Cetuximab, an IgG1 monoclonal antibody against the epidermal growth factor receptor (EGFR), is widely used for the treatment of metastatic colorectal cancer (mCRC). One of the mechanisms of action is considered to be antibody-dependent cell-mediated cytotoxicity (ADCC) triggered by Fcγ-R on natural killer cells. However, whether ADCC is associated with EGFR expression and/or the mutational status of EGF downstream effectors (KRAS and BRAF) in colorectal cancer (CRC) remains unclear. The aim of the present study was to verify whether ADCC activities are associated with the cell surface expression levels of EGFR and/or the mutational status of KRAS and BRAF. Five human CRC cell lines with different cell surface expression levels of EGFR and different KRAS and BRAF mutational statuses were selected to evaluate ADCC activity using peripheral blood mononuclear cells (PBMCs) from healthy human donors. Furthermore, tumor cells from resected specimens of CRC patients were used to evaluate the cell surface expression level of EGFR using immunohistochemistry and the KRAS and BRAF mutational statuses using direct sequencing, while the ADCC activity was examined using PBMCs from the same CRC patients. A strong correlation was observed between the expression levels of EGFR and the ADCC activities in the cell lines (correlation coefficient: 0.949; P=0.003). Of the 13 resected specimens, a high ADCC activity level was significantly observed in tumor cells with high expression levels of cell surface EGFR, when compared with that in the tumor cells with low expression levels (P=0.027). In both CRC cell lines and tumor cells from CRC patients, the ADCC activities were significantly associated with the cell surface expression levels of EGFR [standard partial regression coefficients: 0.911 (P=0.017) and 0.660 (P=0.018), respectively], but not with the mutational status of KRAS and BRAF [standard partial regression coefficient: -0.101 (P=0.631) and 0.160 (P=0.510), respectively]. Cetuximab-mediated ADCC activity may be correlated with the cell surface expression level of EGFR, regardless of the mutational statuses of KRAS and BRAF, in CRC.
BACKGROUND Emergency surgical resection is a standard treatment for right-sided malignant colonic obstruction; however, the procedure is associated with high rates of mortality and morbidity. Although a bridge to surgery can be created to obviate the need for emergency surgery, its effects on long-term outcomes and the most practical management strategies for right-sided malignant colonic obstruction remain unclear. AIM To determine the appropriate management approach for right-sided malignant colonic obstruction. METHODS Forty patients with right-sided malignant colonic obstruction who underwent curative resection from January 2007 to April 2017 were included in the study. We compared the perioperative and long-term outcomes of patients who received bridges to surgery established using decompression tubes and those created using self-expandable metallic stents (SEMS). The primary outcome was the overall survival duration (OS) and the secondary endpoints were the disease-free survival (DFS) duration and the preoperative and postoperative morbidity rates. Analysis was performed on an intention-to-treat basis. RESULTS There were 21 patients in the decompression tube group and 19 in the SEMS group. There were no significant differences in the perioperative morbidity rates of the two groups. The OS rate was significantly higher in the decompression tube group than in the SEMS group (5-year OS rate; decompression tube 79.5%, SEMS 32%, P = 0.043). Multivariate analysis revealed that the bridge to surgery using a decompression tube was significantly associated with the OS (hazard ratio, 17.41; P = 0.004). The 3-year DFS rate was significantly higher in the decompression tube group than in the SEMS group (68.9% vs 45.9%; log-rank test, P = 0.032). A propensity score–adjusted analysis also demonstrated that the prognosis was significantly better in the decompression tube group than in the SEMS group. CONCLUSION The bridge to surgery using trans-nasal and trans-anal decompression tubes for right-sided malignant colonic obstruction is safe and may improve long-term outcomes.
Objectives: Few studies have compared management and outcomes of bridge to surgery (BTS) for obstructive colonic cancer according to the location of the tumor. Additional information is needed about this procedure's characteristics and short-term and long-term outcomes. We aimed to compare patient and tumor characteristics, and outcomes of BTS for obstructive right-sided versus left-sided colonic cancers. Methods: This was a retrospective, single center, cohort study. The study cohort comprised 149 patients, including 48 with right-sided and 101 with left-sided obstructive colonic cancers, who were treated with BTS between January 2007 and December 2017. Data on medical history, investigations, treatments, and prognosis were collected from an electronic database of a single hospital. The primary end points were overall (OS) and disease-free (DFS) survival and short-term surgical outcomes. Results: Significantly more patients with right-sided cancers had postoperative complications (29.2% vs. 14.9%, p = 0.039). Additionally, postoperative chemotherapy was administered to a marginally significantly greater proportion of patients with left-sided cancers (29.2% vs 45.5%, p = 0.057). The long-term outcomes were comparable between the two groups (the 5-year OS rates were 67.6% and 80.9% [p = 0.117] and the 5-year DFS rates were 62.2% and 58.6% [p = 0.671]). Multivariate analyses using all studied variables showed that lymphovascular invasion, advanced T stage, and adjuvant chemotherapy were independent poor prognostic factors. Conclusions: The long-term outcome was not different between the right- and left-sided groups. In a BTS setting, postoperative complications may reduce the compliance of adjuvant chemotherapy in right-sided cancers and affect long-term outcomes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.