Publications by authors named "Yilong Li"

68 Publications

Integrating Genetic and Transcriptomic Data to Reveal Pathogenesis and Prognostic Markers of Pancreatic Adenocarcinoma.

Front Genet 2021 9;12:747270. Epub 2021 Sep 9.

Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies and mortality for PAAD have remained increasing under the conditions of substantial improvements in mortality for other major cancers. Although multiple of studies exists on PAAD, few studies have dissected the oncogenic mechanisms of PAAD based on genomic variation. In this study, we integrated somatic mutation data and gene expression profiles obtained by high-throughput sequencing to characterize the pathogenesis of PAAD. The mutation profile containing 182 samples with 25,470 somatic mutations was obtained from The Cancer Genome Atlas (TCGA). The mutation landscape was generated and somatic mutations in PAAD were found to have preference for mutation location. The combination of mutation matrix and gene expression profiles identified 31 driver genes that were closely associated with tumor cell invasion and apoptosis. Co-expression networks were constructed based on 461 genes significantly associated with driver genes and the hub gene FAM133A in the network was identified to be associated with tumor metastasis. Further, the cascade relationship of somatic mutation-Long non-coding RNA (lncRNA)-microRNA (miRNA) was constructed to reveal a new mechanism for the involvement of mutations in post-transcriptional regulation. We have also identified prognostic markers that are significantly associated with overall survival (OS) of PAAD patients and constructed a risk score model to identify patients' survival risk. In summary, our study revealed the pathogenic mechanisms and prognostic markers of PAAD providing theoretical support for the development of precision medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.747270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458879PMC
September 2021

Integrated Suzuki Cross-Coupling/Reduction Cascade Reaction of meta-/para-Chloroacetophenones and Arylboronic Acids under Batch and Continuous Flow Conditions.

Chem Asian J 2021 Aug 9;16(16):2338-2345. Epub 2021 Jul 9.

Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai, 200234, China.

Overcoming the incompatibility of a pair of conflicting catalysts via a flow methodology has great significance in the practical applications for multistep organic transformations. In this study, a multiple continuous-flow system is developed, which can boost the reactivity and selectivity in a sequential enantioselective cascade reaction. During this process, a periodic mesoporous organosilica-supported Pd/carbene species as a Suzuki cross-coupling catalyst is packed in the first column reactor, whereas another periodic mesoporous organosilica-supported Ru/diamine species as an asymmetric transfer hydrogenation catalyst is packed in the second column reactor. As we envisioned, the initially Pd-catalyzed cross-coupling reaction of meta-/para-chloroacetophenones and aryl boronic acids followed by the subsequentially Ru-catalyzed reduction provides chiral biarylols with enhanced yields and enantioselectivities. Furthermore, the advantages of the easy handling and the simple procedure make this system an attractive application in a scale-up preparation of optically pure organic molecules under environmentally-friendly conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/asia.202100479DOI Listing
August 2021

Comparability of thyroid-stimulating hormone immunoassays using fresh frozen human sera and external quality assessment data.

PLoS One 2021 15;16(6):e0253324. Epub 2021 Jun 15.

Department of Clinical Laboratory, Beijing Chaoyang Hospital, Beijing Center for Clinical Laboratories, The Third Clinical Medical College of Capital Medical University, Beijing, P.R. China.

Background: This study aimed to assess the comparability among assays using freshly frozen human sera and external quality assessment (EQA) data in China.

Methods: Twenty-nine serum samples and two commercial EQA materials, obtained from the National Center for Clinical Laboratories (NCCL), were analyzed in triplicate using eight routine TSH assays. The commutability of commercial EQA materials (NCCL materials) was evaluated in accordance with the CLSI EP30-A and IFCC bias analysis. Median values obtained for the NCCL EQA materials were used to determine the systematic and commutability-related biases among immunoassays through back-calculation. The comparability of TSH measurements from a panel of clinical samples and NCCL EQA data was determined on the basis of Passing-Bablok regression. Furthermore, human serum pools were used to perform commutable EQA.

Results: NCCL EQA materials displayed commutability among three or five of seven assay combinations according CLSI or IFCC approach, respectively. The mean of systematic bias ranged from -13.78% to 9.85% for the eight routine TSH assays. After correcting for systematic bias, averaged commutability-related biases ranged between -42.26% and 12.19%. After correction for systematic and commutability -related biases, the slopes indicating interassay relatedness ranged from 0.801 to 1.299 using individual human sera, from 0.735 to 1.254 using NCCL EQA data, and from 0.729 to 1.115 using pooled human serum EQA(the commutable EQA).

Conclusions: The harmonization of TSH measurement is challenging; hence, systematic and commutability-related biases should be determined and corrected for accurate comparisons among assays when using human individual serum and the commercial EQA materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253324PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205121PMC
June 2021

Variations of root-associated bacterial cooccurrence relationships in paddy soils under chlorantraniliprole (CAP) stress.

