crossing96/oncoscreening huggingface dataset:
Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma.	Esophageal adenocarcinoma (EAC) is often diagnosed at an advanced stage, thus understanding the molecular basis for EAC invasion and metastasis is critical. Here we report that SPP1/OPN was highly overexpressed in primary EACs and intracellularly localized to tumor cells. We further demonstrate that all known OPN isoforms (OPNa, b, c, 4 and 5) were frequently co-overexpressed in primary EACs. Distinct pro-invasion and dissemination phenotypes of isoform-specific OPNb and OPNc stable transfectants were observed. Expression of OPNb significantly enhanced cell migration and adhesion to laminin. In contrast, OPNc cells showed significantly decreased cell migration yet increased cell detachment. Enhanced invasion, both in vitro and in vivo, was observed for OPNb- but not OPNc-expressing cells. Inhibition of RGD integrins, one family of OPN receptors, attenuated OPNb cell migration, abrogated OPNb cell adhesion and significantly reduced OPNb cell clonogenic survival but did not affect OPNc phenotypes, indicating that OPNb but not OPNc acts through integrin-dependent signaling. Differential expression of vimentin, E-cadherin and β-catenin in OPN stable cells may account for the variation in cell adhesion and detachment between these isoforms. We conclude that while all OPN isoforms are frequently co-overexpressed in primary EACs, isoforms OPNb and OPNc enhance invasion and dissemination through collective yet distinct mechanisms.	esophagus
Management of high grade dysplasia in Barrett's oesophagus with underlying oesophageal varices: A retrospective study.	BACKGROUND: Endoscopic treatment of Barrett's oesophagus leading to high grade dysplasia with oesophageal varices may lead to bleeding complications. AIMS: Estimate effectiveness of endoscopic band-ligation in oesophageal varices patients treated for high grade dysplasia, and compare to endoscopically treated non-oesophageal varices high grade dysplasia patients. METHODS: Retrospective comparative study. All 8 high grade dysplasia patients with varices who were treated initially with band-ligation at Mayo Clinic between 8/1/1999 and 2/28/2014 were compared with reference group of 52 high grade dysplasia patients treated endoscopically. RESULTS: One high grade dysplasia patients patient with oesophageal varices (12.5%) achieved complete remission of intestinal metaplasia defined by at least one followup endoscopy with normal biopsies, and 3 (37.5%) achieved complete remission of dysplasia defined by at least one followup endoscopy with non-dysplastic biopsies. 39 (75.0%) endomucosal resection/radiofrequency ablation patients experienced at least one followup endoscopy with normal biopsies, and 49 (94.2%) experienced non-dysplastic biopsies. Both of these endpoints occurred significantly more often in the endomucosal resection/radiofrequency ablation group compared to the high grade dysplasia with oesophageal varices group (p=0.016 and p=0.025, respectively). CONCLUSIONS: High grade dysplastic Barrett's can be safely managed with band-ligation. However, resolution of Barrett's epithelium is rarely achieved with banding alone.	esophagus
Impact of Adjuvant Chemotherapy on Patients with Lymph Node-Positive Esophageal Cancer who are primarily Treated with Surgery.	BACKGROUND: Whereas the optimal therapeutic strategy in node positive esophageal cancer primarily treated by surgery remains unknown, the study was designed to evaluate the impact of adjuvant chemotherapy on survival in such population. METHODS: Among 2944 consecutive patients operated on for esophageal cancer between 2000 and 2010 in 30 European centers, patients with lymph node metastasis treated by adjuvant treatment (n = 178) were compared to patients who did not received adjuvant treatment (n = 378). Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. RESULTS: After matching, patients were comparable between the two groups. When comparing adjuvant treatment and nonadjuvant treatment groups, there was no significant differences in 3-year overall (40.9 vs. 35.8 %, P = 0.560) and disease-free (33.9 vs. 28.5 %, P = 0.190) survivals. Locoregional recurrence was lower in the adjuvant treatment group (14.4 vs. 30.9 %, P = 0.012). In the adjuvant treatment group, 94 patients received chemotherapy and 84 chemoradiotherapy, without significant survival benefit over chemoradiotherapy compared with chemotherapy alone (P = 0.280). Predictive factors of overall survival were age ≥60 years, ASA III-IV score, and pN+ classification. No survival benefit was observed according to histological subtype or occurrence of postoperative complications. CONCLUSIONS: Adjuvant chemo(radio)therapy did not offer survival benefit in lymph node-positive esophageal cancer patients primarily treated with surgery.	esophagus
