crossing96/oncoscreening huggingface dataset:
AKT serine/threonine kinase 2-mediated phosphorylation of fascin threonine 403 regulates esophageal cancer progression.	Fascin is the main actin-bundling protein in filopodia and is highly expressed in metastatic tumor cells. The overexpression of Fascin has been associated with poor clinical prognosis and metastatic progression. Post-translational modifications of Fascin, such as phosphorylation, can affect the proliferation and invasion of tumor cells by regulating the actin-bundling activity of Fascin. However, the phosphorylation sites of Fascin and their corresponding kinases require further exploration. In the current study, we identified novel phosphorylation of Fascin Threonine 403 (Fascin-T403) mediated by AKT serine/threonine kinase 2 (AKT2), which was studied using mass spectrometry data from esophageal cancer tissues (iProX database: IPX0002501000). A molecular dynamics simulation revealed that Fascin-Threonine 403 phosphorylation (Fascin-T403D) had a distinct spatial structure and correlation of amino acid residues, which was different from that of the wild type (Fascin-WT). Low-speed centrifugation assay results showed that Fascin-T403D affected actin cross-linking. To investigate whether Fascin-T403D affected the function of esophageal cancer cells, either Fascin-WT or Fascin-T403D were rescued in Fascin-knockout or siRNA cell lines. We observed that Fascin-T403D could suppress the biological behavior of esophageal cancer cells, including filopodia formation, cell proliferation, and migration. Co-immunoprecipitation (Co-IP) and Duolink in situ proximity ligation assay (PLA) were performed to measure the interaction between Fascin and AKT2. Using in vitro and in vivo kinase assays, we confirmed that AKT2, but not AKT1 or AKT3, is an upstream kinase of Fascin Threonine 403. Taken together, the AKT2-catalyzed phosphorylation of Fascin Threonine 403 suppressed esophageal cancer cell behavior, actin-bundling activity, and filopodia formation.	esophagus
Prediction of Progression in Barrett's Esophagus Using a Tissue Systems Pathology Test: A Pooled Analysis of International Multicenter Studies.	BACKGROUND & AIMS: Prediction of progression risk in Barrett's esophagus (BE) may enable personalized management. We aimed to assess the adjunct value of a tissue systems pathology test (TissueCypher) performed on paraffin-embedded biopsy tissue, when added to expert pathology review in predicting incident progression, pooling individual patient-level data from multiple international studies METHODS: Demographics, clinical features, the TissueCypher risk class/score, and progression status were analyzed. Conditional logistical regression analysis was used to develop multivariable models predicting incident progression with and without the TissueCypher risk class (low, intermediate, high). Concordance (c-) statistics were calculated and compared with likelihood ratio tests to assess predictive ability of models. A risk prediction calculator integrating clinical variables and TissueCypher risk class was also developed. RESULTS: Data from 552 patients with baseline no (n = 472), indefinite (n = 32), or low-grade dysplasia (n = 48) (comprising 152 incident progressors and 400 non-progressors) were analyzed. A high-risk test class independently predicted increased risk of progression to high-grade dysplasia/adenocarcinoma (odds ratio, 6.0; 95% confidence interval, 2.9-12.0), along with expert confirmed low-grade dysplasia (odds ratio, 2.9; 95% confidence interval, 1.2-7.2). Model prediction of progression with the TissueCypher risk class incorporated was significantly superior than without, in the whole cohort (c-statistic 0.75 vs 0.68; P < .0001) and the nondysplastic BE subset (c-statistic 0.72 vs 0.63; P < .0001). Sensitivity and specificity of the high risk TissueCypher class were 38% and 94%, respectively. CONCLUSIONS: An objective tissue systems pathology test high-risk class is a strong independent predictor of incident progression in patients with BE, substantially improving progression risk prediction over clinical variables alone. Although test specificity was high, sensitivity was modest.	esophagus
