Predictive value of combination of MRI tumor regression grade and apparent diffusion coefficient for pathological complete remission after neoadjuvant treatment of locally advanced rectal cancer / 中华胃肠外科杂志

Objective: Pelvic high-resolution magnetic resonance imaging (MRI) has now become a standard method for evaluating the efficacy of neoadjuvant treatment for locally advanced rectal cancer (LARC). However, this traditional morphological qualitative assessment method based on T2-weighted imaging (T2WI) is not effective in predicting pathological complete remission (pCR). The purpose of this study is to investigate whether combining the magnetic resonance tumor regression grade (mrTRG) with apparent diffusion coefficient (ADC) can improve diagnostic value for pCR after preoperative neoadjuvant chemoradiotherapy (nCRT) of LARC. Methods: This was a diagnostic study. Clinicopathological data of 134 LARC patients who received nCRT and radical surgery in the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2019 were retrospectively analyzed. All the patients underwent MRI which included T2WI and DWI sequences before and 8 weeks after nCRT. Two radiologists independently drew ROIs on T2WI and DWI to estimate mrTRG stage and calculate the mean ADC value. Receiver operating characteristics (ROC) method was applied to evaluate the predict value of mrTRG combined with mean ADC value for pCR. Results: Of 134 LARC patients, 85 were male and 49 were female with median age of 58 (28-82) years. After nCRT, MRI suggested 21 patients (15.7%) had clinical complete remission (cCR), e.g. mrTRG stage 1-2. Postoperative pathology revealed 31 (23.1%) patients had pCR. The evaluations of mrTRG and ADC value by the two readers were highly consistent, and the intra-group correlation coefficients were 0.83 (95% CI: 0.703-0.881) and 0.96 (95% CI: 0.989-0.996), respectively. There was a negative correlation between mrTRG and pCR (r(s)=-0.505, P<0.01), and a positive correlation between mean ADC value and pCR (r(s)=0.693, P<0.01). The ROC curve showed that mrTRG alone had a medium predictive value for pCR, with an area under the curve (AUC) of 0.832 (95% CI: 0.743-0.921); the mean ADC value had a higher predictive value for pCR, with AUC of 0.906 (95% CI: 0.869-0.962). The predictive value of the combined model of mrTRG and ADC value for pCR was significantly better than that of mrTRG alone (P=0.015), and the AUC was 0.908 (95% CI: 0.849-0.968). Conclusion: Both mrTRG and mean ADC value can be non-invasive methods to predict the efficacy of nCRT for LARC. Combining the mean ADC value with mrTRG can result in better pCR prediction.

Inhibitory effect of apatinib on HCT-116 cells and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of apatinib on colorectal carcinoma HCT-116 cells in vitro and the signaling pathways involved.</p><p><b>METHODS</b>The cytotoxicity of different concentrations (0, 0.5, 1, 1.5, and 2 µmol/L) of apatinib in HCT-116 cells was assessed by MTT assay, using capecitabine as the positive control. The apoptosis rate of apatinib-treated HCT-116 cells was detected using flow cytometry, and the expressions of Bcl-2, Bax, and caspase-3 were determined with quantitative real-time PCR and Western blotting. The effect of apatinib on the expressions of Akt, pAkt, Erk1/2 and pErk1/2 in HCT-116 cells was evaluated using Western blotting.</p><p><b>RESULTS</b>Apatinib significantly inhibited the proliferation of HCT-116 cells in a concentration-dependent manner with an ICvalue of 1.335 µmol/L. Flow cytometric analysis showed that apatinib significantly increased the apoptotic rate of HCT-116 cells dose-dependently. Apatinib induced the expression of the pro-apoptotic genes Bax and caspase-3 at both the mRNA and protein levels while inhibited the expression of the anti- apoptotic gene Bcl-2. The expressions of p-Akt and p-Erk1/2 were decreased in HCT-116 cells after apatinib treatment, but the total protein levels did not undergo obvious changes.</p><p><b>CONCLUSION</b>Apatinib inhibits the proliferation and induces apoptosis of HCT-116 cells by suppressing the phosphorylation of Erk1/2 and Akt in the MAPK/Erk and PI3K/Akt signaling pathways.</p>