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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

Oncology Research 2025年第1期33卷 225-234页

作者： WEI ZHANG WEICHENG WANG RUI WANG XIAO HAN LIJUN ZHU WENJIE guO yanhong gu Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Department of Oncology The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou225300China

Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse ***,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against *** study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating *** and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against *** we employed various techniques to evaluate different aspects of the experimental *** was used to detect cell proliferation and angiogenesis in tumor *** blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor ***,immunofluorescence was employed to measure cytokine ***:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug *** was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell ***:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune *** study presents the justification for utilizing the fruquintinib and venetoclax combination in treating *** holds promise in being assimilated into anticancer medications for CRC.

关键词： Colorectal cancer(CRC) B-cell lymphoma protein 2(BCL2) Venetoclax Vascular endothelial growth factor receptor(VEGFR) Fruquintinib Anti-angiogenesis Immunotherapy

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SOME EXTENDED KNAPSACK PROBLEMS INVOLVING JOB PARTITION BETWEEN TWO PARTIES

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Applied Mathematics(A Journal of Chinese Universities) 2007年第3期22卷 366-370页

作者： gu yanhong Chen Quanle Department of Applied Mathematics Shenzhen University Shenzhen 518060 China Department of Systems Engineering and Engineering Management The Chinese University of HongKong Shatin N.T. Hong Kong China

Some novel applications and pragmatic variations of knapsack problem （KP） are presented and constructed, which are formulated and developed from a model initiated in this paper on profit allocation from partition of... 详细信息

关键词： knapsack problem profit allocation job partition.

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Corrosion Behavior of Pipeline Steel in Oilfield Produced Water under Dynamic Corrosion System

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Journal of Wuhan University of Technology(Materials Science) 2022年第4期37卷 677-691页

作者： ZHAO Jie LIU Yida YANG Xiaoyu HE Xin WANG Lei XIONG Dan gu yanhong School of Mechanical Engineering Beijing Institute of Petrochemical TechnologyBeijing 102617China School of Safety Engineering Beijing Institute of Petrochemical TechnologyBeijing 102617China

In order to predict the corrosion trendency of X100 pipeline steel in flowing oilfield produced water,the effect of flow rate on the corrosion behavior of X100 pipeline steel was studied under general dynamic condition and simulated real working condition at the flow rate of 0.2,0.4,and 0.6 m·s^(-1).Potentiodynamic polarization curves and electrochemical impedance spectroscopy were used to study the corrosion behavior of X100 *** dispersive spectroscopy,X-ray diffraction and scanning electron microscopy were used to analyze corrosion product composition and *** experimental results show that the corrosion is more serious under simulated real working conditions than that under the general dynamic *** any case the corrosion current density increases with the increase of the flow rate,and the total impedance value *** corrosion products include Fe_(3)O_(4),Fe_(2)O_(3),and *** mass transfer and electrochemistry were simulated by flow coupled in COMSOL *** multiphysical field coupling simulation results are closer to the engineering practice than the single flow field simulation,and similar results from the experiments were *** experimental and simulation results reveal that the higher flow rate is,the more serious corrosion appear and the more corrosion products *** combining experimental and COMSOL simulation data,the corrosion process model of X100 steel was proposed.

关键词： X100 steel flow rate oilfield produced water corrosion behavior COMSOL simulation

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Analytical study of seashell using laser-induced breakdown spectroscopy

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Plasma Science and Technology 2017年第2期19卷 52-55页

作者： Ying LI yanhong gu Ying ZHANG Yuandong LI Yuan LU Optics and Optoelectronics Laboratory Ocean University of ChinaQingdao 266100People's Republic of China

Seashell has been applied as an indicator for ocean research and element analysis of the seashell is used to track biological or environmental evolution. In this work, laser-induced breakdown spectroscopy （LIBS） was applied for elementary analysis of an ezo scallop-shell, and a graphite enrichment method was used as the assistance. It was found that LIBS signal intensity of Ca fluctuated less than 5%, in spite of the sampling positions, and Sr/Ca was related to the shell growth. A similar variation was also found when using a direct LIBS analysis on the shell surface, and it might be more practicable to track shell growth by investigating Sr/Ca ratio with Sr ionic line at 421.6 nm. The obtained results prove that calcium （Ca） is qualified as an internal reference for shell analysis, and LIBS is a potential analytical method for seashell study.

