TAMI-10. CIRCULATING ANGIOGENIC CELLS (CACS) IN GLIOBLASTOMA: TOWARDS DEFINING CRUCIAL FUNCTIONAL DIFFERENCES IN CAC-INDUCED NEOPLASTIC VERSUS REACTIVE NEOVASCULARIZATION

Abstract In order to identify suitable therapeutic targets for glioma anti-angiogenic therapy, the process of neovascularization mediated by circulating angiogenic cells (CACs) needs to be scrutinized. In the present study we compared the expression of neovascularization-related genes by three circulating CAC subsets (HPCs, CD34+ and KDR+ cells; internal controls: PBMCs and circulating endothelial cells) of treatment-naïve patients with glioblastoma (GBM) to those of patients undergoing reactive neovascularization (myocardial infarction (MI). CACs from umbilical cord (representing developmental neovascularization) and healthy subjects served as controls. Fluorescent activated cell sorting was used to isolate CACs, RT-PCR to determine the expression levels of a panel of 48 neovascularization-related genes, Luminex assays to measure plasma levels of 21 CAC-related circulating molecules. We found essential differences in gene expression between GBM and MI CACs. GBM CACs had a higher expression of pro-angiogenic factors (esp. KITL, CXCL12 and JAG1); growth factor and chemotactic receptors (IGF1R, TGFbR2, CXCR4 and CCR2); adhesion receptor monomers (ITGA5 and ITGA6) and matricellular factor POSTN. In addition, we found major differences in the levels of neovascularization-related plasma factors. A strong positive correlation between plasma MMP9 levels and expression of CXCR4 in the CAC subset of hematopoietic progenitor cells (HPCs) was found in GBM patients. Our findings indicate that CAC-mediated neovascularization in GBM is characterized by more efficient CAC homing to target tissue and a more potent pro-angiogenic response than in physiologic tissue repair in MI. Our findings can aid in selecting targets for therapeutic strategies acting against GBM-specific CACs.

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Circulating angiogenic cells in glioblastoma: toward defining crucial functional differences in CAC-induced neoplastic versus reactive neovascularization

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa040 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Karin Huizer ◽

Andrea Sacchetti ◽

Sigrid Swagemakers ◽

Peter J van der Spek ◽

Wim Dik ◽

...

Keyword(s):

Mononuclear Cells ◽

Internal Controls ◽

Circulating Endothelial Cells ◽

Target Tissue ◽

Strong Positive Correlation ◽

Peripheral Blood Mononuclear ◽

Circulating Angiogenic Cells ◽

Angiogenic Therapy ◽

Treatment Naïve ◽

Plasma Factors

Abstract Background In order to identify suitable therapeutic targets for glioma anti-angiogenic therapy, the process of neovascularization mediated by circulating angiogenic cells (CACs) needs to be scrutinized. Methods In the present study, we compared the expression of neovascularization-related genes by 3 circulating CAC subsets (hematopoietic progenitor cells [HPCs], CD34+, and KDR+ cells; internal controls: peripheral blood mononuclear cells and circulating endothelial cells) of treatment-naïve patients with glioblastoma (GBM) to those of patients undergoing reactive neovascularization (myocardial infarction (MI). CACs from umbilical cord (representing developmental neovascularization) and healthy subjects served as controls. Fluorescent-activated cell sorting was used to isolate CACs, RT-PCR to determine the expression levels of a panel of 48 neovascularization-related genes, and Luminex assays to measure plasma levels of 21 CAC-related circulating molecules. Results We found essential differences in gene expression between GBM and MI CACs. GBM CACs had a higher expression of proangiogenic factors (especially, KITL, CXCL12, and JAG1), growth factor and chemotactic receptors (IGF1R, TGFBR2, CXCR4, and CCR2), adhesion receptor monomers (ITGA5 and ITGA6), and matricellular factor POSTN. In addition, we found major differences in the levels of neovascularization-related plasma factors. A strong positive correlation between plasma MMP9 levels and expression of CXCR4 in the CAC subset of HPCs was found in GBM patients. Conclusions Our findings indicate that CAC-mediated neovascularization in GBM is characterized by more efficient CAC homing to target tissue and a more potent proangiogenic response than in physiologic tissue repair in MI. Our findings can aid in selecting targets for therapeutic strategies acting against GBM-specific CACs.

