Abstract:
:Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular matrix (ECM) generating collagen fragments that are released into circulation. We evaluated the association of specific collagen fragments measured in pre-treatment serum with outcome in patients with PDAC. Matrix metalloprotease (MMP)-degraded type I collagen (C1M), type III collagen (C3M), type IV collagen (C4M) and a pro-peptide of type III collagen (PRO-C3) were measured by ELISA in pre-treatment serum from a randomized phase 3 clinical trial of patients with stage III/IV PDAC treated with 5-fluorouracil based therapy (n = 176). The collagen fragments were evaluated for their correlation (r, Spearman) with serum CA19-9 and for their association with overall survival (OS) based on Cox-regression analyses. In this phase 3 PDAC trial, pre-treatment serum collagen fragment levels were above the reference range for 67%-98% of patients, with median values in PDAC approximately two-fold higher than reference levels. Collagen fragment levels did not correlate with CA19-9 (r = 0.049-0.141, p = ns). On a continuous basis, higher levels of all collagen fragments were associated with significantly shorter OS. When evaluating degradation (C3M) and formation (PRO-C3) of type III collagen further, higher PRO-C3 was associated with poor OS (>25th percentile cut-point, HR = 2.01, 95%CI = 1.33-3.05) and higher C3M/PRO-C3 ratio was associated with improved OS (>25th percentile cut-point, HR = 0.53, 95%CI = 0.34-0.80). When adjusting for CA19-9 and clinical covariates, PRO-C3 remained significant (HR = 1.65, 95%CI = 1.09-2.48). In conclusion, collagen remodeling quantified in pre-treatment serum as a surrogate measure of desmoplasia was significantly associated with OS in a phase 3 clinical PDAC trial, supporting the link between desmoplasia, tumorigenesis, and response to treatment. If validated, these biomarkers may have prognostic and/or predictive potential in future PDAC trials.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Willumsen N,Ali SM,Leitzel K,Drabick JJ,Yee N,Polimera HV,Nagabhairu V,Krecko L,Ali A,Maddukuri A,Moku P,Ali A,Poulose J,Menon H,Pancholy N,Costa L,Karsdal MA,Lipton Adoi
10.1038/s41598-019-56268-3subject
Has Abstractpub_date
2019-12-24 00:00:00pages
19761issue
1issn
2045-2322pii
10.1038/s41598-019-56268-3journal_volume
9pub_type
杂志文章,多中心研究,随机对照试验abstract::APOBEC3 family members are cytidine deaminases with roles in intrinsic responses to infection by retroviruses and retrotransposons, and in the control of other DNA viruses, such as herpesviruses, parvoviruses and hepatitis B virus. Although effects of APOBEC3 members on viral DNA have been demonstrated, it is not know...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-24448-2
更新日期:2018-04-13 00:00:00
abstract::Extensive mapping of neuronal connections in the central nervous system requires high-throughput µm-scale imaging of large volumes. In recent years, different approaches have been developed to overcome the limitations due to tissue light scattering. These methods are generally developed to improve the performance of a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep09808
更新日期:2015-05-07 00:00:00
abstract::Nanotips made of metal and semiconductor have been widely utilized in versatile applications to strengthen the electric field through lightning rod effect and localized surface plasmon resonance (LSPR) effect. Here, we present the utilization of ferroelectric nanotips to assist photoreduction of silver nanostructures ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-47523-8
更新日期:2019-07-29 00:00:00
abstract::PP2A is a master controller of multiple inflammatory signaling pathways. It is a target in asthma; however the molecular mechanisms by which PP2A controls inflammation warrant further investigation. In A549 lung epithelial cells in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases rest...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep10063
更新日期:2015-05-18 00:00:00
abstract::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. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-018-23047-5
更新日期:2018-03-12 00:00:00
abstract::Ooids are typically spherical sediment grains characterised by concentric layers encapsulating a core. There is no universally accepted explanation for ooid genesis, though factors such as agitation, abiotic and/or microbial mineralisation and size limitation have been variously invoked. Here we examine the possible i...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-18908-4
更新日期:2018-01-11 00:00:00
abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. ...
