suppressive roles in various human cancers. Nevertheless, the biological functions of circRNAs in small cell lung cancer (SCLC) are still elusive. Methods CircVAPA (annotated as hsa_circ_0006990) was identified by mining the circRNA profiling dataset of six paired SCLC tissues and the RNA-seq data of serum samples from 36 SCLC patients and 118 healthy controls. The circVAPA expression level was evaluated using quantitative real-time PCR in SCLC cells and tissues. Cell viability, colony formation, cell cycle and apoptosis analysis assays and in vivo tumorigenesis were used to reveal the biological roles of circVAPA. The underlying mechanism of circVAPA was investigated by Western blot, RNA pulldown, RNA immunoprecipitation, dual-luciferase reporter assay and rescue experiments. Results We revealed that circVAPA, derived from exons 2-4 of the vesicle-associated membrane protein-associated protein A (VAPA) gene, exhibited higher expression levels in SCLC cell lines, clinical tissues, and serum from SCLC patients than the controls, and facilitated SCLC progression in vitro and in vivo. Mechanistically, circVAPA activated the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway by modulating the miR-377-3p and miR-494-3p/insulin-like growth factor 1 receptor (IGF1R) axis to accelerate SCLC progression. Furthermore, circVAPA depletion markedly enhanced the inhibitory effects of BMS-536924, an IGF1R kinase inhibitor in cellular and xenograft mouse models. Conclusions CircVAPA promotes SCLC progression via the miR-377-3p and miR-494-3p/IGF1R/AKT axis. We hope to develop clinical protocols of combinations of circVAPA inhibition and BMS-536924 addition for treating SCLC with circVAPA upregulation.
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- 2022
22. Sheep tail fat inhibits the proliferation of non-small-cell lung cancer cells
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Changzhi, Xu, Lanlan, Zhang, Huimin, He, Xiaoyi, Liu, Xinxin, Pei, Tengfei, Ma, Bingbing, Ma, Wenchu, Lin, and Buchang, Zhang
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Increasing evidence suggests that numerous edible oils may function as adjuvant dietary therapies to treat cancer. We previously reported that the odd-chain saturated fatty acid (OCSFA), heptadecanoic acid (C17:0), profoundly inhibits non-small-cell lung cancer (NSCLC) cell proliferation. However, the antitumor potential of edible lipids rich in C17:0 remains unclear. Here, we determined that sheep tail fat (STF) is a dietary lipid rich in C17:0 and exhibited the greatest inhibitory effect against three NSCLC cell lines (A549, PC-9, and PC-9/GR) among common dietary lipids. Cell migration experiments demonstrated that STF could significantly inhibit the wound healing capacity of three NSCLC cell lines by promoting the generation of reactive oxygen species (ROS) and subsequent cell death. Mechanistic studies showed that STF suppressed NSCLC cell growth by downregulating the Akt/S6K signaling pathway. Furthermore, administration of STF reduced tumor growth, weight, and expression of the proliferative marker Ki-67 in nude mice bearing A549 xenografts. Collectively, our data show that STF has antitumor activity against NSCLC, implying that dietary intake of C17:0-rich STF may be a potential adjuvant therapy for NSCLC.
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- 2022
23. Combinations of proteasome inhibitors with obatoclax are effective for small cell lung cancer
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Hong Li, Bo Hong, Chen Ding, Xiaoli Liu, Vivian Wai Yan Lui, Ke Deng, Xiao-tong Lv, Wenchu Lin, Wen-hao Shi, and Yan-ping Yin
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0301 basic medicine ,Indoles ,Lung Neoplasms ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,Article ,Bortezomib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pyrroles ,Pharmacology (medical) ,neoplasms ,Pharmacology ,Forkhead Box Protein M1 ,Drug Synergism ,General Medicine ,Small Cell Lung Carcinoma ,Xenograft Model Antitumor Assays ,Carfilzomib ,Up-Regulation ,respiratory tract diseases ,HEK293 Cells ,030104 developmental biology ,chemistry ,Proteasome ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,FOXM1 ,Myeloid Cell Leukemia Sequence 1 Protein ,Growth inhibition ,Oligopeptides ,Proteasome Inhibitors ,medicine.drug ,Obatoclax - Abstract
Proteasome inhibitors, bortezomib (BTZ), and carfilzomib (CFZ) are approved drugs for hematological malignancies, but lack anticancer activities against most solid tumors. Small cell lung cancer (SCLC) is a very aggressive neuroendocrine carcinoma of the lungs demanding effective therapy. In this study we investigated whether BTZ or CFZ combined with obatoclax (OBX), an antagonist for MCL-1 and a pan-BCL family inhibitor, could cause synergistic growth inhibition of SCLC cells. We showed that combined application of BTZ or CFZ with OBX caused synergistic growth inhibition of human SCLC cell lines (H82, H526, DMS79, H196, H1963, and H69) than single agent alone. Both BTZ-OBX and CFZ-OBX combinations displayed marked synergism on inducing apoptosis (~50% increase vs BTZ or CFZ alone). A comprehensive proteomics analysis revealed that BTZ preferentially induced the expression of MCL-1, an antiapoptotic protein, in SCLC cells. Thus, proteasome inhibitor-OBX combinations could specifically induce massive growth inhibition and apoptosis in SCLC cells. Subsequent proteome-wide profiling analysis of activated transcription factors suggested that BTZ- or CFZ-induced MCL-1 upregulation was transcriptionally driven by FOXM1. In nude mice bearing in SCLC H82 xenografts, both BTZ-OBX, and CFZ-OBX combinations exhibited remarkable antitumor activities against SCLC tumors evidenced by significant reduction of tumor size and the proliferation marker Ki-67 signals in tumor tissues as compared with single agent alone. Thus, proteasome inhibitor-OBX combinations are worth immediate assessments for SCLC in clinical settings.
