crossing96/oncoscreening huggingface dataset:
Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting survivin directly and indirectly through CUG-BP1.	Based on its marked overexpression in multiple malignancies and its roles in promoting cell survival and proliferation, survivin is an attractive candidate for targeted therapy. Toward this end, a detailed understanding of the mechanisms regulating survivin expression in different cancer cells will be critical. We have previously shown that the RNA-binding protein (RBP) CUG-BP1 is overexpressed in esophageal cancer cells and post-transcriptionally regulates survivin in these cells. The objective of this study was to investigate the role of microRNAs (miRs) in regulating survivin expression in esophageal cancer cells. Using miR expression profiling analysis, we found that miR-214-3p is one of the most markedly downregulated miRs in two esophageal squamous cancer cell lines compared with esophageal epithelial cells. Interestingly, using miR target prediction programs, both survivin and CUG-BP1 mRNA were found to contain potential binding sites for miR-214-3p. Forced expression of miR-214-3p in esophageal cancer cells leads to a decrease in the mRNA and protein levels of both survivin and CUG-BP1. This effect is due to decreased mRNA stability of both targets. By contrast, silencing miR-214-3p in esophageal epithelial cells leads to an increase in both survivin and CUG-BP1 mRNA and protein. To determine whether the observed effect of miR-214-3p on survivin expression was direct, mediated through CUG-BP1, or both, binding studies utilizing biotin pull-down assays and heterologous luciferase reporter constructs were performed. These demonstrated that the mRNA of survivin and CUG-BP1 each contain two functional miR-214-3p-binding sites as confirmed by mutational analysis. Finally, forced expression of miR-214-3p enhances the sensitivity of esophageal cancer cells to cisplatin-induced apoptosis. This effect is abrogated with rescue expression of survivin or CUG-BP1. These findings suggest that miR-214-3p acts as a tumor suppressor and that its downregulation contributes to chemoresistance in esophageal cancer cells by targeting both survivin and CUG-BP1.	esophagus
Serum 25-Hydroxyvitamin D Levels and the Risk of Dysplasia and Esophageal Adenocarcinoma in Patients with Barrett's Esophagus.	BACKGROUND: To date, there are no studies reporting an association between vitamin D and Barrett's esophagus (BE), the precursor for esophageal adenocarcinoma (EAC). AIMS: Our aim was to study the association between serum 25-hydroxyvitamin D (25(OH)D) levels and prevalence and incidence of dysplasia/EAC in BE. METHODS: Patients from our BE Registry cohort seen between 2000 and 2012 who had serum 25(OH)D levels measured were included. Age, gender, race, BE length, hiatal hernia size, and histological findings were recorded. Patients without high-grade dysplasia (HGD)/EAC at or within 1 year of index biopsy and who had follow-up endoscopies and 25(OH)D levels were studied for incidence of dysplasia/EAC. RESULTS: Among 429 patients with BE, the mean 25(OH)D level was 72 ± 31.2 nmol/L. Hundred and one (23.6 %) patients had deficiency (<50 nmol/L), 149 (34.7 %) had insufficiency (50-74.9 nmol/L), and 179 (41.7 %) had normal levels of 25(OH)D. There was no association between serum 25(OH)D levels and dysplasia (p = 0.90). In the incidence cohort of 246 patients with median follow-up of 46 months, there were 34 cases of low-grade dysplasia, 12 of HGD, and 5 of EAC. Change in 25(OH)D levels did not impact progression to dysplasia/EAC (every 5 nmol/L increase from baseline, hazard ratio 0.98; p = 0.62). CONCLUSIONS: Serum 25(OH)D levels were low in 58.3 % of our BE cohort. There was no association between 25(OH)D levels and prevalence or incidence of HGD/EAC in patients with BE. Further long-term studies are needed to study the association between vitamin D status and progression of dysplasia in BE.	esophagus
