crossing96/oncoscreening huggingface dataset:
HPV16 E6-E7 induces cancer stem-like cells phenotypes in esophageal squamous cell carcinoma through the activation of PI3K/Akt signaling pathway in vitro and in vivo.	High-risk human papillomavirus (HPV), especially HPV16, correlates with cancerogenesis of human esophageal squamous cell carcinoma (ESCC) and we have reported that HPV16 related with a poor prognosis of ESCC patients in China. We aim to investigate the potential role and mechanism of HPV16 in ESCC development and progress. Our following researches demonstrated that ESCC cells which were stably transfected by HPV16 E6-E7 lentiviral vector showed a remarkable cancer stem-like cells (CSCs) phenotype, such as: migration, invasion, spherogenesis, high expression of CSCs marker in ESCC---p75NTR, chemoresistance, radioresistance, anti-apoptosis ability in vitro and cancerogenesis in vivo. HPV16 E6-E7 induced PI3K/Akt signaling pathway activation and this affect could be effectively inhibited by LY294002, a specific PI3K inhibitor. It was also indicated that the inhibition of PI3K/Akt signaling pathway by PI3K and Akt siRNA reverse the effect which induced by HPV16 E6-E7 in ESCC cells. Taken together, the present study demonstrates that HPV16 E6-E7 promotes CSCs phenotype in ESCC cells through the activation of PI3K/Akt signaling pathway. Targeting the PI3K/Akt signaling pathway in HPV16 positive tissues is an available therapeutic for ESCC patients.	esophagus
Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma.	OBJECTIVE: Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA. DESIGN: We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. RESULTS: We identified a significant signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate q=0.03), and in gene-level analyses found an association with microsomal glutathione-S-transferase 1 (MGST1); (p=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of these were subsequently confirmed (p<5.5×10(-5)) in a meta-analysis encompassing an independent set of 1851 BE cases and 3496 controls, and are known strong expression quantitative trait loci for MGST1. Three such variants were associated with similar elevations in OA risk. CONCLUSIONS: This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/OA and suggests that variants in MGST1 influence disease susceptibility.	esophagus
ypN0: Does It Matter How You Get There? Nodal Downstaging in Esophageal Cancer.	"BACKGROUND: ypN0 following induction treatment for advanced esophageal cancer improves survival. Importance of how ypN0 is achieved is unknown. This study evaluates survival in ""natural"" N0 (cN0/ypN0) and ""downstaged"" N0 (cN+/ypN0) patients. METHODS: Among patients treated with induction treatment and surgery, 83 CT scans were retrieved in digital format and re-evaluated by a radiologist, blinded to pathological nodal status: 28 natural N0, 37 downstaged N0, and 18 ypN+. Impact of N0 classification on survival and associations with survival were identified. RESULTS: Survival varied with ypN: 3-year survival was 84 % for natural N0 patients, 59 % for downstaged N0, and 20 % for ypN+ (p < .001). Compared with natural N0 patients, risk of cancer mortality was 3.8 for downstaged N0 and 7.6 for ypN+ (p = .01). Survival was also stratified by ypT: compared with ypT0 natural N0, who had the best survival, intermediate survival was seen in ypT+ natural N0 [hazard ratio (HR), 1.3] and ypT0 downstaged N0 (HR, 1.8), and poor survival in ypT+ downstaged N0 (HR, 9.5) and ypN+ (HR, 12.0) (p = .026). CONCLUSIONS: Natural N0 and downstaged N0 patients are different clinical entities: downstaging cN+ with induction treatment producing downstaged N0 improves survival only if there is concomitant primary cancer downstaging to ypT0. Intermediate survival is seen in downstaged N0 patients with complete tumor response. Natural N0 patients experience intermediate survival with incomplete response (ypT+). Complete response in natural N0 patients produces the best survival. Means of obtaining ypN0 status matters and requires a complete response for downstaged N0 patients to benefit from induction treatment."	esophagus
[Risk factors of Barrett's esophagus].	Barret's esophagus, and accompanying esophageal adenocarcinoma have been increasing over the last 3-4 decades in Western countries. Although the prevalence of the esophageal adenocarcinoma has not obviously increased in Japan, GERD, a precursor condition of the can- cer, has recently increased in that country. Recognized risk factors for Barrett's esophagus are male gender, higher age, GERD, obesity, and protective factor for the disease is H. pyloi infection. Identification of risk factors for Barrett's esophagus should be useful to estimate the future trend of esophageal adenocarcinoma in Japan.	esophagus