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- 2020
24. Graphitic Carbon Nitride Quantum Dots Embedded in Carbon Nanosheets for Near-Infrared Imaging-Guided Combined Photo-Chemotherapy
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Yong Qian, Xiaotong Lv, Xiangfu Meng, Hong Li, Hongji Liu, Xingyu Wang, Junchao Qian, Wenchu Lin, and Hui Wang
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Materials science ,General Physics and Astronomy ,chemistry.chemical_element ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Quantum Dots ,medicine ,General Materials Science ,Doxorubicin ,Nitrogen Compounds ,Singlet oxygen ,General Engineering ,Rational design ,Graphitic carbon nitride ,021001 nanoscience & nanotechnology ,Fluorescence ,Carbon ,0104 chemical sciences ,chemistry ,Quantum dot ,Graphite ,Nanocarriers ,0210 nano-technology ,medicine.drug - Abstract
Rational design of metal-free multifunctional therapeutic reagents offers great opportunities for cancer treatment in the clinic. Here, graphitic carbon nitride (g-C3N4) quantum dots embedded in carbon nanosheets (CNQD-CN) are in situ prepared via a one-pot hydrothermal approach with formamide as carbon and nitrogen source. The CNQD-CN not only serves as an excellent near-infrared (NIR) fluorescent marker but also acts as a pH-responsive nanocarrier. Moreover, the CNQD-CN possesses both light-to-heat conversion and singlet oxygen generation capabilities under a single NIR excitation wavelength. Further investigations show that systemic delivery of doxorubicin (DOX) using the multifunctional CNQD-CN nanocarrier under NIR irradiation was highly effective to cause cancer cell apoptosis in vitro and inhibit tumor growth in vivo. CNQD-CN represents a multifunctional therapeutic platform for synchronous cancer imaging and treatment through the synergistic effect of phototherapy and chemotherapy.
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- 2020
25. BRD4 Targets the KEAP1-Nrf2-G6PD Axis and Suppresses Redox Metabolism in Small Cell Lung Cancer
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Yang Lv, Xiaotong Lv, Jiahui Zhang, Guozhen Cao, Changzhi Xu, Buchang Zhang, and Wenchu Lin
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Physiology ,Clinical Biochemistry ,Cell Biology ,Molecular Biology ,Biochemistry ,small cell lung cancer ,BRD4 ,KEAP1 ,Nrf2 ,pentose phosphate pathway - Abstract
Accumulating evidence has witnessed the Kelch-like ECH-associated protein 1(KEAP1)- nuclear factor (erythroid-derived 2)-like 2 (Nrf2) axis is the main regulatory factor of cell resistance to endogenous and exogenous oxidative assaults. However, there are few studies addressing the upstream regulatory factors of KEAP1. Herein, bioinformatic analysis suggests bromodomain-containing protein 4 (BRD4) as a potential top transcriptional regulator of KEAP1 in lung cancer. Using molecular and pharmacological approaches, we then discovered that BRD4 can directly bind to the promoter of KEAP1 to activate its transcription and down-regulate the stability of Nrf2 which in turn transcriptionally suppresses glucose-6-phosphate dehydrogenase (G6PD) in small cell lung cancer (SCLC), a highly proliferative and aggressive disease with limited treatment options. In addition, BRD4 could associate with the Nrf2 protein in a non-KEAP1-dependent manner to inhibit Nrf2 activity. Furthermore, simultaneous application of JQ1 and ATRA or RRx-001 yielded synergistic inhibition both in vitro and in vivo. These data suggest metabolic reprogramming by JQ1 treatment improves cell resistance to oxidative stress and might be a resistance mechanism to bromodomain and extra-terminal domain (BET) inhibition therapy. Altogether, our findings provide novel insight into the transcriptional regulatory network of BRD4 and KEAP1 and transcriptional regulation of the pentose phosphate pathway in SCLC.
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- 2022
26. NIR-II responsive PEGylated nickel nanoclusters for photothermal enhanced chemodynamic synergistic oncotherapy
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Yong Qian, Jiahui Zhang, Jinglu Zou, Xingyu Wang, Xiangfu Meng, Hongji Liu, Yefeng Lin, Qianwang Chen, Lei Sun, Wenchu Lin, and Hui Wang
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Nickel ,Photothermal Therapy ,Cell Line, Tumor ,Medicine (miscellaneous) ,Nanoparticles ,Hyperthermia, Induced ,Phototherapy ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Polyethylene Glycols - Published
- 2022
27. Comprehensive analysis of the expression, prognosis, and immune infiltrates for CHDs in human lung cancer
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Yang Lv and Wenchu Lin
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Cancer Research ,Endocrinology ,Oncology ,Endocrine and Autonomic Systems ,Endocrinology, Diabetes and Metabolism - Abstract
Background The chromodomain helicase DNA-binding (CHD) family, a group of genes that regulate nucleosome spacing and access to transcription factors, contributes to tumorigenesis in various cancers. However, the roles of CHD family members in lung cancer remain poorly understood. Methods We investigated the transcriptional, survival, and immune data of CHDs in patients with lung cancer from the Oncomine, UALCAN, GEPIA, Kaplan–Meier Plotter, TCGA, TIMER, cBioPortal, and CR2Cancer databases. Then, perform functional enrichment analysis of CHDs was performed using the Metascape. Finally, the expression of CHD7, CHD8 and DNA damage response genes were evaluated by quantitative real-time PCR and western blot.The effects of CHD7 or CHD8 knockdown on A549 and PC9 cells were measured in vitro by flow cytometry, cell viability and colony formation assays. Results We found that except for CHD5, nearly all members of CHDs in lung cancer showed altered expression compared with adjacent normal tissues. Moreover, the abnormal expression levels of CHDs were related to the clinical outcome of patients with lung adenocarcinoma and, to a lesser extent, patients with lung squamous cell carcinoma, which were significantly associated with the immune infiltrating levels of immune cells. Furthermore, the functions of CHDs and their neighboring genes are mainly related to DNA repair, the cell cycle, and organelle organization. Finally, cellular experiments conducted in vitro confirmed that CHD7/8 played indispensable roles in DNA damage signaling and cell cycle progression in lung adenocarcinoma cells. Conclusion This study implied that CHD family members, especially in subclass III, are potential targets of precision therapy and new biomarkers for patients with lung cancer.
