Subjects -> MEDICAL SCIENCES (Total: 8359 journals)
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MEDICAL SCIENCES (2268 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 3562 Journals sorted alphabetically
16 de Abril     Open Access   (Followers: 1)
3D Printing in Medicine     Open Access   (Followers: 4)
4 open     Open Access  
AADE in Practice     Hybrid Journal   (Followers: 6)
ABCS Health Sciences     Open Access   (Followers: 8)
Abia State University Medical Students' Association Journal     Full-text available via subscription   (Followers: 2)
AboutOpen     Open Access  
ACIMED     Open Access   (Followers: 1)
ACS Medicinal Chemistry Letters     Hybrid Journal   (Followers: 48)
Acta Bio Medica     Full-text available via subscription   (Followers: 2)
Acta Bioethica     Open Access  
Acta Bioquimica Clinica Latinoamericana     Open Access   (Followers: 1)
Acta Científica Estudiantil     Open Access  
Acta Facultatis Medicae Naissensis     Open Access   (Followers: 1)
Acta Herediana     Open Access  
Acta Informatica Medica     Open Access  
Acta Medica (Hradec Králové)     Open Access  
Acta Medica Bulgarica     Open Access  
Acta Medica Colombiana     Open Access   (Followers: 1)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Medica Indonesiana     Open Access  
Acta Medica International     Open Access  
Acta medica Lituanica     Open Access  
Acta Medica Marisiensis     Open Access  
Acta Medica Martiniana     Open Access  
Acta Medica Nagasakiensia     Open Access   (Followers: 1)
Acta Medica Peruana     Open Access   (Followers: 2)
Acta Médica Portuguesa     Open Access  
Acta Medica Saliniana     Open Access  
Acta Scientiarum. Health Sciences     Open Access   (Followers: 2)
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 6)
Acupuncture and Natural Medicine     Open Access  
Addiction Science & Clinical Practice     Open Access   (Followers: 8)
Addictive Behaviors Reports     Open Access   (Followers: 9)
Adıyaman Üniversitesi Sağlık Bilimleri Dergisi / Health Sciences Journal of Adıyaman University     Open Access   (Followers: 1)
Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi     Open Access   (Followers: 1)
Advanced Biomedical Research     Open Access  
Advanced Health Care Technologies     Open Access   (Followers: 8)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 8)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Advances in Bioscience and Clinical Medicine     Open Access   (Followers: 7)
Advances in Cell and Gene Therapy     Hybrid Journal   (Followers: 1)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26)
Advances in Life Course Research     Hybrid Journal   (Followers: 9)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Medical Education and Practice     Open Access   (Followers: 32)
Advances in Medical Ethics     Open Access   (Followers: 1)
Advances in Medical Research     Open Access   (Followers: 1)
Advances in Medical Sciences     Hybrid Journal   (Followers: 9)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Medicine     Open Access   (Followers: 3)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5)
Advances in Molecular Oncology     Open Access   (Followers: 2)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7)
Advances in Parkinson's Disease     Open Access  
Advances in Phytomedicine     Full-text available via subscription  
Advances in Preventive Medicine     Open Access   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Regenerative Medicine     Open Access   (Followers: 3)
Advances in Skeletal Muscle Function Assessment     Open Access  
Advances in Therapy     Hybrid Journal   (Followers: 5)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 6)
Advances in Wound Care     Hybrid Journal   (Followers: 12)
Aerospace Medicine and Human Performance     Full-text available via subscription   (Followers: 13)
African Health Sciences     Open Access   (Followers: 3)
African Journal of Biomedical Research     Open Access   (Followers: 1)
African Journal of Clinical and Experimental Microbiology     Open Access   (Followers: 4)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
African Journal of Medical and Health Sciences     Open Access   (Followers: 3)
African Journal of Thoracic and Critical Care Medicine     Open Access  
African Journal of Trauma     Open Access   (Followers: 1)
Afrimedic Journal     Open Access   (Followers: 2)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 9)
AJOB Empirical Bioethics     Hybrid Journal   (Followers: 3)
AJSP: Reviews & Reports     Hybrid Journal  
Aktuelle Ernährungsmedizin     Hybrid Journal   (Followers: 4)
Al-Azhar Assiut Medical Journal     Open Access   (Followers: 2)
ALERTA : Revista Científica del Instituto Nacional de Salud     Open Access  
Alexandria Journal of Medicine     Open Access   (Followers: 1)
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 3)
Alpha Omegan     Full-text available via subscription  
