Circulating endothelial progenitor cells correlate to stage in patients with invasive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 616-616
Author(s):  
R. Naik ◽  
D. Jin ◽  
E. Chuang ◽  
E. Gold ◽  
E. Tousimis ◽  
...  

616 Background: Tumor growth and metastasis is dependent on neo-angiogenesis. Both pre-existing and circulating vascular cells have been shown to contribute to the assembly of tumor neo-vessels in specific tumors. Mobilization of endothelial progenitor cells (EPCs) from the bone marrow constitutes a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be increased in certain malignant states. However, the role of circulating EPCs in breast cancer is largely unknown. Methods: We recruited twenty-five patients with biopsy-proven invasive breast cancer (BC) at Weill Cornell Breast Center to participate in a pilot study investigating the correlation of circulating EPCs to extent of disease and initiation of chemotherapy. For each patient, a baseline sample was drawn before systemic treatment, and for seventeen of those patients, a second sample was taken after the first round of chemotherapy. Levels of peripheral blood EPCs, as defined by co-expression of CD133 and VEGFR2, were quantified by flow cytometry. Results: BC patients with stage III & IV disease had statistically higher levels of circulating EPCs than did patients with stage I & II disease (median=165,000 EPCs/5×106MNCs vs. median=6,920 EPCs/5x106MNCs, respectively, p < 0.0001 by Wilcoxon rank-sum test). In addition, in late-stage patients, levels of EPCs demonstrated a statistically significant drop after initiation of chemotherapy (median=162,500 EPCs/5x106MNCs [pre] vs. median=117,500 EPCs/5x106MNCs [post], p = 0.01 by Wilcoxon signed-rank test). Conclusion: These results suggest that circulating EPCs may serve as a potential tumor biomarker in breast cancer and that EPCs may represent a plausible target for future therapeutic intervention. Supported in part by the Mentored Medical Student in Clinical Research Program (General Clinical Research Center/National Institutes of Health Grant M01RR00047), Madeline & Stephen Anbinder Clinical Scholar Award, and Anne Moore Breast Cancer Research Fund No significant financial relationships to disclose.

2010 ◽  
Vol 93 (1) ◽  
pp. 123-125 ◽  
Author(s):  
Takashi Kimura ◽  
Hirao Kohno ◽  
Yoshikazu Matsuoka ◽  
Ryusuke Nakatsuka ◽  
Yutaka Sasaki ◽  
...  

2003 ◽  
Vol 198 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Hyun Kyung Kim ◽  
Kyung Soon Song ◽  
Hyun Ok Kim ◽  
Jun-Ho Chung ◽  
Kyoung Rhan Lee ◽  
...  

Author(s):  
T. Bulduk ◽  
A. U. Yalcin ◽  
O. M. Akay ◽  
S. G. Ozkurt ◽  
H. U. Teke ◽  
...  

Anemia is a common complication of chronic kidney disease (CKD). The most common cause of anemia in CKD is erythropoietin deficiency; and the most important cause of mortality in CKD patients is atherosclerotic vascular complications which are associated with endothelial damage. One of the methods evaluating vascular integrity is the cytometric measurement of circulating endothelial cells and endothelial progenitor cells in peripheral blood. The study aimed to investigate the effects of erythropoietin therapy on endothelial dysfunction by evaluating circulating endothelial cells and endothelial progenitor cells in peripheral blood using the technique of flow cytometry. Methods. A total of 55 hemodialysis patients were evaluated in three groups; those having erythropoietin therapy for at least last 3 months (n = 20) / not having erythropoietin for at least the last 3 months (n = 20) and the patients who started erythropoietin treatment during the study (n = 5). The control group consisted of 20 people. Blood values of the 3rd Group were investigated three times as baseline, 2nd week and 8th week CD34 +, CD105 + cells were evaluated as activated circulating endothelial cells; CD133 +, CD146 + cells were evaluated as activated endothelial progenitor cells. Results. There was no difference between the patients and healthy individuals in terms of circulating endothelial cells and endothelial progenitor cells. In the third group, no differences were observed in circulating endothelial cells / endothelial progenitor cell levels at baseline / 2nd and 8th weeks. There was no correlation between erythropoietin and circulating endothelial cells / endothelial progenitor cells. Conclusion. A correlation is not available between the therapeutic doses of erythropoietin used in hemodialysis patients and circulating endothelial cells / endothelial progenitor cell levels; supratherapeutic doses could change the results.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
H Duckers ◽  
Yoshinobu Onuma ◽  
Edouard Benit ◽  
Robert J de Winter ◽  
William Wijns ◽  
...  

