FAP positive cancer-associated fibroblasts promote tumor progression and radioresistance in esophageal squamous cell carcinoma by transferring exosomal lncRNA AFAP1-AS1.

Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in the tumor microenvironment, which play important roles in regulating tumor progression and therapy resistance by transferring exosomes to cancer cells. However, how CAFs modulate esophageal squamous cell carcinoma (ESCC) progression and radioresistance remains incompletely understood. The expression of fibroblast activation protein (FAP) in CAFs was evaluated by immunohistochemistry in 174 ESCC patients who underwent surgery and 78 pretreatment biopsy specimens of ESCC patients who underwent definitive chemoradiotherapy. We sorted CAFs according to FAP expression, and the conditioned medium (CM) was collected to culture ESCC cells. The expression levels of several lncRNAs that were considered to regulate ESCC progression and/or radioresistance were measured in exosomes derived from FAP+ CAFs and FAP- CAFs. Subsequently, cell counting kit-8, 5-ethynyl-2'-deoxyuridine, transwell, colony formation, and xenograft assays were performed to investigate the functional differences between FAP+ CAFs and FAP- CAFs. Finally, a series of in vitro and in vivo assays were used to evaluate the effect of AFAP1-AS1 on radiosensitivity of ESCC cells. FAP expression in stromal CAFs was positively correlated with nerve invasion, vascular invasion, depth of invasion, lymph node metastasis, lack of clinical complete response and poor survival. Culture of ESCC cells with CM/FAP+ CAFs significantly increased cancer proliferation, migration, invasion and radioresistance, compared with culture with CM/FAP- CAFs. Importantly, FAP+ CAFs exert their roles by directly transferring the functional lncRNA AFAP1-AS1 to ESCC cells via exosomes. Functional studies showed that AFAP1-AS1 promoted radioresistance by enhancing DNA damage repair in ESCC cells. Clinically, high levels of plasma AFAP1-AS1 correlated with poor responses to dCRT in ESCC patients. Our findings demonstrated that FAP+ CAFs promoted radioresistance in ESCC cells through transferring exosomal lncRNA AFAP1-AS1; and may be a potential therapeutic target for ESCC treatment.

Reduction of acute radiation-induced brain injury in rats by anlotinib.

OBJECTIVES: Radiation therapy in the treatment of brain tumors also leads to the occurrence of radiation brain injury (RBI). Anlotinib is a small-molecule inhibitor of multi-receptor tyrosine kinase with high selectivity for vascular endothelial growth factor receptor-2. In this study, we constructed a rat model of RBI and investigated the effect of anlotinib on RBI and its mechanism of action through drug intervention during the acute phase of RBI. METHODS: Six-week-old male (Sprague-Dawley) rats were used to construct an animal model of RBI to evaluate the protective effect of anlotinib on acute RBI by histopathological staining, brain edema determination, blood-brain barrier integrity evaluation and quick real time-polymerase chain reaction , ELISA detection of inflammation-related indexes, and western-blot detection of related gene protein expression. RESULTS: Anlotinib reduced the degree of edema in the hippocampal region of rats, improved the pathological morphology of neural cells and vascular endothelial cells, and decreased blood-brain barrier permeability. Anlotinib reduced glial fibrillary acidic protein protein expression in the hippocampal region of rat brain tissue and inhibited astrocyte activation. It inhibited the release of inflammatory factors (interleukin [IL]-6, IL-8 and vascular endothelial growth factor) and down-regulated the expression of janus kinase-2/signal transducer and activator of transcription-3 (JAK2/STAT3) signaling pathway-related proteins. CONCLUSION: This study found that anlotinib has a protective effect against RBI in rats and anlotinib may be a new candidate for the treatment of RBI.

Association of Sarcopenia With Toxicity and Survival in Postoperative Recurrent Esophageal Squamous Cell Carcinoma Patients Receiving Chemoradiotherapy.

