Jichao Wang

Chinese Academy of Medical Sciences & Peking Union Medical College

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Yonggang Wu

People's Hospital of Xinjiang Uygur Autonomous Region

Xiaopeng Yang

Handong Global University

Yazhuo Zhang

Second People's Hospital of Yunnan Province

Guangwen Lu

Sichuan University

Yong Zheng

Guangdong Academy of Medical Sciences

Xuemei Zhang

Chongqing Medical University

Yunyu Feng

Sichuan University

Yibing Yin

Chongqing Medical University

Liangxue Zhou

Sichuan University

Wenchun Xu

Chongqing Medical University

Cooperative Institutions

Sichuan University

State Key Laboratory of Biotherapy

West China Hospital of Sichuan University

Chinese Academy of Medical Sciences & Peking Union Medical College

Chongqing Medical University

Capital Medical University

People's Hospital of Xinjiang Uygur Autonomous Region

Chinese Academy of Sciences

Zhejiang University

University of Chinese Academy of Sciences

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The correlation between microvessel density, IDH1 mutation and the malignancy of glioma and its clinical significance

Zhongliu yanjiu yu linchuang (2015)

Yong Zheng Yu Hong Yonggang Wu Cheng Zhang Jichao Wang

Objective To study the correlation between microvessel density (MVD), isocitrate dehydrogenase 1 (IDH1) mutation and the malignancy of glioma, and its clinic significance. Methods The data and specimens of 40 patients with gliomas confirmed by surgery and pathology were collected. The relation between IDH1 mutation (detected by genetic sequence), MVD (detected by immunohistochemical coloration) and the malignancy of glioma was explored. 5 cases of normal human brain tissues were used for comparative study. Results In normal brain tissue, Ⅰ, Ⅱ, Ⅲ, Ⅳ glioma, MVD counts were 8.12±1.64, 25.10±1.27, 27.00±1.98, 42.80±10.75 and 56.50±5.23, respectively, and the overall difference was statistically significant (H=35.42, P<0.05). The MVD counts in low-grade glioma (Ⅰ-Ⅱ) and high-grade glioma (Ⅲ-Ⅳ) were 23.94±8.03 and 45.54±8.19, respectively, and the difference was statistically significant (t=-8.369, P<0.001). No mutation was found in normal human brain tissue, while in 20 cases of glioma specimens, there was IDH1 mutation with R132 as the mutation site and a MVD count of 31.11±13.47, and the other 20 cases of glioma specimens experienced no IDH1 mutation and the corresponding MVD count was 40.54±12.11. The difference of MVD counts of low-grade glioma and high-grade glioma was statistically significant (t=2.328, P=0.025). Conclusion MVD can be used as one of the histopathological grading metrics for glioma. IDH1 mutation occurs more frequently in grade Ⅱ and Ⅲ gliomas with R132 as the mutation site. Key words: Microvessel density; IDH1 mutation; Glioma

Isocitrate dehydrogenase

Grading (engineering)

Clinical Significance

10.3760/cma.j.issn.1006-9801.2015.01.006

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Heterologous prime-boost immunization with live SPY1 and DnaJ protein of Streptococcus pneumoniae induces strong Th1 and Th17 cellular immune responses in mice

The Journal of Microbiology (2017)

Yulan Qiu Xuemei Zhang Hong Wang Xinyuan Zhang Yunjun Mo

Heterologous

Attenuated vaccine

Pneumococcal infections

10.1007/s12275-017-7262-1

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Citations (7)

Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy

Theranostics (2020)

