26 results on '"Hailin Ding"'
Search Results
2. Data from Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
- Author
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Kwok-Kin Wong, Sylvie Vincent, Rachael Brake, Victor M. Rivera, Haiquan Chen, Francois Gonzalvez, Sittinon Tang, Eleni Papadopoulos, Cassandra Thakurdin, Val Pyon, Hai Hu, Hailin Ding, Yuanwang Pan, Hua Zhang, Fei Li, Theresa E. Baker, Zhendong Gao, Jiehui Deng, David Peng, Jiansheng Wu, Johara Chouitar, Shougen Cao, Kwan Ho Tang, Chengwei Peng, Shengwu Liu, Michael Fitzgerald, Ting Chen, Shuai Li, and Han Han
- Abstract
No targeted treatments are currently approved for HER2 exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (HER2/ERBB2) exon 20 insertion mutations. However, the function of mobocertinib on HER2 exon 20 insertion–mutant lung cancer is still unclear. Here we conducted systematic characterization of preclinical models to understand the activity profile of mobocertinib against HER2 exon 20 insertions. In HER2 exon 20 insertion–mutant cell lines, the IC50 of mobocertinib was higher than poziotinib and comparable with or slightly lower than afatinib, neratinib, and pyrotinib. Mobocertinib had the lowest HER2 exon 20 insertion IC50/wild-type (WT) EGFR IC50 ratio, indicating that mobocertinib displayed the best selectivity profile in these models. Also, mobocertinib showed strong inhibitory activity in HER2 exon 20YVMA allograft and patient-derived xenograft models. In genetically engineered mouse models, HER2 exon 20G776>VC lung tumors exhibited a sustained complete response to mobocertinib, whereas HER2 exon 20YVMA tumors showed only partial and transient response. Combined treatment with a second antibody–drug conjugate (ADC) against HER2, ado-trastuzumab emtansine (T-DM1), synergized with mobocertinib in HER2 exon 20YVMA tumors. In addition to the tumor cell autonomous effect, sustained tumor growth control derived from M1 macrophage infiltration and CD4+ T-cell activation. These findings support the ongoing clinical development of mobocertinib (NCT02716116) and provide a rationale for future clinical evaluation of T-DM1 combinational therapy in HER2 exon 20YVMA insertion–mutant lung adenocarcinoma patients.Significance:This study elucidates the potent inhibitory activity of mobocertinib against HER2 exon 20 insertion–mutant lung cancer and the synergic effect of combined mobocertinib and T-DM1, providing a strong rationale for clinical investigation.
- Published
- 2023
3. Table S1 from Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
- Author
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Kwok-Kin Wong, Sylvie Vincent, Rachael Brake, Victor M. Rivera, Haiquan Chen, Francois Gonzalvez, Sittinon Tang, Eleni Papadopoulos, Cassandra Thakurdin, Val Pyon, Hai Hu, Hailin Ding, Yuanwang Pan, Hua Zhang, Fei Li, Theresa E. Baker, Zhendong Gao, Jiehui Deng, David Peng, Jiansheng Wu, Johara Chouitar, Shougen Cao, Kwan Ho Tang, Chengwei Peng, Shengwu Liu, Michael Fitzgerald, Ting Chen, Shuai Li, and Han Han
- Abstract
GSEA analysis of mobocertinib acquired resistant tumors versus response tumors Genes involved in "G2M CHECKPOINT", "MITOTIC SPINDLE" and "MTORC1 SIGNALING" pathways of HALLMARK gene sets.
- Published
- 2023
4. Figure S1 from Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
- Author
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Kwok-Kin Wong, Sylvie Vincent, Rachael Brake, Victor M. Rivera, Haiquan Chen, Francois Gonzalvez, Sittinon Tang, Eleni Papadopoulos, Cassandra Thakurdin, Val Pyon, Hai Hu, Hailin Ding, Yuanwang Pan, Hua Zhang, Fei Li, Theresa E. Baker, Zhendong Gao, Jiehui Deng, David Peng, Jiansheng Wu, Johara Chouitar, Shougen Cao, Kwan Ho Tang, Chengwei Peng, Shengwu Liu, Michael Fitzgerald, Ting Chen, Shuai Li, and Han Han
- Abstract
Figure S1
- Published
- 2023
5. Figure S2 from Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
- Author
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Kwok-Kin Wong, Sylvie Vincent, Rachael Brake, Victor M. Rivera, Haiquan Chen, Francois Gonzalvez, Sittinon Tang, Eleni Papadopoulos, Cassandra Thakurdin, Val Pyon, Hai Hu, Hailin Ding, Yuanwang Pan, Hua Zhang, Fei Li, Theresa E. Baker, Zhendong Gao, Jiehui Deng, David Peng, Jiansheng Wu, Johara Chouitar, Shougen Cao, Kwan Ho Tang, Chengwei Peng, Shengwu Liu, Michael Fitzgerald, Ting Chen, Shuai Li, and Han Han
- Abstract
Figure S2
- Published
- 2023
6. Figure S3 from Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
- Author
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Kwok-Kin Wong, Sylvie Vincent, Rachael Brake, Victor M. Rivera, Haiquan Chen, Francois Gonzalvez, Sittinon Tang, Eleni Papadopoulos, Cassandra Thakurdin, Val Pyon, Hai Hu, Hailin Ding, Yuanwang Pan, Hua Zhang, Fei Li, Theresa E. Baker, Zhendong Gao, Jiehui Deng, David Peng, Jiansheng Wu, Johara Chouitar, Shougen Cao, Kwan Ho Tang, Chengwei Peng, Shengwu Liu, Michael Fitzgerald, Ting Chen, Shuai Li, and Han Han
- Abstract
Figure S3
- Published
- 2023
7. Figure S4 from Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
- Author
