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| 1 | Characterization of drug responses of mini patient-derived xenografts in mice for predicting cancer patient clinical therapeutic response显示文摘Background:Patient-derived organoids and xenografts(PDXs)have emerged as powerful models in functional diag-nostics with high predictive power for anticancer drug response.However,limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy,and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic.The present study aimed to develop an advanced PDX model,namely MiniPDX,for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment.Methods:We developed a rapid in vivo drug sensitivity assay,OncoVee®MiniPDX,for screening clinically relevant regimens for cancer.In this model,patient-derived tumor cells were arrayed within hollow fiber capsules,implanted subcutaneously into mice and cultured for 7 days.The cellular activity morphology and pharmacokinetics were systematically evaluated.MiniPDX performance(sensitivity,specificity,positive and negative predictive values)was examined using PDX as the reference.Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively.The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes.Results:Morphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors.Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients,including 14 gastric cancer,10 lung cancer and 2 pancreatic cancer.The positive predictive value of MiniPDX was 92%,and the negative predictive value was 81%with a sensitivity of 80%and a specificity of 93%.Through expanding to clinical tumor samples,Min-iPDX assay showed potential of wide clinical application.Conclusions:Fast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens.The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay,as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment. | Feifei Zhang Wenjie Wang Yuan Long Hui Liu Jijun Cheng Lin Guo Rongyu Li Chao Meng Shan Yu Qingchuan Zhao Shun Lu Lili Wang Haitao Wang Danyi Wen | 2018 | Cancer Communications2018，38，1： | 20 |
| 2 | Characterization of glucose-6-phosphate dehydrogenase deficiency and identification of a novel haplotype 487G>A/IVS5-612(G>C) in the Achang population of southwestern China显示文摘The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its gene mutations were studied in the Achang population from Lianghe County in Southwestern China. We found that 7.31% (19 of 260) males and 4.35% (10 of 230) females had G6PD deficiency. The molecular analysis of G6PD gene exons 2―13 was performed by a PCR-DHPLC-Sequencing or PCR-Sequencing. Sixteen inde-pendent subjects with G6PD Mahidol (487G>A) and the new polymorphism IVS5-612 (G>C), which combined into a novel haplotype, were identified accounting for 84.2% (16/19). And 100% Achang G6PD Mahidol were linked to the IVS5-612 C. The percentage of G6PD Mahidol in the Achang group is close to that in the Myanmar population (91.3% 73/80), which implies that there are some gene flows between Achang and Myanmar populations. Interestingly, G6PD Canton (1376G>T) and G6PD Kaiping (1388G>A), which were the most common G6PD variants from other ethnic groups in China, were not found in this Achang group, suggesting that there are different G6PD mutation profiles in the Achang group and other ethnic groups in China. Our findings appear to be the first documented report on the G6PD genetics of the AChang people, which will provide important clues to the Achang ethnic group origin and will help prevention and treatment of malaria in this area. | YANG YinFeng, ZHU YueChun, LI DanYi, LI ZhiGang, Lü HuiRu, WU Jing, TANG Jing & TONG ShuFen Department of Biochemistry, Faculty of Basic Medicine, Kunming University of Medical Sciences, Kunming 650031, China These authors contributed equally to this work | 2007 | Science China(Life Sciences)2007，50，4： | 6 |
| 3 | A new coumarin glycoside from the husks of Xanthoceras sorbifolia 显示文摘 | LI Zhanlin LI Xian LI Danyi | 2007 | Fitoterapia2007，78，： | 1 |
