Objective To explore the research status and development tendency of relation between indoleamine 2，3-dioxygenase （IDO） and immune escape of gastric cancer. Methods The related literatures about IDO， immune escape of gastric cancer， and their the relationship at domestic and international in recent ten years were collected and reviewed. Results Gastric cancers induced that dendritic cells expressed IDO by the CD4＋ CD8＋ regulatory T cells， which made the microenviroment tryptophan starvation， thus inhibited T cell proliferation. While tryptophan metabolites existed T cell cytotoxicity that inhibited T cell proliferation. IDO-specific inhibitor 1-MT combinated with chemotherapy drugs in the treatment for gastric cancer was a synergistic effect. Conclusions IDO as an immune modulating enzymes may play a key role in the process of immune tolerance that induced by gastric body. IDO may become a new target for inhibition of gastric malignancy formation and enhance the effectiveness of tumor immune treatment.
ObjectiveBased on a large sample of data, study the factors affecting the survival and prognosis of patients with rectal cancer and construct a prediction model for the survival and prognosis.MethodsThe clinical data of 26 028 patients with rectal cancer were screened from the Surveillance, Epidemiology, and End Results (SEER) clinical database of the National Cancer Institute. Univariate and multivariate Cox proportional hazard regression analysis were used to screen related risk factors. Finally, the Nomogram prediction model was summarized and its accuracy was verified.ResultsResult of multivariate Cox proportional hazard regression analysis showed that the risk factors affecting the survival probability of rectal cancer included: age, gender, marital status, TMN staging, T staging, tumor size, degree of tissue differentiation, total number of lymph nodes removed, positive lymph node ratio, radiotherapy, and chemotherapy (P<0.05). Then we further built the Nomogram prediction model. The C index of the training cohort and the validation cohort were 0.764 and 0.770, respectively. The area under the ROC curve (0.777 and 0.762) for 3 years and 5 years, and the calibration curves of internal and external validation all indicated that the model could effectively predict the survival probability of rectal cancer.ConclusionThe constructed Nomogram model can predict the survival probability of rectal cancer, and has clinical guiding significance for the prognostic intervention of rectal cancer.
Primary human hepatocytes (PHH) are the gold standard of in vitro human liver model for drug screening. However, a problem of culturing PHH in vitro is the rapid decline of cytochrome P450 (CYP450) activity, which plays an important role in drug metabolism. In this study, thermo-responsive culture dishes were used to explore the conditions for murine embryonic 3T3-J2 fibroblasts to form cell sheet. Based on the cell sheet engineering technology, a three-dimensional (3D) “sandwich” co-culture system of 3T3-J2 cell sheet/PHH/collagen gel was constructed. The tissue structure and protein expression of the model section were observed by hematoxylin eosin staining and immunofluorescence staining respectively. Phenacetin and bupropion were used as substrates to determine the activity of CYP450. The contents of albumin and urea in the system were determined by enzyme linked immunosorbent assay (ELISA). The results showed that the complete 3T3-J2 cell sheet could be obtained when the cell seeding density was 1.5×106 /dish (35 mm dish) and the incubation time at low temperature was 60 min. Through cell sheet stacking, a 3D in vitro liver model was developed. Compared with the two-dimensional (2D) model, in the 3D model, the cell-cell and cell-matrix connections were tighter, the activities of cytochrome P450 CYP1A2 and cytochrome P450 CYP2B6 were significantly increased, and the secretion levels of albumin and urea were increased. These indexes could be maintained stably for 21 d. Therefore, cell sheet stacking is helpful to improve the level of liver function of 3D liver model. This model is expected to be used to predict the metabolism of low-clearance drugs in preclinical, which is of great significance for drug evaluation and other studies.
