crossing96/oncoscreening huggingface dataset:
Deoxypodophyllotoxin, a Lignan from Anthriscus sylvestris, Induces Apoptosis and Cell Cycle Arrest by Inhibiting the EGFR Signaling Pathways in Esophageal Squamous Cell Carcinoma Cells.	Deoxypodophyllotoxin (DPT) derived from Anthriscus sylvestris (L.) Hoffm has attracted considerable interest in recent years because of its anti-inflammatory, antitumor, and antiviral activity. However, the mechanisms underlying DPT mediated antitumor activity have yet to be fully elucidated in esophageal squamous cell carcinoma (ESCC). We show here that DPT inhibited the kinase activity of epidermal growth factor receptor (EGFR) directly, as well as phosphorylation of its downstream signaling kinases, AKT, GSK-3β, and ERK. We confirmed a direct interaction between DPT and EGFR by pull-down assay using DPT-beads. DPT treatment suppressed ESCC cell viability and colony formation in a time- and dose-dependent manner, as shown by MTT analysis and soft agar assay. DPT also down-regulated cyclin B1 and cdc2 expression to induce G2/M phase arrest of the cell cycle and upregulated p21 and p27 expression. DPT treatment of ESCC cells triggered the release of cytochrome c via loss of mitochondrial membrane potential, thereby inducing apoptosis by upregulation of related proteins. In addition, treatment of KYSE 30 and KYSE 450 cells with DPT increased endoplasmic reticulum stress, reactive oxygen species generation, and multi-caspase activation. Consequently, our results suggest that DPT has the potential to become a new anticancer therapeutic by inhibiting EGFR mediated AKT/ERK signaling pathway in ESCC.	esophagus
Abandoning resectional intent in patients initially deemed suitable for esophagectomy: a nationwide study of risk factors and outcomes.	The main curative treatment modality for esophageal cancer is resection. Patients initially deemed suitable for resection may become unsuitable, most commonly due to signs of generalized disease or having become unfit for surgery. The aim was to assess risk factors for abandoning esophagectomy and its impact on survival. All patients diagnosed with an esophageal or gastroesophageal junction cancer in the Swedish National Register for Esophageal and Gastric Cancer from 2006-2016 were included and risk factors associated with becoming ineligible for resection were analyzed in multivariable logistic regression analysis. Overall survival was explored by multivariable Cox regression models. Among 1,792 patients planned for resection, 189 (11%) became unsuitable for resection before surgery and 114 (6%) had exploratory surgery without resection. Intermediate and high educational levels were associated with an increased probability of resection (odds ratio (OR) 1.46, 95% CI 1.05-2.05, OR 1.92, 95% CI 1.28-2.87, respectively) as was marital status (married: OR 1.37, 95% CI 1.01-1.85). Clinically advanced disease (cT4: OR 0.38, 95% CI 0.16-0.87; cN3: OR 0.27, 95% CI 0.09-0.81) and neoadjuvant treatment were associated with a decreased probability of resection (OR 0.62, 95% CI 0.46-0.88). Five-year survival for non-resected patients was only 4.5% although neoadjuvant treatment was associated with improved survival (HR 0.75, 95% CI 0.56-0.99). Non-resected patients with squamous cell carcinoma had comparatively reduced survival (HR 1.64, 95% CI 1.10-2.43). High socioeconomic status was associated with an increased probability of completing the plan to resect whereas clinically advanced disease and neoadjuvant treatment were independent factors associated with increased risk of abandoning resectional intent.	esophagus
Minimally Invasive Thoracoabdominal Esophagectomy Is Superior to Minimally Invasive Gastrectomy in Terms of Health-Related Quality of Life.	Background and Objectives: There are two operative approaches for adenocarcinomas of the esophagogastric junction: thoracoabdominal esophagectomy or transhiatal extended gastrectomy. Both procedures can be performed minimally invasively. Dependent on the exact localization of the tumor, both approaches are feasible. Aim of this study was to compare the health-related quality of life (HRQOL) of patients after minimally invasive esophagectomy (MIE) with patients who underwent minimally invasive gastrectomy (MIG). Methods: All patients who underwent MIE or gastrectomy for malignoma since 2014 were identified from our clinical database. The identified patients were contacted and asked to fill out a quality of life questionnaire (QLQ) for general and gastrointestinal QOL (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25). Results: Global HRQOL scores were higher in patients after MIE than after MIG. After MIE, global HRQOL scores were close to the control population. In cancer-specific syndromes, patients after MIE reported lower symptom scores for financial problems, eating, reflux, and eating with others than patients after MIG. Conclusion: In terms of HRQOL, MIE proved superior to MIG in long-term follow-up in this study. Patients after MIE reported a HRQOL close to that of a healthy reference population.	esophagus