Insights into the leaves of Ceriscoides campanulata: Natural proanthocyanidins alleviate diabetes, inflammation, and esophageal squamous cell cancer via in vitro and in silico models.	Fourteen flavones (1-14) including twelve polymethoxylated flavones, two A-type proanthocyanidins (oligomeric flavonoids) (15, 16), one benzoyl glucoside (17), one triterpenoid (18), and one phenylpropanoid (19) were isolated from the leaves of the South Asian medicinal plant Ceriscoides campanulata (Roxb.) Tirveng (Rubiaceae). The structures of the compounds were identified based on their spectroscopic and spectrometric data and in comparison with literature data. Isolated compounds were tested in vitro against inflammatory enzymes (COX-2, iNOS), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), esophageal squamous carcinoma cell line (TE13), and carbohydrate digestion enzymes (α-amylase, α-glucosidase). Proanthocyanidins 15 and 16 significantly attenuated the LPS-induced inflammatory response of COX-2, iNOS, IL-1β, IL-6, TNF-α in RAW 264.7 cells. Proanthocyanidins also satisfactorily inhibited the regrowth (64%), migration (51%), and formation of tumor-spheres (48%) in ESCC cell line TE13 at 50% toxic concentration. Compounds 15 and 16 showed the most potent effect against mammalian α-amylase (IC(50) 8.4 ± 0.3 μM and 3.5 ± 0.0 μM, respectively) compared to reference standard acarbose (IC(50) 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 15 and 16 also displayed significant activities (IC(50) 6.2 ± 0.3 and 4.7 ± 0.1 μM, respectively), while compounds 1-6 displayed weaker α-glucosidase inhibitory activities, ranging from 49 to 142 μM, compared to acarbose (IC(50) 665 ± 42 μM). In an anticholinesterase assay, compounds 1, 2, 6 (IC(50) 51 ± 2, 53 ± 7, 64 ± 5 μM, respectively), and 4 (IC(50) 44 ± 1 μM) showed moderate inhibitory activities against acetylcholinesterase and butyrylcholinesterase, respectively. Furthermore, molecular docking and molecular dynamic simulation analyses of compounds 15 and 16 were performed against human pancreatic α-amylase and human lysosomal acid α-glucosidase to elucidate the interactions of these compounds in the respective enzymes' active sites.	esophagus
PTK7, a Catalytically Inactive Receptor Tyrosine Kinase, Increases Oncogenic Phenotypes in Xenograft Tumors of Esophageal Squamous Cell Carcinoma KYSE-30 Cells.	Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase, is upregulated in tumor tissues and cell lines of esophageal squamous cell carcinoma (ESCC). We showed that PTK7 plays an oncogenic role in various ESCC cell lines. However, its role as an oncogene has not been demonstrated in vivo. Here, we examined the influence of PTK7 on the tumorigenic potential of ESCC KYSE-30 cells, which are known to establish xenograft tumors. Overexpression of PTK7 enhanced the proliferation, adhesion, wound healing, and migration of KYSE-30 cells, and these effects were reversed by the knockdown of PTK7. PTK7 overexpression and knockdown, respectively, increased and decreased the tyrosine phosphorylation of cellular proteins and the phosphorylation of ERK, AKT, and FAK, which are important for cell proliferation, survival, adhesion, and migration. Additionally, PTK7 overexpression and silencing, respectively, increased and decreased the weight, volume, and number of Ki-67-positive proliferating cells in xenograft tumors of KYSE-30 cells. Therefore, we propose that PTK7 plays an important role in the tumorigenesis of ESCC cells in vivo and is a potential therapeutic target for ESCC.	esophagus
Esophageal Second Primary Tumors in Patients With Head and Neck Squamous Cell Carcinoma: Incidence, Risk Factors, and Overall Survival.	INTRODUCTION: The aim of this registry-based cohort study was to evaluate the potential role of endoscopic esophageal surveillance for esophageal second primary tumors (ESPTs) in Western patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Outcomes were cumulative incidence and risk factors for ESPTs and its effect on overall survival. RESULTS: A total of 47 ESPTs were observed in 1,708 patients with HNSCC, with 10-year cumulative incidence (95% confidence interval) of 2.9% (2.1-3.7). Alcohol and HNSCC location were significant predictors for ESPTs. ESPTs significantly increased the risk of dying (adjusted hazard ratio 3.36, 95% confidence interval 2.16-5.22). DISCUSSION: Endoscopic esophageal surveillance of Western patients with HNSCC with high risk of ESPTs seems justified.	esophagus
