Objective To investigate the effect of caffeic acid phenethyl ester (CAPE) on the growth of human colorectal carcinoma cell line HCT116 transplanted subcutaneously in nude mice. Methods Nude mouse model of human colorectal carcinoma by subcutaneous transplantation of HCT116 cell line was reproduced. A total of 20 mice were divided into 2 groups: control group and CAPE group (oral administration of CAPE at 5mg/mice/d). The growth of the subcutaneously transplanted tumor and changes in mouse body weight in each group after treatment were observed on 7, 14, 21 and 28d. Histopathological examination of xenograft, heart, liver, lung, kidney and intestine of nude mice was also conducted. Apoptosis index was detected by terminal dUTP nick end labeling (TUNEL) technique. Results CAPE had significantly inhibitory effect on growth of the transplanted xenograft in vivo. Tumor volume and tumor weight were decreased (P

0.05),but the MLD values at the tumor margin were significantly higher than that of normal mucosa(P

Objective To investigate the role of APE1 in the carcinogenesis and progression of colorectal carcinoma (CRC). Methods Expression of APE1 was determined with SP immunohistochemical technique in 40 specimens of normal colorectal mucosa, 60 specimens of colorectal mucosa adjacent to CRC, 72 specimens of colorectal adenoma, and 125 specimens of colorectal carcinoma. Results In normal colorectal mucosa, APE1 was detected in nuclei of epithelial cells. Shift of APE1 from nucleus to cytoplasm was observed in 6 of 60 (10%) specimens of mucosa adjacent to cancer. Such shift was observed in 92 of 125 (73.6%) CRC tissues and 60 of 72 (83.3%) colorectal adenoma, the incidence of both of them was significantly higher than that observed in normal colorectal mucosa and colorectal mucosa adjacent to CRC (P

Objective To study the effect of caffeic acid phenethyl ester (CAPE) on the expression of ?-catenin in the cultured colorectal cancer cell lines. Methods HCT116 and W480 cells were treated with CAPE at serial concentrations of 2.5, 5, and 10 mg/L. ?-catenin protein expression was assayed by Western blot analysis. ?-catenin localization was detected by indirect immunofluorescence. Results CAPE treatment was associated with decreased total ?-catenin protein expression. The expression of ?-catenin at the cell nucleus and cytoplasm was downregulated, but at the cell-cell linked site the ?-catenin protein expression was upregulated. Conclusion CAPE can downregulate the expression of ?-catenin and inhibit the translocation of ?-catenin to nucleus, which may play an important role in the anticancer activity of CAPE.

In causal inference, the concept of temporality (or directionality) has not been fully clarified. Starting from causal thinking, this paper divides the time axis in nature into three time domains and two time points by the occurrence timings of both a real cause and a real effect. This has anchored that causal inference can only be realized in the third domain. The measured temporalities can be divided into five types: cross-first-to-third-domain longitudinal (or experimental temporalities), cross-second-to-third-domain longitudinal, within-domain longitudinal, within-domain reversely longitudinal, and within-domain transversal (or observational temporalities). This new classification encompasses all measurement strategies, either for first or multiple measurements, or timely and delayed measurements. Except that the actual measurement for the cause occurs either before its occurrence (only in experiment) or within the second domain, all other measurements are similar to the act of historical reconstruction or "archaeology" , where the importance of measured temporalities may be inferior to the accuracy of the measurements. From the point of view that research design should integrate bias design, this new classification for measured temporalities based on the time axis in Nature, which has a clear meaning and helps to judge the possible biases in the observation methods, provides a basis for correct causal inferences.

Epidemiological analysis describes and compares the characteristics of a certain number of people to make causal inferences. The formation of the study population is always the first step. In this paper, we first define the concepts of cross-sections at both individual level and population level and introduce the three assumptions needed in the measurements in observational studies, i. e. the true values of the attributes are stable with time, the attribute variables are independent and the individuals are independent during the measuring process. We also determine that the causal inference research should be unified based on the time of the occurrence or beginning of a postulated cause, or exposure, should be in. Then, based on the dual roles of the population cross-section with causal thinking, we propose that research designs can be classified into two types with different characteristics: history reconstruction research and future exploration research. Finally, we briefly analyze the research design framework and the relationship between estimated effects and different designs. The discussion of the formation of a study population from the perspective of causal thinking can make a foundation for the classification of causal inference research design with appropriate effect parameters, which needs to be further studied.