Mucosa-Associated Microbiota in Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls.	INTRODUCTION: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett's microbiota could link to risk factors, providing risk of progression to neoplasia. METHODS: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria and analyzed by 16S ribosomal ribonucleic acid V4 gene DNA sequencing. Taxa composition was tested using a generalized linear model based on the negative binomial distribution and the log link functions of the R Bioconductor package edgeR. RESULTS: The microbe composition of paired samples (disease vs nondisease) comparing normal esophagus with intestinal metaplasia, low grade dysplasia, high grade dysplasia, and adenocarcinoma showed significant decreases in the phylum Planctomycetes and the archaean phylum Crenarchaeota (P < 0.05, false discovery rate corrected) in diseased tissue compared with healthy controls and intrasample controls (gastric juice and unaffected mucosa). Genera Siphonobacter, Balneola, Nitrosopumilus, and Planctomyces were significantly decreased (P < 0.05, false discovery rate corrected), representing <10% of the entire genus community. These changes were unaffected by age, tobacco use, or sex for Crenarcha. DISCUSSSION: There are similar significant changes in bacterial genera in Barrett's esophageal mucosa, dysplasia, and adenocarcinoma compared with controls and intrapatient unaffected esophagus. Further work will establish the biologic plausibility of these specific microbes' contributions to protection from or induction of esophageal epithelial dysplasia.	esophagus
Hypertrophic pulmonary osteoarthropathy with esophageal sarcomatoid carcinoma: a case report.	Hypertrophic pulmonary osteoarthropathy (HPOA), mainly manifested clubbing, is rare in patients with esophageal sarcomatoid carcinoma. We herein describe a 48-year-old Chinese man whose advanced sarcomatoid carcinoma was diagnosed while examining his symptoms of HPOA. The patient had no opportunity of surgery after surgical evaluation. Chemoradiation, including 5 cycles of chemotherapy (Paclitaxel liposome 60 mg day 1 and nedaplatin 30 mg day 1, q1w) and 6MV-X/VMAT-95%PGTV 59.92 Gy/2.14 Gy/28 F and 95%PTV 50.4 Gy/1.8 Gy/28 F, and subsequent 6 cycles of chemotherapy (paclitaxel liposome 210 mg day 1 and nedaplatin 50 mg day 1, 60 mg day 2, q3w) shrank the tumor and the condition of the patient became stable without clubbing remission or exacerbation. No medical case report found in a PubMed search in the indexed English-language literature in the past 20 years, though there are some reports of HPOA combined with other pathologic types of esophageal carcinoma. The patient's condition was effectively controlled by chemotherapy and radiotherapy and showed stable disease. However, the five-year survival rate of advanced esophageal carcinoma patients is very low with low life quality, and the adverse reactions also contribute to low life quality. The purpose of this report is to present the feature and our treatment for primary esophageal sarcomatoid carcinoma with HPOA, which could be helpful for further understanding of the disease and clinical decision making. Moreover, this article also reviews esophageal carcinoma with HPOA and sarcomatoid carcinoma in the esophagus. We look forward to the breakthrough of immunotherapy and molecular targeting therapy to improve the situation.	esophagus
