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Article ; Online: Pediatric Respiratory Syncytial Virus Diagnostic Testing Performance: A Systematic Review and Meta-analysis.

Onwuchekwa, Chukwuemeka / Atwell, Jessica / Moreo, Laura Mora / Menon, Sonia / Machado, Belen / Siapka, Mariana / Agarwal, Neha / Rubbrecht, Michelle / Aponte-Torres, Zuleika / Rozenbaum, Mark / Curcio, Daniel / Nair, Harish / Kalina, Warren V / Vroling, Hilde / Gessner, Bradford / Begier, Elizabeth

The Journal of infectious diseases

2023 Volume 228, Issue 11, Page(s) 1516–1527

Abstract: Background: Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar ... ...

Abstract	Background: Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing. Methods: We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance. Results: We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%. Conclusions: RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.
MeSH term(s)	Adult ; Child ; Humans ; Respiratory Syncytial Virus Infections/diagnosis ; Sensitivity and Specificity ; Respiratory Syncytial Virus, Human/genetics ; Viruses ; Diagnostic Techniques and Procedures ; Nasopharynx ; Reverse Transcriptase Polymerase Chain Reaction
Language	English
Publishing date	2023-06-07
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad185
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Article ; Online: Underascertainment of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing Limitations: A Systematic Literature Review and Meta-analysis.

Onwuchekwa, Chukwuemeka / Moreo, Laura Mora / Menon, Sonia / Machado, Belen / Curcio, Daniel / Kalina, Warren / Atwell, Jessica E / Gessner, Bradford D / Siapka, Mariana / Agarwal, Neha / Rubbrecht, Michelle / Nair, Harish / Rozenbaum, Mark / Aponte-Torres, Zuleika / Vroling, Hilde / Begier, Elizabeth

The Journal of infectious diseases

2022 Volume 228, Issue 2, Page(s) 173–184

Abstract: Background: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen ... ...

Abstract	Background: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection. Methods: EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types. Results: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable. Conclusions: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.
MeSH term(s)	Adult ; Humans ; Respiratory Syncytial Virus Infections/diagnosis ; Sensitivity and Specificity ; Respiratory Syncytial Virus, Human/genetics ; Nasopharynx ; Diagnostic Techniques and Procedures ; Reverse Transcriptase Polymerase Chain Reaction
Language	English
Publishing date	2022-12-12
Publishing country	United States
Document type	Systematic Review ; Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad012
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Article: Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential.

Tasev, Dimitar / Dekker-Vroling, Laura / van Wijhe, Michiel / Broxterman, Henk J / Koolwijk, Pieter / van Hinsbergh, Victor W M

Frontiers in medicine

2018 Volume 5, Page(s) 356

Abstract: Vascular homeostasis and regeneration in ischemic tissue relies on intrinsic competence of the tissue to rapidly recruit endothelial cells for vascularization. The mononuclear cell (MNC) fraction of blood contains circulating progenitors committed to ... ...

Abstract	Vascular homeostasis and regeneration in ischemic tissue relies on intrinsic competence of the tissue to rapidly recruit endothelial cells for vascularization. The mononuclear cell (MNC) fraction of blood contains circulating progenitors committed to endothelial lineage. These progenitors give rise to endothelial colony-forming cells (ECFCs) that actively participate in neovascularization of ischemic tissue. To evaluate if the initial clonal outgrowth of ECFCs from cord (CB) and peripheral blood (PB) was stimulated by hypoxic conditions, MNCs obtained from CB and PB were subjected to 20 and 1% O
Language	English
Publishing date	2018-12-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2018.00356
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Article ; Online: Hypoxia Impairs Initial Outgrowth of Endothelial Colony Forming Cells and Reduces Their Proliferative and Sprouting Potential

Dimitar Tasev / Laura Dekker-Vroling / Michiel van Wijhe / Henk J. Broxterman / Pieter Koolwijk / Victor W. M. van Hinsbergh

