19 results on '"Wuhu Zhang"'
Search Results
2. Hypoxia-reprogrammed regulatory group 2 innate lymphoid cells promote immunosuppression in pancreatic cancer
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Longyun Ye, Kaizhou Jin, Zhenyu Liao, Zhiwen Xiao, Huaxiang Xu, Xuan Lin, Hao Li, Tianjiao Li, Wuhu Zhang, Xuan Han, Wenquan Wang, Heli Gao, Liang Liu, Weiding Wu, and Xianjun Yu
- Subjects
Group 2 innate lymphoid cells (ILC2s) ,Pancreatic ductal adenocarcinoma (PDAC) ,Hypoxia ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Previously, we uncovered a patient subgroup with highly malignant pancreatic cancer with serum markers CEA+/CA125+/CA19-9 ≥ 1000 U/mL (triple-positive, TP). However, the underlying immunosuppressive mechanism in the tumor immune microenvironment (TIME) of this subgroup is still unknown. Methods: Human tissues were analyzed by flow cytometry, mass cytometry, and immunofluorescence staining. Mouse pancreatic ILC2s were expanded in vivo and used for RNA sequencing, chromatin immunoprecipitation (ChIP), and chemotaxis assays. Findings: Through microarray data, we identified the accumulation of the hypoxia-induced factor-1α (HIF-1α) pathway in these TP patients. Via flow and mass cytometry, we discovered that a special subset of ILC2s were highly infiltrated in TP patients. Under the hypoxia microenvironment, ILC2s were found undergo a transition to a IL10+ regulatory phenotype, we named ILCregs which was correlated with pancreatic ductal adenocarcinoma (PDAC) progression. Further, neoadjuvant chemotherapy could ameliorate hypoxic tumor microenvironments so that significantly reverse the regulatory phenotype of ILCregs. Moreover, most tumor ILC2 were CD103−, which indicated its circulatory origin. The expression of Ccr2 was significantly upregulated on mouse ILCregs, and these cells selectively migrated to CCL2. Interpretation: Our results indicate that the hypoxia microenvironment creates an immunosuppressive TIME by inducing ILCregs from a population of circulating group 2 ILCs in TP PDAC patients. Funding: This study was jointly supported by the National Natural Science Foundation of China (U21A20374, 82173091, and 81701630)
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- 2022
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- View/download PDF
3. The Interplay of Four Main Pathways Recomposes Immune Landscape in Primary and Metastatic Gastroenteropancreatic Neuroendocrine Tumors
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Xin Lou, Heli Gao, Xiaowu Xu, Zeng Ye, Wuhu Zhang, Fei Wang, Jie Chen, Yue Zhang, Xuemin Chen, Yi Qin, Xianjun Yu, and Shunrong Ji
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gastroenteropancreatic neuroendocrine neoplasms ,chromosomal instability ,telomere maintenance ,MTOR signaling ,DNA damage repair ,immune landscape ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundThe four major pathways in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) including chromatin remodeling, DNA damage repair, activation of mTOR signaling, and telomere maintenance were mediated by some critical molecules and constituted critical processes of regulation in cancer-causing processes. However, the interplay and potential role of these pathway-related molecules in the tumor microenvironment of the primary and metastatic site remained unknown.MethodsWe systematically evaluated the mRNA expression of 34 molecules associated with the four pathways in 227 GEP−NEN samples from 5 datasets. We assigned the samples into two expression patterns of pathway-related molecules by an unsupervised clustering method. Subsequently, we explored the specific cell-related molecules, especially immune and stromal cells using the WGCNA method, based on differentially expressed genes (DEGs) responsible for the different patterns of pathway-related molecules, which provided a new method