crossing96/oncoscreening huggingface dataset:
Genetic variation in miR-100 rs1834306 is associated with decreased risk for esophageal squamous cell carcinoma in Kazakh patients in northwest China.	MicroRNAs (miRNAs) are a family of small noncoding RNAs that act as oncogenes and tumor suppressors. Single nucleotide polymorphisms (SNPs) in miRNAs may be associated with changes in phenotype and function. The aim of this study was to verify whether genetic variations in candidate microRNA (miRNA or miR) genes could contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. A case-control study in 248 Kazakh patients with ESCC and 300 frequency matched control subjects was carried out to examine the potential association of six miRNA (miR-100 rs1834306, miR-34b/c rs4938723, miR-375 rs6715345, miR-146a rs2910164, miR-423 rs6505162 and miR-373 rs12983273) polymorphisms with risk of ESCC. We found that miR-100 rs1834306 T>C polymorphism was associated with a significant decreased risk of ESCC. In the recessive model, when the miR-100 rs1834306 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant decreased risk for ESCC (adjusted OR=0.495, 95% CI: 0.349-0.702, P=8.05×10(-5)). In the dominant model, when the miR-100 rs1834306 TT genotypes was used as the reference group, the TC/CC genotype were associated with a borderline statistically decreased risk for ESCC (adjusted OR=0.665, 95% CI: 0.430-1.031, P=0.067). In addition, the miR-100 rs1834306 C allele in the Kazakh population was significantly associated with decreased risk of ESCC (OR=0.609, 95% CI: 0.48-0.78, P=8.37×10(-5)). These findings indicated that functional polymorphism miR-100 rs1834306 C>T might contribute to decreased ESCC risk.	esophagus
Glasgow Prognostic Score as a Prognostic Clinical Marker in T4 Esophageal Squamous Cell Carcinoma.	Patients with clinical T4 esophageal squamous cell carcinoma (ESCC) have an unfavorable prognosis, mainly indicated by the response to chemoradiotherapy (CRT), crucial to estimating long-term survival. Other prognostic measures include systemic inflammatory or immunonutritional indices such as the Glasgow Prognostic Score (GPS) and Prognostic Nutritional Index (PNI) that have not been sufficiently documented. PATIENTS AND METHODS: This study retrospectively evaluated 91 patients with T4 ESCC treated at our Hospital between 2000 and 2013. All patients initially received CRT, including 5-fluorouracil (5FU) and cisplatin or nedaplatin with concurrent 2-Gy/fraction radiation (total dose, 40-60 Gy). Curative tumor resection was undertaken in suitable patients on completing CRT. Patients were classified as GPS0, GPS1, or GPS2 based on C-reactive protein (CRP) ≤ 10 mg/l and albumin ≥ 35 g/l, CRP >10 mg/l or albumin <35 g/l, or CRP >10 mg/l and albumin <35 g/l, respectively. PNI was calculated as 10-times the serum albumin (g/dl)+0.005 × total lymphocyte count (/mm(3)). The impact of the pre-treatment GPS and PNI on the prognosis of patients with T4 ESCC was investigated in univariate and multivariate analyses. RESULTS: Sixty (67%) patients responded to CRT (9 complete responses and 51 partial responses). Forty-one (45%) patients also underwent surgical resection of the residual tumor. The overall 5-year survival rate and median survival time were 27.0% and 11.8 months, respectively. In the cohort of CRT-plus-surgical resection, the 5-year survival rate was significantly higher than in the groups treated with CRT-alone (51.1% vs. 6.5%; p < 0.01). On multivariate analysis, good response to CRT [hazard ratio (HR) =0.449, p<0.01], GPS1/2 (HR=2.151, p=0.015), and surgical resection (HR=0.282, p<0.01) were significant prognostic factors, whereas PNI was not. CONCLUSION: The GPS is a useful, simple survival marker for patients with T4 ESCC undergoing multimodal therapy.	esophagus
