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Article ; Online: The ontogeny of endothelial progenitor cells through flow cytometry.

Mund, Julie A / Case, Jamie

2011 Volume 18, Issue 3, Page(s) 166–170

Abstract: Purpose of review: Since the discovery of endothelial progenitor cells (EPCs), there have been conflicting reports as to the precise phenotypic identity, and thus an accurate description of the function of these cells in disease pathology is lacking. ... ...

Abstract	Purpose of review: Since the discovery of endothelial progenitor cells (EPCs), there have been conflicting reports as to the precise phenotypic identity, and thus an accurate description of the function of these cells in disease pathology is lacking. This review will detail the protocols that have been published within 2010 to help decipher the true identity of the various cells that have been reported as EPCs in numerous clinical trials. Recent findings: Throughout 2010, three protocols have been published alleging to identify EPCs, yet only one provides a true nonhematopoietic origin for a cell that is classified as an EPC. In addition to the protocols published to try to establish a consensus definition, 10 studies involving EPCs across disease pathologies were published with various degrees of correlation to disease phenotype and cellular level. Summary: A true phenotypic definition of a circulating EPC capable of becoming an endothelial colony forming cell with proliferative potential has been given. It is now time the EPC field drops this ambiguous term (i.e. EPCs), as many studies purporting to measure EPCs are in fact still quantifying cells of a hematopoietic origin. It is necessary for cross study comparisons that a uniform phenotypic definition be adhered to when using the term EPC.
MeSH term(s)	Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Flow Cytometry ; Humans ; Phenotype
Language	English
Publishing date	2011-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0b013e328345a16a
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Article ; Online: Weight loss achieved using an energy restriction diet with normal or higher dietary protein decreased the number of CD14

Kim, Jung Eun / Lin, Ge / Zhou, Jing / Mund, Julie A / Case, Jamie / Campbell, Wayne W

Nutrition research (New York, N.Y.)

2017 Volume 40, Page(s) 75–84

Abstract: Monocytes are involved in immune responses, and specific monocyte subpopulations (MS) that express intermediate to high levels of CD16 are associated with obesity and cardiovascular events. Consuming high protein (HP) when dieting improves body ... ...

Abstract	Monocytes are involved in immune responses, and specific monocyte subpopulations (MS) that express intermediate to high levels of CD16 are associated with obesity and cardiovascular events. Consuming high protein (HP) when dieting improves body composition and cardiometabolic health outcomes, but whether HP affects MS during weight loss remains unknown. We assessed the effect of HP on energy restriction (ER)-induced changes in MS in overweight and obese adults. The relations between MS and plasma lipids and lipoproteins were also examined. We hypothesized that, independent of protein intake, ER-induced weight loss would decrease the numbers of MS and that MS and plasma lipids and lipoproteins would be related. Thirty-two adults (age 52 ± 1 years, body mass index 31.3 ± 0.5 kg/m
Language	English
Publishing date	2017-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	582432-1
ISSN	1879-0739 ; 0271-5317
ISSN (online)	1879-0739
ISSN	0271-5317
DOI	10.1016/j.nutres.2017.02.007
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Article ; Online: The role of circulating endothelial progenitor cells in tumor angiogenesis.

Mund, Julie A / Case, Jamie

Current stem cell research & therapy

2009 Volume 6, Issue 2, Page(s) 115–121

Abstract: There is great controversy over the origin and definition of murine endothelial progenitor cells (EPCs). EPCs are reportedly important for the repair and remodeling of the vasculature and are implicated in tumor angiogenesis. Many conflicting reports ... ...

Abstract	There is great controversy over the origin and definition of murine endothelial progenitor cells (EPCs). EPCs are reportedly important for the repair and remodeling of the vasculature and are implicated in tumor angiogenesis. Many conflicting reports exist as to whether these EPCs arise from the bone marrow hematopoietic compartment or whether they are non-hematopoietic in origin, and these differences could be attributed to the wide variance in assays used to identify the cells and time points at which the data are collected. Recently, circulating murine EPCs have been characterized as CD45(-)CD13(+)CD117(+)FLK-1(+) expressing cells via flow cytometry and this phenotype varies from prior descriptions. This review will focus on the changing phenotypic definition of murine circulating EPCs and the evidence that has been published in support of the lineage of origin of circulating EPCs and the role EPCs play in tumor angiogenesis in the adult mouse.
MeSH term(s)	Adult ; Animals ; Endothelium, Vascular/pathology ; Humans ; Mice ; Neoplasms/blood supply ; Neoplasms/pathology ; Neovascularization, Pathologic/pathology ; Stem Cells/pathology
Language	English
Publishing date	2009-12-10
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2251937-3
ISSN	2212-3946 ; 1574-888X
ISSN (online)	2212-3946
ISSN	1574-888X
DOI	10.2174/157488811795495468
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Article ; Online: In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG), and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing dogs.