to qualify the pathway-related subtypes of individual tumors, then the PC_Score and PI_Score scoring systems were also constructed using obtained specific cell-related molecules. Furthermore, we performed the association of pathway-related subtypes with characteristics of immune landscape in primary and metastatic GEP-NENs.ResultsWe demonstrated that the specific pathway-related molecules (SMARCA4, MLH1, TSC1, ATRX, and ATR) were associated with cytolytic activity. Then we identified the two distinct patterns of pathway-related molecules, which were characteristic with a significantly distinct immune landscape. Using WGCNA, we also identified the fibroblast-related molecules, including ASPN, COL10A1, COL3A1, EDNRA, MYL9, PRELP, RAB31, SPARC, and THBS2, and immune-related molecules including CASP1, CCL5, CTSS, CYBRD1, PMP22, and TFEC. Based on these specific markers, we identified four distinct pathway-related subtypes, characterized by immune and fibrotic enriched (I/FE), immune enriched (IE), fibrotic enriched (FE), and immune and fibrotic desert (I/FD), of which I/FE was characteristic with the highest PC_Score and PI_Score whereas I/FD presents the opposite trend. I/FE was positively correlated with immune landscape of T-cell activation and immunosuppression. Furthermore, the I/FE marked GEP-NENs with increased immune activation scores (T-cell costimulation, MHC I presentation, and APC costimulation). Importantly, the four distinct pathway-related subtypes were not conserved in different tumor sites, because I/FE was lacking in the liver metastatic site even though IE, FE, and I/FD also could be observed in the metastatic site.ConclusionsThis study was the first to perform a comprehensive analysis of the four major pathways in GEP-NENs. We demonstrated the potential function of these pathway-related molecules in immune landscapes. Our findings indicated that the primary and metastatic GEP-NENs had distinct antitumor phenotypes. This work highlighted the interplay and potential clinical utility of these pathway-related molecules in GEP-NENs.
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- 2022
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4. Research progress and design optimization of CAR‐T therapy for pancreatic ductal adenocarcinoma
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Tianjiao Li, Hao Li, Shuo Li, Shuaishuai Xu, Wuhu Zhang, Heli Gao, Huaxiang Xu, Chuntao Wu, Wenquan Wang, Xianjun Yu, and Liang Liu
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CAR‐T ,design optimization ,immunotherapy ,PDAC ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Chimeric antigen receptor T cells (CAR‐T) are genetically engineered T cells that can specifically kill tumor cells without major histocompatibility complex restriction. Encouraging progress in CAR‐T therapy for PDAC has been made in preclinical and early phase clinical trials. Challenges in CAR‐T therapy for solid tumors still exist, including immunosuppressive microenvironment, interstitial barrier, poor chemotaxis, and the “on‐target, off‐tumor” effect. Applying neoantigens of PDAC as targets for CAR‐T therapy, recognizing the CAR‐T subgroup with better antitumor effect, and designing a CAR‐T system targeting stroma of PDAC may contribute to develop a powerful CAR‐T therapy for PDAC in the future.
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- 2019
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5. The role of collagen in cancer: from bench to bedside
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Shuaishuai Xu, Huaxiang Xu, Wenquan Wang, Shuo Li, Hao Li, Tianjiao Li, Wuhu Zhang, Xianjun Yu, and Liang Liu
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Collagen ,Cancer ,Mutated genes ,Signaling pathways ,Tumor microenvironment ,Prognosis ,Medicine - Abstract
Abstract Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.