Comparison of GFP-Expressing Imageable Mouse Models of Human Esophageal Squamous Cell Carcinoma Established in Various Anatomical Sites.	BACKGROUND/AIMS: Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. Mouse models of this disease could be used for discovery of more effective therapy for ESCC. MATERIALS AND METHODS: The green fluorescent protein (GFP)-expressing human esophageal cancer EC1 cell line was established with a lentiviral expression system. Subsequently, nude mice were injected subcutaneously, intracardiac or intravenously, or orthotopically implanted with EC1-GFP cells. Tumor growth and metastasis were examined by fluorescence in vivo imaging or by open fluorescence imaging after autopsy. RESULTS: Four different mouse xenograft models of ESCC expressing GFP were established. In the subcutaneous model, primary tumor growth was monitored in real-time by whole-body fluorescence imaging. No metastasis was observed in the subcutaneous or surgical orthotopic implantation model. By 55 days after implantation, all mice had developed orthotopic esophageal cancer, but without detectable metastasis. In contrast, experimental metastasis occurred in the intracardiac and intravenous models. In the intravenous injection model, the lung was the sole organ of experimental metastasis. In the intracardiac model, extensive experimental metastases occurred in the bone, brain and lung. CONCLUSION: The mouse xenograft models of ESCC developed in the present study can provide a means of discovering more effective therapy of this recalcitrant type of cancer.	esophagus
Preoperative airway colonization prior to transthoracic esophagectomy predicts postoperative pulmonary complications.	PURPOSE: Respiratory complications are responsible to a high degree for postoperative morbidity and mortality after Ivor-Lewis esophagectomy. The etiology of respiratory failure is known to be multifactorial with preoperative impaired lung function being the most important one. The aim of this study was to investigate the correlation between preoperative airway colonization (PAC) and postoperative respiratory complications. METHODS: In this observational study, 64 patients with esophageal cancer were included. All patients underwent Ivor-Lewis esophagectomy with laparoscopic or open gastric mobilization. After induction of anesthesia and intubation with a double-lumen tube, bronchial exudate was collected by random endoluminal suction for further microbiological work-up. Length of postoperative mechanical ventilation (<24 h, 24-72 h, >72 h), re-intubation, and tracheostomy were recorded as primary and secondary study endpoints. RESULTS: In 13 of 64 study patients (20.3 %), pathological colonization of the bronchial airways could be proved prior to esophagectomy. Haemophilus species was the most frequently identified pathogen. PAC was associated with a longer history of smoking (p = 0.025), a lower preoperative forced expiratory volume (FEV1, p = 0.009) or vital capacity (VC, p = 0.038), a prolonged postoperative mechanical ventilation (p < 0.001), and a higher frequency of re-intubation (p < 0.001) and tracheostomy (p = 0.017). In the multivariate analysis, PAC was identified as an independent predictor of respiratory failure (hazard ratio 11.4, 95 % confidence interval 2.6-54, p = 0.002). Mortality in the PAC group was 30.8 % compared to 0 % in patients without PAC (p < 0.0001). CONCLUSION: PAC is a significant risk factor for postoperative respiratory failure. A routine bronchoscopy and bronchoalveolar lavage as part of preoperative management prior to esophagectomy need to be discussed.	esophagus
RND1 is up-regulated in esophageal squamous cell carcinoma and promotes the growth and migration of cancer cells.	RND1 is reported to control the dynamics of cytoskeleton, cell growth, and survival, and dysregulation of RND1 is involved in the tumorigenesis. However, its expression and functions in the esophageal squamous cell carcinoma (ESCC) are unknown. In the present study, it was found that the expression of RND1 was up-regulated in ESCC tissues compared with the adjacent normal tissues. Forced expression of RND1 promoted the growth and migration of ESCC cells, while knocking down the expression of RND1 inhibited the growth, migration, and metastasis of ESCC cells. Molecular mechanism studies showed that RND1 activated ERK signaling. In summary, our study suggested that RND1 plays an important role in the progression of ESCC, and RND1 might be a promising target for the treatment of ESCC.	esophagus
