crossing96/oncoscreening huggingface dataset:
Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples. RESULTS: Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC. CONCLUSIONS: Our results suggest that FAM84B and the NOTCH pathway are involved in the progression of ESCC and may be potential diagnostic targets for ESCC susceptibility.	esophagus
Integrated analysis of DNA methylation and mutations in esophageal squamous cell carcinoma.	The recent development of next-generation sequencing technology for extensive mutation analysis, and beadarray technology for genome-wide DNA methylation analysis has made it possible to obtain integrated pictures of genetic and epigenetic alterations, using the same cancer samples. In this study, we aimed to characterize such a picture in esophageal squamous cell carcinomas (ESCCs). Base substitutions of 55 cancer-related genes and copy number alterations (CNAs) of 28 cancer-related genes were analyzed by targeted sequencing. Forty-four of 57 ESCCs (77%) had 64 non-synonymous somatic mutations, and 24 ESCCs (42%) had 35 CNAs. A genome-wide DNA methylation analysis using an Infinium HumanMethylation450 BeadChip array showed that the CpG island methylator phenotype was unlikely to be present in ESCCs, a different situation from gastric and colon cancers. Regarding individual pathways affected in ESCCs, the WNT pathway was activated potentially by aberrant methylation of its negative regulators, such as SFRP1, SFRP2, SFRP4, SFRP5, SOX17, and WIF1 (33%). The p53 pathway was inactivated by TP53 mutations (70%), and potentially by aberrant methylation of its downstream genes. The cell cycle was deregulated by mutations of CDKN2A (9%), deletions of CDKN2A and RB1 (32%), and by aberrant methylation of CDKN2A and CHFR (9%). In conclusion, ESCCs had unique methylation profiles different from gastric and colon cancers. The genes involved in the WNT pathway were affected mainly by epigenetic alterations, and those involved in the p53 pathway and cell cycle regulation were affected mainly by genetic alterations. © 2016 Wiley Periodicals, Inc.	esophagus
Endoscopic submucosal tunnel dissection for large superficial esophageal squamous cell neoplasms.	Endoscopic submucosal dissection (ESD) is a well-established treatment for superficial esophageal squamous cell neoplasms (SESCNs) with no risk of lymphatic metastasis. However, for large SESCNs, especially when exceeding two-thirds of the esophageal circumference, conventional ESD is time-consuming and has an increased risk of adverse events. Based on the submucosal tunnel conception, endoscopic submucosal tunnel dissection (ESTD) was first introduced by us to remove large SESCNs, with excellent results. Studies from different centers also reported favorable results. Compared with conventional ESD, ESTD has a more rapid dissection speed and R0 resection rate. Currently in China, ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique, as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria. However, not all patients with SESCNs are candidates for ESTD, and postoperative esophageal strictures should also be taken into consideration, especially for lesions with a circumference greater than three-quarters. In this article, we describe our experience, review the literature of ESTD, and provide detailed information on indications, standard procedures, outcomes, and complications of ESTD.	esophagus
Cumulative scores based on plasma D-dimer and serum albumin levels predict survival in esophageal squamous cell carcinoma patients treated with transthoracic esophagectomy.	BACKGROUND: Recently, studies have shown that plasma D-dimer and serum albumin are prognostic markers for esophageal cancer. The purpose of this study was to evaluate a novel prognostic scoring system--DA score (combination of preoperative plasma D-dimer and serum albumin levels)--and analyze the association between survival of patients with esophageal squamous cell carcinoma (ESCC) and their Glasgow prognostic score. METHODS: In this retrospective study, preoperative biochemical markers and clinicopathologic factors in 260 ESCC patients treated with transthoracic esophagectomy were reviewed. According to receiver operating characteristic analysis, the cutoff values of D-dimer and albumin were defined as 0.5 μg/mL and 43.8 g/L, respectively. Patients with high D-dimer levels (≥0.5 μg/mL) and