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Quantitative real time RT-PCR study of pathogen-induced gene expression in rock bream (Oplegnathus fasciatus): Internal controls for data normalization

Marine Genomics ◽

10.1016/j.margen.2014.03.001 ◽

2014 ◽

Vol 15 ◽

pp. 75-84 ◽

Cited By ~ 10

Author(s):

Bao-cun Zhang ◽

Li Sun ◽

Zhi-zhong Xiao ◽

Yong-hua Hu

Keyword(s):

Gene Expression ◽

Real Time ◽

Internal Controls ◽

Data Normalization ◽

Rt Pcr ◽

Oplegnathus Fasciatus ◽

Rock Bream

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P11.11 Circulating Pro-Angiogenic Cells and Proteins in Patients with Glioma and Acute Myocardial Infarction: Differences in Neovascularization between Neoplasia and Tissue Regeneration

Neuro-Oncology ◽

10.1093/neuonc/noz126.157 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii44-iii44

Author(s):

K Huizer ◽

A Sacchetti ◽

W Dik ◽

J M Kros ◽

D Mustafa

Keyword(s):

Myocardial Infarction ◽

Tissue Regeneration ◽

Peripheral Circulation ◽

Myocardial Infarctions ◽

Luminex Assay ◽

Angiogenic Therapy ◽

Secreted Factors ◽

Cell Fractions ◽

Plasma Factors ◽

The Brain

Abstract BACKGROUND Although extensive angiogenesis takes place in glial tumors, anti-angiogenic therapies have remained without the expected success. In the peripheral circulation of glioma patients increased numbers of endothelial precursor cells (EPCs) are present, potentially offering targets for anti-angiogenic therapy (Zheng et al., Ann Neurol, 2007). However, for an anti-angiogenic therapy to be successful, the therapy should specifically target glioma-related EPC subsets and secreted factors. Here we compared the EPC subsets and plasma factors in the peripheral circulation of patients with gliomas to acute myocardial infarctions (representing fysiologic regeneration). MATERIAL AND METHODS We investigated the five most important EPC subsets and 21 angiogenesis-related plasma factors in peripheral blood samples of 29 patients with glioma, 14 patients with myocardial infarction and 20 healthy people as controls, by an advanced FACS protocol (Huizer et al., PlosOne 2018) and Luminex assay. RESULTS In GBM patients all EPC subsets were elevated as compared to healthy subjects. In addition, HPC and KDR+ cell fractions were higher than in MI, while CD133+ and KDR+CD133+ cell fractions were lower. There were differences in relative EPC fractions between the groups: KDR+ cells were the largest fraction in GBM while CD133+ cells were the largest fraction in MI. An increase in glioma malignancy grade coincided with an increase in the KDR+ fraction while the CD133+ cell fraction decreased relatively. Most plasma angiogenic factors were higher in GBM than MI patients. In both MI and GBM, the ratio of CD133+ HPCs correlated significantly with elevated levels of MMP9. In the GBM patients MMP9 correlated strongly with levels of all HPCs. CONCLUSION In conclusion, the data demonstrate that EPC traffic in patients with glioma is different from that in normal tissue regeneration. Therefore, the effects of glioma extent beyond the brain, and future therapies aimed at lowering KDR+ cells and HPCs may add to effective treatment.

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1117 DETECTION OF MINORITY HBV RESISTANT STRAINS IN HBV TREATMENT NAIVE PATIENTS USING A HIGHLY SENSITIVE ASSAY BASED ON ARMS RT-PCR WITH MOLECULAR BEACON

Journal of Hepatology ◽

10.1016/s0168-8278(11)61119-7 ◽

2011 ◽

Vol 54 ◽

pp. S442

Author(s):

F. Ntziora ◽

D. Paraskevis ◽

G. Papatheodoridis ◽

E. Manesis ◽

S. Manolakopoulos ◽

...