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Kwok-Kin Wong, Sylvie Vincent, Rachael Brake, Victor M. Rivera, Haiquan Chen, Francois Gonzalvez, Sittinon Tang, Eleni Papadopoulos, Cassandra Thakurdin, Val Pyon, Hai Hu, Hailin Ding, Yuanwang Pan, Hua Zhang, Fei Li, Theresa E. Baker, Zhendong Gao, Jiehui Deng, David Peng, Jiansheng Wu, Johara Chouitar, Shougen Cao, Kwan Ho Tang, Chengwei Peng, Shengwu Liu, Michael Fitzgerald, Ting Chen, Shuai Li, and Han Han
- Abstract
Figure S4
- Published
- 2023
8. Elevated Placental microRNA-155 Is a Biomarker of a Preeclamptic Subtype
- Author
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Zhiyin Wang, Dan Liu, Yimin Dai, Ruotian Li, Yaowu Zheng, Guangfeng Zhao, Jingmei Wang, Zhenyu Diao, Chenrui Cao, Haining Lv, Ning Gu, Hang Zhou, Hailin Ding, Jie Li, Xiangyu Zhu, Honglei Duan, Li Shen, Qun Zhang, Jing Chen, Huilian Hu, Xiaoyan Wang, Mingming Zheng, Yan Zhou, and Yali Hu
- Subjects
Internal Medicine - Abstract
Background: Preeclampsia is a complicated syndrome with marked heterogeneity. The biomarker-based classification for this syndrome is more constructive to the targeted prevention and treatment of preeclampsia. It has been reported that preeclamptic patients had elevated microRNA-155 (miR-155) in placentas or circulation. Here, we investigated the characteristics of patients with high placental miR-155 (pl-miR-155). Methods: Based on the 95th percentile (P95) of pl-miR-155 in controls, preeclamptic patients were divided into high miR-155 group (≥P95) and normal miR-155 group ( Results: About one-third of preeclamptic patients had high pl-miR-155 expression, which was positively correlated with circulating miR-155 levels. These patients could be clustered as 1 group, according to clinical manifestation, placental pathology, or transcriptomes by t-distributed stochastic neighbor embedding and hierarchical clustering analysis. Further, the pregnant mice with placental restricted miR-155 overexpression could simulate the changes of clinical signs, pathology, and transcriptome of placentas in patients with high pl-miR-155. AntagomiR-155 treatment relieved the preeclampsia-like phenotype and improved the placental vascular development in mice. Conclusions: There is at least 1 type of preeclampsia with upregulated miR-155 presenting more severe clinical manifestations. MiR-155 may be a potential therapeutic target in patients with high pl-miR-155.
- Published
- 2022
9. Targeting HER2 Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
- Author
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Hua Zhang, Haiquan Chen, Sittinon Tang, Shougen Cao, Yuanwang Pan, Victor M. Rivera, Shuai Li, Fei Li, Kwan Ho Tang, Hai Hu, Chengwei Peng, Francois Gonzalvez, Hailin Ding, Jiehui Deng, Johara Chouitar, Han Han, Sylvie Vincent, Theresa E. Baker, Michael Fitzgerald, Val Pyon, Ting Chen, Zhendong Gao, Rachael L. Brake, Eleni Papadopoulos, David H. Peng, Jiansheng Wu, Cassandra Thakurdin, Kwok-Kin Wong, and Shengwu Liu
- Subjects
Cancer Research ,medicine.drug_class ,Afatinib ,T cell ,Poziotinib ,Biology ,medicine.disease ,Tyrosine-kinase inhibitor ,Exon ,medicine.anatomical_structure ,Oncology ,Neratinib ,medicine ,Cancer research ,Adenocarcinoma ,skin and connective tissue diseases ,Lung cancer ,medicine.drug - Abstract
No targeted treatments are currently approved for HER2 exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (HER2/ERBB2) exon 20 insertion mutations. However, the function of mobocertinib on HER2 exon 20 insertion–mutant lung cancer is still unclear. Here we conducted systematic characterization of preclinical models to understand the activity profile of mobocertinib against HER2 exon 20 insertions. In HER2 exon 20 insertion–mutant cell lines, the IC50 of mobocertinib was higher than poziotinib and comparable with or slightly lower than afatinib, neratinib, and pyrotinib. Mobocertinib had the lowest HER2 exon 20 insertion IC50/wild-type (WT) EGFR IC50 ratio, indicating that mobocertinib displayed the best selectivity profile in these models. Also, mobocertinib showed strong inhibitory activity in HER2 exon 20YVMA allograft and patient-derived xenograft models. In genetically engineered mouse models, HER2 exon 20G776>VC lung tumors exhibited a sustained complete response to mobocertinib, whereas HER2 exon 20YVMA tumors showed only partial and transient response. Combined treatment with a second antibody–drug conjugate (ADC) against HER2, ado-trastuzumab emtansine (T-DM1), synergized with mobocertinib in HER2 exon 20YVMA tumors. In addition to the tumor cell autonomous effect, sustained tumor growth control derived from M1 macrophage infiltration and CD4+ T-cell activation. These findings support the ongoing clinical development of mobocertinib (NCT02716116) and provide a rationale for future clinical evaluation of T-DM1 combinational therapy in HER2 exon 20YVMA insertion–mutant lung adenocarcinoma patients. Significance: This study elucidates the potent inhibitory activity of mobocertinib against HER2 exon 20 insertion–mutant lung cancer and the synergic effect of combined mobocertinib and T-DM1, providing a strong rationale for clinical investigation.