Leukotriene receptor expression in esophageal squamous cell cancer and non-transformed esophageal epithelium: a matched case control study.	BACKGROUND: Leukotriene B4 (LTB4R and LTB4R2) and cysteinyl leukotriene receptors (CYSLTR1 and CYSLTR2) contribute to malignant cell transformation. We aimed to investigate the expression of LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 in esophageal squamous cell carcinoma and adjacent non-transformed squamous epithelium of the esophagus, as well as in control biopsy samples from esophageal squamous epithelium of patients with functional dyspepsia. METHODS: Expression of LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 was analyzed by immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in biopsy samples of 19 patients with esophageal squamous cell cancer and 9 sex- and age-matched patients with functional dyspepsia. RESULTS: LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 were expressed in all biopsy samples. Major findings were: 1) protein levels of all leukotriene receptors were significantly increased in esophageal squamous cell cancer compared to control mucosa (p < 0.05); 2) CYSLTR1 and CYSLTR2 gene expression was decreased in cancer tissue compared to control at 0.26-fold and 0.23-fold respectively; 3) an up-regulation of LTB4R (mRNA and protein expression) and a down-regulation of CYSLTR2 (mRNA expression) in non-transformed epithelium of cancer patients compared to control (p < 0.05) was observed. CONCLUSIONS: The expression of leukotriene receptors was deregulated in esophageal squamous cell cancer. Up-regulation of LTB4R and down-regulation of CYSLTR2 gene expression may occur already in normal squamous esophageal epithelium of patients with esophageal cancer suggesting a potential role of these receptors in early steps of esophageal carcinogenesis. Larger studies are warranted to confirm these observations.	esophagus
Trainee competence in thoracoscopic esophagectomy in the prone position: evaluation using cumulative sum techniques.	PURPOSE: Minimally invasive esophagectomy (MIE) has less morbidity than the open approach. In particular, thoracoscopic esophagectomy in the prone position (TEP) has been performed worldwide. Using the cumulative sum control chart (CUSUM) method, this study aimed to confirm whether a trainee surgeon who learned established standards would become skilled in TEP with a shorter learning curve than that of the mentoring surgeon. METHODS: Surgeon A performed TEP in 100 patients; the first 22 patients comprised period 1. His learning curve, defined based on the operation time (OT) of the thoracic procedure, was evaluated using the CUSUM method, and short-term outcomes were assessed. Another 22 patients underwent TEP performed by surgeon B, with outcomes compared to those of surgeon A's period 1. RESULTS: Using the CUSUM chart, the peak point of the thoracic procedure OT occurred at the 44th case in surgeon A's experience of 100 cases. With surgeon A's first 22 cases (period 1), the peak point of the thoracic procedure OT could not be confirmed and graph is expanding soaring at CUSUM chart. The CUSUM chart of surgeon B's experience of 22 cases clearly indicated that the peak point of the thoracic procedure OT occurred at the 17th case. The rate of recurrent laryngeal nerve palsy for surgeon B (9 %) was significantly lower than for surgeon A in period 1 (36 %) (p = 0.0266). CONCLUSIONS: There is some possibility for a trainee surgeon to attain the required basic skills to perform TEP in a relatively short period of time using a standardized procedure developed by a mentoring surgeon. The CUSUM method should be useful in evaluating trainee competence during an initial series of procedures, by assessing the learning curve defined by OT.	esophagus
Blood flow speed of the gastric conduit assessed by indocyanine green fluorescence: New predictive evaluation of anastomotic leakage after esophagectomy.	