Frontiers in Medicine, Vol

2018 Volume 5

Abstract	Vascular homeostasis and regeneration in ischemic tissue relies on intrinsic competence of the tissue to rapidly recruit endothelial cells for vascularization. The mononuclear cell (MNC) fraction of blood contains circulating progenitors committed to endothelial lineage. These progenitors give rise to endothelial colony-forming cells (ECFCs) that actively participate in neovascularization of ischemic tissue. To evaluate if the initial clonal outgrowth of ECFCs from cord (CB) and peripheral blood (PB) was stimulated by hypoxic conditions, MNCs obtained from CB and PB were subjected to 20 and 1% O2 cell culture conditions. Clonal outgrowth was followed during a 30 day incubation period. Hypoxia impaired the initial outgrowth of ECFC colonies from CB and also reduced their number that were developing from PB MNCs. Three days of oxygenation (20% O2) prior to hypoxia could overcome the initial CB-ECFC outgrowth. Once proliferating and subcultured the CB-ECFCs growth was only modestly affected by hypoxia; proliferation of PB-ECFCs was reduced to a similar extent (18–30% reduction). Early passages of subcultured CB- and PB-ECFCs contained only viable cells and few if any senescent cells. Tube formation by subcultured PB-ECFCs was also markedly inhibited by continuous exposure to 1% O2. Gene expression profiles point to regulation of the cell cycle and metabolism as major altered gene clusters. Finally we discuss our counterintuitive observations in the context of the important role that hypoxia has in promoting neovascularization.
Keywords	ECFCs ; hypoxia ; colony growth ; angiogenesis ; tissue repair ; proliferation ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: High frequency of the 3R/3R polymorphism in the thymidylate synthase enhancer region in Indonesian childhood acute lymphoblastic leukemia

IDG Ugrasena / Sutaryo Sutaryo / Edy Supriadi / Laura Vroling / Jacqueline Cloos / Jan Hendrik Hooijberg / AJP Veerman

Paediatrica Indonesiana, Vol 46, Iss 3, Pp 103-

2016 Volume 12

Abstract: Background Deoxyuridylate monophosphate (dTMP) is neces- sary for DNA synthesis and thymidylate synthase (TS) is an im- portant target of cancer chemotherapy. Ethnic variations of the polymorphic tandem repeat sequence in the enhancer region of the TS ... ...

Abstract	Background Deoxyuridylate monophosphate (dTMP) is neces- sary for DNA synthesis and thymidylate synthase (TS) is an im- portant target of cancer chemotherapy. Ethnic variations of the polymorphic tandem repeat sequence in the enhancer region of the TS promoter has previously been described to influence the outcome of acute lymphoblastic leukemia (ALL). A triple repeat is associated with a higher TS gene expression than a double re- peat, resulting in poorer outcome of ALL patients treated with anti- folate methotrexate (MTX). Objective In this study, we determined the incidences of TS and methylenetetrahydrofolate reductase (MTHFR) polymorphism and ethnic variations between Indonesian and Caucasian ALL cell samples obtained at diagnosis. Furthermore, we determined the involvement of TS polymorphisms in MTX sensitivity using a thymidilate synthase inhibition assay (TSIA). Methods ALL cell samples were obtained at diagnosis from 101 Indonesian and 157 Caucasian children treated with MTX prospec- tively. Genotyping for TS and MTHFR was analyzed by Genescan and Lightcycler. TS polymorphism was determined by PCR assay and MTHFR polymorphism and was analyzed by melting curve analyses on lightcycler. Results Homozygous TS triple repeats were more than twice as common in Indonesian samples (76.3%) than in Caucasian samples (33.1%). Heterozygotes of the MTHFR mutations were seen in 15% of the screened Indonesian samples. Conclusion There are significant ethnic variations in TS gene regulatory elements of leukemic cells. A difference was found be- tween the MTX sensitivity and a double or triple repeat in the Cau- casian ALL group. The samples with a triple repeat show a shift in their distribution towards hypersensitivity to MTX. Further investi- gation on Indonesian samples may give insight in the role of poly- morphisms in MTX sensitivity
Keywords	polymorphism ; acute lymphoblastic leukemia ; thymidilate synthase ; methotrexate ; children ; Medicine ; R ; Pediatrics ; RJ1-570
Subject code	616
Language	English
Publishing date	2016-10-01T00:00:00Z
Publisher	Indonesian Pediatric Society Publishing House
Document type	Article ; Online
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Article ; Online: Sunitinib-induced hemoglobin changes are related to the dosing schedule.

