Publications by authors named "Zhengtao Zhang"

16 Publications

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Mannosylated gelatin nanoparticles enhanced inactivated PRRSV targeting dendritic cells and increased T cell immunity.

Vet Immunol Immunopathol 2021 May 5;235:110237. Epub 2021 Apr 5.

College of Life Science and Technology, Dalian University, Dalian, 116622, PR China; Institute of Immunology, Dalian University, Dalian, 116622, PR China. Electronic address:

The objective of the present work was to evaluate the efficacy of a novel antigen carrier using mannosylated gelatin nanoparticles with entrapped inactivated porcine reproductive and respiratory syndrome virus (PRRSV) in inducing T cell mediated immunity in vitro. Gelatin nanoparticles (GNP) were modified with mannose to form mannosylated gelatin nanoparticles (MnGNP), which can efficiently and specifically target monocyte derived dendritic cells (MoDCs). The inactivated PRRSV was encapsulated in the MnGNP and GNP, referred to as MnGNP-PRRSV and GNP-PRRSV, respectively. All these prepared nanometer particles were characterized for size, surface charge, drug encapsulation efficiency, and drug release. The efficacy of MnGNP in targeting MoDCs was investigated, as well as the subsequent MoDCs maturation and T cell mediated cytotoxicity. The developed MnGNP-PRRSV particle was characterized with a nanometric size of 302.67 ± 3.2 nm, surface charge of 23.81 ± 1.26 mV, and PRRSV encapsulation efficiency of 63.2 ± 1.85 %. The maximum uptake of MnGNP in MoDCs in vitro was 15.5 times higher than GNP with a shorter reaction time that peaked 4 h earlier. The uptake of MnGNP-PRRSV induced maturation of MoDCs and significantly enhanced expression of SWC-3a, CD80, CD1, SLA I, SLA II on MoDCs, compared to PRRSV (p < 0.001). The cytokine secretion of IL-1β, IL-6, IL-10, and IL-12 was also increased in MoDCs when treated with MnGNP-PRRSV, compared to PRRSV (p < 0.05). The matured MoDCs triggered T lymphocytes in autologous peripheral blood mononuclear cells (PBMCs) activation, proliferation, and differentiation into effector cytotoxic T lymphocyte, suggesting increased amount of activated T cells after MnGNP-PRRSV treatment. Additionally, the function of T cells to kill PRRSV infected cells was 83.98 ± 2.62 % when triggered by MnGNP-PRRSV, compared to 60 ± 4.7 % in PRRSV group (p < 0.001). These results indicate that MnGNP with entrapped inactivated PRRSV can effectively and specifically target dendritic cells for maturation and activation, and subsequently improve T cell activation, proliferation and function to kill PRRSV infected cells.
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http://dx.doi.org/10.1016/j.vetimm.2021.110237DOI Listing
May 2021

RePhine: An Integrative Method for Identification of Drug Response-related Transcriptional Regulators.

Genomics Proteomics Bioinformatics 2021 Mar 10. Epub 2021 Mar 10.

SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA; Department of Biostatistics, Yale School of Public Health, New Haven, CT 06511, USA; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China; Center for Biomedical informatics, Shanghai Children's Hospital, Shanghai 200040, China. Electronic address:

Transcriptional regulators (TRs) participate in essential processes in cancer pathogenesis and are critical therapeutic targets. Identification of drug response-related TRs from cell line-based compound screening data is often challenging due to low mRNA expression levels of TRs, protein modifications, and other confounders. In this study, we developed a regression-based pharmacogenomic and ChIP-seq data integration method (RePhine) to infer the impact of TRs on drug response through integrative analysis of pharmacogenomic and ChIP-seq data. RePhine was evaluated in simulation and pharmacogenomic data and was applied to pan-cancer datasets with the goal of biological discovery. In simulation data with added noise or confounders and in pharmacogenomic data RePhine demonstrated an improved performance in comparison with several commonly used methods such as correlation analysis and gene set enrichment analysis. Utilizing RePhine and Cancer Cell Line Encyclopedia data, we observed that RePhine-derived TR signatures could effectively cluster drugs with different mechanisms of action. RePhine predicted that loss of function of EZH2/PRC2 reduces cancer cell sensitivity toward the BRAF inhibitor PLX4720. Experimental validation confirmed that pharmacological EZH2 inhibition increases the resistance of cancer cells to PLX4720 treatment. Our results support that RePhine is a useful tool for inference of the TRs related to drug response and for potential therapeutic applications. The source code for RePhine is freely available at https://github.com/coexps/RePhine.
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http://dx.doi.org/10.1016/j.gpb.2019.09.008DOI Listing
March 2021