Anastomotic leakage is considered as an independent risk factor for postoperative mortality after esophagectomy, and an insufficient blood flow in the reconstructed conduit may be a risk factor of anastomotic leakage. We investigated the clinical significance of blood flow visualization by indocyanine green (ICG) fluorescence in the gastric conduit as a means of predicting the leakage of esophagogastric anastomosis after esophagectomy.Forty patients who underwent an esophagectomy with gastric conduit reconstruction were prospectively investigated. ICG fluorescence imaging of the gastric conduit was detected by a near-infrared camera system during esophagectomy and correlated with clinical parameters or surgical outcomes.In 25 patients, the flow speed of ICG fluorescence in the gastric conduit wall was simultaneous with that of the greater curvature vessels (simultaneous group), whereas in 15 patients this was slower than that of the greater curvature vessels (delayed group). The reduced speed of ICG fluorescence stream in the gastric conduit wall was associated with intraoperative blood loss (P = 0.008). Although anastomotic leakage was not found in the simultaneous group, it occurred in 7 patients of the delayed group (P < 0.001). A flow speed of ICG fluorescence in the gastric conduit wall of 1.76 cm/s or less was determined by a receiver operating characteristic (ROC) curve, identified as a significant independent predictor of anastomotic leakage after esophagectomy (P = 0.004).This preliminary study demonstrates that intraoperative evaluation of blood flow speed by ICG fluorescence in the gastric conduit wall is a useful means to predict the risk of anastomotic leakage after esophagectomy.	esophagus
PI3K/mTOR Dual Inhibitor, LY3023414, Demonstrates Potent Antitumor Efficacy Against Esophageal Adenocarcinoma in a Rat Model.	OBJECTIVE: The purpose of the current study is to determine the efficacy of a PI3K/mTOR dual inhibitor, LY3023414, on established EAC in an in vivo model. BACKGROUND: Esophageal adenocarcinoma (EAC) is a highly lethal cancer with limited treatment options. The PI3K/mTOR pathway is upregulated in EAC and may be a target for novel therapies. METHODS: Esophagojejunostomy was performed on Sprague-Dawley rats to induce carcinogenesis, and LY3023414 was cyclically administered intraperitoneally between 32 and 40 weeks postsurgery to treatment animals. Magnetic resonance imaging (MRI) and histology were used to determine clinical response. Immunohistochemistry, immunofluorescence, and Western blot were used to validate apoptosis by cleaved caspase-3, proliferation by Ki67, and pathway inhibition, respectively. RESULTS: Mean MRI tumor volume increased by 109.2% in controls (n = 32) and decreased by 56.8% in treatment animals (n=17) (P < 0.01). Treatment with LY3023414 demonstrated tumor volume increase in 0% (control = 46.4%) (P < 0.01), decrease in 58.8% (control = 7.1%) (P < 0.01), and stable volume in 41.2% (control = 46.4%) (P = 0.77). EAC prevalence in controls increased by 25%; whereas, prevalence in treatment animals decreased by 29.4% (P < 0.01). Approximately, 75% of treatment animals presenting with residual masses on MRI had a histological response >50%. Increased apoptosis by cleaved caspase-3 (P = 0.03) and decreased proliferation by Ki67 (P < 0.01) were demonstrated in the treatment arm, when compared with the control arm. On Western blot analysis of pathway checkpoints, p-mTOR (p=0.03) and PI3K-α (P = 0.04) were downregulated in treatment responsive residual tumors, when compared with controls. CONCLUSIONS: LY3023414 demonstrates efficacy against EAC in a preclinical model, establishing the rationale for clinical testing.	esophagus
Role of endoscopy to predict a leak after esophagectomy.	PURPOSE: After esophageal surgery, many centers conduct a routine diagnostic test before reintroducing oral intake. However, the clinical value in asymptomatic patients has been questioned. Therefore, we left this decision to the discretion of the operating surgeon and documented the data prospectively. METHODS: Between 2007 and 2013, 185 consecutive patients underwent elective esophageal resection in our institution. The decision as to whether an endoscopy was to be performed as a routine-check or when a leak was clinically suspected was at the discretion of the operating surgeon. An immediate endoscopy was performed on emerging clinical signs of a leak. If a routine check was planned, it was performed between postoperative days 5-7. RESULTS: Of the 185 patients, 84 % had an endoscopy of the anastomosis during the hospital stay. Of the patients who underwent an endoscopy, 61 % were on a routine-check. In this group, one patient showed a leak at the time of endoscopy, 11 patients had pathological findings, 3 of these patients developed a leak later. Eighty-three patients had no pathological findings; nevertheless, 7 developed a leak later. In the on-demand-group, 10 patients showed a leak at the time of endoscopy. CONCLUSIONS: In a minority of patients, a routine-check of the anastomosis between days 5-7 revealed pathological findings that later led to an anastomotic leak (3/11). In contrast, a routine-check without pathological findings could not rule out the development of a future leak (7/83). Therefore, we conclude that routine postoperative studies to identify leaks after esophageal resection are not justified.	esophagus