Reese, Michael J / Knapp, Deborah W / Anderson, Kimberly M / Mund, Julie A / Case, Jamie / Jones, David R / Packer, Rebecca A

PloS one

2018 Volume 13, Issue 9, Page(s) e0203517

Abstract: The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 ...

Abstract	The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma cell lines, human microvascular endothelial cells (HMVECs) and human endothelial colony forming cells (ECFCs). Results were analyzed in the context of chlorambucil concentrations measured in the plasma of tumor-bearing dogs receiving 4 mg m-2 metronomic chlorambucil. The LD50 and IC50 of chlorambucil were 270 μM and 114 μM for SF767, and 390 μM and 96 μM for U87-MG, respectively. The IC50 of chlorambucil was 0.53 μM and 145 μM for the HMVECs and ECFCs, respectively. In pharmacokinetic studies, the mean plasma Cmax of chlorambucil was 0.06 μM. Results suggest that metronomic chlorambucil in dogs does not achieve plasma concentrations high enough to cause direct cytotoxic or growth inhibitory effects on either glioma or endothelial cells.
MeSH term(s)	Animals ; Antineoplastic Agents, Alkylating/blood ; Antineoplastic Agents, Alkylating/pharmacokinetics ; Antineoplastic Agents, Alkylating/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cells, Cultured ; Chlorambucil/blood ; Chlorambucil/pharmacokinetics ; Chlorambucil/pharmacology ; Dogs ; Dose-Response Relationship, Drug ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Endothelial Progenitor Cells/cytology ; Endothelial Progenitor Cells/drug effects ; Glioma/blood ; Glioma/blood supply ; Glioma/metabolism ; Humans ; Metabolic Clearance Rate
Chemical Substances	Antineoplastic Agents, Alkylating ; Chlorambucil (18D0SL7309)
Language	English
Publishing date	2018-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0203517
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Article ; Online: Brief report: Endothelial colony-forming cells and inflammatory monocytes in HIV.

Hays, Travis R / Mund, Julie A / Liu, Ziyue / Case, Jamie / Ingram, David A / Gupta, Samir K

Journal of acquired immune deficiency syndromes (1999)

2015 Volume 68, Issue 5, Page(s) 550–553

Abstract: The relationships between HIV infection, monocyte activation, and endothelial colony-forming cells (ECFCs) are unknown. We compared ECFC, intermediate monocytes (CD14 CD16), and nonclassical monocytes (CD14 CD16) levels in HIV-infected participants ... ...

Abstract	The relationships between HIV infection, monocyte activation, and endothelial colony-forming cells (ECFCs) are unknown. We compared ECFC, intermediate monocytes (CD14 CD16), and nonclassical monocytes (CD14 CD16) levels in HIV-infected participants virologically suppressed on antiretroviral therapy, HIV-infected treatment-naive participants, and HIV-uninfected healthy controls. ECFC levels were significantly higher in the HIV-infected virologically suppressed group compared with the uninfected controls. CD14 CD16 percentages (but not CD14 CD16 cells) were significantly higher in both HIV-infected groups vs. uninfected controls. In the HIV-infected groups, ECFCs and CD14 CD16 intermediate monocytes were significantly and inversely correlated. Lower availability of ECFCs may partly explain the relationship between greater intermediate monocytes and atherosclerosis in HIV.
MeSH term(s)	Adult ; Cell Count ; Cross-Sectional Studies ; Endothelial Progenitor Cells/physiology ; Female ; HIV Infections/immunology ; HIV Infections/pathology ; Humans ; Male ; Middle Aged ; Monocytes/immunology ; Prospective Studies ; Young Adult
Language	English
Publishing date	2015-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000000506
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Zs.A 2442: Show issues

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Article: Peripheral blood biomarkers of solid tumor angiogenesis in dogs: A polychromatic flow cytometry pilot study

Bentley, R. Timothy / Mund, Julie A / Pollok, Karen E / Childress, Michael O / Case, Jamie

The Veterinary Journal. 2013 May, v. 196, no. 2

2013

Abstract: A subset of peripheral blood hematopoietic stem and progenitor cells of bone marrow origin is elevated in humans with solid cancers before treatment and declines with therapy. This biomarker of angiogenesis is not specific to tumor type and has great ... ...