What Is the Consensus from Multiple Conclusions of Future Crop Yield Changes Affected by Climate Change in China?

Int J Environ Res Public Health 2020 12 10;17(24). Epub 2020 Dec 10.

Academy of Plateau Science and Sustainability, Xining 810008, China.

Many studies have shown that climate change has a significant impact on crop yield in China, while results have varied due to uncertain factors. This study has drawn a highly consistent consensus from the scientific evidence based on numerous existing studies. By a highly rational systematic review methodology, we obtained 737 result samples with the theme of climate change affecting China's crop yields. Then, we used likelihood scale and trend analysis methods to quantify the consensus level and uncertainty interval of these samples. The results showed that: (i) The crop yield decrease in the second half of the 21st century will be greater than 5% of that in the first half. (ii) The crop most affected by climate change will be maize, with the decreased value exceeding -25% at the end of this century, followed by rice and wheat exceeding -10% and -5%. (iii) The positive impact of CO on crop yield will change by nearly 10%. Our conclusions clarify the consensus of the impact of future climate change on China's crop yield, and this study helps exclude the differences and examine the policies and actions that China has taken and should take in response to climate change.
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http://dx.doi.org/10.3390/ijerph17249241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763021PMC
December 2020

Integrative analysis reveals novel driver genes and molecular subclasses of hepatocellular carcinoma.

Aging (Albany NY) 2020 11 20;12(23):23849-23871. Epub 2020 Nov 20.

Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Hepatocellular carcinoma (HCC) is a heterogeneous disease with various genetic and epigenetic abnormalities. Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from 377 HCC patients to identify driver genes that regulate gene expression in HCC. This integrative approach has significant advantages over single-platform analyses for identifying cancer drivers. Using this approach, HCC tissues were divided into four subgroups, based on expression of the transcription factor E2F and the mutation status of TP53. HCC tissues with E2F overexpression and TP53 mutation had the highest cell cycle activity, indicating a synergistic effect of E2F and TP53. We found that overexpression of the identified driver genes, stratifin (SFN) and SPP1, correlates with tumor grade and poor survival in HCC and promotes HCC cell proliferation. These findings indicate SFN and SPP1 function as oncogenes in HCC and highlight the important role of enhancers in the regulation of gene expression in HCC.
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http://dx.doi.org/10.18632/aging.104047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762459PMC
November 2020

Changes in hydrological behaviours triggered by earthquake disturbance in a mountainous watershed.

Sci Total Environ 2021 Mar 28;760:143349. Epub 2020 Oct 28.

Research Institute for Geo-hydrological Protection, Italian National Research Council, Padova 351127, Italy.