- Published
- 2021
10. The landscape of lung microbiota predicts the outcome of severe community-acquired pneumonia by interacting with the host immune response
- Author
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Yi Han, Mengna Lin, Feixiang Xu, Keyu Sun, Bin Yang, Su Lu, Hailin Ding, Jianli Wang, Guorong Gu, Min Min, Zhongshu Kuang, Mingming Xue, Lingyu Xing, Yunqiang Zhang, Huifang Liu, Weibing Wang, Yun Zhang, Chaoyang Tong, Hong Zhang, and Zhenju Song
- Abstract
Background: The lung microbiota and host immune response is thought to be a key player in the progression of pneumonia. However, the critical features of the microbiota have rarely been studied in severe community-acquired pneumonia (SCAP) patients. This study aimed to explore the correlations among the lung microbiota and the host immune defense, the disease severity, and the outcome in SCAP patients. Methods: A prospective and observational study in the intensive care unit (ICU) of four hospitals in China was performed. The lung microbiota was quantified and characterized using metagenomic next-generation sequencing (mNGS), collecting sputum and bronchoalveolar lavage fluid (BALF) in SCAP and CAP patients. Risk factors for disease progress and prognosis were investigated by logistic regression. In addition, transcriptomics was applied to explore host immune variation and the interaction between microbiota and host immune responses. Results: Our results showed that the microbiome α- and β-diversity in SCAP patients were significantly lower than those in CAP patients and lower in nonsurvivors than survivors. The Simpson index, the existence of Streptococcus pneumonia, the delta-SOFA score, the use of immunosuppressor, and activated partial thromboplastin time (APTT) were independently associated with the 28-day mortality of SCAP patients. Furthermore, the differentially expressed genes, including Opiorphin Prepropeptide (OPRPN), Histatin 1 (HTN1), Histatin 3 (HTN3), Lipocalin 1 (LCN1), Follicular Dendritic Cell Secreted Protein (FDCSP) and Statherin (STATH) in SCAP were correlated with immune response pathways. The neutrophil proportions and degranulation were suppressed in the nonsurvivors of SCAP. At the same time, interleukin-10 signaling was activated, while interferon-α, -β, and -γ responses were suppressed in the dismal outcome patients. Conclusions: Our findings confirmed that the lung microbiota played an essential role in association with the severity of pneumonia and represented a significant contributor to heterogeneity in SCAP by altering host immune responses.
- Published
- 2022
11. Nemvaleukin alfa, a novel engineered IL-2 fusion protein, drives antitumor immunity and inhibits tumor growth in small cell lung cancer
- Author
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Yuanwang Pan, Yuan Hao, Han Han, Ting Chen, Hailin Ding, Kristen E Labbe, Elaine Shum, Kayla Guidry, Hai Hu, Fiona Sherman, Ke Geng, Janaye Stephens, Alison Chafitz, Sittinon Tang, Hsin-Yi Huang, Chengwei Peng, Christina Almonte, Jared E Lopes, Heather C Losey, Raymond J Winquist, Vamsidhar Velcheti, Hua Zhang, and Kwok-Kin Wong
- Subjects
Pharmacology ,Cancer Research ,Oncology ,Immunology ,Molecular Medicine ,Immunology and Allergy - Abstract
BackgroundSmall cell lung cancer (SCLC) is a deadly disease with a 5-year survival of less than 7%. The addition of immunotherapy to chemotherapy was recently approved as first-line treatment; however, the improved clinical benefit is modest, highlighting an urgent need for new treatment strategies. Nemvaleukin alfa, a novel engineered interleukin-2 fusion protein currently in phase I–III studies, is designed to selectively expand cytotoxic natural killer (NK) cells and CD8+ T cells. Here, using a novel SCLC murine model, we investigated the effects of a mouse version of nemvaleukin (mNemvaleukin) on tumor growth and antitumor immunity.MethodsA novel Rb1−/−p53−/−p130−/− SCLC model that mimics human disease was generated. After confirming tumor burden by MRI, mice were randomized into four treatment groups: vehicle, mNemvaleukin alone, chemotherapy (cisplatin+etoposide) alone, or the combination of mNemvaleukin and chemotherapy. Tumor growth was measured by MRI and survival was recorded. Tumor-infiltrating lymphocytes and peripheral blood immune cells were analyzed by flow cytometry. Cytokine and chemokine secretion were quantified and transcriptomic analysis was performed to characterize the immune gene signatures.ResultsmNemvaleukin significantly inhibited SCLC tumor growth, which was further enhanced by the addition of chemotherapy. Combining mNemvaleukin with chemotherapy provided the most significant survival benefit. Profiling of tumor-infiltrating lymphocytes revealed mNemvaleukin expanded the total number of tumor-infiltrating NK and CD8+ T cells. Furthermore, mNemvaleukin increased the frequencies of activated and proliferating NK and CD8+ T cells in tumors. Similar immune alterations were observed in the peripheral blood of mNemvaleukin-treated mice. Of note, combining mNemvaleukin with chemotherapy had the strongest effects in activating effector and cytotoxic CD8+ T cells. mNemvaleukin alone, and in combination with chemotherapy, promoted proinflammatory cytokine and chemokine production, which was further confirmed by transcriptomic analysis.ConclusionsmNemvaleukin, a novel cytokine-based immunotherapy, significantly inhibited murine SCLC tumor growth and prolonged survival, which was further enhanced by the addition of chemotherapy. mNemvaleukin alone, and in combination with chemotherapy, drove a strong antitumor immune program elicited by cytotoxic immune cells. Our findings support the evaluation of nemvaleukin alone or in combination with chemotherapy in clinical trials for the treatment of SCLC.
- Published
- 2022
12. Placenta-derived IL-32β activates neutrophils to promote preeclampsia development
- Author
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Mingming Zheng, Qianwen Wu, Chenrui Cao, Yali Hu, Lu Xianyan, Zhiyin Wang, Qiang Li, Ya Wang, Guangfeng Zhao, Yayi Hou, Honglei Duan, Xiangyu Zhu, Huirong Tang, Dan Liu, Yimin Dai, and Hailin Ding
- Subjects
Male ,0301 basic medicine ,Neutrophils ,Placenta ,Immunology ,Syncytiotrophoblasts ,Article ,Andrology ,Pathogenesis ,Mice ,03 medical and health sciences ,HUVEC ,0302 clinical medicine ,Phagocytosis ,Pre-Eclampsia ,Downregulation and upregulation ,Pregnancy ,Proteinase 3 ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cell adhesion ,Cells, Cultured ,NADPH oxidase ,biology ,Chemistry ,Interleukins ,Neutrophil ,ROS ,Preeclampsia ,Mice, Inbred C57BL ,Innate immune cells ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,embryonic structures ,IL-32 ,biology.protein ,Cytokines ,Female ,Endothelium, Vascular ,Intracellular - Abstract
Immune activation at the maternal-fetal interface is a main pathogenic factor of preeclampsia (PE). Neutrophils (PMNs) are activated in PE patients, but the mechanism and consequences of PMN activation need to be further explored. Here, we demonstrated that interleukin-32 (IL-32) expression was significantly upregulated in syncytiotrophoblasts (STBs) and that IL-32β was the major isoform with increased expression in the placenta of severe PE (sPE) patients. Furthermore, the level of IL-32 expression in the placenta was correlated with its level in the serum of sPE patients, indicating that IL-32 in the serum is derived mainly from the placenta. Then, in vitro experiments showed that IL-32β could highly activate PMNs and that these IL-32β-activated PMNs were better able to adhere to endothelial cells (HUVECs) and enhance the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) in HUVECs, which could be reversed by preincubation with the NADPH oxidase inhibitor VAS 2870. In addition, we showed that IL-32β mainly activated PMNs by binding to proteinase 3. Finally, IL-32β administration induced a PE-like phenotype in a pregnant mouse model. This study provides evidence of the involvement of IL-32β in the pathogenesis of PE.
