Changes in circulating endothelial cells (CECs) during treatment with cisplatin-based chemotherapy for testicular cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16009-e16009
Author(s):  
R. Altena ◽  
E. C. De Haas ◽  
A. G. Tibbe ◽  
A. J. Smit ◽  
A. van Roon ◽  
...  

e16009 Background: Chemotherapy (CT)-induced endothelial damage is an important pathogenic factor for cardiovascular morbidity in testicular cancer (TC) patients (pts). Therefore, we studied early markers of endothelial damage as predictors of cancer treatment-related cardiovascular morbidity. Methods: We prospectively assessed markers of endothelial damage in TC pts treated at the University Medical Center Groningen, before, during, 4 weeks and one year after completion of standard CT (3 or 4 three weekly cycles with bleomycin, etoposide and cisplatin). The number of circulating endothelial cells (CECs), identified by CD146+, CD105+ and CD45− using the CellSearch system, and plasma levels of von Willebrand Factor (vWF) were measured. Results: 30 TC pts were included (median age 34 years, range 20–47). Before start of CT, CECs were not associated with disease stage or leukocyte count. The number of CECs progressively increased over the 9–12 week CT period [baseline: median (range) 25/mL (6–137); maximum number during CT: 134/mL (28–320; p<0.001); 4 weeks after completion of CT: 66/mL (18–316; p=0.005)]. One year post treatment, CECs were not different from baseline [N= 10; 13/mL (6–31; p=0.263)]. vWF levels also progressively increased during CT [baseline: median 105% (range 50–377); maximum level during CT: 289% (175–464; p<0.001); 4 weeks after completion of CT: vWF 124% (56–274; p=0.149)]. One year after CT, vWF levels were 115% (61–184; p=0.285). During CT, numbers of CECs and vWF levels correlated positively (r=0.283; p<0.001), whereas maximum CECs increase and maximum vWF increase were not associated (r=0.098; p=0.605). Two pts had a cerebral infarction during CT. In one pt, vWF increased before the event; in both pts CECs increased directly afterwards. Conclusions: During CT for disseminated TC, CECs and vWF progressively increased during consecutive cycles. CECs remained increased 4 wks after completion of CT, whereas vWF returned to baseline levels. The magnitude of changes was not equal in every pt. Therefore, both CECs and vWF might be early predictive markers for chemotherapy-induced cardiovascular toxicity, and may serve as intermediate endpoint in intervention studies. [Table: see text]

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 441.1-441
Author(s):  
F. Pignataro ◽  
L. Zorzino ◽  
W. Maglione ◽  
A. Minniti ◽  
G. Clericuzio ◽  
...  