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- 2022
28. Circulating miR-92b and miR-375 for monitoring the chemoresistance and prognosis of small cell lung cancer
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Hong Li, Wenchu Lin, Lailing Li, Bo Hong, Dandan Han, Wulin Shan, Dan Li, Ming Li, Yang Zhang, and Jinglu Zou
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0301 basic medicine ,Male ,Lung Neoplasms ,medicine.medical_treatment ,Science ,Drug resistance ,Article ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Mir-375 ,microRNA ,medicine ,Biomarkers, Tumor ,Humans ,Survival analysis ,Cancer ,Aged ,Aged, 80 and over ,Chemotherapy ,Multidisciplinary ,Receiver operating characteristic ,business.industry ,Area under the curve ,Middle Aged ,Prognosis ,Small Cell Lung Carcinoma ,Survival Analysis ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Risk factors ,ROC Curve ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,Female ,business ,Biomarkers - Abstract
miRNAs have been reported to be stably detectable in plasma and to function as potent biomarkers in multiple cancers. The study aimed to evaluate the expression of candidate circulating miRNAs in patients with small cell lung cancer (SCLC) to identify potential noninvasive biomarkers. The expression of five miRNAs (miR-92b, miR-146a, miR-375, miR-1224, and miR-1246) was significantly upregulated in plasma after chemoresistance induction. Receiver operating characteristic curve (ROC) analysis showed that the area under the curve (AUC) values of miR-92b and miR-375 were 0.766 and 0.791, respectively. The data demonstrated that among the five miRNAs assessed, these two miRNAs had better diagnostic accuracy for monitoring drug resistance. In addition, miR-92b and miR-375 levels were decreased after effective chemotherapy. Furthermore, Kaplan–Meier survival analysis confirmed that high expression of miR-92b and miR-375 was closely related to shorter progression-free survival (PFS) in SCLC patients. In conclusion, these findings indicate that circulating miR-92b and miR-375 might be ideal noninvasive biomarkers for monitoring drug resistance during chemotherapy and evaluating the prognosis of patients with SCLC.
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- 2020
29. Direct carbonization of organic solvents toward graphene quantum dots
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Yong Qian, Yucai Wang, Hui Wang, Wenchu Lin, Changwei Li, Xingyu Wang, Lin Hu, Xiao-tong Lv, and Hongji Liu
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chemistry.chemical_classification ,Materials science ,Double bond ,Biocompatibility ,Graphene ,Carbonization ,Fluorescence ,law.invention ,Catalysis ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,law ,Quantum dot ,General Materials Science ,Benzene - Abstract
The bottom-up synthesis of graphene quantum dots (GQDs) using solvothermal methods has attracted considerable attention because of their fewer defects and controllable size/morphology. However, the influence of organic solvents on the preparation of GQDs is still unknown. Herein, a systematic study on the carbonization of organic solvents toward GQDs is reported. The results show that organic solvents with the double bond or benzene ring or double hydrophilic groups could be directly decomposed into GQDs without the addition of catalysts or molecular precursors. The as-synthesized GQDs demonstrate ultra-small size distribution, high stability, tunable excitation wavelength and upconverted fluorescence. Both hematological and histopathological analyses show that the as-synthesized GQDs demonstrate a very good safety profile and excellent biocompatibility. The versatility of this synthesis strategy offers easy control of the surface group, composition, and optical properties of GQDs at the molecular level.
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- 2020
30. CircURI1 interacts with hnRNPM to inhibit metastasis by modulating alternative splicing in gastric cancer
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Jinghan Hua, Shanshan Hu, Wenchu Lin, Tianyi Yu, Cheng Wu, Xiaolin Wang, Jingxin Li, Yongxiang Li, Ge Shan, Shuhui Chang, Xing Bian, and Hong Li
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Multidisciplinary ,Unconventional prefoldin RPB5 interactor ,biology ,Chemistry ,Alternative splicing ,Cancer ,Cell migration ,Biological Sciences ,medicine.disease ,Heterogeneous Nuclear Ribonucleoprotein M ,Metastasis ,Exon ,biology.protein ,Cancer research ,medicine ,Gene - Abstract
Circular RNAs (circRNAs) have emerged as key regulators of human cancers, yet their modes of action in gastric cancer (GC) remain largely unknown. Here, we identified circURI1 back-spliced from exons 3 and 4 of unconventional prefoldin RPB5 interactor 1 (URI1) from circRNA profiling of five-paired human gastric and the corresponding nontumor adjacent specimens (paraGC). CircURI1 exhibits the significantly higher expression in GC compared with paraGC and inhibitory effects on cell migration and invasion in vitro and GC metastasis in vivo. Mechanistically, circURI1 directly interacts with heterogeneous nuclear ribonucleoprotein M (hnRNPM) to modulate alternative splicing of genes, involved in the process of cell migration, thus suppressing GC metastasis. Collectively, our study expands the current knowledge regarding the molecular mechanism of circRNA-mediated cancer metastasis via modulating alternative splicing.