- Published
- 2021
13. Down-regulation of B2R contributes to preeclampsia by inhibiting human trophoblast cell invasion and angiogenesis
- Author
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Yanfang Peng, Guangfeng Zhao, Zhenyu Diao, Bin Cai, Dan Liu, Mingming Zheng, Yali Hu, Hailin Ding, and Zhiyin Wang
- Subjects
Adult ,Placental growth factor ,Receptor, Bradykinin B2 ,Angiogenesis ,Placenta ,Down-Regulation ,030204 cardiovascular system & hematology ,Umbilical vein ,Preeclampsia ,Andrology ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Pre-Eclampsia ,Downregulation and upregulation ,Cell Movement ,Pregnancy ,Human Umbilical Vein Endothelial Cells ,Internal Medicine ,medicine ,Animals ,Humans ,Placenta Growth Factor ,030219 obstetrics & reproductive medicine ,Chemistry ,Obstetrics and Gynecology ,Trophoblast ,medicine.disease ,Rats ,medicine.anatomical_structure ,Case-Control Studies ,embryonic structures ,Chorionic villi ,Female - Abstract
Objective Bradykinin B2 receptor (B2R) was decreased in early chorionic villi of pregnancies who progressed to severe preeclampsia (PE), suggesting downregulation of B2R may be involved in the pathogenesis of PE. The aim of this study was to investigate the possible roles of B2R in the pathophysiology of PE and its function in trophoblastic cells. Study design The expression of B2R in placentas from patients with early-onset severe PE (sPE) and LPS induced PE-like rats were detected. The roles of B2R in HTR-8/SVneo cells migration and invasion were analyzed through transfecting B2R overexpressing plasmid vector or B2R-specific siRNA. The effect of HTR-8/SVneo cells culture supernatant with high and low expressing B2R on human umbilical vein endothelial cells (HUVEC) capillary formation ability was also investigated. Results We found that B2R expression was significantly decreased in placentas of patients with sPE and PE-like rats. In addition, siRNA-mediated down-regulation of B2R markedly inhibited the migration and invasion of HTR-8/SVneo cells. Conversely, over-expression of B2R significantly promoted the migration and invasion of HTR-8/SVneo cells. Furthermore, the culture supernatant from B2R-overexpressed-HTR-8/SVneo cells promoted the capillary formation of HUVEC through increasing placental growth factor (PlGF) levels, while the culture supernatant from si-B2R-HTR-8/SVneo cells had the opposite effects. Conclusions The decrease of B2R in placentas leads to the dysfunction of invasion, migration and angiogenesis of trophoblasts, which may be involved in the pathogenesis of PE.
- Published
- 2020
14. Optimization Design of Remanufacturing Line-Starting Permanent Magnet Synchronous Motor Based on Ant Colony Algorithm
- Author
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Zhiwei Wen, Bin Xiong, Yong Wang, Hailin Ding, and Weiliang Liu
- Published
- 2022
15. ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1 mutant lung cancer
- Author
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Aristotelis Tsirigos, Subhadip Mukhopadhyay, Ting Chen, Mark R. Philips, Jiehui Deng, Hailin Ding, Val Pyon, Ian M. Ahearn, Fei Li, Mirna Bulatović, Antonio Marzio, Justin F. Gainor, Shuai Li, Cassandra Thakurdin, Heather Silver, Peter S. Hammerman, David H. Peng, Eli Rothenberg, John V. Heymach, Michele Pagano, Vajira K. Weerasekara, Yuanwang Pan, Hai Hu, Nathanael S. Gray, Charles M. Perou, Aatish Thennavan, Thales Papagiannakopoulos, Han Han, Baishan Jiang, John T. Poirier, Eleni Papadopoulos, Igor Dolgalev, Kwok-Kin Wong, Gordon J. Freeman, Charles M. Rudin, Nabeel Bardeesy, Eric S. Wang, and Jie Li
- Subjects
Cancer Research ,Antigen Presentation ,Lung Neoplasms ,biology ,Antigen processing ,business.industry ,medicine.medical_treatment ,Antigen presentation ,Autophagy ,Intracellular Signaling Peptides and Proteins ,Cancer ,Immunotherapy ,medicine.disease ,Article ,Immune system ,Oncology ,Carcinoma, Non-Small-Cell Lung ,medicine ,biology.protein ,Cancer research ,Autophagy-Related Protein-1 Homolog ,Humans ,Antibody ,Lung cancer ,business - Abstract
Inactivating mutations in LKB1/STK11 are present in roughly 20% of nonsmall cell lung cancers (NSCLC) and portend poor response to anti-PD-1 immunotherapy. Unexpectedly, we found that LKB1 deficiency correlated with elevated tumor mutational burden (TMB) in NSCLCs from nonsmokers and genetically engineered mouse models, despite the frequent association between high-TMB and anti-PD-1 treatment efficacy. However, LKB1 deficiency also suppressed antigen processing and presentation, which are associated with compromised immunoproteasome activity and increased autophagic flux. Immunoproteasome activity and antigen presentation were restored by inhibiting autophagy through targeting the ATG1/ULK1 pathway. Accordingly, ULK1 inhibition synergized with PD-1 antibody blockade, provoking effector T-cell expansion and tumor regression in Lkb1-mutant tumor models. This study reveals an interplay between the immunoproteasome and autophagic catabolism in antigen processing and immune recognition, and proposes the therapeutic potential of dual ULK1 and PD-1 inhibition in LKB1-mutant NSCLC as a strategy to enhance antigen presentation and to promote antitumor immunity. Wong and colleagues show that LKB1-deficient lung tumors are sensitive to autophagy inhibition, which can restore impaired antigen presentation and antitumor immune responses, and propose dual targeting of ULK1 and PD-1 for these tumors.