[Are extensive fields useful for radiotherapy of esophageal cancer?].	PURPOSE: Study of the pattern of relapse for locally advanced oesophageal cancer and analysis of the local recurrences according to irradiated volume. PATIENTS AND METHODS: We performed a monocentric retrospective study of patients treated in the integrated centre of oncology (Angers, France). Two treatment strategies were used: concurrent chemoradiation alone or followed by surgery. Recurrences were classified as: locoregional, either isolated or associated with distant metastasis, and metastatic only. Locoregional relapses were subclassified as in-field, out-field, or mixed. RESULTS: Between March 2004 and October 2011, 168 patients were treated: 130 by chemoradiation, and 38 by chemoradiation followed by surgery. The median supero-inferior margins added to the gross tumour volume in order to create the planning tumour volume was 5cm (range: 0.5-21). Sixty-two percent of patients (n=104) relapsed: 82 locoregional relapses (49%), including 45 isolated relapses (27%) and 37 associated with distant metastasis relapses (22%), and 22 metastatic relapses (13%). From the 82 locoregional relapses, only four isolated relapses were exclusively out-field. CONCLUSION: With 5cm supero-inferior margins added to gross tumour volume, less than 3% of patients had an isolated out-field recurrence. However, half of the patients suffered in-field local recurrence and one third had metastases. These findings advocate for a limited prophylactic nodal irradiation. Trials are ongoing to assess dose escalation or surgery in order to increase local control.	esophagus
Aggressive surgical resection does not improve survival in operable esophageal squamous cell carcinoma with N2-3 status.	AIM: To investigate the influence of nodal status on response and clarify the optimal treatment for operable esophageal squamous cell carcinoma (OSCC). METHODS: We retrospectively analyzed 1490 OSCC patients who underwent transthoracic esophagectomy and lymphadenectomy between December 1996 and December 2009 at the Sun Yat-sen University Cancer Center. The surgical approach and the number of resected lymph nodes (LNs) were considered in the assessment of surgery. Patients were classified according to their nodal statuses (N0 vs N1 vs N2-3). Overall survival was defined as the time from the date of death or final follow-up. Survival analysis was performed using the Kaplan-Meier method and differences between curves were assessed by the log-rank test. Univariate and multivariate Cox regression analyses were used to identify factors associated with prognosis. Statistical significance was assumed at a P < 0.05. RESULTS: With a median time from surgery to the last censoring date for the entire cohort of 72.2 mo, a total of 631 patients were still alive at the last follow-up and the median survival time was 35.5 mo. The surgical approach (left transthoracic vs Ivor-Lewis/tri-incisional) was verified as independent prognostic significance in patients with N0 or N1 status, but not in those with N2-3 status. Similar results were also observed with the number of resected LNs (≤ 14 vs ≥ 15). Compared with surgery alone, combined therapy achieved better outcomes in patients with N1 or N2-3 status, but not in those with N0 status. For those with N2-3 status, neither the surgical approach nor the number of resected LNs reached significance by univariate analysis, with unadjusted HRs of 0.826 (95%CI: 0.644-1.058) and 0.849 (95%CI: 0.668-1.078), respectively, and aggressiveness of surgery did not influence the outcome; the longest survival was observed in those patients who received the combined therapy. CONCLUSION: Combined therapy has a positive role in OSCC with LN metastasis, and aggressive surgical resection does not improve survival in patients with N2-3 status.	esophagus
Mapping of failures after radiochemotherapy in patients with non-metastatic esophageal cancer: A posteriori analysis of the dose distribution in the sites of loco-regional relapse.	BACKGROUND AND PURPOSE: We aimed to evaluate the patterns of loco-regional failure (LRF) after exclusive chemoradiotherapy (eCRT) for esophageal cancer with respect to planned dose and/or the incidental (unplanned) dose outside target volumes. MATERIALS AND METHODS: Co-image registration of CT or (18)F-FDG PET-CT at the time of failure (tf) and at the time of CRT (t0) was performed in 34 patients with LRF. Dosimetric parameters with regard to local failure (LF), nodal failure (NF) and involved nodal stations (NS) were derived. RESULTS: Twenty-two patients (64.7%) had LF, the majority of which (95.5%) were located at the epicenter of the GTV of the primary tumor. The mean doses recalculated to the NS at tf were more likely to be lower than the planned dose delivered to the PTV at t0: Dmean=33.9 ± 20.8 Gy vs 52.2 ± 8.5 Gy (p=0.0009), D95%=27.5 ± 21 Gy vs 46.1 ± 4.8 Gy (p=0.004). Among the 12 patients with NF outside the elective nodal irradiation (ENI) volume, Dmean of NS outside the ENI was significantly lower (19.4 ± 21.4 Gy) than the Dmean of NS with failure within the ENI (45.1 ± 6.1 Gy, p=0.01). CONCLUSION: Loco-regional failure after exclusive chemoradiotherapy for esophageal cancer may be due to an inadequately low dose.	esophagus
