The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels an...The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels and cancer.Tumors need blood perfusion but there are mounting evidences that angiogenesis alone does not explain it in all the neoplasms.In this editorial,for a special issue on tumor and vessels published in the Chinese Journal of Cancer,we briefly introduce the history of the evidences that solid tumors can sometimes obtain blood perfusion by alternative approaches other than sprouting angiogenesis,i.e.,vessel co-option and vasculogenic mimicry.This editorial provides also the links to several most recently published discoveries and hypotheses on tumor interaction with blood vessels.展开更多
Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects ...Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine(6-OHDA).Methods:Wnt3a-conditioned medium(Wnt3a-CM)was used to intervene dopaminegic SH-SY5Y cells treated with 6-OHDA.Cell toxicity was determined by cell viability and lactate dehydrogenase leakage(LDH)assay.The mitochondria function was measured by the mitochondrial membrane potential,while oxidative stress was monitored with intracellular reactive oxygen species(ROS).Western blot analysis was used to detect the expression of GSK3β,β-catenin as well as Akt.Results:Our results showed that 100μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential,reduced the level ofβ-catenin and p-Akt,increased LDH leakage,ROS production and the ratio of p-GSK3β(Tyr216)to p-GSK3β(Ser9).However,Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these changes.Conclusions:Activating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly,which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.展开更多
Over the last half century,surgical aortic valve replacement(SAVR)has evolved to offer a durable and efficient valve haemodynamically,with low procedural complications that allows favourable remodelling of left ventri...Over the last half century,surgical aortic valve replacement(SAVR)has evolved to offer a durable and efficient valve haemodynamically,with low procedural complications that allows favourable remodelling of left ventricular(LV)structure and function.The latter has become more challenging among elderly patients,particularly following trans-catheter aortic valve implantation(TAVI).Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss,valvular-vascular impedance to myocardial activation,force-velocity relationship,and myocardial strain.LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour.Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome.Physiological pacing via the His-Purkinje system for conduction abnormalities,further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression,LV coordinate contraction,and global vascular function.TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions.Until comparable long-term durability and the resolution of TAVI related complications become available,SAVR remains the first choice for lower risk younger patients.展开更多
The World Health Organisation(WHO)classifies clinical diagnoses with the International Statistical Classification of Disease and Related Health Problems(ICD).There have been various iterations of ICD since it is incep...The World Health Organisation(WHO)classifies clinical diagnoses with the International Statistical Classification of Disease and Related Health Problems(ICD).There have been various iterations of ICD since it is inception.For oncology,ICD-O was introduced in 1976 as a special adaption of ICD for cancers to facilitate greater coding detail of the topography,which describes the anatomical location of the tumour origin,and the morphology concerns the histology of a neoplasm.ICD-10 began in 1983 and was first used in 1994.At the same time,a code for cholangiocarcinoma(CCA)was also introduced(https://icd.who.int/browse10/2010/en).展开更多
Hailed as the cancer treatment to end all the resistance to treatment,anti-angiogenic therapy turned out to be not quite what was promised.The hope that this therapeutic approach would not have suffered by the phenome...Hailed as the cancer treatment to end all the resistance to treatment,anti-angiogenic therapy turned out to be not quite what was promised.The hope that this therapeutic approach would not have suffered by the phenomenon of resistance was based on the fact that was targeting normal vessels rather than tumour cells prone to mutation and subject to drug induced selection.However,reality turned out to be more complex and since 1997,several mechanisms of resistance have been described to the point that the study of resistance to these drugs is now a very large field.Far from being exhaustive,this paper presents the main mechanisms discovered trough some examples.展开更多