Abstract	A subset of peripheral blood hematopoietic stem and progenitor cells of bone marrow origin is elevated in humans with solid cancers before treatment and declines with therapy. This biomarker of angiogenesis is not specific to tumor type and has great potential in the objective assessment of treatment response in clinical trials. This pilot study was designed to develop a biomarker of neoangiogenesis in dogs for the diagnosis of cancer, the measurement of treatment response, and the provision of objective data in clinical trials. Polychromatic flow cytometry was used to quantify two subsets of circulating hematopoietic stem and progenitor cells in dogs with spontaneous solid tumors before (n=8) and after (n=3) treatment, and normal controls (n=6). Pro-angiogenic peripheral blood cells of bone marrow origin were detected in all eight cases and the six normal controls; however, there was no statistically significant difference between the two groups. Interestingly, an apparent decline in pro-angiogenic cells was observed after treatment. Bone marrow derived hematopoietic cells appear to contribute to tumor angiogenesis in dogs, as has been previously reported in humans. While the methodology for pro-angiogenic cell quantification in a small number of dogs in the current study did not result in a significant difference from normal controls, an optimized canine polychromatic flow cytometry protocol holds great promise in the development of a canine cancer model and for the objective measurements of treatment response in clinical trials.
Keywords	angiogenesis ; biomarkers ; blood cells ; bone marrow ; bone marrow cells ; clinical trials ; dogs ; flow cytometry ; humans ; models ; neoplasms ; stem cells ; therapeutics
Language	English
Dates of publication	2013-05
Size	p. 236-240.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	428614-5
ISSN	1532-2971 ; 0372-5545 ; 1090-0233
ISSN (online)	1532-2971
ISSN	0372-5545 ; 1090-0233
DOI	10.1016/j.tvjl.2012.09.002
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Article ; Online: Correction: Genetic disruption of the small GTPase RAC1 prevents plexiform neurofibroma formation in mice with neurofibromatosis type 17.

Mund, Julie A / Park, SuJung / Smith, Abbi E / He, Yongzheng / Jiang, Li / Hawley, Eric / Roberson, Michelle J / Mitchell, Dana K / Abu-Sultanah, Mohannad / Yuan, Jin / Bessler, Waylan K / Sandusky, George / Chen, Shi / Zhang, Chi / Rhodes, Steven D / Clapp, D Wade

The Journal of biological chemistry

2020 Volume 295, Issue 46, Page(s) 15795

Language	English
Publishing date	2020-11-10
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.AAC120.016426
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Article ; Online: Genetic disruption of the small GTPase RAC1 prevents plexiform neurofibroma formation in mice with neurofibromatosis type 1

The Journal of biological chemistry

2020 Volume 295, Issue 29, Page(s) 9948–9958

Abstract: Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome caused by mutations in ... ...

Abstract	Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome caused by mutations in the
MeSH term(s)	Animals ; Gene Knockdown Techniques ; Mice ; Mice, Knockout ; Neoplasms, Second Primary/enzymology ; Neoplasms, Second Primary/genetics ; Neoplasms, Second Primary/pathology ; Neoplasms, Second Primary/prevention & control ; Neurofibroma, Plexiform/enzymology ; Neurofibroma, Plexiform/genetics ; Neurofibroma, Plexiform/prevention & control ; Neurofibromatosis 1/enzymology ; Neurofibromatosis 1/genetics ; Neurofibromatosis 1/pathology ; Neurofibromin 1/deficiency ; Neurofibromin 1/metabolism ; Neuropeptides/deficiency ; Neuropeptides/metabolism ; Proto-Oncogene Mas ; rac1 GTP-Binding Protein/deficiency ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	MAS1 protein, human ; Neurofibromin 1 ; Neuropeptides ; Proto-Oncogene Mas ; Rac1 protein, mouse ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2020-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.010981
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Article ; Online: Identification of endothelial cells and progenitor cell subsets in human peripheral blood.

Estes, Myka L / Mund, Julie A / Ingram, David A / Case, Jamie

Current protocols in cytometry

2010 Volume Chapter 9, Page(s) Unit 9.33.1–11

Abstract: An assay for circulating cell subsets in human peripheral blood by flow cytometry is used as a biomarker to determine cardiovascular disease risk and tumor responsiveness to chemotherapy since endothelial progenitor cells (EPCs) function in ... ...