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- 2019
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6. Prognostic value of γ‐glutamyltransferase‐to‐albumin ratio in patients with pancreatic ductal adenocarcinoma following radical surgery
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Shuo Li, Huaxiang Xu, Chuntao Wu, Wenquan Wang, Wei Jin, Heli Gao, Hao Li, Shirong Zhang, Jinzhi Xu, Wuhu Zhang, Shuaishuai Xu, Tianjiao Li, Quanxing Ni, Xianjun Yu, and Liang Liu
- Subjects
γ‐glutamyltransferase‐to‐albumin ratio ,overall survival ,pancreatic ductal adenocarcinoma ,prognosis ,recurrence‐free survival ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis. Many preoperative biomarkers can predict postoperative survival of PDAC patients. In this study, we created a novel ratio index based on preoperative liver function test, γ‐glutamyltransferase‐to‐albumin ratio (GAR), and evaluated its prognostic value in predicting clinical outcomes of PDAC patients following radical surgery. We retrospectively enrolled 833 PDAC patients who had underwent radical surgery at our institution between January 2010 and January 2017. Patients were divided into two groups according to the cut‐off value of GAR. Univariate and multivariate survival analysis between the groups were evaluated. TNM stage, GAR, preoperative serum carbohydrate antigen 19‐9 (CA19‐9) and tumor differentiation were combined to generate a more accurate prognostic model. The optimal cut‐off value of GAR was 0.65. Significant correlations were found between GAR and tumor location, tumor size, vascular invasion, obstructive jaundice, biliary drainage and parameters of liver function test. Univariate and multivariate analysis showed that high level of GAR independently predicted poorer postoperative overall survival (OS, P < 0.001) and recurrence‐free survival (RFS, P < 0.001). Subgroup analysis demonstrated that GAR was predictive of survival in patients without biliary obstruction or severely impaired liver function. In addition, integration of GAR, preoperative serum CA19‐9, and tumor differentiation into TNM staging system could better stratify the prognosis for PDAC patients compared with TNM stage alone. Our study demonstrates that preoperative GAR is an independent prognostic factor for prediction of surgical outcomes in PDAC patients. Combination of TNM stage, GAR, preoperative serum CA19‐9, and tumor differentiation can enhance the prognostic accuracy.
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- 2019
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7. Follicular Helper T Cells Remodel the Immune Microenvironment of Pancreatic Cancer via Secreting CXCL13 and IL-21
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Xuan Lin, Longyun Ye, Xu Wang, Zhenyu Liao, Jia Dong, Ying Yang, Rulin Zhang, Hao Li, Pengcheng Li, Lei Ding, Tianjiao Li, Wuhu Zhang, Shuaishuai Xu, Xuan Han, Huaxiang Xu, Wenquan Wang, Heli Gao, Xianjun Yu, and Liang Liu
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follicular helper T cells ,immune microenvironment ,immunosuppression ,neoadjuvant chemotherapy ,pancreatic ductal adenocarcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Immunosuppression is an important factor for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Follicular helper T cells (Tfh cells) play an anti-tumor role in various malignant solid tumors and predict better patient prognosis. In the present study, we aimed to determine the immunosuppressive mechanism associated with Tfh cells and explore a new strategy to improve the tumor microenvironment of PDAC. Flow cytometry was used to detect the infiltration and proportion of Tfh cells in tumor tissues and peripheral blood from patients with PDAC. The spatial correlations of Tfh cells with related immune cells were evaluated using immunofluorescence. The function of Tfh cells was examined using in vitro and in vivo model systems. The high infiltration of Tfh cells predicted better prognosis in patients with PDAC. Tfh cells recruited CD8+ T cells and B cells by secreting C-X-C motif chemokine ligand 13 (CXCL13), and promoted the maturation of B cells into antibody-producing plasma cells by secreting interleukin 21 (IL-21), thereby promoting the formation of an immunoactive tumor microenvironment. The function of Tfh cells was inhibited by the programmed cell death 1 ligand 1 (PD-L1)/programmed cell death 1 (PD-1) signaling pathway in PDAC, which could be reversed using neoadjuvant chemotherapy. Treatment with recombinant CXCL13, IL-21 and Tfh cells alleviated tumor growth and enhanced the infiltration of CD8+ T cells and B cells, as well as B cell maturation in a PDAC mouse model. Our results revealed the important role of Tfh cells in mediating anti-tumor cellular immunity and humoral immunity in PDAC via secreting CXCL13 and IL-21 and determined a novel mechanism of immunosuppression in PDAC.
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- 2021
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8. Lightweight Investigation of Extended-Range Electric Vehicle Based on Collision Failure Using Numerical Simulation
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Jiangqi Long, Wenhao Huang, and Wuhu Zhang
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Physics ,QC1-999 - Abstract
The total weight of Extended-Range Electric Vehicle (E-REV) is too heavy, which affects rear-end collision safety. Using numerical simulation, a lightweight method is designed to reduce E-REV body and key parts weight based on rear-end collision failure analysis. To calculate and optimize the performance of vehicle safety, the simulation model of E-REV rear-end collision safety is built by using finite element analysis. Drive battery pack lightweight design method is analyzed and the bending mode and torsional mode of E-REV before and after lightweight are compared to evaluate E-REV rear-end collision safety performance. The simulation results of optimized E-REV safety structure are verified by both numerical simulation and experimental investigation of the entire vehicle crash test.