- Published
- 2021
16. Targeting
- Author
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Han, Han, Shuai, Li, Ting, Chen, Michael, Fitzgerald, Shengwu, Liu, Chengwei, Peng, Kwan Ho, Tang, Shougen, Cao, Johara, Chouitar, Jiansheng, Wu, David, Peng, Jiehui, Deng, Zhendong, Gao, Theresa E, Baker, Fei, Li, Hua, Zhang, Yuanwang, Pan, Hailin, Ding, Hai, Hu, Val, Pyon, Cassandra, Thakurdin, Eleni, Papadopoulos, Sittinon, Tang, Francois, Gonzalvez, Haiquan, Chen, Victor M, Rivera, Rachael, Brake, Sylvie, Vincent, and Kwok-Kin, Wong
- Subjects
Lung Neoplasms ,Receptor, ErbB-2 ,Adenocarcinoma of Lung ,Apoptosis ,Exons ,Mice, SCID ,Ado-Trastuzumab Emtansine ,Xenograft Model Antitumor Assays ,Article ,Gene Expression Regulation, Neoplastic ,Mice ,INDEL Mutation ,Mice, Inbred NOD ,Antibodies, Bispecific ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Cells, Cultured ,Animals ,Humans ,Female ,skin and connective tissue diseases ,Cell Proliferation - Abstract
No targeted treatments are currently approved for HER2 exon 20 insertion-mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (HER2/ERBB2) exon 20 insertion mutations. However, the function of mobocertinib on HER2 exon 20 insertion-mutant lung cancer is still unclear. Here we conducted systematic characterization of pre-clinical models to understand the activity profile of mobocertinib against HER2 exon 20 insertions. In HER2 exon 20 insertion mutant cell lines, the IC(50) of mobocertinib was higher than poziotinib and comparable or slightly lower than afatinib, neratinib, and pyrotinib. Mobocertinib had the lowest HER2 exon 20 insertion IC(50) / WT EGFR IC(50) ratio, indicating that mobocertinib displayed the best selectivity profile in these models. Also, mobocertinib showed strong inhibitory activity in HER2 exon 20(YVMA) allograft and patient-derived xenograft models. In genetically engineered mouse models, HER2 exon 20(G776>VC) lung tumors exhibited a sustained complete response to mobocertinib, while HER2 exon 20(YVMA) tumors showed only partial and transient response. Combined treatment with a second antibody-drug conjugate (ADC) against HER2, ado-trastuzumab emtansine (T-DM1) synergized with mobocertinib in HER2 exon 20(YVMA) tumors. In addition to the tumor cell autonomous effect, sustained tumor growth control derived from M1 macrophage infiltration and CD4(+) T cell activation. These findings support the ongoing clinical development of mobocertinib (NCT02716116) and provide a rationale for future clinical evaluation of T-DM1 combinational therapy in HER2 exon 20(YVMA) insertion-mutant lung adenocarcinoma patients.
- Published
- 2021
17. Vascular endothelial growth factor 165 inhibits pro-fibrotic differentiation of stromal cells via the DLL4/Notch4/smad7 pathway
- Author
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Haining Lv, Dan Liu, Yaowu Zheng, Minmin Song, Yali Hu, Zhiyin Wang, Hailin Ding, Ziqing Nan, Guangfeng Zhao, and Peipei Jiang
- Subjects
Adult ,Vascular Endothelial Growth Factor A ,Cancer Research ,Cell biology ,Stromal cell ,Genotyping Techniques ,Immunology ,Blotting, Western ,Notch signaling pathway ,Endometrium ,Article ,Smad7 Protein ,Cellular and Molecular Neuroscience ,Mice ,Young Adult ,medicine ,Animals ,Humans ,Receptor, Notch1 ,lcsh:QH573-671 ,Receptor ,Receptor, Notch4 ,Chemistry ,lcsh:Cytology ,Intracellular Signaling Peptides and Proteins ,Membrane Proteins ,Cell Differentiation ,Phenotype ,Collagen, type I, alpha 1 ,Vascular endothelial growth factor A ,medicine.anatomical_structure ,Infertility ,Cancer research ,Female ,Signal transduction ,Stromal Cells ,Signal Transduction - Abstract
Endometrial fibrosis is the main pathological feature of Asherman’s syndrome (AS), which is the leading cause of uterine infertility. Much is known about the expression of VEGF165 in luminal/glandular epithelial cells and stromal cells of the endometrium in normal menstrual cycles; however, less is known about the role and mechanism of VEGF165 in endometrial fibrosis. Herein, we report that VEGF165 is a key regulator in endometrial stromal cells to inhibit α-SMA and collagen 1 expression. Compared to human control subjects, patients with AS exhibited decreased VEGF165 expression in the endometrium along with increased fibrotic marker expression and collagen production. A fibrotic phenotype was shown in both mice with conditional VEGF reduction and VEGF165-deleted endometrial stromal cells. Exogenous VEGF165 could suppress TGFβ1-induced α-SMA and collagen 1 expression in human primary endometrial stromal cells. However, this beneficial effect was hindered when the expression of smad7 or Notch4 was inhibited or when Notch signaling was blocked, suggesting that smad7 and Notch4 are essential downstream molecules for VEGFA functioning. Overall, our results uncover a clinical targeting strategy for VEGF165 to inhibit pro-fibrotic differentiation of stromal cells by inducing DLL4/Notch4/smad7, which paves the way for AS treatment.