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 2)
Althea Medical Journal     Open Access   (Followers: 2)
American Journal of Biomedical Engineering     Open Access   (Followers: 15)
American Journal of Biomedical Research     Open Access   (Followers: 2)
American Journal of Biomedicine     Full-text available via subscription   (Followers: 7)
American Journal of Chinese Medicine, The     Hybrid Journal   (Followers: 4)
American Journal of Clinical Medicine Research     Open Access   (Followers: 8)
American Journal of Family Therapy     Hybrid Journal   (Followers: 10)
American Journal of Law & Medicine     Full-text available via subscription   (Followers: 11)
American Journal of Lifestyle Medicine     Hybrid Journal   (Followers: 5)
American Journal of Managed Care     Full-text available via subscription   (Followers: 12)
American Journal of Medical Case Reports     Open Access   (Followers: 1)
American Journal of Medical Sciences and Medicine     Open Access   (Followers: 4)
American Journal of Medicine     Hybrid Journal   (Followers: 50)
American Journal of Medicine and Medical Sciences     Open Access   (Followers: 1)
American Journal of Medicine Studies     Open Access   (Followers: 2)
American Journal of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American Journal of the Medical Sciences     Hybrid Journal   (Followers: 12)
American Journal on Addictions     Hybrid Journal   (Followers: 10)
American medical news     Free   (Followers: 3)
American Medical Writers Association Journal     Full-text available via subscription   (Followers: 6)
Amyloid: The Journal of Protein Folding Disorders     Hybrid Journal   (Followers: 5)
Anales de la Facultad de Medicina     Open Access  
Anales de la Facultad de Medicina, Universidad de la República, Uruguay     Open Access  
Anales del Sistema Sanitario de Navarra     Open Access   (Followers: 1)
Analgesia & Resuscitation : Current Research     Hybrid Journal   (Followers: 6)
Anatolian Clinic the Journal of Medical Sciences     Open Access  
Anatomica Medical Journal     Open Access  
Anatomical Science International     Hybrid Journal   (Followers: 3)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1)
Anatomy     Open Access   (Followers: 2)
Anatomy Research International     Open Access   (Followers: 3)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3)
Ankara Medical Journal     Open Access   (Followers: 2)
Ankara Üniversitesi Tıp Fakültesi Mecmuası     Open Access  
Annales de Pathologie     Full-text available via subscription  
Annales des Sciences de la Santé     Open Access  
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annals of African Medicine     Open Access   (Followers: 2)
Annals of Anatomy - Anatomischer Anzeiger     Hybrid Journal   (Followers: 3)
Annals of Bioanthropology     Open Access   (Followers: 5)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 19)
Annals of Biomedical Sciences     Full-text available via subscription   (Followers: 4)
Annals of Clinical Hypertension     Open Access  
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 14)
Annals of Family Medicine     Open Access   (Followers: 14)
Annals of Health Research     Open Access   (Followers: 1)
Annals of Ibadan Postgraduate Medicine     Open Access  
Annals of Medical and Health Sciences Research     Open Access   (Followers: 7)
Annals of Medicine     Hybrid Journal   (Followers: 12)
Annals of Medicine and Surgery     Open Access   (Followers: 7)
Annals of Microbiology     Hybrid Journal   (Followers: 13)
Annals of Nigerian Medicine     Open Access   (Followers: 1)
Annals of Rehabilitation Medicine     Open Access  
Annals of Saudi Medicine     Open Access  
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5)
Annals of The Royal College of Surgeons of England     Full-text available via subscription   (Followers: 3)
Annual Reports in Medicinal Chemistry     Full-text available via subscription   (Followers: 7)
Annual Reports on NMR Spectroscopy     Full-text available via subscription   (Followers: 5)
Annual Review of Medicine     Full-text available via subscription   (Followers: 17)
Anthropological Review     Open Access   (Followers: 24)
Anthropologie et santé     Open Access   (Followers: 5)
Antibiotics     Open Access   (Followers: 9)
Antibodies     Open Access   (Followers: 2)
Antibody Technology Journal     Open Access   (Followers: 1)
Antibody Therapeutics     Open Access  
Anuradhapura Medical Journal     Open Access  
Anwer Khan Modern Medical College Journal     Open Access   (Followers: 2)
Apmis     Hybrid Journal   (Followers: 1)
Apparence(s)     Open Access   (Followers: 1)
Applied Clinical Informatics     Hybrid Journal   (Followers: 4)
Applied Clinical Research, Clinical Trials and Regulatory Affairs     Hybrid Journal   (Followers: 2)
Applied Medical Informatics     Open Access   (Followers: 13)
Arab Journal of Nephrology and Transplantation     Open Access   (Followers: 1)