low albumin levels (<43.8 g/L) were assigned a score of 2, those with only one of the two abnormalities were assigned a score of 1, and those with neither of the two abnormalities were assigned a score of 0. RESULTS: ESCC patients with a DA score of 0, 1, and 2 numbered 55, 116, and 89, respectively. Survival analysis showed that patients with a DA score of 2 had lower overall survival (OS) rates than those with DA scores of 1 and 0 (37.1% vs. 52.6% and 76.4%, P < 0.001); similar findings were observed for disease-free survival (DFS) rates (32.6% vs. 44.8% and 67.3%, P < 0.001). In addition, the predictive value of the DA score was also significant in patients with stages I-IIA and stages IIB-IV ESCC. Multivariate Cox regression analyses indicated that hazard ratios (HRs) for predicting OS of patients with DA scores 1 and 2 were 2.25 (P = 0.010) and 3.14 (P < 0.001), respectively, compared with those with a DA score of 0, and HRs for predicting DFS of patients with DA scores of 1 and 2 were 1.86 (P = 0.023) and 2.68 (P < 0.001), respectively, compared with those with a DA scores of 0. CONCLUSIONS: Our study suggests that preoperative DA scores are notably associated with postoperative survival of ESCC patients.	esophagus
Postoperative Infectious Complications are Associated with Adverse Oncologic Outcomes in Esophageal Cancer Patients Undergoing Preoperative Chemotherapy.	BACKGROUND: For some types of cancer, postoperative complications can negatively influence survival, but the association between these complications and oncological outcomes is unclear for patients with esophageal cancer who receive preoperative treatments. METHODS: Data were retrospectively analyzed for patients who underwent curative resection following preoperative chemotherapy for esophageal squamous cell carcinoma from 2001 to 2011. Clinicopathological parameters and cancer-specific survival (CSS) were compared between patients with and without severe postoperative complications, grade III or higher, using the Clavien-Dindo classification. RESULTS: Of 255 patients identified, 104 (40.8 %) postoperatively developed severe complications. The most common complication was atelectasis in 61 (23.9 %), followed by pulmonary infection in 22 (8.6 %). Three-field lymphadenectomy, longer operation time, and more blood loss were significantly associated with a higher incidence of severe complications. Multivariate analysis of CSS revealed severe complications [hazard ratio (HR) = 1.642, 95 % confidence interval (95 % CI) 1.095-2.460, p = 0.016] as a significant prognostic factor along with pT stage [HR = 2.081, 95 % CI 1.351-3.266, p < 0.001] and pN stage [HR = 3.724, 95 % CI 2.111-7.126, p < 0.001], whereas postoperative serum C-reactive protein value was not statistically significant. Among all complications, severe pulmonary infection was the only independent prognostic factor [HR = 2.504, 95 % CI 1.308-4.427, p = 0.007]. CONCLUSIONS: The incidence of postoperative infectious complications, in particular pulmonary infection, is associated with unfavorable prognosis in patients with esophageal cancer undergoing preoperative chemotherapy.	esophagus
REV3L, the catalytic subunit of DNA polymerase ζ, is involved in the progression and chemoresistance of esophageal squamous cell carcinoma.	Protein reversionless 3-like (REV3L), the catalytic subunit of DNA polymerase (pol) ζ, is well known to participate in error-prone translesion synthesis (TLS) with less stringent and lower processivity. Recent evidence has demonstrated that REV3L is involved in carcinogenesis and tumor progression. However, the function of REV3L remains unclear in esophageal squamous cell carcinoma (ESCC). In the present study, we examined REV3L expression in ESCC tissues and its association with clinicopathological parameters. REV3L was found to be significantly upregulated and correlated with lymph node metastasis and clinical stage in the ESCC tissues. To further investigate the potential role of REV3L in esophageal cancer, stable ESCC cell lines with suppression of REV3L expression were established. Downregulation of REV3L expression led to a decrease in cell proliferation and invasive capacity partly through suppression of cyclin D1 and survivin expression, and an increase in cellular sensitivity to 5-fluorouracil (5-FU) by induction of G1 phase arrest and apoptosis. Therefore, REV3L plays an important role in ESCC progression and chemoresistance, and is a potential diagnostic marker and therapeutic target for ESCC.	esophagus
