crossing96/oncoscreening huggingface dataset:
Thymidylate synthase genotype-directed chemotherapy for patients with gastric and gastroesophageal junction cancers.	"BACKGROUND: Retrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking. METHODS: In this phase II study (NCT00515216 registered through ClinicalTrials.gov, http://clinicaltrials.gov/show/NCT00515216), patients with ""good risk"" TSER genotypes (at least one TSER*2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%). RESULTS: The ORR in genotype-selected patients was 39.1% (9 partial responses out of 23 evaluable patients, 95% CI, 22.2 to 59.2), not achieving the primary objective of improving ORR. An encouraging disease control rate (DCR, consisting of partial responses and stable diseases) of 95.7% was noted and patients with homozygous TSER*2 genotype showed better tumor response. CONCLUSIONS: In this first prospective, multi-institutional study in patients with gastric or GEJ cancers, selecting patients with at least one TSER*2 allele did not improve the ORR but led to an encouraging DCR. Further studies are needed to investigate the utility of selecting patients homozygous for the TSER*2 allele and additional genomic markers in improving clinical outcomes for patients with gastric and GEJ cancers. TRIAL REGISTRATION: ClinicalTrials.gov NCT00515216."	esophagus
Association of promoter methylation of RUNX3 gene with the development of esophageal cancer: a meta analysis.	BACKGROUND: Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors. Emerging evidence indicates that RUNX3 is a tumor suppressor gene in several types of human cancers including esophageal cancer. However, the association between RUNX3 promoter methylation and esophageal cancer remains unclear. Here we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 promoter methylation on the incidence of esophageal cancer. METHODS: A detailed literature search was made on Medline, Pubmed and Web of Science for related research publications written in English and/or Chinese. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, the odds ratios (OR) were calculated and summarized respectively. RESULTS: Final analysis of 558 patients from 9 eligible studies was performed. The result showed that RUNX3 methylation was significantly higher in esophageal cancer than in normal squamous mucosa from the proximal resection margin or esophageal benign lesions (OR = 2.85, CI = 2.01-4.05, P<0.00001). The prevalence of lymph node involvement, tumor size (T1-T2 vs T3-T4) and histological grade was significantly greater in RUNX3-negative cases (RUNX3 unmethylated groups) than in RUNX3-positive cases (OR = 0.25, CI = 0.14-0.43, P<0.00001). RUNX3 methylation was significantly higher in esophageal adenocarcinoma (EAC) than Barrett's esophagus (OR = 0.35, CI = 0.20-0.59, P<0.0001). In addition, the pooled HR for overall survival (OS) showed that decreased RUNX3 expression was associated with worse survival in esophageal cancer (HR = 4.31, 95% CI = 2.57-7.37, P<0.00001). CONCLUSIONS: The results of this meta-analysis suggest that RUNX3 methylation is associated with an increased risk, progression as well as worse survival in esophageal cancer. RUNX3 methylation, which induces the inactivation of RUNX3 gene, plays an important role in esophageal carcinogenesis.	esophagus
O-MAX chemotherapy: high activity in metastatic esophagogastric adenocarcinoma and possible relation to subclinical hemolysis.	OBJECTIVES: Our objectives were to confirm the activity of O-MAX chemotherapy in adenocarcinoma of the stomach and esophagus, particularly the high rate of complete remission (CR) and the relation of subclinical hemolysis to CR. PATIENTS AND METHODS: Twenty-five patients with metastatic esophagogastric adenocarcinoma were treated with O-MAX. Two developed cancer-related hemolytic-uremic syndrome (C-HUS); both achieved CR. Subsequent patients were monitored for serum haptoglobin for subclinical hemolysis. RESULTS: Median survival was 16.5 months. The objective response rate was 90%, with 38% CR. Three patients achieving CR relapsed in the central nervous system and died (2 without systemic disease). Four patients have remained alive, off therapy, the longest for 20 years. Two patients developed clinical C-HUS and 5 of 8 monitored patients developed subclinical hemolysis based on abnormal serum haptoglobin. Four of the patients with subclinical hemolysis achieved CR. Of the 7 patients developing clinical C-HUS or subclinical hemolysis, 6 (86%) achieved CR. CONCLUSIONS: O-MAX appears highly active in esophagogastric adenocarcinoma. A few long-term survivors of metastatic disease are being seen. CR and long-term survival appear to correlate with the development of hemolysis. Although highly promising, these results should be considered only as hypothesis-generating and require confirmation in a prospective trial.	esophagus