Recent traction methods for endoscopic submucosal dissection.	Endoscopic mucosal resection (EMR) is problematic with regard to en bloc and curable resection rates. Advancements in endoscopic techniques have enabled novel endoscopic approaches such as endoscopic submucosal dissection (ESD), which has overcome some EMR problems, and has become the standard treatment for gastrointestinal tumors. However, ESD is technically difficult. Procedure time is longer and complications such as intraoperative perforation and bleeding occur more frequently than in EMR. Recently various traction methods have been introduced to facilitate ESD procedures, such as clip with line, external forceps, clip and snare, internal traction, double scope, and magnetic anchor. Each method must be used appropriately according to the anatomical characteristics. In this review we discuss recently proposed traction methods for ESD based on the characteristics of various anatomical sites.	esophagus
Association Between Germline Mutation in VSIG10L and Familial Barrett Neoplasia.	IMPORTANCE: Esophageal adenocarcinoma and its precursor lesion Barrett esophagus have seen a dramatic increase in incidence over the past 4 decades yet marked genetic heterogeneity of this disease has precluded advances in understanding its pathogenesis and improving treatment. OBJECTIVE: To identify novel disease susceptibility variants in a familial syndrome of esophageal adenocarcinoma and Barrett esophagus, termed familial Barrett esophagus, by using high-throughput sequencing in affected individuals from a large, multigenerational family. DESIGN, SETTING, AND PARTICIPANTS: We performed whole exome sequencing (WES) from peripheral lymphocyte DNA on 4 distant relatives from our multiplex, multigenerational familial Barrett esophagus family to identify candidate disease susceptibility variants. Gene variants were filtered, verified, and segregation analysis performed to identify a single candidate variant. Gene expression analysis was done with both quantitative real-time polymerase chain reaction and in situ RNA hybridization. A 3-dimensional organotypic cell culture model of esophageal maturation was utilized to determine the phenotypic effects of our gene variant. We used electron microscopy on esophageal mucosa from an affected family member carrying the gene variant to assess ultrastructural changes. MAIN OUTCOMES AND MEASURES: Identification of a novel, germline disease susceptibility variant in a previously uncharacterized gene. RESULTS: A multiplex, multigenerational family with 14 members affected (3 members with esophageal adenocarcinoma and 11 with Barrett esophagus) was identified, and whole-exome sequencing identified a germline mutation (S631G) at a highly conserved serine residue in the uncharacterized gene VSIG10L that segregated in affected members. Transfection of S631G variant into a 3-dimensional organotypic culture model of normal esophageal squamous cells dramatically inhibited epithelial maturation compared with the wild-type. VSIG10L exhibited high expression in normal squamous esophagus with marked loss of expression in Barrett-associated lesions. Electron microscopy of squamous esophageal mucosa harboring the S631G variant revealed dilated intercellular spaces and reduced desmosomes. CONCLUSIONS AND RELEVANCE: This study presents VSIG10L as a candidate familial Barrett esophagus susceptibility gene, with a putative role in maintaining normal esophageal homeostasis. Further research assessing VSIG10L function may reveal pathways important for esophageal maturation and the pathogenesis of Barrett esophagus and esophageal adenocarcinoma.	esophagus
An integrative framework to identify cell death-related microRNAs in esophageal squamous cell carcinoma.	Cell death is a critical biological process involved in many important functions, and defects in this system are usually linked with numerous human diseases including cancers. Esophageal squamous cell carcinoma is one of the most chemo- and biological therapy resistant cancers. Based on knowledge repository and four miRNAs profiling data, we proposed a general framework to hunt for cell death miRNAs in a context dependent manner. We predicted 12 candidate miRNAs from hundreds of others. Follow-up experimental verification of 7 miRNAs indicated at least 3 miRNAs (MIR20b, MIR498 and MIR196) were involved in both apoptosis and autophagy processes. These results indicated miRNAs intimately connected the two cell death modules in esophageal squamous cell carcinoma. This integrative framework can also be easily extended to identify miRNAs in other key cellular signaling pathways or may find conditional specific miRNAs in other cancer types.	esophagus