Sci Total Environ 2021 Jul 5;779:146247. Epub 2021 Mar 5.

MOE Laboratory for Earth Surface Processes, College of Urban & Environmental Sciences, Peking University, Beijing 100871, China. Electronic address:

Root-associated microbiomes are beneficial for plant development and health. However, the assembly of root-associated bacterial communities and their feedback under chlorantraniliprole (CAP) stress are unclear. This study investigated the response of root-associated bacterial microbiota to CAP dosage during the two developmental phases of rice. The results showed that CAP application had little effect on the bacterial diversity of bulk and rhizosphere soils, whereas that of the endosphere samples demonstrated a large variability. Moreover, the CAP stress exhibited less influence than the plant compartment and developmental stage contributing to microbiome variation. The core bacterial co-occurrence relationships also changed with the CAP application, especially, in the endosphere of the roots. These results further elucidate the impacts of CAP application on root-associated bacterial communities in intensive agricultural ecosystems and provide new insights for CAP ecological risk assessments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.146247DOI Listing
July 2021

Invadopodia: A potential target for pancreatic cancer therapy.

Crit Rev Oncol Hematol 2021 Mar 20;159:103236. Epub 2021 Jan 20.

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address:

Dissemination of cancer cells is an intricate multistep process that represents the most deadly aspect of cancer. Cancer cells form F-actin-rich protrusions known as invadopodia to invade surrounding tissues, blood vessels and lymphatics. A number of studies have demonstrated the significant roles of invadopodia in cancer. Therefore, the specific cells and molecules involved in invadopodia activity can provide as therapeutic targets. In this review, we included a thorough overview of studies in invadopodia and discussed their functions in cancer metastasis. We then presented the specific cells and molecules involved in invadopodia activity in pancreatic cancer and analyzed their suitability to be effective therapeutic targets. Currently, drugs targeting invadopodia and relevant clinical trials are negligible. Here, we highlighted the significance of potential drugs and discussed future obstacles in implementing clinical trials. This review presents a new perspective on invadopodia-induced pancreatic cancer metastasis and may prosper the development of targeted therapeutics against pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.critrevonc.2021.103236DOI Listing
March 2021

Deep Learning Methods for Lung Cancer Segmentation in Whole-Slide Histopathology Images-The [email protected] Challenge 2019.

IEEE J Biomed Health Inform 2021 02 5;25(2):429-440. Epub 2021 Feb 5.

Accurate segmentation of lung cancer in pathology slides is a critical step in improving patient care. We proposed the [email protected] (Automatic Cancer Detection and Classification in Whole-slide Lung Histopathology) challenge for evaluating different computer-aided diagnosis (CADs) methods on the automatic diagnosis of lung cancer. The [email protected] 2019 focused on segmentation (pixel-wise detection) of cancer tissue in whole slide imaging (WSI), using an annotated dataset of 150 training images and 50 test images from 200 patients. This paper reviews this challenge and summarizes the top 10 submitted methods for lung cancer segmentation. All methods were evaluated using metrics using the precision, accuracy, sensitivity, specificity, and DICE coefficient (DC). The DC ranged from 0.7354 ±0.1149 to 0.8372 ±0.0858. The DC of the best method was close to the inter-observer agreement (0.8398 ±0.0890). All methods were based on deep learning and categorized into two groups: multi-model method and single model method. In general, multi-model methods were significantly better (p 0.01) than single model methods, with mean DC of 0.7966 and 0.7544, respectively. Deep learning based methods could potentially help pathologists find suspicious regions for further analysis of lung cancer in WSI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/JBHI.2020.3039741DOI Listing
February 2021

Suspended particulate matter (SPM)-bound polycyclic aromatic hydrocarbons (PAHs) in lakes and reservoirs across a large geographical scale.

Sci Total Environ 2021 Jan 9;752:142863. Epub 2020 Oct 9.

MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. Electronic address:

Suspended particulate matter (SPM) plays a key role in the environmental fate of polycyclic aromatic hydrocarbons (PAHs) in lake environment. However, less is known about the occurrence, compositions and sources of SPM-bound PAHs as well as the correlations between SPM-bound PAHs and different suspended particulate organic matter (SPOM) on large geographical scale. In this study, we focused on the SPM-bound PAHs in 46 lakes and reservoirs across China to fill this gap. Our results showed that the concentrations of Σ PAHs ranged from 334 to 38427 ng·g with a geometric mean (GM) of 3915 ng·g. The occurrence of SPM-bound PAHs in this study was at a moderate level with large variations, which was associated with location and water depth according to linear discriminant analysis (LDA). Phenanthrene (Phe) was investigated as the overwhelming species with a GM of 1777 ng·g, and was followed by fluoranthene (Fla), fluorene (Flu) and pyrene (Pyr) with GMs of 499 ng·g, 276 ng·g and 184 ng·g, respectively. The profiles of SPM-bound PAHs were primarily dominated by low-ring PAHs ranging from 56.0% to 97.1% (85.5% ± 7.7%, mean ± standard deviation). Four diagnostic ratios were applied for preliminary diagnoses, but inconsistent results were obtained in most samples. Ridge regression was applied to ascertain the potential influences of different SPOM on SPM-bound PAHs. The results revealed that the presence of SPM-bound PAHs was not only influenced by anthropogenic emissions, but also associated with biogenic organic matter. Our results provided a higher explanation than those just preliminarily estimated by total organic carbon (TOC). Nevertheless, there still exist over 50% of variance unexplained for most PAHs, and further study could focus more on the information of SPOM structures and potential local effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.142863DOI Listing
January 2021

