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ABSTRACT: Abnormal circulating endothelial cell (CEC) and circulating progenitor cell (CPC) numbers are present in cancer, but their relationship with angiogenesis, apoptosis, vascular biology, and prognosis is unclear. We prospectively studied 160 patients with breast cancer and 63 age-matched controls free of breast cancer, measuring CECs (CD45(-)/CD146(+)/CD34(+)) and CPCs (CD45(-)/CD133(+)/CD34(+)) by flow cytometry and plasma markers of endothelial damage/dysfunction (von Willebrand factor), apoptosis (Fas/Fas-L) and angiogenesis (vascular endothelial growth factor [VEGF], angiogenin) by ELISA. These were compared with clinicopathophysiologic features and the Nottingham Prognostic Index (NPI). An additional blood sample was taken 6 to 8 weeks after surgery from 15 women to test the effect of tumor removal.
CECs were significantly higher in the NPI poor prognostic group compared with moderate and good prognostic groups, and the cancer-free controls, whereas CPCs were lower in the poor prognosis group (both P < .05). Levels of von Willebrand factor, VEGF, angiogenin, and Fas-L (but not soluble Fas) were abnormal in breast cancer compared with controls (P < .05), with no relationship to prognosis groups. VEGF (P = .04) and angiogenin (P = .001) were markedly different after surgery. In multivariate analysis, vascular invasion (P < .05) and tumor size (P < .001) were independently associated with CECs. CPCs did not significantly associate with NPI in a linear regression model; age (P < .05) was a negative predictor, whereas Her-2 status (P < .05) positively predicted CPCs. After adjustment, no variable independently predicted CPC levels.
CECs and CPCs demonstrate a strong relationship with NPI groups, but only CECs positively predict higher NPI scores and correlate with tumor invasiveness and size, possibly reflecting total tumor vascular volume.
Neoplasia (New York, N.Y.) 09/2009; 11(8):771-9. · 5.48 Impact Factor
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ABSTRACT: With a prevalence in excess of 20%, hypertension is a common finding among Western adult populations. Hypertension is directly implicated in the pathophysiology of various cardiovascular disease states and is a significant contributor to ill health, leading to an excess of both morbidity and mortality. The etiology of hypertension has been explored in depth, but the pathophysiology is multifactorial, complex, and poorly understood. Recent interest has been directed toward investigating the purported role of the endothelium, which acts as an important regulator of vascular homeostasis. Endothelial dysfunction is now recognized to occur in hypertension, regardless of whether the etiology is essential or secondary to endocrine or renal processes. Nitric oxide (NO) is a volatile gas produced by endothelial cells that acts to maintain vascular tone. Reduced bioavailability of NO appears to be the key process through which endothelial dysfunction is manifested in hypertension. The result is of an imbalance of counteracting mechanisms, normally designed to maintain vascular homeostasis, leading to vasoconstriction and impaired vascular function. It has become increasingly apparent that these changes may be effected in response to enhanced oxidative stress, possibly as a result of systemic and localized inflammatory responses. This article provides an overview of endothelial dysfunction in hypertension and focuses on the purported role of oxidative stress and inflammation as the catalysts for this process.
Antioxidants and Redox Signaling 07/2008; 10(6):1079-88. · 8.46 Impact Factor
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Cytometry Part B Clinical Cytometry 10/2007; 72(5):416. · 2.53 Impact Factor
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Heart (British Cardiac Society) 10/2007; 93(9):1020-1. · 4.22 Impact Factor
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American Journal of Respiratory and Critical Care Medicine 07/2007; 175(12):1346; author reply 1347. · 11.08 Impact Factor
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ABSTRACT: The link between cancer, hypertension and anti-hypertensive drug treatment is controversial. Despite numerous studies looking either directly or indirectly at cancer and hypertension, the results are often conflicting and do little to answer the dominant questions of cause and effect. Also, the treatment of hypertension has continued to evolve, with newer therapies being made available including angiotensin-converting enzyme inhibitors. Whilst the potential link with cancer is thought to be small at worst, with the overall benefits of hypertension far outweighing its negative impacts, the suggestion of a carcinogenic role for either hypertension or its treatment continues to be an emotive issue, and needs firm answers. In this review, we provide an overview establishing the strengths and weaknesses of the arguments presented and highlight possible pharmacophysiological pathways involved.
Current pharmaceutical design 02/2007; 13(25):2539-44. · 4.41 Impact Factor
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Journal of Thrombosis and Thrombolysis 11/2006; 22(2):155-6. · 1.48 Impact Factor
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ABSTRACT: The quantification of circulating endothelial cells (CECs) in whole blood has evolved as a novel method for the assessment of endothelial function, although major methodological issues remain. We hypothesized that there is a temporal decline in CEC counts in static venesected blood and that venepuncture itself may lead to increased CEC detachment.
CEC isolation was performed using the immunobead method. For the temporal decline experiment, we included 52 patients presenting with acute coronary syndrome (ACS). We performed CEC counts immediately and at 4 and 24 h later. For the venepuncture decline experiment, we studied 40 patients with stable cardiovascular disease (CVD). CEC counts were determined from the first 4 mL of aspirated venous blood and compared with counts obtained from a subsequent 4 mL sample of blood after at least 7.5 mL of blood had been collected.
Among the ACS patients there was a significant temporal decline in CEC counts in static venous blood over a 24 h period (p = 0.013). Among the patients with stable CVD, the median CEC counts obtained from the initial 4 mL of aspirated venous blood were significantly higher (by 32%) than that obtained from the later 4 mL of aspirated venous blood (p = 0.041).
We demonstrated a significant temporal fall in CEC numbers in static venous blood over 24 h following venesection. Furthermore, we have shown that CEC counts are higher in the initial aspirated blood compared with that aspirated from the same needle subsequently. These data would have implications for how CEC determination is undertaken by researchers in studies related to ACS or CVD.
Journal of Thrombosis and Thrombolysis 11/2006; 22(2):125-31. · 1.48 Impact Factor
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Thrombosis and Haemostasis 09/2006; 96(2):111-2. · 5.04 Impact Factor
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ABSTRACT: Mature circulating endothelial cells (CECs) are novel cellular markers of endothelial damage/dysfunction. The two main techniques of CEC enumeration are flow cytometry (FC) and immunomagnetic bead (IB) isolation. Both quantify CECs accurately, but a direct comparison of both methods has not been reported. We sought to assess the agreement between the two methods in two patient populations, and a group of healthy subjects, with emphasis given to methodological issues. We included 34 patients with acute coronary syndrome (ACS), 60 patients with primary breast cancer (PBC) and 30 healthy controls (HC). We quantified CECs using the IB method [CD146 and FITCUlex europaeus lectin-1] and FC [CD45, CD34 and CD146]. Bland-Altman plots suggested reasonable agreement (<5% of events >2 standard deviations from the mean) between FC and the IB methods for CEC quantification in whole blood in the two disease groups (ACS and PBC), but not among the HCs. There were no statistically significant differences in CEC levels by the two methods amongst all three patient groups. There is reasonable agreement between the FC and the IB methods for mature CEC quantification in whole blood, especially amongst disease groups. The agreement between the two methods appears to weaken in healthy controls, and at lower and higher absolute CEC counts.
Thrombosis and Haemostasis 07/2006; 96(1):45-52. · 5.04 Impact Factor
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Clinical Pharmacology & Therapeutics 02/2006; 79(1):20-2. · 6.04 Impact Factor
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ABSTRACT: Cancer is a disease largely dependent on neoangiogenesis. Cancer neoangiogenesis is often disordered and abnormal, with evidence of coexisting vascular endothelial dysfunction. A novel method of assessing vascular endothelial function in cancer is via the quantification of circulating endothelial cells (CEC). Unusual in healthy individuals, their presence in elevated numbers often indicates substantial vascular endothelial perturbation. Another interesting cell type is the endothelial progenitor cell (EPC), whose numbers increase in the presence of vascular damage. Recent research suggests that EPCs have an important role in tumor vasculogenesis. Another marker being investigated in the context of vascular dysfunction and coagulopathy is the endothelial microparticle (EMP). Thus, CECs, EPCs and EMPs may represent potentially novel methods for evaluating the vascular status of cancer patients. This review will summarize the current position of CECs, EPCs and EMPs in cell biology terms, with particular emphasis on their relationship to malignant disease.
Future Oncology 01/2006; 1(6):813-20. · 3.16 Impact Factor
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New England Journal of Medicine 01/2006; 353(24):2613-6; author reply 2613-6. · 53.30 Impact Factor
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ABSTRACT: Recurrence of breast cancer discovered at the time of reconstruction is rare. However, with increasing numbers of delayed postmastectomy reconstructions being performed, this scenario may become more common. There are no guidelines on how to manage this dilemma. There are two main issues: the effect on the patient and the effect on the reconstruction itself. The authors present two cases and discuss the factors involved in this difficult decision, along with their recommendations.
Aesthetic Plastic Surgery 11/2004; 28(6):399-400. · 1.41 Impact Factor
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ABSTRACT: Rhinophyma is a benign condition of the nose that often is severely disfiguring and occasionally causes functional problems. A considerable proportion of the patients, with rhinophyma are elderly with chronic medical problems. Electrocautery, heated scalpel, carbon dioxide (CO(2)) laser, argon laser, Weck blade, dermabrasion, cryotherapy, radiotherapy, full-thickness excision, skin graft, flap reconstruction, and cold scalpel have been used either alone or in combination. All these techniques have disadvantages that are resolved by using the combined erbium:yttrium-aluminum-garnet (YAG)/CO(2) laser. The authors present their technique and the results from decortication of rhinophyma using a combined erbium:YAG/CO(2) laser. The technique requires only local anesthesia with a vasoconstrictor. The combination of an efficient vaporization tool consisting of the erbium:YAG laser and the CO(2) coagulation laser provides a nearly bloodless field for accurate sculpting of the nose and produces cosmetically pleasing results.
Aesthetic Plastic Surgery 11/2004; 28(6):456-60. · 1.41 Impact Factor