Delayed Bronchial Obstruction following Esophageal Stent Implantation: A Case Report.	Airway compression is a rare complication of esophageal stent placement. With the introduction of self-expanding metal stents, the incidence of bronchial obstruction by esophageal stents has decreased. Delayed external airway compression after esophageal stent implantation is rarely reported. We describe a case of left main bronchial obstruction after self-expandable esophageal stent placement. A 70-year-old patient with advanced esophageal cancer visited the emergency room (ER) with worsening cough and dyspnea. He had received palliative concurrent chemoradiotherapy after esophageal self-expanding metal stent (SEMS) insertion three months ago. One month before the ER visit, additional esophageal SEMS placement (stent-in-stent) was performed owing to the development of a tracheoesophageal fistula. After hospitalization, chest radiography revealed a patchy consolidation in the left lower lobe. A diagnosis of pneumonia was made, and the patient was treated with antibiotics. Seven days after antibiotic treatment, the patient developed a fever and severe dyspnea. Auscultation revealed the absence of breath sounds in the left hemithorax. A follow-up chest radiograph showed a white-out of the left hemithorax. Flexible bronchoscopy revealed luminal narrowing of the left main bronchus (LMB) due to external compression. Chest computed tomography further demonstrated compression of the LMB by esophageal stents. This case highlights that esophageal SEMS can present as an emergent and often life-threatening airway obstruction.	esophagus
[Oncological surgery in the interdisciplinary context-On the way to personalized medicine].	Oncological surgery is a discipline which closely interacts with other clinical partners and remains in many cases the cornerstone of a curative treatment of solid tumors. Due to the progress in the field of systemic tumor treatment as well as innovations in surgical techniques, the indications in oncological surgery are also changing, such as extended indications for patients with oligometastatic disease. Surgery of metastases has long been established for colorectal cancer and is being further tested for other entities, such as pancreatic and gastric cancer, within randomized controlled clinical trials (e.g. RENAISSANCE and METAPANC). A new challenge is the handling of a clinical complete remission after total neoadjuvant therapy, for example in locally advanced rectal cancer or in esophageal cancer. Here, organ and function preservation are increasingly propagated but should only be performed within clinical trials until stratification enables the identification of patients in whom this concept is oncologically safe. The personalized use of oncological surgery is dependent on the patient, the tumor and on the total multimodal concept.	esophagus
Endoscopic Diagnosis and Treatment of Superficial Esophageal Squamous Cell Cancer: Present Status and Future Perspectives.	This review provides information regarding the preoperative examinations, indications for endoscopic resection (ER), and curability assessment in subjects with superficial esophageal squamous cell carcinoma (SCC). Narrow-band imaging (NBI) is a more sensitive modality for detecting esophageal cancer than conventional observation, and esophageal observation using NBI is thus recommended for the detection of superficial esophageal cancer. It is also important to adjust the volume of air in the esophagus during observation. Workup by non-magnifying followed by magnifying endoscopy is a common process for diagnosing the invasion depth of superficial esophageal SCCs in Japan. Endoscopic ultrasonography carries a risk of overdiagnosis, and its routine use is therefore not recommended. The Japanese endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer considered the indications for ER based on the results of studies focusing on clinical MM/SM1 cancers, and concluded that clinical MM/SM1 carcinomas, except circumferential carcinoma, were an indication for ER. The curative effect of ER should be assessed based on histologic examination of the resected specimens. ER should be conducted based on a thorough understanding of the preoperative diagnosis, indication, curability, and additional treatment of esophageal SCC.	esophagus
Efficacy and Safety of Four Different Endoscopic Treatments for Early Esophageal Cancer: a Network Meta-analysis.	PURPOSE: Cap-assisted endoscopic mucosal resection (EMRC), ligation-assisted endoscopic mucosal resection (EMRL), endoscopic submucosal dissection (ESD), and multiband mucosectomy (MBM) are used for treating early esophageal cancer patients. Our aim was to compare the efficacy and safety of four different endoscopic treatments. METHODS: Electronic databases (PubMed, Cochrane, Embase, and Web of Science) were systematically searched to include relevant studies published from database inception until February 15, 2021. There were no date or language restrictions. Data related to study such as characteristics, methods, outcomes, and risks of bias were extracted by two reviewers. RESULTS: A total of 11 articles with 1880 patients were included. The results of the network meta-analysis showed that ESD was a better choice considering the