Geographical location and water depth are important driving factors for the differences of suspended particulate organic matter (SPOM) in lake environment across nationwide scale: Evidences from n-alkane fingerprints.

Sci Total Environ 2021 Jan 14;752:142948. Epub 2020 Oct 14.

MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China. Electronic address:

Suspended particulate organic matter (SPOM) plays a connective role in global biogeochemical carbon cycles and energy flows in aquatic ecosystems. However, little is known about the occurrence and source of SPOM in lake environment and their driving factors across nationwide scale. Here, we utilize the molecular markers of n-alkanes and their fingerprints in 46 typical lakes and reservoirs with different water depths across China from both sides of the Hu Line to study this issue. Σn-alkanes, Σ biogenic n-alkanes and Σ anthropogenic n-alkanes ranged from 104.8 to 10332 ng·L, from 88.5 to 4843 ng·L, and from 16.2 to 5488 ng·L, respectively. Their occurrences were only associated with water depth. Then, we compared the differences of carbon-chain distribution of both biogenic and anthropogenic n-alkanes and related proxies in different lake groups. The profiles of different biogenic and anthropogenic n-alkanes posed large differences in different lake groups. Finally, linear discriminant analysis (LDA) was applied to test the possible effects of geographical location and water depth on the holistic differences of SPOM in different lakes and reservoirs across China. The results illustrated that both geographical location and water depth were important driving factors for the holistic differences of SPOM in different lakes and reservoirs across China. Intensive anthropogenic activities narrowed the differences between shallow and deep lakes in eastern China. In conclusion, this study provided new insights into the driving factor analysis of SPOM in lakes and reservoirs on large scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.142948DOI Listing
January 2021

Tuning the Structure and Performance of Bulk and Porous Vapor Sensors Based on Co-continuous Carbon Nanotube-Filled Blends of Poly(vinylidene fluoride) and Polycarbonates by Varying Melt Viscosity.

ACS Appl Mater Interfaces 2020 Oct 28;12(40):45404-45419. Epub 2020 Sep 28.

Leibniz Institute of Polymer Research Dresden, Hohe Straße 6, 01069 Dresden, Germany.

This work describes a new concept of porous vapor sensor materials based on co-continuous polycarbonate/poly(vinylidene fluoride)/multiwalled carbon nanotube (PC/PVDF/MWCNT) blend composites. The blend composites were fabricated by melt mixing in a one-step mixing process, and the MWCNT containing component (here PC) was extracted, leaving a MWCNT network on the continuous surface of the remaining component (here PVDF). First, by selecting three PCs with different molecular weights, the blend viscosity ratio and blend fineness and interfacial area were varied. At the chosen blend composition of 40/60 wt %, the desired co-continuous structure was achieved with MWCNTs selectively localized in PC. The conductive polymer composites (CPCs) with low-viscosity PC had the highest conductivity due to a combination of the best MWCNT dispersion and the coarsest blend morphology. The vapor sensing of CPC sensor materials with 1 wt % MWCNT was tested using saturated vapors of dichloromethane, acetone, tetrahydrofuran, and ethyl acetate, showing good interaction with PC. The compact compression molded CPC materials with low-viscosity PC showed the lowest relative resistance changes () during the cyclic sensing tests, but a better recovery compared to corresponding CPCs with medium and high viscosity PC. The porous CPC sensors showed remarkable vapor sensing performance compared to the corresponding compact sensors with better sensing stability, reproducibility, and reversibility. Scanning electron microscopy (SEM) confirmed that a fraction of the nanotubes remained on the surface of the continuous, nonsoluble PVDF after PC extraction. The porous sensor material from which the low-viscosity PC was extracted showed the highest (e.g., around 1300% after 100 s immersion in acetone vapor) compared to all other organic vapors investigated. The difference in vapor measurement between compact and porous sensor materials was attributed to the different sensing mechanisms of polymer swelling for the compact and vapor absorption on the free CNT networks for the porous samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c15184DOI Listing
October 2020

Tuning the Piezoresistive Behavior of Poly(Vinylidene Fluoride)/Carbon Nanotube Composites Using Poly(Methyl Methacrylate).

