Profiles of endoglin and vascular endothelial growth factor based on staging and histological grading of colorectal cancer and their relationship with bevacizumab therapy / Perfis da endoglina e do fator de crescimento endotelial vascular com base no estadiamento e na graduação histológica do câncer colorretal e sua relação coma terapia com bevacizumabe

Objective: The present study evaluated the profile of endoglin (CD105) and vascular endothelial growth factor (VEGF) based on staging and histopathological grading of colorectal cancer as well as their relationship with bevacizumab therapy. Methods: A total of 88 cases of colorectal adenocarcinoma were included in the present study. The levels of VEGF and CD105 protein were evaluated with enzymelinked immunosorbent assay (ELISA). Results: There was a significant difference in the level of CD105 (p=0.002) between metastases and non-metastases subjects, showing that CD105 was higher in metastases subjects (4.59 ng/ml). Therewas no significant difference in the level of VEGF based on the presence of metastasis (p=0.625). There was a significant difference in the levels of CD105 (p=0.038) and VEGF (p=0.010) between the subjects who received chemotherapy and those who did not. The CD105 level was higher in the subjects who received chemotherapy (4.43 ng/ml); conversely, the level of VEGF was lower in subjects who received chemotherapy (543.65 pg/ml). There was a statistically significant difference in the levels of CD105 (p=0.003) and VEGF (p=0.002) between subjects who received bevacizumab therapy and subjects who did not. The levels of CD105 were higher in subjects who received bevacizumab therapy (5.11 ng/ml); in contrast, the level of VEGF was higher in subjects who did not receive bevacizumab therapy (645.92 pg/ml). There was a significant positive correlation between CD105 and VEGF in subjects who did not receive bevacizumab (p<0.01). Conclusion: The results of this study support a hypothesis of "escape mechanism" in the failure of anti-angiogenesis therapy (anti-VEGF). (AU)

Objetivo: Este estudo avaliou o perfil da endoglina (CD105) e do fator de crescimento endotelial vascular (FCEV) com base no estadiamento e graduação histopatológica do câncer colorretal, assim como sua relação com a terapia com bevacizumabe. Métodos: No total, 88 casos de adenocarcinoma colorretal foram incluídos no presente estudo. Os níveis das proteínas FCEV e CD105 foram avaliados com ensaio imunoenzimático (ELISA, na sigla em inglês). Resultados Houve uma diferença significativa no nível de CD105 (p=0,002) entre indivíduos commetástases e semmetástases, que indicou que o nível de CD105 émais alto em indivíduos com metástases (4,59 ng/ml). Não houve diferença significativa no nível de FCEV com base na presença de metástases (p=0,625). Houve diferença significativa nos níveis de CD105 (p=0,038) e de FCEV (p=0,010) entre os indivíduos que receberam quimioterapia e os que não receberam. Encontrou-se um nível de CD105 mais alto nos indivíduos que submetidos a quimioterapia (4,43 ng/ml); Em contrapartida, encontrou-se um nível de FCEV mais baixo em indivíduos que submetidos a quimioterapia (543,65 pg/ml). Houve uma diferença estatisticamente significativa nos níveis de CD105 (p=0,003) e de FCEV (p=0,002) entre os indivíduos submetidos e não submetidos à terapia com bevacizumabe. Os níveis de CD105 foram mais elevados em indivíduos submetidos à terapia combevacizumab (5,11 ng/ml); em contraste, observou-se um nível de FCEV mais alto em indivíduos que não foram submetidos à terapia com bevacizumabe (645,92 pg/ml). Houve uma correlação positiva significativa entre CD105 e FCEV em indivíduos que não receberam bevacizumabe (p<0.01). Conclusão: Os resultados deste estudo corroboram a hipótese de "mecanismo de escape" na falha da terapia anti-angiogênica (anti-FCEV). (AU)

Proatherogenic or antiatherogenic high density lipoprotein type in acute coronary syndrome and healthy male person.