Background: In contrast to a cytotoxic or cytostatic pharmacotherapy, promoting the vascular healing response by capturing and sequestering circulating endothelial progenitor cells (EPC) to the stent surface by a CD34 antibody coating (Genous ™ stent) may accelerate stent reendo-thelialization and prevent restenosis formation, as well as stent thrombosis (ST) Methods: The HEALING IIB study was a multi-center, prospective trial designed to assess the safety and efficacy of the Genous ™ bio-engineered stent in conjunction with HmG CoA reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions (n=100 pts). The primary safety endpoint was major adverse cardiac events (MACE) at 30 days, whereas the primary efficacy endpoint was late luminal loss by QCA at 6 months follow-up. Results: At interim analysis of the first 45 patients that completed the 6-month angiographic follow-up, the composite MACE rate was 11.1%, whereas 6.6% clinically justified target lesion revascularizations were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified stent thrombosis. Low circulating EPC titers were previously associated with a poor response to the EPC capture stent with TLR events and high late loss. Therefore, patients were pre-treated with Atorvastatin 80 mg qd prior to the PCI in order to augment EPC levels. Statin therapy stimulated the levels of committed EPCs by +294%, but failed to increase the titer of CD34+cells (+25%). Although statin pretreatment stimulated EPC levels, the angiographic outcome of the EPC capture stent was not improved in these patients: in-stent late luminal loss was 0.77±0.46 mm. We anticipate to complete analysis of the 6 month angiographic follow-up of all 100 patients by the time of the AHA2008. Conclusions: The HEALING-IIB study suggests that the EPC capture coronary stent in combination with statin therapy does not sufficiently impede stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it failed to stimulate CD34+ stem cell levels and did not improve the angiographic outcome of the bioengineered EPC capture stent.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Martina Knoedler ◽  
Eliane Weidl ◽  
Sandra Gawehn ◽  
Maren Schurmann ◽  
Andreas Stein ◽  
...  

Background: Recent studies suggest that endothelial progenitor cells (EPC) from bone marrow or peripheral blood improve myocardial function in experimental myocardial infarction (MI). Since applications for cell therapy are limited by the number of available cells, expansion of EPC may facilitate its therapeutic use in ischemic disease. The aim of this study was to expand late outgrowth EPC from peripheral blood from patients with acute myocardial infarction, characterize them and investigate their therapeutic effect in experimental MI. Methods and Results: Venous blood samples were obtained from patients with acute MI (n=51), stable angina (sAP, n=57) and healthy controls (H,n=47). CD34+ cells were isolated using immunomagnetic beads (Miltenyi Biotec). CD34+ cells cultured on fibronectin in endothelial cell medium formed colonies after 1–2 weeks and were further expanded for up to 3 months to generate late outgrowth EPC (eEPC). Expansion was observed up to 2.9x10′9 (MI), 11x10′9 (sAP) and 7x10′9 cells (H) with a mean culture duration of 61 days. Expanded cells showed an endothelial morphology and expressed endothelial surface markers (CD31, VEGF-R2, CD105). Intramyocardial transplantion of 1x10′6 eEPC in experimental myocardial infarction in athymic nude rats revealed improvement in echocardiographic ejection fraction after 2 weeks. This was associated with enhanced vessel density after 1 week and increased mRNA expression of HGF. No differences in infarct size were observed. Similarly in a chronic model of myocardial infarction (eEPC transplantation 1 week after MI) myocardial function significantly improved after 5 weeks in comparison to the control group. Conclusion: Expansion of eEPC from circulating CD34+ cells in patients with coronary artery disease is feasible and improves myocardial function after local transplantation in acute and chronic myocardial infarction. The large number of generated eEPC may prove benefical for therapeutic use and this advantage may prevail time-consuming expansion procedures.


2007 ◽  
Vol 98 (11) ◽  
pp. 930-939 ◽  
Author(s):  
Derya Tilki ◽  
Hans-Peter Hohn ◽  
Ursula Gehling ◽  
Nerbil Kilic ◽  
Süleyman Ergün

SummaryA rapidly increasing body of data suggests an essential role of endothelial progenitor cells (EPCs) in vascular regeneration, formation of new vessels in cardiovascular diseases and also in tumor vasculogenesis. Moreover, recent data obtained from clinical studies with anti-angiogenic drugs in tumor therapy or with pro-angiogenic stimuli in ischemic disorders implicate a predictive role of the number of EPCs circulating in the peripheral blood in monitoring of these diseases. However, there is still some controversial data regarding the relevance of the EPCs in vascular formation depending on models used and diseases studied. One of the essential prerequisites for a better understanding of the whole contribution of EPCs to vascular formation in adult, a process called postnatal vasculogenesis, is to identify their exact sources. We could recently discover the existence of EPCs in a distinct zone of the vascular wall of large and middle sized adult blood vessels and showed that these cells are capable to differentiate into mature endothelial cells, to form capillary sprouts in arterial ring assay and to build vasa vasorumlike structures within the vascular wall. They also can be mobilized very rapidly from the vascular wall by tumor cells. This review will discuss the functional implications of these vascular wall resident endothelial progenitor cells (VW-EPCs) in relation to those of EPCs circulating in peripheral blood or derived from the bone marrow in cardiovascular and neoplastic diseases.


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