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64. c-Met-mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma

Author

Huang, Menggui, Liu, Tianrun, Ma, Peihong, Mitteer, Jr., R. Alan, Zhang, Zhenting, Kim, Hyun Jun, Yeo, Eujin, Zhang, Duo, Cai, Peiqiang, Li, Chunsheng, Zhang, Lin, Zhao, Botao, Roccograndi, Laura, O'Rourke, Donald M., Dahmane, Nadia, Gong, Yanqing, Koumenis, Constantinos, and Fan, Yi

Subjects
Neovascularization -- Analysis -- Health aspects, Glioblastoma multiforme -- Development and progression -- Analysis -- Care and treatment, Permeability -- Analysis, Health care industry
Abstract

Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors., Introduction Overgrown, abnormal vasculature characterizes the microenvironment that fuels cancer progression and induces therapeutic resistance in malignant solid tumors (1-3). Glioblastoma multiforme (GBM), the grade IV glioma, is among the [...]

Published
2016
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68. The Role of the Clinical Pharmacist on the Health Outcomes of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)

Author

Gong,Yanqing, Chen,Qiying, Zhang,Yin, Gong,Yanqing, Chen,Qiying, and Zhang,Yin

Abstract

Yanqing Gong,1,2,* Qiying Chen,1,* Yin Zhang1 1Department of Pharmacy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China; 2Department of Pharmacy, Gaoxin Branch of the First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yin Zhang, Department of Pharmacy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China, Email zyin1973@163.comBackground: Clinical pharmacists play a significant role in clinical practice, but their work in the clinical pathway (CP) of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains undefined.Methods: This prospective study included patients who met the discharge criteria during hospitalization at the department of respiratory medicine of the Second Affiliated Hospital of Fujian Medical University from March to December 2017 (no pharmacists involved) and from March 2018 to January 2019 (pharmacists involved). The adverse drug reaction (ADR) reporting rate, the average DDD number of antibacterial drugs, the per capita cost of pharmaceutical services, and the benefit-cost ratio (B/C) were analyzed.Results and Discussion: Eighty participants were enrolled during the traditional period and eighty-five participants during the clinical pharmacist period. The average hospital stays (9.2± 0.4 vs 10.7± 0.6 days, P=0.032), the total cost of hospitalization expenses (¥ 14,058± 826 vs ¥ 18,765± 1434, P=0.004), the total cost of drugs (¥ 5717± 449 vs ¥ 8002± 755, P=0.004), and cost of antimicrobial drugs (¥ 3639± 379 vs ¥ 5636± 641, P=0.007) were all lower in the clinical pharmacist group than in the traditional group. The B/C was 10.38 and 5.05 in the total cost of hospitalization expenses and the total cost of drugs, respectively. The clinical pharmacists’ participation was independently associated

Published
2022

69. Transient expansion and myofibroblast conversion of adipogenic lineage precursors mediate bone marrow repair after radiation

Author

Zhong, Leilei, primary, Yao, Lutian, additional, Holdreith, Nicholas, additional, Yu, Wei, additional, Gui, Tao, additional, Miao, Zhen, additional, Elkaim, Yehuda, additional, Li, Mingyao, additional, Gong, Yanqing, additional, Pacifici, Maurizio, additional, Maity, Amit, additional, Busch, Theresa M., additional, Joeng, Kyu Sang, additional, Cengel, Keith, additional, Seale, Patrick, additional, Tong, Wei, additional, and Qin, Ling, additional

Published
2022
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70. Metabolism-Related Signature Analysis Uncovers the Prognostic and Immunotherapeutic Characteristics of Renal Cell Carcinoma

Author

Zhang, Jianye, primary, Zhang, Qi, additional, Shi, Yue, additional, Wang, Ping, additional, Gong, Yanqing, additional, He, Shiming, additional, Li, Zhihua, additional, Feng, Ninghan, additional, Wang, Yang, additional, Jiang, Peng, additional, Ci, Weimin, additional, Li, Xuesong, additional, and Zhou, Liqun, additional

Published
2022
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71. Single‐Cell RNA‐seq Reveals a Developmental Hierarchy Super‐Imposed Over Subclonal Evolution in the Cellular Ecosystem of Prostate Cancer

Author

Ge, Guangzhe, primary, Han, Yang, additional, Zhang, Jianye, additional, Li, Xinxin, additional, Liu, Xiaodan, additional, Gong, Yanqing, additional, Lei, Zhentao, additional, Wang, Jie, additional, Zhu, Weijie, additional, Xu, Yangyang, additional, Peng, Yiji, additional, Deng, Jianhua, additional, Zhang, Bao, additional, Li, Xuesong, additional, Zhou, Liqun, additional, He, Huiying, additional, and Ci, Weimin, additional

Published
2022
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72. Identification of Germline Mutations in Upper Tract Urothelial Carcinoma With Suspected Lynch Syndrome

Author

Guan, Bao, primary, Wang, Jie, additional, Li, Xuesong, additional, Lin, Lin, additional, Fang, Dong, additional, Kong, Wenwen, additional, Tian, Chuangyu, additional, Li, Juan, additional, Yang, Kunlin, additional, Han, Guanpeng, additional, Wu, Yucai, additional, He, Yuhui, additional, Peng, Yiji, additional, Yu, Yanfei, additional, He, Qun, additional, He, Shiming, additional, Gong, Yanqing, additional, Zhou, Liqun, additional, and Tang, Qi, additional