The influence of smoking on radiation-induced bystander signal production in esophageal cancer patients.	The relevance of radiation-induced bystander effects in humans is unclear. Much of the existing data relate to cell lines but the effect of bystander signals in complex human tissues is unclear. A phase II clinical study was untaken, where blood sera from 60 patients along with 15 cancer-free volunteers were used to detect whether measurable bystander factor(s) could be found in the blood following high dose rate (HDR) brachytherapy. Overall, there was no significant change in bystander signal production (measured in a human keratinocyte reporter system) before and after one treatment fraction of HDR brachytherapy (p>0.05). Further assessment of patient characteristics and environmental modifiable factors including smoking were also analyzed. Similar to previously published data, samples taken from smokers produced weaker signals compared to non-smokers (p<0.05). Although the number of non-smoking subjects was low, there was a clear decrease in cloning efficiency observed in keratinocyte cultures for these patients that requires further study. This study found that samples taken from smokers do not produce bystander signals, whereas samples taken from non-smokers can produce such signals following HDR brachytherapy. These findings highlight the importance of studying the interactions of multiple stressors including environmental modifiers with radiation, since some factors such as smoking may elicit protection in tumor cells which could counteract the effectiveness of radiation therapy.	esophagus
Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma.	BACKGROUND: The phase III RAINBOW trial demonstrated that the addition of ramucirumab to paclitaxel improved overall survival, progression-free survival, and tumor response rate in fluoropyrimidine-platinum previously treated patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Here, we present results from quality-of-life (QoL) and performance status (PS) analyses. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group PS of 0/1 were randomized to receive ramucirumab (8 mg/kg i.v.) or placebo on days 1 and 15 of a 4-week cycle, with both arms receiving paclitaxel (80 mg/m(2)) on days 1, 8, and 15. Patient-reported outcomes were assessed with the QoL/health status questionnaires EORTC QLQ-C30 and EQ-5D at baseline and 6-week intervals. PS was assessed at baseline and day 1 of every cycle. Time to deterioration (TtD) in each QLQ-C30 scale was defined as randomization to first worsening of ≥10 points (on 100-point scale) and TtD in PS was defined as first worsening to ≥2. Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. RESULTS: Of the 665 patients randomized, 650 (98%) provided baseline QLQ-C30 and EQ-5D data, and 560 (84%) also provided data from ≥1 postbaseline time point. Baseline scores for both instruments were similar between arms. Of the 15 QLQ-C30 scales, 14 had HR < 1, indicating similar or longer TtD in QoL for ramucirumab + paclitaxel. Treatment with ramucirumab + paclitaxel was also associated with a delay in TtD in PS to ≥2 (HR = 0.798, P = 0.0941). Alternate definitions of PS deterioration yielded similar results: PS ≥ 3 (HR = 0.656, P = 0.0508), deterioration by ≥1 PS level (HR = 0.802, P = 0.0444), and deterioration by ≥2 PS levels (HR = 0.608, P = 0.0063). EQ-5D scores were comparable between treatment arms, stable during treatment, and worsened at discontinuation. CONCLUSION: In patients with previously treated advanced gastric/GEJ adenocarcinoma, addition of ramucirumab to paclitaxel prolonged overall survival while maintaining patient QoL with delayed symptom worsening and functional status deterioration. CLINICALTRIALSGOV: NCT01170663.	esophagus
