crossing96/oncoscreening huggingface dataset:
Janus kinase 2 inhibition by Licochalcone B suppresses esophageal squamous cell carcinoma growth.	Esophageal cancer (EC) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma (ESCC). Still, ESCC-targeted therapy has not been covered yet. In the present study we have identified that Licochalcone B (Lico B) inhibited the ESCC growth by directly blocking the Janus kinase (JAK) 2 activity and its downstream signaling pathway. Lico B suppressed KYSE450 and KYSE510 ESCC cell growth, arrested cell cycle at G2/M phase and induced apoptosis. Direct target of Lico B was identified by kinase assay and verified with in vitro and ex vivo binding. Computational docking model predicted for Lico B interaction to ATP-binding pocket of JAK2. Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.	esophagus
Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study.	BACKGROUND: After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. METHODS: Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. DISCUSSION: If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). TRIAL REGISTRATION: The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).	esophagus
Relevant issues in tumor regression grading of histopathological response to neoadjuvant treatment in adenocarcinomas of the esophagus and gastroesophageal junction.	Multimodality treatment combining surgery and oncologic treatment has become widely applied in curative treatment of esophageal and gastroesophageal junction adenocarcinoma. There is a need for a standardized tumor regression grade scoring system for clinically relevant effects of neoadjuvant treatment effects. There are numerous tumor regression grading systems in use and there is no international standardization. This review has found nine different international systems currently in use. These systems all differ in detail, which inhibits valid comparisons of results between studies. Tumor regression grading in esophageal and gastroesophageal junction adenocarcinoma needs to be improved and standardized. To achieve this goal, we have invited a significant group of international esophageal and gastroesophageal junction adenocarcinoma pathology experts to perform a structured review in the form of a Delphi process. The aims of the Delphi include specifying the details for the disposal of the surgical specimen and defining the details of, and the reporting from, the agreed histological tumor regression grade system including resected lymph nodes. The second step will be to perform a validation study of the agreed tumor regression grading system to ensure a scientifically robust inter- and intra-observer variability and to incorporate the consented tumor regression grading system in clinical studies to assess its predictive and prognostic role in treatment of esophageal and gastroesophageal junction adenocarcinomas. The ultimate aim of the project is to improve survival in esophageal and gastroesophageal adenocarcinoma by increasing the quality of tumor regression grading, which is a key component in treatment evaluation and future studies of individualized treatment of esophageal cancer.	esophagus
Dietary Polyunsaturated Fat Intake in Relation to Head and Neck, Esophageal, and Gastric Cancer Incidence in the National Institutes of Health-AARP Diet and Health Study.	Recent epidemiologic studies have examined the association of fish consumption with upper gastrointestinal cancer risk, but the associations with n-3 and n-6 polyunsaturated fatty acid (PUFA) subtypes remain unclear. Using the National Institutes of Health-AARP Diet and Health Study (United States, 1995-2011), we prospectively investigated the associations of PUFA subtypes, ratios, and fish with the incidence of head and neck cancer (HNC; n = 2,453), esophageal adenocarcinoma (EA; n = 855), esophageal squamous cell carcinoma (n = 267), and gastric cancer (cardia: n = 603; noncardia: n = 631) among 468,952 participants (median follow-up, 15.5 years). A food frequency questionnaire assessed diet. Multivariable-adjusted hazard ratios were estimated using Cox proportional hazards regression. A Benjamini-Hochberg (BH) procedure was used for false-discovery control. Long-chain n-3 PUFAs were associated with a 20% decreased HNC and EA risk (for HNC, quintile5 vs. 1 hazard ratio = 0.81, 95% confidence interval: 0.71, 0.92, and BH-adjusted Ptrend = 0.001; and for EA, quintile5 vs. 1 hazard ratio = 0.79, 95% confidence interval: 0.64, 0.98, and BH-adjusted Ptrend = 0.1). Similar associations were observed for nonfried fish but only for high intake. Further, the ratio of long-chain n-3:n-6 was associated with a decreased HNC and EA risk. No consistent associations were observed for gastric cancer. Our results indicate that dietary long-chain n-3 PUFA and nonfried fish intake are associated with lower HNC and EA risk.	esophagus