- Published
- 2021
31. Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway
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Ming Li, Wulin Shan, Yan Hua, Fengmei Chao, Yayun Cui, Lei Lv, Xiaoyan Dou, Xing Bian, Jinglu Zou, Hong Li, and Wenchu Lin
- Subjects
QH301-705.5 ,migration ,Exosome ,Cell and Developmental Biology ,microRNA ,Medicine ,PTEN ,exosome ,Biology (General) ,miR-92b-3p ,Protein kinase B ,neoplasms ,PI3K/AKT/mTOR pathway ,Original Research ,biology ,business.industry ,chemoresistance ,Cell migration ,Cell Biology ,Microvesicles ,humanities ,respiratory tract diseases ,biology.protein ,Cancer research ,Biomarker (medicine) ,small cell lung cancer ,business ,Developmental Biology - Abstract
Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never been explored. In this study, we observed that the expression of exosomal miR-92b-3p was significantly increased in patients who developed chemoresistance. Luciferase reporter analysis confirmed that PTEN was a target gene of miR-92b-3p. The PTEN/AKT regulatory network was related to miR-92b-3p-mediated cell migration and chemoresistance in vitro and in vivo in SCLC. Importantly, exosomes isolated from the conditioned medium of SBC-3 cells overexpressing miR-92b-3p could promote SCLC chemoresistance and cell migration. Furthermore, we found that plasma miR-92b-3p levels were significantly higher in patients with chemoresistant SCLC than in those with chemosensitive SCLC, but the levels were down-regulated in patients who achieved remission. Kaplan–Meier analysis showed that SCLC patients with high miR-92b-3p expression were associated with shorter progression-free survival. Overall, our results suggested that exosomal miR-92b-3p is a potential dynamic biomarker to monitor chemoresistance in SCLC and represents a promising therapeutic target for chemoresistant SCLC.
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- 2021
32. NIR-II Responsive Hollow Magnetite Nanoclusters for Targeted Magnetic Resonance Imaging-Guided Photothermal/Chemo-Therapy and Chemodynamic Therapy
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Hongji Liu, Wenchu Lin, Hong Li, Xiaotong Lv, Xingyu Wang, Changwei Li, Hui Wang, Junchao Qian, Xiangfu Meng, Yong Qian, Jinglu Zou, and Jiahui Zhang
- Subjects
Materials science ,Cancer therapy ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Nanoclusters ,Biomaterials ,chemistry.chemical_compound ,medicine ,General Materials Science ,Hydrogen peroxide ,Magnetite ,medicine.diagnostic_test ,Magnetic resonance imaging ,General Chemistry ,Hyperthermia, Induced ,Photothermal therapy ,Phototherapy ,021001 nanoscience & nanotechnology ,Magnetic Resonance Imaging ,Ferrosoferric Oxide ,0104 chemical sciences ,Drug Liberation ,chemistry ,Doxorubicin ,Chemo therapy ,Nanoparticles ,Hydroxyl radical ,0210 nano-technology ,Biotechnology - Abstract
Phototherapy in the second near-IR (1000-1700 nm, NIR-II) window has achieved much progress because of its high efficiency and relatively minor side effects. In this paper, a new NIR-II responsive hollow magnetite nanocluster (HMNC) for targeted and imaging-guided cancer therapy is reported. The HMNC not only provides a hollow cavity for drug loading but also serves as a contrast agent for tumor-targeted magnetic resonance imaging. The acid-induced dissolution of the HMNCs can trigger a pH-responsive drug release for chemotherapy and catalyze the hydroxyl radical (·OH) formation from the decomposition of hydrogen peroxide for chemodynamic therapy. Moreover, the HMNCs can adsorb and convert NIR-II light into local heat (photothermal conversion efficacy: 36.3%), which can accelerate drug release and enhance the synergistic effect of chemo-photothermal therapy. The HMNCs show great potential as a versatile nanoplatform for targeted imaging-guided trimodal cancer therapy.
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- 2021
33. Germline mutation and aberrant transcripts of WWOX in a syndrome with multiple primary tumors
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Bo Hong, Vivian Wy Lui, Jinfu Nie, Ao Xu, Wei Wang, and Wenchu Lin
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0301 basic medicine ,WWOX ,Mutation ,Cancer ,Biology ,medicine.disease_cause ,medicine.disease ,Germline ,Pathology and Forensic Medicine ,Metastasis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Germline mutation ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,HRAS ,CHEK2 - Abstract
Multiple primary tumors are defined by the presence of two or more independent primary tumors in the same or different organs of an individual patient. However, the underlying genetic cause for the development of multiple primary tumors is largely unknown. In the study, we report a rare case with four synchronous distinct histological cancer types in a 26 years old Chinese female. In the patient, whole-exome sequencing identified a homozygous germline insertion mutation in WWOX which encodes the DNA repair-related enzyme, WW domain containing oxidoreductase. The mutation was found in a heterozygous state in her parents and brother without any cancer phenotype thus far. Surprisingly, we found multiple novel aberrant WWOX transcripts in the patient's normal colon tissue. The patient's colon metastasis from clear cell adenocarcinoma of the ovary showed a nonhypermutated profile enriched for C-T transition, and harbored somatic pathogenic mutations of HRAS, BRCA2, SMAD4, CHEK2, and AKT1 genes. To our knowledge, this is the first study reporting WWOX gene aberrations in a young patient with the early occurrence of multiple primary tumors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Published
- 2019
34. A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer
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Wei Wang, Hang Xiang, Xiaoli Liu, Bo Hong, Wenchu Lin, Yan-ping Yin, Xiaodong Mei, Ming Li, Ao Xu, and Hong Li
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0301 basic medicine ,Drug ,Auranofin ,Cell cycle checkpoint ,DNA damage ,media_common.quotation_subject ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,medicine ,Pharmacology (medical) ,neoplasms ,media_common ,Pharmacology ,Cisplatin ,business.industry ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Cancer research ,business ,medicine.drug - Abstract
Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput drug screen strategy to identify new drugs that can enhance the sensitivity of chemo-drug cisplatin in SCLC. This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.
