Abstract:
:In pancreatic cancer (PDAC) intratumor infiltration of polymorphonuclear neutrophils (PMN) is associated with histologically apparent alterations of the tumor growth pattern. The aim of this study was to examine possible associations between PMN infiltration, tumor microarchitecture, and water diffusivity in diffusion-weighted magnetic resonance imaging (DW-MRI), and to further asses the underlying mechanisms. Methods: DW-MRI was performed in 33 PDAC patients prior to surgery. In parallel, tissue specimen were examined histologically for growth pattern, azurocidin-positive PMN infiltrates, and the presence of alpha-smooth muscle actin (α-SMA) and metalloproteinase 9 (MMP9)-positive myofibroblastic cells. For confirmation of the histological findings, a tissue microarray of a second cohort of patients (n=109) was prepared and examined similarly. For in vitro studies, the pancreatic stellate cell line RLT was co-cultivated either with isolated PMN, PMN-lysates, or recombinant azurocidin and characterized by Western blot, flow cytometry, and proteome profiler arrays. Results: Tumors with high PMN density showed restricted water diffusion in DW-MRI and histologic apparent alterations of the tumor microarchitecture (microglandular, micropapillary, or overall poorly differentiated growth pattern) as opposed to tumors with scattered PMN. Areas with altered growth pattern lacked α-SMA-positive myofibroblastic cells. Tissue microarrays confirmed a close association of high PMN density with alterations of the tumor microarchitecture and revealed a significant association of high PMN density with poor histologic grade of differentiation (G3). In vitro experiments provided evidence for direct effects of PMN on stellate cells, where a change to a spindle shaped cell morphology in response to PMN and to PMN-derived azurocidin was seen. Azurocidin incorporated into stellate cells, where it associated with F-actin. Down-regulation of α-SMA was seen within hours, as was activation of the p38-cofilin axis, up-regulation of MMP9, and acquisition of intracellular lipid droplets, which together indicate a phenotype switch of the stellate cells. Conclusion: In PDAC, PMN infiltrates are associated with alterations of the tumor microarchitecture. As a causal relationship, we propose a reprogramming of stellate cells by PMN-derived azurocidin towards a phenotype, which affects the microarchitecture of the tumor.
journal_name
Theranosticsjournal_title
Theranosticsauthors
Mayer P,Dinkic C,Jesenofsky R,Klauss M,Schirmacher P,Dapunt U,Hackert T,Uhle F,Hänsch GM,Gaida MMdoi
10.7150/thno.21089subject
Has Abstractpub_date
2018-01-01 00:00:00pages
13-30issue
1issn
1838-7640pii
thnov08p0013journal_volume
8pub_type
杂志文章相关文献
Theranostics文献大全abstract::Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.40664
更新日期:2020-03-04 00:00:00
abstract::Intraoperative fluorescence imaging is particularly well-suited for surgical applications due to its inherently high sensitivity, resolution, and ability to provide images in real-time. To date, the intraoperative observation of fluorescence has largely been subjective. With the need to show objective evidence in orde...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.27384
更新日期:2018-10-22 00:00:00
abstract::Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-mi...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.19898
更新日期:2017-06-14 00:00:00
abstract::The α-chemokine CXCL12 (stromal derived factor-1; SDF-1) and its corresponding G(αI) protein-coupled CXCR4 receptor axis play an important role in retention of hematopoietic stem progenitor cells (HSPCs) in bone marrow (BM) stem cell niches. CXCL12 has also been identified as a strong chemoattractant for HSPCs and imp...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.4621
更新日期:2013-01-01 00:00:00
abstract::The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.29247
更新日期:2019-02-12 00:00:00
abstract::Biological cancer therapies, such as oncolytic, or replication-selective viruses have advantages over traditional therapeutics as they can employ multiple different mechanisms to target and destroy cancers (including direct cell lysis, immune activation and vascular collapse). This has led to their rapid recent clinic...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.3724