Postoperative Morbidity and Mortality Rates are Not Increased for Patients with Gastric and Gastroesophageal Cancer Who Undergo Preoperative Chemoradiation Therapy.	BACKGROUND: This study aimed to determine whether postoperative morbidity and mortality rates increased after preoperative chemoradiation in patients who underwent gastrectomy. METHODS: The medical records of 7404 patients with gastric or gastroesophageal cancer seen from January 1995 to August 2012 were reviewed to identify patients who underwent gastrectomy. χ (2) and logistic regression analysis were used to determine differences in the 90-day postoperative morbidity and mortality rates of patients who underwent upfront surgery (SURG), preoperative chemotherapy (CHEMO), or preoperative chemoradiation (CHEMOXRT). RESULTS: Of the 500 patients included in this study, 200 underwent SURG, 65 had CHEMO, and 235 had CHEMOXRT. Respectively, 33, 43, and 58 % of these patients underwent total gastrectomy (p < 0.01). Resection of other organs was performed respectively in 19, 26, and 23 % of the patients (p = 0.37). Minor complications within 90 days (Clavien-Dindo 1 or 2) occurred for 41 % of the SURG patients, 43 % of the CHEMO patients, and 45 % of the CHEMOXRT patients (p = 0.68). Major complications or death within 90 days (Clavien-Dindo 3, 4, or 5) occurred for 21, 28, and 29 % of the patients, respectively (p = 0.15). The 90-day mortality (Clavien-Dindo 5) rates were 2 % for the SURG patients, 6 % for the CHEMO patients, and 3 % for the CHEMOXRT patients (p = 0.25). The median hospital stays were respectively 12, 12, and 13 days (p = 0.09). In the multivariate analysis, male sex, gastroesophageal junction cancer, total gastrectomy, and resection of other organs were associated with increased major morbidity and mortality rates, whereas preoperative therapy was not. CONCLUSIONS: The CHEMOXRT patients had postoperative morbidity and mortality rates similar to those for the SURG and CHEMO patients.	esophagus
Increased phosphorylation on residue S795 of the retinoblastoma protein in esophageal adenocarcinoma.	Due to its increasing incidence and relatively poor prognosis, esophageal adenocarcinoma (EAC) is becoming a significant health problem. Elucidating the mechanisms underlying EAC development is of great importance to improve upon current conventional treatment strategies. Insight into phosphorylation has proven to be useful for the development of diagnostic and molecular treatment strategies in cancer. A pathway largely dependent on phosphorylation and frequently deregulated in cancer is the cell cycle regulating p16-retinoblastoma (Rb) pathway. We investigated kinase activity, specifically phosphorylation within the p16-Rb pathway, in EAC. A high-throughput peptide tyrosine kinase array containing short peptides representing 100 proteins with known phosphorylation sites, was used to assess phosphorylation activity in EAC. Also, specific phosphorylation changes of the cell cycle protein Rb and its upstream regulator P16 were validated through immunoblotting in EAC and normal esophageal cells and tissues. Phosphorylation activity was higher in EAC tissues as compared to normal squamous esophageal tissues. A majority of the proteins significantly higher phosphorylated in EAC were found to be involved in cell structure maintenance and immunity. Validation of Rb phosphorylation in EAC biopsy specimens and cell lines showed hyper phosphorylation of Rb associated with aberrant P16 expression in the cancer tissues. The specific Rb (S795) residue was significantly higher phosphorylated in EAC compared to normal esophageal tissue (Wilcoxon paired rank test, p=0.004). Investigation of Rb (S795) phosphorylation may indicate targets for intervention and give more molecular insight in EAC.	esophagus
