Search

Multiple factors including host–microbiota interaction could contribute to the conversion of healthy mucosa to sporadic precancerous lesions. An imbalance of the gut microbiota may be a cause or consequence of this process. The goal was to investigate and analyze the composition of gut microbiota during the genesis of precancerous lesions of colorectal cancer. To analyze the composition of gut microbiota in the genesis of precancerous lesions, a rat model of 1, 2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) was established. The feces of these rats and healthy rats were collected for 16S rRNA sequencing. The diversity and density of the rat intestinal microbiota were significantly different between ACF-bearing and non-bearing group. ACF were induced in rats treated with DMH and showed increased expression of the inflammatory cytokines IL-6, IL-8, and TNF-α. Firmicutes was the most predominant phylum in both ACF-bearing and non-bearing group, followed by Bacteroidetes. Interestingly, although the density of Bacteroidetes decreased from the fifth week to the 17th week in both groups, it was significantly reduced in ACF-bearing group at the 13th week (P

To study the effect and underlying molecular mechanism of eugenol on CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). The effect of eugenol on the inhibition of immortalized MDSC cell line MSC-2 and murine peritoneal macrophages was detected by MTT. Flow cytometry was used to detect the pro-apoptosis effect of eugenol on MDSCs. The expression levels of apoptosis-related proteins were detected by western blot. Eugenol has a selective inhibitory effect on MDSCs in a dose-dependent manner, which activates an endogenous apoptosis pathway, leading to apoptosis. Eugenol promotes the apoptosis of MDSCs via the intrinsic pathway.

The purpose of this work was to study the effects and underlying molecular mechanisms of ligustilide on cancer-associated fibroblasts (CAFs). The effects of ligustilide on the growth of CAFs and splenocytes were detected by MTT assay, and flow cytometry was used to detect effects on T-cell proliferation. Western blotting was used to detect the expression levels of CAF-related proteins after ligustilide treatment. This study found that ligustilide had no effect on the growth of splenocytes but that it could change the immunosuppressive function of CAFs through the TLR4-NF-κB pathway and restore T-cell proliferation previously inhibited by the CAF supernatant. Thus, ligustilide is expected to be a candidate for new antitumor drugs.

Single nucleotide polymorphisms (SNPs) in tumor-related genes have been reported to play important roles in cancer development. Recent studies have shown that 3'-untranslated regions (UTR) polymorphisms are associated with the occurrence and prognosis of cancers. The aim of this study is to analyze the association between KRAS and VEGF gene 3'-UTR SNPs and genetic susceptibility to colorectal cancer (CRC). In this case-control study of 371 CRC cases and 246 healthy controls, we analyzed the association between one SNP (rs1137188G > A) in the KRAS gene and four SNPs (rs3025039C > T, rs3025040C > T, rs3025053G > A and rs10434A > G) in the VEGF gene and CRC susceptibility by the improved multiplex ligase detection reaction (iMLDR) method. We checked the selected SNPs' minor allele frequency and its distribution in the frequency of Chinese people by Hap-map database and Hardy-Weinberg equilibrium, and used multivariate logistic regression models to estimate adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs). We found that the rs3025039C variant genotype in the VEGF gene was associated with a significant protection for CRC (AOR = 0.693, 95% CI = 0.485-0.989; P = 0.043 for CC and CT+TT). Nevertheless, the difference was no longer significant after Bonferroni correction (Bonferroni-adjusted P = 0.172). In genetic polymorphisms analysis, we found that the KRAS rs1137188 variant AA genotype had higher portion of tumor size (≥ 5 cm) (P = 0.01; Bonferroni-adjusted P = 0.04), which suggested that the rs1137188 variant AA genotype may significantly be associated with increased progression of CRC. In conclusion, our study suggested that these five SNPs in the KRAS gene and the VEGF gene were not associated with CRC susceptibility in Han Chinese in Sichuan province.