- Published
- 2019
18. Protective role of (5R)-5-hydroxytriptolide in lipopolysaccharide-induced acute lung injury by suppressing dendritic cell activation
- Author
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Yao, Chen, Zhongshu, Kuang, Wei, Wei, Yanyan, Hu, Sucheng, Mu, Hailin, Ding, Yi, Han, Chaoyang, Tong, Yilin, Yang, and Zhenju, Song
- Subjects
Lipopolysaccharides ,Male ,Pharmacology ,Dose-Response Relationship, Drug ,Acute Lung Injury ,Immunology ,NF-kappa B ,Dendritic Cells ,Mice, Inbred C57BL ,Toll-Like Receptor 4 ,Mice ,NF-KappaB Inhibitor alpha ,Animals ,Immunology and Allergy ,Female ,Diterpenes ,Immunosuppressive Agents - Abstract
(5R)-5-hydroxytriptolide (LLDT-8) is a triptolide derivative with potent immunosuppressive property. This study aimed to investigate whether LLDT-8 manifests anti-inflammatory effects and influences dendritic cell function in early phase of lipopolysaccharide (LPS)-induced acute lung injury (ALI). C57BL/6 mice were administrated with LPS (6 mg/kg) to induce ALI and LLDT-8 were administrated at different doses (0.125 mg, 0.25 mg, 0.5 mg/kg). Histological changes were demonstrated by hematoxylin and eosin staining. Activation of dendritic cells were measured by flow cytometry. The concentrations of cytokines were measured by enzyme-linked immunosorbent assay. Bone marrow-derived dendritic cells (BMDCs) were acquired to explore immunosuppressive effects of LLDT-8 in vitro. Expression of Toll-like receptor 4 (TLR4), phosphorylation of inhibitor kappa B alpha (IκBα) and nuclear translocation of nuclear factor kappa B (NF-κB) were explored by immunoblot. Immunosuppressive property of LLDT-8-treated BMDCs were measured by adoptive transfer. The survival rate of ALI mice was significantly improved by LLDT-8 at the dose of 0.25 mg/kg. Moreover, systemic inflammatory response was suppressed and lung injury was relieved. LLDT-8 inhibited the activation of dendritic cells in vivo and influenced maturation, apoptosis and cytokine secretion capacity of BMDCs in vitro. Additionally, LLDT-8-treated BMDCs manifested reduced expression of TLR4, phosphorylation of IκBα and nuclear translocation of NF-κB. Adoptive transfer of LLDT-8-treated BMDCs alleviated LPS-induced lung injury. LLDT-8 also had protective effects on Pseudomonas aeruginosa-induced ALI. In conclusion, LLDT-8 played a protective role against ALI and suppressed dendritic cell activation potentially through affecting TLR4 expression and NF-κB signaling.
- Published
- 2022
19. Corrigendum to 'Down-regulation of B2R contributes to preeclampsia by inhibiting human trophoblast cell invasion and angiogenesis' [Pregnancy Hypertens. 21 (2020) 14–22]
- Author
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Dan Liu, Yali Hu, Guangfeng Zhao, Bin Cai, Hailin Ding, Zhenyu Diao, Mingming Zheng, Yanfang Peng, and Zhiyin Wang
- Subjects
Pregnancy ,Downregulation and upregulation ,Angiogenesis ,business.industry ,Internal Medicine ,medicine ,Cancer research ,Obstetrics and Gynecology ,Trophoblast cell ,medicine.disease ,business ,Preeclampsia - Published
- 2021
20. MA11.02 Targeting HER2 Exon 20–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor, Mobocertinib
- Author
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Hao Chen, Zhendong Gao, Hailin Ding, Jiansheng Wu, Yuanwang Pan, Michael Fitzgerald, Sittinon Tang, Kwan Ho Tang, Cassandra Thakurdin, Sylvie Vincent, Rachael L. Brake, Kwok K. Wong, Ting Chen, S. Cao, Val Pyon, C. Peng, Jiehui Deng, Victor M. Rivera, Theresa E. Baker, Fei Li, Hai Hu, Francois Gonzalvez, David H. Peng, Simin Liu, Shihua Li, Eleni Papadopoulos, Johara Chouitar, Han Han, and Hua Zhang
- Subjects
Pulmonary and Respiratory Medicine ,Lung ,business.industry ,medicine.drug_class ,Mutant ,medicine.disease ,Tyrosine-kinase inhibitor ,Exon ,medicine.anatomical_structure ,Oncology ,medicine ,Cancer research ,Adenocarcinoma ,business - Published
- 2021
21. Endoscopic Supracerebellar Transtentorial Approach to Atrium of Lateral Ventricle: Preliminary Surgical and Optical Considerations
- Author
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Wei Sun, Linjun Zhou, Ye Gu, Chongjing Sun, Xiaobiao Zhang, Fan Hu, Tao Xie, Tengfei Liu, Hailin Ding, and Wei Zhu
- Subjects
Male ,Microsurgery ,medicine.medical_specialty ,Neuronavigation ,Endoscope ,03 medical and health sciences ,0302 clinical medicine ,Lateral Ventricles ,Humans ,Medicine ,Atrium (heart) ,Aged ,business.industry ,Middle Aged ,Tentorium ,Surgery ,Prone position ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Ventricle ,030220 oncology & carcinogenesis ,Neuroendoscopy ,Female ,Dura Mater ,Neurology (clinical) ,Radiology ,Glioblastoma ,Meningioma ,business ,Craniotomy ,030217 neurology & neurosurgery ,Diffusion MRI ,Corticotomy - Abstract
Objective We sought to report the operative techniques of the endoscopic supracerebellar transtentorial approach (ESTA) to the atrium of the lateral ventricle, especially focusing on the role of the endoscope and analyzing optically related issues. Methods A retrospective data review was performed on 5 patients with lesions in the atrium of the lateral ventricle undergoing the ESTA. The patients were positioned in the three quarters prone position, and a paramidline linear incision was used. After performing a suboccipital craniotomy extending immediately above the transverse sinus and tentorium incision with precisely neuronavigation, corticotomy in the posterior mediobasal temporal region created a corridor to the tumor. All of the procedures were performed with an endoscope in a pneumatic arm holder. The preoperative and postoperative perimetry test and diffusion tensor imaging fiber tracking of the optic radiations were compared and analyzed. Results Three patients had meningiomas, and 2 patients had high-grade gliomas in the atrium. The meningiomas were totally removed, and the gliomas were subtotally resected. One patient with glioblastoma died 2 months later after surgery because of the tumor progression; the remaining 4 patients had a visual field deficit without any other neurologic complications. The endoscope improved the surgical viewing angle, which was restricted by the microscope and slope of the tentorium. Conclusions ESTA is an alternative route to the atrium of the lateral ventricle. However, the collateral sulcus, which is highly relied on in neuronavigation, is illegible in the limited area. And the visual field deficit remains the primary challenge with this approach.