Identification of New Candidate Genes and Chemicals Related to Esophageal Cancer Using a Hybrid Interaction Network of Chemicals and Proteins.	Cancer is a serious disease responsible for many deaths every year in both developed and developing countries. One reason is that the mechanisms underlying most types of cancer are still mysterious, creating a great block for the design of effective treatments. In this study, we attempted to clarify the mechanism underlying esophageal cancer by searching for novel genes and chemicals. To this end, we constructed a hybrid network containing both proteins and chemicals, and generalized an existing computational method previously used to identify disease genes to identify new candidate genes and chemicals simultaneously. Based on jackknife test, our generalized method outperforms or at least performs at the same level as those obtained by a widely used method--the Random Walk with Restart (RWR). The analysis results of the final obtained genes and chemicals demonstrated that they highly shared gene ontology (GO) terms and KEGG pathways with direct and indirect associations with esophageal cancer. In addition, we also discussed the likelihood of selected candidate genes and chemicals being novel genes and chemicals related to esophageal cancer.	esophagus
Nomogram predicted survival of patients with adenocarcinoma of esophagogastric junction.	BACKGROUND: The aim of this study is to develop a prognostic nomogram for patients with adenocarcinoma of esophagogastric junction and compare its predictive accuracy with the traditional tumor-node-metastasis (TNM) malignant staging system. METHODS: Patients from the Surveillance, Epidemiology, and End Results Program (from 1988 to 2011) and the First Affiliated Hospital of Xi'an Jiaotong University (from 2005 to 2010) were collected retrospectively. Preselected multiple potential interactions were tested irrespective of significance as nomogram parameters. And the Harrell's C-index was used to estimate the accuracy of the nomogram system. Model validation was performed using bootstrap to quantify our modeling strategy. RESULTS: In our study, six clinical associated factors (age, sex, depth of invasion, metastasized lymph nodes, examined lymph nodes, histological grade) were evaluated in the nomogram. In the training set, the nomogram exhibited superior discrimination power compared with the American Joint Committee on Cancer (AJCC) TNM classification (Harrell's C-index, 0.69 and 0.63, respectively). Calibration of the nomogram predicted survival was similar to the actual overall survival. In the validation set, the discrimination of nomogram was also better than the AJCC TNM staging system (C-index, 0.75 and 0.65, respectively), and the calibration of nomogram predicted survival was within a 10 % margin of actual overall survival. CONCLUSIONS: Based on the patients with adenocarcinoma of esophagogastric junction from a Western and an Eastern database, the nomogram provided significantly improved discrimination than the traditional AJCC TNM classification and also provided an accurate individualized prediction of the survival.	esophagus
Genetic risk of subsequent esophageal cancer in lymphoma and breast cancer long-term survival patients: a pilot study.	The occurrence of a second primary esophageal carcinoma (EC) in long-term cancer survivors may represent a late effect of previous radio-chemotherapeutic treatment. To identify the genetic factors that could increase this risk, we analyzed nine variants within ERCC1, XPD, XRCC1 and XRCC3 DNA repair pathway genes, and GSTP1, TP53 and MDM2 genes in 61 patients who received radio-chemotherapy for a prior lymphoma or breast cancer; 29 of them had a second primary EC. This cohort consists of 22 esophageal squamous cell carcinoma (ESCC) and 7 esophageal adenocarcinoma (EADC) patients. A validation cohort of 154 patients with sporadic EC was also included. The XPD Asp312Asn (rs1799793) was found to be associated with the risk of developing second primary ESCC (P=0.015). The resultant variant was also involved in the onset of sporadic ESCC (P=0.0018). To know in advance who among long-term cancer survivors have an increased risk of EC could lead to a more appropriate follow-up strategy.	esophagus
