crossing96/oncoscreening huggingface dataset:
Insulin receptor substrate-1 and Golgi phosphoprotein 3 are downstream targets of miR‑126 in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a common histologic subtype in China. It has been suggested that abnormal expression of microRNAs (miRNAs) is associated with carcinogenesis. We investigated miR-126 expression and its potential targets in ESCC. The expression of miR-126 was detected in cancerous and paired paracancer tissues from 102 patients with ESCC. Target analysis of miR-126 was predicted using online tools. The effect of miR-126 expression on target proteins was assessed using miR-126 mimics or miR-126 inhibitors in ESCC cell lines. In addition, the impact of miR-126 on cell proliferation, apoptosis, migration and invasion was detected in ESCC cell lines. The expression of miR-126 was significantly lower in ESCC tissues, which was associated with tumor differentiation, lymph node metastasis, tumor in-depth and TNM stage. Insulin receptor substrate-1 (IRS-1) and Golgi phosphoprotein 3 (GOLPH3) were overexpressed in ESCC. Overexpression of IRS-1 was associated with cell differentiation, whereas GOLPH3 was related to lymph node metastasis, tumor invasion in-depth and TNM stage in ESCC patients. miR-126 mimics downregulated the expression of IRS-1 and GOLPH3 protein and suppressed the proliferation, migration and invasion of ESCC cells, whereas miR-126 inhibitors led to the opposite results. miR-126 suppressed the proliferation, migration and invasion of ESCC cells, and acted as a tumor suppressor in the carcinogenesis of ESCC. IRS-1 and GOLPH3 are downstream targets of miR-126 at the post-transcriptional level in ESCC.	esophagus
HPV seropositivity joints with susceptibility loci identified in GWASs at apoptosis associated genes to increase the risk of Esophageal Squamous Cell Carcinoma (ESCC).	BACKGROUND: We previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; however, HPV increased the risk in smokers. METHODS: Here we investigated possible interactions between HPV16 serostatus and three susceptibility loci identified in GWASs at apoptosis associated genes with regard to risk of ESCC in a case-control study of 313 patients with ESCC and 314 healthy controls. The loci (CHK2 rs738722, C12orf51 rs2074356, and PLCE1 rs2274223) were genotyped, and the presence or absence of HPV16 in serum was measured by ELISA. Multivariable logistic regression was used to evaluate possible interactions of HPV16 serostatus and the three loci on the risk of ESCC. RESULTS: A significant interaction was found between HPV16 serology and rs2074356 (P = 0.005, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77) or rs2274223 (P < 0.001, OR 1.53, 95% CI 1.23-1.91), but not for rs738722. For rs2074356, risk of ESCC was increased substantially in smokers (P < 0.001, OR 8.25, 95% CI 3.84-17.71) and drinkers (OR4.04, P = 0.001, 95% CI 1.79-9.10) who carried risk alleles (TT or TC genotype) and were HPV16-seropositive. Similar results were observed for rs2274223 in smokers (P < 0.001, OR6.06, 95% CI 2.85-12.88) and drinkers (P < 0.001, OR 5.43, 95% CI 2.51-11.76), but not for rs738722. CONCLUSION: Consistent with the previous study, loci at rs2074356 and rs2274223 could increase the risk of ESCC, furthermore, there were significant interactions between HPV sero-status and the susceptibility loci on the risk of ESCC. This effect could be modified obviously by smoking and drinking.	esophagus
Cronkhite-Canada syndrome associated with esophageal and gastric cancers: report of a case.	Cronkhite-Canada Syndrome (CCS) is a rare non-inherited gastrointestinal polyposis syndrome with characteristic ectodermal changes. We report an extremely unusual case of CCS associated with primary esophageal and gastric cancers. A 74-year-old Japanese man with symptoms of anorexia and diarrhea was found to have primary esophageal and gastric cancers, as well as multiple gastric and colonic polyps. Based on the physical findings of onychodystrophy and alopecia, we diagnosed CCS. Because of his age and nutritional status, we decided to perform total gastrectomy for gastric cancer and chemoradiotherapy for esophageal cancer, upon completion of which the patient was started on steroid therapy for the CCS. After 1 week of steroid therapy, the patient's watery diarrhea improved. We recommend that for patients with CCS, the therapeutic strategy be carefully considered based on the patient's nutritional status, the severity of the CCS, and the extent of gastrointestinal cancer.	esophagus
