Abstract:
BACKGROUND:In patients with resectable colorectal liver metastases (CRLM), distinct histopathological growth patterns (HGPs) develop at the interface between the tumour and surrounding tissue. The desmoplastic (d) HGP is characterised by angiogenesis and a peripheral fibrotic rim, whereas non-angiogenic HGPs co-opt endogenous sinusoidal hepatic vasculature. Evidence from previous studies has suggested that patients with dHGP in their CRLM have improved prognosis as compared to patients with non-desmoplastic HGPs. However, these studies were relatively small and applied arbitrary cut-off values for the determination of the predominant HGP. We have now investigated the prognostic effect of dHGP in a large cohort of patients with CRLM resected either with or without neoadjuvant chemotherapy. METHODS:All consecutive patients undergoing a first partial hepatectomy for CRLM between 2000 and 2015 at a tertiary referral centre were considered for inclusion. HGPs were assessed in archival H&E stained slides according to recently published international consensus guidelines. The dHGP was defined as desmoplastic growth being present in 100% of the interface between the tumour and surrounding liver. RESULTS:In total, HGPs in CRLMs from 732 patients were assessed. In the chemo-naive patient cohort (n = 367), the dHGP was present in 19% (n = 68) and the non-dHGP was present in 81% (n = 299) of patients. This dHGP subgroup was independently associated with good overall survival (OS) (HR: 0.39, p < 0.001) and progression-free survival (PFS) (HR: 0.54, p = 0.001). All patients with any CRLM with a non-dHGP had significantly reduced OS compared to those patients with 100% dHGP, regardless of the proportion of non-dHGP (all p values ≤ 0.001). In the neoadjuvantly treated patient cohort (n = 365), more patients were found to express dHGP (n = 109, 30%) (adjusted odds ratio: 2.71, p < 0.001). On univariable analysis, dHGP was associated with better OS (HR 0.66, p = 0.009) and PFS (HR 0.67, p = 0.002). However, after correction for confounding by means of multivariable analysis no significant association of dHGP with OS (HR 0.92, p = 0.623) or PFS (HR 0.76, p = 0.065) was seen. CONCLUSIONS:The current study demonstrates that the angiogenic dHGP in CRLM resected from chemo-naive patients acts as a strong, positive prognostic marker, unmatched by any other prognosticator. This observation warrants the evaluation of the clinical utility of HGPs in prospective clinical trials.
journal_name
Angiogenesisjournal_title
Angiogenesisauthors
Galjart B,Nierop PMH,van der Stok EP,van den Braak RRJC,Höppener DJ,Daelemans S,Dirix LY,Verhoef C,Vermeulen PB,Grünhagen DJdoi
10.1007/s10456-019-09661-5subject
Has Abstractpub_date
2019-05-01 00:00:00pages
355-368issue
2eissn
0969-6970issn
1573-7209pii
10.1007/s10456-019-09661-5journal_volume
22pub_type
杂志文章相关文献
ANGIOGENESIS文献大全abstract:INTRODUCTION:Alterations in vascular morphogenesis are hallmarks of antiangiogenesis-resistant tumor vessels. Vascular morphogenesis is regulated by ephrinB2-EphB4 system which may induce different biological effects depending on the oncological and molecular contexts. It was the aim of the current study to characteriz...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-018-9633-6
更新日期:2018-11-01 00:00:00
abstract::Intermittent Hypoxia (IH) that develops in neovascularized solid tumours has been described to positively influence the tumour growth by modulating the behaviour of cancer cells as well as of endothelial cells. However, the molecular mechanisms regulated by IH still remain poorly understood. In this work, the effects ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9156-2
更新日期:2009-01-01 00:00:00
abstract::Following arterial occlusion, blood vessels respond by forming a new network of functional capillaries (angiogenesis), by reorganizing preexisting capillaries through the recruitment of smooth muscle cells to generate new arteries (arteriogenesis) and by growing and remodeling preexisting collateral arterioles into ph...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-016-9535-4
更新日期:2017-02-01 00:00:00
abstract::During embryonic development, the lymphatic system emerges by transdifferentiation from the cardinal vein. Although lymphatic and blood vasculature share a close molecular and developmental relationship, they display distinct features and functions. However, even after terminal differentiation, transitions between blo...