- Published
- 2017
22. Novel Biomarkers for Non-functioning Invasive Pituitary Adenomas were Identified by Using Analysis of microRNAs Expression Profile
- Author
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Yuying Huang, Hailin Ding, Yu Zhang, Tyh-Chai Wong, Silin Wu, Tengfei Liu, Xiaobiao Zhang, and Ye Gu
- Subjects
Adenoma ,Adult ,Male ,0301 basic medicine ,Microarray ,Notch signaling pathway ,Computational biology ,Biology ,Real-Time Polymerase Chain Reaction ,Bioinformatics ,Biochemistry ,Cohort Studies ,03 medical and health sciences ,Prolactin signaling pathway ,0302 clinical medicine ,Pituitary adenoma ,microRNA ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Neoplasm Invasiveness ,Pituitary Neoplasms ,KEGG ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Gene Expression Profiling ,Computational Biology ,General Medicine ,Middle Aged ,Sodium ion transport ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Potassium channel activity ,MicroRNAs ,030104 developmental biology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female - Abstract
The microRNAs (miRNAs) are involved in multiple pathological processes among various types of tumors. However, the functions of miRNAs in benign brain tumors are largely unexplored. In order to explore the pathogenesis of the invasiveness in non-functional pituitary adenoma (NFPA), the miRNAs expression profile was analyzed between invasive and non-invasive non-functional pituitary adenoma by miRNAs microarray. Six most significant differentially expressed miRNAs were identified including four upregulated miRNAs hsa-miR-181b-5p, hsa-miR-181d, hsa-miR-191-3p, and hsa-miR-598 and two downregulated miRNAs hsa-miR-3676-5p and hsa-miR-383. The functions and corresponding signaling pathways of differentially expressed miRNAs were investigated by bioinformatics techniques, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The result of GO analysis indicates regulation of voltage-gated potassium channel activity, positive regulation of sodium ion transport, positive regulation of GTPase activity, negative regulation of Notch signaling pathway, etc. KEGG pathway reveals a series of biological processes, including prolactin signaling pathway, endocrine and other factor-regulated calcium reabsorption, fatty acid metabolism, neuroactive ligand-receptor interaction, etc. The miRNAs hsa-miR-181a-5p was verified by quantitative real-time PCR, and the expression level was in accordance with the microarray result. Our result can provide the evidence on featured miRNAs which play a prominent role in pituitary adenoma as effective biomarkers and therapeutic targets in the future.
- Published
- 2017
23. CSF1-associated decrease in endometrial macrophages may contribute to Asherman's syndrome
- Author
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Guangfeng Zhao, Minmin Song, Dan Liu, Peipei Jiang, Haining Lv, Zhiyin Wang, Hailin Ding, Yali Hu, and Jiali Wang
- Subjects
0301 basic medicine ,Immunology ,Inflammation ,Asherman's syndrome ,Gynatresia ,CCL2 ,Cell Line ,Andrology ,03 medical and health sciences ,Endometrium ,0302 clinical medicine ,Fibrosis ,Immunology and Allergy ,Medicine ,Macrophage ,Humans ,030219 obstetrics & reproductive medicine ,business.industry ,Macrophage Colony-Stimulating Factor ,Macrophages ,Obstetrics and Gynecology ,medicine.disease ,030104 developmental biology ,Reproductive Medicine ,Apoptosis ,Immunohistochemistry ,Female ,medicine.symptom ,business ,Immunostaining - Abstract
Problem Asherman's syndrome (AS) is characterized by endometrial fibrosis leading to intrauterine adhesions and symptoms like hypomenorrhea, infertility, and recurrent pregnancy loss. Macrophages are key regulators of inflammation, tissue repair, regeneration, and fibrosis. However, the role of macrophages in AS remains unclear. Method of study Endometrial biopsies of AS patients and controls were collected during the late proliferating phase of menstrual cycle. Fibrosis and proliferation markers were detected by Masson's trichrome staining and immunohistochemistry. Macrophages were examined by immunostaining and flow cytometry. The expression levels of CCL2, CSF1, CSF1R, and GM-CSF were detected by quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry. A well-differentiated endometrial cell line Ishikawa (IK) was used for in vitro studies. Macrophages differentiating from THP-1 monocytic cells were polarized by IL-4/IL-13. Their culture supernatants (M(IL-4/13)-S) were applied to H2 O2 or bleomycin-damaged IK cells. Results In AS patients, endometrial stroma was replaced by fibrous tissue and cell proliferation was reduced. Macrophages in endometrial tissue were mainly alternative activated macrophages and their number was significantly decreased in AS patients. The CSF1 expression level was reduced in AS patients. M(IL-4/13)-S promoted the growth and migration of IK cells and inhibited H2 O2 -induced apoptosis. M(IL-4/13)-S protected IK cells from bleomycin-induced fibrosis. Conclusion Macrophages are critical cells involved in the process of endometrial repair and fibrosis. The decreased amount of endometrial macrophages may be attributed to the reduced expression level of CSF1. Manipulation of macrophage activation/function may provide a novel therapeutic target for AS.