ACS Appl Mater Interfaces 2020 Sep 8;12(38):43125-43137. Epub 2020 Sep 8.

Leibniz Institute of Polymer Research Dresden (IPF), Hohe Str. 6, 01069 Dresden Germany.

In conductive polymer composites (CPCs), which can be used as both strain sensors and materials with self-diagnosis capabilities for structural health monitoring, the piezoresistive sensitivity can be tuned by changing the electrical filler network structure, mainly influenced by the conductive filler content. Typically, the electrical resistance increases exponentially with strain, and the piezoresistive sensitivity and linearity cannot be improved simultaneously. In this work, we report a facile method to tune the piezoresistive behavior of melt-mixed poly(vinylidene fluoride) (PVDF)/carbon nanotube (CNT, 0.75-2.0 wt %) composites using blending with poly(methyl methacrylate) (PMMA, 5-30 wt %). PVDF and PMMA are completely miscible in the melt state regardless of the proportion. For PVDF-rich blends, the crystallization of PVDF induces separation of the PVDF crystal region from the miscible PVDF/PMMA amorphous blend part during the cooling process. Addition of PMMA tuned the piezoresistive strain behavior and improved the electrical conductivity and toughness at the same time. The PVDF/PMMA/CNT composites show higher sensitivity at low strains than their PVDF/CNT counterparts with comparable initial resistivity. For example, Δ/ at 5% strain is 18.6% for the PVDF(80)/PMMA(20) blend containing 0.75 wt % CNT versus 11.0% for PVDF containing 1 wt % CNT, both having a volume resistivity of around 10 Ω·cm. The PVDF/PMMA/CNT blend composites also show a less steep exponential increase in the sensing response at higher strains, indicating better linearity. These differences are due to the altered microstructure of the composites and the more homogeneous distribution of CNTs between the smaller and less numerous PVDF crystallites when PMMA is added. The concept of modifying the composite microstructure by adding another commercially available miscible polymer offers a simple and effective way to tune the piezoresistive behavior and improve mechanical properties of CPC sensor materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c11610DOI Listing
September 2020

Small Molecule Inhibitor C188-9 Synergistically Enhances the Demethylated Activity of Low-Dose 5-Aza-2'-Deoxycytidine Against Pancreatic Cancer.

Front Oncol 2020 8;10:612. Epub 2020 May 8.

Department of Pancreatic and Biliary Surgery, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.

Aberrant DNA methylation, especially hypermethylation of tumor suppressor genes, has been associated with many cancers' progression. 5-Aza-2'-deoxycytidine (DAC) can reverse hypermethylation-induced gene silencing via regulating DNA methyltransferases (DNMTs) activity, In addition, low-dose of DAC was proved to exert durable antitumor effects against solid tumor cells. Nevertheless, no clinical effect of DAC has been made when fighting against pancreatic cancer. Hence, it is necessary to raise a novel therapeutic strategy that further enhance the efficacy of DAC but not increase side effect, which impede the utilization of DAC. In the present study, we have discovered that C188-9, a novel signal transduction activator of transcription (STAT) inhibitor, could improve the antitumor effects of low-dose DAC and . Further study demonstrated that such improvement was attributed to re-expression of Ras association domain family member 1A (RASSF1A), a well-known tumor suppressor gene. Bisulfite sequencing PCR (BSP) assay showed that C188-9 combined with DAC treatment could significantly reverse the hypermethylation status of RASSF1A promoter, which indicated that C188-9 could enhance the demethylation efficacy of DAC. Our data demonstrated that DNA methyltransferase 1 (DNMT1) was the underlying mechanism that C188-9 regulates the demethylation efficacy of DAC. Overall, these findings provide a novel therapeutic strategy combining low-dose DAC and C188-9 to improve therapeutic efficacy by inhibiting DNMT1-inducing promoter methylation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225308PMC
May 2020

FNDC3B, Targeted by miR-125a-5p and miR-217, Promotes the Proliferation and Invasion of Colorectal Cancer Cells via PI3K/mTOR Signaling.

Onco Targets Ther 2020 30;13:3501-3510. Epub 2020 Apr 30.

First Department of General Surgery, Ninth Hospital of Xi'an, Xi'an 710054, Shaanxi, People's Republic of China.

Background: Fibronectin type III domain containing 3B (FNDC3B) acts as an oncogene in various cancers, and abnormal expression of FNDC3B has been found in colorectal cancer (CRC). Our study aimed to illustrate the role of FNDC3B in CRC development.