SIRT3 is a novel prognostic biomarker for esophageal squamous cell carcinoma.	Sirtuin-3 (SIRT3) protein is a member of Sirtuins family. It functions as a critical mitochondrial deacetylase, which is involved in a variety of diseases, such as cancer, cardiovascular disease and diabetes. However, its role in esophageal squamous cell carcinoma (ESCC) has never been investigated before. With the help of immunohistochemistry, we studied the clinical significance of SIRT3 expression in ESCC. The receiver operating characteristic method was used to define the SIRT3 IRS cutoff value. The correlations between SIRT3 expression and clinicopathological variables were assessed using Pearson's χ (2) test. To evaluate the clinical significance of SIRT3 expression, Kaplan-Meier analysis was used to compare postoperative survival between different SIRT3 expression groups of ESCC patients. High expression of SIRT3 in ESCC tissues was more frequently observed than corresponding adjacent non-malignant esophageal mucosa tissues. No correlations were found between SIRT3 expression and clinical parameters. Multivariate analysis revealed that SIRT3 expression was an independent prognostic factor in ESCC (HR 1.454, P = 0.034). Increased SIRT3 expression suggests unfavorable prognosis for ESCC patients. Further studies are warranted.	esophagus
Photodynamic therapy downregulates the function of regulatory T cells in patients with esophageal squamous cell carcinoma.	Photodynamic therapy (PDT) by selective photosensitization of cancer cells and subsequent laser application results in local tumor necrosis. However, the effects of PDT on immune function, which may depend on the type of immune response, are controversial. We investigated the immunological changes induced by PDT and the effect of PDT on level and function of regulatory T cells (Treg) in patients with invasive esophageal squamous cell carcinoma (ESCC). We analyzed patient's blood samples before and after PDT. Blood CD4+CD25+CD127-FoxP3+ Treg levels were quantified by FACS, and Treg function was evaluated by coculture proliferation assays with T effector (Teff) cells. We found that PDT abrogated the suppressive capacity of peripheral Treg (Days 7 and 14, p = 0.016) but had no effect on Treg levels. The effect of PDT on Treg function at Day 7 was accompanied by slight but statistically significant increases in peripheral neutrophil granulocytes (p = 0.035) and monocytes (p = 0.013) and a statistically significant increase (approximately 18-fold) in serum IL-6 levels (p = 0.008). In conclusion, PDT abolished Treg function, possibly due to increased IL-6 levels in treated ESCC patients. This may be crucial for an improved therapeutic outcome.	esophagus
The development of bevacizumab in noncolorectal gastrointestinal malignancies: gastroesophageal, pancreatic, and hepatocellular carcinoma.	Bevacizumab (Avastin, Genentech) is a potent inhibitor of vascular endothelial growth factor A that has demonstrated modest antitumor activity across a broad range of malignancies when combined with chemotherapy. In colorectal cancer, bevacizumab in combination with chemotherapy is a standard of care for first-line therapy, and is used as second-line therapy in both bevacizumab-naive patients and those who have progressed on first-line therapy containing bevacizumab. Bevacizumab has been examined in nongastrointestinal malignancies as well. Across these multiple studies, virtually all of which demonstrate some improvement in progression-free survival, the combination of chemotherapy and bevacizumab has not led to a significant improvement in overall survival. Unfortunately, the addition of bevacizumab to chemotherapy translates into only slight improvement in overall survival in a few malignancies, including colorectal cancer. In this review, we highlight the development of bevacizumab in noncolorectal gastrointestinal malignancies, and potential future directions in antiangiogenic drug development.	esophagus
High mortality from hepatic, gastric and esophageal cancers in mainland China: 40 years of experience and development.	