Size of Lugol-unstained lesions as a predictor for risk of progression in premalignant lesions of the esophagus.	BACKGROUND AND AIMS: At present, the surveillance strategy for premalignant esophageal lesions in China is based solely on the pathologic diagnosis in Lugol's chromoendoscopy (LCE). In this study, we sought to determine the degree to which various unstained features under LCE may lead to improved ability to predict the risk of progression in esophageal lesions. METHODS: We re-examined and followed up on 1058 subjects who had Lugol-unstained lesions (LULs) together with a pathologic diagnosis that was lower than severe dysplasia at baseline screening based on a population-based randomized controlled trial over a median time of 5.8 years. We established a logistic regression model and calculated the adjusted cumulative incidence of severe dysplasia or malignancy. RESULTS: LUL size was predictive of progression to malignant lesions in individuals with a nondysplastic diagnosis (adjusted odd ratio(6-10 mm vs ≤5 mm), 6.7; 95% confidence interval, 1.7-25.7; adjusted odds ratio(>10 mm vs ≤5 mm), 27.9; 95% confidence interval, 7.3-105.7), and the corresponding adjusted cumulative incidence of malignant lesions was 3.6 and 13.2 per 100 persons. This is higher than that of small (≤5 mm) lesions, which showed mild dysplasia (2.7 per 100 persons), a condition for which surveillance every 3 years is recommended. Under the current approach, 65.3% of interval cancers missed at surveillance would be detected if individuals with medium (6-10 mm) and large (>10 mm) nondysplastic LULs were additionally monitored. CONCLUSIONS: We propose a modified surveillance strategy that combines findings under LCE examination and the pathologic analysis, where follow-up endoscopy is recommended for individuals with relatively large nondysplastic lesions.	esophagus
Computed tomography-based deep-learning prediction of neoadjuvant chemoradiotherapy treatment response in esophageal squamous cell carcinoma.	BACKGROUND: Deep learning is promising to predict treatment response. We aimed to evaluate and validate the predictive performance of the CT-based model using deep learning features for predicting pathologic complete response to neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Patients were retrospectively enrolled between April 2007 and December 2018 from two institutions. We extracted deep learning features of six pre-trained convolutional neural networks, respectively, from pretreatment CT images in the training cohort (n = 161). Support vector machine was adopted as the classifier. Validation was performed in an external testing cohort (n = 70). We assessed the performance using the area under the receiver operating characteristics curve (AUC) and selected an optimal model, which was compared with a radiomics model developed from the training cohort. A clinical model consisting of clinical factors only was also built for baseline comparison. We further conducted a radiogenomics analysis using gene expression profiles to reveal underlying biology associated with radiological prediction. RESULTS: The optimal model with features extracted from ResNet50 achieved an AUC and accuracy of 0.805 (95% CI, 0.696-0.913) and 77.1% (65.6%-86.3%) in the testing cohort, compared with 0.725 (0.605-0.846)) and 67.1% (54.9%-77.9%) for the radiomics model. All the radiological models showed better predictive performance than the clinical model. Radiogenomics analysis suggested a potential association mainly with WNT signaling pathway and tumor microenvironment. CONCLUSIONS: The novel and noninvasive deep learning approach could provide efficient and accurate prediction of treatment response to nCRT in ESCC, and benefit clinical decision making of therapeutic strategy.	esophagus
It's not always too late: a case for minimally invasive salvage esophagectomy.	INTRODUCTION: Standard of care for locally advanced esophageal carcinoma is neoadjuvant chemoradiation (nCRT) and surgical resection 4-8 weeks after completion of nCRT. It is recommended that the CRT to surgery interval not exceed 90 days. Many patients do not undergo surgery within this timeframe due to patient/physician preference, complete clinical response, or poor performance status. Select patients are offered salvage esophagectomy (SE), defined in two ways: resection for recurrent/persistent disease after complete response to definitive CRT (dCRT) or esophagectomy performed > 90 days after completion of nCRT. Salvage esophagectomy reportedly has higher postoperative morbidity and poor survival outcomes. In this study, we assessed outcomes, overall, and disease-free survival of patients undergoing salvage esophagectomy by both definitions (recurrent/persistent disease after dCRT and/or > 90 days), compared to planned (resection after nCRT/within 90 days) esophagectomy (PE). MATERIALS AND METHODS: Retrospective review of a prospectively maintained database identified patients who underwent minimally invasive esophagectomy at a single institution from 2009 to 2019. Esophagectomy for benign disease and patients who did not receive nCRT were excluded. Outcomes included postoperative complications, length of stay (LOS), disease-free survival, and overall survival. RESULTS: 97 patients underwent minimally invasive esophageal resection for esophageal carcinoma. 