Background: The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC.Methods: Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive (n = 3) and radioresistant (n = 3) ESCC tumor tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in 35 ESCC tumor tissues (20 radiosensitive and 15 radioresistant tissues, respectively) to validate the lncRNA that contributed the most to the radiosensitivity of ESCC (named the candidate lncRNA). MTT, flow cytometry, and western blot assays were conducted to assess the effect of the candidate lncRNA on radiosensitivity in vitro in ECA109/ECA109R ESCC cells. A mouse xenograft model was established to confirm the function of the candidate lncRNA in the radiosensitivity of ESCC in vivo. The putative downstream target genes regulated by the candidate lncRNA were predicted using Starbase 2.0 software and the TargetScan database. The interactions between the candidate lncRNA and the putative downstream target genes were examined by Luciferase reporter assay, and were confirmed by PCR.Results: A total of 113 aberrantly expressed lncRNAs were identified by microarray analysis, of which family with sequence similarity 201-member A (FAM201A) was identified as the lncRNA that contributed the most to the radiosensitivity of ESCC. FAM201A was upregulated in radioresistant ESCC tumor tissues and had a poorer short-term response to radiotherapy resulting in inferior overall survival. FAM201A knockdown enhanced the radiosensitivity of ECA109/ECA109R cells by upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) expression via the negative regulation of miR-101 expression. The mouse xenograft model demonstrated that FAM201A knockdown improved the radiosensitivity of ESCC.Conclusion: The lncRNA FAM201A, which mediated the radiosensitivity of ESCC by regulating ATM and mTOR expression via miR-101 in the present study, may be a potential biomarker for predicting radiosensitivity and patient prognosis, and may be a therapeutic target for enhancing cancer radiosensitivity in ESCC.

BackgroundThe aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).MethodsThe clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were analyzed statistically.ResultsA total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and 78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term response to CRT were identified as significant factors that influenced patient prognosis. No significant differences in OS, LFFS or DFFS were observed between the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage, clinical M-stage and short-term response subgroups.ConclusionsThe short-term response to CRT and the tumor clinical stage were significant prognosis factors for patients with ESCC treated with CRT. With current chemotherapy regimens, AC did not improve survival for patients with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT.

PurposeTo evaluate the short-term efficacy and safety of recombinant human endostatin (Endostar) combined with chemoradiotherapy for the treatment of advanced, locally recurrent nasopharyngeal carcinoma (NPC).Materials and MethodsBetween March 2010 and October 2013, a total of 22 patients with stage rIII-IVb locally recurrent NPC underwent salvage radiotherapy with Endostar in Sun Yat-Sen University Cancer Center. Intensity-modulated radiotherapy (IMRT) was delivered. Platinum-based chemotherapy was used in a neoadjuvant protocol. Endostar was continuously administered intravenously (105 mg/m2) for 14 days (Days 1–14) from the first day of treatment during a 21-day cycle. Tumor response and treatment toxicities were observed.ResultsUntil January 2014, the median follow-up time was 13 months (range, 4–41 months). All patients completed the planned radiotherapy. A complete response was achieved in 20 patients, and a partial response was achieved in 2 patients. The incidence of grade 3–5 late radiation injury in this study was 50% (11/22) and that of nasopharyngeal mucosal necrosis was 31.8% (7/22).ConclusionsEndostar combined with chemoradiotherapy may be effective in decreasing both the incidence of nasopharyngeal mucosal necrosis. Studies with a larger sample size and longer follow-up are warranted.

BackgroundThe TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopathologic factors for predicting the overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments.MethodsWe retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to examine the extensibility of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index (c-index).ResultsWe identified and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging system for predicting the survival in both the primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63).ConclusionWe developed and validated a novel nomogram that outperformed the TNM staging system in predicting the OS of non-metastatic NPC patients who underwent curative therapy.