Methods: Through RT-qPCR and western blotting assays, the mRNA and protein expressions of target genes were measured. CCK-8 and MTT methods were used to detect cell proliferation. Invasion ability was determined using Transwell assay. TargetScan platform and luciferase reporter gene assay were performed to predict and validate the bindings between FNDC3B and miR-125a-5p or miR-217. Besides, the expression correlation was measured by Pearson's Correlation analysis.

Results: We found that FNDC3B was significantly upregulated in CRC tissues and tumor cell lines, and high expression of FNDC3B predicted a poor survival outcome. The bindings between FNDC3B and miR-125a-5p and miR-217 were respectively at the motifs of CUCAGGG and AUGCAGU. MiR-125a-5p and miR-217 were downregulated in CRC tissues, and both were negatively correlated with FNDC3B expression. Subsequently, the downregulated miR-125a-5p and miR-217 were confirmed as contributors FNDC3B upregulation in CRC. A loss-of-function assay demonstrated that FNDC3B knockdown inhibited the proliferation of CRC cells, while FNDC3B overexpression promoted the proliferation and invasion of tumor cells. Besides, we validated that PI3K/mTOR signaling was involved in the regulation of FNDC3B on the proliferation and invasion of CRC cells.

Conclusion: Generally, our findings demonstrated that FNDC3B facilitated cell proliferation and invasion via PI3K/mTOR signaling, and further promoted CRC progression. The novel miR-125a-5p/FNDC3B and miR-217/FNDC3B axes might be new targets for CRC prognosis and therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S226520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201223PMC
April 2020

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

Nature 2020 02 5;578(7793):102-111. Epub 2020 Feb 5.

Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.

The discovery of drivers of cancer has traditionally focused on protein-coding genes. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-1965-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054214PMC
February 2020

Patterns of somatic structural variation in human cancer genomes.

Nature 2020 02 5;578(7793):112-121. Epub 2020 Feb 5.

Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2-7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and-in liver cancer-frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-019-1913-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025897PMC
February 2020

Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer.

Nat Genet 2020 03 5;52(3):294-305. Epub 2020 Feb 5.

Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0564-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058537PMC
March 2020

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition.

Nat Genet 2020 03 5;52(3):306-319. Epub 2020 Feb 5.

Cancer Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Cambridge, UK.

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage-fusion-bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0562-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058536PMC
March 2020

Cell-in-Cell Phenomenon and Its Relationship With Tumor Microenvironment and Tumor Progression: A Review.

Front Cell Dev Biol 2019 3;7:311. Epub 2019 Dec 3.

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

The term cell-in-cell, morphologically, refers to the presence of one cell within another. This phenomenon can occur in tumors but also among non-tumor cells. The cell-in-cell phenomenon was first observed 100 years ago, and it has since been found in a variety of tumor types. Recently, increasing attention has been paid to this phenomenon and the underlying mechanism has gradually been elucidated. There are three main related process: cannibalism, emperipolesis, and entosis. These processes are affected by many factors, including the tumor microenvironment, mitosis, and genetic factors. There is considerable evidence to suggest that the cell-in-cell phenomenon is associated with the prognosis of cancers, and it promotes tumor progression in most situations. Notably, in pancreatic cancer, the cell-in-cell phenomenon is associated with reduced metastasis, which is the opposite of what happens in other tumor types. Thus, it can also inhibit tumor progression. Studies show that cell-in-cell structure formation is affected by the tumor microenvironment, and that it may lead to changes in cellular characteristics. In this review, we summarize the different cell-in-cell processes and discuss their role in tumor progression and how they are regulated by different mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2019.00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901391PMC
December 2019

High-Performance Wearable Strain Sensor Based on Graphene/Cotton Fabric with High Durability and Low Detection Limit.

ACS Appl Mater Interfaces 2020 Jan 24;12(1):1474-1485. Epub 2019 Dec 24.

Key Laboratory of Materials Processing and Mold (Zhengzhou University), Ministry of Education; School of Materials Science and Engineering; National Engineering Research Center for Advanced Polymer Processing Technology; Henan Key Laboratory of Advanced Nylon Materials and Application (Zhengzhou University) , Zhengzhou University , Zhengzhou , Henan 450001 , P. R. China.

Electronic textiles featuring a controllable strain sensing capability and comfortable wearability have attracted huge interests with the rapid development of wearable strain sensor systems. It is still a great challenge to simultaneously achieve a strain sensor with low cost, biocompatibility, large-area compatibility, and excellent sensing performances. Here, two kinds of cotton fabric-based strain sensors (CFSSs) with different conductive network structures are prepared, i.e., CFSS-90° and CFSS-45° (90° and 45° represent the angles between intertwined direction in cotton yarns and the stretching direction in tension). After multiple dipping processes, graphene nanosheets are deposited onto cotton fabrics, and then, the fabrics are encapsulated by polydimethylsiloxane (PDMS). Morphology analyses reveal that an interpenetrating structure is generated between cotton fabric and PDMS. The strength and elongation at break of CFSS-45° are about 4.5 MPa and 75% strain, which are higher than the counterparts of CFSS-90° (1.75 MPa and 30% strain, respectively). In a uniaxial stretching test, the two strain sensors exhibit excellent linear current-voltage behavior and fast response time (∼90 ms). During the cyclic stretching-releasing test, CFSSs present remarkable reproducibility, durability (10 000 cycles at 30% strain for CFSS-45°), and a sensing capability for detecting very low strain (∼0.4% strain).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b17173DOI Listing
January 2020

Nuomici-Inspired Universal Strategy for Boosting Piezoresistive Sensitivity and Elasticity of Polymer Nanocomposite-Based Strain Sensors.

