CDC20 Holds Novel Regulation Mechanism in RPA1 during Different Stages of DNA Damage to Induce Radio-Chemoresistance.

Targeting CDC20 can enhance the radiosensitivity of tumor cells, but the function and mechanism of CDC20 on DNA damage repair response remains vague. To examine that issue, tumor cell lines, including KYSE200, KYSE450, and HCT116, were utilized to detect the expression, function, and underlying mechanism of CDC20 in radio-chemoresistance. Western blot and immunofluorescence staining were employed to confirm CDC20 expression and location, and radiation could upregulate the expression of CDC20 in the cell nucleus. The homologous recombination (HR) and non-homologous end joining (NHEJ) reporter gene systems were utilized to explore the impact of CDC20 on DNA damage repair, indicating that CDC20 could promote HR repair and radio/chemo-resistance. In the early stages of DNA damage, CDC20 stabilizes the RPA1 protein through protein-protein interactions, activating the ATR-mediated signaling cascade, thereby aiding in genomic repair. In the later stages, CDC20 assists in the subsequent steps of damage repair by the ubiquitin-mediated degradation of RPA1. CCK-8 and colony formation assay were used to detect the function of CDC20 in cell vitality and proliferation, and targeting CDC20 can exacerbate the increase in DNA damage levels caused by cisplatin or etoposide. A tumor xenograft model was conducted in BALB/c-nu/nu mice to confirm the function of CDC20 in vivo, confirming the in vitro results. In conclusion, this study provides further validation of the potential clinical significance of CDC20 as a strategy to overcome radio-chemoresistance via uncovering a novel role of CDC20 in regulating RPA1 during DNA damage repair.

Perineal wound complication risk factors and effects on survival after abdominoperineal resection of rectal cancer: a single-centre retrospective study.

PURPOSE: This study determined the risk factors associated with perineal wound complications (PWCs) and investigated their effect on overall survival in patients with rectal cancer who underwent abdominoperineal resection (APR). METHODS: The clinicopathologic and follow-up data of patients who underwent APR for primary rectal cancer between 1998 and 2018 were reviewed. PWCs were defined as any perineal wound that required surgical intervention, antibiotics, or delayed healing for more than 2 weeks. The primary objective was identifying the risk factors of PWC after APR. The effect of PWC on survival was also investigated as a secondary objective. RESULTS: Two hundred and twenty patients were included in the final analyses and 49 had PWCs. An operative time of > 285 min (odds ratio: 2.440, 95% confidence interval (CI): 1.257-4.889) was found to be independently associated with PWCs. When the follow-up time was > 60 months, patients with PWCs had a significantly lower overall survival rate than patients without PWC (n = 156; mean over survival: 187 and 164 months in patients without and with PWCs, respectively; P = 0.045). Poor differentiation (hazard ratio (HR): 1.893, 95% CI: 1.127-3.179), lymph node metastasis (HR: 2.063, 95% CI: 1.228-3.467), and distant metastasis (HR: 3.046, 95% CI: 1.551-5.983) were associated with poor prognosis. CONCLUSION: Prolonged operative time increases the risk of PWCs, and patients with PWCs have a lower long-term survival rate than patients without PWCs. Therefore, surgeons should aim to reduce the operative time to minimise the risk of PWC in patients undergoing APR for rectal cancer.

Dysregulated expression of T cell immunoglobulin and mucin domain 3 is associated with the disease severity and the outcome of patients with spontaneous intracerebral hemorrhage.

OBJECTIVES: We aimed to investigate the expression of T cell immunoglobulin and mucin domain 3 (Tim-3) on peripheral blood cells in spontaneous intracerebral hemorrhage (ICH) patients and to analyze its clinical significance. DESIGN AND METHODS: Tim-3 expression on peripheral immunocytes from ICH patients and healthy volunteers was measured by flow cytometry. The correlation between Tim-3 expression and the clinical indices was estimated using linear regression. RESULTS: Tim-3 expressions on peripheral CD3⁺ T cells and CD8⁺ T cells in ICH patients are significantly downregulated, while Tim-3 expressions on CD14⁺ monocytes and CD16⁺CD56⁺ NK cells are increased. Furthermore, Tim-3 expression on peripheral CD8⁺ cells was negatively correlated with the inflammatory response, the disease severity and the outcome of ICH patients. However, there was no relationship between Tim-3 expression and blood glucose concentration. CONCLUSIONS: Altered expression of Tim-3 might play an important role in the pathogenesis of ICH, demonstrating that Tim-3 might be a novel candidate molecule for prognosis evaluation of ICH patients.