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- 2019
35. The distinct clinicopathological and prognostic implications of PIK3CA mutations in breast cancer patients from Central China
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Jing Xie, Wenchu Lin, Haibo Wu, Xiaoli Liu, Jun Du, Liangliang Huang, Hang Xiang, Heng Li, Huogang Wang, Hong Li, and Wei Wang
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,medicine.drug_class ,Central china ,medicine.disease_cause ,DNA sequencing ,03 medical and health sciences ,Exon ,symbols.namesake ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,neoplasms ,Pathological ,Sanger sequencing ,Mutation ,business.industry ,medicine.disease ,030104 developmental biology ,Estrogen ,030220 oncology & carcinogenesis ,symbols ,business - Abstract
Purpose The mutation status and prognostic value of PIK3CA in breast cancer were widely investigated, which showed significant difference among the patients from vast areas around the world. In this study, the frequency, distribution, bias, and burden of PIK3CA mutations and their relationships with clinicopathologic variables and prognostic significances were investigated in the breast cancer patients from Central China. Materials and methods Somatic mutations in exon 9 and exon 20 of PIK3CA gene were analyzed using Sanger sequencing combining with targeted next generation sequencing in 494 breast cancer patients from Central China. The correlations between PIK3CA mutations and clinicopathological characteristics and the prognostic values of multiple PIK3CA mutation statuses were evaluated. Results PIK3CA mutations were found in 38% of the patients and associated with estrogen receptor-positive, progesterone receptor-positive, low Ki67 labeling index, and luminal/human epidermal growth factor receptor 2-enriched subtypes. Meanwhile, the prognosis of the total patients and the patients in old diagnostic age, progesterone receptor-negative, low Ki67 labeling index, and luminal/human epidermal growth factor receptor 2-enriched subgroups was significantly related to PIK3CA mutations. Most interestingly, the distribution, bias, and burden of PIK3CA mutations were correlated with different clinical, pathological, and molecular features as well as distinct prognostic implications in multiple breast cancer subgroups. Conclusion The frequency, distribution, bias, and burden of PIK3CA mutations were associated with various clinical, pathological, and molecular characteristics in the breast cancer patients from Central China. These different mutation statuses can be used as potential indicators of prognosis in multiple breast cancer subgroups.
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- 2019
36. FK228 sensitizes radioresistant small cell lung cancer cells to radiation
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Yang Lv, Liying Ma, Xing Bian, Wenchu Lin, and Hong Li
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FK228 ,Radiation-Sensitizing Agents ,Lung Neoplasms ,DNA Repair ,DNA damage ,medicine.medical_treatment ,Apoptosis ,PI3K ,Radiation Tolerance ,Radioresistance ,Cell Line, Tumor ,Depsipeptides ,Genetics ,medicine ,DNA damage repair ,Humans ,Histone deacetylase ,Homologous Recombination ,Molecular Biology ,neoplasms ,Genetics (clinical) ,PI3K/AKT/mTOR pathway ,Neoplasm Staging ,Phosphoinositide-3 Kinase Inhibitors ,Chemotherapy ,Small cell lung cancer ,business.industry ,Research ,Combined Modality Therapy ,Small Cell Lung Carcinoma ,respiratory tract diseases ,Radiation therapy ,Histone Deacetylase Inhibitors ,Cancer research ,Radiosensitizing Agent ,Homologous recombination ,business ,Developmental Biology ,DNA Damage - Abstract
BackgroundConcurrent thoracic radiation plus chemotherapy is the mainstay of first-line treatment for limited-stage small cell lung cancer (LS-SCLC). Despite initial high responsiveness to combined chemo- and radiotherapy, SCLC almost invariably relapses and develops resistance within one year, leading to poor prognosis in patients with LS-SCLC. Developing new chemical agents that increase ionizing radiation’s cytotoxicity against SCLC is urgently needed.ResultsDual histone deacetylase (HDAC) and PI3K inhibitor FK228 not only displayed potent anticancer activity, but also enhanced the therapeutic effects of radiotherapy in SCLC cells. Mechanistically, radioresistant SCLC cells exhibit a lower level of histone H3K9 acetylation and a higher expression level of the MRE11-RAD50-NBS1 (MRN) complex and show more efficient and redundant DNA damage repair capacities than radiosensitive SCLC cells. FK228 pretreatment resulted in marked induction of H3k9 acetylation, attenuated homologous recombination (HR) repair competency and impaired non-homologous end joining (NHEJ) repair efficacy, leading to the accumulation of radiation-induced DNA damage and radiosensitization.ConclusionThe study uncovered that FK228 sensitized human radioresistant SCLC cells to radiation mainly through induction of chromatin decondensation and suppression of DNA damage signaling and repair. Our study provides a rational basis for a further clinical study to test the potential of FK228 as a radiosensitizing agent to increase the radiation-induced tumor cell kill in LS-SCLC patients.