Cheng Huang Hongjian Li Yunyu Feng Xiaoling Li Zongliang Zhang

Rationale: Current traditional treatment options are frequently ineffective to fight against ovarian cancer due to late diagnosis and high recurrence. Therefore, there is a vital need for the development of novel therapeutic agents. B7H3, an immune checkpoint protein, is highly expressed in various cancers, representing it a promising target for cancer immunotherapy. Although targeting B7H3 by bispecific T cell-engaging antibodies (BiTE) has achieved successes in hematological malignancies during recent years, attempts to use them for the treatment of solid cancers are less favorable, in part due to the heterogeneity of tumors. Sorafenib is an unselective inhibitor of multiple kinases currently being tested in clinical trials for several tumors, including ovarian cancer which showed limited activity and inevitable side effect for ovarian cancer treatment. However, it is able to enhance antitumor immune response, which indicates sorafenib may improve the efficiency of immunotherapy. Methods: We evaluated the expression of B7H3 in ovarian cancer using online database and validated its expression of tumor tissues by immunohistochemistry staining. Then, B7H3 expression and the effects of sorafenib on ovarian cancer cell lines were determined by flow cytometry. In addition, 2D and 3D ovarian cancer models were established to test the combined therapeutic effect in vitro. Finally, the efficiency of B7H3×CD3 BiTE alone and its combination with sorafenib were evaluated both in vitro and in vivo. Results: Our data showed that B7H3 was highly expressed in ovarian cancer compared with normal samples. Treatment with sorafenib inhibited ovarian cancer cell proliferation and induced a noticeable upregulation of B7H3 expression level. Further study suggested that B7H3×CD3 BiTE was effective in mediating T cell killing to cancer cells. Combined treatment of sorafenib and B7H3×CD3 BiTE had synergistic anti-tumor effects in ovarian cancer models. Conclusions: Overall, our study indicates that combination therapy with sorafenib and B7H3×CD3 BiTE may be a new therapeutic option for the further study of preclinical treatment of OC.

Bispecific antibody

Antibody therapy

10.7150/thno.49480

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Citations (16)

Solution degradant of mirabegron extended release tablets resulting from a Strecker-like reaction between mirabegron, minute amounts of hydrogen cyanide in acetonitrile, and formaldehyde in PEG during sample preparation

Journal of Pharmaceutical and Biomedical Analysis (2019)

Jinsheng Lin Tianpei Huang Mengxue Feng Dan Li Danna Zhao

Trimethylsilyl cyanide

Mirabegron

10.1016/j.jpba.2019.01.045

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Citations (13)

Mast cell degranulation impairs pneumococcus clearance in mice via IL-6 dependent and TNF-α independent mechanisms

World Allergy Organization Journal (2019)

Jing Yang Jichao Wang Xuemei Zhang Yulan Qiu Jurong Yan

Mast cells participate in immune responses by releasing potent immune system modifiers via degranulation. Due to currently reported controversial roles of mast cells in Streptococcus pneumoniae infections, this study aimed to determine the role and mechanism of mast cells in clearing S. pneumoniae in mice.In vivo mouse model of mast cell degranulation established by administration of C48/80 was evaluated for the influences of mast cell degranulation on bacterial colonization and inflammation. In vitro model was established to observe the influences of mast cell degranulation on phagocytic and bactericidal functions of neutrophils and macrophages. IL-6 null and TNF-α null mice on the C57BL/6 background were used to investigate the effects of inflammatory factors released by mast cell degranulation on bacterial clearance.Mast cell degranulation increased IL-6 and TNF-α levels and immune cell numbers in nasal lavage fluid, and inhibited the bactericidal function of macrophages and neutrophils in vitro. It decreased the number of neutrophils and macrophages recruited to respiratory tract after S. pneumoniae challenge and inhibited the clearance of S. pneumoniae in mice. After pretreatment with C48/80, S. pneumoniae loads were significantly lower in IL-6 null mice than in wild type mice, while no differences were observed between TNF-α null and wild type mice.Mast cell degranulation can cause inflammation and impair immune cell recruitment to respiratory tract after S. pneumoniae challenge. Products of mast cell degranulation including IL-6 decreased the bactericidal function of neutrophils and macrophages. Through these mechanisms, mast cell degranulation inhibited clearance of S. pneumoniae in mice.

10.1016/j.waojou.2019.100028

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Citations (19)

[Pneumococcal HSP40 induces the immune response in mouse macrophages via p38MAPK and JNK signaling pathways].