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- 2015
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9. Recent progress of experimental model in pancreatic neuroendocrine tumors: drawbacks and challenges
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Yan Wang, Fei Wang, Yi Qin, Xin Lou, Zeng Ye, Wuhu Zhang, Heli Gao, Jie Chen, Xiaowu Xu, Xianjun Yu, and Shunrong Ji
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Endocrinology ,Endocrinology, Diabetes and Metabolism - Published
- 2023
10. MEN1 promotes ferroptosis by inhibiting mTOR-SCD1 axis in pancreatic neuroendocrine tumors
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Zeng Ye, Haidi Chen, Shunrong Ji, Yuheng Hu, Xin Lou, Wuhu Zhang, Desheng Jing, Guixiong Fan, Yue Zhang, Xuemin Chen, Qifeng Zhuo, Jie Chen, Xiaowu Xu, Xianjun Yu, Jin Xu, Yi Qin, and Heli Gao
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Biophysics ,General Medicine ,Biochemistry - Abstract
Pancreatic neuroendocrine tumor (pNET) is the second most common malignant tumors of the pancreas. Multiple endocrine neoplasia 1 (
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- 2023
11. ASO Visual Abstract: Maximum Value on Arterial Phase Computed Tomography Predicts Prognosis and Treatment Efficacy of Sunitinib for Pancreatic Neuroendocrine Tumours
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Haidi Chen, Zheng Li, Yuheng Hu, Xiaowu Xu, Zeng Ye, Xin Lou, Wuhu Zhang, Heli Gao, Yi Qin, Yue Zhang, Xuemin Chen, Jie Chen, Wei Tang, Xianjun Yu, and Shunrong Ji
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Oncology ,Surgery - Published
- 2023
12. Maximum Value on Arterial Phase Computed Tomography Predicts Prognosis and Treatment Efficacy of Sunitinib for Pancreatic Neuroendocrine Tumours
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Haidi Chen, Zheng Li, Yuheng Hu, Xiaowu Xu, Zeng Ye, Xin Lou, Wuhu Zhang, Heli Gao, Yi Qin, Yue Zhang, Xuemin Chen, Jie Chen, Wei Tang, Xianjun Yu, and Shunrong Ji
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Oncology ,Surgery - Abstract
This study was designed to assess the computed tomography maximum (CTmax) value on pretherapeutic arterial phase computed tomography (APCT) images to predict pancreatic neuroendocrine tumours (pNETs) recurrence and clarify its role in predicting the outcome of tumour therapy.This retrospective study enrolled 250 surgical patients and 24 nonsurgical patients with sunitinib-based treatment in our hospital from 2008 to 2019. CT images were assessed, the maximum value was defined as "CTmax," and recurrence-free survival (RFS) or progression-free survival (PFS) was compared between a high-CTmax group and a low-CTmax group among patients who underwent surgical resection or nonsurgical, sunitinib-based treatment according to the CTmax cutoff value.In ROC curve analysis, a CTmax of 108 Hounsfield units, as the cutoff value, achieved an AUC of 0.796 in predicting recurrence. Compared with the low-CTmax group, the high-CTmax group had a longer RFS (p0.001). Low CTmax was identified as an independent factor for RFS (p0.001) in multivariate analysis; these results were confirmed using the internal validation set. The CTmax value was significantly correlated with the microvascular density (MVD) value (p0.001) and the vascular endothelial growth factor receptor 2 (VEGFR2) score (p0.001). Furthermore, the high-CTmax group had a better PFS than the low-CTmax group among the sunitinib treatment group (p = 0.007).The tumour CTmax on APCT might be a potential and independent indicator for predicting recurrence in patients who have undergone surgical resection and assessing the efficacy of sunitinib for patients with advanced metastatic pNETs.