The close relationship between metastasis and establishment of tumor vasculature has inspired enormous research interests aiming to suppress metastasis via inhibiting the development of tumor vasculature.International...The close relationship between metastasis and establishment of tumor vasculature has inspired enormous research interests aiming to suppress metastasis via inhibiting the development of tumor vasculature.International experts gathered in Guangzhou,China on May 10-12,2018 in The 4th International Meeting of Cancer and Blood Vessels to discuss the multiple ways for solid tumors to establish their vasculature.Vessel co-option is a mean by which a solid tumor takes advantage of the existing or newly induced blood vessels in the surrounding normal tissues to sustain tumor growth and metastasis.The underlying mechanisms of vessel co-option,the roles of pericyte,and the potential novel therapeutic targets have been discussed in the meeting.展开更多
Haematopoietic microenvironmental niches have been described as the‘gatekeepers’for the blood and immune systems.These niches change during ontogeny,with the bone marrow becoming the predominant site of haematopoies...Haematopoietic microenvironmental niches have been described as the‘gatekeepers’for the blood and immune systems.These niches change during ontogeny,with the bone marrow becoming the predominant site of haematopoiesis in post-natal life under steady state conditions.To determine the structure and function of different haematopoietic microenvironmental niches,it is essential to clearly define specific haematopoietic stem and progenitor cell subsets during ontogeny and to understand their temporal appearance and anatomical positioning.A variety of haematopoietic and non-haematopoietic cells contribute to haematopoietic stem and progenitor cell niches.The latter is reported to include endothelial cells and mesenchymal stromal cells(MSCs),skeletal stem cells and/or C-X-C motif chemokine ligand 12-abundant-reticular cell populations,which form crucial components of these microenvironments under homeostatic conditions.Dysregulation or deterioration of such cells contributes to significant clinical disorders and diseases worldwide and is associated with the ageing process.A critical appraisal of these issues and of the roles of MSC/C-X-C motif chemokine ligand 12-abundant-reticular cells and the more recently identified skeletal stem cell subsets in bone marrow haematopoietic niche function under homeostatic conditions and during ageing will form the basis of this research review.In the context of haematopoiesis,clinical translation will deal with lessons learned from the vast experience garnered from the development and use of MSC therapies to treat graft versus host disease in the context of allogeneic haematopoietic transplants,the recent application of these MSC therapies to treating emerging and severe coronavirus disease 2019(COVID-19)infections,and,given that skeletal stem cell ageing is one proposed driver for haematopoietic ageing,the potential contributions of these stem cells to haematopoiesis in healthy bone marrow and the benefits and challenges of using this knowledge for rejuvenating the age-compromised bone marrow haematopoietic niches and restoring haematopoiesis.展开更多
文摘The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels and cancer.Tumors need blood perfusion but there are mounting evidences that angiogenesis alone does not explain it in all the neoplasms.In this editorial,for a special issue on tumor and vessels published in the Chinese Journal of Cancer,we briefly introduce the history of the evidences that solid tumors can sometimes obtain blood perfusion by alternative approaches other than sprouting angiogenesis,i.e.,vessel co-option and vasculogenic mimicry.This editorial provides also the links to several most recently published discoveries and hypotheses on tumor interaction with blood vessels.
基金by Nature Science Foundation of China(81401058,81401645,81271428 and 81471292)a grant from the State Key Development Program for Basic Research of China(2011CB510000)+1 种基金a grant from Medical Scientific Research Foundation of Guangdong Province(B2014139)a grant supported by assisting research project of science and technology for Xinjiang(201591160).
文摘Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine(6-OHDA).Methods:Wnt3a-conditioned medium(Wnt3a-CM)was used to intervene dopaminegic SH-SY5Y cells treated with 6-OHDA.Cell toxicity was determined by cell viability and lactate dehydrogenase leakage(LDH)assay.The mitochondria function was measured by the mitochondrial membrane potential,while oxidative stress was monitored with intracellular reactive oxygen species(ROS).Western blot analysis was used to detect the expression of GSK3β,β-catenin as well as Akt.Results:Our results showed that 100μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential,reduced the level ofβ-catenin and p-Akt,increased LDH leakage,ROS production and the ratio of p-GSK3β(Tyr216)to p-GSK3β(Ser9).However,Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these changes.Conclusions:Activating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly,which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.
基金The authors received financial support for the research work in cardiac physiology and aortic valve surgery by research grant from Garfield Weston Trust,London(to Xu Yu Jin and John R Pepper)from Oxford Hospital Charity,Oxford(to Xu Yu Jin).