Landslides induced by strong earthquakes often destroy large amounts of landscape vegetation which can trigger significant changes in runoff potential and flood flow. Little is known about hydrological behaviours imposed by co-seismic landslides and their post-earthquake evolution. Therefore, we collected time-series datasets (2007-2018) of underlying surface conditions (USC) changes including landslide expansion and recovery in a watershed affected by the Wenchuan earthquake to further quantify how the large physical disturbance affected the flood hydrological behaviours. The hydrological model HEC-HMS was calibrated and validated to predict the historical hydrological behaviours based on 5 min time-series data in rainfalls and streamflow (2018-2019), showing a good model performance with a mean Nash-Sutcliffe efficiency of 0.76. It was found that, shortly after the earthquake, the sharp expansion with 11% of landslide areas elevated the magnitudes of runoff potential, peak discharge, and runoff volume by >10%, and the peak to time for the high-magnitude flood was advanced by 25 min compared to the pre-earthquake levels. The tipping point along the hydrological disturbance-recovery trajectory was detected within 2011 with higher flood peaks and volumes, and the periods of 2011-2013 (i.e. 3-5 years post-earthquake) were deemed to be a rapid recovery period, revealing an unstable hydrological function. These findings are significant for clearly understanding the magnitude and timing, as well as greater risks of post-earthquake catastrophic flooding in earthquake-stricken regions. Additionally, the post-earthquake accompanied rainstorm-induced geohazards, which limited the recovery of landscape vegetation, triggering an undulant but clear recovery process (1-7 years post-earthquake) of hydrological behaviours. These findings promoted our understanding of the spatiotemporal evolution of hydrological behaviours triggered by the earthquake, and further contribute to the development of adaptation and mitigation strategies for the unpredictable flash floods triggered by future abrupt natural hazards in earthquake-affected regions.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143349DOI Listing
March 2021

Dual-recognition-based determination of ctDNA the clamping function of peptide nucleic acid and terminal protection of small-molecule-linked DNA.

Analyst 2020 Nov;145(23):7603-7608

Institute for Interdisciplinary Research, Jianghan University, Wuhan 430056, P. R. China.

A new dual-recognition fluorescent biosensor for circulating tumor DNA (ctDNA) detection has been developed, which combines the clamping function of peptide nucleic acid (PNA) and terminal protection of small-molecule-linked DNA (TPSMLD). Taking the tumor-specific E542K mutation and methylation of the PIK3CA gene as the target ctDNA, a low detection limit of 0.3161 pM ctDNA is achieved with good selectivity. This study not only offers a sensitive, selective and accurate ctDNA detection method, but can also be used to detect the target in complex biological samples.
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http://dx.doi.org/10.1039/d0an01305fDOI Listing
November 2020

The central trend in crop yields under climate change in China: A systematic review.

Sci Total Environ 2020 Feb 23;704:135355. Epub 2019 Nov 23.

Key Laboratory of Environmental Change and Natural Disaster, Ministry of Education, Beijing Normal University, Beijing 100875, China; Faculty of Geographical Science, Academy of Disaster Reduction and Emergency Management, Beijing Normal University, Beijing 100875, China.

Evidence from numerous studies has confirmed the impact of climate change on crop yields in China since the IPCC AR4. However, the results from different studies can differ widely due to differences in crops, regions, scenarios, and analytical approaches. We assessed the projected impacts of climate change on the yield of major crops (wheat, rice, and maize) in China using a systematic review at the national and subregional levels based on a data set of 667 published simulations. The results show that (1) the impact of climate change on crop yields was mainly reflected in temperature increases, with an average yield loss of 2.58% per °C at the national level. Subregional yield changes ranged from -12.70% to -2.57% per °C, with crop yields being more vulnerable in Northeast China and Northwest China than in other subregions. (2) The yields of crop samples that included CO effects were 9.23% higher than the yields of those without CO effects. (3) Evidence of the impacts of precipitation on crop yield was robust for Northeast China, Northwest China and North China and was absent or contradictory for the other subregions. (4) Of the three different crops, the response of wheat yields to warming was the most evident, especially in Northwest China, followed by that of maize yields in Northeast China. The negative effects of temperature increases on rice yields were significant at the national level but not at the subregional level. This study synthesized the results from all available studies in a systematic and unbiased manner and provided a robust assessment of the likely impacts of climate change on crop yields.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135355DOI Listing
February 2020

A Pharmacogenomic Landscape in Human Liver Cancers.

Cancer Cell 2019 08 1;36(2):179-193.e11. Epub 2019 Aug 1.

Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 211166, China. Electronic address:

Liver cancers are highly heterogeneous with poor prognosis and drug response. A better understanding between genetic alterations and drug responses would facilitate precision treatment for liver cancers. To characterize the landscape of pharmacogenomic interactions in liver cancers, we developed a protocol to establish human liver cancer cell models at a success rate of around 50% and generated the Liver Cancer Model Repository (LIMORE) with 81 cell models. LIMORE represented genomic and transcriptomic heterogeneity of primary cancers. Interrogation of the pharmacogenomic landscape of LIMORE discovered unexplored gene-drug associations, including synthetic lethalities to prevalent alterations in liver cancers. Moreover, predictive biomarker candidates were suggested for the selection of sorafenib-responding patients. LIMORE provides a rich resource facilitating drug discovery in liver cancers.
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http://dx.doi.org/10.1016/j.ccell.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505724PMC
August 2019

Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes.

Nat Cell Biol 2019 08 22;21(8):1015-1026. Epub 2019 Jul 22.

State Key Laboratory of Cell Biology, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Human liver cancers, including hepatocellular carcinomas and intra-hepatic cholangiocarcinomas, are often diagnosed late with poor prognosis. A better understanding of cancer initiation could provide potential preventive therapies and increase survival. Models for studying human liver cancer initiation are largely missing. Here, using directly reprogrammed human hepatocytes (hiHeps) and inactivation of p53 and RB, we established organoids possessing liver architecture and function. HiHep organoids were genetically engineered to model the initial alterations in human liver cancers. Bona fide hepatocellular carcinomas were developed by overexpressing c-Myc. Excessive mitochondrion-endoplasmic reticulum coupling induced by c-Myc facilitated hepatocellular carcinoma initiation and seemed to be a target of preventive treatment. Furthermore, through the analysis of human intra-hepatic cholangiocarcinoma-enriched mutations, we demonstrate that the RAS-induced lineage conversion from hepatocytes to intra-hepatic cholangiocarcinoma cells can be prevented by the combined inhibition of Notch and JAK-STAT. Together, hiHep organoids represent a system that can be genetically manipulated to model cancer initiation and identify potential preventive therapies.
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http://dx.doi.org/10.1038/s41556-019-0359-5DOI Listing
August 2019

How to Integrate Labor Disruption into an Economic Impact Evaluation Model for Postdisaster Recovery Periods.

Risk Anal 2019 11 28;39(11):2443-2456. Epub 2019 Jun 28.

The Key Laboratory of Environmental Change and Natural Disaster, MOE, Beijing Normal University, Beijing, China.

Evaluating the economic impacts caused by capital destruction is an effective method for disaster management and prevention, but the magnitude of the economic impact of labor disruption on an economic system remains unclear. This article emphasizes the importance of considering labor disruption when evaluating the economic impact of natural disasters. Based on the principle of disasters and resilience theory, our model integrates nonlinear recovery of labor losses and the demand of labor from outside the disaster area into the dynamic evaluation of the economic impact in the postdisaster recovery period. We exemplify this through a case study: the flood disaster that occurred in Wuhan city, China, on July 6, 2016 (the "7.6 Wuhan flood disaster"). The results indicate that (i) the indirect economic impacts of the "7.6 Wuhan flood disaster" will underestimate 15.12% if we do not consider labor disruption; (ii) the economic impact in secondary industry caused by insufficient labor forces accounts for 42.27% of its total impact, while that in the tertiary industry is 36.29%, which can cause enormous losses if both industries suffer shocks; and (iii) the agricultural sector of Wuhan city experiences an increase in output demand of 0.07% that is created by the introduction of 50,000 short-term laborers from outside the disaster area to meet the postdisaster reconstruction need. These results provide evidence for the important role of labor disruption and prove that it is a nonnegligible component of postdisaster economic recovery and postdisaster reduction.
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http://dx.doi.org/10.1111/risa.13365DOI Listing
November 2019

Global Heat Wave Hazard Considering Humidity Effects during the 21st Century.