Archive of Clinical Medicine     Open Access   (Followers: 1)
Archive of Community Health     Open Access   (Followers: 1)
Archives Medical Review Journal / Arşiv Kaynak Tarama Dergisi     Open Access  
Archives of Asthma, Allergy and Immunology     Open Access  
Archives of Medical and Biomedical Research     Open Access   (Followers: 3)
Archives of Medical Laboratory Sciences     Open Access   (Followers: 1)
Archives of Medicine and Health Sciences     Open Access   (Followers: 4)
Archives of Medicine and Surgery     Open Access  
Archives of Trauma Research     Open Access   (Followers: 3)
Archivos de Medicina (Manizales)     Open Access  
ArgoSpine News & Journal     Hybrid Journal  
Arquivos Brasileiros de Oftalmologia     Open Access   (Followers: 1)
Arquivos de Ciências da Saúde     Open Access  
Arquivos de Medicina     Open Access  
Ars Medica : Revista de Ciencias Médicas     Open Access  
ARS Medica Tomitana     Open Access   (Followers: 1)
Art Therapy: Journal of the American Art Therapy Association     Hybrid Journal   (Followers: 17)
Arterial Hypertension     Open Access   (Followers: 1)
Artificial Intelligence in Medicine     Hybrid Journal   (Followers: 18)
Artificial Organs     Hybrid Journal   (Followers: 1)
ASHA Leader     Open Access  
Asia Pacific Family Medicine Journal     Open Access   (Followers: 1)
Asia Pacific Journal of Clinical Nutrition     Full-text available via subscription   (Followers: 12)
Asia Pacific Journal of Clinical Trials : Nervous System Diseases     Open Access  
Asian Bioethics Review     Full-text available via subscription   (Followers: 3)
Asian Biomedicine     Open Access   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 6)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 4)
Asian Journal of Medical and Pharmaceutical Researches     Open Access   (Followers: 2)
Asian Journal of Medical Sciences     Open Access   (Followers: 2)
Asian Journal of Medicine and Health     Open Access   (Followers: 1)
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access   (Followers: 1)
Asian Journal of Scientific Research     Open Access   (Followers: 3)
Asian Journal of Transfusion Science     Open Access   (Followers: 1)
Asian Medicine     Hybrid Journal   (Followers: 5)
Asian Pacific Journal of Cancer Prevention     Open Access  
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
Atención Familiar     Open Access  
Atención Primaria     Open Access   (Followers: 1)
Atti della Accademia Peloritana dei Pericolanti - Classe di Scienze Medico-Biologiche     Open Access  

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Similar Journals
Journal Cover
Journal Prestige (SJR): 2.177
Citation Impact (citeScore): 5
Number of Followers: 3  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1573-7209 - ISSN (Online) 0969-6970
Published by Springer-Verlag Homepage  [2570 journals]
  • Targeting endothelial thioredoxin-interacting protein (TXNIP) protects
           from metabolic disorder-related impairment of vascular function and
           post-ischemic revascularisation
    • Abstract: Introduction Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biological functions, the contribution of endothelial TXNIP has not been well-defined in regards to endothelial and vascular function or in post-ischemic revascularisation. We postulated that inhibition of endothelial TXNIP with siRNA or in a Cre-LoxP system could be involved in protection from high fat, high protein, low carbohydrate (HFHPLC) diet-induced oxidative stress and endothelial dysfunction, leading to vascular damage and impaired revascularisation in vivo. Methods and results To investigate the role of endothelial TXNIP, the TXNIP gene was deleted in endothelial cells using anti-TXNIP siRNA treatment or the Cre-LoxP system. Murine models were fed a HFHPLC diet, known to induce metabolic disorders. Endothelial TXNIP targeting resulted in protection against metabolic disorder-related endothelial oxidative stress and endothelial dysfunction. This protective effect mitigates media cell loss induced by metabolic disorders and hampered metabolic disorder-related vascular dysfunction assessed by aortic reactivity and distensibility. In aortic ring cultures, metabolic disorders impaired vessel sprouting and this alteration was alleviated by deletion of endothelial TXNIP. When subjected to ischemia, mice fed a HFHPLC diet exhibited defective post-ischemic angiogenesis and impaired blood flow recovery in hind limb ischemia. However, reducing endothelial TXNIP rescued metabolic disorder-related impairment of ischemia-induced revascularisation. Conclusion Collectively, these results show that targeting endothelial TXNIP in metabolic disorders is essential to maintaining endothelial function, vascular function and improving ischemia-induced revascularisation, making TXNIP a potential therapeutic target for therapy of vascular complications related to metabolic disorders.