| 4 | Seven facts and five initiatives for gut microbiome research显示文摘The gut microbiome has attracted increasing attention over the past 15 years.Along with the fast-growing body of research literature and media reports,the public's opinions on the gut microbiome have begun to appear polarized.Some believe that the gut microbiome is at the core of human health and is related to every single disease.To the opposite,some people question the scientific basis of gut microbiome studies and criticize that many of them are farfetched;there is even a joke spreading in the biomedical research field—'keeping gut microbiome in mind,no mechanism is hard to find'. | Danyi Li Chunhui Gao Faming Zhang Ruifu Yang Canhui Lan Yonghui Ma Jun Wang | 2020 | Protein & Cell2020，11，6： | 1 |
| 5 | Intrinsic gemcitabine resistance in a novel pancreatic cancer cell lineis associated with cancer stem cell-like phenotype显示文摘 | Gang Hu Fu Li Kedong Ouyang Fubo Xie Xuzhen Tang Ke Wang Sufang Han Zhenzhou Jiang Minghua Zhu Danyi Wen Xiaoran Qin Luyong Zhang | 2012 | International Journal of Oncology2012，，3： | 1 |
| 6 | A new coumarin glycoside from the husks of Xanthoceras sorbifolia 显示文摘 | LI Zhan-lin LI Xian LI Danyi | 2007 | Fitoterapia2007，78，78： | 1 |
| 7 | Transactivation of the human NME5 gene by Sp1 in pancreatic cancer cells显示文摘 | Fu Li Zhenzhou Jiang Ke Wang Jingjing Guo Gang Hu Lixin Sun Tao Wang Xuzhen Tang Ling He Jincheng Yao Danyi Wen Xiaoran Qin Luyong Zhang | 2012 | Gene2012，，2： | 1 |
| 8 | Microbiome research outlook:past,present,and future显示文摘With its critical role in human health and disease,the microbiome has transformed modern biology.Over the past few years,microbiome research has evolved rapidly,with microbiologists gradually shifting their focus from cataloging microorganisms in the human microbiome to understanding their functional roles and how they interact with the host.Here,we present the global trends in microbiome research and summarize the past and current work on microbiome published in Protein&Cell. | Yunyun Gao Danyi Li Yong-Xin Liu | 2023 | Protein & Cell2023，14，10： | 0 |
| 9 | Dnmt3a is required for the tumor stemness of B16 melanoma cells显示文摘The relationship of carcinogenesis and DNA methyltransferases has attracted extensive attention in tumor research. We reported previously that inhibition of de novo DNA methyltransferase 3a (Dnmt3a) in murine B16 melanoma cells significantly suppressed tumor growth and metastasis in xenografted mouse model. Here, we further demonstrated that knockdown of Dnmt3a enhanced the proliferation in anchor-independent conditions of B16 cells, but severely disrupted its multipotent differentiation capacity in vitro. Furthermore, transforming growth factor β1, a key trigger in stem cell differentiation and tumor cell epithelial–mesenchymal transition (EMT), mainly induced apoptosis, but not EMT in Dnmt3a-deficient B16 cells. These data suggested that Dnmt3a is required for maintaining the tumor stemness of B16 cells and it assists B16 cells to escape from death during cell differentiation. Thus it is hypothesized that not only extraordinary self-renewal ability, but also the capacity of multipotent differentiation is necessary for the melanoma tumorigenesis. Inhibition of multipotent differentiation of tumor cells may shed light on the tumor treatment. | Haoyue Wang Ying Kuang Jun Li Ruling Shen Ruilin Sun Danyi Huang Zhejin Sheng Jiahao Shi Mengjie Zhang Fang Huang Hua Yang Jian Fei | 2019 | Acta Biochimica et Biophysica Sinica2019，51，9： | 0 |
| 10 | 用于预测癌症患者临床治疗方案的小鼠mini人源肿瘤异种移植模型的建立显示文摘背景与目的患者来源的类器官(patient-derived organoids,PDOs)和异种移植物(patientderivedxenografts,PDXs)具有较强的预测抗癌药物药效的能力,是功能检测的重要模型。然而,移植失败、构建PDX模型和随后检测药效的耗时过长、体外器官培养无法进行系统性给药等限制因素严重阻碍了其在临床上的应用,无法快速地筛选正确、可行的治疗方案。本研究旨在开发一种名为'miniPDX'的改良的PDX模型,用于快速检测药效,提高其在个体化癌症治疗中的应用价值。方法我们开发了一种快速检测体内药物敏感性的方法——OncoVee?MiniPDX,用于筛选癌症临床治疗方案。本模型将患者来源的肿瘤细胞注入中空纤维胶囊内,皮下植入小鼠体内培养7 d。系统评价了细胞的活性形态和药代动力学。以PDX为对照评估miniPDX的性能(敏感性、特异性、阳性和阴性预测值)。分别采用PDX和miniPDX模型以肿瘤生长抑制率和肿瘤细胞生长抑制率为指标检测药物反应。评价miniPDX模型对临床疗效的预测能力。结果MiniPDX胶囊内肿瘤细胞的形态学和组织病理学特征与PDX模型和原发肿瘤细胞的形态学和组织病理学特征均保持一致。26例(包括14例胃癌、10例肺癌和2例胰腺癌)来自患者的PDX肿瘤移植试验的药物反应与相应的miniPDX试验的药物反应结果具有良好的相关性。MiniPDX阳性预测值为92%,阴性预测值为81%,敏感性为80%,特异性为93%。通过扩大临床肿瘤样本,miniPDX检测显示出广泛的临床应用潜力。结论我们建立了基于胶囊植入技术的miniPDX快速体内检测方法,用于评估PDX肿瘤移植物和临床肿瘤标本的药物反应。PDX模型和其对应的miniPDX药效结果具有良好的相关性,结合转化研究数据最终表明miniPDX模型是一种先进的个体化癌症治疗工具。 | Feifei Zhang Wenjie Wang Yuan Long Hui Liu Jijun Cheng Lin Guo Rongyu Li Chao Meng Shan Yu Qingchuan Zhao Shun Lu Lili Wang Haitao Wang Danyi Wen | 2019 | 癌症2019，38，4： | 0 |