关键词： seashell analysis LIBS graphite enriched process Sr/Ca shell growth

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Effects of Ba and Ti co-doping on BiFeO3 multiferroic ceramics optimized through two-step doping

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Journal of Advanced Ceramics 2016年第3期5卷 204-209页

作者： Sheng ZHU yanhong gu Yao XIONG Xi ZHOU Yong LIU Yu WANG Wanping CHEN Key Laboratory of Artificial Micro-and Nano-structures of Ministry of Education School of Physics and Technology Wuhan University Wuhan Hubei 430072 China School of Physics and Electronic Information Luoyang Normal College Luoyang Henan 471022 China School of Materials Science and Engineering Nanchang University Nanchang Jiangxi 330031 China

Ceramics of Bi0.9Ba0.1Fe0.925TixO3 (x = 0.0625, 0.08125, 0.0875, and 0.11) were prepared according to two doping strategies: one is called single-step doping in which Ba and Ti were doped together in calcination, while the other one is called two-step doping in which Ba and Ti were doped in calcination and sintering, respectively. Compared with samples prepared with single-step doping, those prepared with two-step doping have obviously different XRD patterns and small grains, and are dramatically improved in dielectric loss, resistivity, and remnant magnetization. A low dielectric loss of 0.05 at 10(3) Hz, a high resistivity of 4x10(12) ***, and a large remnant magnetization of 1.5 emu/g, have been obtained simultaneously for Bi0.9Ba0.1Fe0.925Ti0.11O3 prepared with two-step doping. The contrast between these two doping strategies clearly reveals the importance of establishing a proper doping strategy when two or more elements are co-doped to BiFeO3.

关键词： BiFeO3 doping multiferroic nonstoichiometric

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Strengthening mechanisms in carbon nanotube reinforced bioglass composites

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Frontiers of Chemical Science and Engineering 2012年第2期6卷 126-131页

作者： Jing ZHANG Chengchang JIA Zhizhong JIA Jillian LADEGARD yanhong gu Junhui NIE Department of Mechanical Engineering Indiana University-Purdue University Indianapolis Indianapolis IN 46202 USA School of Materials Science and Engineering University of Science and Technology Beijing Beijing 100083 China Department of Mechanical Engineering University of Alaska Fairbanks Fairbanks AK 99775 USA

Carbon nanotube reinforced bioglass composites have been successfully synthesized by two comparative sintering techniques, i.e., spark plasma sintering （SPS） and conventional compaction and sinteirng. The composites show improved mechanical properties, with SPS technique substantially better than conventional compact and sintering approach. Using SPS, compared with the 45S5Bioglass matrix, the maximum flexural strength and fracture toughness increased by 159% and 105%, respectively. Enhanced strength and toughness are attributed to the interfacial bonding and bridging effects between the carbon nanotubes and bioglass powders during crack propagations.

关键词： 45S5Bioglass multi-wall carbon nanotubes biocomposite mechanical properties sintering

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DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS-STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

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Acta Pharmaceutica Sinica B 2022年第1期12卷 262-273页

作者： Yuanyuan Wang Bin Wei Danping Wang Jingjing Wu Jianhua Gao Haiqing Zhong Yang Sun Qiang Xu Wen Liu yanhong gu Wenjie guo Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Cancer Rehabilitation Center Jiangsu Province HospitalNanjing 210029China Department of Oncology the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical UniversityHuai'an 223300China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing 210023China

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan(CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA(ds DNA) from the intestine, leading to cyclic-GMP-AMP synthase(c GAS)-stimulator of interferon genes(STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination(HR) repair and downregulate ds DNA-c GAS-STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

关键词： CPT-11 Gastrointestinal mucositis Andrographolide Homologous recombination cGAS-STING

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Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

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Journal of Pharmaceutical Analysis 2023年第7期13卷 726-744页