Adenocarcinoma of the Distal Esophagus in a Patient With a Magnetic Sphincter Augmentation Device: First of Many to Come?	Recently an alternative treatment option utilizing a laparoscopically placed magnetic sphincter device has been introduced for gastroesophageal reflux disease patients who are hesitant to undergo Nissen-fundoplication. Based on previous experience with similar devices, concerns have been raised about migration, and in case of a subsequently developing esophageal cancer, technical challenges during the endoscopic or surgical treatment caused by the foreign body reaction around the abdominal esophagus. In this article, we report of the first case of esophagectomy for cancer in a patient with a previously implanted magnetic sphincter augmentation device.	esophagus
Molecular pathology and potential therapeutic targets in esophageal basaloid squamous cell carcinoma.	Basaloid squamous cell carcinoma (BSCC) is a rare and poorly differentiated variant of typical squamous cell carcinoma. Emerging studies show that genetic alterations are more frequent in BSCC than in conventional SCC, and some of which led to the identification of potential therapeutic targets in esophageal BSCC. Approximately half of the esophageal BSCC cases harbor either an EGFR mutation or amplification, and these occur in a mutually exclusive fashion. Therefore, the application of tyrosine kinase inhibitors may be beneficial to esophageal BSCC patients. This tumor is partly characterized by the activation of the Wnt and Hedgehog (HH) signaling pathways. Wnt signaling is activated by SFRP2 promoter hypermethylation and HH signaling is activated by the frequent mutations in PTCH1. Increasing evidence shows that the Wnt signaling pathway is involved in cross-talk with other developmental pathways, including the HH pathway. Therefore, pharmaceutical therapy targeting both the HH and Wnt pathways would be quite effective in patients with esophageal BSCC with highly malignant potential. In this review, we discuss the pathology, prognostic factors, genetic alterations and potential therapeutic targets in BSCC of esophagus.	esophagus
Preoperative carboplatin and paclitaxel-based chemoradiotherapy for esophageal carcinoma: results of a modified CROSS regimen utilizing radiation doses greater than 41.4 Gy.	Trimodality therapy for resectable esophageal and gastroesophageal junction cancers utilizing preoperative radiotherapy with concurrent carboplatin and paclitaxel-based chemotherapy is being increasingly utilized secondary to the results of the phase III CROSS trial. However, there is a paucity of reports of this regimen as a component of chemoradiotherapy in North America. We aim to report on our clinical experience using a modified CROSS regimen with higher radiotherapy doses. Patients with advanced (cT2-cT4 or node positive) esophageal or gastroesophageal junction carcinoma who received preoperative carboplatin/paclitaxel-based chemoradiotherapy with radiation doses of greater than 41.4 Gray (Gy) followed by esophagectomy were identified from an institutional database. Patient, imaging, treatment, and tumor response characteristics were analyzed. Twenty-four patients were analyzed. All but one tumor had adenocarcinoma histology. The median radiation dose was 50.4 Gy. Pathologic complete response was achieved in 29% of patients, with all receiving 50.4 Gy. Three early postoperative deaths were seen, due in part to acute respiratory distress syndrome and all three patients received 50-50.4 Gy. With a median follow-up of 9.4 months (23 days-2 years), median survival was 24 months. Trimodality therapy utilizing concurrent carboplatin/paclitaxel with North American radiotherapy doses appeared to have similar pathologic complete response rates compared with the CROSS trial, but may be associated with higher toxicity. Although the sample size is small and further follow-up is necessary, radiation doses greater than 41.4 Gy may not be warranted secondary to a potentially increased risk of severe radiation-induced acute lung injury.	esophagus