BACKGROUND: Sarcopenia has been associated with treatment-related toxicities and poor survival in cancer patients. Our aim was to investigate the prevalence of sarcopenia in postoperative recurrent esophageal squamous cell carcinoma (ESCC) patients receiving chemoradiotherapy (CRT) and evaluate associations with treatment-related toxicity and prognosis. METHODS: One hundred and eighty-four patients with postoperative locoregional recurrent ESCC receiving CRT between January 2014 and December 2016 were included. The skeletal muscle area (SMA) was measured at the third lumbar vertebra level. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) less than 47.24/cm2/m2 for men and 36.92/cm2/m2 for women. Association of sarcopenia with overall survival (OS) was analyzed using univariate and multivariate cox regression models. RESULTS: Sarcopenia was observed in 94 of 184 (51.1%) patients. Sarcopenic patients had significantly higher rates of grade 3-4 toxicities compared to those without sarcopenia (36.2% vs 21.1%, p = 0.034). The survival rate at 12 and 24 months was 36.2% and 3.2% in the sarcopenic patients and 57.8% and 17.8% in the non-sarcopenic patients (p < 0.001). Multivariate cox regression analysis showed that sarcopenia was significantly associated with decreased OS (HR = 1.729, 95% CI 1.231-2.428, p = 0.002). CONCLUSIONS: Sarcopenia is an independent indicator of poor survival in postoperative locoregional recurrent ESCC patients treated with CRT. Early nutritional interventions before treatment may improve the prognosis.

Concurrent chemoradiotherapy with S-1 compared with concurrent chemoradiotherapy with docetaxel and cisplatin for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1-14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8-2.0 Gy per fraction to a total dose of 50-60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. RESULTS: A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3-4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3-4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). CONCLUSION: CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

Xigua Video as a Source of Information on Breast Cancer: Content Analysis.

BACKGROUND: Seeking health information on the internet is a popular trend. Xigua Video, a short video platform in China, ranks among the most accessed websites in the country and hosts an increasing number of videos with medical information. However, the nature of these videos is frequently unscientific, misleading, or even harmful. OBJECTIVE: Little is known about Xigua Video as a source of information on breast cancer. Thus, the study aimed to investigate the contents, quality, and reliability of breast cancer-related content on Xigua Video. METHODS: On February 4, 2020, a Xigua Video search was performed using the keyword "breast cancer." Videos were categorized by 2 doctors based on whether the video content provided useful or misleading information. Furthermore, the reliability and quality of the videos were assessed using the 5-point DISCERN tool and 5-point global quality score criteria. RESULTS: Out of the 170 videos selected for the study, 64 (37.6%) were classified as useful, whereas 106 (62.4%) provided misleading information. A total of 41.8% videos (71/170) were generated by individuals compared to 19.4% videos (33/170) contributed by health care professionals. The topics mainly covered etiology, anatomy, symptoms, preventions, treatments, and prognosis. The top topic was "treatments" (119/170, 70%). The reliability scores and global quality scores of the videos in the useful information group were high (P<.001). No differences were observed between the 2 groups in terms of video length, duration in months, and comments. The number of total views was higher for the misleading information group (819,478.5 vs 647,940) but did not reach a level of statistical significance (P=.112). The uploading sources of the videos were mainly health care professionals, health information websites, medical advertisements, and individuals. Statistical differences were found between the uploading source groups in terms of reliability scores and global quality scores (P<.001). In terms of total views, video length, duration, and comments, no statistical differences were indicated among the said groups. However, a statistical difference was noted between the useful and misleading information video groups with respect to the uploading sources (P<.001). CONCLUSIONS: A large number of Xigua videos pertaining to breast cancer contain misleading information. There is a need for accurate health information to be provided on Xigua Video and other social media; health care professionals should address this challenge.

Tumor-Secreted Exosomal lncRNA POU3F3 Promotes Cisplatin Resistance in ESCC by Inducing Fibroblast Differentiation into CAFs.