Treatment of advanced oesophagogastric cancer with FOLFOX-4 regimen followed by leucovorin/bolus and continuous infusion 5-FU as maintenance chemotherapy in patients aged ≥ 75 years with impaired performance status.	OBJECTIVES: To evaluate the efficacy and safety of FOLFOX-4 combination chemotherapy, followed by leucovorin (LV)/bolus and continuous infusion 5-fluorouracil (5-FU) as maintenance chemotherapy in elderly (≥ 75 years) patients with advanced oesophagogastric cancer with impaired performance status (PS). MATERIALS AND METHODS: Patients with a PS score >1 were included in this study. PS evaluations were performed by a geriatrician and two medical oncologists. FOLFOX-4 consisted of oxaliplatin concurrently with LV/bolus and continuous infusion 5-FU every 2 weeks. After a maximum of six FOLFOX-4 cycles, patients with no evidence of disease progression received maintenance treatment with LV/bolus and continuous infusion 5-FU every 2 weeks until disease progression or unacceptable toxicity. RESULTS: Thirty-eight patients were enrolled in this study. Of these, 32 (84.2%) patients had a PS score of 2 and six (15.7%) patients had a PS score of 3. After completion of FOLFOX-4, 18 (47.3%) patients achieved a partial response and 14 (36.8%) patients had stable disease. Thirty-two patients (84.2%) received maintenance chemotherapy for a median of eight cycles (range one to 26 cycles). The 6-month disease-control rate was 47.3% [95% confidence interval (CI) 30.9-64.1]. The median progression-free survival was 5.9 months (95% CI 4.7-6.8) and the median overall survival was 9.6 months (95% CI 8.1-11.7). Grade 3 neutropenia occurred in six patients (15.7%), and Grade 3 anaemia and thrombocytopenia occurred in two patients (5.2%). CONCLUSION: FOLFOX-4 followed by LV/bolus and continuous infusion 5-FU as maintenance chemotherapy seems to be an active and well-tolerated first-line treatment strategy for elderly patients with advanced oesophagogastric cancer and impaired PS.	esophagus
Gene-environment interactions in esophageal cancer.	Esophageal cancer (EC) is one of the most common malignancies in low- and medium-income countries and represents a disease of public health importance because of its poor prognosis and high mortality rate in these regions. The striking variation in the prevalence of EC among different ethnic groups suggests a significant contribution of population-specific environmental and dietary factors to susceptibility to the disease. Although individuals within a demarcated geographical area are exposed to the same environment and share similar dietary habits, not all of them will develop the disease; thus genetic susceptibility to environmental risk factors may play a key role in the development of EC. A wide range of xenobiotic-metabolizing enzymes are responsible for the metabolism of carcinogens introduced via the diet or inhaled from the environment. Such dietary or environmental carcinogens can bind to DNA, resulting in mutations that may lead to carcinogenesis. Genes involved in the biosynthesis of these enzymes are all subject to genetic polymorphisms that can lead to altered expression or activity of the encoded proteins. Genetic polymorphisms may, therefore, act as molecular biomarkers that can provide important predictive information about carcinogenesis. The aim of this review is to discuss our current knowledge on the genetic risk factors associated with the development of EC in different populations; it addresses mainly the topics of genetic polymorphisms, gene-environment interactions, and carcinogenesis. We have reviewed the published data on genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and discuss some of the potential gene-environment interactions underlying esophageal carcinogenesis. The main enzymes discussed in this review are the glutathione S-transferases (GSTs), N-acetyltransferases (NATs), cytochrome P450s (CYPs), sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and epoxide hydrolases (EHs), all of which have key roles in the detoxification of environmental and dietary carcinogens. Finally, we discuss recent advances in the study of genetic polymorphisms associated with EC risk, specifically with regard to genome-wide association studies, and examine possible challenges of case-control studies that need to be addressed to better understand the interaction between genetic and environmental factors in esophageal carcinogenesis.	esophagus