文摘Over the last half century,surgical aortic valve replacement(SAVR)has evolved to offer a durable and efficient valve haemodynamically,with low procedural complications that allows favourable remodelling of left ventricular(LV)structure and function.The latter has become more challenging among elderly patients,particularly following trans-catheter aortic valve implantation(TAVI).Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss,valvular-vascular impedance to myocardial activation,force-velocity relationship,and myocardial strain.LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour.Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome.Physiological pacing via the His-Purkinje system for conduction abnormalities,further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression,LV coordinate contraction,and global vascular function.TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions.Until comparable long-term durability and the resolution of TAVI related complications become available,SAVR remains the first choice for lower risk younger patients.
文摘The World Health Organisation(WHO)classifies clinical diagnoses with the International Statistical Classification of Disease and Related Health Problems(ICD).There have been various iterations of ICD since it is inception.For oncology,ICD-O was introduced in 1976 as a special adaption of ICD for cancers to facilitate greater coding detail of the topography,which describes the anatomical location of the tumour origin,and the morphology concerns the histology of a neoplasm.ICD-10 began in 1983 and was first used in 1994.At the same time,a code for cholangiocarcinoma(CCA)was also introduced(https://icd.who.int/browse10/2010/en).
文摘Hailed as the cancer treatment to end all the resistance to treatment,anti-angiogenic therapy turned out to be not quite what was promised.The hope that this therapeutic approach would not have suffered by the phenomenon of resistance was based on the fact that was targeting normal vessels rather than tumour cells prone to mutation and subject to drug induced selection.However,reality turned out to be more complex and since 1997,several mechanisms of resistance have been described to the point that the study of resistance to these drugs is now a very large field.Far from being exhaustive,this paper presents the main mechanisms discovered trough some examples.
文摘The close relationship between metastasis and establishment of tumor vasculature has inspired enormous research interests aiming to suppress metastasis via inhibiting the development of tumor vasculature.International experts gathered in Guangzhou,China on May 10-12,2018 in The 4th International Meeting of Cancer and Blood Vessels to discuss the multiple ways for solid tumors to establish their vasculature.Vessel co-option is a mean by which a solid tumor takes advantage of the existing or newly induced blood vessels in the surrounding normal tissues to sustain tumor growth and metastasis.The underlying mechanisms of vessel co-option,the roles of pericyte,and the potential novel therapeutic targets have been discussed in the meeting.
基金I wish to thank the Nuffield Department of Clinical Laboratory Sciences,Radcliffe Department of Medicine,University of Oxford,Oxford,UK,and the Faculty of Health and Medical Sciences,University of Adelaide,and South Australian Health and Medical Research Institute,Adelaide,Australia,for their support.
文摘Haematopoietic microenvironmental niches have been described as the‘gatekeepers’for the blood and immune systems.These niches change during ontogeny,with the bone marrow becoming the predominant site of haematopoiesis in post-natal life under steady state conditions.To determine the structure and function of different haematopoietic microenvironmental niches,it is essential to clearly define specific haematopoietic stem and progenitor cell subsets during ontogeny and to understand their temporal appearance and anatomical positioning.A variety of haematopoietic and non-haematopoietic cells contribute to haematopoietic stem and progenitor cell niches.The latter is reported to include endothelial cells and mesenchymal stromal cells(MSCs),skeletal stem cells and/or C-X-C motif chemokine ligand 12-abundant-reticular cell populations,which form crucial components of these microenvironments under homeostatic conditions.Dysregulation or deterioration of such cells contributes to significant clinical disorders and diseases worldwide and is associated with the ageing process.A critical appraisal of these issues and of the roles of MSC/C-X-C motif chemokine ligand 12-abundant-reticular cells and the more recently identified skeletal stem cell subsets in bone marrow haematopoietic niche function under homeostatic conditions and during ageing will form the basis of this research review.In the context of haematopoiesis,clinical translation will deal with lessons learned from the vast experience garnered from the development and use of MSC therapies to treat graft versus host disease in the context of allogeneic haematopoietic transplants,the recent application of these MSC therapies to treating emerging and severe coronavirus disease 2019(COVID-19)infections,and,given that skeletal stem cell ageing is one proposed driver for haematopoietic ageing,the potential contributions of these stem cells to haematopoiesis in healthy bone marrow and the benefits and challenges of using this knowledge for rejuvenating the age-compromised bone marrow haematopoietic niches and restoring haematopoiesis.