Cancer-associated fibroblasts (CAFs), an activated subpopulation of fibroblasts, occupy a central position in the tumor microenvironment and have been shown to promote chemoresistance in multiple cancer types by secreting inflammatory cytokines. Herein, we report that tumor-secreted exosomal long non-coding RNAs (lncRNAs) can regulate cisplatin resistance in esophageal squamous cell carcinoma (ESCC) through transformation of normal fibroblasts (NFs) to CAFs. Primary CAFs and matched NFs were isolated from tumor tissues and matched normal esophageal epithelial tissues of ESCC patients. Fluorescence microscopy and qRT-PCR were used to investigate the transportation of exosomal lncRNAs from ESCC cells to NFs. To identify the specific lncRNAs involved, 14 ESCC-related lncRNAs were measured in NFs after incubation with exosomes from ESCC cells. We demonstrated that lncRNA POU3F3 can be transferred from ESCC cells to NFs via exosomes and that it mediated fibroblast activation. Activated fibroblasts further promoted proliferation and cisplatin resistance of ESCC cells through secreting interleukin 6 (IL-6). Moreover, our clinical data showed that high levels of plasma exosomal lncRNA POU3F3 correlated significantly with lack of complete response and poor survival in ESCC patients. Therefore, these data demonstrate that lncRNA POU3F3 is involved in cisplatin resistance in ESCC and that this effect is mediated through exosomal lncRNA POU3F3-induced transformation of NFs to CAFs.

Lymphopenia in Esophageal Squamous Cell Carcinoma: Relationship to Malnutrition, Various Disease Parameters, and Response to Concurrent Chemoradiotherapy.

BACKGROUND: Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). MATERIALS AND METHODS: A total of 286 patients with stage II-IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count <1,000 cells per mm3 at diagnosis, and treatment-related lymphopenia was defined as total lymphocyte count <200 cells per mm3 with 6 weeks after starting CCRT. Univariate and multivariate logistic regression methods were used to analyze factors associated treatment-related lymphopenia and treatment response. RESULTS: Lymphopenia was observed in 44 patients (15.4%) at initial diagnosis. Pretreatment lymphopenia was significantly associated with greater tumor length, worse T status, body mass index ≤18.5 kg/m2, and weight loss ≥3 kg in the previous 3 months. Six weeks after starting CCRT, 89 patients (31%) developed treatment-related lymphopenia. Tumor progression and cancer-related death were more frequently observed in treatment-related lymphopenia group than those without (76.4% vs. 52.8% and 58.4% vs. 39.6%). A complete response (CR) was achieved in 62 patients (21.7%). In multivariate analysis, treatment-related lymphopenia was significantly associated with lack of clinical CR, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. CONCLUSION: Treatment-related lymphopenia during CCRT is an independent predictor for poor treatment response in ESCC. IMPLICATIONS FOR PRACTICE: A total of 286 patients with locally advanced esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy (CCRT), and treatment-related lymphopenia occurred in 31% of patients within 6 weeks from the start of CCRT. Treatment-related lymphopenia was significantly associated with lack of treatment response, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment-related lymphopenia. Lymphocyte count is an inexpensive biomarker that may be easily used by clinicians to identify patients who are most likely to benefit from CCRT.

Combination of long noncoding RNA MALAT1 and carcinoembryonic antigen for the diagnosis of malignant pleural effusion caused by lung cancer.

PURPOSE: Long noncoding RNAs (lncRNAs) are present in body fluids, but their potential as tumor biomarkers has never been investigated in malignant pleural effusion (MPE) caused by lung cancer. The aim of this study was to assess the clinical significance of lncRNAs in pleural effusion, which could potentially serve as diagnostic and predictive markers for lung cancer-associated MPE (LC-MPE). PATIENTS AND METHODS: RNAs from pleural effusion were extracted in 217 cases of LC-MPE and 132 cases of benign pleural effusion (BPE). Thirty-one lung cancer-associated lncRNAs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The level of carcinoembryonic antigen (CEA) was also determined. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were established to evaluate the sensitivity and specificity of the identified lncRNAs and other biomarkers. The correlations between baseline pleural effusion lncRNAs expression and response to chemotherapy were also analyzed. RESULTS: Three lncRNAs (MALAT1, H19, and CUDR) were found to have potential as diagnostic markers in LC-MPE. The AUCs for MALAT1, H19, CUDR, and CEA were 0.891, 0.783, 0.824, and 0.826, respectively. Using a logistic model, the combination of MALAT1 and CEA (AUC, 0.924) provided higher sensitivity and accuracy in predicting LC-MPE than CEA (AUC, 0.826) alone. Moreover, baseline MALAT1 expression in pleural fluid was inversely correlated with chemotherapy response in patients with LC-MPE. CONCLUSION: Pleural effusion lncRNAs were effective in differentiating LC-MPE from BPE. The combination of MALAT1 and CEA was more effective for LC-MPE diagnosis.