作者： Xiaofan Sun Lisha Zhou Yi Wang guoliang Deng Xinran Cao Bowen Ke Xiaoqi Wu yanhong gu Haibo Cheng Qiang Xu Qianming Du Hongqi Chen Yang Sun Department of Rheumatology and Immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210008China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Colon and Rectal Surgery Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing210001China Laboratory of Anesthesia and Critical Care Medicine Department of AnesthesiologyTranslational Neuroscience CenterWest China Hospital and State Key Laboratory of BiotherapySichuan UniversityChengdu610044China Genergy Bio-technology(Shanghai)Co. LtdShanghai200241China The First Affiliated Hospital of Nanjing Medical University Jiangsu Province HospitalNanjing210029China Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor The First Clinical College of Nanjing University of Chinese MedicineNanjing210023China General Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjing210006China School of Basic Medicine&Clinical Pharmacy China Pharmaceutical UniversityNanjing210009China Department of General Surgery Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200030China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to ***(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic *** study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)***,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and ***,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor ***,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling *** found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target ***,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted *** together,we provide new insights into the anti-tumor effects of CBD.

关键词： scRNA-seq scATAC-seq Cannabidiol Colorectal cancer Tumor microenvironment Macrophage

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SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

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Acta Pharmaceutica Sinica B 2019年第2期9卷 304-315页

作者： Mingxia Zhao Wenjie guo Yuanyuan Wu Chenxi Yang Liang Zhong guoliang Deng Yuyu Zhu Wen Liu yanhong gu Yin Lu Lingdong Kong Xiangbao Meng Qiang Xu Yang Sun State Key Laboratory of Pharmaceutical Biotechnology Deparment of Biotechnology and Pharmaceutical Sciences School of Life Sciences Nanjing University Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of Natural and Biomimetic Drugs Department of Chemical Biology School of Pharmaceutical Sciences Peking University Department of Oncology the First Affiliated Hospital with Nanjing Medical University

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both in vitro and in vivo. However, whether SHP099-mediated SHP2 inhibition retards tumor growth in vivo via anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to ***, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune ***099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8tIFN-γtT cells and the upregulation of cytotoxic T-cell related genes including Granzyme B andPerforin, which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and antiPD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growthin two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

关键词： Cancer immunotherapy SHP2 SHP099 PD-1 Colon cancer

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Protonation induced high-T_c phases in iron-based superconductors evidenced by NMR and magnetization measurements

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Science Bulletin 2018年第1期63卷 11-16页

作者： Yi Cui Gehui Zhang Haobo Li Hai Lin Xiyu Zhu Hai-Hu Wen guoqing Wang Jinzhao Sun Mingwei Ma Yuan Li Dongliang Gong Tao Xie yanhong gu Shiliang Lie Huiqian Luo Pu Yu Weiqiang Yu Department of Physics Renmin University of China Beijing 100872 China State Key Laboratory of Low Dimensional Quantum Physics and Department of Physics Tsinghua University Beijing 100084 China Center for Superconducting Physics and Materials National Laboratory of Solid State Microstructures and Department of Physics Collaborative Innovation Center for Advanced Microstructures Nanjing University Nanjing 210093 China International Center for Quantum Materials School of Physics Peking University Beijing 100871 China Collaborative Innovation Center of Quantum Matter Beijing 100871 China Beijing National Laboratory for Condensed Matter Physics Institute of Physics Chinese Academy of Sciences Beijing 100190 China University of Chinese Academy of Sdences Beijing 100049 China

Chemical substitution during growth is a well-established method to manipulate electronic states of quantum materials, and leads to rich spectra of phase diagrams in cuprate and iron-based superconductors. Here we report a novel and generic strategy to achieve nonvolatile electron doping in series of(i.e.11 and 122 structures) Fe-based superconductors by ionic liquid gating induced protonation at room temperature. Accumulation of protons in bulk compounds induces superconductivity in the parent compounds, and enhances the Tclargely in some superconducting ones. Furthermore, the existence of proton in the lattice enables the first proton nuclear magnetic resonance(NMR) study to probe directly superconductivity. Using Fe S as a model system, our NMR study reveals an emergent high-Tcphase with no coherence peak which is hard to measure by NMR with other isotopes. This novel electric-fieldinduced proton evolution opens up an avenue for manipulation of competing electronic states(*** insulators), and may provide an innovative way for a broad perspective of NMR measurements with greatly enhanced detecting resolution.

关键词： Ion liquid gating Protonation NMR Iron-based superconductors

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