Human papillomavirus burden in different cancers in Iran: a systematic assessment.	Certain types of human papillomaviruses (HPVs) are undoubtedly involved in genesis of human malignancies. HPV plays an etiological role in cervical cancer, but also in many vaginal, vulvar, anal and penile cancers, as well as head and neck cancers. In addition, a number of non-malignant diseases such as genital warts and recurrent respiratory papillomatosis are attributable to HPV. Moreover, HPV forms have detected in several other cancers including esophageal squamous cell carcinoma, lung, prostate, ovarian, breast, skin, colorectal and urinary tract cancers, but associations with etiology in these cases is controversial. The aim of this systematic assessment was to estimate the prevalence of HPV infection and HPV types in HPV-associated cancers, HPV-related non-malignant diseases and in cancers that may be associated with HPV in Iran. The present investigation covered 61 studies on a variety of cancers in Iranian populations. HPV prevalence was 77.5 % and 32.4% in cervical cancer and head and neck cancers, respectively. HPV was detected in 23.1%, 22.2%, 10.4%, 30.9%, 14% and 25.2% of esophageal squamous cell, lung, prostate, urinary tract cancers, breast and skin cancers, respectively. HPV16 and 18 were the most frequent HPV types in all cancers. The findings of present study imply that current HPV vaccines for cervical cancer may decrease the burden of other cancers if they are really related to HPV.	esophagus
Overexpression of human β-defensin 2 promotes growth and invasion during esophageal carcinogenesis.	Human β-defensin 2 (HBD-2) is an antimicrobial peptide produced by mucosal surfaces in response to microbial exposure or inflammatory cytokines. Although HBD-2 is expressed in the esophagus in response to stress and infectious agents, little is known regarding its expression and functional role in esophageal carcinogenesis. In the current investigation, normal esophagus and N-nitrosomethylbenzylamine (NMBA)-induced precancerous and papillomatous lesions of the rat esophagus were characterized for HBD-2 encoding gene Defb4 and protein. HBD-2 was found to be overexpressed in esophagi of rats treated with NMBA compared to animals in control group. Results of Real-time PCR, Western blot and immunohistochemistry demonstrated a positive correlation between the overexpression of HBD-2 and the progression of rat squamous cell carcinogenesis (SCC) in the esophagus. We also observed that HBD-2 is overexpressed in tumor tissues removed from patients with esophageal SCC. Moreover, Defb4 silencing in vitro suppresses the tumor cell proliferation, mobility and invasion in esophageal SCC cell line KYSE-150. The results from this study provide experimental evidence that HBD-2 may play an oncogenic role in the initiation and progression of esophageal SCC and thus serves as a target for chemopreventive and therapeutic interventions.	esophagus
Importance of surveillance and success of salvage strategies after definitive chemoradiation in patients with esophageal cancer.	PURPOSE: Patients with esophageal carcinoma (EC) who are treated with definitive chemoradiotherapy (bimodality therapy [BMT]) experience frequent relapses. In a large cohort, we assessed the timing, frequency, and types of relapses during an aggressive surveillance program and the value of the salvage strategies. PATIENTS AND METHODS: Patients with EC (N = 276) who received BMT were analyzed. Patients who had surgery within 6 months of chemoradiotherapy were excluded to reduce bias. We focused on local relapse (LR) and distant metastases (DM) and the salvage treatment of patients with LR only. Standard statistical methods were applied. RESULTS: The median follow-up time was 54.3 months (95% CI, 48.4 to 62.4). First relapses included LR only in 23.2% (n = 64), DM with or without LR in 43.5% (n = 120), and no relapses in 33.3% (n = 92) of patients. Final relapses included no relapses in 33.3%, LR only in 14.5%, DM only in 15.9%, and DM plus LR in 36.2% of patients. Ninety-one percent of LRs occurred within 2 years and 98% occurred within 3 years of BMT. Twenty-three (36%) of 64 patients with LR only underwent salvage surgery, and their median overall survival was 58.6 months (95% CI, 28.8 to not reached) compared with those patients with LR only who were unable to undergo surgery (9.5 months; 95% CI, 7.8 to 13.3). CONCLUSION: Unlike in patients undergoing trimodality therapy, for whom surveillance/salvage treatment plays a lesser role,(1) in the BMT population, approximately 8% of all patients (or 36% of patients with LR only) with LRs occurring more than 6 months after chemoradiotherapy can undergo salvage treatment, and their survival is excellent. Our data support vigilant surveillance, at least in the first 24 months after chemotherapy, in these patients.	