      PubDate: 2020-01-03
  • Continuous endoglin (CD105) overexpression disrupts angiogenesis and
           facilitates tumor cell metastasis
    • Abstract: Abstract Endoglin (CD105) is an auxiliary receptor for members of the TFG-β superfamily. Whereas it has been demonstrated that the deficiency of endoglin leads to minor and defective angiogenesis, little is known about the effect of its increased expression, characteristic of several types of cancer. Angiogenesis is essential for tumor growth, so high levels of proangiogenic molecules, such as endoglin, are supposed to be related to greater tumor growth leading to a poor cancer prognosis. However, we demonstrate here that endoglin overexpression do not stimulate sprouting or vascularization in several in vitro and in vivo models. Instead, steady endoglin overexpression keep endothelial cells in an active phenotype that results in an impairment of the correct stabilization of the endothelium and the recruitment of mural cells. In a context of continuous enhanced angiogenesis, such as in tumors, endoglin overexpression gives rise to altered vessels with an incomplete mural coverage that permit the extravasation of blood. Moreover, these alterations allow the intravasation of tumor cells, the subsequent development of metastases and, thus, a worse cancer prognosis.
      PubDate: 2020-01-03
  • Impaired vascular endothelial growth factor expression and secretion
           during in vitro differentiation of human primary term cytotrophoblasts
    • Abstract: Abstract Vascular endothelial growth factor A (VEGF-A) is one of the main growth factors involved in placental vasculogenesis and angiogenesis, but its placental expression is still ambiguous. During in vitro cultures of primary term cytotrophoblasts, VEGF could not be detected in the supernatants by enzyme-linked immunosorbent assays (ELISA). One hypothesis is that VEGF is immediately and completely bound to its soluble receptor after secretion, and cannot be recognized by the antibodies used in the commercial ELISA kits. We decided to verify this hypothesis by measuring VEGF-A expression during in vitro cultures of primary term cytotrophoblasts. Term cytotrophoblasts were cultured under 21% and 2.5% O2 for 4 days. VEGF-A transcripts were quantified by real-time polymerase chain reaction. The proteins from cell lysates and concentrated media were separated by polyacrylamide gel electrophoresis (PAGE) under denaturing and reducing conditions, and VEGF-A immunodetected by western blotting. VEGF mRNA expression did not increase during in vitro cell differentiation under 21% O2, but slightly increased under 2.5% O2 only at 24 h. VEGF-A monomer was not detected in the cell lysates and in the concentrated supernatants, while a ~ 42 KDa band corresponding to the precursor L-VEGF was detected in all the cellular extracts. Isolated term villous cytotrophoblasts produce the L-VEGF precursor but they do not secrete VEGF-A even under low-oxygen tension. The question remains about the origin of VEGF in pregnancy but also about the biological role of L-VEGF, which can represent a form of storage for rapid VEGF secretion when needed.
      PubDate: 2020-01-01
  • Vessel co-option and resistance to anti-angiogenic therapy
    • Abstract: Abstract Vessel co-option is a non-angiogenic mechanism of tumour vascularisation in which cancer cells utilise pre-existing blood vessels instead of inducing new blood vessel formation. Vessel co-option has been observed across a range of different tumour types, in both primary cancers and metastatic disease. Importantly, vessel co-option is now implicated as a major mechanism that mediates resistance to conventional anti-angiogenic drugs and this may help to explain the limited efficacy of this therapeutic approach in certain clinical settings. This includes the use of anti-angiogenic drugs to treat advanced-stage/metastatic disease, treatment in the adjuvant setting and the treatment of primary disease. In this article, we review the available evidence linking vessel co-option with resistance to anti-angiogenic therapy in numerous tumour types, including breast, colorectal, lung and pancreatic cancer, glioblastoma, melanoma, hepatocellular carcinoma, and renal cell carcinoma. The finding that vessel co-option is a significant mechanism of resistance to anti-angiogenic therapy may have important implications for the future of anti-cancer therapy, including (a) predicting response to anti-angiogenic drugs, (b) the need to develop therapies that target both angiogenesis and vessel co-option in tumours, and (c) predicting the response to other therapeutic modalities, including immunotherapy.