Background:Endothelial damage and fibroproliferative vasculopathy of small vessels are pathological hallmarks of Systemic Sclerosis (SSc). Detection and analysis of circulating endothelial cells (CECs) detached from affected blood vessels may be an informative tool to study vascular dysfunction and could be considered a novel biomarker of scleroderma vasculopathy. Our group first showed the presence of CECs in SSc by fluorescence-activated cell sorting (FACS), demonstrating that a raised counts of active CECs may represent direct evidence of active vascular disease in SSc. Despite these interesting data, issues related to difficulties in CEC counting through FACS analysis, due their very low concentration in peripheral blood, prevented further investigations in this field. Recently, a specific kit for the detection of CECs has been developed through the CellSearch System (CS), a semi-automated device for the standardized analysis of rare cells, such as CECs, in peripheral blood.Objectives:To assess the counts of CECs determined by the CS in SSc patients and to evaluate their clinical implication and potential as vascular biomarker in SSc.Methods:10mL of blood samples were collected from 29 subjects (19 SSc patients and 10 healthy donors - HDs) and stored in tubes containing a specific preservative, to allow the analysis of 4mL of blood within 72 hours, according to manufacturer instructions. Out of 19 SSc patients, 18 were female, 10 had the limited form and 9 the diffuse cutaneous variant of SSc. CS uses a proprietary kit containing a ferrofluid-based reagent, that target CD146 to magnetically capture CECs, and the immunofluorescent reagents to stain the CECs, defined as CD146+, CD105-PE+, DAPI+ and CD45-APC-. Clinical, laboratoristic and demographic data were also collected.Results:The mean number of CECs in patients with SSc was significantly higher in comparison to HDs (554/4mL vs. 53.5/4 mL, p=0.0042). When analyzed according to disease subset, both lcSSc and dcSSc showed significantly increased levels of CECs in comparison with HDs (p=0.003 and p=0.005, respectively). No statistical difference was observed in the mean number of CECs in patients with lcSSc compared to those with dcSSc. Regarding vascular involvement, the CECs counts strictly correlated with the presence of digital ulcers (DUs) (p=0.0001) showing a median of 863cells/4mL for the SSc patients with DUs versus a median of 276.2/4mL for the SSc patients without DUs. No statistical correlation was found between CECs and serological autoantibody pattern, skin parameters, or joint and muscle involvement. Patients with active disease, according to the EUSTAR Activity Index, showed a higher CECs value than those with inactive disease (p=0.0012).Conclusion:The amount of CECs detectable in peripheral blood has been recently proposed as a marker of endothelial damage in different vascular diseases, including SSc. However, currently no standardized method is available to determine CEC counts, which makes reported data on CECs reliable and suitable. The CS system is a commercially available semi-automated system that enables standardized determination of CECs. Thus, we examined clinical utility of CECs count by this system in SSc patients. Our results confirm that baseline CEC counts, evaluated by a new standardized method, may represent direct evidence of endothelial damage in SSc and could be a promising tool for monitoring active disease and evaluating therapeutic responses to vascular and immunosuppressive treatments.References:[1]Del Papa N, Pignataro F. Front Immunol. 2018 Jun 18;9:1383[2]De Simone C et al. J Eur Acad Dermatol Venereol. 2014 May;28(5):590-6[3]Del Papa N et al. Arthritis Rheum. 2004 Apr;50(4):1296-304Disclosure of Interests:Francesca Pignataro: None declared, Laura Zorzino: None declared, Wanda Maglione: None declared, Antonina Minniti: None declared, Giulia Clericuzio: None declared, Marco Picozzi: None declared, Cecilia Simonelli Employee of: Menarini Silicon Biosystems, Francesco Picardo Employee of: Menarini Silicon Biosystems, Roberto Caporali: None declared, Nicoletta Del Papa: None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 811.1-811
Author(s):  
S. Smiyan ◽  
A. Bilukha ◽  
B. Koshak

Background:Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which develops in patients with psoriasis. Mortality among patients with PsA is 1.28 times higher than population levels and in most cases it is caused by cardio-vascular diseases (CVD). Those patients have increased risk of clinical and subclinical CVD, mostly due to endothelial dysfunction (ED) and accelerated atherosclerosis. Elevated levels of circulating endothelial cells (CEC) have been described in different cardiovascular pathologies, suggesting their potential use as diagnostic biomarkers for dysfunction of endothelium.Objectives:To identify the potential role of circulating endothelial cells as a marker of cardiovascular diseases in patients with psoriatic arthritis.Methods:In total, ninety-four patients with PsA, who fulfilled the disease criteria (CASPAR) were examined using standard diagnostic methods (including C-reactive protein (CRP), lipid profile) and evaluation endothelium-dependent vasodilation in response to reactive hyperemia (EDVD). Circulating endothelial cells were determined in the peripheral venous blood samples by flow cytometry and counted according to a standardized protocol using a fluorescence microscope after acridine orange labeling. The control group, which were consisted from thirty healthy adults were also examined.Results:CEC were quantified in patients with PsA (7,15 ± 0,19 cells mL−1) and in the control group (4,05 ± 0,11 cells mL−1). Comparing two groups of patients, endothelial circulating cell level was significantly different (p = 0.0001). Finally, we analyzed the relationship between CEC count, comorbidities, cardiovascular risk factors and EDVD in patients with PsA. Increased CEC levels were associated with obesity (r=0,62), duration of disease (r=0,65), age (r=0,67), increased CRP (r=0,76), high blood pressure (r=0,87) and decreased EDVD (r=–0,91).Conclusion:CEC counts were significantly higher in patients with PsA, positively correlated with the main factors of CVD, and another specific marker of ED - EDVD. Elevated CEC levels were also associated with high concentrations of CRP, which plays a direct role in promoting vascular inflammation, vessel damage and clinical CVD events. In conclusion, increased CEC counts provide a direct proof of endothelial damage in patient with PsA and a clinically informative diagnostic tool for endothelial damage in pre-symptomatic CVD. As CEC are one of the most sensitive biomarker for ED, further efforts should concentrate on improving the sensitivity of its detection in order to increase diagnostic sensitivity.References:[1]Maura Farinacci, Thomas Krahn, Wilfried Dinh, et al. Circulating endothelial cells as biomarker for cardiovascular diseases. Res Pract Thromb Haemost, Vol. 3, Issue, 2019, P.49-58;[2]C. Horreau, C. Pouplard, E. Brenautet, et al. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol, Vol. 27, Issue 3, 2013, P.12-19;[3]Frank Verhoeven, Clément Prati, Céline Demougeot, Daniel Wendling. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine, Vol. 87, Issue 5, 2020, P.413-418;Disclosure of Interests:None declared.