Published
2022
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76. Single-cell atlases link macrophages and CD8+ T-cell subpopulations to disease progression and immunotherapy response in urothelial carcinoma

Author

Liang, Yuan, primary, Tan, Yezhen, additional, Guan, Bao, additional, Guo, Bin, additional, Xia, Mancheng, additional, Li, Juan, additional, Shi, Yue, additional, Yu, Zihui, additional, Zhang, Qi, additional, Liu, Di, additional, Yang, Xiaopeng, additional, Hao, Junfeng, additional, Gong, Yanqing, additional, Shakeel, Muhammad, additional, Zhou, Liqun, additional, Ci, Weimin, additional, and Li, Xuesong, additional

Published
2022
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81. Patient‐Derived Upper Tract Urothelial Carcinoma Organoids as a Platform for Drug Screening

Author

Li, Zhichao, primary, Xu, Haibo, additional, Gong, Yanqing, additional, Chen, Wei, additional, Zhan, Yonghao, additional, Yu, Lei, additional, Sun, Yangyang, additional, Li, Aolin, additional, He, Shiming, additional, Guan, Bao, additional, Wu, Yucai, additional, Xiong, Gengyan, additional, Fang, Dong, additional, He, Yuhui, additional, Tang, Qi, additional, Yao, Lin, additional, Hu, Zheng, additional, Mei, Hongbing, additional, He, Zhisong, additional, Cai, Zhiming, additional, Guo, Yinglu, additional, Li, Xuesong, additional, Zhou, Liqun, additional, and Huang, Weiren, additional

Published
2021
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88. Copy Number Signatures and Clinical Outcomes in Upper Tract Urothelial Carcinoma

Author

Guan, Bao, primary, Liang, Yuan, additional, Lu, Huan, additional, Xu, Zhengzheng, additional, Shi, Yue, additional, Li, Juan, additional, Kong, Wenwen, additional, Tian, Chuanyu, additional, Tan, Yezhen, additional, Gong, Yanqing, additional, Liu, Jin, additional, Fang, Dong, additional, Shen, Qi, additional, He, Shiming, additional, Shakeel, Muhammad, additional, Zhang, Zhongyuan, additional, He, Qun, additional, Li, Xuesong, additional, Ci, Weimin, additional, and Zhou, Liqun, additional

Published
2021
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92. Genotype–phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions

Author

Zhang, Kenan, Yang, Wuping, Ma, Kaifang, Qiu, Jianhui, Li, Lei, Xu, Yawei, Zhang, Zedan, Yu, Chaojian, Zhou, Jingcheng, Gong, Yanqing, Cai, Lin, and Gong, Kan

Abstract

BackgroundApproximately 20%–40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate the genotype–phenotype correlations and clinical outcomes in VHL patients with LDs.MethodsIn this retrospective study, we included 119 patients with VHL disease from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods. Other germline mutations were confirmed by Sanger sequencing. Genotype–phenotype correlations and survival were analysed in different groups using Kaplan-Meier and Cox regression. We also evaluated therapeutic response to tyrosine kinase inhibitor (TKI) therapy.ResultsThe overall penetrance of patients aged <60 was 95.2%. Two VHL patients with LDs also carried CHEK2and FLCNgermline mutations. An earlier age of onset of retinal haemangioblastoma was observed in the next generation. Patients with exon 2 deletion of VHLhad an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1deletion. The group with earlier age of onset received poorer prognosis. Four of eight (50%) patients showed partial response to TKI therapy.ConclusionThe number of generations and the status of exon 2 could affect age of onset of VHL-related manifestations. Onset age was an independent risk factor for overall survival. TKI therapy was effective in VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes.

Published
2023
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97. Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice

Author

Gong, Yanqing, Hart, Erika, Shchurin, Aleksey, and Hoover-Plow, Jane

Subjects
Cell migration -- Physiological aspects -- Research -- Genetic aspects, Cardiovascular diseases -- Risk factors -- Physiological aspects -- Prevention -- Research -- Genetic aspects, Macrophages -- Physiological aspects -- Genetic aspects -- Research, Health care industry
Abstract

Inflammation plays a critical role in the development of cardiovascular diseases. Infiltration of leukocytes to sites of injury requires their exit from the blood and migration across basement membrane; this process has been postulated to require remodeling of the ECM. Plasminogen (Plg) is a protease that binds to the ECM and, upon conversion to plasmin, degrades multiple ECM proteins. In addition, plasmin directly activates MMPs. Here, we used Plg-/- mice to investigate the role of Plg in inflammatory leukocyte migration. After induction of peritonitis by thioglycollate injection, we found that Plg-/- mice displayed diminished macrophage trans-ECM migration and decreased MMP-9 activation. Furthermore, injection of the active form of MMP-9 in Plg-/- mice rescued macrophage migration in this model. We used periaortic application of [CaCl.sub.2] to induce abdominal aortic aneurysm (AAA) and found that Plg-/- mice displayed reduced macrophage infiltration and were protected from aneurysm formation. Administration of active MMP-9 to Plg-/- mice promoted macrophage infiltration and the development of AAA. These data suggest that Plg regulates macrophage migration in inflammation via activation of MMP-9, which, in turn, regulates the ability of the cells to migrate across ECM. Thus, targeting the Plg/MMP-9 pathway may be an attractive approach to regulate inflammatory responses and AAA development., Introduction Cardiovascular disease (CVD) is the leading cause of mortality in the United States and is responsible for nearly 50% of adult deaths. Numerous studies (reviewed in ref. (1)) document [...]

Published
2008

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