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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 | Personalized treatment based on mini patient-derived xenografts and WES/RNA sequencing in a patient with metastatic duodenal adenocarcinoma显示文摘Background:Treatment guidelines for a variety of cancers have been increasingly used in clinical practice,and have resulted in major improvement in patient outcomes.However,recommended regimens(even first-line treat-ments)are clearly not ideal for every patients.In the present study,we used mini patient-derived xenograft(mini-PDX)and next-generation sequencing to develop personalized treatment in a patient with metastatic duodenal adenocarcinoma.Methods:Resected metachronous metastatic tumor tissues were implanted into SCID mice to determine the sensitivity to a variety of drug regimens.Mutation profiles were assessed using both DNA whole-exome sequencing(DNA-WES)and RNA sequencing.The results of the analyses were used to select optimal treatment for the patient with metastatic duodenal adenocarcinoma.Results:Assessment with mini-PDX models took only 7 days.The results showed high sensitivity to S-1 plus cis-platin,gemcitabine plus cisplatin and everolimus alone.The patient received gemcitabine plus cisplatin initially,but the treatment was terminated due to toxicity.The patient was then switched to treatment with S-1 alone.The overall disease-free survival was 34 months.DNA-WES and RNA sequencing identified KRAS mutation(A146T),TP53(C229Yfs*10)and RICTOR amplification in the metastatic duodenal adenocarcinoma.These findings provided further support to the results of the mini-PDX,and suggest mTOR inhibitors should be used if and when relapse eventually occurs in this patient.Conclusions:Mini-PDX model combined with WES/RNA sequencing can rapidly assess drug sensitivity in cancer patients and reveal key genetic alterations.Further research on this technology for personalized therapy in patients with refractory malignant tumors is warranted. | Peng Zhao Hui Chen Danyi Wen Shuo Mou Feifei Zhang Shusen Zheng | 2018 | Cancer Communications2018，38，1： | 11 |
| 3 | Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance显示文摘Background:Non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations or anaplastic lymphoma kinase(ALK)fusions show dramatic responses to specific tyrosine kinase inhibitors(TKIs);however,after 10-12 months,secondary mutations arise that confer resistance.We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK-and EGFR-targeted TKIs crizotinib and osimertinib,respectively.Methods:Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing(WES),and patients and xenograft-bearing mice received targeted treatment(crizotinib or osimertinib)accordingly.Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size.Finally,the pathology of patients biopsies and xenograft tumors were compared histologically.Results:The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients.WES showed that the genotypes of the xenograft and patient tumors were similar(an echinoderm microtu-bule-associated protein-like 4-ALK(EML4-ALK)gene fusion(patient/xenograft:CTC15035EML4-ALK)and EGFR L858R and T790M mutations(patient/xenograft:CTC15063EGFR L858R,T790M)).After continuous crizotinib or osimertinib treatment,WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4-ALK xenograft,while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B(BRAF)G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha(PIK3C2A)A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R,T790M xenografts.Conclusions:We successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology,which might be a useful tool to investigate the mechanisms of drug resist-ance in NSCLC. | Yunhua Xu Feifei Zhang Xiaoqing Pan Guan Wang Lei Zhu Jie Zhang Danyi Wen Shun Lu | 2018 | Cancer Communications2018，38，1： | 7 |
| 4 | 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 |
| 5 | Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice显示文摘Alveolar epithelial cells(AECs)injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis(PF).Nevertheless,the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear.SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF,which is essential for kidney and heart fibrosis.We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II(ATII)cells.Moreover,we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice(SOSM4D/D)model,as well as a new SMARCA4-deleted alveolar type II(ATII)-like mle-12 cell line.We found that the bleomycin-induced PF was more aggressive in SOSM4D/D mice.Also,the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro.In addition,we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections.These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells,which might affect the progression of PF. | Danyi Peng Daozhu Si Rong Zhang Jiang Liu Hao Gou Yunqiu Xia Daiyin Tian Jihong Dai Ke Yang Enmei Liu Yujun Shi Q.Richard Lu Lin Zou Zhou Fu | 2017 | Genes & Diseases2017，4，4： | 3 |