The disability-adjusted life-years caused by hepatic, gastric and esophageal cancers in mainland China are among the highest in the world. During the past four decades, improvements in primary prevention of these cancers, particularly in the isolation of risk factors, have been a nationwide goal, and secondary prevention has also been advanced. Nationwide primary preventative measures, including active vaccination against hepatitis B virus in neonates, consensus on screening and eradication of Helicobacter pylori, and quality improvement of dietary and drinking water, have been performed. Additionally, serum alpha-fetoprotein and endoscopic screening were developed and implemented as efficient secondary preventative measures for early diagnosis. Substantial strides toward cancer prevention were taken and have resulted in improved risk factors identification and more efficient screening in mainland China. Despite a reduction, HBV prevalence remained relatively high, potentially contributing to the increase in hepatic cancer-induced mortality. Because the slight decrease in H. pylori prevalence was not associated with an increase in the proportion of early diagnosis of gastric cancer, gastric cancer mortality appeared stable. Esophageal cancer incidence and mortality was reduced, principally due to the improvement in dietary habits and quality, as well as nutritional status. Nationwide isolation of risk factors and the implementation of high-risk candidate screening have been useful approaches to control mortality due to hepatic, gastric and esophageal cancers, and must be continued to secure a future reduction in mortality.	esophagus
Hyperglycemia 3 days after esophageal cancer surgery is associated with an increased risk of postoperative infection.	PURPOSE: Postoperative hyperglycemia is associated with infectious complications after various types of surgery. Our objective was to determine whether postoperative blood glucose levels up to 1 week after highly invasive esophageal cancer surgery are associated with the incidence of postoperative infections (POIs). METHODS: We conducted a retrospective chart review of 109 consecutive thoracic esophageal squamous cell cancer patients who underwent invasive esophagectomy with thoracotomy and laparotomy. The incidence of postoperative POIs and risk factors for POIs, including postoperative blood glucose levels, were evaluated. RESULTS: Of the 109 patients, 37 (34.0 %) developed POIs. Clinically, 73.0 % of the POIs became evident on or after postoperative day 4 (median, 5.25 days; interquartile range, 3.00-9.25 days). On and after postoperative day 3, chronological changes in blood glucose levels were significantly different between two groups of patients with or without POIs, as indicated by repeated measures ANOVA (P = 0.006). Multivariate logistic regression analysis results showed that an increased blood glucose concentration on postoperative day 3 was a significant risk factor for POIs. CONCLUSIONS: Our findings suggested that postoperative hyperglycemia on postoperative day 3 was a predictive factor of POIs after highly invasive esophageal cancer surgery.	esophagus
Definitive chemoradiotherapy for oesophageal cancer -- a promising start on an exciting journey.	Despite many advances in the management of oesophageal cancer, survival rates remain poor. Currently there is no clear consensus on the optimum management modality for localised disease. Surgery alone or combined with neoadjuvant chemotherapy or chemoradiotherapy and definitive chemoradiotherapy are all treatment options used for treating selected patient groups throughout the world. This overview discusses the evidence for definitive chemoradiotherapy, its role for certain patient groups and compared with other treatment options and how it has evolved with emerging technologies over recent decades. It highlights some key areas of research for future trials, including more precise treatment delivery, treatment intensification and a possible randomised controlled trial comparing radiation and surgical-based treatment.	esophagus
Absolute quantitation of Met using mass spectrometry for clinical application: assay precision, stability, and correlation with MET gene amplification in FFPE tumor tissue.	BACKGROUND: Overexpression of Met tyrosine kinase receptor is associated with poor prognosis. Overexpression, and particularly MET amplification, are predictive of response to Met-specific therapy in preclinical models. Immunohistochemistry (IHC) of formalin-fixed paraffin-embedded (FFPE) tissues is currently used to select for 'high Met' expressing tumors for Met inhibitor trials. IHC suffers from antibody non-specificity, lack of quantitative resolution, and, when quantifying multiple proteins, inefficient use of scarce tissue. METHODS: After describing the development of the Liquid-Tissue-Selected Reaction Monitoring-mass spectrometry (LT-SRM-MS) Met assay, we evaluated the expression level of Met in 130 FFPE gastroesophageal cancer (GEC) tissues. We assessed the correlation of SRM Met expression to IHC and mean MET gene copy number (GCN)/nucleus or MET/CEP7 ratio by fluorescence in situ hybridization (FISH). RESULTS: Proteomic mapping of recombinant Met identified 418TEFTTALQR426 as the optimal SRM peptide. Limits of detection (LOD) and