      PubDate: 2019-12-21
  • Role of VEGFs in metabolic disorders
    • Abstract: Abstract Obesity and metabolic disorders are important public health problems. In this review, the role of vasculature network and VEGF in the adipose tissue maintenance and supplementation is discussed. Angiogenesis is a key process implicated in regulation of tissues homeostasis. Dysregulation of new blood vessels formation may be crucial and contribute to the onset of several pathological conditions, including metabolic syndrome-associated disorders. Adipose tissue homeostasis is fine regulated by vascular network. Vessels support adipose structure. Vasculature modulates the balance between positive and negative regulator factors. In white adipose tissue, vascular endothelial growth factor (VEGF) controls the metabolic activities of adipocytes promoting the trans-differentiation from white to beige phenotype. Trans-differentiation results in an increase of energy consumption. VEGF exerts an opposite effect on brown adipose tissue, where VEGF increases oxygen supply and improves energy expenditure inducing the whitening of adipocytes.
      PubDate: 2019-12-18
  • BMP10-mediated ALK1 signaling is continuously required for vascular
           development and maintenance
    • Abstract: Abstract Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder characterized by development of high-flow arteriovenous malformations (AVMs) that can lead to stroke or high-output heart failure. HHT2 is caused by heterozygous mutations in ACVRL1, which encodes an endothelial cell bone morphogenetic protein (BMP) receptor, ALK1. BMP9 and BMP10 are established ALK1 ligands. However, the unique and overlapping roles of these ligands remain poorly understood. To define the physiologically relevant ALK1 ligand(s) required for vascular development and maintenance, we generated zebrafish harboring mutations in bmp9 and duplicate BMP10 paralogs, bmp10 and bmp10-like. bmp9 mutants survive to adulthood with no overt phenotype. In contrast, combined loss of bmp10 and bmp10-like results in embryonic lethal cranial AVMs indistinguishable from acvrl1 mutants. However, despite embryonic functional redundancy of bmp10 and bmp10-like, bmp10 encodes the only required Alk1 ligand in the juvenile-to-adult period. bmp10 mutants exhibit blood vessel abnormalities in anterior skin and liver, heart dysmorphology, and premature death, and vascular defects correlate with increased cardiac output. Together, our findings support a unique role for Bmp10 as a non-redundant Alk1 ligand required to maintain the post-embryonic vasculature and establish zebrafish bmp10 mutants as a model for AVM-associated high-output heart failure, which is an increasingly recognized complication of severe liver involvement in HHT2.
      PubDate: 2019-12-11
  • Introduction to special issue: vascular co-option in cancer
    • PubDate: 2019-12-04
  • Prognostic value of CEC count in HER2-negative metastatic breast cancer
           patients treated with bevacizumab and chemotherapy: a prospective
           validation study (UCBG COMET)
    • Abstract: Background Proof of concept studies has reported that circulating endothelial cell (CEC) count may be associated with the outcome of HER2-negative metastatic breast cancer (mBC) patients treated by chemotherapy and the anti-VEGF antibody bevacizumab. We report the results obtained in an independent prospective validation cohort (COMET study, NCT01745757). Methods The main baseline criteria were HER2-negative mBC, performance status 0–2 and no prior chemotherapy for metastatic disease. CECs were detected by CellSearch® from 4 ml of blood at baseline and after 4 weeks of weekly paclitaxel and bevacizumab therapy. CEC counts (considered both as a continuous variable and using the previously described 20 CEC/4 ml cutoff) were associated with clinical characteristics and progression-free survival (PFS). Results CEC count was obtained in 251 patients at baseline and in 207 patients at 4 weeks. Median baseline CEC count was 22 CEC/4 ml (range 0–2231). Baseline CEC counts were associated with performance status (p = 0.02). No statistically significant change in CEC counts was observed between baseline and 4 weeks of therapy. High baseline CEC count was associated with shorter PFS in univariate and multivariate analyses (continuous: p < 0.001; dichotomized: HR 1.52, 95% CI [1.15–2.02], p = 0.004). CEC counts at 4 weeks had no prognostic impact. Conclusion This study confirms that CEC count may be associated with the outcome of mBC patients treated with chemotherapy and bevacizumab. However, discrepancies with previous reports in terms of both the timing of CEC count and the direction of the prognostic impact warrant further clinical investigation.
