The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) consists of YSPTSPS heptapeptide repeats, and the phosphorylation status of the repeats controls multiple transcriptional steps and co-transcriptional events. However, how CTD phosphorylation status responds to distinct environmental stresses is not fully understood. In this study, we found that a drastic reduction in phosphorylation of a subset of Ser2 residues occurs rapidly but transiently following exposure to H2O2. ChIP analysis indicated that Ser2-P, and to a lesser extent Tyr1-P was reduced only at the gene 3' end. Significantly, the levels of polyadenylation factor CstF77, as well as Pol II, were also reduced. However, no increase in uncleaved or readthrough RNA products was observed, suggesting transcribing Pol II prematurely terminates at the gene end in response to H2O2. Further analysis found that the reduction of Ser2-P is, at least in part, regulated by CK2 but independent of FCP1 and other known Ser2 phosphatases. Finally, the H2O2 treatment also affected snRNA 3' processing although surprisingly the U2 processing was not impaired. Together, our data suggest that H2O2 exposure creates a unique CTD phosphorylation state that rapidly alters transcription to deal with acute oxidative stress, perhaps creating a novel "emergency brake" mechanism to transiently dampen gene expression.
To investigate the prognostic significance of MR-detected mandibular nerve involvement (MNI) and its value for induction chemotherapy (IC) administration in patients with nasopharyngeal carcinoma (NPC) and T4 disease.This retrospective study enrolled 792 non-metastatic, biopsy-proven NPC patients. Univariate and multivariate analysis were used to evaluate potential prognosticators. The inter-observer agreement was assessed by the kappa values.MR-detected MNI was observed in 141 (72.3%) patients among 195 patients with T4 disease, with excellent agreement between the readers (kappa = 0.926). Patients with MR-detected MNI presented better 5-year overall survival (OS) (hazard ratio [HR], 0.40; P = 0.006) than those with MR-negative MNI. Of these patients, IC treatment was verified as an independent factor (HR: 0.35; P = 0.014) with preferable effect on OS.MR-detected MNI could serve as an independent favorable prognostic predictor for OS in NPC patients with stage T4, which should be considered for stratifying these patients for IC administration.
Preoperative staging is important for optimal therapy planning and prognosis prediction of rectal carcinoma. The role of conventional computed tomography (CT) in preoperative staging of rectal carcinoma is controversial. This study was to evaluate the value of multislice spiral computed tomography (MSCT) in preoperative staging of rectal carcinoma.From Mar. 2006 to Feb. 2007, 87 patients with pathologically proved rectal cancer underwent preoperative plain and enhanced MSCT. Two radiologists evaluated independently tumor location, size, the depth of tumor invasion into the rectal wall (T), the involvement of regional lymph nodes (N) and the presence of distant metastases (M) on CT images. TNM staging was made according to CT findings and compared with the pathologic results. The accuracy, sensitivity, and specificity were assessed.All the 87 cases of rectal carcinoma were detected clearly by MSCT. The accuracy was 81.6% for TNM staging, 94.3% for T staging, 82.8% for N staging, and 98.9% for M staging. The sensitivity was 90.5% for T1-2 staging, 91.3% for T3 staging, and 97.7% for T4 staging. The specificity was 98.5% for T1-2 staging, 94.2% for T3 staging, and 97.7% for T4 staging. The sensitivity was 92.9% for N0 staging, 72.0% for N1 staging, and 82.4% for N2 staging. The specificity was 88.9% for N0 staging, 88.5% for N1 staging, and 91.7% for N2 staging. Only 1 case of distant metastasis was missed due to the liver lesion of less than 5 mm.MSCT is an accurate technique for preoperative staging of rectal carcinoma, which can assess the extension to adjacent tissues and the presence of lymph node and distant metastases exactly.
<p>Figure S1. Flow chart of patient inclusion. NPC, nasopharyngeal carcinoma; PET/CT, positron emission tomography with computed tomography; CCRT, concurrent chemoradiotherapy; IC, induction chemotherapy; IMRT, intensity-modulated radiotherapy. Figure S2. The manual segmentation of (A) a patient with disease progression and (B) a patient without disease progression. Red region, the segmented tumors; green region, the segmented lymph nodes. Figure S3. DCNN architectures used in the study. (A) DCNN for CT image in training step; (B) DCNN for CT image in feature extraction step; (C) DCNN for PET image in training step; (D) DCNN for PET image in feature extraction step. Figure S4. Time-dependent ROC curves of radiomics nomogram in the training (A) and test (B) sets. ROC, receiver operating characteristic; AUC, area under the curve. Figure S5. Radiomics nomogram score for each patients in the training (A) and test (B) sets. Figure S6. Kaplan-Meier survival curves of disease-free survival between high-risk and low-risk groups stratified by age, gender, overall stage, and pre-DNA. Figure S7. Kaplan-Meier survival curves of overall survival between high-risk and low-risk groups stratified by age, gender, overall stage and pre-DNA. Figure S8. Kaplan-Meier survival curves of DFS (A), OS (B), DMFS (C) and LRRFS (D) between IC+CCRT and CCRT alone for the whole 707 patients. IC, induction chemotherapy; CCRT, concurrent chemoradiotherapy; DFS, disease-free survival; OS, overall survival; DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival. Figure S9. Kaplan-Meier survival curves of DFS (A), OS (B), DMFS (C) and LRRFS (D) between IC+CCRT and CCRT alone for the 521 patients with low risk. IC, induction chemotherapy; CCRT, concurrent chemoradiotherapy. DFS, disease-free survival; OS, overall survival; DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival. Figure S10. An example of the feature maps generated from the DCNNs. Figure S11. Kaplan-Meier survival curves of DFS (A), OS (B), DMFS (C) and LRRFS (D) between IC+CCRT and CCRT alone for nomogram A-defined low-risk group. IC, induction chemotherapy; CCRT, concurrent chemoradiotherapy; DFS, disease-free survival; S, overall survival; DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival. Figure S12. Kaplan-Meier survival curves of DFS (A), OS (B), DMFS (C) and LRRFS (D) between IC+CCRT and CCRT alone for nomogram A-defined high-risk group. IC, induction chemotherapy; CCRT, concurrent chemoradiotherapy; DFS, disease-free survival; S, overall survival; DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival. Figure S13. Kaplan-Meier survival curves of DFS (A), OS (B), DMFS (C) and LRRFS (D) between IC+CCRT and CCRT alone for nomogram B-defined low-risk group. IC, induction chemotherapy; CCRT, concurrent chemoradiotherapy; DFS, disease-free survival; S, overall survival; DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival. Figure S14. Kaplan-Meier survival curves of DFS (A), OS (B), DMFS (C) and LRRFS (D) between IC+CCRT and CCRT alone for nomogram B-defined high-risk group. IC, induction chemotherapy; CCRT, concurrent chemoradiotherapy; DFS, disease-free survival; S, overall survival; DMFS, distant metastasis-free survival; LRRFS, locoregional relapse-free survival.</p>
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