efficacy of en bloc resection rate (surface under the cumulative ranking curves (SUCRA) = ESD: 99.5%, EMRC: 26.5%, MBM: 24.1%) and local recurrence rate (SUCRA = EMRC: 95.6%, MBM: 42.9%, ESD: 11.6%). MBM had a lower rate of side effects compared to the other treatments: perforation rate (SUCRA = ESD: 100%, EMRC: 48.1%, MBM: 1.9%), stricture rate (SUCRA = ESD: 99.8%, MBM: 40.8%, EMRC: 9.4%), and bleeding rate (SUCRA = EMRC: 69.4%, ESD: 62.2%, EMRL: 61.6%, MBM: 6.8%). MBM also had the shortest operation time and smallest diameter of the specimens. CONCLUSION: The MBM endoscopic treatment was recommended for early esophageal cancer patients, but considering the increase in lesion size, ESD would be better.	esophagus
High expression of nuclear NRF2 combined with NFE2L2 alterations predicts poor prognosis in esophageal squamous cell carcinoma patients.	Nuclear factor erythroid-2 related factor-2 (NFE2L2 or NRF2) is a frequently mutated gene in esophageal squamous cell carcinoma (ESCC). However, the roles of NFE2L2 alterations in ESCC remain elusive. In order to elucidate this issue, 130 ESCC patients who underwent esophagectomy were enrolled. The majority of tumor tissues were positive for NRF2, which was significantly enriched in the nucleus of the primary tumor tissues compared with the noncancerous mucosae. Primary ESCC tumors positive for NRF2 tended to be positive for NAD(P)H quinone oxidoreductase 1 (NQO1) as the downstream target of NRF2. There was a positive correlation between NRF2 and NQO1 expression level in primary tumors. NQO1 staining in primary tumors with NRF2 nuclear expression was significantly stronger than that with NRF2 cytoplasmic expression. In addition, high concordance for the status of NRF2 expression between primary tumors and corresponding metastatic lesions was observed. Next, we found high expression of nuclear NRF2 (the proportion of nuclear NRF2 expression >20% or nuclear NRF2 immunohistochemistry score >20) predicted shorter overall survival in patients with dual-positive expression of NRF2 and NQO1. Captured-based targeted sequencing revealed that NFE2L2 somatic alterations were observed in 52.8% of ESCC patients with dual-positive expression of NRF2 and NQO1. NFE2L2 amplification and mutations within the DLG/ETGE motifs were seen more frequently in ESCC tumors with nuclear or nucleocytoplasmic expression of NRF2 compared with those with cytoplasmic expression of NRF2. We also found high expression of nuclear NRF2 plus the status of NFE2L2 alteration exhibited high performance in predicting prognosis of ESCC patients. Our study demonstrated that high nuclear NRF2 expression and NFE2L2 alterations were associated with poor prognosis of ESCC patients. These findings suggest that NRF2 signaling pathway might play vital roles in ESCC malignancy and the aberrant activation of NRF2 pathway predicts unfavorable prognosis in ESCC.	esophagus
Endoscopic Submucosal Dissection Versus Radical Surgery for T1 Superficial Esophageal Cell Carcinoma: a Subgroup Survival Analysis.	BACKGROUND: With the continuous advent of magnifying endoscopy, endoscopic submucosal dissection (ESD) has gradually become the mainstream treatment for early esophageal cancer. We aimed to compare the outcomes of patients with T1 superficial esophageal cell carcinoma treated with ESD vs. esophagectomy. METHODS: We retrospectively analyzed patients who underwent ESD or radical surgery at the First Affiliated Hospital of Nanchang University from January 1, 2010, to December 31, 2018. The purpose of propensity score matching is to reduce selection bias. Precise subgroup analysis according to depth of invasion was performed to reduce the influence of confounding factors. RESULT: We reviewed patients who underwent ESD (n = 117) or radical surgery (n = 217) at the First Affiliated Hospital of Nanchang University from 2010 to 2018. The OS rate and progression-free survival rate in the ESD group were better than those in the surgery group (OS, P = 0.002. PFS, P = 0.004). The ESD group had a lower early adverse event rate (74.6% vs. 91%, P = 0.012), shorter hospital stays (median 10 days vs. 18 days, P < 0.001), and lower hospitalization costs (median 15,455 vs. 62,376 RMB, P < 0.001). Multivariate Cox regression analysis found that the treatment method was an independent risk factor affecting the prognosis of patients with superficial esophageal cancer, and the death risk of patients in the ESD group was 0.377 times that of the radical surgery group (HR = 0.377, P = 0.023). We conducted a subgroup analysis of patients again according to the depth of invasion; 37 pairs of patients were included in the T1a stage, and 19 pairs of patients were included in the T1b stage. In T1a and T1b patients, the difference in OS rate and PFS rate between the two treatments was statistically significant (T1a, OS, P = 0.002, PFS, P = 0.004; T1b, OS, P = 0.019, PFS, P = 0.022), and the OS rates in the ESD group were better than those in the radical surgery group. CONCLUSION: For patients with T1b superficial esophageal cancer, ESD has a longer overall survival and progression-free survival compared with radical surgery. These results support ESD as the preferred treatment for stage T1b superficial esophageal cancer.	esophagus