van der Veldt, Astrid A M / Boven, Epie / Vroling, Laura / Broxterman, Henk J / van den Eertwegh, Alfons J M / Haanen, John G

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2009 Volume 27, Issue 8, Page(s) 1339–40; author reply 1340–2

MeSH term(s)	Animals ; Antineoplastic Agents/adverse effects ; Drug Administration Schedule ; Hemoglobins/analysis ; Humans ; Indoles/administration & dosage ; Indoles/adverse effects ; Polycythemia/chemically induced ; Pyrroles/administration & dosage ; Pyrroles/adverse effects ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-2/physiology
Chemical Substances	Antineoplastic Agents ; Hemoglobins ; Indoles ; Pyrroles ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; sunitinib (V99T50803M)
Language	English
Publishing date	2009-03-10
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2008.20.6151
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Article ; Online: Sunitinib-induced changes in circulating endothelial cell-related proteins in patients with metastatic renal cell cancer.

van der Veldt, Astrid A M / Vroling, Laura / de Haas, Richard R / Koolwijk, Pieter / van den Eertwegh, Alfons J M / Haanen, John B A G / van Hinsbergh, Victor W M / Broxterman, Henk J / Boven, Epie

International journal of cancer

2012 Volume 131, Issue 4, Page(s) E484–93

Abstract: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors are effective agents in the treatment of metastatic renal cell cancer (mRCC). We here investigated whether inhibition of VEGFR signalin by sunitinib causes changes in plasma ... ...

Abstract	Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors are effective agents in the treatment of metastatic renal cell cancer (mRCC). We here investigated whether inhibition of VEGFR signalin by sunitinib causes changes in plasma proteins associated with tumor endothelium. Forty-three patients with mRCC received sunitinib 50 mg/day in a 4-weeks on 2-weeks off schedule. Sequential plasma samples were obtained before treatment (C1D1), on C1D14, on C1D28, and on C2D1 before start of cycle 2. Plasma levels were assessed for VEGF, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), von Willebrand factor (vWF), circulating angiopoietin-2 (Ang-2) and soluble Tie-2 (sTie-2). Total tumor burden was calculated at baseline and at first evaluation. Progression-free survival (PFS) and overall survival (OS) were determined. Tumor burden was positively associated with baseline circulating Ang-2 [Spearman's rho (ρ) = 0.378, p = 0.028] and vWF (ρ = 0.417, p = 0.008). During sunitinib treatment, circulating Ang-2 and sTie-2 significantly decreased (p < 0.001 for both), plasma levels of sVCAM-1 and VEGF significantly increased (p = 0.022 and p < 0.001), whereas those of sICAM-1 and vWF remained stable. These protein changes had recovered on C2D1. The reduction in circulating Ang-2 levels on C1D28 was positively correlated with the percentage decrease in tumor burden (ρ = 0.605; p = 0.002). Baseline protein levels and subsequent changes were not associated with PFS or OS. In conclusion, sunitinib-induced changes in Ang-2, sTie-2, sVCAM-1 and VEGF are related to the administration schedule, while reduction in Ang-2 is also associated with decrease in tumor burden.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Endothelium, Vascular/drug effects ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Indoles/pharmacology ; Indoles/therapeutic use ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Pyrroles/pharmacology ; Pyrroles/therapeutic use
Chemical Substances	Antineoplastic Agents ; Indoles ; Pyrroles ; sunitinib (V99T50803M)
Language	English
Publishing date	2012-08-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.26456
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia.