- Published
- 2019
24. Dynamic changes in the distribution of facial and abdominal adipose tissue correlated with surgical treatment in acromegaly
- Author
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Wei Sun, Tao Xie, Ye Gu, Chongjing Sun, Xiaobiao Zhang, Mingfeng Xia, Tengfei Liu, Hailin Ding, and Fan Hu
- Subjects
0301 basic medicine ,Adenoma ,Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Urology ,Subcutaneous Fat ,Adipose tissue ,030209 endocrinology & metabolism ,Intra-Abdominal Fat ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pituitary adenoma ,Diabetes mellitus ,Acromegaly ,Abdominal fat ,medicine ,Humans ,Pituitary Neoplasms ,Metabolic disease ,Surgical treatment ,Adiposity ,Aged ,business.industry ,Perioperative ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,030104 developmental biology ,Treatment Outcome ,Female ,business - Abstract
Acromegaly is a systemic metabolic disease. Growth hormone (GH) have a significant impact on adipose tissue (AT). A huge reduction of serum GH after surgical treatment may cause substantial AT redistribution. The objective of this study was to illustrate the dynamic changes in distribution of facial and abdominal AT correlated with surgical treatment in patients with acromegaly. Abdominal AT in 17 acromegaly patients (group 1) was studied longitudinally preoperatively and 1 month to 1 year postoperatively. The facial and abdominal subcutaneous AT (fSAT and aSAT) of another 17 acromegaly patients (group 2) were compared with 7 nonfunctional pituitary adenoma (NFPA) controls. The areas of fSAT, aSAT, and visceral adipose tissue (VAT) were obtained by MRI and quantified by image analysis software, and intrahepatic lipid (IHL) was assessed by 1H magnetic resonance spectroscopy (MRS). Abdominal adipose tissue (aSAT, VAT, and IHL) increased overall after surgical treatment. However, IHL first decreased and then continuously increased during the follow-up. Compared with the increased amount of aSAT, the fSAT amount decreased after surgical treatment. The inconsistency of this phenomenon did not appear in the NFPA control subjects. The perioperative dynamic distribution of the facial and abdominal fat in acromegaly revealed regional differences in the intricate effect of GH on adipose tissue. Reduction of serum GH after surgical treatment of acromegaly was associated with dynamic increases of IHL, abdominal visceral, and subcutaneous fat, but a reduction of facial subcutaneous fat.
- Published
- 2018
25. Upregulation of CD81 in trophoblasts induces an imbalance of Treg/Th17 cells by promoting IL-6 expression in preeclampsia
- Author
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Yi Lei, Yimin Dai, Hailin Ding, Xiangyu Zhu, Ning Gu, Zhiyin Wang, Dan Liu, Yali Hu, Ruotian Li, Mingming Zheng, Guangfeng Zhao, and Li Shen
- Subjects
0301 basic medicine ,Adult ,Immunology ,chemical and pharmacologic phenomena ,T-Lymphocytes, Regulatory ,Article ,Immune tolerance ,Tetraspanin 28 ,Rats, Sprague-Dawley ,03 medical and health sciences ,Paracrine signalling ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,Pre-Eclampsia ,Pregnancy ,Paracrine Communication ,medicine ,Immunology and Allergy ,Animals ,Humans ,Interleukin 6 ,biology ,Interleukin-6 ,NF-kappa B ,Trophoblast ,hemic and immune systems ,Cell Differentiation ,biochemical phenomena, metabolism, and nutrition ,Cell biology ,Trophoblasts ,Up-Regulation ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,biology.protein ,Th17 Cells ,Female ,Antibody ,030215 immunology ,CD81 ,Signal Transduction - Abstract
The disturbance of maternal immune tolerance to a semiallogeneic fetus is recognized as one of the key pathologies of preeclampsia (PE), in which an imbalance between the inflammation-limiting regulatory T cells (Tregs) and the inflammation-mediating Th17 cells plays an essential role. Previously, we reported that the abnormal upregulation of tetraspannin CD81 in trophoblast cells (fetal component) participated in the pathogenesis of PE. However, as one of the potential immune regulatory molecules, whether CD81 induces PE by interfering with the balance of the maternal immune system has not yet been clarified. Thus, we investigated the relationship between the upregulation of CD81 in trophoblast cells and the imbalance of Treg and Th17 cells in mothers. Here, we demonstrated that upregulation of CD81 in trophoblast cells was accompanied by a decrease in Treg cells and an increase in Th17 cells in both the basal plate (placental maternal side) and peripheral blood of patients with PE. In vitro culture of naive T cells with medium from the CD81-overexpressing trophoblast cell line HTR-8 resulted in enhanced differentiation of T cells into Th17 cells and decreased the formation of Tregs, which was dependent on the paracrine signaling of IL-6 in trophocytes, induced by CD81. In a CD81-induced PE rat model, we found a significant shift of T cell differentiation towards Th17 cells, and administration of IL-6 antibody mitigated the PE phenotype and the imbalance of the Treg/Th17 cells. These results define a vital regulatory cascade involving trophocyte-derived CD81, IL-6, and maternal Treg/Th17 cells in the pathogenesis of PE and suggests new therapeutic approaches based on CD81 and IL-6 downregulation to prevent human PE.
- Published
- 2018
26. Learning curve for the endoscopic endonasal approach for suprasellar craniopharyngiomas
- Author
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Xiaobiao Zhang, Yong Yu, Tengfei Liu, Fan Hu, Hailin Ding, Tao Xie, Ye Gu, and Chongjing Sun
- Subjects
Adult ,Male ,Natural Orifice Endoscopic Surgery ,medicine.medical_specialty ,Cerebrospinal Fluid Rhinorrhea ,Hypopituitarism ,Nose ,03 medical and health sciences ,Craniopharyngioma ,0302 clinical medicine ,Postoperative Complications ,Physiology (medical) ,medicine ,Humans ,Pituitary Neoplasms ,Csf leakage ,Aged ,CRANIAL NERVE PARALYSIS ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Gross Total Resection ,Tumor recurrence ,Surgery ,Neurology ,030220 oncology & carcinogenesis ,Female ,Neurology (clinical) ,business ,Complication ,Meningitis ,030217 neurology & neurosurgery ,Learning Curve - Abstract
The endoscopic endonasal approach is considered an alternative minimally invasive approach for suprasellar craniopharyngiomas. However, the complicated surgical manipulations required by this approach have limited its application. We evaluate whether the approach features a learning curve. Thirty-three patients were retrospectively reviewed and grouped as early (17 patients) and late (16 patient) groups. The operation time, extent of removal, ophthalmology, endocrinology, reconstruction and modifications of standard technique were evaluated. Between the two groups, the operation time decreased from 201.1±105.3min in the early group to 107.6±90.0min in the late group (p
- Published
- 2016
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