Effect of standard chemotherapy and antiangiogenic therapy on plasma markers and endothelial cells in colorectal cancer

Abstract

Introduction:The importance of the endothelium in angiogenesis and cancer is undisputed, and its integrity may be assessed by laboratory markers such as circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), plasma von Willebrand factor (vWf), soluble E selectin, vascular endothelial growth factor (VEGF) and angiogenin. Antiantigenic therapy may be added to standard cytotoxic chemotherapy as a new treatment modality. We hypothesised that additional antiangiogenic therapy acts in a contrasting manner to that of standard chemotherapy on the laboratory markers.Methods:We recruited 68 patients with CRC, of whom 16 were treated with surgery alone, 32 were treated with surgery followed by standard chemotherapy (5-flurouracil), and 20 were treated with surgery followed by standard chemotherapy plus anti-VEGF therapy (Avastin). Peripheral blood was taken before surgery, and again 3 months and 6 months later. CD34+/CD45−/CD146+ CECs and CD34+/CD45−/CD309[KDR]+ EPCs were measured by flow cytometry, plasma markers by ELISA.Results:In each of the three groups, CECs and EPCs fell at 3 months but were back at pre-surgery levels at 6 months (P<0.05). VEGF was lower in both 3-and 6-month samples in the surgery-only and surgery plus standard chemotherapy groups (P<0.05), but in those on surgery followed by standard chemotherapy plus anti-VEGF therapy, low levels at 3 months (P<0.01) increased to pre-surgery levels at 6 months. In those having surgery and standard chemotherapy, soluble E selectin was lower, whereas angiogenin was higher at 6 months than at baseline (both P<0.05).Conclusions:We found disturbances in endotheliod cells regardless of treatment, whereas VEGF returned to levels before surgery in those on antiangiogenic therapy. These observations may have clinical and pathophysiological implications.

Complex Analysis of Endothelial Markers as Potential Prognostic Indicators in Luminal Invasive Breast Carcinoma Patients: Outcomes of a Six-Year Observational Study

“…Surprisingly, subjects with a pre-treatment sE-selectin concentration lower than 25.04 ng/mL appear to have a higher risk of disease recurrence. However, this observation is inconsistent with previous studies of Ramcharan et al, Mann et al and Muz et al [ 36 , 37 , 38 ]. Since, we should expect opposite results due to the fact that high sE-selectin concentration is associated with a shorter survival rate [ 50 ].…”

“…Authors suggest to analyze their results with caution due to limited number of patients in each subgroups. They speculate that it was probably nonspecific response of the endothelium to the different types of treatment [ 36 ]. Considering that sE-selectin is involved in leukocyte and cancer cell extravasation, homing, adhesion, proliferation, cellular dormancy, drug resistance, and tumor progression.…”

Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies

“…In particular, CEP may generate new blood vessels in the tumor (vasculogenesis) whereas CEC could derive from shedded endothelial cells [ 13 ]. The change of CEC and CEP levels we observed in this study was comparable to other studies [ 13 , 36 , 37 ]. Moreover we found that other CEC subpopulations such as VEGFR2 + CEC, whose pathophysiological role has not been investigated intensively so far, react differently to antiangiogenic therapies and decrease at the time point of resistance.…”

Percutaneous coronary intervention in patients with cancer using bare metal stents compared to drug-eluting stents

“…Several comorbid conditions affect patients with cancer, which influence their treatment in the setting of PCI. While cancer and its treatment can predispose patients to bleeding tendencies and thrombocytopenia, neoplasia by itself is a pro-coagulant state ( 14 ). This poses a unique challenge and highlights the need to evaluate thrombosis and bleeding risks carefully.…”

“…This poses a unique challenge and highlights the need to evaluate thrombosis and bleeding risks carefully. In the setting of PCI, this information has a tremendous impact on the options for stenting and antiplatelet therapy ( 14 ). Several clinical studies have proven the superiority of DES over BMS in reducing the risk of restenosis and stent thrombosis compared with bare-metal stents (BMS) in non-cancer high-risk patients ( 9 ).…”