ACS Appl Mater Interfaces 2019 Sep 11;11(38):35362-35370. Epub 2019 Sep 11.

Leibniz Institute of Polymer Research Dresden (IPF) , Hohe Str. 6 , 01069 Dresden , Germany.

Electrically conductive polymer composites (CPCs) are potential alternatives to conventional strain gauges due to their tunable sensitivity and strain ranges. Currently, to achieve very high piezoresistive sensitivity in thermoplastic-based CPCs with Gauge factors above 20 at low tensile strains (ε ≤ 5%) is a big challenge, but critical for structural health monitoring application in infrastructures. Here, inspired by the unique structures of a famous Chinese food, nuomici, we coat carbon nanotubes (CNTs) onto sticky acrylic rubber (AR) granules (ARG) to form nuomici-like [email protected] composite granules, which are employed as unique conductive filler to fabricate highly piezoresistive and flexible CPCs based on poly(vinylidene fluoride) (PVDF). This strategy of localizing CNTs densely on the surface of touching rubbery particles resulted in a much more sensitive elastic conductive network built by the [email protected] composite and showed a big gain effect. The resultant PVDF/[email protected] nanocomposites (AR content ranging from 0 to 10 wt %) show extremely high piezoresistive sensitivity at low strain, depending on the AR content. In particular, the value of PVDF with 1.5 wt % [email protected] wt % AR is 41 at 5% strain, which is more than one magnitude higher than that (ca. 3) of traditional PVDF/CNT nanocomposite sensors. Moreover, the elongation at break increases by about 60% with the addition of 1.5 wt [email protected] wt % AR. This study introduces a universal effective strategy for tailoring the mechanical properties and strain sensitivity of conductive network in CPCs, which is critical for the fabrication of high-performance strain sensors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b13510DOI Listing
September 2019

Overexpression of KLF5 is associated with poor survival and G1/S progression in pancreatic cancer.

Aging (Albany NY) 2019 07;11(14):5035-5057

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

Despite improvements in surgical procedures and comprehensive therapies, pancreatic cancer remains one of the most aggressive and deadly human malignancies. It is therefore necessary to determine which cellular mediators associate with prognosis in pancreatic cancer so as to improve the treatment of this disease. In the present study, mRNA array and immunohistochemical analyses showed that KLF5 is highly expressed in tissue samples from three short-surviving patients with pancreatic cancer. Survival analysis using data from The Cancer Genome Atlas showed that patients highly expressing KLF5 exhibited shorter overall and tumor-free survival times. Mechanistically, KLF5 promoted expression of E2F1, cyclin D1 and Rad51, while inhibiting expression of p16 in pancreatic cancer cells. Finally, flow cytometric analyses verified that KLF5 promotes G1/S progression of the cell cycle in pancreatic cancer cells. Collectively, these findings demonstrate that KLF5 is an important prognostic biomarker in pancreatic cancer patients, and they shed light on the molecular mechanism by which KLF5 stimulates cell cycle progression in pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.102096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682527PMC
July 2019

UBL4A inhibits autophagy-mediated proliferation and metastasis of pancreatic ductal adenocarcinoma via targeting LAMP1.

J Exp Clin Cancer Res 2019 Jul 9;38(1):297. Epub 2019 Jul 9.

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang Province, China.

Background: Ubiquitin-like protein 4A (UBL4A) plays a significant role in protein metabolism and the maintenance of cellular homeostasis. In cancer, UBL4A represses tumorigenesis and is involved in various signaling pathways. Pancreatic ductal adenocarcinoma (PDAC) is still a major cause of cancer-related death and the underlying molecular mechanism of UBL4A and PDAC remains unknown.

Methods: First, the prognostic role of UBL4A and its expression in human PDAC patients and in pancreatic cancer cell lines were detected by survival analysis and qRT-PCR, western blotting, and immunohistochemistry. Next, the effects of UBL4A on proliferation and metastasis in pancreatic cancer were evaluated by functional assays in vitro and in vivo. In addition, chloroquine was introduced to determine the role of autophagy in UBL4A-related tumor proliferation and metastasis. Ultimately, coimmunoprecipitation was used to confirm the interaction between UBL4A and lysosome associated membrane protein-1 (LAMP1), and western blotting was performed to explore the UBL4A mechanism.