      PubDate: 2019-11-26
  • The potassium channel Kcne3 is a VEGFA-inducible gene selectively
           expressed by vascular endothelial tip cells
    • Abstract: Abstract Angiogenesis is largely driven by motile endothelial tip-cells capable of invading avascular tissue domains and enabling new vessel formation. Highly responsive to Vascular Endothelial Growth-Factor-A (VEGFA), endothelial tip-cells also suppress angiogenic sprouting in adjacent stalk cells, and thus have been a primary therapeutic focus in addressing neovascular pathologies. Surprisingly, however, there remains a paucity of specific endothelial tip-cell markers. Here, we employ transcriptional profiling and a lacZ reporter allele to identify Kcne3 as an early and selective endothelial tip-cell marker in multiple angiogenic contexts. In development, Kcne3 expression initiates during early phases of angiogenesis (E9) and remains specific to endothelial tip-cells, often adjacent to regions expressing VEGFA. Consistently, Kcne3 activation is highly responsive to exogenous VEGFA but maintains tip-cell specificity throughout normal retinal angiogenesis. We also demonstrate endothelial tip-cell selectivity of Kcne3 in several injury and tumor models. Together, our data show that Kcne3 is a unique marker of sprouting angiogenic tip-cells and offers new opportunities for investigating and targeting this cell type.
      PubDate: 2019-11-21
  • Angiotropism, pericytic mimicry and extravascular migratory metastasis: an
           embryogenesis-derived program of tumor spread
    • Abstract: Abstract Intravascular dissemination of tumor cells is the accepted mechanism of cancer metastasis. However, the phenomenon of angiotropism, pericyte mimicry (PM), and extravascular migratory metastasis (EVMM) has questioned the concept that tumor cells metastasize exclusively via circulation within vascular channels. This new paradigm of cancer spread and metastasis suggests that metastatic cells employ embryonic mechanisms for attachment to the abluminal surfaces of blood vessels (angiotropism) and spread via continuous migration, competing with and replacing pericytes, i.e., pericyte mimicry (PM). This is an entirely extravascular phenomenon (i.e., extravascular migratory metastasis or EVMM) without entry (intravasation) into vascular channels. PM and EVMM have mainly been studied in melanoma but also occur in other cancer types. PM and EVMM appear to be a reversion to an embryogenesis-derived program. There are many analogies between embryogenesis and cancer progression, including the important role of laminins, epithelial–mesenchymal transition, and the re-activation of embryonic signals by cancer cells. Furthermore, there is no circulation of blood during the first trimester of embryogenesis, despite the fact that there is extensive migration of cells to distant sites and formation of organs and tissues during this period. Embryonic migration therefore is a continuous extravascular migration as are PM and EVMM, supporting the concept that these embryonic migratory events appear to recur abnormally during the metastatic process. Finally, the perivascular location of tumor cells intrinsically links PM to vascular co-option. Taken together, these two new paradigms may greatly influence the development of new effective therapeutics for metastasis. In particular, targeting embryonic factors linked to migration that are detected during cancer metastasis may be particularly relevant to PM/EVMM.
      PubDate: 2019-11-12
  • Reconciling the distinct roles of angiogenic/anti-angiogenic factors in
           the placenta and maternal circulation of normal and pathological
    • Abstract: Abstract A branched vascular network is crucial to placental development and is dependent on factors such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) to regulate blood vessel growth. Imbalances in these factors can lead to aberrant placental vascular development. Throughout pregnancy, these factors are also released into the maternal circulation to aid in adapting the maternal cardiovascular system to pregnancy. Increased secretion of anti-angiogenic factors can lead to the development of an anti-angiogenic state in the mother and contribute to the development of pregnancy pathologies such as pre-eclampsia and foetal growth restriction (FGR). Thus, what are commonly referred to as ‘angiogenic factors’ have distinct functions in the maternal and placental circulations making this a misnomer. Indeed, technical issues in this field such as assay methodology and lack of data considering different placental cell types mean that the physiological roles of these factors in the maternal and placental circulations are frequently muddled in the literature. This review aims to (1) unpick the distinct roles of factors that influence placental vascular development and separate these from the roles of the same factors within the maternal circulation in normal pregnancy and (2) critically assess how imbalances may contribute to the distinct pathophysiological mechanisms underlying pregnancy disorders. Together, this critical assessment of the field endeavours to improve our ability to accurately use these factors as predictive/diagnostic biomarkers in the future.