A Prospective Randomized Trial of Enteral Nutrition After Thoracoscopic Esophagectomy for Esophageal Cancer.	BACKGROUND: Several studies have reported that postoperative enteral nutrition (EN) reduced complications and decreased weight loss and hospital stay periods; however, the majority of patients analyzed in these studies underwent open thoracic surgery. No studies have been conducted regarding EN in patients after thoracoscopic esophagectomy as a less invasive surgery. The aim of this study was to investigate the efficacy of EN after thoracoscopic esophagectomy. METHODS: Fifty patients who underwent thoracoscopic esophagectomy for esophageal cancer were divided into two groups: parenteral nutrition (PN; n = 25) and EN (n = 25). The rate of weight loss at postoperative day (POD) 14, levels of prealbumin at POD 10, postoperative complications until POD 14, and other perioperative data were collected for each group. RESULTS: This study analyzed data for 47 patients. The rate of weight loss at POD 14 was significantly lower in the EN group (3.0 ± 3.2 %) than in the PN group (5.1 ± 3.7 %; p = 0.020). Prealbumin levels were 21.0 ± 7.5 mg/dL in the PN group and 18.4 ± 5.8 mg/dL in the EN group at POD 10, with no significant differences between the groups. However, the incidence of postoperative pneumonia was higher in the PN group (30.4 %) than in the EN group (12.5 %). CONCLUSIONS: EN could suppress weight loss and reduce the incidence of pneumonia after thoracoscopic esophagectomy.	esophagus
[Long-term outcome of neoadjuvant radiochemotherapy followed by surgery for esophageal cancer: a single institution retrospective study of 102 patients].	"PURPOSE AND OBJECTIVES: To report survival and morbidity of a large homogeneous cohort of patients with a locally advanced esophageal or cardia carcinoma and put in evidence predictive factors of locoregional control and survival. PATIENTS AND METHODS: Hundred and two patients were treated at the university hospital of Tours between 1990 and 2010 and received neo-adjuvant chemoradiation therapy with external irradiation (40Gy-44Gy) and two courses of chemotherapy (5-fluoro-uracile and cisplatine). Esophagectomy associated with lymph node dissection was performed about ten weeks after the end of chemoradiation therapy. RESULTS: The median follow-up was 22.4 months [6-185 months]. The overall survival rates at 2 and 5years were 53% and 27%, respectively. The median overall survival was estimated at 27months. The overall 2-year survival between patients ""responders"" and patients ""non-responders"" was 67% vs 26%, respectively (P<0.0001). In case of histological response, there was a benefit in terms of overall survival (P<0.0001), locoregional control (P<0.0036) and disease-free survival (P<0.001). Overall survival at 2years was 64% for ypN0 group vs 32% for ypN1 group (P<0.0001). The median survival was estimated at 37months against 15months in the absence of lymph node involvement (P<0.0001). CONCLUSION: Our results in terms of survival, tolerance and morbidity and mortality were comparable to those in the literature. Complete histological response of lymph node was associated with an improvement of local control, disease-free survival and overall survival."	esophagus
[Effect of Qige Powder on Angiogenesis Induced by Esophageal Cancer Cell Line Eca-9706].	OBJECTIVE: To study the effect Qige powder on esophageal cancer angiogenesis. METHODS: Inhibitive effect of Qige powder ethanol extract on proliferation of Esophageal cancer cell line Eca-9706 was detected by MTT assay. The Eca-9706 cells conditioned medium in Qige powder IC50 concentration were collected. Angiogenesis, as well as proliferation, migration and tube formation of human umbilical vein endothelial cells were observed by Chick embryo chorioallantoic membrane model(CAM), MTT assay, the migration and tube formation assay. VEGF and IL-6 contents in culture medium supernatant of Eca-9706 cells and human umbilical vein endothelial cells were detected by ELISA. RESULTS: Qige powder ethanol extract could inhibit the proliferation of Eca-9706 cells, with a certain dose-effect relationship, IC50 value was 96 µg/mL. Eca-9706 cells conditioned medium could significantly increase the CAM generating total vessel area, human umbilical vein endothelial cells proliferation,migration and tube formation, while the Eca-9706 cell conditioned medium of Qige powder ethanol extract could reduce CAM angiogenesis, human umbilical vein endothelial cells proliferation and tube formation, but increase endothelial cells migration. Qige powder ethanol extract could reduce endothelial cells secreting VEGF and IL-6 while increase Eca-9706 cells secreting. CONCLUSION: Qige powder ethanol extract can inhibit angiogenesis, endothelial cell proliferation, and tube formation induced by Eca-9706 cells, while reduce VEGF and IL-6 secretion of endothelial cells.	esophagus
