To investigate whether ABL specific tyrosine kinase specific inhibitor STI571 can restore beta1 integrin mediated negative effect on Ph(+) chronic myeloid leukemia(CML), the inhibitory effect of beta 1 integrin activator (beta1 integrin activating antibody 8A2, cytokines such as GM-CSF, G-CSF and SCF) and/or FN on the granulocyte-macrophage colony forming unit (CFU-GM) from 16 patients with Ph(+)CML and 13 normal individuals were examined; the bone marrow mononuclear cells (BMMNC) before and after ABL kinase specific inhibitor STI571 pretreatment (0.1 micro mol/L for 30-60 minutes) were target cells in this study. The roles which VLA4 and VLA5 played in this process were evaluated through blocking assay. The results showed: (1) beta1 integrin activator(s) or FN alone have no effect on CFU-GM from CML or normal bone marrow mononuclear cells before or after STI571 pretreatment, nor STI571 pretreatment itself. (2) The inhibitory effect of beta1 integrin activator(s) plus FN on CML CFU-GM are significantly lower than that on normal CFU-GM. (3) The inhibitory effect of beta1 integrin activator(s) plus FN on CML CFU-GM after STI571 pretreatment is comparable to that on normal CFU-GM. (4) Monoclonal antibody to VLA4 and VLA5 or to total beta1 integrins almost completely abrogate the above effect of STI571. The results suggested enhancing beta1 integrin mediated negative effect on myeloid progenitors in Ph(+)CML is one of the therapeutic mechanisms of STI571 on Ph(+)CML.

Objective To reduce the cancer burden in the Jinchang cohort and provide evidence for developing cancer prevention strategies and performing effectiveness evaluation in the Jinchang cohort.We are fitting thirteen years of cancer mortality data from the Jinchang cohort by using six kinds of predicting methods to compare relative fitness and to select good predicting methods for the prediction of cancer mortality trends.Methods The mortality data of cancer in Jinchnag cohort from 2001-2013 were fitted using six kinds of predicting methods:dynamic series,linear regression,exponential smoothing,autoregressive integrated moving average (ARIMA) model,grey model (GM),and Joinpoint regression.Weight coefficients of combination models were calculated by four methods:the arithmetic average method,the variance inverse method,the mean square error inverse method,and the simple weighted average method.Results The cancer mortality was fitted and compared by using six kinds of forecasting methods;the fitting precision of the Joinpoint linear regression had the highest accuracy (87.64％),followed by linear regression (87.32％),the dynamic series (86.99％),GM (1,1) (86.25％),exponential smoothing (85.72％) and ARIMA (1,0,0) (81.98％),respectively.Prediction accuracy of the combination model derived from GM (1,1) and linear regression (＞99％) was higher than that of the combination model derived from ARIMA (1,0,0) and GM (1,1).The combination model derived from the GM (1,1) and linear regression,with weight coefficients based on the arithmetic average method and the mean square error inverse method,had the best prediction effect of the four weight calculation methods.Conclusion Prediction accuracy of the combination model,with accuracy ＞95％,was higher than that of the single prediction methods.

Vascular endothelial growth factor (VEGF) is one of the main angiogenic cytokines and plays an important role in the development of human solid tumors. However, it is not clarified whether VEGF governs the progress of the chronic myelogenous leukemia (CML). This study is to estimate VEGF expression in the bone marrow cells from normal and adult CML patients and various leukemic cell lines. Reverse transcription-polymerase chain reaction (RT-PCR) was used for detection of VEGF mRNA. VEGF concentrations in the cell cultural supernatant and the plasma from normal and CML patient bone marrows were determined by enzyme linked immunosorbent assay (ELISA). VEGF mRNA was positive in 67 of 72 cases of bcr/abl(+) CML patient bone marrow cells (93.1%), in 5 of 10 CML patients post Allo-BMT bone marrow cells (50%), and in 6 of 10 normal bone marrow cells (60%), the expression rate of VEGF mRNA in CML patients bone marrow cells was higher than that in CML patients post Allo-BMT and normal bone marrow cells. VEGF mRNA also expressed in the HL-60, K562, CEM, KG1a, NB4, and Nalm6 cells, but not in the Jurkat cells. The mean VEGF concentration in the plasma (380.6 pg/ml) from 22 untreated CML patients was 9 folds higher than that from 9 CML patients post Allo-BMT (38.0 pg/ml). The mean VEGF concentration in the cultural supernatant (499.8 pg/ml) of 17 newly diagnosed CML bone marrows was 2.5-folds higher than that in 11 normal donors (141.3 pg/ml). The CML marrow cells secrete more VEGF than normal marrow cells do. Our results suggest that the abnormality of VEGF transcription and translation expression may play an important role in the development of CML.