| 11 | Deflagration characteristics of freely propagating flames in magnesium hydride dust clouds显示文摘The flame propagation processes of MgH_(2)dust clouds with four different particle sizes were recorded by a high-speed camera.The dynamic flame temperature distributions of MgH_(2)dust clouds were reconstructed by the two-color pyrometer technique,and the chemical composition of solid combustion residues were analyzed.The experimental results showed that the average flame propagation velocities of 23μm,40μm,60μm and 103μm MgH_(2)dust clouds in the stable propagation stage were 3.7 m/s,2.8 m/s,2.1 m/s and 0.9 m/s,respectively.The dust clouds with smaller particle sizes had faster flame propagation velocity and stronger oscillation intensity,and their flame temperature distributions were more even and the temperature gradients were smaller.The flame structures of MgH_(2)dust clouds were significantly affected by the particle sinking velocity,and the combustion processes were accompanied by micro-explosion of particles.The falling velocities of 23μm and 40μm MgH_(2)particles were 2.24 cm/s and 6.71 cm/s,respectively.While the falling velocities of 60μm and 103μm MgH_(2)particles were as high as 15.07 cm/s and 44.42 cm/s,respectively,leading to a more rapid downward development and irregular shape of the flame.Furthermore,the dehydrogenation reaction had a significant effect on the combustion performance of MgH_(2)dust.The combustion of H_(2)enhanced the ignition and combustion characteristics of MgH_(2)dust,resulting in a much higher explosion power than the pure Mg dust.The micro-structure characteristics and combustion residues composition analysis of MgH_(2)dust indicated that the combustion control mechanism of MgH_(2)dust flame was mainly the heterogeneous reaction,which was affected by the dehydrogenation reaction. | Qiwei Zhang Yangfan Cheng Beibei Zhang Danyi Li Zhaowu Shen | 2024 | Defence Technology(防务技术)2024，31，1： | 0 |
| 12 | Structure-based drug discovery of novel fusedpyrazolone carboxamide derivatives as potent and selective AXL inhibitors显示文摘a novel and promising antitumor target,AXL plays an important role in tumor growth,metastasis,immunosuppression and drug resistance of various malignancies,which has attracted extensive research interest in recent years.In this study,by employing the structure-based drug design and bioisosterism strategies,we designed and synthesized in total 54 novel AXL inhibitors featuring a fusedpyrazolone carboxamide scaffold,of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions.Notably,compound 59 showed a desirable AXL kinase inhibitory activity(IC_(50):3.5 nmol/L)as well as good kinase selectivity,and it effectively blocked the cellular AXL signaling.In turn,compound 59 could potently inhibit BaF3/TEL-AXL cell viability(IC_(50):1.5 nmol/L)and significantly suppress GAS6/AXL-mediated cancer cell invasion,migration and wound healing at the nanomolar level.More importantly,compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency,in which we observed significant AXL phosphorylation suppression,and its antitumor efficacy at 20 mg/kg(qd)was comparable to that of BGB324 at 50 mg/kg(bid),the most advanced AXL inhibitor.Taken together,this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development. | Feifei Fang Yang Dai Hao Wang Yinchun Ji Xuewu Liang Xia Peng Jiyuan Li Yangrong Zhao Chunpu Li Danyi Wangh Yazhou Li Dong Zhang Dan Zhang Meiyu Geng Hong Liu Jing Ai Yu Zhou | 2023 | Acta Pharmaceutica Sinica B2023，13，12： | 0 |