- Published
- 2021
37. The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
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Liying Ma, Xing Bian, and wenchu Lin
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Morpholines ,Poly (ADP-Ribose) Polymerase-1 ,Apoptosis ,Mice, SCID ,Poly(ADP-ribose) Polymerase Inhibitors ,lcsh:RC254-282 ,PI3K ,CUDC-907 ,PARP1 ,DSB repair ,Histone Deacetylases ,Piperazines ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Olaparib ,Mice, Inbred NOD ,HDAC ,Tumor Cells, Cultured ,Animals ,Humans ,Cell Proliferation ,Phosphoinositide-3 Kinase Inhibitors ,Research ,Correction ,SCLC ,Drug Synergism ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Small Cell Lung Carcinoma ,Xenograft Model Antitumor Assays ,respiratory tract diseases ,Histone Deacetylase Inhibitors ,Pyrimidines ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Combination treatment ,Phthalazines ,Drug Therapy, Combination ,Female ,Phosphatidylinositol 3-Kinase - Abstract
BackgroundSmall cell lung cancer (SCLC) is a deadly neuroendocrine tumor with limited therapeutic options. Recent data suggest that histone deacetylases (HDACs) and the phosphatidylinositol 3-kinase (PI3K) pathway play essential roles in SCLC cell proliferation and survival.MethodsThe inhibition of the PI3K signaling and HDAC activity by CUDC-907 was analyzed by western blotting. The effect of CUDC-907 on olaparib-induced DNA damage response was assessed by western blotting and Immunofluorescence staining. The cytotoxicity of CUDC-907 alone or in combination with olaparib in a panel of SCLC cell lines were evaluated by the CellTiter-Glo Luminescent Cell Viability Assay and flow cytometry. The in vivo effects of CUDC-907 and olaparib alone or in combination were examined using a patient-derived xenografts (PDX) model of SCLC.ResultsCUDC-907 treatment downregulated MYC paralogs and FoxM1, induced G1 cell-cycle arrest, and impaired DNA double-strand break (DSB) repair capacity in SCLC cells, which produced a potent antiproliferative effect. Furthermore, we showed that CUDC-907 treatment enhanced the therapeutic efficacy of PARP inhibitor olaparib in SCLC cellular models and a PDX model. Mechanistic investigations demonstrated that CUDC-907 synergized with olaparib through the blockade of DSB repair pathways and downregulation of MYC paralogs and FoxM1.ConclusionsOur study uncovers that dual PI3K and HDAC inhibition by CUDC-907 exerts significant single-agent activity and strong synergistic effects with PARP inhibitor olaparib in SCLC, which thus provides a rational combination treatment strategy for SCLC clinical investigation.
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- 2020
38. The MYC Paralog-PARP1 Axis as a Potential Therapeutic Target in MYC Paralog-Activated Small Cell Lung Cancer
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Xing Bian, Xiaolin Wang, Qiuyan Zhang, Liying Ma, Guozhen Cao, Ao Xu, Jinhua Han, Jun Huang, and Wenchu Lin
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0301 basic medicine ,Cancer Research ,animal structures ,DNA damage ,Poly ADP ribose polymerase ,Cell ,DNA damage response ,PARP1 ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,neoplasms ,Gene ,Polymerase ,biology ,fungi ,BET ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,humanities ,respiratory tract diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,MYC paralog ,small cell lung cancer ,Regulatory Pathway ,Homologous recombination - Abstract
Poly (ADP-ribose) polymerase 1 (PARP1) is highly expressed in small cell lung cancer (SCLC) and has emerged as an attractive target for treatment of SCLC. However, the clinical significance of PARP1 expression in SCLC remains elusive. In this study, we showed that high PARP1 expression was associated with better overall survival (OS), and was positively correlated with the expression of MYC paralogs in patients with SCLC. We demonstrated that PARP1 was transcriptionally regulated by MYC paralogs. Integrative analysis of multiple RNA-seq data sets indicated that DNA damage response (DDR) genes involved in the replication stress response (RSR) and homologous recombination (HR) repair pathways were highly enriched in MYC paralog-addicted SCLC cell models and in human SCLC specimens. Targeting the MYC paralog-PARP1 axis with concomitant BET and PARP inhibition resulted in synergistic effects in MYC paralog-activated SCLC. Our study identified a critical PARP1 regulatory pathway, and provided evidence for a rational combination treatment strategy for MYC paralog-activated SCLC.
- Published
- 2020
39. NIR‐II Responsive Hollow Magnetite Nanoclusters for Targeted Magnetic Resonance Imaging‐Guided Photothermal/Chemo‐Therapy and Chemodynamic Therapy
- Author
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Xingyu Wang, Changwei Li, Junchao Qian, Xiaotong Lv, Hong Li, Jinglu Zou, Jiahui Zhang, Xiangfu Meng, Hongji Liu, Yong Qian, Wenchu Lin, and Hui Wang
- Subjects
Biomaterials ,General Materials Science ,General Chemistry ,Biotechnology - Published
- 2022
40. The
- Author
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Xing, Bian, Xiaolin, Wang, Qiuyan, Zhang, Liying, Ma, Guozhen, Cao, Ao, Xu, Jinhua, Han, Jun, Huang, and Wenchu, Lin
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animal structures ,Oncology ,fungi ,MYC paralog ,small cell lung cancer ,BET ,DNA damage response ,neoplasms ,PARP1 ,humanities ,respiratory tract diseases ,Original Research - Abstract
Poly (ADP-ribose) polymerase 1 (PARP1) is highly expressed in small cell lung cancer (SCLC) and has emerged as an attractive target for treatment of SCLC. However, the clinical significance of PARP1 expression in SCLC remains elusive. In this study, we showed that high PARP1 expression was associated with better overall survival (OS), and was positively correlated with the expression of MYC paralogs in patients with SCLC. We demonstrated that PARP1 was transcriptionally regulated by MYC paralogs. Integrative analysis of multiple RNA-seq data sets indicated that DNA damage response (DDR) genes involved in the replication stress response (RSR) and homologous recombination (HR) repair pathways were highly enriched in MYC paralog-addicted SCLC cell models and in human SCLC specimens. Targeting the MYC paralog-PARP1 axis with concomitant BET and PARP inhibition resulted in synergistic effects in MYC paralog-activated SCLC. Our study identified a critical PARP1 regulatory pathway, and provided evidence for a rational combination treatment strategy for MYC paralog-activated SCLC.