Aim: To make proatherogenic/antiatherogenic HDL type criteria using Apolipoprotein A-I (ApoA-I), Paraoxonase-1 (PON-1), Neopterin and HDL-cholesterol levels, which may be useful in clinical practice. Methods: This was a case control study recruiting 52 subjects with Acute Coronary Syndrome (ACS) and 30 control healthy subjects. HDL type was classifi ed into antiatherogenic and proatherogenic based on the levels of ApoA-I, PON-1, Neopterin and HDL-cholesterol. Concentrations of ApoA-I was measured by immunoturbidimetry method, PON-1 was measured by colorimetric method, Neopterin was measured by ELISA, and HDL-C was determined by homogenous method. Univariate logistic regression analysis was done using ACS as a dependent variable and levels of ApoA-I, PON-1, Neopterin and HDL-cholesterol as independent variables. Proatherogenic/antiatherogenic HDL type was determined by using ApoA-I, PON-1, Neopterin and HDL-cholesterol cut off and odd ratios. Results: Patient’s age was 50.89 + 12.63 year, HDL-C was 39.82 + 9.84 mg/dL, Apo A-1 was 119.77 + 32.05 mg/ dL, PON-1 was 41.26 + 18.19 kU/L, Neopterin was 16.22 + 38.10 nmol/L. Cut offs of ApoA-I, PON-1 and Neopterin successively were 124.5 mg/dL, 40.8 kU/L, and 7.016 nmol/L. On univariate logistic regression analysis showed that OR of ApoA-I, PON-1 and Neopterin respectively were 29.759 (95% CI : 4.074 – 217.382), 1.647 (95% CI : 0.412 – 6.586), 4.317 (95% CI : 1.098 – 16.977). Using scoring system, we concluded that total score > 18 was proatherogenic HDL type, and total score < 18 was antiatherogenic HDL type. With this scoring we found 78.85% had proatherogenic HDL type in ACS population. Conclusions: Dysfunctional HDL or proatherogenic/antiatherogenic HDL type can be predicted by using ApoA-I – PON-1 – Neopterin – HDL-cholesterol scoring system. Those with score of 18 are supposed to have antiatherogenic HDL type, and those with score of > 18 were having proatherogenic HDL type.

Correlation between F2-Isoprostane with stromal cell-derived factor-1 (SDF-1) and endothelial progenitor cell in nonhypertensive and hypertensive patients.

diseases. On the other hand, hypertension is related with excess angiotensin II which would lead to oxidative stress. In this study, we investigated the correlation between F2-Isoprostane (as marker of oxidative stress) with Stromal Cell-Derived Factor-1 (SDF-1) and CD34 viable in non hypertension and hypertension subjects. Methods This was a cross sectional study conducted on 54 nonhypertension and 64 hypertension subjects visiting Prodia laboratory, Jakarta. F2-Isoprostane (as marker of oxidative stress) and SDF-1 (a strmal cell growth factor) were measured by ELISA method, and CD34 viable (marker of progenitor cell) was measured by fl ow cytometry. Results F2-Isoprostane concentration was higher in hypertensive subjects compared to nonhypertensive subjects, although statistically non signifi ant (mean + SD: 0.13 ± 0.120 vs 0.10 ± 0.16; ρg/mL; p = 0.091). SDF-1 concentration was signifi cantly higher in hypertensive subjects compare to nonhypertensive subjects (2821.63 ± 281.94 vs 2623.04 ± 356.28 ρg/mL; P < 0.05). CD34 viable level was signifi cantly lower in hypertensive subjects compare to nonhypertensive subjects (1.9 ± 0.9 /μL vs 2.7 ± 1.7; P < 0.05). F2-Isoprostane had negative correlation with CD34 viable in circulation (r = 0.022, p < 0.05) but no correlation with SDF-1 (p > 0.05). Conclusions F2-Isoprostane was higher, but CD34 was lower, in hypertensive subjects compared to nonhypertensive. It seems that high F2-Isoprostane impaired the CD34 viable level as shown by negative correlation between F2- Isoprostane and CD34.