Statin use reduces risk of esophageal adenocarcinoma in US veterans with Barrett's esophagus: a nested case-control study.	BACKGROUND & AIMS: Statins have been reported to protect against esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). However, there are few data from adequately powered cohort studies of subjects with BE. METHODS: We conducted a nested case-control study of a cohort of BE patients identified from national Veteran Affairs (VA) outpatient files, diagnosed with BE from 2004 through 2009. New cases of EAC recorded after BE diagnosis were identified during a follow-up period that ended in 2011 and verified using electronic medical records. We selected patients with BE without EAC (controls) using incidence density sampling; 3 controls were matched to each case based on birth year and date of BE diagnosis. Our analysis included only male patients with at least 1 VA visit per year of follow up. We identified prescriptions for statins and non-statin lipid lowering medications filled after BE diagnosis and up to 90 days before EAC diagnosis for cases and controls (during the corresponding time period); we examined the association between statin use and EAC in conditional logistic regression models. RESULTS: We compared 311 EAC cases to 856 controls. Cases were less likely to use any statins than controls (40.2% vs 54.0%; P < .01). Significantly lower proportions of cases used statins for 6-18 months (10.0% cases vs 17.1% controls) and >18 months (19.3% vs 24.0%, respectively; P < .01). Simvastatin was the most commonly prescribed statin (accounting for 86.9% of statin use); the defined daily dose of simvastatin was lower in cases than in controls (21-40 mg/day, 9.3% vs 14.5%, respectively; and >40 mg/day, 8.4% vs 12.6%, respectively; P < .01). In multivariate analysis, statin use was inversely associated with development of EAC (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.47-0.91). This protective association was strongest for patients with advanced-stage EAC: in a stratified analysis, comparison of 189 cases with stage 0-1 EAC to 520 controls produced an adjusted OR of 0.85 (95% CI, 0.54-1.33). Among patients with late-stage EAC (stages 2-4, n = 106) and 291 controls, the adjusted OR was 0.44 (95% CI, 0.25-0.79). We found no association between EAC and non-statin lipid-lowering medications. CONCLUSIONS: In a case-control study of US veterans, statin use among those with BE appeared to decrease the risk of EAC. This protective effect was strongest against advanced-stage EAC, and increased with statin dose.	esophagus
Dietary inflammatory index and risk of esophageal squamous cell cancer in a case-control study from Italy.	PURPOSE: Diet and inflammation have been suggested to be important risk factors for esophageal squamous cell cancer (ESCC). In this study, we examined the association between the dietary inflammatory index (DII) and ESCC in a case-control study conducted between 1992 and 1997 in Italy. METHODS: This study included 304 ESCC cases and 743 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a reproducible and valid 78-item food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) conditioned on age, sex, year of interview, and area of residence and adjusted for education, smoking, alcohol drinking, BMI, physical activity, and aspirin use. Energy adjustment was performed using the residual method. RESULTS: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of ESCC, with the DII being used as both a continuous variable (ORcontinuous 1.39, 95 % confidence interval, CI, 1.25-1.54; one-unit increase corresponding to ≈12 % of its range in the current study) and a categorical variable (ORquintile5vs1 2.46, 95 % CI 1.40-4.36; p trend < 0.001). CONCLUSION: These results indicate that a pro-inflammatory diet is associated with a higher risk of ESCC, even after controlling for alcohol and tobacco exposure.	esophagus