Int J Environ Res Public Health 2019 04 29;16(9). Epub 2019 Apr 29.

Key Laboratory of Environmental Change and Natural Disaster of Ministry of Education, Faculty of Geographical Science, Beijing Normal University, Beijing 100875, China.

Humidity is a significant factor contributing to heat stress, but without enough consideration in studies of quantifying heat hazard or heat risk assessment. Here, the simplified wet-bulb globe temperature (WBGT) considering joint effects of temperature and humidity was utilized as a heat index and the number of annual total heat wave days (HWDs) was employed to quantify heat hazard. In order to evaluate the humidity effects on heat waves, we quantified the difference in the number of HWDs over global land based on air temperature and WBGT. Spatial and temporal changes in surface air temperature, relative humidity, WBGT, and the difference in HWDs were analyzed using multi-model simulations for the reference period (1986-2005) and different greenhouse gas emission scenarios. Our analysis suggests that annual mean WBGT has been increasing since 1986, which is consistent with the rising trend in surface air temperature despite a slight decrease in relative humidity. Additionally, changes in annual mean WBGT are smaller and more spatially uniform than those in annual mean air temperature as a cancelation effect between temperature and water vapor. Results show that there is an underestimation of around 40-140 days in the number of HWDs per year in most regions within 15° latitude of the equator (the humid and warm tropics) during 2076-2095 without considering humidity effects. However, the estimation of HWDs has limited distinction between using WBGT and temperature alone in arid or cold regions.
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http://dx.doi.org/10.3390/ijerph16091513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539408PMC
April 2019

In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity.

Cell Stem Cell 2018 12 8;23(6):806-819.e4. Epub 2018 Nov 8.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China; Stem Cell and Regenerative Medicine Innovation Academy, Beijing 100101, China. Electronic address:

Transplantation of human hepatocytes (HHs) holds significant potential for treating liver diseases. However, the supply of transplantable HHs is severely constrained by limited donor availability and compromised capacity for in vitro expansion. In response to chronic injury, some HHs are reprogrammed into proliferative cells that express both hepatocyte and progenitor markers, suggesting exploitable strategies for expanding HHs in vitro. Here, we report defined medium conditions that allow 10,000-fold expansion of HHs. These proliferating HHs are bi-phenotypic, partially retaining hepatic features while gaining expression of progenitor-associated genes. Importantly, these cells engraft into injured mouse liver at a level comparable to primary HHs, and they undergo maturation following transplantation in vivo or differentiation in vitro. Thus, this study provides a protocol that enables large-scale expansion of transplantable HHs, which could be further developed for modeling and treating human liver disease.
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http://dx.doi.org/10.1016/j.stem.2018.10.018DOI Listing
December 2018

TiO Nanorod Arrays with Mesoscopic Micro-Nano Interfaces for in Situ Regulation of Cell Morphology and Nucleus Deformation.

ACS Appl Mater Interfaces 2018 Jan 21;10(1):66-74. Epub 2017 Dec 21.

Institute for Interdisciplinary Research & Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, Jianghan University , Wuhan 430056, China.

Cell morphology and nucleus deformation are important when circulating tumor cells break away from the primary tumor and migrate to a distant organ. Cells are sensitive to the microenvironment and respond to the cell-material interfaces. We fabricated TiO nanorod arrays with mesoscopic micro-nano interfaces through a two-step hydrothermal reaction method to induce severe changes in cell morphology and nucleus deformation. The average size of the microscale voids was increased from 5.1 to 10.5 μm when the hydrothermal etching time was increased from 3 to 10 h, whereas the average distances between voids were decreased from 0.88 to 0.40 μm. The nucleus of the MCF-7 cells on the TiO nanorod substrate that was etched for 10 h exhibited a significant deformation, because of the large size of the voids and the small distance between voids. Nucleus defromation was reversible during the cells proliferate process when the cells were cultured on the mesoscopic micro-nano interface.This reversible process was regulated by combining of the uniform pressure applied by the actin cap and the localized pressure applied by the actin underneath the nucleus. Cell morphology and nucleus shape interacted with each other to adapt to the microenvironment. This mesoscopic micro-nano interface provided a new insight into the cell-biomaterial interface to investigate cell behaviors.
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http://dx.doi.org/10.1021/acsami.7b11257DOI Listing
January 2018

The dual effect of vegetation green-up date and strong wind on the return period of spring dust storms.

