Role of CD44 high /CD133 high HCT-116 cells in the tumorigenesis of colon cancer

The modified Si-Jun-Zi Decoction (SJZ), a Chinese medicine formula, is clinically used against multiple malignancies including colorectal cancer (CRC). This study aims to evaluate the effect of modified SJZ on CRC liver metastasis and identify the therapeutic mechanisms. Human CRC cells with GFP fluorescence were transplanted into Balb/c nude mice spleens. Modified SJZ, 5-fluorouracil or the combined treatment was given for 3 weeks. CRC liver metastasis was measured by fluorescence imaging and plasma cytokines were analyzed. Furthermore, the effects of administration time and doses for the modified SJZ were investigated in nude mice. Modified SJZ could increase the survival rate and reduce CRC liver metastasis in the nude mice model. Plasma GM-CSF level was elevated. Three weeks of treatment with the modified SJZ at the full dose (45 g/kg) could significantly increase the number of macrophages but not neutrophils in the spleen. These results indicate that modified SJZ can inhibit CRC liver metastasis by activating the innate immune system, providing a complementary and alternative therapy for CRC.

Guan Chang Fu Fang (GCFF) is a natural compound, which is extracted from three medicinal plants, Agrimonia pilosa Ledeb., Patrinia scabiosaefolia and Solanum nigrum L. GCFF has demonstrated clinical efficacy in the treatment of colon cancer. At present, 5‑fluorouracil (5‑FU) is the primary active chemotherapeutic agent used for treating colon cancer. Using median‑effect and apoptosis analyses, fluorescence microscopy and western blotting, the present study analyzed the association between GCFF and 5‑FU in the human colon adenocarcinoma LoVo cell line. The effect of GCFF on the expression of chemotherapeutic agent‑associated genes was also investigated. The results of the synergistic analysis revealed that GCFF exhibited a significant effect upon 5‑FU‑associated cytotoxicity within the LoVo cell line. This effect was observed over a broad dose‑inhibition range (5‑95%), but was particularly significant in the lower concentrations. The flow cytometry results revealed that low doses of GCFF or 5‑FU induced S‑phase arrest, as did a low‑dose combination of the two drugs. After 48 h, GCFF significantly suppressed the expression levels of the chemotherapeutic agent resistance‑associated genes within the colon cancer cells. The western blot analysis revealed that the combined effects of 5‑FU and GCFF were due to a regulation of the B‑cell lymphoma‑2 family of proteins. The findings of the present study suggested that GCFF, when combined with 5‑FU, has the potential to be a novel, chemotherapeutic compound for the treatment of colon cancer.

Background: As one of the most immunogenic malignancies, skin cutaneous melanoma (SKCM) is mainly characterized by a high prevalence in immune-compromised patients and a brisk lymphocyte infiltration in the tumor microenvironment (TME). However, to date, studies on deubiquitination in SKCM are still very limited. Methods: Public data with regard to this study in SKCM patients were acquired from The Cancer Genome Atlas (TCGA) and the Gene-Expression Omnibus (GEO) databases. We stratified TCGA-SKCM cases using consensus clustering and identified independent prognostic factors in deubiquitinating enzymes encoding genes (DECGs) by LASSO-Cox analysis. USP35 transcriptome level was examined using public data and validated by Immunohistochemical (IHC) staining at the protein level. Enrichment analysis was used to explore the potential functions of USP35, and the TISCH database, providing further evidence at the single-cell level. The CIBERSORT algorithm was used to assess the relationship between USP35 and the immune microenvironment, and IHC was used to further evaluate the relationship between USP35 and immunotherapy response. Finally, we used the cBioPortal and the Methsurv database to analyze the significance of genomic alterations of USP35 in melanoma. Results: Our results showed that DECGs can be effectively used to stratify SKCM patients, suggesting their potential significance in the development of SKCM. Furthermore, USP35 overexpression was significantly associated with an unfavorable prognosis. We further revealed that USP35 may be involved in the activation of TORC1 signaling. Most importantly, USP35 was found to be significantly associated with an immunosuppressive TME, both in terms of negative correlation with the abundance of infiltrating CD8+ T cells and in terms of the fact that patients with high USP35 expression may benefit less from immunotherapy than those with low USP35 expression. Conclusion: Deubiquitinating enzymes are of great importance in the diagnosis and treatment of SKCM, and USP35 is an extremely promising target for immunotherapy.

Background: Gastric cancer is a common gastrointestinal tumor, seriously threatening human health. Radical surgery is the preferred treatment for gastric cancer. However, due to the late diagnosis and postoperative recurrence and metastasis, the prognosis is dismal. In China, traditional Chinese medicine (TCM) has been used to treat gastric cancer for many years. The purpose of this study is to explore the efficacy and safety of Yiqi Huayu Jiedu decoction in the treatment of postoperative gastric caner. Methods/design: 226 eligibility patients altogether will be randomly allocated to the treatment group and the control group at a ratio of 1:1. After enrollment, every patients will obtain 6 months of treatment, as well as 2 years of follow-up. At the end of this study, primary outcomes including 1-year progression-free survival rate, 2-year progression-free survival rate and disease-free survival, secondary outcomes containing tumor markers, TCM syndrome points, quality of life scale, imageological examination and the safety indicators will be assessed. Discussion: This study will provide the evidence-based evidence for the efficacy of Yiqi Huayu Jiedu decoction reducing the risk of postoperative gastric cancer recurrence and metastasis, which will be beneficial to form the therapeutic regimen in postoperative gastric cancer with integrated TCM and Western medicine. Trail registration: ChiCTR2000032802

Emerging evidence suggests a profound connection between oral health status and esophageal diseases. Nevertheless, the causal relationship remains controversial. This Mendelian randomization (MR) study was performed to probe into the genetic causality between oral health status and esophageal diseases. Summary statistics from genome-wide association studies were obtained from the FinnGen project and the UK Biobank consortium. The number of instrumental single nucleotide polymorphisms per trait ranged from approximately 8.97 million to 16.38 million. The analyzed datasets included sample sizes of up to 4,63,010 individuals. Univariable MR analyses were conducted to explore the potential bidirectional causality between oral health status and esophageal diseases. Inverse-variance weighted method was primarily employed. To confirm the reliability of our findings, we conducted sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, and leave-one-out test. Furthermore, we conducted multivariable MR analysis to adjust for potential confounders. Mouth ulcers were strongly associated with esophageal carcinoma and Barrett’s esophagus. Toothache tended to increase the risk of Barrett’s esophagus. Excessive attrition of teeth was an increased risk for gastro-esophageal reflux. Patients with dental caries exhibited an increased susceptibility to ulcer of esophagus. In reverse, Barrett’s esophagus increased the risk of chronic periodontitis and excessive attrition of teeth. Ulcer of esophagus tended to increase the risk of excessive attrition of teeth. Sensitivity analysis yielded consistent results, indicating no heterogeneity or pleiotropy. This study suggests potential causal associations between oral health status and esophageal diseases.