journal_title:Scientific reports
pub_type: 已发布勘误
doi:10.1038/s41598-018-22369-8
更新日期:2018-03-06 00:00:00
abstract::Fairly poor data are available on the relationship between taste perception, food preferences and oral microbiota. In the present study, we investigated the hypothesis that subjects with higher responsiveness to 6-n-propylthiuracil (PROP) might be characterized by a different taste sensitivity and tongue microbiota co...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-40374-3
更新日期:2019-03-05 00:00:00
abstract::Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericyte...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03994-1
更新日期:2017-06-20 00:00:00
abstract::The triple negative basal-like (TNBL) breast carcinoma is an aggressive and unfavorable prognosis disease. Inhibitors of poly(ADP-ribose) polymerase such as Olaparib could represent a promising targeted therapy but their sensitivity against Multidrug Resistance proteins (MDR), which causes resistance, is not well defi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep12670
更新日期:2015-08-03 00:00:00
abstract::Parthenocarpy is the development of an ovary into a seedless fruit without pollination. The ubiquitous downregulation of SlIAA9 induces not only parthenocarpic fruit formation but also an abnormal vegetative phenotype. To make parthenocarpic transgenic tomato plants without unwanted phenotypes, we found two genes, nam...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-55400-7
更新日期:2019-12-11 00:00:00
abstract::Deforestation associated with the initial settlement of New Zealand is a dramatic example of how humans can alter landscapes through fire. However, evidence linking early human presence and land-cover change is inferential in most continental sites. We employed a multi-proxy approach to reconstruct anthropogenic land ...
journal_title:Scientific reports
pub_type: 历史文章,杂志文章
doi:10.1038/s41598-018-30606-3
更新日期:2018-08-14 00:00:00
abstract::Rheumatoid arthritis (RA) is a chronic inflammatory condition with variable clinical presentation and disease progression. Importantly, animal models of RA are widely used to examine disease pathophysiology/treatments. Here, we exploited known vendor colony-based differences in endocrine/immune responses to gain insig...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-00652-4
更新日期:2017-04-06 00:00:00
abstract::This study was performed to compare the area of the foveal avascular zone (FAZ-area) obtained by three optical coherence tomography angiography (OCTA) instruments. This was a cross-sectional, non-interventional study of twenty-seven healthy right eyes. The superficial and deep FAZ-area was measured manually with three...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-09255-5
更新日期:2017-08-29 00:00:00
abstract::The Schumann Resonances (ScR) are Extremely Low Frequency (ELF) electromagnetic resonances in the Earth-ionosphere cavity excited by global lightning discharges. This natural electromagnetic noise has likely existed on the Earth ever since the Earth had an atmosphere and an ionosphere, hence surrounding us throughout ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-36341-z
更新日期:2019-02-07 00:00:00
abstract::The composition of plant cell walls is important in determining cereal end uses. Unlike other widely consumed cereal grains barley is comparatively rich in (1,3;1,4)-β-glucan, a source of dietary fibre. Previous work showed Cellulose synthase-like genes synthesise (1,3;1,4)-β-glucan in several tissues. HvCslF6 encodes...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-53798-8
更新日期:2019-11-21 00:00:00
abstract::MicroRNA (miRNA) regulates gene expression by binding to specific sites in the 3'untranslated regions of its target genes. Machine learning based miRNA target prediction algorithms first extract a set of features from potential binding sites (PBSs) in the mRNA and then train a classifier to distinguish targets from no...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep08004
更新日期:2015-01-23 00:00:00
abstract::Comet assay is a widely used method, especially in the field of genotoxicity, to quantify and measure DNA damage visually at the level of individual cells with high sensitivity and efficiency. Generally, computer programs are used to analyze comet assay output images following two main steps. First, each comet region ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-75592-7
更新日期:2020-11-03 00:00:00