2019 ◽  
Vol 142 (2) ◽  
pp. 113-119
Author(s):  
Martin Řádek ◽  
Eva Babuňková ◽  
Martin Špaček ◽  
Tomáš Kvasnička ◽  
Jan Kvasnička

Background/Aims: Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) have been described as markers of endothelial damage and dysfunction in several diseases, including deep venous thrombosis. Their role in patients with known thrombophilia has not yet been evaluated. Both EPCs and CECs represent extremely rare cell populations. Therefore, it is essential to use standardized methods for their identification and quantification. Methods: In this study, we used multicolor flow cytometry to analyze the number of EPCs and CECs in patients with thrombophilia with or without a history of thrombosis. Patients with hematological malignancies after high-dose chemotherapy and patients with acute myocardial infarction were used as positive controls. Results: EPC and CEC immunophenotypes were determined as CD45dim/–CD34+CD146+CD133+ and CD45dim/–CD34+CD146+CD133–, respectively. Increased levels of endothelial cells were observed in positive control groups. No significant changes in the number of EPCs or CECs were detected in patients with thrombophilia compared to healthy controls. Conclusion: Our optimized multicolor flow cytometry method allows unambiguous identification and quantification of endothelial cells in the peripheral blood. Our results support previous studies showing that elevated levels of CECs could serve as an indicator of endothelial injury or dysfunction. Normal levels of CECs or EPCs were found in patients with thrombophilia.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Camillo Almici ◽  
Arabella Neva ◽  
Cristina Skert ◽  
Benedetto Bruno ◽  
Rosanna Verardi ◽  
...  

Perfusion ◽  
2006 ◽  
Vol 21 (3) ◽  
pp. 133-137 ◽  
Author(s):  
Franz-Xaver Schmid ◽  
Bernhard Floerchinger ◽  
Nalini Kumar Vudattu ◽  
Günther Eissner ◽  
Marion Haubitz ◽  
...  

Endothelial activation is considered a key process in the development of a whole body inflammatory response secondary to cardiopulmonary bypass (CPB). Increased levels of a multitude of soluble mediators have been described as being released during and after cardiac surgery. Circulating endothelial cells have recently been established as a novel marker of endothelial damage in a variety of vascular disorders. Blood samples from 20 patients undergoing elective coronary artery bypass surgery were obtained preoperatively and 1, 6, 12, 24, and 48 h after termination of CPB. Control samples were obtained from ten healthy volunteers. Circulating endothelial cells (CEC) were isolated with immunomagnetic anti-CD146-coated Dynabeads, and counted in a Nageotte chamber. Low numbers of CEC were observed in healthy control volunteers (12±6 cells/mL; median: 9 cells/mL). CEC numbers were already significantly elevated in all patients before CPB, and there was a further significant increase after weaning from CPB (maximum increase at 6 h after CPB: 73±30 cells/mL; range: 30-153 cells/mL, p < 0.001). The number of CEC provides further and direct evidence that CPB is associated with a pronounced endothelial injury and/or damage. CEC appear to be most useful markers for vascular endothelial activation because they are specific, stable, and circulating components of injured vessel wall.


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