esophagus
Omentoplasty in the prevention of anastomotic leakage after oesophagectomy: a meta-analysis.	OBJECTIVE: To evaluate the efficacy of omentoplasty for the prevention of anastomotic leakage after oesophagectomy. METHODS: A systemic review of the Cochrane Library database CENTRAL, MEDLINE and EMBASE from inception to March 2014 was performed. Randomized controlled trials comparing omentoplasty with non-omentoplasty after oesophageal resection for a primary oncological indication were included. Meta-analysis was performed for anastomotic leakage, specific complication rates, in hospital mortality, local recurrence and duration of hospitalization. Data was reported as a Peto odds ratio (Peto OR), odds ratio (OR), weighted mean difference (WMD) or relative risk (RR) with 95% confidence intervals (CI). RESULTS: Three randomized controlled trials with a total of 633 anastamoses were included. The omentoplasty group demonstrated a significantly lower incidence of postoperative anastomotic leakage (Peto OR: 0.26; 95% CI 0.14 to 0.52), and reduced duration of hospitalization (WMD -2.13; 95% CI -3.57 to -0.69). There was no significant difference between the omentoplasty and non-omentoplasty groups in the incidence of anastomotic strictures (RR: 0.91, 95% CI: 0.33 to 2.57), hospital mortality (RR: 0.86, 95% CI: 0.29 to 2.51), pulmonary complications (RR: 0.90, 95% CI: 0.59 to 1.35) and recurrence after surgery (RR: 1.17, 95% CI: 0.95 to 1.43). CONCLUSIONS: Omentoplasty may reduce the incidence of anastomotic leakage following oesophagectomy for oesophageal cancer.	esophagus
High expression of MAGE-A4 and MHC class I antigens in tumor cells and induction of MAGE-A4 immune responses are prognostic markers of CHP-MAGE-A4 cancer vaccine.	PURPOSE: We conducted a cancer vaccine clinical trial with MAGE-A4 protein. Safety, clinical response, and antigen-specific immune responses were analyzed and the prognostic factors by vaccination were investigated. EXPERIMENTAL DESIGN: Twenty patients with advanced esophageal, stomach or lung cancer were administered MAGE-A4 vaccine containing 300μg protein subcutaneously once every 2 weeks in six doses. Primary endpoints of this study were safety and MAGE-A4 immune responses. RESULTS: The vaccine was well tolerated. Fifteen of 20 patients completed one cycle of vaccination and two patients showed SD. A MAGE-A4-specific humoral immune response was observed in four patients who had high expression of MAGE-A4 and MHC class I on tumor cells. These four patients showed significantly longer overall survival than patients without an antibody response after vaccination (p=0.009). Patients with tumor cells expressing high MAGE-A4 or MHC class I antigen showed significantly longer overall survival than those with low expression. Induction of CD4 and CD8T cell responses was observed in three and six patients, respectively, and patients with induction of MAGE-A4-specific IFNγ-producing CD8T cells, but not CD4T cells, lived longer than those without induction. CONCLUSIONS: The CHP-MAGE-A4 vaccine was safe. Expression of MAGE-A4 and MHC class I in tumor tissue and the induction of a MAGE-A4-specific immune response after vaccination would be feasible prognostic markers for patients vaccinated with MAGE-A4.	esophagus
Increased expression levels of S100A4 associated with hypoxia-induced invasion and metastasis in esophageal squamous cell cancer.	Here, we explored the expression of S100A4 in esophageal squamous cell cancer (ESCC) tissues and investigated its role in hypoxia-induced invasion and metastasis in ESCC cell lines EC-1 and EC-9706. Immunohistochemistry analysis demonstrated that S100A4 was overexpressed in human ESCC tissues especially in ESCC tissues with deep invasion and lymph node metastasis. Hypoxia-induced S100A4 overexpression was observed in EC-1 and EC-9706 cells, in which it was associated with invasion and metastasis. Furthermore, we used EC-1 and EC-9706 cells again to upregulate or knockdown the expression S100A4 to investigate the mechanism role of S100A4 in hypoxia-induced invasion and metastasis in ESCC cells. And the results showed that S100A4 played an important role in promoting the invasion and metastasis of EC-1 and EC-9706 cells under hypoxia. Therefore, S100A4 overexpression might be an important mechanism by which hypoxia induced invasion and metastasis, and S100A4 could also be a potential target for the treatment of ESCC.	esophagus