An elevated level of S100A6 is associated with poor outcomes of many tumor types, but, how S100A6 contributes to nasopharyngeal carcinoma (NPC) progression remains unknown. Here, we investigated the expression and prognostic significance of S100A6 in NPC and explored the molecular mechanisms under-lying the role of S100A6 in NPC development. The results showed that S100A6 was markedly up-regulated in NPC tissues and cell lines compared to paired peritumoral normal tissues and a normal nasopharyngeal epithelial cell line, respectively. In tissues from 92 NPC patients, high S100A6 expression was associated with advanced N stage, locoregional failure and disease progression and was predictive of poor locoregional recurrence-free survival (LRRFS, P = 0.001) and progression-free survival (PFS, P = 0.001). Multivariate analysis showed that S100A6 is an independent prognostic factor for LRRFS and PFS. Silencing S100A6 using siRNA or shRNA significantly suppressed NPC cell proliferation, colony formation and p38/mitogen-activated protein kinase (MAPK) activity in vitro and inhibited tumor growth in a xenograft mouse model of NPC. In contrast, overexpressing S100A6 via plasmid transfection resulted in increased NPC cell proliferation and p38/MAPK activation. S100A6-induced proliferation was abolished by a p38 inhibitor. In summary, S100A6 may be a new prognostic marker of NPC and may promote NPC development via the activation of p38/MAPK signaling pathways. These findings suggest S100A6/p38/MAPK signaling as a potential therapeutic target for NPC. © 2016 Wiley Periodicals, Inc.

Acute lymphoblastic leukemia (ALL) is a common hematological malignancy characterized by the uncontrolled proliferation of leukemia cells in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL. In this study, we investigated the anti-leukemic activity of butein and its action mechanisms in ALL. Butein was found to significantly suppress the cellular proliferation of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also induced cell cycle arrest by decreasing the expression of cyclin E and CDK2. We also found that butein promoted nuclear Forkhead Class box O3a (FOXO3a) localization, enhanced the binding of FOXO3a on the p27kip1 gene promoter and then increased the expression of p27kip1. Moreover, we showed that FOXO3a knockdown significantly decreased the proliferation inhibition by butein, whereas overexpression of FOXO3a enhanced the butein-mediated proliferation inhibition. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the proliferation inhibition by butein through decreasing the expression of p27kip1. Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a/p27kip1 pathway.

ObjectiveTo explore the value of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in predicting downstaging to stage 0–I cancer after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer.Materials and methodsWe respectively investigated pretreatment CEA, pretreatment CA19-9, posttreatment CEA, posttreatment CA19-9, pre–post-CA19-9 ratio, and pre–post-CEA ratio in 674 patients with locally advanced rectal cancer receiving nCRT and determined the patients’ thresholds by using the receiver operating characteristic curve analysis. The association between downstaging (stage 0–I after nCRT), pathological complete response, and clinicopathological parameters was evaluated using the Pearson χ2 test. The clinicopathological parameters which were found to be significantly associated with downstaging were analyzed by logistic regression models and were incorporated into a scoring system.ResultsMultivariate analysis showed that pretreatment CA19-9 level, posttreatment CEA level, pre–post-CEA ratio, and pre–post-CA19-9 ratio were significantly correlated with downstaging. Area under the curve of the scoring system was higher than that of parameters alone.ConclusionThe 4-factor scoring system with CA19-9 level, posttreatment CEA level, pre– post-CEA ratio, and pre–post-CA19-9 ratio is of more value in predicting downstaging to stage 0–I patients with locally advanced rectal cancer after nCRT than using the parameters alone.

Purpose The aim of this study was to identify the clinical predictors of pathological good response (PGR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) to clarify the indications for local excision. Methods and materials A total of 173 patients with LARC (cT3–4/N +) who were treated with nCRT followed by surgery were enrolled in our retrospective study. Patients were categorized into two groups according to the different tumor responses of surgical pathology. Stage ypT0–1N0 was defined as the group with PGR, and stage ypT2–4N0/ypTanyN + was the defined as the pathological poor response (PPR) group, and the potential predictors were compared. Results Of 173 patients, PGR was achieved in 57 patients (32.95%). The distance from the inferior margin of the tumor to the anal verge, cT classification, pretreatment carcinoembryonic antigen (CEA) and the interval from the end of radiation to surgery were correlated with pathological response. In the multivariate analysis, the distance from anal verge < 5 cm (OR = 0.443, p = 0.019), pretreatment CEA < 5 ng/mL (OR = 0.412, p = 0.015) and the interval from the end of radiation to surgery ≥ 84 days (OR = 2.652, p = 0.005) were independent predictors of PGR. Conclusions The distance from the inferior margin of the tumor to the anal verge, pretreatment CEA and the interval from the end of radiation to surgery were significant predictors of PGR in LARC. A prospective study is needed to further validate these results in the future.