ABSTRACT
Background: This study sought to evaluate the efficacy of a novel intraoperative chemotherapy (IOC) regimen that consists of hydroxycamptothecin, tumor necrosis factor (TNF), 5-fluorouracil (5-FU), and calcium folinate (CF) on the outcomes of colorectal cancer (CRC). Methods: In total, 551 CRC patients who had undergone surgical resection were evaluated. Among these patients, 247 were treated with postoperative adjuvant chemotherapy, and 193 were treated with intraoperative chemotherapy. Of the CRC patients who underwent chemotherapy, 52 were treated with both postoperative adjuvant chemotherapy and intraoperative chemotherapy. Patients' characteristics, including age, sex, stage, differentiation, lymph node metastasis, surgical-pathological staging, tumor location, tumor size, and relapse-free survival, were collected. Results: IOC for CRC therapy was associated with a more favorable survival prognosis (HR, 0.30, 95%CI, 0.19-0.48, P<0.001) independent of other clinical covariates. CRC patients treated with IOC survived longer than patients who were not treated with IOC did during surgery (P<0.0001, Kaplan-Meier log rank). Meanwhile, a Kaplan-Meier analysis demonstrated that individuals who received both IOC and POC survived longer than patients who received only POC: for stage II and stage III patients (P=0.0001, Kaplan-Meier log rank), stage II patients alone (P=0.02, Kaplan-Meier log rank), and stage III patients alone (P=0.046, Kaplan-Meier log rank). Conclusions: The therapeutic effects of colorectal cancer by intraoperative chemotherapy with a novel regimen were enhanced, which improved the prognosis of patients with CRC.
ABSTRACT
BACKGROUND/AIMS: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. METHODS: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot. RESULTS: Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function. CONCLUSION: Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.
Subject(s)
Gastrointestinal Diseases/diagnosis , MicroRNAs/metabolism , Occludin/genetics , p38 Mitogen-Activated Protein Kinases/metabolism , Adult , Aged , Animals , Biomarkers/metabolism , Cholera Toxin/blood , Cholera Toxin/genetics , Cholera Toxin/metabolism , Colon/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/metabolism , Haptoglobins , Humans , Interleukin-6/blood , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/blood , MicroRNAs/genetics , Middle Aged , Occludin/metabolism , Protein Precursors , Signal Transduction , Tumor Necrosis Factor-alpha/bloodABSTRACT
BACKGROUND/AIMS: This study aimed to investigate the role of microRNA (miR)-122a in regulating zonulin during the modulation of intestinal barrier. METHODS: Zonulin proteins and their target gene expression were analyzed in miR-122a-overexpressing cell lines and in the target gene of epidermal growth factor receptor (EGFR). An mmu-miR-122a intestinal epithelial conditional transgenic (miR-122a-TG) mouse model was established to investigate EGFR and zonulin expression. MiR-122a was also detected in the clinical specimens of inflammatory bowel disease. RESULTS: EGFR was identified as a target gene of miR-122a. The expression level of miR-122a was positively correlated with that of zonulin. The expression level of zonulin was significantly increased, whereas the expression level of EGFR was significantly decreased in the miR-122a-TG mice and in the corresponding primary epithelial culture (P < 0.05). These results were consistent with the data of the clinical specimens. CONCLUSIONS: miR-122a could be a positive factor of zonulin by targeting EGFR, which increased the intestinal epithelial permeability in vivo and in vitro.