- Published
- 2020
41. Additional file 5 of The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
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Liying Ma, Bian, Xing, and Wenchu Lin
- Abstract
Additional file 5: Supplementary Figure 5. Effects of CUDC-907 and olaparib on the expression of MYC targets in vivo. RT-qPCR analysis of the expression of MYC targets in PDX tissues treated as indicated drugs for 15 days. Gene expression was normalized to β-actin. Error bars represent mean ± S.D. *P
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- 2020
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42. Additional file 6 of The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
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Liying Ma, Bian, Xing, and Wenchu Lin
- Abstract
Additional file 6: Supplementary Figure 6. Relative amount of DDR proteins were determined by densitometric analysis. The quantification data presented were the average densitometric value of three independent western blotting experiments. One of three experiments with similar results is shown in Fig. 5b.
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- 2020
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43. Additional file 3 of The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
- Author
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Liying Ma, Bian, Xing, and Wenchu Lin
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Additional file 3: Supplementary Figure 3. Effects of CUDC-907 and olaparib on the expression of RAD51 in SCLC cells. RT-qPCR analysis of RAD51 expression in SCLC cells treated with 10 nM CUDC-907 and 10 μM olaparib alone or in combination for 24 h. Gene expression was normalized to β-actin. Error bars represent mean ± S.D. *P
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- 2020
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44. Additional file 2 of The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
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Liying Ma, Bian, Xing, and Wenchu Lin
- Subjects
respiratory tract diseases - Abstract
Additional file 2: Supplementary Figure 2. Effects of CUDC-907 and olaparib on the expression of MYC targets in SCLC cells. RT-qPCR analysis of the expression of MYC targets in SCLC cells treated as indicated drugs for 24 h. Gene expression was normalized to β-actin. Error bars represent mean ± S.D. *P
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- 2020
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45. Additional file 7 of The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
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Liying Ma, Bian, Xing, and Wenchu Lin
- Subjects
respiratory tract diseases - Abstract
Additional file 7: Supplementary Figure 7. Representative images of H & E and Immunohistochemical staining for c-MYC (1:500, abcam, ab32072) in SCLC primary tumors and PDX specimens.
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- 2020
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46. Additional file 1 of The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
- Author
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Liying Ma, Bian, Xing, and Wenchu Lin
- Abstract
Additional file 1: Supplementary Figure 1. Relative amount of phosphorylated proteins were determined by densitometric analysis.The quantification data presented were the average densitometric value of three independent western blotting experiments. One of three experiments with similar results is shown in Fig. 1d.
- Published
- 2020
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47. Additional file 4 of The dual HDAC-PI3K inhibitor CUDC-907 displays single-agent activity and synergizes with PARP inhibitor olaparib in small cell lung cancer
- Author
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Liying Ma, Bian, Xing, and Wenchu Lin
- Abstract
Additional file 4: Supplementary Figure 4. Relative amount of DDR proteins were determined by densitometric analysis. The quantification data presented were the average densitometric value of three independent western blotting experiments. One of three experiments with similar results is shown in Fig. 2c.
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- 2020
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48. Sodium chloride (NaCl) potentiates digoxin-induced anti-tumor activity in small cell lung cancer
- Author
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Cheng Chen, Tian Xue, Ke Deng, Qingsong Liu, Hong Li, Wenchu Lin, Mei Zhang, Ming Li, Huan Zhao, Hong Bo, Vivian Wai Yan Lui, Wei Wang, and Jiawei Shen
- Subjects
0301 basic medicine ,Digoxin ,Cancer Research ,Lung Neoplasms ,ATPase ,Sodium Chloride ,Pharmacology ,Membrane Potentials ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,neoplasms ,Cardiac glycoside ,biology ,Cell growth ,Chemistry ,Cytochrome c ,Sodium ,Drug Synergism ,Small Cell Lung Carcinoma ,humanities ,In vitro ,High-Throughput Screening Assays ,respiratory tract diseases ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Sodium-Potassium-Exchanging ATPase ,Intracellular ,Research Paper ,medicine.drug - Abstract
Small cell lung cancer (SCLC) is a malignant neuroendocrine tumor with very high mortality. Effective new therapy for advanced SCLC patients is urgently needed. By screening a FDA-approved drug library, we identified a cardiac glycoside (CG), namely digoxin (an inhibitor of cellular Na(+)/K(+) ATPase pump), which was highly effective in inhibiting SCLC cell growth. Intriguing findings showed that NaCl supplement markedly enhanced the anti-tumor activities of digoxin in both in vitro and in vivo models of SCLC. Subsequent analysis revealed that this novel combination of digoxin/NaCl caused an up-regulation of intracellular Na(+) and Ca(2+) levels with an induction of higher resting membrane potential of SCLC cells. We also found that this combination lead to morphological shrinking of SCLC cells, together with high levels of cytochrome C release. Lastly, our data revealed that NaCl supplement was able to induce the expression of ATP1A1 (a Na(+)/K(+) ATPase subunit), in which contributes directly to the increased sensitivity of SCLC cells to digoxin. Thus, this is the first demonstration that NaCl is a potent supplement necessitating superior anti-cancer effects of digoxin for SCLC. Further, our study suggests that digoxin treatment could need to be combined with NaCl supplement in future clinical trial of SCLC, particularly where low Na(+) is often present in SCLC patients.