更新日期:2012-01-01 00:00:00
abstract::Aims: Pathological cardiac fibrosis and hypertrophy are common features of left ventricular remodeling that often progress to heart failure (HF). Endothelial cells (ECs) are the most abundant non-myocyte cells in adult mouse heart. Simvastatin, a strong inducer of Krüppel-like Factor 2 (Klf2) in ECs, ameliorates press...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.48153
更新日期:2021-01-01 00:00:00
abstract::Aplastic anemia (AA) is characterized as hypoplasia of bone marrow hematopoietic cells and hematopenia of peripheral blood cells. Though the supplement of exogenous erythropoietin (EPO) has been clinically approved for AA treatment, the side-effects hinder its further application. Here a robust treatment for AA induce...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.46794
更新日期:2020-05-23 00:00:00
abstract::Hair regenerative medicine, a promising strategy for the treatment of hair loss, will likely involve the transplantation of autologous hair follicular stem cells (HFSCs) and dermal papilla cells (DPCs) into regions of hair loss. Cyclic hair regeneration results from the periodic partial activation of HFSCs. However, p...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.48723
更新日期:2020-09-22 00:00:00
abstract::Cerebrospinal fluid (CSF) leakage can lead to brain and spine pathologies and there is an urgent need for a rapid diagnostic method for determining CSF leakage. Beta-2 transferrin (β2TF), asialotransferrin, is a specific CSF glycoprotein biomarker used to determine CSF leakage when distinguished from serum sialotransf...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.34411
更新日期:2019-05-31 00:00:00
abstract::Rationale: Saliva as a sample matrix is rapidly gaining interest for disease diagnosis and point-of-care assays because it is easy to collect (non-invasive) and contains many health-related biomarkers. However, saliva poses particular problems relative to more common urine and blood matrices, which includes low analyt...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.24941
更新日期:2018-06-13 00:00:00
abstract::We describe the preparation of monodisperse, lanthanide-doped hexagonal-phase NaYF4 upconverting luminescent nanoparticles for protein conjugation. Their core was coated with a silica shell which then was modified with a poly(ethylene glycol) spacer and N-hydroxysuccinimide ester groups. The nanoparticles were charact...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.5113
更新日期:2013-03-13 00:00:00
abstract::Molecular subtyping of breast cancer is of considerable interest owing to its potential for personalized therapy and prognosis. However, current methodologies cannot be used for precise subtyping, thereby posing a challenge in clinical practice. The aim of the present study is to develop a cell-specific single-strande...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.28949
更新日期:2018-11-10 00:00:00
abstract::[This corrects the article DOI: 10.7150/thno.21477.]. ...
journal_title:Theranostics
pub_type: 已发布勘误
doi:10.7150/thno.56462
更新日期:2021-01-01 00:00:00
abstract::Exosomes play critical roles in intercellular communication in both nearby and distant cells in individuals and organs. Polymerase I and transcript release factor (PTRF), also known as Cavin1, has previously been described as a critical factor in caveola formation, and aberrant PTRF expression has been reported in var...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.22952
更新日期:2018-02-07 00:00:00
abstract::Background: Lung cancer has a high mortality rate and is resistant to multiple chemotherapeutics. Natural Borneol (NB) is a monoterpenoid compound that facilitates the bioavailability of drugs. In this study, we investigated the effects of NB on chemosensitivity in the A549 human lung adenocarcinoma cell line and to e...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.45861
更新日期:2020-08-13 00:00:00
abstract::Uncontrollable cell proliferation and irreversible neurological damage make glioma one of the most deadly diseases in clinic. Besides the multiple biological barriers, glioma stem cells (GSCs) that are responsible for the maintenance and recurrence of tumor tissues also hinder the therapeutic efficacy of chemotherapy....