journal_title:Angiogenesis
pub_type: 临床试验,杂志文章
doi:10.1007/s10456-012-9264-2
更新日期:2012-06-01 00:00:00
abstract::Prothrombin, a protein involved in blood coagulation, is a plasma glycoprotein composed of the Gla domain, two adjacent kringle domains, and a serine protease domain. Kringles are triple-disulfide-loop folding domains, which are found in several other blood proteins. In this study, we showed that recombinant human pro...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1023835102832
更新日期:2002-01-01 00:00:00
abstract::The sprouting of endothelial cells is the first step of tumor angiogenesis. Our previous study suggests that miR-153 suppresses breast tumor angiogenesis partially through targeting hypoxia-induced factor (HIF1α). In this study, we demonstrated that miR-153 also suppresses the migration and the tube formation of endot...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-018-9630-9
更新日期:2018-11-01 00:00:00
abstract::Angiogenesis is important for tumor growth and metastasis. CLT1 (CGLIIQKNEC), a peptide that binds to tumor interstitial spaces in the presence of fibrin-fibronectin, has structural similarity to the anti-angiogenic β-sheet peptides anastellin and anginex. This similarity is reflected in the ability of CLT1 to form co...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-011-9247-8
更新日期:2012-03-01 00:00:00
abstract::Anti-VEGF (vascular endothelial growth factor) therapy with the monoclonal antibody bevacizumab can cause gastrointestinal (GI) perforations. In recent years it became apparent that GI perforations also occur during treatment with antiangiogenic tyrosine kinase inhibitors (TKIs). It is of clinical importance to consid...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-010-9197-6
更新日期:2011-05-01 00:00:00
abstract::Angiopoietin-like (ANGPTL) proteins are secreted proteins showing structural similarity to members of the angiopoietin family. Some ANGPTL proteins possess pleiotropic activities, being involved in cancer lipid, glucose energy metabolisms, and angiogenesis. ANGPTL7 is the less characterized member of the family whose ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-014-9435-4
更新日期:2014-10-01 00:00:00
abstract::The sprouting of endothelial cells from pre-existing blood vessels represents a critical event in the angiogenesis cascade. However, only a fraction of cultured or transplanted endothelial cells form new vessels. Moreover, it is unclear whether this results from a stochastic process or instead relates to certain endot...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-014-9414-9
更新日期:2014-07-01 00:00:00
abstract::Among the key effects of fluid shear stress on vascular endothelial cells is modulation of gene expression. Promoter sequences termed shear stress response elements (SSREs) mediate the responsiveness of endothelial genes to shear stress. While previous studies showed that shear stress responsiveness is mediated by a s...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9143-7
更新日期:2009-01-01 00:00:00
abstract::Matrix Gla protein (MGP) is an antagonist of bone morphogenetic proteins and expressed in vascular endothelial cells. Lack of MGP causes vascular abnormalities in multiple organs in mice. The objective of this study is to define the role of MGP in early endothelial differentiation. We find that expression of endotheli...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-015-9484-3
更新日期:2016-01-01 00:00:00
abstract::Ocular angiogenesis is responsible for the majority of irreversible blindness in the developed world [1]. This debilitating complication affects all age groups and characterizes such diverse and widespread diseases as trachoma, retinopathy of prematurity, diabetic retinopathy, neovascular glaucoma and age-related macu...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1009071601454
更新日期:1999-01-01 00:00:00
abstract::During prolonged hypoxic conditions, endothelial cells change their gene expression to adjust to the low oxygen environment. This process is mainly regulated by the hypoxia-inducible factors, HIF-1α and HIF-2α. Although endothelial cells do not form sprouts during prolonged hypoxic culturing, silencing of HIF-2α parti...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-016-9527-4
更新日期:2017-02-01 00:00:00
abstract:BACKGROUND:Vascular endothelial growth factor (VEGF) that is secreted by tumor cells plays a key role in angiogenesis. Matrix metalloproteinase 9 (MMP-9) is produced by inflammatory cells, such as stromal granulocytes (PMN), remodels the extracellular matrix and is known to promote angiogenesis indirectly by interactin...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-011-9207-3
更新日期:2011-09-01 00:00:00
abstract::In the adult, new vessels and red blood cells form in response to hypoxia. Here, the oxygen-sensing system (PHD-HIF) has recently been put into focus, since the prolyl-hydroxylase domain proteins (PHD) and hypoxia-inducible factors (HIF) are considered as potential therapeutic targets to treat ischemia, cancers or age...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-015-9492-3
更新日期:2016-04-01 00:00:00
abstract::Chemokine (C-C motif) receptor-2 (CCR2) regulates arteriogenesis and angiogenesis, facilitating the MCP-1-dependent recruitment of growth factor-secreting bone marrow-derived cells (BMCs). Here, we tested the hypothesis that the BMC-specific expression of CCR2 is also required for new arteriole formation via capillary...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-009-9157-1