ObjectiveTo investigate expression and clinical significance of long chain noncoding RNA POU6F2-AS2 in human gastric cancer tissues.MethodsSeventy-three pairs of human gastric cancer and matched paracancerous tissues from May 2017 to May 2018 in the Affiliated Hospital of North Sichuan Medical College were collected. The real-time fluorescence quantitative polymerase chain reaction was used to detect the expression level of POU6F2-AS2 in the gastric cancer tissue and its paracancerous tissue. The correlations between its expression level and clinicalpathologic features of patients were analyzed by the chi-square text. The relationship between the expression of POU6F2-AS2 and the overall survival rate of patient with gastric cancer was analyzed by the Kaplan Meier Plotter database data.ResultsThe relative expression of POU6F2-AS2 in the gastric cancer tissues was significantly higher than that in the corresponding adjacent tissues (P<0.050). The patients were divided into the high expression (43 cases) and low expression group (30 cases) according to the expression level of POU6F2-AS2 in the gastric cancer tissues and their corresponding adjacent tissues. The results of the relationship between the expression of POU6F2-AS2 and the clinicopathologic characteristics of patients with gastric cancer showed that the POU6F2-AS2 expression was significantly correlated with the depth of invasion (P=0.022) or the TNM stage (P=0.032). There were no significant differences in the gender, age, smoking history, drinking history, tumor diameter, degree of differentiation, lymph node metastasis, distant metastasis, vascular invasion, nerve invasion, liver metastasis, ascites, and fat nodule metastasis (P>0.050). The overall survival rate of high expression of POU6F2-AS2 in the patient with gastric cancer was significantly worse than that of the low expression of POU6F2-AS2 by the Kaplan Meier Plotter database.ConclusionsHigh expression of POU6F2-AS2 is related to depth of tumor invasion and TNM stage, which indicates that POU6F2-AS2 might play an important role in regulating occurrence and development of gastric cancer. It may be used as an important target for gene diagnosis and treatment of gastric cancer and as a biomarker for evaluating prognosis of patients with gastric cancer.
Objective To study the therapeutic effect of Roux-en-Y gastric bypass （RYGB） on type 2 diabetes mellitus （T2DM） rats and explore the possible mechanism of vaspin in RYGB on T2DM. Methods Twenty SD rats with T2DM and 20 age- and sex-matched normal SD rats were randomly divided into 4 groups according to the random digits table：T2DM-RYGB group， T2DM-sham operation （SO） group，RYGB group，and SO group，10 rats in each group. Fasting plasma glucose （FPG） level，serum insulin （INS） level，vaspin level，and homeostasis model of insulin resistance （HOMA-IR） were determined before operation and on week 4，8 after operation，respectively．At the same time，the correlation between vaspin and the indicators （FPG，INS，or HOMA-IR） was analyzed．Results Compared the indicators after operation with before operation，the FPG level，INS level，vaspin level，and HOMA-IR were not significantly different between the T2DM-RYGB group and T2DM-SO group （P＞0.05） or between the RYGB group and SO group （P＞0.05），but the FPG level，INS level，vaspin level，and HOMA-IR in the T2DM-RYGB group and T2DM-SO group were significantly higher than those in the RYGB group （P＜0.05） and SO group （P＜0.05），respectively. On week 4 after operation，the FPG level，INS level，vaspin level，and HOMA-IR decreased in the T2DM-RYGB group，except for the FPG level，the other indexes had no significant differences as compared with the values before operation. On week 8 after operation，the FPG level，INS level，vaspin level，and HOMA-IR further decreased in the T2DM-RYGB group，there were significant differences of these indicators between before operation and on week 8 after operation. Compared the indicators after operation with before operation，the FPG level，INS level，vaspin level，and HOMA-IR were not statistically significant （P＞0.05） in the T2DM-SO group，RYGB group，or SO group. The changes in serum vaspin level correlated positively with those in INS and HOMA-IR before operaion and on week 4，8 after operaion in the T2DM-RYGB group and T2DM SO group rats （P＜0.05），respectively. Conclusions RYGB surgery has a therapeutic effect on T2DM rats，and serum vaspin level decreases and insulin resistance is improved after RYGB surgery，which may be one of the mechanisms of the treatment for T2DM.
Objective To clarify the role of gastrokine 1 in the process of formation and development of gastric cancer. Methods The expressions of gastrokine 1 in gastric cancer and paracancerous tissues of 52 patients with gastriccancer were detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR） and immunohistochemistry. Meanwhile the relationship of the expression level of gastrokine 1 with clinicopathologic characteristics were analyzed. Results The expression levels of gastrokine 1 gene and protein in the gastric cancer tissues were significantly lower than those in the paracancerous tissues （P＜0.01）. No significant relationship was found between expression of gastrokine 1 gene and clinicopathologic features including tumor location， depth of invasion， differentiation， lymph node metastasis， tumor stage， gender， age， and preoperative peripheral blood CEA and CA19-9 levels （P＞0.05，respectively）. What’s more， the expression level of gastrokine 1 gene in gastric cancer tissues of Helicobacter pylori （HP）-positive patients was lower than that in the negative ones （P＜0.05）. Conclusions Gastrokine 1 may play a significant role as an anti-oncogene in the process of the formation and development of gastric cancer. Its effect may become weak due to HP infection in gastric cancer patients.