      PubDate: 2019-11-09
  • Vascular co-option in brain metastasis
    • Abstract: Abstract Vascular co-option by brain metastasis-initiating cells has been demonstrated as a critical step in organ colonization. The physical interaction between the cancer cell and the endothelial cell is mediated by integrins and L1CAM and could be involved in aggressive growth but also latency and immune evasion. The key involvement of vascular co-option in brain metastasis has created an emerging field that aims to identify critical targets as well as effective inhibitors with the goal of preventing brain metastases.
      PubDate: 2019-11-07
  • Vessel co-option in glioblastoma: emerging insights and opportunities
    • Abstract: Abstract Vessel co-option is the movement of cancer cells towards and along the pre-existing vasculature and is an alternative to angiogenesis to gain access to nutrients. Vessel co-option has been shown as a strategy employed by some glioblastoma (GBM) cells to invade further into the brain, leading to one of the greatest challenges in treating GBM. In GBM, vessel co-option may be an intrinsic feature or an acquired mechanism of resistance to anti-angiogenic treatment. Here, we describe the histological features and the dynamics visualized through intravital microscopy of vessel co-option in GBM, as well as the molecular players discovered until now. We also highlight key unanswered questions, as answering these is critical to improve understanding of GBM progression and for developing more effective approaches for GBM treatment.
      PubDate: 2019-11-02
  • Successful therapy with bevacizumab combined with corticosteroids for
           crizotinib-induced interstitial lung disease
    • Abstract: Abstract We present the case of an old woman with ALK-rearranged stage IV lung adenocarcinoma who received crizotinib. She presented with severe dyspnea on the 34th day, and diffuse ground-glass opacifications in her chest. A diagnosis of crizotinib-induced ILD was confirmed. Corticosteroids were administered. However, the disease was still progressing rapidly. Therefore, as a monoclonal antibody against vascular endothelial growth factor, bevacizumab was administered in low doses (200 mg on days one and three). Her symptoms began to improve. Our clinical experience indicates that bevacizumab combined with corticosteroids might be a promising treatment in crizotinib-induced ILD patients.
      PubDate: 2019-11-01
  • The role of receptor MAS in microglia-driven retinal vascular development
    • Abstract: Objective The receptor MAS, encoded by Mas1, is expressed in microglia and its activation has been linked to anti-inflammatory actions. However, microglia are involved in several different processes in the central nervous system, including the promotion of angiogenesis. We therefore hypothesized that the receptor MAS also plays a role in angiogenesis via microglia. Approach and results To assess the role of MAS on vascular network development, flat-mounted retinas from 3-day-old wild-type (WT) and Mas1−/− mice were subjected to Isolectin B4 staining. The progression of the vascular front was reduced (− 24%, p < 0.0001) and vascular density decreased (− 38%, p < 0.001) in Mas1−/− compared to WT mice with no change in the junction density. The number of filopodia and filopodia bursts were decreased in Mas1−/− mice at the vascular front (− 21%, p < 0.05; − 29%, p < 0.0001, respectively). This was associated with a decreased number of vascular loops and decreased microglial density at the vascular front in Mas1−/− mice (-32%, p < 0.001; − 26%, p < 0.05, respectively). As the front of the developing vasculature is characterized by reduced oxygen levels, we determined the expression of Mas1 following hypoxia in primary microglia from 3-day-old WT mice. Hypoxia induced a 14-fold increase of Mas1 mRNA expression (p < 0.01). Moreover, stimulation of primary microglia with a MAS agonist induced expression of Notch1 (+ 57%, p < 0.05), Dll4 (+ 220%, p  < 0.001) and Jag1 (+ 137%, p < 0.001), genes previously described to mediate microglia/endothelial cell interaction during angiogenesis. Conclusions Our study demonstrates that the activation of MAS is important for microglia recruitment and vascular growth in the developing retina.
      PubDate: 2019-11-01
  • VEGFR2 activation mediates the pro-angiogenic activity of BMP4
    • Abstract: Abstract The Bone Morphogenetic Protein 4 (BMP4) regulates multiple biological processes, including vascular development and angiogenesis. Here, we investigated the role of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in mediating the angiogenic activity of BMP4. BMP4 induces a rapid relocation and phosphorylation of VEGFR2 on the endothelial cell membrane. These effects occur in the absence of a direct interaction of BMP4 and/or BMP receptors with VEGFR2. At variance, BMP4, by interacting with the BMPRI-II hetero-complex, induces c-Src phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic response. Accordingly, the BMPR inhibitor dorsomorphin prevents c-Src activation and specific inhibition of c-Src significantly reduces downstream VEGFR2 phosphorylation and the angiogenic activity exerted by BMP4 in a chick embryo chorioallantoic membrane assay. Together, our data indicate that the pro-angiogenic activity exerted by BMP4 in endothelial cells is mediated by a BMPR-mediated intracellular transactivation of VEGFR2 via c-Src.