Abstract	An assay for circulating cell subsets in human peripheral blood by flow cytometry is used as a biomarker to determine cardiovascular disease risk and tumor responsiveness to chemotherapy since endothelial progenitor cells (EPCs) function in vasculogenesis and angiogenesis. Despite analytical advances in polychromatic flow cytometry (PFC), conventional approaches are routinely utilized to enumerate and isolate EPCs, which has led to varied results in clinical studies, potential cellular misidentification, and thus a lack of a plausible biological explanation for how purported EPCs function. Herein, a reproducible PFC protocol is provided to identify a rare circulating endothelial colony-forming cell (ECFC) with proliferative potential, along with a population of circulating progenitor cells (CPCs) in which the ratio analysis distinguishes between healthy and disease populations. In sum, a reliable PFC protocol, which can be used to investigate the roles of human hematopoietic and endothelial elements in the growth and maintenance of the vasculature, is described.
MeSH term(s)	Cell Proliferation ; Cell Separation ; Endothelial Cells/cytology ; Flow Cytometry/methods ; Hematopoietic Stem Cells/cytology ; Humans ; Leukocytes, Mononuclear/cytology ; Neovascularization, Pathologic ; Software ; Stem Cells/cytology
Language	English
Publishing date	2010-04
Publishing country	United States
Document type	Journal Article
ISSN	1934-9300
ISSN (online)	1934-9300
DOI	10.1002/0471142956.cy0933s52
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Article ; Online: Impaired compensation to femoral artery ligation in diet-induced obese mice is primarily mediated via suppression of collateral growth by Nox2 and p47phox.

DiStasi, Matthew R / Mund, Julie A / Bohlen, H Glenn / Miller, Steven J / Ingram, David A / Dalsing, Michael C / Unthank, Joseph L

American journal of physiology. Heart and circulatory physiology

2015 Volume 309, Issue 7, Page(s) H1207–17

Abstract: The present study was undertaken to establish the role of NADPH oxidase (Nox) in impaired vascular compensation to arterial occlusion that occurs in the presence of risk factors associated with oxidative stress. Diet-induced obese (DIO) mice ... ...

Abstract	The present study was undertaken to establish the role of NADPH oxidase (Nox) in impaired vascular compensation to arterial occlusion that occurs in the presence of risk factors associated with oxidative stress. Diet-induced obese (DIO) mice characterized by multiple comorbidities including diabetes and hyperlipidemia were used as a preclinical model. Arterial occlusion was induced by distal femoral artery ligation in lean and DIO mice. Proximal collateral arteries were identified as the site of major (∼70%) vascular resistance to calf perfusion by distal arterial pressures, which decreased from ∼80 to ∼30 mmHg with ligation in both lean and DIO mice. Two weeks after ligation, significant vascular compensation occurred in lean but not DIO mice as evidenced by increased perfusion (147 ± 48% vs. 49 ± 29%) and collateral diameter (151 ± 30% vs. 44 ± 17%). Vascular mRNA expression of p22(phox), Nox2, Nox4, and p47(phox) were all increased in DIO mice. Treatment of DIO mice with either apocynin or Nox2ds-tat or with whole body ablation of either Nox2 or p47(phox) ameliorated the impairment in both collateral growth and hindlimb perfusion. Multiparametric flow cytometry analysis demonstrated elevated levels of circulating monocytes in DIO mice without impaired mobilization and demargination after femoral artery ligation. These results establish collateral resistance as the major limitation to calf perfusion in this preclinical model, demonstrate than monocyte mobilization and demarginatin is not suppressed, implicate Nox2-p47(phox) interactions in the impairment of vascular compensation to arterial occlusion in DIO mice, and suggest that selective Nox component suppression/inhibition may be effective as either primary or adjuvant therapy for claudicants.
MeSH term(s)	Acetophenones/pharmacology ; Adaptation, Physiological ; Animals ; Antioxidants/pharmacology ; Collateral Circulation ; Cytochrome b Group/genetics ; Cytochrome b Group/metabolism ; Femoral Artery/surgery ; Hindlimb/blood supply ; Ligation ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Mice ; NADPH Oxidase 2 ; NADPH Oxidase 4 ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; Neovascularization, Physiologic ; Obesity/metabolism ; Oxidative Stress ; RNA, Messenger/metabolism
Chemical Substances	Acetophenones ; Antioxidants ; Cytochrome b Group ; Membrane Glycoproteins ; RNA, Messenger ; acetovanillone (B6J7B9UDTR) ; Cybb protein, mouse (EC 1.6.3.-) ; NADPH Oxidase 2 (EC 1.6.3.-) ; NADPH Oxidase 4 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-) ; Nox4 protein, mouse (EC 1.6.3.-) ; Cyba protein, mouse (EC 1.6.3.1) ; neutrophil cytosolic factor 1 (EC 1.6.3.1)
Language	English
Publishing date	2015-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00180.2015
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