Polymorphisms in Heat Shock Proteins A1B and A1L (HOM) as Risk Factors for Oesophageal Carcinoma in Northeast India.	BACKGROUND: To investigate polymorphisms in heat shock proteins A1B and A1L (HOM) and associated risk of oesophageal carcinoma in Northeast India. MATERIALS AND METHODS: The study includes oesophageal cancer (ECA) patients attending general outpatient department (OPD) and endoscopic unit of Gauhati Medical College. Patients were diagnosed based on endoscopic and histopathological findings. Genomic DNA was typed for HSPA1B1267 and HSPA1L2437 SNPs using the polymerase chain reaction with restriction fragment length polymorphisms. RESULTS: A total of 78 cases and 100 age-sex matched healthy controls were included in the study with a male: female ratio of 5:3 and a mean age of 61.4±8.5 years. Clinico-pathological evaluation showed 84% had squamous cell carcinoma and 16% were adenocarcinoma. Dysphagia grades 4 (43.5%) and 5 (37.1%) were observed by endoscopic and hispathological evaluation. The frequency of genomic variation of A1B from wild type A/A to heterozygous A/G and mutant G/G showed a positive association [chi sq=19.9, p= <0.05] and the allelic frequency also showed a significant correlation [chi sq=10.3, with cases vs. controls, OR=0.32, p≤0.05]. The genomic variation of A1L from wild T/T to heterozygous T/C and mutant C/C were found positively associated [chi sq= 7.02, p<0.05] with development of ECA. While analyzing the allelic frequency, there was no significant association [chi sq= 3.19, OR=0.49, p=0.07]. Among all the risk factors, betel quid [OR =9.79, Chi square= 35.0, p<0.05], tobacco [OR = 2.95, chi square=10.6, p<0.05], smoking [OR=3.23, chi square=10.1, p<0.05] demonstrated significant differences between consumers vs. non consumers regarding EC development. Alcohol did not show any significant association [OR= 1.34, chi square=0.69, p=0.4] independently. CONCLUSIONS: It can be concluded that the present study provides marked evidence that polymorphisms of HSP70 A1B and HSP70 A1L genes are associated with the development of ECA in a population in Northeast India, A1B having a stronger influence. Betel quid consumption was found to be a highly significant risk factor, followed by smoking and tobacco chewing. Although alcohol was not a potent risk factor independently, alcohol consumption along with tobacco, smoking and betel nut was found to contribute to development of ECA.	esophagus
Propofol suppresses invasion, angiogenesis and survival of EC-1 cells in vitro by regulation of S100A4 expression.	OBJECTIVE: Propofol possess anticancer properties in several cancers. In the present study, we investigate the effect of propofol on the human esophageal squamous cell carcinomas (ESCC) EC-1 cells in vitro and its molecular mechanisms of action. MATERIALS AND METHODS: EC-1 cells were explored to 10-100 μmol/L propofol for 72 h or 100 μmol/L/mL propofol for 24-72 h. EC-1 cells were explored to 100 μmol/L propofol for 24 h, then was transiently transfected into PcDNA3.1-S100A4 cDNA or PcDNA3.1 plasmid for 48 hrs. MTT, TUNEL, ELISA, migration, tube formation and immunoblotting were analized. RESULTS: Propofol inhibits invasion, angiogenesis, proliferation and induces apoptosis in a dose and time-dependence manner, followed by deseased S100A4 expression by Western blot assay. Pre-transfection of PcDNA3.1-S100A4 cDNA inhibits propofol-induced apoptosis and promotes invasion and angiogenesis in EC-1 cells in vitro. CONCLUSIONS: Propofol inhibited invasion, angiogenesis and induces apoptosis of human EC-1 cells in vitro through regulation of S100A4 expression. It not only can be an anesthesia agent, but also plays a important role of inhibiting the migration and angiogenesis of ESCC cells in the therapy of ESCC patients.	esophagus
Leptomeningeal carcinomatosis from oesophageal cancer, presenting as meningitis.	A 47-year-old woman presented with headache, neck pain, dizziness, nausea and vomiting for 4-5 days. She also had a history of weight loss and difficulty in swallowing. On physical examination, she had nuchal rigidity with a positive Kernig's sign. Cerebrospinal fluid analysis revealed mild pleocytosis but some atypical cells were also noted. Cytopathological analysis of the atypical cells showed high nuclear/cytoplasmic ratios and eccentric nuclei with prominent nucleoli, consistent with malignancy. A CT scan of the head and neck showed multiple lytic lesions involving the left calvarium, and diffuse thickening and enhancement of meninges over the left cerebral area. Extensive osteolytic lesions were also noted on the vertebral bodies, pedicles and lamina, at multiple levels of the cervical spine. An endoscopy revealed a mass at the gastro-oesophageal junction, and biopsy confirmed moderately differentiated adenocarcinoma of the oesophagus. The patient was started on chemotherapy along with radiation therapy.	esophagus