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- 2018
49. JQ1 synergizes with the Bcl-2 inhibitor ABT-263 against MYCN-amplified small cell lung cancer
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Huogang Wang, Vivian Wai Yan Lui, Wenchu Lin, Xuemin Li, Ke Deng, Bo Hong, and Hong Li
- Subjects
0301 basic medicine ,Poor prognosis ,Programmed cell death ,JQ1 ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,ABT-263 ,Medicine ,Bcl-2 ,neoplasms ,Gene knockdown ,N-Myc ,business.industry ,humanities ,Bromodomain ,respiratory tract diseases ,Bcl-2 Inhibitor ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Non small cell ,small cell lung cancer ,business ,Research Paper - Abstract
// Huogang Wang 1, 2, 3, * , Bo Hong 1, 3, * , Xuemin Li 1, 3 , Ke Deng 1, 2, 3 , Hong Li 1, 3 , Vivian Wai Yan Lui 4 and Wenchu Lin 1, 3 1 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, Anhui, P.R. China 2 University of Science and Technology of China, Hefei 230036, Anhui, P.R. China 3 Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui, P.R. China 4 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, P.R. China * Co-first authorship Correspondence to: Wenchu Lin, email: wenchu@hmfl.ac.cn Keywords: small cell lung cancer, N-Myc, Bcl-2, JQ1, ABT-263 Received: April 05, 2017 Accepted: August 26, 2017 Published: September 21, 2017 ABSTRACT Small cell lung cancer (SCLC) is a clinically aggressive cancer with very poor prognosis. Amplification of MYC family genes and overexpression of Bcl-2 protein are common in SCLC, and they are likely therapeutic targets for SCLC. Previous clinical study showed that single agent targeting Bcl-2 with ABT-263 was of limited efficacy in SCLC. In this study, we demonstrated for the first time that co-targeting of N-Myc and Bcl-2 resulted in marked synergistic antitumor effects in MYCN -amplified SCLC. We found that MYCN -amplified SCLC cells were highly sensitive to a Bromodomain and Extra-Terminal domain (BET) inhibitor JQ1, which was able to inhibit N-Myc protein expression. The inhibition of N-Myc by JQ1 induced the expression of Bim, and thereby sensitizing MYCN -amplified SCLC cells to ABT-263. The knockdown on Bim by siRNA reduced this JQ1/ABT-263 induced cell death. ABT-263 and JQ1 co-treatment in MYCN -amplified SCLC cells markedly disrupted Bim/Bcl-2 interaction, and prevented Bim’s interaction with Mcl-1. Importantly, this JQ1/ABT-263 co-targeting substantially inhibited the growth of MYCN -amplified SCLC xenografts in vivo . Our study demonstrates a new JQ-1/ABT-263 co-targeting strategy that can be employed for MYCN -amplified SCLC with high efficacy.
- Published
- 2017
50. Kmt2acooperates with menin to suppress tumorigenesis in mouse pancreatic islets
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Hong Li, Joshua M. Francis, Wenchu Lin, Gao Xiaoping, Matthew Meyerson, Patricia Ernst, and Chandra Sekhar Pedamallu
- Subjects
0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,Cancer Research ,Methyltransferase ,endocrine system diseases ,Carcinogenesis ,Loss of Heterozygosity ,Biology ,medicine.disease_cause ,Islets of Langerhans ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Proto-Oncogene Proteins ,PanNETs ,medicine ,Animals ,MEN1 ,Cell Proliferation ,Mice, Knockout ,Pharmacology ,geography ,geography.geographical_feature_category ,Molecular pathology ,Pancreatic islets ,Histone-Lysine N-Methyltransferase ,Neoplasms, Experimental ,Islet ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,tumorigenesis ,Men1 ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Histone methyltransferase ,Knockout mouse ,Cancer research ,Molecular Medicine ,methyltransferase ,Kmt2a ,Myeloid-Lymphoid Leukemia Protein ,Research Paper - Abstract
The reported incidence of pancreatic neuroendocrine tumors (PanNETs) has increased, due in large part to improvements in detection and awareness. However, therapeutic options are limited and a critical need exists for understanding a more thorough characterization of the molecular pathology underlying this disease. The Men1 knockout mouse model recapitulates the early stage of human PanNET development and can serve as a foundation for the development of advanced mouse models that are necessary for preclinical testing. Menin, the product of the MEN1 gene, has been shown to physically interact with the KMT2A and KMT2B histone methyltransferases. Both the KMT2A and MEN1 genes are located on chromosome 11q, which frequently undergoes loss of heterozygosity (LOH) in PanNETs. We report herein that inactivation of Kmt2a in Men1-deficient mice accelerated pancreatic islet tumorigenesis and shortened the average life span. Increases in cell proliferation were observed in mouse pancreatic islet tumors upon inactivation of both Kmt2a and Men1. The Kmt2a/Men1 double knockout mouse model can be used as a mouse model to study advanced PanNETs.
- Published
- 2016
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