Results: We found that UBL4A was decreased in PDAC and that high levels of UBL4A correlated with a favorable prognosis. We observed that UBL4A inhibited tumor proliferation and metastasis through suppression of autophagy, a critical intracellular catabolic process that reportedly protects cells from nutrient starvation and other stress conditions. UBL4A caused impaired autophagic degradation in vitro, a crucial process in autophagy, by disturbing the function of lysosomes and contributing to autophagosome accumulation. We found a positive correlation between UBL4A and LAMP1. Furthermore, UBL4A caused lysosomal dysfunction by directly interacting with LAMP1, and LAMP1 overexpression reversed the antitumor effects of UBL4A in pancreatic cancer. In addition, we demonstrated that UBL4A suppressed tumor growth and metastasis in a pancreatic orthotopic tumor model.

Conclusions: These findings suggest that UBL4A exerts an antitumor effect on autophagy-related proliferation and metastasis in PDAC by directly targeting LAMP1. Herein, we describe a novel mechanism of UBL4A that suppresses the progression of pancreatic cancer. UBL4A might be a promising target for the treatment and prognostication of PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-019-1278-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617940PMC
July 2019

Author Correction: Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

Nature 2019 02;566(7742):E1

Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.

In the Methods section of this Article, 'greater than' should have been 'less than' in the sentence 'Putative regions of clustered rearrangements were identified as having an average inter-rearrangement distance that was at least 10 times greater than the whole-genome average for the individual sample. '. The Article has not been corrected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-019-0883-2DOI Listing
February 2019

Fast and accurate genomic analyses using genome graphs.

Nat Genet 2019 02 14;51(2):354-362. Epub 2019 Jan 14.

Seven Bridges Genomics, Inc, Cambridge, MA, USA.

The human reference genome serves as the foundation for genomics by providing a scaffold for alignment of sequencing reads, but currently only reflects a single consensus haplotype, thus impairing analysis accuracy. Here we present a graph reference genome implementation that enables read alignment across 2,800 diploid genomes encompassing 12.6 million SNPs and 4.0 million insertions and deletions (indels). The pipeline processes one whole-genome sequencing sample in 6.5 h using a system with 36 CPU cores. We show that using a graph genome reference improves read mapping sensitivity and produces a 0.5% increase in variant calling recall, with unaffected specificity. Structural variations incorporated into a graph genome can be genotyped accurately under a unified framework. Finally, we show that iterative augmentation of graph genomes yields incremental gains in variant calling accuracy. Our implementation is an important advance toward fulfilling the promise of graph genomes to radically enhance the scalability and accuracy of genomic analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-018-0316-4DOI Listing
February 2019

Yolk-Shell-Mesostructured Silica-Supported Dual Molecular Catalyst for Enantioselective Tandem Reactions.

Chempluschem 2018 Sep;83(9):861-867

Key Laboratory of Resource Chemistry of Ministry of Education Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, No.100 Guilin Road, Shanghai, China.

Yolk-shell-mesostructured silica was used as a support in the development of an active-site-isolated bifunctional catalyst that can mediate a sequential organic transformation. Herein, through immobilization, the location of two catalytic species is controlled: a base functionality is anchored in the channels of the outer silica shell and a chiral ruthenium/diamine functionality is anchored on the inner silica yolk. The result is a yolk-shell-mesostructured silica-supported active-site-isolated dual molecule catalyst. Structural analysis through solid-state carbon C NMR spectroscopy reveals its well-defined single-site dual active centers. Electron microscopy investigations disclose its uniformly distributed mesoporous nanoparticles. As envisaged, this bifunctional catalyst enables a controllable aza-Michael addition/asymmetric transfer hydrogenation catalytic sequence, where the base-catalyzed aza-Michael addition of enones and amines to aryl-substituted -secondary amino ketones is followed by a Ru-catalyzed asymmetric transfer hydrogenation. Various aryl-substituted γ-secondary amino alcohols are obtained in high yields and enantioselectivities via this one-pot enantioselective organic transformation. Furthermore, the heterogeneous catalyst can be applied in a continuous-flow process, which was shown to be particularly attractive for the practical preparation of aryl-substituted γ-secondary amino alcohols in an environmentally friendly medium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cplu.201800377DOI Listing
September 2018

MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma.

Cell Death Dis 2018 07 24;9(8):807. Epub 2018 Jul 24.

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang Province, China.

