Abstract. The aim of the present study was to investigate the effect of hepatocyte growth factor receptor (c-MET) inhibition on the viability of colon cancer cells and xenografts exposed to irradiation using short hairpin (sh)RNA or the c-MET inhibitor PHA665752. The underlying mechanisms were also investigated. Human colorectal adenocarcinoma HT-29 cells were infected with a lentivirus expressing shRNAs against c-MET and were irradiated at 0, 2, 4, 6 and 8 Gy. The viability of the cells was assessed by alamarBlue ® assays. Mice bearing human colon carcinoma SW620 xenografts were randomly selected to receive 2.5% dimethyl sulfoxide (DMSO), 25 mg/kg PHA665752 intraperitoneally once every 2 days for 3 weeks, irradiation at 10 Gy, or 25 mg/kg PHA665752 intraperitoneally once every 2 days for 3 weeks followed 24 h later by irradiation at 10 Gy. The mean tumor volume (MTV) was measured. The apoptotic rate of cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays, and double stranded break marker antibody γ-H2AX and hypoxia inducible factor (HIF)-1α expression was examined by immunohistochemistry. alamarBlue assays revealed that c-MET downregulation by shRNA markedly accentuated the irradiation-induced reduction in the viability of HT-29 cells compared with HT-29 cells irradiated at the same doses (P<0.05). A combination of irradiation and PHA665752 caused an additional reduction in the MTV (382.8±42.4 mm 3 ; P<0.01 vs. irradiation and PHA665752, 998.0±180.6 and 844.8±190.0 mm 3 , respectively). TUNEL assays revealed that irradiation and PHA665752 alone caused significant apoptosis of the SW620 cells in the tumor xenografts (P<0.01 vs. DMSO). The apoptotic index in the tumor xenografts of mice treated with a combination of irradiation and PHA665752 was significantly increased compared with mice treated with either agent alone (P<0.01). The combination of irradiation and PHA665752 was also associated with a marked increase in γ-H2AX levels and a significant decrease in HIF-1α expression in the xenografts (P<0.01). In conclusion, c-MET inhibition sensitizes colorectal cancer cells to irradiation by enhancing the formation of DNA double strand breaks and possibly alleviating tumor hypoxia. IntroductionWorldwide, colorectal cancer (CRC) is the third most common cancer (1). Currently, the standard regimen for newly diagnosed patients with locally advanced rectal cancer (grade, cT3/T4 and cN + ) is surgery in combination with neoadjuvant radiochemotherapy (2,3). However, the majority of patients have mid to advanced stage CRC at the time of diagnosis. Neoadjuvant radiochemotherapy improves the survival and anus-preservation rates by shrinking tumors, decreasing the clinical stage and reducing the pathological grade (4). While patients with local CRC have a more favorable outcome, with a 5-year survival rate of 90%, patients with metastatic CRC have a poor 5-year survival rate of 12%, despite the good therapeutic regimens that are available, including surgical resection, ad...
Background: Pilonidal sinus is a common disease in the sacrococcygeal region. Although many treatments have been described in recent years, the recurrence of each method remains high. Surgeons did not reach a consensus on the preferred approach for pilonidal sinus. We carried out a meta-analysis of controlled clinical trials comparing the outcomes of endoscopic treatment versus conventional treatment for pilonidal sinus disease in this study.Methods: We performed a systematic literature search, and we used electronic databases such as PubMed/Medline, Embase, and the Cochrane library to search for the relevant literature comparing endoscopic management to other conventional treatments for pilonidal sinus disease. The primary outcome parameters were operative time, recurrence, postoperative complications and pain, and total healing time.Results: Six studies were included in the review. Endoscopic pilonidal sinus treatment had a lower overall complication rate than the conventional surgery group (risk ratio = 0.33 [0.19-0.58], P = .0001) and lower pain score with a weighted mean difference of −2.44 (95% confidence interval: (−3.96) to (−0.92), I 2 = 99%, P = .002). There was no significant difference in recurrence (risk ratio = 0.75, 95% confidence interval [0.30-1.90],P = .55). Compared to the excision followed by the primary closure technique, the operation time, time to complete wound healing, and satisfaction were similar.Conclusions: Endoscopic pilonidal sinus treatment is a unique and potential method of sacrococcygeal pilonidal disease treatment. The foremost benefits of this technique are mild postoperative pain, lower complications rate, and return to routine for a shorter time. However, due to the limited number of articles, we need to conduct more rigorous large-sample prospective randomized controlled trials to clarify the efficiency of endoscopic treatment for pilonidal cysts.Abbreviations: CI = confidence interval, EHSI = en-bloc excision and healing by secondary intention, EPC = excision and primary closure, EPSiT = endoscopic pilonidal sinus treatment, ERAS = enhanced recovery after surgery, NA = Not available, PSD = pilonidal sinus disease, RCT = randomized controlled trial, RR = risk ratio.
Background: The prognosis of obstructive colorectal cancer (oCRC) is worse than non-obstructive CRC, but the individualized prediction model for the prognosis of oCRC patients has not been established. The aim of this study was to select prognostic predictors to built a Nomogram model to predic the prognosis of oCRC patients. Methods: A retrospective study was conducted on 181 oCRC partients between February 2012 to December 2017 from three medical hospitals. 129 patients in one of the hospitals were assigned to the training chort.Univariate and multivariate analysis were used to select independent prognostic indicators in a training cohort and a Nomogram model was constructed. 52 patients foom another two hospital were used as the testing cohort to validate the model.Results: Multivariate analysis illustrated the CEA [p=0.037, HR=2.872 (1.065-7.740)], N stage [N1 vs. N0, p=0.028, HR=3.187 (1.137-8.938) ; N2 vs. N0, p=0.010, HR=4.098 (1.393-12.051)] and surgical procedure [p=0.002, HR=0.299 (0.139-0.643)] were independent prognostic factors for OS of oCRC patients. These factors were used to construct the Nomogram model. Both internal and external validation shows it relatively accuracy.Conclusions: CEA, N stage and surgical procedure were independent prognostic factors for OS of oCRC patients, Which can be visually exhibited by Nomogram model.
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