PubMed (2015)

Yingying Wu Song Gao Feng Ma Jingjing Cui Hua Yao

To investigate the mechanism of immune response in mouse macrophage induced by Pneumococcal heat shock protein 40 (HSP40).After recombinant HSP40 (rHSP40) underwent expression detection and purification, lipopolysaccharide (LPS) was removed from it. Then rHSP40 was used to stimulate bone marrow derived macrophages (BMDMs) derived from C57BL/6 wild-type mice. The mRNA levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1β, IL-23p19, IL-12p40, IL-12p35 and IL-10 in BMDMs were determined by reverse transcription PCR; the expressions of TNF-α, IL-6 and IL-12p40 were measured by ELISA. After stimulated by rHSP40, the levels of TNF-α and IL-6 expressed by wide-type, TLR2-/- and TLR4-/- BMDMs were detected by ELISA. The effects of the pretreatment of mitogen-activated protein kinases (MAPK) inhibitors on the secretion of TNF-α and IL-6 induced by rHSP40 were also evaluated by ELISA in BMDMs. The phosphorylation levels of p38MAPK and c-Jun N-terminal kinase (JNK) were determined by Western blotting.The rHSP40 protein reached a purity of more than 90%. It significantly enhanced the phosphorylation levels of p38MAPK and JNK as well as the expressions of TNF-α and IL-6. The p38MAPK and JNK inhibitors significantly suppressed the expressions of TNF-α and IL-6. The expressions of TNF-α and IL-6 in TLR4-/- BMDMs significantly decreased compared with wide-type BMDMs.HSP40-induced immune response of mouse macrophages is regulated by p38MAPK and JNK signaling pathways, and this induction process depends on TLR4.

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Complications's prophylaxis in neuroendoscopic endonasal transsphenoidal surgery for pituitary adenomas

Zhonghua shenjing waike zazhi (2011)

Yong Zheng Yonggang Wu Jichao Wang You-mu Abuduke Xiaopeng Yang

Objective To discuss the complicatiaons's prophylaxis of removing pituitary adenomas of neuroendoscopy in tranasphenoidal surgery. Method To analayze 253 cases Clinically date of pituitary adenoma were treated by endoscopic endonasal transsphenoidal surgery. Results The tumor removal was total in 216 ( 85.38% ) cases, subtotal in 26 ( 10. 28% ), and partial in 11 ( 4. 34% ). Temporary diabetes insipidus in 45 cases, pituitary function subnomorlity in 9 cases, cerebrospinal fluid leaks in 2 cases, nostril stenoses in 2 cases, anodmia in 2 cases, there were no internal carotid artery and optic nerve lesion, no subarachnoid hemorrhage and intracranial infection, no nasoseptal tresis. Conclusions Featured by minimal invasion and less postoperative complications, neurendoscopic endonasal transsphenoidal surgery is a safe and effective method for the treatment of pituitary adenoma. Key words: Pituitary neoplasms; Endoscopes; Transsphenoidal surgery; Complication

Transsphenoidal surgery

Endoscopic endonasal surgery

Pituitary Tumors

10.3760/cma.j.issn.1001-2346.2011.03.004

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Structural Analysis of Rabies Virus Glycoprotein Reveals pH-Dependent Conformational Changes and Interactions with a Neutralizing Antibody

Cell Host & Microbe (2020)

Fanli Yang Sheng Lin Fei Ye Jing Yang Jianxun Qi

10.1016/j.chom.2019.12.012

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Citations (79)

Lipid Nanoparticle Delivery System for mRNA Encoding B7H3‐redirected Bispecific Antibody Displays Potent Antitumor Effects on Malignant Tumors

Advanced Science (2022)

Cheng Huang Xing Duan Jichao Wang Qingqing Tian Yangmei Ren

The therapeutic use of bispecific T-cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half-life of BiTE have dampened some of the promise and impeded the pace of BiTE-based therapeutics to combat diseases. Nowadays, in vitro-transcribed mRNA has achieved programmed production, which is more flexible and cost-effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE-based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA-LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half-life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects.

Bispecific antibody

Delivery system

10.1002/advs.202205532

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Citations (33)

Differences in Dural Penetration of Clival Chordomas Are Associated with Different Prognosis and Expression of Platelet-Derived Growth Factor Receptor-β

World Neurosurgery (2016)

Yixuan Zhai Jiwei Bai Shuai Wang Jiang Du Jichao Wang

Tensin

Penetration (warfare)

10.1016/j.wneu.2016.07.096

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Citations (24)