Influence of body mass index on the prevalence and progression of dysplasia in Barrett's esophagus: a retrospective analysis (.).	OBJECTIVE: High body mass index (BMI) is a risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Our aim was to determine if prevalence of dysplasia in BE varies by BMI and study the effect of BMI on progression to high-grade dysplasia (HGD) or EAC. MATERIALS AND METHODS: This is a retrospective review of patients with endoscopic evidence of BE confirmed by presence of intestinal metaplasia on histology from January 2000 to December 2012 at Cleveland Clinic. Patient demographics, BMI and endoscopic findings such as length of BE, dysplasia in BE and size of hiatal hernia were reviewed. Dysplasia was classified as no dysplasia (NDBE), low-grade dysplasia (LGD), HGD and EAC. RESULTS: In this cohort of 1239 patients, average BMI was 29.8 ± 6 kg/m(2). There were 228 (18.4%) in group with BMI <25, 236 (19%) in BMI group 25-27.4, 262 (21.1%) in BMI 27.5-29.9, 303 (24.5%) in BMI 30-34.9, 126 (10.2%) in BMI 35-39.9 and 86 (6.8%) in BMI ≥40. Lower BMI groups had lower prevalence of dysplasia while higher BMI groups had higher prevalence of dysplasia (p = 0.002). During mean follow up of 31.6 ± 26 months, there were 14 cases of HGD/EAC in NDBE group and 29 cases of HGD/EAC in LGD group. BMI or BMI change was not associated with progression to HGD/EAC in NDBE. CONCLUSIONS: High BMI was associated with higher prevalence of dysplasia in BE. But once in a surveillance program, higher BMI is not associated with progression of dysplasia in NDBE.	esophagus
Knockdown of Zinc Transporter ZIP5 by RNA Interference Inhibits Esophageal Cancer Growth In Vivo.	We recently found that SLC39A5 (ZIP5), a zinc transporter, is overexpressed in esophageal cancer. Downregulation of ZIP5 inhibited the proliferation, migration, and invasion of the esophageal cancer cell line KYSE170 in vitro. In this study, we found that downregulation of SLC39A5 (ZIP5) by interference resulted in a significant reduction in esophageal cancer tumor volume and weight in vivo. COX2 (cyclooxygenase 2) expression was decreased and E-cadherin expression was increased in the KYSE170K xenografts, which was caused by the downregulation of ZIP5. However, we did not find that the downregulation of ZIP5 caused a change in the relative expressions of cyclin D1, VEGF (vascular endothelial growth factor), MMP9 (matrix metalloprotein 9), and Bcl-2 (B-cell lymphoma/leukmia-2) mRNA or an alteration in the average level of zinc in the peripheral blood and xenografts in vivo. Collectively, these findings indicate that knocking down ZIP5 by small interfering RNA (siRNA) might be a novel treatment strategy for esophageal cancer with ZIP5 overexpression.	esophagus
C-reactive protein is a useful negative predictor of anastomotic leak in oesophago-gastric resection.	BACKGROUND: Post-operative C-reactive protein (CRP) has been investigated as a predictor of anastomotic leak (AL) following colorectal surgery, but its role in oesophago-gastric surgery is not yet established. METHODS: Clinical data and post-operative CRP values of patients who underwent elective oesophago-gastric resection between January 2004 and July 2014 were analysed retrospectively. Only patients with an oesophageal anastomosis were included. AL was defined as leakage of contrast material seen on imaging or a leak confirmed intraoperatively on return to theatre. RESULTS: One hundred and forty-five patients were identified. Of the 145 patients, 13 (9%) developed AL. The CRP on post-operative days (POD) 2, 3 and 6 had the greatest diagnostic accuracy, with an area under the curve of 0.82, 0.80 and 0.91 respectively. Using a cut-off value of 209 mg/L on POD 2, the sensitivity was 100%, the specificity was 61%, the positive predictive value (PPV) was 21% and the negative predictive value (NPV) was 100%. Using a cut-off value of 190 mg/L on POD 3, the sensitivity was 100%, the specificity was 59%, the PPV was 21% and the NPV was 100%. Using a cut-off value of 154 mg/L on POD 6, the sensitivity was 100%, the specificity was 78%, the PPV was 29% and the NPV was 100%. CONCLUSION: Post-operative CRP is an accurate negative predictive test for the development of AL following oesophago-gastric surgery. It may help to discriminate between patients with a high risk of leak and those in which AL is unlikely to occur.	esophagus