The BRCA2 polymorphic stop codon: stuff or nonsense?	BACKGROUND: Despite classification of the BRCA2c.9976A>T, p.(Lys3326Ter) variant as a polymorphism, it has been associated with increased risks of pancreatic, lung, oesophageal and breast cancer. METHODS: We have noticed multiple co-occurrences of the BRCA2 c.9976A>T variant with the pathogenic BRCA2c.6275_6276delTT frameshift mutation p.(Leu2092ProfsTer7) and using a cohort study have assessed if this might account for these tumour risk associations. RESULTS: We identified 52 families with BRCA2c.6275_6276delTT, all of which occur in cis with the BRCA2c.9976A>T variant allele as demonstrated by co-segregation in all family members tested. Of 3245 breast/ovarian cancer samples sequenced for BRCA2, only 43/3245 (1.3%) carried BRCA2 c.9976A>T alone, after excluding individuals with BRCA2c.6275_6276delTT (n=22) or other BRCA1 (n=3) or BRCA2 (n=2) pathogenic mutations. The resultant frequency (1.3%) after removal of co-occurring mutations is lower than the 1.7% and 1.67% frequencies from two control populations for BRCA2 c.9976A>T, but similar to the 1.39% seen in the Exome Aggregation Consortium database. We did not identify increased frequencies of oesophageal, pancreatic or lung cancer in families with just BRCA2 c.9976A>T using person-years at risk analysis. CONCLUSIONS: It is likely that the previous associations of increased cancer risks due to BRCA2c.9976A>T represent reporting bias and are contributed to because the variant is in LD with BRCA2c.6275_6276delTT.	esophagus
Impact of alcohol dehydrogenase gene 4 polymorphisms on esophageal squamous cell carcinoma risk in a Chinese population.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is very common in China and is also one of the most common cancers worldwide. The purpose of this study was to examine the associations between genetic variants of various cancer-related genes and the risk of ESCC. METHODS: In this study, we first examined the association between 18 potentially disruptive genetic variants of 17 genes, including alcohol dehydrogenase 4 (ADH4) and checkpoint kinase 2 (CHEK2), and ESCC risk in a Hangzhou population of 617 patients matched with 534 controls. Among the 18 single nucleotide polymorphisms (SNPs), two were validated in a Jinan population of 540 patients matched with 550 controls. RESULTS: Sixteen SNPs in 15 genes, including CHEK2, did not have significantly different allele frequency distributions between ESCC patients and control subjects. A significantly increased risk of developing ESCC was revealed in subjects with the AA genotype of rs3805322 (ADH4) compared with those with the AG or GG genotype by unconditional univariate logistic regression analysis. Using a dominant model, the CC genotype of rs4822983 (CHEK2) had a marginally significant protective effect compared to the CT and TT genotypes. The association of ESCC risk with these two SNPs (rs3805322 and rs4822983) was further validated in a Jinan case-control set. Individuals with the ADH4 rs3805322 AA or AG genotype had ORs of 1.10 (95% CI = 0.81-1.49, P < 0.001) or 1.86 (95% CI = 1.33-2.59, P = 0.559), respectively, for developing ESCC compared with individuals with the GG genotype. CHEK2 rs4822983 CC carriers showed a marginally significantly decreased ESCC risk compared with those carrying the CT and TT genotypes in the validation set (95% CI = 0.61-1.01, P = 0.064). However, no evidence of interaction existed between the two SNPs and smoking or drinking in the Jinan case-control set. CONCLUSIONS: In conclusion, this current study provides substantial evidence that genetic polymorphisms of rs3805322 in the ADH4 gene may be associated with an increased risk of developing ESCC in two Chinese Han populations. Future studies to address the biological function of this polymorphism in the development of ESCC are warranted.	esophagus
MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.	Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P<0.05) of 29 SNPs with EA risk, and 25 SNPs with BE risk, were observed. None remained significant after correction for multiple comparisons (FDR q>0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.	esophagus