abstract::Uveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. S100A8 is a calcium-binding protein which mainly expresses in granulocytes and monocytes and plays a prominent role in the regulation of inflammatory processes and immune response. Here, we determined t...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep36140
更新日期:2016-10-27 00:00:00
abstract::Carbonaceous particulate matter (PM), comprising black carbon (BC), primary organic aerosol (POA) and secondary organic aerosol (SOA, from atmospheric aging of precursors), is a highly toxic vehicle exhaust component. Therefore, understanding vehicle pollution requires knowledge of both primary emissions, and how thes...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-03714-9
更新日期:2017-07-13 00:00:00
abstract::Chemokine receptor 5 (CCR5) belongs to G protein coupled receptors (GPCRs) and plays an important role in treatment of human immunodeficiency virus (HIV) infection since HIV uses CCR5 protein as a co-receptor. Recently, the crystal structure of CCR5-bound complex with an approved anti-retroviral drug (maroviroc) was r...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep13180
更新日期:2015-08-24 00:00:00
abstract::Whether hybridization generates or erodes species diversity has long been debated, but to date most studies have been conducted at small taxonomic scales. Salamanders (order Caudata) represent a taxonomic order in which hybridization plays a prevalent ecological and evolutionary role. We employed a recently developed ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-63378-w
更新日期:2020-04-16 00:00:00
abstract::The current anaesthesia information management system (AIMS) has limited capability for the acquisition of high-quality vital signs data. We have developed a Vital Recorder program to overcome the disadvantages of AIMS and to support research. Physiological data of surgical patients were collected from 10 operating ro...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-20062-4
更新日期:2018-01-24 00:00:00
abstract::Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-05806-y
更新日期:2017-07-14 00:00:00
abstract::Colon cancer stem cells have been attributed to poor prognosis, therapeutic resistance and aggressive nature of the malignancy. Recent reports associated CD44v6 expression with relapse, metastasis and reduced 5-year survival of colon cancer patients, thereby making it a potential therapeutic target. Thus, in this stud...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-35069-0
更新日期:2018-11-19 00:00:00
abstract::Sexual spores are important for the dispersal and population dynamics of fungi. They show remarkable morphological diversity, but the underlying forces driving spore evolution are poorly known. We investigated whether trophic status and substrate associations are associated with morphology in 787 macrofungal genera. W...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-23292-8
更新日期:2018-03-29 00:00:00
abstract::Although 3,5,3'-triiodothyronine (T3) is considered to be the primary bioactive thyroid hormone (TH) due to its high affinity for TH nuclear receptors (TRs), new data suggest that 3,5-diiodothyronine (T2) can also regulate transcriptional networks. To determine the functional relevance of these bioactive THs, RNA-seq ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-14913-9
更新日期:2017-11-08 00:00:00
abstract::Alumina toughened zirconia (ATZ) and zirconia toughened alumina (ZTA) are currently the materials of choice to meet the need for tough, strong, and bioinert ceramics for medical devices. However, the mechanical properties of ZrO2/Al2O3 dispersion ceramics could be considerably increased by reducing the corresponding g...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep20589
更新日期:2016-02-05 00:00:00
abstract::Acute traumatic intraparenchymal hematoma (tICH) expansion is a devastating neurological complication that is associated with poor outcome after cerebral contusion. This study aimed to develop and validate a novel noncontrast computed tomography (CT) (NCCT) multihematoma fuzzy sign to predict acute tICH expansion. In ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-021-81685-8
更新日期:2021-01-21 00:00:00
abstract::The 70-kD heat shock proteins (Hsp70s) are highly conserved molecular chaperones that play essential roles in cellular processes including abiotic stress responses. Physcomitrella patens serves as a representative of the first terrestrial plants and can recover from serious dehydration. To assess the possible relation...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep33650
更新日期:2016-09-20 00:00:00