Background： Angiopoietin-2 （Ang-2） plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and othe...Background： Angiopoietin-2 （Ang-2） plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and other regulators with exposure to hypoxia. The objective of this study was to investigate the influence of percutaneous coronary intervention （PCI） on serum Ang-2 concentrations, and analyze the correlation between serum Ang-2 and the severity of coronary artery stenosis in patients with coronary heart disease （CHD）. Methods： Sixty-four patients with CHD were selected as the study group, each undergone PC1. Thirty-two healthy subjects were selected as the control group. Pre-PCI and post-PCl serum Ang-2 were measured by enzyme-linked immunosorbent assay. The severity of coronary artery stenosis was evaluated using angiographic Gensini scores, and the coronary collateral vessels were scored according to Rentrop＇s classification. Results： Concentrations of pre-PCI serum Ang-2 in the study group were significantly higher than those in the control group （4625.06 ~ 1838.06 vs. 1945.74 ：k 1588.17 pg/ml, P 〈 0.01 ）; however, concentrations of post-PCl serum Ang-2 were significantly lower than those of pre-PCI （3042.63 ＋ 1845.33 pg/ml vs. 4625.06 .k 1838.06 pg/ml, P 〈 0.01）. Concentrations of pre-PCl serum Ang-2 were significantly correlated with Gensini scores （r= 0.488, P〈 0.01）; however, the decrease in serum Ang-2 after PC1 was not correlated with Gensini scores, coronary collateral vessel grading, or left ventricular ejection fraction. Conclusions： Serum Ang-2 concentrations significantly increased in patients with CHD, and PCI treatment significantly decreased these concentrations. Serum Ang-2 concentrations, but not the decrease in serum Ang-2 concentrations, were significantly correlated with the severity of coronary artery stenosis. These results suggested that Ang-2 may be a biomarker of myocardial ischemia and vessel remodeling.展开更多
In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without...In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without hemorrhagic transformation.We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome,and it disappears promptly once the effective recanalization is achieved.Contrary to the belief that collateral vessels develop over time in chronic stenotic condition,there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress,which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries.We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1,which is a known shear-stress mechanosensing protein.展开更多
Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,whic...Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,which are known to be significantly attributed to treatment failures.Over the past decades,efforts have been made to understand the difference between nor-mal and tumor vessels.It has been demonstrated that tumor vasculature is structurally immature with chaotic and leaky phenotypes,which provides opportunities for developing novel anticancer strategies.Targeting tumor vasculature is not only a unique therapeutic interven-tion to starve neoplastic cells,but also enhances the efficacy of conventional cancer treatments.Vascular dis-rupting agents(VDAs) have been developed to disrupt the already existing neovasculature in actively growing tumors,cause catastrophic vascular shutdown within short time,and induce secondary tumor necrosis.VDAs are cytostatic;they can only inhibit tumor growth,but not eradicate the tumor.This novel drug mechanism has urged us to develop multiparametric imaging biomark-ers to monitor early hemodynamic alterations,cellular dysfunctions and metabolic impairments before tumor dimensional changes can be detected.In this article,we review the characteristics of tumor vessels,tubulin-destabilizing mechanisms of VDAs,and in vivo effects of the VDAs that have been mostly studied in preclinical studies and clinical trials.We also compare the differ-ent tumor models adopted in the preclinical studies on VDAs.Multiparametric imaging biomarkers,mainly diffu-sion-weighted imaging and dynamic contrast-enhanced imaging from magnetic resonance imaging,are evalu-ated for their potential as morphological and functional imaging biomarkers for monitoring therapeutic effects of VDAs.展开更多
Lymph node metastasis is the hallmark of colon cancer progression,and is considered one of the most important prognostic factors.Recently,there has been growing evidence that tumor lymphangiogenesis(formation of new l...Lymph node metastasis is the hallmark of colon cancer progression,and is considered one of the most important prognostic factors.Recently,there has been growing evidence that tumor lymphangiogenesis(formation of new lymphatic vessels) plays an important role in this process.Here,we review the latest f indings of the role of lymphangiogenesis in colorectal cancer progression,and discuss its clinical application as a biomarker and target for new therapy.Understanding the molecular pathways that regulate lymphangiogenesis is mandatory to pave the way for the development of new therapies for cancer.In the future,tailored treatments consisting of combinations of chemotherapy,other targeted therapies,and anti-lymphangiogenesis agents will hopefully improve patient outcomes.This progression to the clinic must be guided by new avenues of research,such as the identif ication of biomarkers that predict response to treatment.展开更多
Chronic subdural hematoma (CSDH) is a common and frequently occurring disease in neurosurgery, whose incidence accounts for around 10% of all intracranial hematomas. There have been many theories about the mechanism o...Chronic subdural hematoma (CSDH) is a common and frequently occurring disease in neurosurgery, whose incidence accounts for around 10% of all intracranial hematomas. There have been many theories about the mechanism of CSDH, including acute subdural hematoma, slow hemorrhage after bridge vein injury, and traumatic subdural effusion evolution With improvements in medical imaging technology and related basic research, the perception of CSDH as an inflammatory vascular proliferative disease has gradually reached consensus In addition to head trauma, brain atrophy leading to expanded subdural space is the premise and primary reason for the occurrence of CSDH in the older adult population.展开更多
基金This study was supported by the grants from National Natural Science Foundation of China，Guangxi Natural Science Foundation，High Level Innovation Team and Outstanding Scholar Program in Guangxi Colleges
文摘Background： Angiopoietin-2 （Ang-2） plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and other regulators with exposure to hypoxia. The objective of this study was to investigate the influence of percutaneous coronary intervention （PCI） on serum Ang-2 concentrations, and analyze the correlation between serum Ang-2 and the severity of coronary artery stenosis in patients with coronary heart disease （CHD）. Methods： Sixty-four patients with CHD were selected as the study group, each undergone PC1. Thirty-two healthy subjects were selected as the control group. Pre-PCI and post-PCl serum Ang-2 were measured by enzyme-linked immunosorbent assay. The severity of coronary artery stenosis was evaluated using angiographic Gensini scores, and the coronary collateral vessels were scored according to Rentrop＇s classification. Results： Concentrations of pre-PCI serum Ang-2 in the study group were significantly higher than those in the control group （4625.06 ~ 1838.06 vs. 1945.74 ：k 1588.17 pg/ml, P 〈 0.01 ）; however, concentrations of post-PCl serum Ang-2 were significantly lower than those of pre-PCI （3042.63 ＋ 1845.33 pg/ml vs. 4625.06 .k 1838.06 pg/ml, P 〈 0.01）. Concentrations of pre-PCl serum Ang-2 were significantly correlated with Gensini scores （r= 0.488, P〈 0.01）; however, the decrease in serum Ang-2 after PC1 was not correlated with Gensini scores, coronary collateral vessel grading, or left ventricular ejection fraction. Conclusions： Serum Ang-2 concentrations significantly increased in patients with CHD, and PCI treatment significantly decreased these concentrations. Serum Ang-2 concentrations, but not the decrease in serum Ang-2 concentrations, were significantly correlated with the severity of coronary artery stenosis. These results suggested that Ang-2 may be a biomarker of myocardial ischemia and vessel remodeling.