Giovannetti, Elisa / Ugrasena, Dewa G / Supriyadi, Eddy / Vroling, Laura / Azzarello, Antonino / de Lange, Desiree / Peters, Godefridus J / Veerman, Anjo J P / Cloos, Jacqueline

Leukemia research

2008 Volume 32, Issue 1, Page(s) 19–24

Abstract: Genetic variations in the polymorphic tandem repeat sequence of the enhancer region of the thymidylate synthase promoter (TSER), as well as in methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, influence methotrexate sensitivity. We studied ... ...

Abstract	Genetic variations in the polymorphic tandem repeat sequence of the enhancer region of the thymidylate synthase promoter (TSER), as well as in methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, influence methotrexate sensitivity. We studied these polymorphisms in children with acute lymphoblastic leukaemia (ALL) and in subjects without malignancy in Indonesia and Holland. The frequencies of TT and CT genotypes were two-fold higher in Dutch children. The TSER 3R/3R repeat was three-fold more frequent in the Indonesian children, while the 2R/2R repeat was only 1% compared to 21% in the Dutch children. No differences of these polymorphisms were found between ALL cells and normal blood cells, indicating an ethnic rather than leukemic origin. These results may have implications for treatment of Indonesian children with ALL.
MeSH term(s)	Adult ; Child ; Child, Preschool ; Drug Resistance, Neoplasm ; Ethnic Groups ; Female ; Genetic Predisposition to Disease ; Humans ; Indonesia ; Male ; Methotrexate/therapeutic use ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Netherlands ; Polymorphism, Genetic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/ethnology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Promoter Regions, Genetic ; Tandem Repeat Sequences ; Thymidylate Synthase/genetics
Chemical Substances	Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20) ; Thymidylate Synthase (EC 2.1.1.45) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2008-01
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752396-8
ISSN	1873-5835 ; 0145-2126
ISSN (online)	1873-5835
ISSN	0145-2126
DOI	10.1016/j.leukres.2007.02.011
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Article: VEGFR2 expressing circulating (progenitor) cell populations in volunteers and cancer patients.

Vroling, Laura / Yuana, Yuana / Schuurhuis, Gerrit Jan / van Hinsbergh, Victor W M / Gundy, Chad / de Haas, Richard / van Cruijsen, Hester / Boven, Epie / Hoekman, Klaas / Broxterman, Henk J

Thrombosis and haemostasis

2007 Volume 98, Issue 2, Page(s) 440–450

Abstract: Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumor-bearing mice have pointed to the potential importance of VEGF-responding circulating (endothelial) progenitor cells in tumor ... ...

Abstract	Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumor-bearing mice have pointed to the potential importance of VEGF-responding circulating (endothelial) progenitor cells in tumor growth. We have studied circulating CD31- and/or CD34-positive cell populations with a low to moderate VEGFR2 expression in human volunteers and cancer patients. We recognized four cell populations, which were further characterized by their content of major hematopoietic progenitor, monocytic, endothelial and platelet markers. After establishing the test-retest stability of the measurements in nine patients, we determined the frequencies of the various cell populations in a group of 20 volunteers and 14 cancer patients. Two populations were markedly increased in cancer patients. Small CD45(neg)/CD34(bright)/VEGFR2+ cells amounted to 12 and 64 cells/ml (P < 0.0001), respectively, and 246/ml and 578/ml VEGFR2+/CD45(bright) (/CD14+) monocytic cells were present in controls and cancer patients, respectively (P = 0.017). A third population of CD45(dim)/CD34(bright)/VEGFR2(low) cells amounted to 25 and 30 cells/ml (P = 0.38). Unexpectedly, a population of mainly anucleated CD45(low)/CD31(bright)/CD41(bright) cells was present in numbers of 9,076 and 16,697/ml (P = 0.04) in volunteers and cancer patients, which contained a VEGFR2(low) (compared to IgG isotype control) expressing population amounting to 1,142 and 1,642 cells/ml (P = 0.12). This fourth population probably reflects large platelets. The role of the herein identified VEGFR2+ circulating cell populations deserve further investigation in cancer patients treated with VEGF(R)-targeted therapies. Quantification of such cell populations in the blood of tumor patients may be valuable to monitor the efficacy of anti-angiogenic treatment.
MeSH term(s)	Antigens, CD34/analysis ; Blood Cells/cytology ; Blood Circulation ; Case-Control Studies ; Endothelial Cells/chemistry ; Endothelial Cells/cytology ; Flow Cytometry ; Humans ; Leukocyte Common Antigens/analysis ; Neoplasms/blood ; Stem Cells/chemistry ; Stem Cells/cytology ; Vascular Endothelial Growth Factor Receptor-2/analysis
Chemical Substances	Antigens, CD34 ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2007-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	518294-3
ISSN	0340-6245
ISSN	0340-6245
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Zs.MO 433: Show issues