Keyword(s):

Molecular Beacon ◽

Sensitive Assay ◽

Rt Pcr ◽

Highly Sensitive ◽

Treatment Naïve ◽

Resistant Strains

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Real-time RT-PCR of CD146 and VE-cadherin mRNA to detect circulating endothelial cells in peripheral blood of patients with breast cancer

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(06)80292-2 ◽

2006 ◽

Vol 4 (2) ◽

pp. 126

Author(s):

I. Van der Auwera ◽

Elst ◽

V. Huygelen ◽

S. Van Laere ◽

G. Van den Eynden ◽

...

Keyword(s):

Breast Cancer ◽

Endothelial Cells ◽

Real Time ◽

Peripheral Blood ◽

Circulating Endothelial Cells ◽

Rt Pcr

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Preserved Respiratory and Phagocytic Functions of Phagocytes Exposed to Flat Sheet Plasmapheresis Equipment

The International Journal of Artificial Organs ◽

10.1177/039139888701000508 ◽

1987 ◽

Vol 10 (5) ◽

pp. 307-314 ◽

Cited By ~ 2

Author(s):

T.W. Jungi ◽

B. Aeschbacher ◽

U.E. Nydegger

Keyword(s):

Respiratory Burst ◽

Polymorphonuclear Leukocytes ◽

Phagocytic Function ◽

Igg Antibodies ◽

Functional Integrity ◽

Functional Differences ◽

Flat Sheet ◽

Artificial Surfaces ◽

Functional Modulation ◽

Plasma Factors

Monocytes and polymorphonuclear leukocytes (PMN) were tested for functional integrity after exposure to flat sheet plasmapheresis equipment. Purified PMN were tested for chemiluminescence activity in response to a variety of triggers of the respiratory burst. Monocytes were assessed for their capacity to ingest erythrocytes sensitized with varying amounts of IgG antibodies. Both assays were demonstrated to be sensitive hallmarks of functional modulation. However, no functional differences were noted between phagocytes from blood collected prior to pheresis and those exposed to flat sheet plasmapheresis cylinders. These data suggest that plasmapheresis with the Au-topheresis C system does not influence the respiratory and phagocytic function of phagocytes returned back to the donor and implies that contact of phagocytes with artificial surfaces and/or their exposure to surface-activated plasma factors generated in the collection cylinder are minimal when using this plasmapheresis method.

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Orexin Receptors Are Expressed in the Adrenal Medulla of the Rat

Endocrinology ◽

10.1210/endo.140.12.7287 ◽

1999 ◽

Vol 140 (12) ◽

pp. 5991-5994 ◽

Cited By ~ 59

Author(s):

M. López ◽

R. Señaris ◽

R. Gallego ◽

T. García-Caballero ◽

F. Lago ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Adrenal Medulla ◽

Autonomous Nervous System ◽

Target Tissue ◽

Rt Pcr ◽

Morphological Studies ◽

Orexin Receptors ◽

G Protein Coupled ◽

Sleep Control

Abstract Two recently discovered hypothalamic peptides, orexin-A and orexin-B, play a role as mediators in the central mechanisms that regulate feeding behavior and sleep control. These peptides bind and activate two orexin receptors that belong to the G-protein coupled receptor superfamily. Morphological studies have detected mRNA expression of orexin receptors exclusively in the rat central nervous system. In this paper we demonstrate a strong level of expression of orexin receptor 1 and 2 in the adrenal medulla of the rat by RT-PCR immunohistochemistry. The results of the present study provide the first evidence showing that the adrenal medulla expresses orexin receptors, and thus appears to be a target tissue for orexins. This could open a new loop in which the central and autonomous nervous system may be involved in body weight homeostasis and sleep control.

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