quantitation (LOQ) for this peptide were 150 and 200 amol/µg tumor protein, respectively. The assay demonstrated excellent precision and temporal stability of measurements in serial sections analyzed one year apart. Expression levels of 130 GEC tissues ranged (<150 amol/µg to 4669.5 amol/µg. High correlation was observed between SRM Met expression and both MET GCN and MET/CEP7 ratio as determined by FISH (n = 30; R2 = 0.898). IHC did not correlate well with SRM (n = 44; R2 = 0.537) nor FISH GCN (n = 31; R2 = 0.509). A Met SRM level of ≥1500 amol/µg was 100% sensitive (95% CI 0.69-1) and 100% specific (95% CI 0.92-1) for MET amplification. CONCLUSIONS: The Met SRM assay measured the absolute Met levels in clinical tissues with high precision. Compared to IHC, SRM provided a quantitative and linear measurement of Met expression, reliably distinguishing between non-amplified and amplified MET tumors. These results demonstrate a novel clinical tool for efficient tumor expression profiling, potentially leading to better informed therapeutic decisions for patients with GEC.	esophagus
Is It Time to Centralize High-risk Cancer Care in the United States? Comparison of Outcomes of Esophagectomy Between England and the United States.	OBJECTIVE: To determine the difference in in-hospital mortality and length of hospital stay (LOS) after esophagectomy between the United States and England. BACKGROUND: Since 2001, complex procedures such as esophagectomy have been centralized in England, but in the United States no formal plan for centralization exists. METHODS: Patients who underwent esophagectomy for cancer between 2005 and 2010 were identified from the Nationwide Inpatient Sample (United States) and the Hospital Episodes Statistics (England). In-hospital mortality and LOS were compared. RESULTS: There were 7433 esophagectomies performed in 66 English hospitals and 5858 resections in 775 US hospitals; median number of resections per center per year was 17.5 in England and 2 in the United States. In-hospital mortality was greater in US hospitals (5.50% vs 4.20%, P = 0.001). In multiple regression analysis, predictors of mortality included patient age, comorbidities, hospital volume, and surgery performed in the United States [odds ratio (OR) = 1.20 (1.02-1.41), P = 0.03]. Median LOS was greater in the English hospitals (15 vs 12 days, P < 0.001). However, when subset analysis was done on high-volume centers in both health systems, mortality was significantly better in US hospitals (2.10% vs 3.50%, P = 0.02). LOS was also seen to decrease in the US high-volume centers but not in England. CONCLUSIONS: The findings from this international comparison suggest that centralization of high-risk cancer surgery to centers of excellence with a high procedural volume translates into an improved clinical outcome. These findings should be factored into discussions regarding future service configuration of major cancer surgery in the United States.	esophagus
The influence of elevated levels of C-reactive protein and hypoalbuminemia on survival in patients with advanced inoperable esophageal cancer undergoing palliative treatment.	BACKGROUND AND OBJECTIVES: Inflammation perpetuates individual tumor progression resulting in decreased survival in cancer patients. The aim of our study was to evaluate the influence of elevated levels of C-reactive protein (CRP) as well as low levels of albumin on patients with inoperable esophageal carcinoma. METHODS: The data of 218 patients with advanced esophageal cancer, who were treated at a single center within 12 years, were evaluated retrospectively. Patient's age, gender, body weight, dysphagia, plasma levels of CRP and albumin, the Glasgow Prognostic Score (GPS) combining both indicators, and survival were assessed for statistical evaluation. RESULTS: Thirty-nine (18.2%) had hypoalbuminemia and 161 (73.9%) had elevated CRP levels. Patients with hypoalbuminemia (P = 0.001) as well as patients with increased CRP levels (P = 0.001) showed a significantly shorter survival. Weight loss was correlated to elevated plasma CRP (P = 0.022), to diarrhea (P = 0.021), and to dysphagia (P = 0.008). Increasing GPS was significantly associated with poor survival (P = 0.001). CONCLUSIONS: Elevated CRP levels and hypoalbuminemia are significantly associated with reduced survival and are considered to be an appropriate predictor for poor outcome in advanced esophageal carcinoma. The GPS provides additional detailed prognostication and should be therefore taken into consideration when the individual palliative strategy has to be scheduled.	esophagus