Sci Total Environ 2017 Aug 21;592:729-737. Epub 2017 Mar 21.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Faculty of Geographical Science, Beijing Normal University, Beijing 100875, China; Academy of Disaster Reduction and Emergency Management, Ministry of Civil Affairs & Ministry of Education, Faculty of Geographical Science, Beijing 100875, China.

Vegetation phenology changes have been widely applied in the disaster risk assessments of the spring dust storms, and vegetation green-up date shifts have a strong influence on dust storms. However, the effect of earlier vegetation green-up dates due to climate warming on the evaluation of dust storms return periods remains an important, but poorly understood issue. In this study, we evaluate the spring dust storm return period (February to June) in Inner Mongolia, Northern China, using 165 observations of severe spring dust storm events from 16 weather stations, and regional vegetation green-up dates as an integrated factor from NDVI (Normalized Difference Vegetation Index), covering a period from 1982 to 2007, by building the bivariate Copula model. We found that the joint return period showed better fitting results than without considering the integrated factor when the actual dust storm return period is longer than 2years. Also, for extremely severe dust storm events, the gap between simulation result and actual return period can be narrowed up to 0.4888years by using integrated factor. Furthermore, the risk map based on the return period results shows that the Mandula, Zhurihe, Sunitezuoqi, Narenbaolige stations are identified as high risk areas. In this study area, land surface is extensively covered by grasses and shrubs, vegetation green-up date can play a significant role in restraining spring dust storm outbreaks. Therefore, we suggest that Copula method can become a useful tool for joint return period evaluation and risk analysis of severe dust storms.
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http://dx.doi.org/10.1016/j.scitotenv.2017.02.028DOI Listing
August 2017

Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers.

Sci Rep 2016 06 7;6:27411. Epub 2016 Jun 7.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China.

Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine.
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http://dx.doi.org/10.1038/srep27411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895220PMC
June 2016

A 3D graphene oxide microchip and a Au-enwrapped silica nanocomposite-based supersandwich cytosensor toward capture and analysis of circulating tumor cells.

Nanoscale 2015 Oct;7(39):16354-60

Flexible Display Mater. & Tech. Co-Innovation Center of Hubei, Institute for Interdisciplinary Research, Jianghan University, Wuhan 430056, PR China.

Determination of the presence and number of circulating tumor cells (CTCs) in peripheral blood can provide clinically important data for prognosis and therapeutic response patterns. In this study, a versatile supersandwich cytosensor was successfully developed for the highly sensitive and selective analysis of CTCs using Au-enwrapped silica nanocomposites (Si/AuNPs) and three-dimensional (3D) microchips. First, 3D microchips were fabricated by a photolithography method. Then, the prepared substrate was applied to bind graphene oxide, streptavidin and biotinylated epithelial-cell adhesion-molecule antibody, resulting in high stability, bioactivity, and capability for CTCs capture. Furthermore, horseradish peroxidase and anti-CA153 were co-linked to the Si/AuNPs for signal amplification. The performance of the cytosensor was evaluated with MCF7 breast cancer cells. Under optimal conditions, the proposed supersandwich cytosensor showed high sensitivity with a wide range of 10(1) to 10(7) cells per mL and a detection limit of 10 cells per mL. More importantly, it could effectively distinguish CTCs from normal cells, which indicated the promising applications of our method for the clinical diagnosis and therapeutic monitoring of cancers.
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http://dx.doi.org/10.1039/c5nr04798fDOI Listing
October 2015