1.Investigation of inhibition of liver metastasis of colon carcinoma on the nude mice models with the system of TK/GCV and CD/5-Fc
Hongxin NIU ; Qingsi HE ; Dong WEI ; Wei TAN
Chinese Journal of Current Advances in General Surgery 1999;0(03):-
Objectives:To explore the inhibition effect of TK/GCV and CD/5-FC system on liver metastasis of colon carcinoma.Methods:Forty nude mice were divided into 4 groups randomly,which were the control group,TK group,CD group and TK-CD group with 10 nude mice in each group.The mice in the control group were injected SW480 cells in the spleen and NS into the peritoneal cavity.The mice in other groups were all injected SW480/TK-CD cells in the spleen.And GVC,5-Fc,GVC+5F-c were injected into the peritoneal cavity of the mice in the TK group,CD group and TK-CD group respectively.Liver metastasis rate,the number of liver metastasis,the pathological changes of the tumor tissues under the electronic microscope,tumor cell's apoptotic index and life span and other indexes of nude mice in four groups were analyzed.Results:Liver metastasis rate of nude mice in every treatment group was lower than that in control group.Compared with control group,average number of liver metastasis decreased,life span of nude mice was prolonged,and the apoptosis rate of cancer cell in liver metastasis increased.The combined genes in the TK-CD group worked more markedly,and there was mutual effect between TK/GCV and CD/5-Fc.Conclusions:Synergistic effect was acquired combining TK/GCV with CD/5-FC system and it inhibited the formation of liver metastasis of colon carcinoma efficiently.
2.The construction of a prognostic model for colorectal cancer based on immune gene correlation and drug screening
Wei ZHENG ; Jiajia ZHAO ; Xiang CHENG ; Hongxin TAN ; Qi HUANG
Acta Universitatis Medicinalis Anhui 2024;59(5):789-796
Objective To search for new biomarkers to predict prognosis in colorectal cancer (CRC) patients.Methods A prognostic model was developed for colorectal cancer with immune-related genes from the cancer ge-nome atlas (TCGA) database using one-way Cox regression analysis and least absolute shrinkage and selection op-erator (LASSO) regression analysis.Moreover, the immune infiltration characteristics of patients in high and low risk groups was compared by sstimation of stromal and immune cells in malignant tumor tissues using expression da-ta (ESTIMATE) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) .In addition, the expression levels of immune checkpoints were analyzed in patients from different risk groups.The sen-sitivity of patients in the two risk groups to chemotherapeutic agents was also compared based on genomics of drug sensitivity in cancer (GDSC).Results It was found that the prognostic model constructed based on immune genes could better predict the overall survival (OS) of CRC patients,and the results showed area under curve (AUC) values of 0.764 (95% CI:0.751-0.793), 0.773 (95% CI:0.761 -0.779), and 0.760 (95% CI:0.742 -0.774) for 1-, 3-, and 5-year OS, respectively.Patients in the low-risk group had higher expression levels of im-mune checkpoints and more abundant immune cells such as T cells (P<0.001) , dendritic cells (P<0.001) , macrophages (P<0.001) , neutrophils (P<0.001) .Patients in the high-risk group might be more sensitive to some chemotherapeutic agents such as axitinib, imatinib, methotrexate, pazopanib, rapamycin, sunitinib and tasig-arnib.Conclusion A prognostic model based on 19 immune genes was effective in predicting the prognosis of CRC patients.The number and activity of immune cells in the immune microenvironment in different patients may be an important factor influencing their response to immunocheck inhibitors and chemotherapeutic agents.
3.Effect of Danggui Niantongtang on Intestinal Flora in Adjuvant-induced Arthritis Rats of Wind-dampness-heat Arthralgia:Based on 16S rDNA Sequencing
Luying LIANG ; Hongxin LIN ; Yisi CAI ; Sicong LIN ; Jingwei TAN ; Guoliang MA ; Lixia YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):18-27
ObjectiveTo explore the mechanism of Danggui Niantongtang (DGNTT) against adjuvant-induced arthritis (AA) in rats with wind-dampness-heat arthralgia (FSR) based on the variation of intestinal flora. MethodA total of 60 SD rats were randomized into normal (control) group, FSR group, low-, medium-, and high-dose DGNTT (5.67, 11.34, 22.68 g·kg-1) groups, and methotrexate (MTX) group (1.35 mg·kg-1), with 10 rats in each group. The rats, except the control group, were injected with Mtb adjuvant and then exposed to artificial climatic chamber (hot and humid with wind) for 64 h for modeling. The rats were treated with water, DGNTT or MTX for 28 days from the day of injection. Arthritis index (AI) of rats was measured and paw volume was determined with a volume meter. The morphology of synovial tissues of the knees was observed based on hematoxylin-eosin (HE) staining and the changes of intestinal flora were analyzed based on 16S rRNA sequencing. ResultDGNTT can alleviate the hyperplasia of synovial tissue and inflammation of AA rats with FSR and inhibit the formation of pannus. The results of 16S rRNA sequencing showed that the relative abundance of Firmicutes, Lactobacillus, Prevotella 9, and Alloprevotella decreased (P<0.05, P<0.01) and the relative abundance of Bacteroidetes and Bacteroides increased (P<0.01) in FSR group compared those in the control group. Compared with the FSR group, all DGNTT groups and MTX group had high relative abundance of Lactobacillus (P<0.05, P<0.01) and low relative abundance of Bacteroidetes (P<0.01) and medium-dose and high-dose DGNTT groups and MTX group showed high abundance of Firmicutes, Prevotella 9, and Alloprevotella and low abundance of Bacteroides (P<0.05, P<0.01). Spearman's correlation analysis suggested that the abundance of Bacteroides and Helicobacter was in positive correlation with AI (P<0.05), while the abundance of Prevotella 9 and Candidatus Saccharimonas was in negative correlation with AI (P<0.01, P<0.05). There was a negative correlation between the abundance of Prevotella 9 and paw volume (P<0.01), and the abundance of Ruminococcaceae NK4A214 group, Christensenellaceae R-7 group, and Bacteroides was in negative correlation with spleen index (P<0.05). The abundance of Prevotella 9 was in negative correlation with spleen index (P<0.01). ConclusionDGNTT is effective for arthritis with FSR, as it can regulate the composition of intestinal flora in AA rats by increasing the abundance of probiotics and inhibiting the growth of pathogenic bacteria. The mechanism is the likelihood that it improves intestinal immune metabolism to ensure intestinal homeostasis.