Research protocol for a diagnostic study of non-invasive exhaled breath analysis for the prediction of oesophago-gastric cancer.	INTRODUCTION: Despite improvements in a range of chemo, radio and surgical therapies, the overall survival at 5 years from oesophago-gastric cancer remains poor and ranges from 10% to 30%. Early diagnosis is a key strategy to improve survival but early disease stage has non-specific symptoms that are very common while the warning clinical picture often indicates advanced disease. The aim of this research is to validate a breath test to predict oesophago-gastric cancer therefore allowing earlier diagnosis and introduction of treatment. METHODS AND ANALYSIS: The study will include 325 patients and be conducted across four major oesophago-gastric cancer centres in London, UK. This research will utilise selected ion flow-tube mass spectrometry (SIFT-MS) exhaled breath analysis, for comparison of predicted cancer risk based on the previously developed volatile organic compound exhaled breath model, with endoscopic findings and histology biopsies. This will determine the overall diagnostic accuracy for non-invasive breath testing for the diagnosis of oesophago-gastric cancer. ETHICS AND DISSEMINATION: Approval was gained from NRES Committee London, on 16 July 2014 (REC reference 14/LO/1136) for the completion of this study. Different methods of dissemination will be employed including international clinical and patient group presentations, and publication of research outputs in a high-impact clinical journal. This is to ensure that the findings from this research will reach patients, primary care practitioners, scientists, hospital specialists in gastroenterology, oncology and surgery, health policymakers and commissioners as well as NHS regulatory bodies. TRIALS REGISTRATION NUMBER: UKCRN18063; Pre-results.	esophagus
Identification of novel NRAGE involved in the radioresistance of esophageal cancer cells.	Radiotherapy (RT) is one main method for the treatment of esophageal squamous cell carcinoma (ESCC), and the radioresistance is the predominant cause of patients with local recurrence. The previous results of gene microarray and subsequent verification showed that NRAGE might be involved in radiation resistance of ESCC cells. In this study, we reestablished human esophageal carcinoma radioresistant cell lines TE13R120 and ECA109R60 with gradient dose irradiation as previously reported, respectively. NRAGE expression was high in TE13R120 and ECA109R60 cells and was correlative with ionizing radiation (IR) resistance in clinic. However, the radiosensitivity of TE13R120 cells had a remarkable increase detected by colony formation assays after siRNA against NRAGE (siNRG) transfection into TE13R120 cells. Compared with TE13 cells, an increasing number of TE13R120 cells with NRAGE overexpression in S phase and a lower ratio in G2/M were observed by flow cytometry method (FCM). Intriguingly, the above changes were partially reversed in TE13R120 cells treated with siNRG. More importantly, the ectopic subcellular localization of NRAGE mediated nuclear translocation of β-catenin which may be one reason of IR resistance of esophageal carcinoma cell. These data indicate that NRAGE extremely may be a pivotal factor involved in Wnt/β-catenin signal pathway, mediating nuclear translocation of β-catenin and then facilitating the formation of radioresistance of ESCC.	esophagus
A randomized Phase III trial of thoracoscopic versus open esophagectomy for thoracic esophageal cancer: Japan Clinical Oncology Group Study JCOG1409.	A randomized Phase III study was commenced in May 2015 to confirm the non-inferiority of thoracoscopic esophagectomy to open esophagectomy in terms of overall survival for clinical Stage I-III esophageal cancer. A total of 300 patients will be accrued from Japanese institutions over 6 years. The primary endpoint is overall survival. The secondary endpoints are relapse-free survival, proportion of patients with R0 resection, proportion of patients who underwent re-operation, adverse events, postoperative respiratory function change, postoperative quality-of-life score (EORTC QLQ-C30), and proportion of patients who need conversion from thoracoscopic surgery to open surgery. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017628.	esophagus