Systemic immune-inflammation index predicting chemoradiation resistance and poor outcome in patients with stage III non-small cell lung cancer.

BACKGROUND: There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the association between systemic immune-inflammation index (SII) and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC). The prognostic values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were also evaluated. METHODS: In total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival. RESULTS: Applying cut-offs of ≥ 660 (SII), ≥ 3.57 (NLR), ≥ 147 (PLR), ≤ 52.95 (PNI), SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001), higher T stage (< 0.001), advanced clinical stage (p = 0.019), and lower response rate (p = 0.018). In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p all < 0.001). Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158-2.626; p = 0.008), T stage (HR, 1.332; 95% CI 1.032-1.718; p = 0.028), N stage (HR, 1.848; 95% CI 1.113-3.068; p = 0.018), SII (HR, 2.105; 95% CI 1.481-2.741; p < 0.001) and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448-2.585; p < 0.001) were independently correlated with overall survival. CONCLUSIONS: This study demonstrates that the SII is an independent prognostic indicator of poor outcomes for patients with stage III NSCLC and is superior to other inflammation-based factors in terms of prognostic ability.

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for patients with locally advanced esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.

The present study evaluated the clinical and prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (dCRT). A total of 517 patients with ESCC were enrolled and analysed retrospectively. The NLR was calculated at three time points: baseline, post-treatment, and at the time of tumor progression. Elevated NLR was defined as a ratio ≥5. High NLR at baseline was present in 204 (39%) patients and was significantly correlated with larger tumour size, advanced TNM stage, worse ECOG performance status, and dCRT response (p < 0.05). At a median follow-up of 17 months, patients with higher NLR at baseline had poorer progression-free survival (PFS) and overall survival (OS). On multivariate analysis, elevated NLR at baseline was independently associated with PFS and OS (HR = 1.529, p < 0.001 for PFS; HR = 1.856, p < 0.001 for OS). In addition, patients with high pre- and post-treatment NLR demonstrated worse clinical outcomes than other groups. Our results suggest that NLR is an independent prognostic indicator for patients with ESCC undergoing dCRT and changes in NLR level with treatment may indicate therapeutic benefit.

Clinical characteristics and prognostic factors of brain central neurocytoma.

BACKGROUND & AIMS: This study is designed for the clinical characteristics and prognostic factors of central neurocytoma (CN). METHODS: CN patients from 2004 to 2012 were enrolled from the Surveillance Epidemiology and End Results (SEER) data. Clinical characteristics including age, sex, race, tumor size, tumor number, surgery, and radiation therapy were summarized. Univariate and multivariate analysis were performed to explore the prognostic factors of CN. RESULTS: CN tended to be borderline malignant and single lesion. Compared with other brain tumor (NCN), Patients with CN (CNs) were more likely to be female, young, and non-white race. Surgery was the primary treatment of CN. Univariate and Multivariate analysis indicated tumor number and surgery were both independent prognostic factors of CN (P < 0.05). Unifocal CNs had a lower mortality risk than multifocal ones (HR 0.167, 95% CI 0.052-0.537), surgery significantly reduced the death risk of CNs (HR 0.284, 95% CI 0.088-0.921). CONCLUSIONS: CN tend to be borderline malignant, single lesion, operated on. Most CNs are female and younger. single lesion and surgery are the independent positive prognostic factors of CN.

Survival benefit of radiotherapy to patients with small cell esophagus carcinoma: an analysis of Surveillance Epidemiology and End Results (SEER) data.