To investigate the effect of vascular endothelial growth factor (VEGF) on beta1 integrin (VLA-4 and VLA-5) activation ability in K562 cells transfected with antisense VEGF121 cDNA, K562 cells were transfected with antisense (As), sense (S) and vector (V, pcDNA(3)). Flow cytometry was used to evaluate the expression rate of VLA-4 (CD49d/CD29) and VLA-5 (CD49e/CD29) and beta1 integrin activation ability in the transfected K562 cells. The results showed that the expression rates of VLA-4 and VLA-5 were more than 92% in the transfected K562 cells and there was no difference among the K562/V, K562/S and K562/As cells. However, beta1 integrin activated 9EG7 expression rate in K562/As cells was higher than that in K562/V cells [(75.6 +/- 10.5)% vs (41.2 +/- 2.1)%, P < 0.01)] after activation with beta1 integrin activator 8A2. It is concluded that function of beta1 integrin to be activated is restored in K562 cells transfected with antisense VEGF121 cDNA.
DNA ; genetics ; DNA, Antisense ; genetics ; Endothelial Growth Factors ; genetics ; metabolism ; Flow Cytometry ; Humans ; Integrin alpha4beta1 ; biosynthesis ; Integrin alpha5beta1 ; biosynthesis ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; K562 Cells ; Lymphokines ; genetics ; metabolism ; Transfection ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Objective To investigate the effectiveness of a new health education pathway for echinococcosis control among primary school students in regions highly prevalent for echinococcosis in China. Methods Six primary schools were randomly selected from echinococcosis hyper-endemic regions, with 13 classes assigned to the intervention group and 9 to the control group, and all students in these 21 classes were recruited as the study subjects. Echinococcosis health education was performed through the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices in the intervention group, while routine health education was given in the control group. A questionnaire survey was performed to assess the score of echinococcosis control knowledge (including theoretical knowledge score and mean daily practical capability score) before and after the health education interventions to evaluate the effectiveness of this new health education pathway for echinococcosis control. Results The mean score of echinococcosis control knowledge was 68.86 ± 18.70 points at baseline, with the mean theoretical knowledge score of 40.97 ± 10.75 points, and the mean daily practical capability score of 27.89 ± 12.50 points. Clustering analysis showed three types of populations, including “unsatisfactory”, “learn and apply creatively”, and “rote learning”, which accounted for 24.62% (240/975), 45.74% (446/975) and 29.64% (289/975), respectively. The mean score of echinococcosis control knowledge was 81.08 ± 18.15 points in the intervention group during the final assessment, with the mean theoretical knowledge score of 43.65 ± 9.40 points, and the mean daily practical capability score of 37.43 ± 12.22 points, and both were significantly higher relative to baseline (t = −4.201 and −15.202, both P values < 0.01). The mean score of echinococcosis control knowledge was comparable between at baseline (70.55 ± 19.46 points) and final assessment (71.74 ± 19.37 points) in the control group (t = −0.87, P > 0.05). Conclusions The awareness of echinococcosis control knowledge is fair among primary school students in echinococcosis hyper-endemic regions; however, the capability of combining theoretical learning and practices requires to be improved. The health education mode based on the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices seems to remarkably improve the understanding of echinococcosis control knowledge among primary school students in echinococcosis hyper-endemic regions.