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.41382
更新日期:2020-03-04 00:00:00
abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in a variety of tumor cells, but not most normal cells. Nevertheless, its therapeutic potential is limited due to the frequent occurrence of resistance in tumor cells, especially hepatocellular carcinoma cell lines. Theref...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.21707
更新日期:2017-10-12 00:00:00
abstract::Long non-coding RNAs (lncRNAs) have emerged as integral components of E2F1-regulated gene regulatory networks (GRNs), but their implication in advanced or treatment-refractory malignancy is unknown. Methods: We combined high-throughput transcriptomic approaches with bioinformatics and structure modeling to search for ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.44176
更新日期:2020-07-29 00:00:00
abstract::Radiotherapy is an extensively used treatment modality in the clinic and can kill malignant cells by generating cytotoxic reactive oxygen species (ROS). Unfortunately, excessive dosages of radiation are typically required because only a small proportion of the radiative energy is adsorbed by the soft tissues of a tumo...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.28033
更新日期:2019-01-01 00:00:00
abstract::Treatments of high specificity are desirable for cancer therapy. Light-triggered nanotheranostics (LTN) mediated cancer therapy could be one such treatment, as they make it possible to visualize and treat the tumor specifically in a light-controlled manner with a single injection. Because of their great potential in c...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.15217
更新日期:2016-04-27 00:00:00
abstract::Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.17573
更新日期:2017-04-10 00:00:00
abstract::Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy. However, the SDT efficacy is severely limited by the hypoxia and high glutathione (GSH) in the tumor microenvironment, and ferroptosis is highly associ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.45511
更新日期:2021-01-01 00:00:00
abstract::Recently, researchers identified a distinct vessel subtype called type H vessels that couple angiogenesis and osteogenesis. We previously found that type H vessels are reduced in ovariectomy (OVX)-induced osteoporotic mice, and preosteoclasts are able to secrete platelet-derived growth factor-BB (PDGF-BB) to stimulate...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.22144
更新日期:2018-03-28 00:00:00
abstract::Salivary adenoid cystic carcinoma (SACC) is a peculiar malignant tumor, characterized by its slow but inexorable growth, with a high incidence of lung metastasis and poor prognosis. Here, we show the upregulated expression of EGFR ligand epiregulin in a subset of SACC cells correlates with lung metastasis and unfavora...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.19712
更新日期:2017-08-23 00:00:00
abstract::Background: Accumulating evidences indicate that nanomedicines greatly decrease the side effects and enhance the efficacy of colorectal cancer (CRC) treatment. In particular, the use of rectal delivery of nanomedicines, with advantages such as fast therapeutic effects and a diminishing hepatic first-pass effect, is cu...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.40318
更新日期:2020-02-18 00:00:00
abstract::Ferroptosis is a newly discovered form of non-apoptotic cell death in multiple human diseases. However, the epigenetic mechanisms underlying ferroptosis remain poorly defined. First, we demonstrated that lymphoid-specific helicase (LSH), which is a DNA methylation modifier, interacted with WDR76 to inhibit ferroptosis...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.19988
更新日期:2017-07-23 00:00:00
abstract::In a report from 2008, The International Agency for Research on Cancer predicted a tripled cancer incidence from 1975, projecting a possible 13-17 million cancer deaths worldwide by 2030. While new treatments are evolving and reaching approval for different cancer types, the main prevention of cancer mortality is thro...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.11544
更新日期:2015-09-01 00:00:00
abstract::Peripheral arterial disease affects nearly 202 million individuals worldwide, sometimes leading to non-healing ulcers or limb amputations in severe cases. Genetically modified stem cells offer potential advantages for therapeutically inducing angiogenesis via augmented paracrine release mechanisms and tuned dynamic re...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.12866
更新日期:2016-05-23 00:00:00
abstract::Long term pulmonary exposure to crystalline silica leads to silicosis that manifests progressive interstitial fibrosis, eventually leading to respiratory failure and death. Despite efforts to eliminate silicosis, clinical cases continue to occur in both developing and developed countries. The exact mechanisms of cryst...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.16180
更新日期:2016-09-09 00:00:00