Aurora-A enhances malignant development of esophageal squamous cell carcinoma (ESCC) by phosphorylating β-catenin.	The Aurora-A gene encodes a serine/threonine protein kinase that is frequently overexpressed in several types of human tumors. The overexpression of Aurora-A has been observed to associate with the grades of differentiation, invasive capability and distant lymph node metastasis of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism by which Aurora-A promotes malignant development of ESCC is still largely unknown. In this study, we show that Aurora-A overexpression enhances tumor cell invasion and metastatic potential in vitro and in vivo. Furthermore, Aurora-A overexpression inhibits the degradation of β-catenin, promotes its dissociation from cell-cell contacts and increases its nuclear translocation. We also demonstrate for the first time that Aurora-A directly interacts with β-catenin and phosphorylates β-catenin at Ser552 and Ser675. Substitutions of serine residue with alanine at single or both positions substantially attenuate Aurora-A-mediated stabilization of β-catenin, abolish its cytosolic and nuclear localization as well as transcriptional activity. In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic β-catenin expression in ESCC tissues. In view of our results, we propose that Aurora-A-mediated phosphorylation of β-catenin is a novel mechanism of malignancy development of tumor.	esophagus
Primary esophageal adenocarcinoma with distant metastasis to the skeletal muscle.	Hematogenous metastasis of esophageal adenocarcinoma to the skeletal muscle is uncommon. We report a rare case of esophageal adenocarcinoma with metastasis to the skeletal muscle. During pretherapeutic examination, a painful mass was detected in the left thigh of a 49-year-old man. Endoscopic biopsy identified poorly differentiated, advanced esophageal adenocarcinoma. Computed tomography (CT) revealed wall thickening in the distal esophagus. Two enlarged lymph nodes were detected--the middle thoracic paraesophageal lymph node in the mediastinum and the right cardiac lymph node. (18)F-fluorodeoxyglucose (FDG) positron emission tomography demonstrated left thigh metastasis, which had not been detected by CT 3 weeks previously, with increased accumulation of FDG. Therefore, ultrasound-guided core-needle biopsy was performed. Histologic and immunohistochemical findings supported a diagnosis of poorly differentiated adenocarcinoma. The final diagnosis was primary esophageal adenocarcinoma with distant metastasis to the skeletal (left thigh) muscle. The rate of disease progression in this case emphasizes the malignant potential of esophageal adenocarcinoma. A few cases of skeletal metastasis from advanced esophageal adenocarcinoma have been previously reported. However, rapid metastasis to a distant skeletal muscle with no other hematogenous metastasis is quite rare. Early detection and rapid treatment are especially important in cases of esophageal adenocarcinoma.	esophagus
Esophageal cancer stem cells express PLGF to increase cancer invasion through MMP9 activation.	Cancer stem cells (CSCs) are a distinct population in tumors and cause cancer relapse and metastasis. Thus, treating CSCs are believed to be potential to cure rapidly growing and highly metastatic cancers. To date, CSCs in esophageal cancer have not been characterized. In the current study, we detected significant higher levels of placental growth factor (PLGF) and matrix metalloproteinase 9 (MMP9) in the esophageal cancers with metastasis, compared to those without metastasis, in which the expression levels of PLGF and MMP9 strongly correlated with each other. Thus, we used a human esophageal cancer cell line, TE-1, to examine the cross talk of PLGF and MMP9. We found that the levels of PLGF in TE-1 cells positively affected the levels of MMP9, while the levels of MMP9 did not affected the levels of PLGF, suggesting that PLGF may activate MMP9 in esophageal cancer cells. Then, we separated PLGF-positive and PLGF-negative TE-1 cells that had been transfected with a GFP reporter under a PLGF promoter by flow cytometry. We found that PLGF-positive cells grew significantly faster than PLGF-negative cells both in vitro and in vivo in a stereotactical implantation model, suggesting that PLGF-positive cells are likely CSCs in esophageal cancer. Taken together, we demonstrate that PLGF-positive cells appear to be CSCs in esophageal cancer, and they may release PLGF to promote cancer metastasis through MMP9 activation.	esophagus