BACKGROUND AND AIMS: Small cell esophageal carcinoma (SCEC) is a rare malignant tumor. So far, few studies are found to research the effect of radiotherapy (RT) to it. This study is designed to explore the prognostic factors, and analyze survival benefit of RT to patients with SCEC. RESULTS: Patients with SCEC were more likely to be in female, older, higher disease stage than those with non-small cell esophageal carcinoma. RT was used in more than 50% SCEC patients. RT tended be reduced as the disease stage raise in SCEC. Univariate and multivariate analysis showed that age, year, disease stage, and RT were the prognostic factors of survival (P < 0.05). RT reduced nearly 75% risks of death in localized stage (P < 0.05), nearly 50% risks of death in regional stage (P > 0.05) and nearly 30% risks of death in distant stage (P > 0.05). METHODS: SCEC patients between 1973 and 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, year, sex, race, stage, surgery, and RT were summarized. Univariate and multivariate analysis were performed to explore the independent prognostic factors of SCEC. Cox regression survival analysis was performed to evaluate the effect of RT to SCEC based on different stages. CONCLUSIONS: Stage, age, year, and RT are independent prognostic factors of SCEC. Survival benefit of RT exists in any disease stage, but is only statistically significant in localized stage of SCEC.

High expression of long non-coding RNA AFAP1-AS1 predicts chemoradioresistance and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.

To evaluate the clinical significance of lncRNAs in the resistance to cisplatin-based chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). We focused on lncRNAs which were frequently reported in ESCC or were involved in chemoradiotherapy resistance. LncRNA expressions were examined in paired cisplatin-resistant and parental ESCC cell lines. Dysregulated lncRNAs were further measured in 162 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (dCRT). Then the correlations between lncRNA expression and response to dCRT and prognosis were analyzed. Three lncRNAs (AFAP1-AS1, UCA1, HOTAIR) were found to be deregulated in cisplatin-resistant cells compared with their parent cells. AFAP1-AS1 was significantly up-regulated in tumor tissues compared with adjacent normal tissues (P = 0.006). Furthermore, overexpression of AFAP1-AS1 was closely associated with lymph node metastasis (P < 0.001), distant metastasis (P = 0.016), advanced clinical stage (P = 0.002), and response to dCRT (P < 0.001). Kaplan-Meier survival analysis revealed that high expression of AFAP1-AS1 was significantly associated with shorter progression free survival (PFS) (median, 15 months vs. 27 months, P < 0.001) and overall survival (OS) (median, 29 months vs. 42 months, P < 0.001). In the multivariate analysis, high expression of AFAP1-AS1 was found to be an independent risk factor to predict poor PFS (HR, 1.626; P = 0.027) and OS (HR, 1.888; P = 0.004). Thus, high expression of AFAP1-AS1 could serve as a potential biomarker to predict tumor response and survival. Determination of this lncRNA expression might be useful for selection ESCC patients for dCRT. © 2016 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) were present in the blood of cancer patients and have shown great potential as powerful and non-invasive tumor markers. However, little is known about the value of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We hypothesized that ESCC-related lncRNAs might be released into the circulation during tumor initiation and could be utilized to detect and monitor ESCC. METHODS: Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) which previously found to be differently expressed in esophageal cancer were selected as candidate targets for subsequent circulating lncRNA assay. A four-stage exploratory study was conducted to test the hypothesis: (1) optimization of detected method to accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2) evaluation of the stability of circulating lncRNAs in human plasma or serum; (3) exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4) evaluation the diagnostic power of circulating lncRNAs for ESCC. RESULTS: ESCC-related lncRNAs were detectable and stable in plasma of cancer patients, and derived largely from ESCC tumor cells. Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls. By receiver operating characteristic curve (ROC) analysis, among the three lncRNAs investigated, plasma POU3F3 provided the highest diagnostic performance for detection of ESCC (the area under the ROC curve (AUC), 0.842; p < 0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926, p < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%). CONCLUSIONS: Plasma POU3F3 could serve as a potential biomarker for diagnosis of ESCC, and the combination of POU3F3 and SCCA was more efficient for ESCC detection, in particular for early tumor screening.

Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy.