89.7% of patients were male. Mean age was 64.9 years (range 36-85 years). 94.8% of patients had adenocarcinoma, with 16 transthoracic and 81 transhiatal approaches. On comparing planned esophagectomy (n = 87) to esophagectomy after dCRT failure (n = 10), no significant differences were identified in overall survival (p = 0.73), disease-free survival (p = 0.32), 30-day or major complication rate, anastomotic leak, or LOS. Similarly, when comparing esophagectomy < 90 days after CRT (n = 62) to > 90 days after CRT completion (n = 35), no significant differences were identified in overall survival (p = 0.39), disease-free survival (p = 0.71), 30-day or major complication rate, LOS, or anastomotic leak rate between groups. In this comparison, local recurrence was noted to be elevated with SE as compared to PE (64.3% vs. 25.0%, p = 0.04). CONCLUSION: Overall survival and disease-free survival were equivalent between SE and PE. Local recurrence was noted to be increased with SE, though this did not appear to affect survival. Although planned esophagectomy remains the standard of care, salvage esophagectomy has comparable outcomes and is appropriate for selected patients.	esophagus
Esophageal cancer surgery: review of complications and their management.	Esophagectomy, even with the progress in surgical technique and perioperative management, is a highly specialized surgery, associated with a high rate of complications. Early recognition and adequate treatment should be a standard of care for the most common postoperative complications: anastomotic leakage, pneumonia, atrial fibrillation, chylothorax, and recurrent laryngeal nerve palsy. Recent progress in endoscopy with vacuum and stent placement, or in radiology with embolization, has changed the management of these complications. The success of nonoperative treatments should be frequently reassessed and reoperation must be proposed in case of failure. We have summarized the clinical signs, diagnostic process, and management of the frequent complications after esophagectomy for esophageal cancer.	esophagus
Matrix metalloproteinase-14 (MMP-14) downregulation inhibits esophageal squamous cell carcinoma cell migration, invasion, and proliferation.	BACKGROUND: Matrix metalloproteinase-14 (MMP-14) is known to be a key regulator of oncogenesis and tumor progression. The present study was designed to assess the relationship between the downregulation of MMP-14 and the in vitro proliferative, migratory, and invasive activity of esophageal squamous cell carcinoma (ESCC) cells. METHODS: MMP-14 expression in human ESCC and paracancerous normal esophageal tissue samples was evaluated via immunohistochemistry, and correlations between MMP-14 staining and patient clinicopathological features were examined. In addition, siRNA was used to knockdown MMP-14 in ESCC cells, and the proliferation and invasive activity of these cells were then evaluated via MTT and Transwell assays, respectively. Flow cytometry was additionally used to assess cell cycle progression, while Western blotting was employed to measure protein levels within these cells. RESULTS: ESCC samples were found to exhibit MMP-14 overexpression relative to paracancerous tissue samples, and this overexpression was positively correlated with tumor T classification (T1-2 vs. T3; P < 0.05), N classification (negative vs. positive; P < 0.001), degree of differentiation (G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05) and clinical stage (I-IIA vs. IIB-III; P < 0.05). When MMP-14 was knocked down in ESCC cells, this induced cell cycle arrest, impairing their proliferative and invasive activity. CONCLUSIONS: MMP-14 is a key regulator of the proliferation and invasion of ESCC cells, making it a viable therapeutic target for the treatment of this cancer.	esophagus