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- 2022
13. Author response for 'The Optimal Duration of Capecitabine Plus Temozolomide in Patients with well‐differentiated Pancreatic NETs ‐ With or Without Maintenance Therapy'
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null Heli Gao, null Jia Dong, null Wuhu Zhang, null Huaxiang Xu, null Longyun Ye, null Hao Li, null Wenquan Wang, null Liang Liu, and null Xianjun Yu
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- 2022
14. The optimal duration of capecitabine plus temozolomide in patients with well-differentiated pancreatic NETs with or without maintenance therapy
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Heli Gao, Jia Dong, Wuhu Zhang, Huaxiang Xu, Longyun Ye, Hao Li, Wenquan Wang, Liang Liu, and Xianjun Yu
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Cellular and Molecular Neuroscience ,Neuroendocrine Tumors ,Endocrinology ,Endocrine and Autonomic Systems ,Endocrinology, Diabetes and Metabolism ,Antineoplastic Combined Chemotherapy Protocols ,Temozolomide ,Humans ,Prospective Studies ,Capecitabine ,Retrospective Studies - Abstract
The optimal duration of capecitabine combined with temozolomide (CapTem) for metastatic pancreatic neuroendocrine tumours (PanNETs) remains controversial. The present study aimed to assess the activity and safety of prolonged CapTem and Cap maintenance therapy in patients with metastatic PanNETs.Retrospective real-world data of 94 patients with metastatic PanNETs were obtained from one cancer centre. Fifteen patients were treated with Cap maintenance therapy after fixed 12-13 cycles of CapTem (group I), 44 patients were treated with prolonged CapTem until disease progression (group II), and 35 patients were treated with fixed 12-13 cycles of CapTem (group III).The mean ± SE follow-up period was 41.79 ± 26.31 months. The median CapTem treatment duration was 12 months in group I and 14 months in group II. The median time to best partial response was 12 months both in groups I and group II. The objective response rates of groups I and II were significantly higher than those of group III (73.3%, 41.9%, and 20%, respectively, p = .002). The median progression-free survival (mPFS) of group I and group II was significantly higher than that of group III (35 months, 26 months vs. 19 months, p .001). Safety analysis of the three groups indicated rare events of grade 3-4 toxicities, with nausea, vomiting, fatigue, and anaemia being the most common adverse effects.Patients with PanNETs who responded well to CapTem treatment may benefit from prolonged CapTem and Cap maintenance therapy after fixed cycles. Prospective studies are encouraged to further explore the prolonged CapTem treatment and maintenance therapy.
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- 2022
15. Establishment and characterization of the third non-functional human pancreatic neuroendocrine tumor cell line
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Xin Lou, Zeng Ye, Xiaowu Xu, Minglei Jiang, Renquan Lu, Desheng Jing, Wuhu Zhang, Heli Gao, Fei Wang, Yue Zhang, Xuemin Chen, Yi Qin, Qifeng Zhuo, Xianjun Yu, and Shunrong Ji
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Adult ,Pancreatic Neoplasms ,Cancer Research ,Neuroendocrine Tumors ,Cell Movement ,Cell Line, Tumor ,Humans ,Female ,Cell Biology - Abstract
The mechanisms of neuroendocrine tumor (NET) were still poorly understood, largely due to the lack of preclinical models of neuroendocrine neoplasms. Herein, we established and characterized SPNE1 cell lines from primary pancreatic NET tissue obtained from a 44-year-old female. Neuroendocrine character of SPNE1 was compared with existing non-functional cell lines BON1 and QGP1, and the results indicated expressions of multiple NET-specific markers in SPNE1 were higher relative to BON1 and QGP1. The growth character measured by Ki67 labeling index, cell cycle analysis, and 3D matrigel spheroid essay indicated that the proliferative rate of SPNE1 was lower than that of BON1 and QGP1. SPNE1 also was characterized with cancer stemness because of the higher proportion of CD44 + and CD117 + subpopulations relative to BON1, whereas it was similar to that of QGP1. Interestingly, SPNE1 highly expressed somatostatin receptors (SSTR2 and SSTR5) and angiogenic factors (VEGF1). SPNE1 had sensitive response to the four clinical treatments including tyrosine kinase inhibitor (TKI), mTOR inhibitors, somatostatin analogs (SSA), chemotherapy, which was similar to the BON1 and QGP1. Subcutaneous transplantations of SPNE1 also present the tumorigenicity, and neuroendocrine marker expression of xenograft tumors resembled the original human NET tissue. Then, we found a total of 8 common mutation in BON1, QGP1 and SPNE1 included CROCC, FAM135A, GPATCH4, CTBP2, FBXL14, HERC2, HYDIN, and PABPC3 using whole-exome sequencing (WES), and more neuroendocrine-related functional processes were enriched based on the private mutation genes in SPNE1, such as neuron migration, insulin secretion, and neuron to neuron synapse. In brief, SPNE1 could be used as a relevant model to study pancreatic NET biology and to develop novel treatment options.