Analysis of dysplasia in patients with Barrett's esophagus based on expression pattern of 90 genes.	BACKGROUND & AIMS: Diagnoses of dysplasia, based on histologic analyses, dictate management decisions for patients with Barrett's esophagus (BE). However, there is much intra- and inter-observer variation in identification of dysplasia-particularly low-grade dysplasia. We aimed to identify a biomarker that could be used to assign patients with low-grade dysplasia to a low- or high-risk group. METHODS: We performed a stringent histologic assessment of 150 frozen esophageal tissues samples collected from 4 centers in the United Kingdom (from 2000 through 2006). The following samples with homogeneous diagnoses were selected for gene expression profiling: 28 from patients with nondysplastic BE, 10 with low-grade dysplasia, 13 with high-grade dysplasia (HGD), and 8 from patients with esophageal adenocarcinoma. A leave-one-out cross-validation analysis was used identify a gene expression signature associated with HGD vs nondysplastic BE. Functional pathways associated with gene signature sets were identified using the MetaCore analysis. Gene expression signature sets were validated using gene expression data on BE and esophageal adenocarcinoma accessed through National Center for Biotechnology Information Gene Expression Omnibus, as well as a separate set of samples (n = 169) collected from patients who underwent endoscopy in the United Kingdom or the Netherlands and analyzed histologically. RESULTS: We identified an expression pattern of 90 genes that could separate nondysplastic BE tissues from those with HGD (P < .0001). Genes in a pathway regulated by retinoic acid-regulated nuclear protein made the largest contribution to this gene set (P < .0001); the transcription factor MYC regulated at least 30% of genes within the signature (P < .0001). In the National Center for Biotechnology Information Gene Expression Omnibus validation set, the signature separated nondysplastic BE samples from esophageal adenocarcinoma samples (P = .0012). In the UK and Netherlands validation cohort, the signature identified dysplastic tissues with an area under the curve value of 0.87 (95% confidence interval: 0.82-0.93). Of samples with low-grade dysplasia (LGD), 64% were considered high risk according to the 90-gene signature; these patients had a higher rate of disease progression than those with a signature categorized as low risk (P = .047). CONCLUSIONS: We identified an expression pattern of 90 genes in esophageal tissues of patients with BE that was associated with low- or high-risk for disease progression. This pattern might be used in combination with histologic analysis of biopsy samples to stratify patients for treatment. It would be most beneficial for analysis of patients without definitive evidence of HGD but for whom early endoscopic intervention is warranted.	esophagus
Systematic review and network meta-analysis: neoadjuvant chemoradiotherapy for locoregional esophageal cancer.	OBJECTIVE: Neoadjuvant chemoradiotherapy improves survival in patients with locoregional esophageal cancer. This study compares the efficacy of two common regimens, paclitaxel plus platinum and platinum plus 5-fluorouracil, based on overall survival. METHODS: We performed a systematic review and network meta-analysis of randomized trials comparing paclitaxel plus platinum-neoadjuvant chemoradiotherapy or and platinum plus 5-fluorouracil-neoadjuvant chemoradiotherapy with surgery alone. The outcome was the hazard ratios for death in the entire population and the two major histologic subgroups, squamous cell carcinoma and adenocarcinoma. RESULTS: Ten clinical trials were included. Compared with surgery alone, the hazard ratios [95% credible interval (CrI)] in the entire, squamous cell carcinoma, and adenocarcinoma population were 0.63 (0.50-0.80), 0.50 (0.36-0.71) and 0.74 (0.54-1.01) for paclitaxel plus platinum, and 0.79 (0.68-0.92), 0.82 (0.67-1.01) and 0.81 (0.63-1.05) for platinum plus 5-fluorouracil, respectively. When paclitaxel plus platinum was compared with platinum plus 5-fluorouracil, the hazard ratios (95% CrI) in the entire, squamous cell carcinoma, and adenocarcinoma population were 0.80 (0.60-1.06), 0.61 (0.41-0.91) and 0.91 (0.61-1.36), respectively. The probability of paclitaxel plus platinum being ranked the optimal treatment for the entire, squamous cell carcinoma, and adenocarcinoma population was 94.2, 99.1 and 67.6%, respectively. CONCLUSIONS: Neoadjuvant chemoradiotherapy with paclitaxel plus platinum regimen seemed to be a better treatment than platinum plus 5-fluorouracil regimen for locoregional esophageal cancer, especially for squamous cell carcinoma.	esophagus