Salvage chemoradiation therapy for recurrence after radical surgery or palliative surgery in esophageal cancer patients: a prospective, multicenter clinical trial protocol.	BACKGROUND: Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell cancer (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety. METHODS: Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established. DISCUSSION: This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection. TRIAL REGISTRATION: Prospectively Registered. ClinicalTrials.gov NCT03731442 , Registered November 6, 2018.	esophagus
The expression of AGGF1, FOXC2, and E-cadherin in esophageal carcinoma and their clinical significance.	Angiogenic factor with G-patch and FHA domain 1 (AGGF1) is a newly initiator of angiogenesis. Forkhead box C2 (FOXC2) that is a member of the winged spiral transcription factor family plays an important role in epithelial-mesenchymal transition (EMT). Epithelial-cadherin (E-cad) that is an adhesion molecule is also involved in EMT. The purpose of this study is to investigate the expression of AGGF1, FOXC2, and E-cad in esophageal squamous cell carcinoma (ESCC) and their clinical significance.Immunohistochemistry was performed to investigate the expression of AGGF1, FOXC2, and E-cad in 170 ESCC specimens and corresponding normal esophageal mucosa tissues. Follow-up data was also collected.The positive rates of AGGF1 and FOXC2 expression were significantly higher in ESCC group when compared with the control group; the positive rate of E-cad expression was significantly lower in ESCC group when compared with the control group. Positive rates of AGGF1, FOXC2, and E-cad expression were significantly associated with grades of differentiation, tumor grades, lymph node metastasis stages, as well as tumor-node-metastasis stages. Kaplan-Meier analysis demonstrated that positive expression of AGGF1 or FOXC2 for ESCC patients had significantly unfavorably overall survival time when compared with patients with negative expression of AGGF1 or FOXC2; and positive expression of E-cad for ESCC patients had significantly longer overall survival time when compared with patients with negative expression of E-cad. Multivariate analysis indicated that AGGF1, FOXC2, and E-cad expression and tumor-node-metastasis stages were postoperative independent prognostic factors for ESCC patients.AGGF1, FOXC2, and E-cad may be considered promising biomarkers of ESCC patients' prognosis.	esophagus
Potential Role of Targeting KDR and Proteasome Inhibitors in the Therapy of Esophageal Squamous Cell Carcinoma.	Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancer types in China. In recent years, progress has been made in various types of cancer genomics including ESCC. However, the clinical significance of genomic variation of ESCC remains poorly defined. In the present study, genomic sequencing data from 469 ESCC cases were analyzed and potential therapeutic targets in the Druggable Genome Interaction Database (DGIdb) were screened. A series of potential therapeutic target genes and pathways were identified, of which treatment of ESCC with bortezomib (a specific inhibitor targeting proteasome) potently inhibited the proliferation of 5 ESCC cell lines and administration of bortezomib led to significant tumor xenograft regression in SCID mice. It was also identified that kinase insert domain receptor (KDR), which had drug recommendations from all 6 sources integrated by the DGldb and harbored significant amplification in ESCC, might be a downstream target of zinc finger protein 750 (ZNF750). ZNF750 acts as a transcription factor and has been demonstrated to harbor frequently inactivating mutations in ESCC by previous independent studies. In the present study, KDR was upregulated upon ZNF750 knockdown and the rescue of ZNF750 also led to marked restoration of KDR. KDR knockdown in stable ZNF750-knockdown KYSE150 and KYSE140 ESCC cells significantly attenuated the promotion of cell growth, colony formation, invasion and migration induced by ZNF750 knockdown. Further experiments found that apatinib treatment, a potent inhibitor of KDR, resulted in profound inhibition of cell proliferation and invasion. Collectively, the present study provided insight for genomic alterations as potential therapeutic targets in ESCC and supported the possibility of a therapeutic strategy targeting the proteasome in ESCC. The present results also suggested that targeting KDR may be an effective way to treat ESCC, not only in KDR variant cases, but also in individuals with ZNF750 mutations and deletions.	esophagus