      PubDate: 2019-11-01
  • Adgrf5 contributes to patterning of the endothelial deep layer in retina
    • Abstract: Abstract Neovascularization of the inner retinal space is a major cause of vision loss. In retinal angiomatous proliferation (RAP) syndrome, newly formed vessels originate from the retinal plexus and invade the inner retinal space. However, the molecular pathways preventing subretinal vascularization remain largely unknown. In most murine models of RAP, pathological neovascularization occurs concomitantly with the development of the retinal vasculature. Here, we demonstrate that disturbing the sequence of morphogenetic events that shape the three-layered retinal vascular network leads to subretinal vascularization. Sprouts emerging from the perivenous region after the first postnatal week extended toward the retinal space where they merged into the deep layer. The small GTPase Rac1 was required for the formation of these vascular extensions and the vascular inner plexus is formed coaxially to the overarching veins. The adhesion receptor Adgrf5 was highly expressed in the endothelium of the central nervous system, where it regulates blood–brain barrier formation. The vascular superficial plexus of Adgrf5 mutant mouse retinae exhibited an increased vascular density in the perivenous areas with increased projections toward the inner plexus where they subsequently created hyper-dense endothelial cells (EC) clusters. Disturbing the perivenous pool of EC thus significantly altered the inner plexus formation. These abnormalities culminated in transient vascular protrusions in the inner retinal space. Taken together, these results reveal a previously unobserved vascular morphogenetic defect in Adgrf5 knockout mice, implicating a role for ADGRF5 in the initiation of subretinal vascularization. Our findings also illustrate how vein-derived EC shape the inner retinal layer formation and could control the appearance of angiomatous malformations.
      PubDate: 2019-11-01
  • Oxygen sensing decoded: a Nobel concept in biology
    • Abstract: Abstract Oxygen is essential to most organisms as it is a necessity for aerobic metabolism and energy production. Too much or too little oxygen can be deadly, such that mechanisms for fast and titrated response to changing oxygen levels are crucial. These mechanisms have evolved from the studies of Gregg L. Semenza, William G. Kaelin and Peter J. Ratcliffe. It is through the work of their three laboratories, performed in the 1990s, that the cellular oxygen sensing mechanisms have been decoded. Their discoveries have had major impact for innovation in medicine, especially in the field of angiogenesis research, where oxygen sensing and its consequences have led to enhanced insight in vascular development and strategies for combating angiogenic diseases. On October 7, the Nobel Assembly in Stockholm announced at the Karolinska Institute that the Nobel Prize for Medicine 2019 is jointly awarded to these three scientists for their seminal discoveries on how cells sense and respond to oxygen.
      PubDate: 2019-10-31
  • The tumor vasculature an attractive CAR T cell target in solid tumors
    • Abstract: Abstract T cells armed with a chimeric antigen receptor, CAR T cells, have shown extraordinary activity against certain B lymphocyte malignancies, when targeted towards the CD19 B cell surface marker. These results have led to the regulatory approval of two CAR T cell approaches. Translation of this result to the solid tumor setting has been problematic until now. A number of differences between liquid and solid tumors are likely to cause this discrepancy. The main ones of these are undoubtedly the uncomplicated availability of the target cell within the blood compartment and the abundant expression of the target molecule on the cancerous cells in the case of hematological malignancies. Targets expressed by solid tumor cells are hard to engage due to the non-adhesive and abnormal vasculature, while conditions in the tumor microenvironment can be extremely immunosuppressive. Targets in the tumor vasculature are readily reachable by CAR T cells and reside outside the immunosuppressive tumor microenvironment. It is therefore hypothesized that targeting CAR T cells towards the tumor vasculature of solid tumors may share the excellent effects of CAR T cell therapy with that against hematological malignancies. A few reports have shown promising results. Suggestions are provided for further improvement.
      PubDate: 2019-10-18
  • Highlights of the 13th International Hereditary Hemorrhagic Telangiectasia
           Scientific conference
    • PubDate: 2019-10-12
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762

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