- Published
- 2022
16. The Interplay of Four Main Pathways Recomposes Immune Landscape in Primary and Metastatic Gastroenteropancreatic Neuroendocrine Tumors
- Author
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Xin Lou, Heli Gao, Xiaowu Xu, Zeng Ye, Wuhu Zhang, Fei Wang, Jie Chen, Yue Zhang, Xuemin Chen, Yi Qin, Xianjun Yu, and Shunrong Ji
- Subjects
Cancer Research ,Oncology - Abstract
BackgroundThe four major pathways in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) including chromatin remodeling, DNA damage repair, activation of mTOR signaling, and telomere maintenance were mediated by some critical molecules and constituted critical processes of regulation in cancer-causing processes. However, the interplay and potential role of these pathway-related molecules in the tumor microenvironment of the primary and metastatic site remained unknown.MethodsWe systematically evaluated the mRNA expression of 34 molecules associated with the four pathways in 227 GEP−NEN samples from 5 datasets. We assigned the samples into two expression patterns of pathway-related molecules by an unsupervised clustering method. Subsequently, we explored the specific cell-related molecules, especially immune and stromal cells using the WGCNA method, based on differentially expressed genes (DEGs) responsible for the different patterns of pathway-related molecules, which provided a new method to qualify the pathway-related subtypes of individual tumors, then the PC_Score and PI_Score scoring systems were also constructed using obtained specific cell-related molecules. Furthermore, we performed the association of pathway-related subtypes with characteristics of immune landscape in primary and metastatic GEP-NENs.ResultsWe demonstrated that the specific pathway-related molecules (SMARCA4, MLH1, TSC1, ATRX, and ATR) were associated with cytolytic activity. Then we identified the two distinct patterns of pathway-related molecules, which were characteristic with a significantly distinct immune landscape. Using WGCNA, we also identified the fibroblast-related molecules, including ASPN, COL10A1, COL3A1, EDNRA, MYL9, PRELP, RAB31, SPARC, and THBS2, and immune-related molecules including CASP1, CCL5, CTSS, CYBRD1, PMP22, and TFEC. Based on these specific markers, we identified four distinct pathway-related subtypes, characterized by immune and fibrotic enriched (I/FE), immune enriched (IE), fibrotic enriched (FE), and immune and fibrotic desert (I/FD), of which I/FE was characteristic with the highest PC_Score and PI_Score whereas I/FD presents the opposite trend. I/FE was positively correlated with immune landscape of T-cell activation and immunosuppression. Furthermore, the I/FE marked GEP-NENs with increased immune activation scores (T-cell costimulation, MHC I presentation, and APC costimulation). Importantly, the four distinct pathway-related subtypes were not conserved in different tumor sites, because I/FE was lacking in the liver metastatic site even though IE, FE, and I/FD also could be observed in the metastatic site.ConclusionsThis study was the first to perform a comprehensive analysis of the four major pathways in GEP-NENs. We demonstrated the potential function of these pathway-related molecules in immune landscapes. Our findings indicated that the primary and metastatic GEP-NENs had distinct antitumor phenotypes. This work highlighted the interplay and potential clinical utility of these pathway-related molecules in GEP-NENs.