microRNA-133a (miR-133a) and miR-133b, located on chromosome 18 in the same bicistronic unit, have been commonly identified as being downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the correlation of miR-133a/b expression with efficacy of paclitaxel-based chemotherapy and clinical outcome of ESCC patients. miR-133a expression and miR-133b expression were examined in 100 newly diagnosed ESCC patients prior to treatment by quantitative real-time PCR. Then, the patients received four cycles of paclitaxel-based chemotherapy, the short-term treatment efficacy was evaluated, and a 3-year follow-up was performed. Expression levels of miR-133a and miR-133b were both significantly lower in ESCC tissues compared to adjacent noncancerous tissues (both P < 0.001). In addition, combined miR-133a/b downregulation was found to be closely correlated with advanced tumor stage (P = 0.02) and poor differentiation (P = 0.01). Moreover, the response rate of ESCC patients to paclitaxel-based chemotherapy was significantly higher in combined miR-133a/b downregulation group compared with other groups (P = 0.02). Furthermore, univariate and multivariate Cox analyses revealed that tumor stage and combined expression of miR-133a/b were independent prognosis factors in ESCC patients. Our data offer the convincing evidence that combined expression of miR-133a and miR-133b may predict chemosensitivity of patients with ESCC undergoing paclitaxel-based chemotherapy, implying its importance in applying 'personalized cancer medicine' in the clinical treatment of ESCC. We also identified combined expression of miR-133a and miR-133b as an effective prognostic marker of this malignancy.

Association of decreased expression of long non-coding RNA LOC285194 with chemoradiotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Expression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients. METHODS: The method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed. RESULTS: LOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002). CONCLUSION: Decreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.

Comparison of efficacy for postoperative chemotherapy and concurrent radiochemotherapy in patients with IIIA-pN2 non-small cell lung cancer: an early closed randomized controlled trial.

OBJECTIVE: The efficacy of postoperative concurrent radiochemotherapy (POCRT) on IIIA-pN2 non-small cell lung cancer (NSCLC) is still unclear. The aim of this randomized controlled trial was to compare POCRT with postoperative chemotherapy (POCT) alone in terms of survival and relapse patterns. METHODS: Patients with completely resected IIIA-pN2 NSCLC were randomized into POCRT or POCT groups. Chemotherapy consisted of paclitaxel (175 mg/m(2)) and cisplatin (60 mg/m(2)) administered intravenously for four cycles on day 1, 22, 43, and 64. Patients in the POCRT group received radiotherapy (50.4 Gy/28 fractions) concurrently with the first 2 cycles of chemotherapy. RESULTS: This study recruited 140 participants and was closed early because of slow accrual. Data were analyzed for 135 of them including 66 cases in the POCRT group and 69 cases in the POCT group. Patients were followed-up for a median period of 45 months. The POCRT group had a median survival (MS) of 40 months and a 5-year overall survival (OS) rate of 37.9%. The POCT group had a MS of 28 months and a 5-year OS rate of 27.5%. The hazard ratio for death in the POCRT group was 0.69 (95% CI: 0.457-1.044, P=0.073). We observed a disease-free survival (DFS) of 28 months and a 5-year DFS rate of 30.3% in the POCRT group. Likewise, we observed a DFS of 18 months and a 5-year DFS rate of 18.8% in the POCT group. The recurrence hazard ratio in the POCT group was 1.49 (95% CI: 1.008-2.204, P=0.041). Subgroup analysis revealed that POCRT significantly increased the OS rate of the patients with ≥2 pN2 lymph nodes (P=0.021). The POCRT group had a significantly lower local relapse (P=0.009) and distant metastasis (P=0.05) rates as compared to that of the POCT group. One case died of pyemia and 9 cases suffered from grade 3 and 4 acute radiation esophagitis. The two groups had similar and tolerable hematologic toxicities. CONCLUSIONS: Compared with POCT, POCRT increased both local/regional and distant DFS rate of the patients with IIIA-pN2 NSCLC, but not the OS rate. Considering the relatively small sample size of the current study, caution should be taken when adopting the conclusions.

[A randomized controlled trial of intensity-modulated radiation therapy plus docetaxel and cisplatin versus simple intensity-modulated radiation therapy in II-III stage esophageal carcinoma].