Paired box 5 increases the chemosensitivity of esophageal squamous cell cancer cells by promoting p53 signaling activity.	BACKGROUND: Gene promoter methylation is a major epigenetic change in cancers, which plays critical roles in carcinogenesis. As a crucial regulator in the early stages of B-cell differentiation and embryonic neurodevelopment, the paired box 5 (PAX5) gene is downregulated by methylation in several kinds of tumors and the role of this downregulation in esophageal squamous cell carcinoma (ESCC) pathogenesis remains unclear. METHODS: To elucidate the role of PAX5 in ESCC, eight ESCC cell lines, 51 primary ESCC tissue samples, and eight normal esophageal mucosa samples were studied and The Cancer Genome Atlas (TCGA) was queried. PAX5 expression was examined by reverse transcription-polymerase chain reaction and western blotting. Cell apoptosis, proliferation, and chemosensitivity were detected by flow cytometry, colony formation assays, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays in ESCC cell lines with PAX5 overexpression or silencing. Tumor xenograft models were established for in vivo verification. RESULTS: PAX5 methylation was found in 37.3% (19/51) of primary ESCC samples, which was significantly associated with age (P = 0.007) and tumor-node-metastasis stage (P = 0.014). TCGA data analysis indicated that PAX5 expression was inversely correlated with promoter region methylation (r = -0.189, P = 0.011 for cg00464519 and r = -0.228, P = 0.002 for cg02538199). Restoration of PAX5 expression suppressed cell proliferation, promoted apoptosis, and inhibited tumor growth of ESCC cell lines, which was verified in xenografted mice. Ectopic PAX5 expression significantly increased p53 reporter luciferase activity and increased p53 messenger RNA and protein levels. A direct interaction of PAX5 with the p53 promoter region was confirmed by chromatin immunoprecipitation assays. Re-expression of PAX5 sensitized ESCC cell lines KYSE150 and KYSE30 to fluorouracil and docetaxel. Silencing of PAX5 induced resistance of KYSE450 cells to these drugs. CONCLUSIONS: As a tumor suppressor gene regulated by promoter region methylation in human ESCC, PAX5 inhibits proliferation, promotes apoptosis, and induces activation of p53 signaling. PAX5 may serve as a chemosensitive marker of ESCC.	esophagus
Life Expectancy in Survivors of Esophageal Cancer Compared with the Background Population.	It is unknown whether the survival of patients cured of esophageal cancer differs from that of the corresponding background population. This nationwide and population-based cohort study included all patients who survived for at least 5 years after surgery for esophageal cancer in Sweden between 1987 and 2015, with follow-up throughout 2020. Relative survival rates with 95% confidence intervals (95% CI) were calculated by dividing the observed with the expected survival. The expected survival was assessed from the entire Swedish population of the corresponding age, sex, and calendar year. Yearly relative survival rates were calculated between 6 and 10 years postoperatively. Among all 762 participants, the relative survival was initially similar to the background population (96.1%, 95% CI 94.3-97.9%), but decreased each following postoperative year to 83.5% (95% CI 79.5-87.6%) by year 10. The drop in relative survival between 6 and 10 years was more pronounced in participants with a history of squamous cell carcinoma [from 94.5% (95% CI 91.2-97.8%) to 70.8% (95% CI 64.0-77.6%)] than in those with adenocarcinoma [from 96.9% (95% CI 94.8-99.0%) to 91.5% (95% CI 86.6-96.3%)], and in men [from 96.0% (95% CI 93.8-98.1%) to 81.8% (95% CI 76.8-86.8%)] than in women [from 96.4% (95% CI 93.4-99.5%) to 88.1% (95% CI 81.5-94.8%)]. No major differences were found between age groups. In conclusion, esophageal cancer survivors had a decline in survival between 6 and 10 years after surgery compared with the corresponding general population, particularly those with a history of squamous cell carcinoma of the esophagus and male sex.	esophagus