文摘In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without hemorrhagic transformation.We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome,and it disappears promptly once the effective recanalization is achieved.Contrary to the belief that collateral vessels develop over time in chronic stenotic condition,there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress,which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries.We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1,which is a known shear-stress mechanosensing protein.
基金Supported by(partially) The grants awarded by Fonds voor Wetenschappelijk Onderzoek-Vlaanderen(FWO Vlaanderen) Impulsfinanciering project(ZWAP/05/018)Geconcerteerde Onderzoeksactie of the Flemish Government,OT project(OT/06/70)+1 种基金the K.U.Leuven Molecular Small Animal Imaging Center MoSAIC (KUL EF/05/08)the center of excellence In vivo Molecular Imaging Research of K.U.Leuven and a EU project Asia-Link CfP 2006-EuropeAid/123738/C/ACT/Multi-Proposal No.128-498/111
文摘Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis;a process known as tumor angiogenesis.Angiogenesis is largely involved in tumor survival,progression and spread,which are known to be significantly attributed to treatment failures.Over the past decades,efforts have been made to understand the difference between nor-mal and tumor vessels.It has been demonstrated that tumor vasculature is structurally immature with chaotic and leaky phenotypes,which provides opportunities for developing novel anticancer strategies.Targeting tumor vasculature is not only a unique therapeutic interven-tion to starve neoplastic cells,but also enhances the efficacy of conventional cancer treatments.Vascular dis-rupting agents(VDAs) have been developed to disrupt the already existing neovasculature in actively growing tumors,cause catastrophic vascular shutdown within short time,and induce secondary tumor necrosis.VDAs are cytostatic;they can only inhibit tumor growth,but not eradicate the tumor.This novel drug mechanism has urged us to develop multiparametric imaging biomark-ers to monitor early hemodynamic alterations,cellular dysfunctions and metabolic impairments before tumor dimensional changes can be detected.In this article,we review the characteristics of tumor vessels,tubulin-destabilizing mechanisms of VDAs,and in vivo effects of the VDAs that have been mostly studied in preclinical studies and clinical trials.We also compare the differ-ent tumor models adopted in the preclinical studies on VDAs.Multiparametric imaging biomarkers,mainly diffu-sion-weighted imaging and dynamic contrast-enhanced imaging from magnetic resonance imaging,are evalu-ated for their potential as morphological and functional imaging biomarkers for monitoring therapeutic effects of VDAs.
基金Supported by SUMITOMO Life Social Welfare Services Foundation (to Nagahashi M)Virginia Commonwealth University Grant BIRCWH K12HD055881,and Susan G Komen for the Cure Career Catalyst Research Grant KG090510 (to Takabe K)
文摘Lymph node metastasis is the hallmark of colon cancer progression,and is considered one of the most important prognostic factors.Recently,there has been growing evidence that tumor lymphangiogenesis(formation of new lymphatic vessels) plays an important role in this process.Here,we review the latest f indings of the role of lymphangiogenesis in colorectal cancer progression,and discuss its clinical application as a biomarker and target for new therapy.Understanding the molecular pathways that regulate lymphangiogenesis is mandatory to pave the way for the development of new therapies for cancer.In the future,tailored treatments consisting of combinations of chemotherapy,other targeted therapies,and anti-lymphangiogenesis agents will hopefully improve patient outcomes.This progression to the clinic must be guided by new avenues of research,such as the identif ication of biomarkers that predict response to treatment.
文摘Chronic subdural hematoma (CSDH) is a common and frequently occurring disease in neurosurgery, whose incidence accounts for around 10% of all intracranial hematomas. There have been many theories about the mechanism of CSDH, including acute subdural hematoma, slow hemorrhage after bridge vein injury, and traumatic subdural effusion evolution With improvements in medical imaging technology and related basic research, the perception of CSDH as an inflammatory vascular proliferative disease has gradually reached consensus In addition to head trauma, brain atrophy leading to expanded subdural space is the premise and primary reason for the occurrence of CSDH in the older adult population.