- Published
- 2021
17. MEN1 promotes ferroptosis by inhibiting mTOR-SCD1 axis in pancreatic neuroendocrine tumors.
- Author
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Zeng Ye, Haidi Chen, Shunrong Ji, Yuheng Hu, Xin Lou, Wuhu Zhang, Desheng Jing, Guixiong Fan, Yue Zhang, Xuemin Chen, Qifeng Zhuo, Jie Chen, Xiaowu Xu, Xianjun Yu, Jin Xu, Yi Qin, and Heli Gao
- Published
- 2022
- Full Text
- View/download PDF
18. The systemic inflammation response index predicts survival and recurrence in patients with resectable pancreatic ductal adenocarcinoma
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Shuo, Li, Huaxiang, Xu, Wenquan, Wang, Heli, Gao, Hao, Li, Shirong, Zhang, Jinzhi, Xu, Wuhu, Zhang, Shuaishuai, Xu, Tianjiao, Li, Quanxing, Ni, Xianjun, Yu, Chuntao, Wu, and Liang, Liu
- Subjects
overall survival ,pancreatic ductal adenocarcinoma ,systemic inflammation response index ,recurrence-free survival ,prognosis ,Original Research - Abstract
Purpose: The systemic inflammation response index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently emerged and used as a novel tool in predicting prognosis in different types of cancer. Our aim was to investigate the clinical significance of preoperative SIRI in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Materials and methods: The SIRI was developed in a training cohort of 371 PDAC patients undergoing radical surgery between 2010 and 2013 and validated in a validation cohort of 310 patients from 2014 to 2015. Baseline clinicopathologic characteristics, preoperative laboratory parameters and follow-up information were collected. The optimal cutoff value of SIRI was determined by receiver operating characteristic curve. Univariate and multivariate analysis were performed to analyze the prognostic value of SIRI. Results: The optimal cutoff value of SIRI stratified patients into low SIRI group (≤0.69) and high SIRI group (>0.69). Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients with low SIRI. The SIRI was an independent predictor of OS and RFS in multivariate analysis. In addition, SIRI remained its prognostic significance both in patients with early-stage diseases and in patients with normal carbohydrate antigen 19-9 levels. High SIRI indicated poor treatment response for patients who received postoperative adjuvant chemotherapy. Conclusion: Preoperative SIRI was an independent prognostic indicator of poor outcomes in PDAC patients after radical resection. It might assist clinicians to identify high-risk patients and choose the optimal individualized treatment strategy.
- Published
- 2018
19. Lightweight Investigation of Extended-Range Electric Vehicle Based on Collision Failure Using Numerical Simulation
- Author
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Wenhao Huang, Jiangqi Long, and Wuhu Zhang
- Subjects
Engineering ,business.product_category ,Article Subject ,Bending (metalworking) ,Computer simulation ,business.industry ,Mechanical Engineering ,Mode (statistics) ,Geotechnical Engineering and Engineering Geology ,Condensed Matter Physics ,Collision ,Battery pack ,lcsh:QC1-999 ,Automotive engineering ,Finite element method ,Mechanics of Materials ,Range (aeronautics) ,Electric vehicle ,business ,lcsh:Physics ,Simulation ,Civil and Structural Engineering - Abstract
The total weight of Extended-Range Electric Vehicle (E-REV) is too heavy, which affects rear-end collision safety. Using numerical simulation, a lightweight method is designed to reduce E-REV body and key parts weight based on rear-end collision failure analysis. To calculate and optimize the performance of vehicle safety, the simulation model of E-REV rear-end collision safety is built by using finite element analysis. Drive battery pack lightweight design method is analyzed and the bending mode and torsional mode of E-REV before and after lightweight are compared to evaluate E-REV rear-end collision safety performance. The simulation results of optimized E-REV safety structure are verified by both numerical simulation and experimental investigation of the entire vehicle crash test.
- Published
- 2015
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