Clinical Importance of Supraclavicular Lymph Node Metastasis After Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.	OBJECTIVE: To examine the clinical implications of supraclavicular (SC) lymph node (LN) metastasis in patients with esophageal squamous cell carcinoma (ESCC) who receive neoadjuvant chemotherapy, followed by surgery. BACKGROUND: Indications for surgery for esophageal cancer often do not include cases with SCLN metastasis because the latter is considered distant metastasis. However, neaodjuvant therapy may change the clinical importance of SCLN metastasis. METHODS: In 323 patients with ESCC who underwent neoadjuvant chemotherapy, the correlations between SCLN metastasis and clinicopathological factors including survival were examined. RESULTS: The incidence of SCLN metastasis was 17.6% before therapy and 14.6% after therapy. In patients with SCLN metastasis at baseline, the incidence of posttherapy SCLN metastasis was significantly lower in major responders to chemotherapy than in minor responders. The total number of metastatic LNs was significantly higher in patients with posttherapy SCLN metastasis than in patients with metastatic LN but no SCLN (10.9 vs 3.9; P ≤ 0.001). Survival was shorter in patients with SCLN metastasis than in those with metastatic LN without SCLN (3-year overall survival rate; 20.1% vs 45.7%; P = 0.003). However, there was no significant difference in survival between patients with SCLN metastasis before but not after therapy and patients without SCLN metastasis before and after chemotherapy (3-year overall survival rate; 64.9% vs 58.2%; P = 0.2071). CONCLUSIONS: This study showed that SCLN metastasis in ESCC reflects the number of metastatic LNs. SCLN metastasis should not be considered as contraindication to curative surgery in multimodal treatment of ESCC because preoperative treatment can change SC nodal status.	esophagus
High definition versus standard definition white light endoscopy for detecting dysplasia in patients with Barrett's esophagus.	High-definition endoscopy systems provide superior image resolution. The aim of this study was to assess the utility of high definition compared with standard definition endoscopy system for detecting dysplastic lesions in patients with Barrett's esophagus. A retrospective cohort study of patients with non-dysplastic Barrett's esophagus undergoing routine surveillance was performed. Data were retrieved from the central hospital electronic database. Procedures performed for non-surveillance indications, Barrett's esophagus Prague C0M1 classification with no specialized intestinal metaplasia on histology, patients diagnosed with any dysplasia or cancer on index endoscopy, and procedures using advanced imaging techniques were excluded. Logistic regression models were constructed to estimate adjusted odds ratios and 95% confidence intervals comparing outcomes with standard definition and high-definition systems. The high definition was superior to standard definition system in targeted detection of all dysplastic lesions (odds ratio 3.27, 95% confidence interval 1.27-8.40) as well as overall dysplasia detected on both random and target biopsies (odds ratio 2.36, 95% confidence interval 1.50-3.72). More non-dysplastic lesions were detected with the high-definition system (odds ratio 1.16, 95% confidence interval 1.01-1.33). There was no difference between high definition and standard definition endoscopy in the overall (random and target) high-grade dysplasia or cancers detected (odds ratio 0.93, 95% confidence interval 0.83-1.04). Trainee endoscopists, number of biopsies taken, and male sex were all significantly associated with a higher yield for dysplastic lesions. The use of the high-definition endoscopy system is associated with better targeted detection of any dysplasia during routine Barrett's esophagus surveillance. However, high-definition endoscopy cannot replace random biopsies at present time.	esophagus