| 6 | Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea显示文摘The aim of this work is to discover the inhibitory mechanism of tea peptides and to analyse the affinities between the peptides and the angiotensin-converting enzyme(ACE)as well as the stability of the complexes using in vitro and in silico methods.Four peptide sequences identified from tea,namely peptides I,II,III,and IV,were used to examine ACE inhibition and kinetics.The half maximal inhibitory concentration(IC_(50))values of the four peptides were(210.03±18.29),(178.91±5.18),(196.31±2.87),and(121.11±3.38)μmol/L,respectively.The results of Lineweaver-Burk plots showed that peptides I,II,and IV inhibited ACE activity in an uncompetitive manner,which requires the presence of substrate.Peptide III inhibited ACE in a noncompetitive manner,for which the presence of substrate is not necessary.The docking simulations showed that the four peptides did not bind to the active sites of ACE,indicating that the four peptides are allosteric inhibitors.The binding free energies calculated from molecular dynamic(MD)simulation were-72.47,-42.20,-52.10,and-67.14 kcal/mol(1 kcal=4.186 kJ),r espectively.The lower IC_(50)value of peptide IV may be attributed to its stability when docking with ACE and changes in the flexibility and unfolding of ACE.These four bioactive peptides with ACE inhibitory ability can be incorporated into novel functional ingredients of black tea. | Yating LU Yu WANG Danyi HUANG Zhuang BIAN Peng LU Dongmei FAN Xiaochang WANG | 2021 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2021，22，7： | 2 |
| 7 | Analysis of EU priority polycyclic aro-matic hydrocarbons in food supplements using high performance liquid chro-matography coupled to an ultraviolet,diode array or fluorescence detector显示文摘 | Danyi S Brose F Brasseur C | 2009 | Anal Chim Acta2009，633，29： | 1 |
| 8 | Simultaneous quantification of six alkaloid components from commercial Stemonae Radix by SPE-HPLC-ELSD 显示文摘 | Zhang RongRong Lu DanYi Yang ZhenYa | 2015 | Phramacognosy magazine2015，，42： | 1 |
| 9 | Solubilisation and binding characteristics of a recombinant beta2-adrenergic receptor expressed in the membrane of Escherichia eoli for the multianalyte detection of beta agonists and antagonists residues in food-producing animals显示文摘 | Danyi S Degand G Duez C | 2007 | Anal Chim Acta2007，589，2： | 1 |
| 10 | A new coumarin glycoside from the husks of Xanthoceras sorbifolia 显示文摘 | LI Zhanlin LI Xian LI Danyi | 2007 | Fitoterapia2007，78，： | 1 |
| 11 | 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 |
| 12 | Oxybutynin enantiomer pharmacokinetics following oral and transdermal delivery显示文摘 | RHoward Z Bernhard S Alexander F Danyi Q Steven W | 2001 | Phar Res2001，18，： | 1 |
| 13 | 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 |
| 14 | Validation of a two- plate microbiological method for screening antibiotic residues in shrimp tissue显示文摘 | Dang P K Degand G Danyi S | 2010 | Analytical Chimica Acta2010，672，： | 1 |
| 15 | Development and application of a method for analysis of phthalates in ham sausages by solid- phase extraction and gas chromatograpy- mass spectrometry显示文摘 | GUO Zhiyong WANG Sui WEI Danyi | 2010 | Meat Sci2010，84，3： | 1 |
| 16 | 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 |
| 17 | Gel-state polybenzimidazole proton exchange membranes with flexible alkyl sulfonic acid side chains for a wider operating temperature range(25–240 ℃)显示文摘High-temperature proton exchange membrane fuel cells(HT-PEMFC) possess distinct technical advantages of high output power, simplified water/heat management, increased tolerance to fuel impurities and diverse fuel sources, within the temperature range of 120–200 ℃. However, for practical automobile applications, it was crucial to broaden their low-temperature operating window and enable cold start-up capability. Herein, gel-state phosphoric acid(PA) doped sulfonated polybenzimidazole(PBI) proton exchange membranes(PEMs) were designed and synthesized via PPA sol-gel process and in-situ sultone ring-opening reactions with various proton transport pathways based on absorbed PA, flexible alkyl chain connected sulfonic acid groups and imidazole sites. The effects of flexible alkyl sulfonic acid side chain length and content on PA doping level, proton conductivity, and membrane stability under different temperature and relative humidity(RH) were thoroughly investigated. The prepared gel-state membranes contained a self-assembled lamellar and porous structure that facilitated the absorption of a large amount of PA with rapid proton transporting mechanisms. At room temperature, the optimized membrane exhibited a proton conductivity of 0.069 S cm^(-1), which was further increased to 0.162 and 0.358 S cm^(-1)at 80 and 200 ℃, respectively, without additional humidification. The most significant contribution of this work was demonstrating the feasibility of gel-state sulfonated PBI membranes in expanding HT-PEMFC application opportunities over a wider operating range of 25 to 240 ℃. | Taizhong Zhu Danyi Zhu Jiazhen Liang Liang Zhang Fei Huang Lixin Xue | 2023 | Journal of Energy Chemistry2023，，10： | 1 |
| 18 | Etiological study on isolated esophageal atresia显示文摘 | Danyi G Czeizel A | 1985 | Hum Genet1985，70，1： | 1 |
| 19 | Align-ing professional preparation and practice: Bringing construetivist learning to kindergarten 显示文摘 | Da Ros-Voseles Danyi & Aurillo | 2003 | Dimensions of Early Childhood2003，31，2： | 1 |
| 20 | Development and application of a method for analysis of phthalates in ham sausages by solid-phase extraction and gas chromatography–mass spectrometry显示文摘 | Zhiyong Guo Sui Wang Danyi Wei Meili Wang Huina Zhang Panpan Gai Jing Duan | 2009 | Meat Science2009，，3： | 1 |
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