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Article ; Online: Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib.

Vroling, Laura / van der Veldt, Astrid A M / de Haas, Richard R / Haanen, John B A G / Schuurhuis, Gerrit Jan / Kuik, Dirk J / van Cruijsen, Hester / Verheul, Henk M W / van den Eertwegh, Alfons J M / Hoekman, Klaas / Boven, Epie / van Hinsbergh, Victor W M / Broxterman, Henk J

Angiogenesis

2009 Volume 12, Issue 1, Page(s) 69–79

Abstract: Mature circulating endothelial cell (CEC) as well as endothelial progenitor populations may reflect the activity of anti-angiogenic agents on tumor neovasculature or even constitute a target for anti-angiogenic therapy. We investigated the behavior of ... ...

Abstract	Mature circulating endothelial cell (CEC) as well as endothelial progenitor populations may reflect the activity of anti-angiogenic agents on tumor neovasculature or even constitute a target for anti-angiogenic therapy. We investigated the behavior of CECs in parallel with hematopoietic progenitor cells (HPCs) in the blood of renal cell cancer patients during sunitinib treatment. We analyzed the kinetics of a specific population of small VEGFR2-expressing CECs (CD45(neg)/CD34(bright)), HPCs (CD45(dim)/CD34(bright)), and monocytes in the blood of 24 renal cell cancer (RCC) patients receiving 50 mg/day of the multitargeted VEGF inhibitor sunitinib, on a 4-week-on/2-week-off schedule. Blood was taken before treatment (C1D1), on C1D14, C1D28, and on C2D1 before the start of cycle 2. Also plasma VEGF and erythropoietin (EPO) were determined. Remarkably, while CD34(bright) HPCs and monocytes decreased during treatment, CD34(bright) CECs increased from 69 cells/ml (C1D1) to 180 cells/ml (C1D14; P = 0.001) and remained high on C1D28. All cell populations recovered to near pre-treatment levels on C2D1. Plasma VEGF and EPO levels were increased on C1D14 and partly normalized to pre-treatment levels on C2D1. In conclusion, opposite kinetics of two circulating CD34(bright) cell populations, HPCs and small CECs, were observed in sunitinib-treated RCC patients. The increase in CECs is likely caused by sunitinib targeting of immature tumor vessels.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antigens, CD34/metabolism ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/blood ; Blood Cell Count ; Carcinoma, Renal Cell/blood ; Carcinoma, Renal Cell/drug therapy ; Endothelial Cells/cytology ; Endothelial Cells/drug effects ; Erythropoietin/blood ; Female ; Flow Cytometry ; Hematopoietic Stem Cells/drug effects ; Humans ; Indoles/pharmacology ; Indoles/therapeutic use ; Kidney Neoplasms/blood ; Kidney Neoplasms/drug therapy ; Kinetics ; Male ; Middle Aged ; Pyrroles/pharmacology ; Pyrroles/therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Vascular Endothelial Growth Factor A/blood
Chemical Substances	Antigens, CD34 ; Antineoplastic Agents ; Biomarkers, Tumor ; Indoles ; Pyrroles ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Erythropoietin (11096-26-7) ; sunitinib (V99T50803M)
Language	English
Publishing date	2009
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1484717-6
ISSN	1573-7209 ; 0969-6970
ISSN (online)	1573-7209
ISSN	0969-6970
DOI	10.1007/s10456-009-9133-9
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