Does Quality of Care Matter? A Study of Adherence to National Comprehensive Cancer Network Guidelines for Patients with Locally Advanced Esophageal Cancer.	INTRODUCTION: The aim of this study was to assess whether adherence to National Comprehensive Cancer Network (NCCN) guidelines leads to differences in survival in patients diagnosed with locally advanced esophageal cancer. METHODS: This is a retrospective cohort study of patients with stage II and III esophageal cancer included in the Cancer Registry at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital from 2008 to 2013. Seven quality indicators were identified using the 2014 NCCN guidelines, and individual and overall quality measure scores were calculated and used to define low and high quality of care groups. RESULTS: One hundred forty-one patients met inclusion criteria, and 88 patients (62.4 %) were identified as receiving high-quality care. Adherence to guidelines ranged from 63.1 to 100.0 %, with an overall compliance of 81.3 %. Risk factors for receiving low quality of care included advanced age, non-white race, lower education level, and unspecified primary site of tumor. A significantly better overall survival was observed in patients who received high-quality care (HR, 0.58; 95 %, 0.37-0.90, p = 0.015). CONCLUSIONS: Delivery of high-quality care is associated with improved survival in these patients. Efforts should be directed at minimizing disparities in treatment in regards to race and educational levels.	esophagus
Expression and role of oncogenic miRNA-224 in esophageal squamous cell carcinoma.	BACKGROUND: Aberrant expression of miR-224 is associated with tumor development and progression. This study investigated the role of miR-224 in esophageal squamous cell carcinoma (ESCC) ex vivo and in vitro. METHODS: A total of 103 esophageal intraepithelial neoplasia, ESCC tissue specimens, and their matched distant normal tissues were collected to test miR-224 expression using qRT-PCR analysis. Western blot was used to quantify the level of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and PHLPP2 in ESCC tissues. Cell viability, apoptosis, invasion, and colony formation assays were used to assess the altered phenotypes of esophageal cancer cell lines after miR-224 expression or inhibition. A luciferase reporter assay was used to confirm miR-224 binding to PHLPP1 and PHLPP2 mRNA. RESULTS: miR-224 was significantly overexpressed in esophageal intraepithelial neoplasia and ESCC tissues, while the expression of PHLPP1 and PHLPP2 proteins, the target genes of miR-224, was downregulated in ESCC tissues. miR-224 expression was associated with advanced clinical TNM stage, pathologic grade, and the level of PHLPP1 and PHLPP2 proteins in ESCC tissues. Ectopic overexpression of miR-224 promoted proliferation, migration, and invasion, but suppressed apoptosis of ESCC cells. miR-224 was able to bind to the 3' untranslated region (3'-UTR) of PHLPP1 and PHLPP2 mRNA to suppress their expression. CONCLUSIONS: The current study demonstrated that miR-224 acts as an oncogenic miRNA in ESCC, possibly by targeting PHLPP1 and PHLPP2.	esophagus
Glomus Tumor of the Esophagus: A Case Report and Review of the Literature.	We report an extremely rare case of primary glomus tumor of the esophagus, and review the corresponding literature. A 66-year-old female underwent a follow-up upper-gastrointestinal endoscopy due to dysphagia and previous history of esophageal lump. Endoscopic ultrasonography revealed a mass involving the deep mucosa and submucosa (Layers 2 and 3). Endoscopic biopsy revealed a mesenchymal tumor composed of nest of epithelioid cells with associated small blood vessels proliferation. Immunohistochemically, the tumor cells were positive for alpha smooth muscle actin and vimentin, but negative for c-kit and the vascular stroma was highlighted by positivity with CD34. Pathological examination confirmed that the tumor was a glomus tumor of the esophagus. The patient remains healthy without any recurrence to date.	esophagus
Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy.	This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800-1800 cm(-1)) and high-wavenumber (HW)(2800-3600 cm(-1)) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy.	esophagus
A novel endoscopic marker for radiological localization and image-guided radiotherapy in esophageal and gastric cancers (with video).	BACKGROUND AND AIMS: Radiotherapy is an accepted modality in the treatment of esophageal cancers and is currently being evaluated in conjunction with chemotherapy for the neoadjuvant treatment of gastric cancers. Our aim was to assess whether a novel endoscopically inserted marker can be used to improve radiological assessment of the primary cancer and allow for image-guided radiotherapy. METHODS: A phase II feasibility study was conducted at a tertiary-care center. Twenty-six consecutive adult patients with esophagogastric cancers underwent endoscopic marking of the tumor margins with a novel radiopaque marker (mixture of lipiodol and n-butyl 2-cyanoacrylate). The main outcome measure was the successful insertion of the marker based on a combination of radiological, endoscopic, and histological assessment. RESULTS: A total of 92 markers were inserted in 26 patients. Twenty-two (88%) had follow-up imaging to assess the 81 markers inserted, 79 of which (97.5%) were visible. There were no postprocedural adverse events noted in our cohort. Radiological assessment of tumor size improved such that it was in line with the endoscopic evaluation after marker placement in 18 of 21 patients (85.7%) who had appropriate follow-up radiology imaging. Ten patients (38.5%) from our cohort underwent image-guided radiotherapy (IGRT) by using the endoscopically inserted markers. CONCLUSION: Within the limitations of our small pilot study, endoscopic placement of our novel marker was successful in the majority of our cohort without significant adverse events. Marker placement resulted in improved radiological localization in the majority of our cohort and allowed for IGRT. (Australian New Zealand Clinical Trials Registry: ACTRN12613000239763.).	esophagus
Quality-of-life measures as predictors of post-esophagectomy survival of patients with esophageal cancer.	PURPOSE: Improving survival after esophagectomy is an important issue in treating patients with esophageal cancer (EC). In addition to standard hospitalization management, periodic assessment of quality-of-life (QOL) measures may be useful to detect disease progression from patients' subjective reports. Therefore, this prospective longitudinal study was undertaken to identify prognostic factors for 3-year survival of EC patients after esophagectomy and to evaluate the impact of QOL measures on these prognostic factors. METHODS: Patients with EC (n = 67) who had a complete tumor resection and were alive 6 months after esophagectomy were followed in this study for 3 years. Data were collected on patients' sociodemographics, cancer characteristics, adjuvant therapy, general QOL and EC-specific QOL (before esophagectomy and 6 months afterward), cancer recurrence, and death. Patients' independent risk factors for 3-year survival were investigated by multivariate Cox regression analysis. RESULTS: Of the 67 participants with EC, 26 had late mortality, with a median survival for the whole cohort of 38.2 months (95 % CI 31.97-44.35). Independent predictors of early death were early cancer recurrence (within 6 months after surgery), poor cognitive function (95 % CI 1.020-1.041), and worse dyspnea (95 % CI 1.007-1.034). CONCLUSIONS: The most predictive factor for early death in EC patients after esophagectomy was cancer recurrence within 6 months after surgery. However, QOL measures could be a tool to provide clinical information from patients' perspective suggesting cancer recurrence.	esophagus
The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121.	Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings.	esophagus