OBJECTIVE: To compare the efficacy and toxicity of intensity- modulated radiation therapy plus chemotherapy (IMRT-TP) with simple intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced esophageal carcinoma. METHODS: A total of 170 eligible patients with locally advanced esophageal carcinoma were recruited prospectively from September 2004 to April 2008 and randomly divided into IMRT-TP group and IMRT group. Two groups were treated with IMRT of 6MV-X. The radiation dose was 60 Gy in 30 fractions in IMRT-TP group and 66 Gy in 30 fractions in IMRT group. The regimen of chemotherapy consisted of docetaxel and cisplatin in IMRT-TP group for 2 cycles. RESULTS: Of 170 patients, 160 completed the trial, including 75 patients of IMRT-TP group and 85 of IMRT group. As compared to IMRT group, total recurrence rate [69.3% (52/75) vs. 84.7% (72/85), P=0.020] and local recurrence rate [50.7% (38/75) vs. 67.1% (57/85), P=0.035] decreased in IMRT-TP group, the 5-year overall survival (29.3% vs. 15.3%, P=0.031) and 5-year recurrence free survival (24.0% vs. 10.6%, P=0.015) increased in IMRT-TP group. While severe side effect ratio increased obviously in IMRT-TP group [54.7% (41/75) vs. 4.7% (4/85), P=0.000]. CONCLUSION: As compare to simple IMRT, IMRT plus docetaxel and cisplatin can decrease the local recurrence rate, prolong the overall survival and regression-free survival, but bring more side effects.

A randomized controlled study of single-agent cisplatin and radiotherapy versus docetaxel/cisplatin and radiotherapy in high-risk early-stage cervical cancer after radical surgery.

BACKGROUND: This study explored whether docetaxel/cisplatin and radiotherapy (TP-R) increases overall survival (OS) and recurrence-free survival (RFS) compared to single-agent cisplatin and radiotherapy (C-R) in patients with high-risk early-stage cervical cancer post surgery. METHODS: Patients with clinical stage IB and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or the diameter of the primary tumor ≥4 cm and/or depth of interstitial infiltration ≥1/2 and/or lymphovascular space invasion were eligible for this study. Patients were randomized to receive C-R or TP-R. Radiotherapy in both groups was external radiation (46-54 Gy) followed by high-dose rate brachytherapy (12-24 Gy). Patients were given cisplatin (40 mg/m(2)) every week for five cycles (C-R group) or docetaxel (30 mg/m(2)) and cisplatin (30 mg/m(2)) every week for five cycles (TP-R group). RESULTS: Between 2003 and 2008, 320 patients were entered onto the study. Final analyses included 285 patients. One hundred and forty patients comprised the C-R group and 145 were in the TP-R group. The 5-year OS were 74.3 % in the C-R group and 82.8 % in the TP-R group. The hazard ratio (HR) for death was 0.65 in the TP-R group (95 % CI: 0.39-1.09, P = 0.098). The RFS were 69.3 % in the C-R group and 79.3 % in the TP-R group, and the HR for recurrence was 0.64 in the TP-R group (95 % CI: 0.40-1.03, P = 0.061). Recurrence rates were similar in both groups (27 in the C-R group and 18 in the TP-R group, P = 0.112). The seriousness of late side effects was similar in the two groups, with a higher rate of reversible hematological effects in the TP-R group. CONCLUSIONS: Compared with single-agent cisplatin and radiotherapy, docetaxel/cisplatin in combination with radiotherapy does not increase OS but has the trend of increasing RFS in patients with high-risk early-stage cervical cancer. However, docetaxel/cisplatin in combination with radiotherapy is associated with a higher incidence of side effects, this effect was reversible, and the incidence of late side effects was similar in the two treatment groups.

A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection.

BACKGROUND AND PURPOSE: The role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established. In this study, we compared postoperative intensity-modulated radiotherapy plus chemotherapy (IMRT-C) with chemotherapy-only in this patient population. MATERIALS AND METHODS: We randomly assigned patients with D2 lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups. The adjuvant IMRT-C consisted of 400 mg of fluorouracil per square meter of body-surface area per day plus 20mg of leucovorin per square meter of body-surface area per day for 5 days, followed by 45 Gy of IMRT for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of IMRT. Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group. RESULTS: The median overall survival (OS) in the chemotherapy-only group was 48 months, as compared with 58 months in the IMRT-C group; the hazard ratio for death was 1.24 (95% confidence interval, 0.94-1.65; P=0.122). IMRT-C was associated with increases in the median duration of recurrence-free survival (RFS) (36 months vs. 50 months), the hazard ratio for recurrence was 1.35 (95% confidence interval, 1.03-1.78; P=0.029). COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors. Rates of all grade adverse events were similar in the two treatment groups. CONCLUSIONS: IMRT-C improved RFS, but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer. Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection.