TF and TFPI in myeloproliferative neoplasms — a preliminary study

Introduction. Haemostatic disturbances such as thrombosis or diathesis are frequent complications in patients with myeloproliferative neoplasms (MPNs). The purpose of this study was to evaluate the concentration of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and thrombin–antithrombin (TAT) complexes in patients with MPNs.Patients and methods. The study involved 43 patients with MPNs (mean age 60.5 years), including 16 patients with essential thrombocythaemia, eight with polycythaemia vera, ten with chronic myeloidleukaemia, and nine with primary myelofibrosis. The control group consisted of 30 healthy volunteers who were age- and sex-matched. TF, TFPI and TAT complexes concentration were measured using the immunoenzyme method.Results. TF and TAT complex concentrations were significantly higher, but the TFPI concentration was lower, in the total study group compared to the control group. TF concentration in each of the subgroups was significantly higher than in the control group. TFPI concentration was significantly lower in essential thrombocythaemia and polycythaemia vera than in controls. In addition, the concentration of TAT complex in patients with chronic myeloid leukaemia was significantly higher than in the control group.Conclusions. Elevated TF levels and decreased TFPI levels in patients with essential thrombocythaemia and polycythaemia vera indicate the activation of blood coagulation process depending on the TF (an extrinsic pathway). These patients represent a group at high risk of thrombotic complications

Tissue factor and tissue factor pathway inhibitor in chronic obstructive pulmonary disease

Background. The inflammatory process in patients with chronic obstructive pulmonary disease (COPD) interferes with the normal function of respiratory lung. There is strong evidence indicating that inflammatory process in patients with COPD may activate blood coagulation. However, little is known about the role of tissue factor (TF) pathway in the coagulation system activation in COPD. Objectives. The aim of the study has been to evaluate the concentration of selected parameters of coagulation process, including TF and tissue factor pathway inhibitor (TFPI), in plasma of patients with COPD. Patients and methods. The study included 66 patients with COPD at different stages of disease according to GOLD 2006, mean age of 60.4 years. The control group consisted of 25 healthy volunteers (non-smokers). Total TF and TFPI concentrations and other haemostatic parameters were measured using Enzyme Linked Immunosorbent Assay (ELISA). Results. Significantly higher concentrations of TF and TFPI (p = 0.03; p = 0.004, respectively) were observed in patients with COPD. The level of fibrinogen was also higher in the study group than in controls (p = 0.002). However, the activated partial thromboplastin time (aPTT) was shortened in COPD patients as compared with the control group (p = 0.0001). Conclusion. The study showed that in patients suffering from COPD, the stimulation of the tissue factor- -dependent activation of coagulation is observed.

Effect of low level laser irradiation on VEGF gene expression in cultured endothelial cells

Background. Endothelial cells play a crucial role in the angiogenesis which is initiated by vascular endothelial growth factor (VEGF). Low level laser therapy (LLLT) stimulates repair processes which are based on the formation of new blood vessels.Aim. The aim of this study was to evaluate the impact of LLLT on VEGF gene expression in endothelial cells cultured in vitro.Material and methods. Freshly isolated endothelial cells from the human umbilical vein endothelial cells (HUVEC) line were used in the study. The cells were irradiated with a semiconductor laser emitting visiblelaser radiation at the wave length of 630 nm and the power of 30 mW, and radiation at the wavelength of 808 nm and the power of 60 mW in the infrared range. The study was performed with cell cultures subjected to four different procedures: I — control cells (not subjected to irradiation); II — cells subjected to an energy dose of 2 J/cm2; III — cells subjected to an energy dose of 4 J/cm2; and IV — cells subjected to an energy dose of 8 J/cm2. The cells were cultured for six days, and exposed to irradiation twice. The next step was to evaluate the VEGF gene expression by applying real-time PCR.Results. By using low power laser irradiation, we obtained a statistically significant increase in VEGF gene expression, particularly at doses of 2 and 8 J/cm2 in the wave length range of 630 nm. The wave length of 808 nm had a similar effect on increases in gene expression. However, the differences were statistically non-significant when compared to the control cells.Conclusions. This study has shown that low-power laser radiation in the visible light spectrum (630 nm) results in de novo formation of VEGF-A in the endothelial cells in culture

KOMÓRKI PROGENITOROWE ŚRÓDBŁONKA W NOWOTWORACH MIELOPROLIFERACYJNYCH – DONIESIENIA WSTĘPNE

The aim of this study was to assess the number of endothelial progenitor cells in patients with chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET). The study involved 21 patients (mean age 61.77) with myeloproliferative neoplasms, hospitalized and diagnosed at the Hematology Clinic of Dr. J. Biziel University Hospital No. 2 in Bydgoszcz, Poland. M a t e r i a l a n d m e t h o d s . The study group included 12 patients with ET, 5 with PV, 4 with CML. The control group consisted of 25 healthy volunteers, age- and sex- matched. The material for the study was venous blood collected from the elbow vein into tube containing K2EDTA. The number of endothelial progenitor cells was measured with FACSCalibur flow cytometer (Becton Dickinson, San Diego, USA) using monoclonal antibodies directed against antigens specific for endothelial progenitor cells (EPCs). R e s u l t s . We observed significantly increased number of EPCs in patients with myeloproliferative neoplasms (MPNs) in comparison to the control group. Detailed analysis showed slightly higher number of EPCs in patients with PV and ET than in the controls, but the differences were not statistically significant. The highest statistically significant number of EPCs was observed in patients with CML. C o n c l u s i o n s . Increased number of EPCs in patients with myeloproliferative neoplasms may indicate increased angiogenesis in these diseases and participation of EPCs in the process of neovascularization.Celem niniejszej pracy była ocena liczby i funkcji komórek progenitorowych śródbłonka w przewlekłej białaczce szpikowej (PBS), czerwienicy prawdziwej (CzP), nadpłytkowości samoistnej (NS). Badaniem objęto 21 pacjentów z nowotworami mieloproliferacyjnymi (średnia wieku 61,77), hospitalizowanych w Oddziale Klinicznym Hematologii i Chorób Rozrostowych Układu Krwiotwórczego Szpitala Uniwersyteckiego nr 2 im. Jana Biziela w Bydgoszczy. M a t e r i a ł i m e t o d y . Badania przeprowadzono u 12 chorych na ET, 4 chorych na CML i 5 chorych na PV. Grupę kontrolną stanowiło 25 zdrowych ochotników. Materiałem do badań była krew pobrana w godzinach porannych z nakłucia żyły łokciowej do probówki zawierającej wersenian dwupotasowy (EDTA). Po inkubacji z odpowiednimi odczynnikami dokonana została analiza cytometryczna przy użyciu cytometru przepływowego FACS Calibur (Becton Dickinson, San Diego, USA) z zastosowaniem programu komputerowego CellQuest. Wy n i k i . U chorych na przewlekłe nowotwory mieloproliferacyjne stwierdzono istotnie statystyczną zwiększoną liczbę EPCs w porównaniu z grupą kontrolną. U chorych z PV i ET stwierdzono nieznacznie zwiększoną liczbę EPCs w porównaniu do grupy kontrolnej, a różnica ta okazała się nieistotna statystycznie. Najwyższą liczbę EPCs stwierdzono u pacjentów z CML i różnica ta była istotna statystycznie. Wn i o s k i . Zwiększenie liczby EPCs w grupie chorych na przewlekłe nowotwory mieloproliferacyjne świadczy o aktywacji procesów angiogenezy w tych nowotworach i prawdopodobnie czynnym udziale tych komórek w procesie nowotworzenia naczyń

ENDOTHELIAL PROGENITOR CELLS IN MYELOPROLIFERATIVE NEOPLASMS – PRELIMINARY REPORT

The aim of this study was to assess the number of endothelial progenitor cells in patients with chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET). The study involved 21 patients (mean age 61.77) with myeloproliferative neoplasms, hospitalized and diagnosed at the Hematology Clinic of Dr. J. Biziel University Hospital No. 2 in Bydgoszcz, Poland. Material and methods. The study group included 12 patients with ET, 5 with PV, 4 with CML. The control group consisted of 25 healthy volunteers, age- and sex- matched. The material for the study was venous blood collected from the elbow vein into tube containing K2EDTA. The number of endothelial progenitor cells was measured with FACSCalibur flow cytometer (Becton Dickinson, San Diego, USA) using monoclonal antibodies directed against antigens specific for endothelial progenitor cells (EPCs). Results. We observed significantly increased number of EPCs in patients with myeloproliferative neoplasms (MPNs) in comparison to the control group. Detailed analysis showed slightly higher number of EPCs in patients with PV and ET than in the controls, but the differences were not statistically significant. The highest statistically significant number of EPCs was observed in patients with CML. Conclusions. Increased number of EPCs in patients with myeloproliferative neoplasms may indicate increased angiogenesis in these diseases and participation of EPCs in the process of neovascularization.Celem niniejszej pracy była ocena liczby i funkcji komórek progenitorowych śródbłonka w przewlekłej białaczce szpikowej (PBS), czerwienicy prawdziwej (CzP), nadpłytkowości samoistnej (NS). Badaniem objęto 21 pacjentów z nowotworami mieloproliferacyjnymi (średnia wieku 61,77), hospitalizowanych w Oddziale Klinicznym Hematologii i Chorób Rozrostowych Układu Krwiotwórczego Szpitala Uniwersyteckiego nr 2 im. Jana Biziela w Bydgoszczy. Materiał i metody. Badania przeprowadzono u 12 chorych na ET, 4 chorych na CML i 5 chorych na PV. Grupę kontrolną stanowiło 25 zdrowych ochotników. Materiałem do badań była krew pobrana w godzinach porannych z nakłucia żyły łokciowej do probówki zawierającej wersenian dwupotasowy (EDTA). Po inkubacji z odpowiednimi odczynnikami dokonana została analiza cytometryczna przy użyciu cytometru przepływowego FACS Calibur (Becton Dickinson, San Diego, USA) z zastosowaniem programu komputerowego CellQuest. Wyniki. U chorych na przewlekłe nowotwory mieloproliferacyjne stwierdzono istotnie statystyczną zwiększoną liczbę EPCs w porównaniu z grupą kontrolną. U chorych z PV i ET stwierdzono nieznacznie zwiększoną liczbę EPCs w porównaniu do grupy kontrolnej, a różnica ta okazała się nieistotna statystycznie. Najwyższą liczbę EPCs stwierdzono u pacjentów z CML i różnica ta była istotna statystycznie. Wnioski. Zwiększenie liczby EPCs w grupie chorych na przewlekłe nowotwory mieloproliferacyjne świadczy o aktywacji procesów angiogenezy w tych nowotworach i prawdopodobnie czynnym udziale tych komórek w procesie nowotworzenia naczyń

A micellar formulation of quercetin prevents cisplatin nephrotoxicity

Producción CientíficaThe antioxidant flavonoid quercetin has been shown to prevent nephrotoxicity in animal models and in a clinical study and is thus a very promising prophylactic candidate under development. Quercetin solubility is very low, which handicaps clinical application. The aim of this work was to study, in rats, the bioavailability and nephroprotective efficacy of a micellar formulation of Pluronic F127-encapsulated quercetin (P-quercetin), with improved hydrosolubility. Intraperitoneal administration of P-quercetin leads to an increased plasma concentration and bioavailability of quercetin compared to the equimolar administration of natural quercetin. Moreover, P-quercetin retains overall nephroprotective properties, and even slightly improves some renal function parameters, when compared to natural quercetin. Specifically, P-quercetin reduced the increment in plasma creatinine (from 3.4 ± 0.5 to 1.2 ± 0.3 mg/dL) and urea (from 490.9 ± 43.8 to 184.1 ± 50.1 mg/dL) and the decrease in creatinine clearance (from 0.08 ± 0.02 to 0.58 ± 0.19 mL/min) induced by the nephrotoxic chemotherapeutic drug cisplatin, and it ameliorated histological evidence of tubular damage. This new formulation with enhanced kinetic and biopharmaceutical properties will allow for further exploration of quercetin as a candidate nephroprotector at lower dosages and by administration routes oriented towards its clinical use.Fundación de Universidades y Enseñanzas Superiores de Castilla y León (FUESCyL) y Banco de Santander - (grant: Ed. 2014– 2015 Desafío UNIV-EMP)Fundación General de la Universidad de Salamanca, Fondo Europeo de Desarrollo Regional (FEDER) y Junta de Castilla y León - (grant: Ed. 2015 Lanzadera TC)Junta de Castilla y León - (grant: VA225U14

Cooperation between Angiogenesis, Vasculogenesis, Chemotaxis, and Coagulation in Breast Cancer Metastases Development: Pathophysiological Point of View

With almost 2.3 million new cases and 685 thousand fatal events in 2020 alone, breast cancer remains one of the main causes of morbidity and mortality in women worldwide. Despite the increasing prevalence of the disease in recent years, the number of deaths has dropped—this is mostly the result of better diagnostic and therapeutic opportunities, allowing to recognize and treat breast cancer earlier and more efficiently. However, metastatic disease still remains a therapeutic challenge. As mechanisms of tumor spread are being explored, new drugs can be implemented in clinical practice, improving the outcomes in patients with advanced disease. Formation of metastases is a complex process, which involves activation of angiogenesis, vasculogenesis, chemotaxis, and coagulation. The actions, which occur during metastatic spread are interrelated and complementary. This review summarizes their importance and mutual connections in formation of secondary tumors in breast cancer

Pre-Operative Combination of Normal BMI with Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study

Adipokines are powerful agents involved in the development of obesity-dependent cancers. This prospective study aimed to investigate the association between pre-treatment body mass index (BMI) and serum YKL-40, leptin, and adiponectin concentrations as well as the plasma activity of tissue factor (TF) and the future prognosis of early, non-metastatic breast cancer (BrC) subjects. The serum levels of YKL-40, leptin, and adiponectin as well as plasma TF activity, anthropometric parameters, and clinicopathological parameters were analysed in 81 treatment-naïve females with invasive BrC. The predictive value of YKL-40, BMI, leptin, adiponectin, and TF was determined with a 95% confidence interval (CI). Kaplan–Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes of progression-free survival (PFS). The median follow-up duration was 44 months with complete follow-up for the first event. Follow-up revealed a significantly higher incidence of disease relapse in BrC patients with a high baseline concentration of YKL-40 (22.22%) and TF activity (21.43%). Body mass index was an independent predictor of survival, with women who were overweight/obese being less prone to relapse (hazard ratio (HR): 0.75; 95% CI: 0.59 to 0.95). The recurrence rates for normal-weight BrC cases was 21.05% versus 7.14% for their overweight counterparts. The receiver operating characteristic analysis showed the strong ability of the analysed biomarkers to predict disease progression, with an area under the receiver operating characteristics (ROC) curve of 0.84 (95% CI, 0.823 to 0.931). In a prospective cohort of invasive BrC patients, overweight/obesity was associated with improved future outcomes. The combination of a normal BMI with high leptin and low adiponectin levels and high TF activity was associated with an increased risk of recurrence and decreased survival

High Post-Treatment Leptin Concentration as a Prognostic Biomarker of the High Risk of Luminal Breast Cancer Relapse: A Six-Year Comprehensive Study

(1) Background: Nowadays, obesity is well-recognised as a significant risk factor for many chronic diseases, for example, hypertension, diabetes, atherosclerosis and cancer. This study is designed to investigate the prognostic value of the pre- and post-treatment serum levels of adiponectin and leptin in luminal A and B invasive breast cancer (IBrC) patients based on six-years follow-up. (2) Methods: Among 70 patients who underwent breast surgery, 35 were Stage I and 35 were Stage II. The concentrations of pre- and post-treatment adiponectin and leptin were evaluated with a specific ELISA kit. The median follow-up was 68.5 months (inter-quartile range (IQR) = 59–72 months) with a recurrence rate of 15.71%. (3) Results: Generally, concentrations of leptin and adiponectin increased after adjuvant therapy. Follow-up showed a significantly higher incidence of disease relapse in IBrC patients with a high post-treatment concentration of leptin (25.71% vs. 5.71% of cases with a low post-treatment concentration of leptin). A post-treatment leptin concentration of 26.88 ng/mL with a specificity of 64.9% and a sensitivity of 88.9% was determined as the best cut-off value to distinguish patients with disease recurrence from those without disease relapse. (4) Conclusions: Our results demonstrated that only the post-treatment serum leptin concentration may be of value as a prognostic indicator and could contribute to predicting a future outcome for patients with early-stage IBrC