Metastasis remains one of the most intractable challenges in pancreatic ductal adenocarcinoma (PDAC) biology, and epithelial-to-mesenchymal transition (EMT) is essential to the epithelium-originated solid tumor metastasis cascade. Emerging evidence demonstrates that aberrant miRNA expression is involved in pancreatic cancer progression. We found that miR-361-3p was associated with an advanced stage of PDAC and poor prognosis. Hence, the effect of miR-361-3p on metastasis of PDAC cells was evaluated using Transwell assay and wound healing assay in vitro as well as orthotopic and liver metastasis pancreatic cancer models in vivo. Overexpression of miR-361-3p promoted pancreatic cancer cell migration and invasion in vitro, and miR-361-3p-elevated PDAC cells were prone to generating metastatic nodules in vivo. However, miR-361-3p showed no significant effect on the proliferation of PDAC cells in vivo or in vitro. Further study demonstrated that miR-361-3p could enhance EMT and ERK pathway activation, and ERK inhibitor could attenuate miR-361-3p-induced EMT. Luciferase assays, qPCR, and western blot and Ago2 co-immunoprecipitation were performed to identify the direct target of miR-361-3p. Mechanistic investigations identified DUSP2 as a direct target of miR-361-3p, and DUSP2 was revealed to be involved in miR-361-3p-induced EMT by directly leading to the inactivation of the ERK pathway. Moreover, we found that miR-361-3p-induced EMT was dependent on Ago2, the core component of RNA-induced silencing complex, while enforced expression of Ago2 enhanced the miR-361-3p-induced effect by promoting interference efficacy and specificity rather than regulating miR-361-3p stability and biogenesis. Thus, this study revealed that miR-361-3p functions as an oncomiR for promoting metastasis and identified the miR-361-3p/DUSP2/ERK axis as a novel EMT axis dependent on Ago2 in PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-0839-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057920PMC
July 2018

Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups.

Leukemia 2018 12 22;32(12):2604-2616. Epub 2018 May 22.

Harvard Medical School, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Boston, MA, USA.

In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-018-0037-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092251PMC
December 2018

Author Correction: Optimised metrics for CRISPR-KO screens with second-generation gRNA libraries.

Sci Rep 2018 Apr 12;8(1):6136. Epub 2018 Apr 12.

Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-24092-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895590PMC
April 2018

SvABA: genome-wide detection of structural variants and indels by local assembly.

Genome Res 2018 04 13;28(4):581-591. Epub 2018 Mar 13.

The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.

Structural variants (SVs), including small insertion and deletion variants (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach to identifying SVs, but is difficult to apply at scale genome-wide for SV detection due to its computational complexity and the difficulty of extracting SVs from assembly contigs. We describe SvABA, an efficient and accurate method for detecting SVs from short-read sequencing data using genome-wide local assembly with low memory and computing requirements. We evaluated SvABA's performance on the NA12878 human genome and in simulated and real cancer genomes. SvABA demonstrates superior sensitivity and specificity across a large spectrum of SVs and substantially improves detection performance for variants in the 20-300 bp range, compared with existing methods. SvABA also identifies complex somatic rearrangements with chains of short (<1000 bp) templated-sequence insertions copied from distant genomic regions. We applied SvABA to 344 cancer genomes from 11 cancer types and found that short templated-sequence insertions occur in ∼4% of all somatic rearrangements. Finally, we demonstrate that SvABA can identify sites of viral integration and cancer driver alterations containing medium-sized (50-300 bp) SVs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.221028.117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880247PMC
April 2018

Silencing IGFBP-2 decreases pancreatic cancer metastasis and enhances chemotherapeutic sensitivity.

Oncotarget 2017 Sep 27;8(37):61674-61686. Epub 2017 Jun 27.

Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Pancreatic cancer has remained one of the most devastating and lethal malignancies characterized by local invasion, distant metastasis and a high degree of chemoresistance. Insulin-like growth factor binding protein 2 (IGFBP-2) is a member of the IGFBP family of proteins, and it is highly expressed in pancreatic cancer patients' serum and tumor tissues. IGFBP-2 also mediates tumor cell growth, invasion and resistance, while the mechanisms remain unclear. In this study, we sought to determine the impact of IGFBP-2 expression on pancreatic cancer tumorigenesis and metastasis and . Wound healing, migration and invasion assays revealed that knockdown of IGFBP-2 inhibits cancer cell migration and invasion. Downregulation of IGFBP-2 attenuates EMT via increasing the E-cadherin and reducing the vimentin and N-cadherin. PTCH-1 is found contribute to the function of IGFBP-2 in suppressing metastasis and EMT of pancreatic cancer. Silencing IGFBP-2 inhibited invasion and metastatic properties, partially through inhibiting PTCH1 in pancreatic cancer. Additionally, inhibition of IGFBP-2 enhanced the sensitivity of pancreatic cancer cells to gemcitabine, suppressed tumor growth and potentiated the anti-tumor effect of gemcitabine in the orthotopic tumor model. Our results provide novel insight of IGFBP-2 as a promising target to inhibit the metastasis and overcome the chemoresistance in pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.18669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617455PMC
September 2017
-->