主要目的:评估HB002.1T联合不同化疗方案在晚期实体瘤患者中的耐受性、安全性和药代动力学特点，确定HB002.1T联合不同化疗方案的最大耐受剂量，为II/III期临床研究推荐HB002.1T联合化疗的给药方案。次要目的:评估HB002.1T的免疫原性；按照实体瘤疗效评价标准（RECIST1.1），通过ORR、DCR、DOR和PFS初步评估HB002.1T联合不同化疗方案的抗肿瘤疗效。

开始日期2020-05-22

申办/合作机构

华博生物医药技术（上海）有限公司

100 项与 VEGFR2 x TGFBR2 相关的临床结果

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100 项与 VEGFR2 x TGFBR2 相关的转化医学

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0 项与 VEGFR2 x TGFBR2 相关的专利（医药）

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项与 VEGFR2 x TGFBR2 相关的文献（医药）

2023-01-01·Frontiers in physiology

The causal associations between growth factors and constipation: a two-sample Mendelian randomization study.

Article

作者: Xu, Peng ; Yu, Hui ; Xie, Jiale ; Wang, Jiachen ; Xu, Ke ; Fang, Jiaxin ; Yang, Mingyi ; Wan, Xianjie ; Wang, Zehua

Introduction: Certain growth factors (GFs) are associated with constipation, but few studies has analyzed the causal associations between the two. Therefore, this study used two-sample Mendelian randomization (MR) to systematically analyze the causal associations between GF levels and constipation based on data from genome-wide association studies (GWAS). Methods: Both GF and constipation data were obtained from European populations. GFs, as an exposure variable, were obtained from a genetic map of the human plasma proteome containing 3,301 samples, another GWAS dataset on 90 circulating proteins containing 30,931 samples, and a GWAS dataset containing 3,788 samples. Constipation, as an outcome variable, was obtained from the FinnGen project containing 26,919 cases and 282,235 controls and another UK Biobank dataset containing 3,328 cases and 459,682 controls. Single-nucleotide polymorphisms strongly associated with GFs were regarded as instrumental variables. Inverse-variance weighting, MR-Egger regression, weight median, simple mode, and weight mode methods were used to determine genetic associations. Cochran's Q test, Egger intercept, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier tests were used to analyze sensitivity. Results: The IVW analysis based on FinnGen showed that NGFI-A-binding protein 2 and vascular endothelial growth factor receptor 2 were inversely associated with constipation, and that fibroblast growth factor 7 and transforming growth factor beta receptor II levels were positively associated with constipation. The IVW analysis based on UK Biobank showed that proheparin-binding epidermal growth factor, platelet-derived growth factor AA, and vascular endothelial growth factor₁₂₁ were inversely associated with constipation. Conclusion: This study showed that some GFs are genetically associated with the risk of constipation.

2021-02-01·Experimental and Molecular Pathology4区 · 医学

The CTGF gene -945 G/C polymorphism is associated with target lesion revascularization for in-stent restenosis

4区 · 医学

Article

作者: Lejawa, Mateusz ; Osadnik, Tadeusz ; Bujak, Kamil ; Gąsior, Mariusz

BACKGROUND AND AIMSPrevious studies have shown that transforming growth factor β (TGF-β) and vascular endothelial growth factor A (VEGF-A) pathways are involved in the in-stent restenosis (ISR) process. The present study aimed to assess the relationship between single-nucleotide polymorphisms (SNPs) in genes encoding downstream proteins of TGF-β and VEGF-A pathways and the risk of target lesion revascularization (TLR) for in-stent restenosis.METHODSA total of 657 patients (with 781 treated lesions) who underwent percutaneous coronary intervention (PCI) with stent implantation at our center between 2007 and 2012 and completed a 4-year follow-up for clinically-driven TLR, were included. SNPs in CTGF (rs6918698), TGFBR2 (rs2228048), SMAD3 (rs17293632), KDR (rs2071559), CCL2 (rs1024610) were genotyped using TaqMan assay.RESULTSMajor allele carriers of CTGF gene -945 G/C polymorphism (rs6918698) were significantly less likely to underwent clinically-driven TLR during follow-up than minor allele carriers. After adjustment for clinical, angiographic, and procedural covariates, CTGF polymorphism was significantly associated with TLR, and minor allele (C) carriers had nearly two times higher risk of developing ISR requiring TLR (HR of 1.93, 95%CI 1.15-3.24) compared to patients with major (GG) genotype. No significant relationship was found between other analyzed polymorphisms and cumulative incidence of TLR at 4-years.CONCLUSIONSOur results suggest that functional -945 G/C polymorphism in the gene encoding connective tissue growth factor is associated with the need for TLR in patients who underwent PCI for stable coronary artery disease.

2020-01-01·Neuro-Oncology Advances

Circulating angiogenic cells in glioblastoma: toward defining crucial functional differences in CAC-induced neoplastic versus reactive neovascularization

Article

作者: Dik, Wim ; Sacchetti, Andrea ; Huizer, Karin ; Mustafa, Dana A ; Swagemakers, Sigrid ; Kros, Johan M ; van der Spek, Peter J

AbstractBackgroundIn order to identify suitable therapeutic targets for glioma anti-angiogenic therapy, the process of neovascularization mediated by circulating angiogenic cells (CACs) needs to be scrutinized.MethodsIn the present study, we compared the expression of neovascularization-related genes by 3 circulating CAC subsets (hematopoietic progenitor cells [HPCs], CD34+, and KDR+ cells; internal controls: peripheral blood mononuclear cells and circulating endothelial cells) of treatment-naïve patients with glioblastoma (GBM) to those of patients undergoing reactive neovascularization (myocardial infarction (MI). CACs from umbilical cord (representing developmental neovascularization) and healthy subjects served as controls. Fluorescent-activated cell sorting was used to isolate CACs, RT-PCR to determine the expression levels of a panel of 48 neovascularization-related genes, and Luminex assays to measure plasma levels of 21 CAC-related circulating molecules.ResultsWe found essential differences in gene expression between GBM and MI CACs. GBM CACs had a higher expression of proangiogenic factors (especially, KITL, CXCL12, and JAG1), growth factor and chemotactic receptors (IGF1R, TGFBR2, CXCR4, and CCR2), adhesion receptor monomers (ITGA5 and ITGA6), and matricellular factor POSTN. In addition, we found major differences in the levels of neovascularization-related plasma factors. A strong positive correlation between plasma MMP9 levels and expression of CXCR4 in the CAC subset of HPCs was found in GBM patients.ConclusionsOur findings indicate that CAC-mediated neovascularization in GBM is characterized by more efficient CAC homing to target tissue and a more potent proangiogenic response than in physiologic tissue repair in MI. Our findings can aid in selecting targets for therapeutic strategies acting against GBM-specific CACs.