[Risk factors and progression predictors of Barrett´s oesophagus to adenocarcinoma].	Gastroesophageal reflux disease is a quite common disorder, and the condition affects some 40 per cent of population in the course of their lifetime. Fortunately, about half of the patients examined due to clear symptoms do not manifest macroscopic damage of the oesophageal mucosa, and serious endoscopic findings (Barrett's oesophagus) are observed in only a small percentage of patients (10%). Barrett's oesophagus is a serious complication - precancerous condition with a 30-fold higher risk of development of oesophageal adenocarcinoma when compared with patients without this condition. The article presents risk factors and predictors of progression of the Barrett's oesophagus into the stage of adenocarcinoma. The main risk factors associated with oesophageal adenocarcinoma are male sex, white race, gastroesophageal reflux.	esophagus
A population-based, retrospective, cohort study of esophageal cancer missed at endoscopy.	BACKGROUND AND STUDY AIMS: Several studies have suggested that a significant minority of esophageal cancers are missed at endoscopy The aim of this study was to estimate the proportion of esophageal cancers missed at endoscopy on a national level, and to investigate the relationship between miss rates and patient and tumor characteristics. PATIENTS AND METHODS: This retrospective, population-based, cohort study identified patients diagnosed with esophageal cancer between April 2011 and March 2012 in England, using two linked databases (National Oesophago-Gastric Cancer Audit and Hospital Episode Statistics). The main outcome was the rate of previous endoscopy within 3 - 36 months of cancer diagnosis. This was calculated for the overall cohort and by patient characteristics, including tumor site and disease stage. RESULTS: A total of 6943 new cases of esophageal cancer were identified, of which 7.8 % (95 % confidence interval 7.1 - 8.4) had undergone endoscopy in the 3 - 36 months preceding diagnosis. Of patients with stage 0/1 cancers, 34.0 % had undergone endoscopy in the 3 - 36 months before diagnosis compared with 10.0 % of stage 2 cancers and 4.5 % of stage 3/4 cancers. Of patients with stage 0/1 cancers, 22.1 % were diagnosed after ≥ 3 endoscopies in the previous 3 years. Patients diagnosed with an upper esophageal lesion were more likely to have had an endoscopy in the previous 3 - 12 months (P = 0.040). The most common diagnosis at previous endoscopy was an esophageal ulcer (48.2 % of investigations). CONCLUSION: Esophageal cancer may be missed at endoscopy in up to 7.8 % of patients who are subsequently diagnosed with cancer. Endoscopists should make a detailed examination of the whole esophageal mucosa to avoid missing subtle early cancers and lesions in the proximal esophagus. Patients with an esophageal cancer may be misdiagnosed as having a benign esophageal ulcer.	esophagus
[Evidence base for minimally invasive esophagectomy for esophageal cancer].	Surgery remains the mainstay of potentially curative treatment of esophageal cancer; however, esophageal resection is still associated with a relevant morbidity and mortality. Furthermore, patients frequently suffer from concomitant comorbidities and present in a reduced nutritional status. The rationale of minimally invasive surgery is the reduction of surgical trauma with subsequent minimization of (pulmonary) complications and mortality without compromising oncological quality. Minimally invasive esophageal resection was established nearly two decades ago and since then some centers worldwide have adopted this approach as the preferred option for surgical treatment of esophageal cancer. Minimally invasive esophageal resection can be safely performed and provides excellent results in experienced hands. Currently, there is only one randomized trial available comparing open and minimally invasive resection. It was demonstrated that the latter significantly reduced pulmonary complications with comparable mortality and oncological outcome. However, in the majority of studies these convincing results could not be confirmed. Reduced blood loss and a shortened hospital stay were shown to be the main advantages of the minimally invasive approach. Due to technical modifications, patient selection and a remarkable heterogeneity of current studies, a final conclusion on the value of minimally invasive esophagectomy is difficult to be drawn. Based on the current evidence, a noncritical use of minimally invasive resection for esophageal cancer cannot be recommended; however, in selected patients and with appropriate expertise this approach is at least comparable to open esophagectomy.	esophagus