| 13 | Genomic evolution during locoregional recurrence in colorectal cancer determined by whole-exome sequencing: a retrospective observational study显示文摘Objective:The genomic landscapes of metastatic colorectal cancer(mCRC)have been extensively studied;however,the genetic mechanisms underlying the locoregional recurrence(LR)of CRC remain unclear.The objective of our study was to investigate genomic evolution during LR in CRC using high-throughput sequencing.Methods:Twenty-three CRC patients with matched primary and LR tissues were recruited from Nanfang Hospital and Zhejiang Cancer Hospital between January 2011 and December 2018.The last date of follow-up was March 2020.Tissue samples were analyzed by whole-exome sequencing and the genomic profiles were depicted by single nucleotide variation,mutational signature,copy number variation,clonal architecture,and other features.The evolutionary process was speculated with comparison of the genetic variations between primary and LR lesions.The disseminating clusters from primary to LR lesions were identified by variant allele frequency dynamics.Furthermore,the early-recurrent biomarker was explored by comparing the indel signature between early-and late-recurrent patients.The study was approved by the Institutional Review Board of Nanfang Hospital of Southern Medical University(approval No.2020010)on September 11,2020.Results:The results highlighted distinct origins of LR between patients with high microsatellite instability and microsatellite stability.LR lesions evolved independently in patients with high microsatellite instability,while LR lesions were highly clonally related to the primary lesions in patients with microsatellite stability.Late-acquired variations in LR lesions encompassed a wide range of driver genes involved in histone methylation,DNA replication,T cell activation,PDCD1 gain,and LMNA loss.Furthermore,clonal analysis of the disseminating cells identified a dominant polyclonal seeding pattern during LR.The indel signature ID4 was associated with significantly shorter disease-free survival in patients with relapsed CRC according to a public dataset.Conclusion:These findings pose a challenge for the development of new approaches targeting the interactions of multiple clones in the establishment of LR and in terms of optimizing the clinical management of susceptible patients. | Xiaoliang Lan Xiaoxiao Wu Chao Zhang Genxia Wei Bingbing Li Weihao Qiu Danyi Li Huanwen Wu Yanqing Ding Jie Yuan Zaixian Tai Zuoquan Yang Zhiyong Liang Dan Su Li Liang | 2022 | Journal of Bio-X Research2022，5，4： | 0 |
| 14 | Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period显示文摘The spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in significant casualties and put immense strain on public health systems worldwide,leading to economic recession and social unrest.In response,various prevention and control strategies have been implemented globally,including vaccine and drug development and the promotion of preventive measures.Implementing these strategies has effectively curbed the transmission of the virus,reduced infection rates,and gradually restored normal social and economic activities.However,the mutations of SARS-CoV-2 have led to inevitable infections and reinfections,and the number of deaths continues to rise.Therefore,there is still a need to improve existing prevention and control strategies,mainly focusing on developing novel vaccines and drugs,expediting medical authorization processes,and keeping epidemic surveillance.These measures are crucial to combat the Coronavirus disease(COVID-19)pandemic and achieve sustained,long-term prevention,management,and disease control.Here,we summarized the characteristics of existing COVID-19 vaccines and drugs and suggested potential future directions for their development.Furthermore,we discussed the COVID-19-related policies implemented over the past years and presented some strategies for the future. | Danyi Ao Xuemei He Jian Liu Li Xu | 2024 | Signal Transduction and Targeted Therapy2024，9，1： | 0 |
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