更新日期:2009-01-01 00:00:00
abstract::A missense mutation from arginine to tryptophan at residue 849 in the kinase domain of Tie2 (Tie2-R849W) is commonly identified in familial venous malformations. The mechanistic action of Tie2-R849W variant expression on angiogenic cascades including smooth muscle cell recruitment, however, remains elusive. To avoid c...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9313-x
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:The term "intramuscular hemangioma capillary type" (IHCT) refers to a fast-flow vascular lesion that is classified as a tumor, although its phenotype overlaps with arteriovenous malformation (AVM). The purpose of this study was to identify somatic mutations in IHCT. METHODS:Affected tissue specimens were ob...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-019-09678-w
更新日期:2019-11-01 00:00:00
abstract::Although we reported that basic fibroblast growth factor (bFGF) levels in pericardial fluid of patients with unstable angina are apparently increased, it was unclear whether vascular endothelial growth factor (VEGF) is also increased in patients with myocardial ischemia. Using an enzyme-linked immunosorbent assay, we ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1023/a:1009062712441
更新日期:1998-01-01 00:00:00
abstract::Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-018-9601-1
更新日期:2018-05-01 00:00:00
abstract::The role of muscle contraction, prostanoids, nitric oxide and adenosine in the regulation of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endothelial cell proliferative compounds in skeletal muscle cell cultures was examined. VEGF and bFGF mRNA, protein release as well as the pr...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-004-4184-4
更新日期:2004-01-01 00:00:00
abstract::Endothelial progenitor cells (EPCs) play a critical role in the repair of damaged blood vessels and/or in the growth of new ones in ischemic tissues. Elevated levels of oxygen radicals, which accumulate in the ischemic tissue, could compromise the angiogenic potential of EPCs. To determine if oxidative stress alters t...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-011-9211-7
更新日期:2011-09-01 00:00:00
abstract::Antiangiogenic therapy, specially sorafenib, has become the standard of care for patients with advanced hepatocellular carcinoma (HCC), however, the improvement in survival time is not satisfactory. Previous studies have found that, in some circumstances, antiangiogenic therapy promoted tumor metastasis and the mechan...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-013-9357-6
更新日期:2013-10-01 00:00:00
abstract::The formation of new tubular structures from a quiescent endothelial lining is one of the hallmarks of sprouting angiogenesis. This process can be mimicked in vitro by inducing capillary-like tubular structures in a three-dimensional (3D) fibrin matrix. We aimed to analyze the differential mRNA expression in two pheno...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-007-9086-9
更新日期:2008-01-01 00:00:00
abstract::Early pregnancy is characterized by decidual adaption to the developing embryo involving angiogenesis and vascular growth. Failure of decidual vascular expansion is linked to diseases of pregnancy. Dendritic cells (DC) have been associated with vascular growth during early gestation, though it is unknown whether their...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9325-6
更新日期:2013-04-01 00:00:00
abstract::Heparan sulfate (HS), a long linear polysaccharide of alternating disaccharide residues, interacts with a wide variety of proteins, including many angiogenic factors. The involvement of HS in signaling of pro-angiogenic factors (e.g. vascular endothelial growth factor and fibroblast growth factor 2), as well as intera...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-013-9401-6
更新日期:2014-07-01 00:00:00
abstract::Ovarian cancer (OC) is associated with poor survival because there are a limited number of effective therapies. Two processes key to OC progression, angiogenesis and immune evasion, act synergistically to promote tumor progression. Tumor-associated angiogenesis promotes immune evasion, and tumor-related immune respons...
journal_title:Angiogenesis
pub_type: 杂志文章,评审
doi:10.1007/s10456-020-09734-w
更新日期:2020-11-01 00:00:00
abstract::De novo synthesis of cytoskeleton-regulatory proteins triggered by the megakaryoblastic leukemia (MKL)/serum response factor (SRF) transcriptional system in response to pro-angiogenic growth factors lies at the heart of endothelial cell (EC) migration (a critical element of angiogenesis) and neovascularization. This s...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-017-9560-y
更新日期:2017-11-01 00:00:00
abstract::Altered RNA processing is an underlying mechanism of amyotrophic lateral sclerosis (ALS). Missense mutations in a number of genes involved in RNA function and metabolisms are associated with ALS. Among these genes is angiogenin (ANG), the fifth member of the vertebrate-specific, secreted ribonuclease superfamily. ANG ...
journal_title:Angiogenesis
pub_type: 杂志文章
doi:10.1007/s10456-012-9322-9
更新日期:2013-04-01 00:00:00