Log odds of positive lymph nodes predicts survival in patients treated with neoadjuvant therapy followed by esophagectomy.	BACKGROUND AND OBJECTIVES: We aimed to evaluate the efficacy of the log odds of positive lymph nodes (LODDS) in survival prediction of patients with esophageal carcinoma receiving neoadjuvant therapy, compared with N descriptor and positive lymph node ratio (LNR). METHODS: Patients with esophageal carcinoma receiving neoadjuvant therapy from 2004 to 2015 were reviewed in Surveillance, Epidemiology, and End Results database. The receiver operating characteristics curve and area under the curve (AUC) were used to compare discriminatory power among N descriptor, LNR, and LODDS. The goodness of fit was measured using the -2 log-likelihood ratio (-2LLR). RESULTS: About 2239 patients with a 22 months median follow-up and a 37.8% 5-year overall survival rate were included. LODDS had the best discriminatory power and goodness of fit (LODDS vs N descriptor, AUC 0.666 vs 0.626, -2LLR 15 680.402 vs 15 746.162; LODDS vs LNR, AUC 0.666 vs 0.635, -2LLR 15 680.402 vs 15 712.379; all P < .001). LODDS was the best for fewer than 15 lymph nodes retrieved (LODDS vs N descriptor, AUC 0.652 vs 0.618, P < .001; LODDS vs LNR, AUC 0.652 vs 0.625, P = .005). The prognosis of patients without metastatic nodes could be discriminated by LODDS. CONCLUSIONS: LODDS could better predict survival of patients with esophageal carcinoma receiving neoadjuvant therapy.	esophagus
Acid/bile exposure triggers TRAIL-mediated apoptosis in esophageal cancer cells by suppressing the decoy receptors and c-FLIP(R).	Esophageal adenocarcinoma essentially develops from esophageal inflammation caused by chronic GERD. During GERD episodes, the lower esophageal epithelium is repeatedly exposed to stomach acid, which often contains duodenal bile salts that prompt malignant transformation. TRAIL is one of the cytokines produced in response to such insults and targets the transformed cells exclusively. In this study, we simulated GERD episodes in vitro by exposing the cancer cells to acid or acid/bile combination and found that the cancer cells lived through acid attacks by expression of the decoy receptors and c-FLIP(R) but died of TRAIL-mediated apoptosis when bile salts were present. Further investigation revealed that acid/bile exposure downregulated the decoy receptors and thereby facilitated TRAIL signaling; meantime, it inhibited protein kinase C activity and thus expedited c-FLIP(R) degradation, allowing apoptosis to take place.	esophagus
PRDX2 plays an oncogenic role in esophageal squamous cell carcinoma via Wnt/β-catenin and AKT pathways.	PURPOSE: To investigate the role of PRDX2 in esophageal carcinoma (ESCA). METHODS: The expression of PRDX2 was detected in ESCA tissues. And PRDX2 expression in two ESCA cell lines was knocked down. Cell proliferation, metastasis and invasion were detected in these cells. RESULTS: Here, we found that PRDX2 expression was significantly increased in ESCA tissues and was associated with a poor prognosis in ESCA patients. In addition, PRDX2 expression was significantly associated with pathological grading, infiltration degree and 5-year survival time in ESCA patients. Next, we knocked down PRDX2 expression by PRDX2-shRNA transfection in two ESCA cell lines, Eca-109 and TE-1. Proliferation analysis indicated that in vitro PRDX2 knockdown decreased growth and clone formation of ESCA cells. Scratch and transwell assays indicated that cell migration and invasion were significantly inhibited by PRDX2 knockdown. In addition, PRDX2 knockdown inhibited cell cycle of ESCA cells and down-regulated Cyclin D1-CDK4/6. Moreover, PRDX2 knockdown regulated proteins involved in mitochondrial-dependent apoptosis, including increased Bax and Caspase9/3 and decreased Bcl2. Mechanism investigation indicated that PRDX2 knockdown led to inactivation of Wnt/β-catenin and AKT pathways. CONCLUSIONS: Our data suggest that PRDX2 may function as an oncogene in the development of ESCA via regulating Wnt/β-catenin and AKT pathways. Our study fills a gap in the understanding of the role of PRDX2 in ESCA and provides a potential target for ESCA treatment.	esophagus
CD24 and CK4 are upregulated by SIM2, and are predictive biomarkers for chemoradiotherapy and surgery in esophageal cancer.	Definitive chemoradiotherapy (CRT) is a less invasive therapy compared with surgery for some types of cancer; however, the 5‑year survival rate of patients with stages II‑III esophageal squamous cell carcinoma (ESCC) is only 37%. Therefore, prediction of CRT responders is necessary. Unfortunately, no definitive biomarker exists that is useful to predict survival outcome following CRT. From our previous microarray study, CD24 and keratin 4 (KRT4), which encodes cytokeratin 4 (CK4), were overexpressed in the favorable prognostic epithelial subtype with SIM bHLH transcription factor 2 (SIM2) expression. This study investigated the association between their mRNA and protein expression levels, and clinicopathological characteristics, and also investigated the functions of CD24 in SIM2‑mediated tumor differentiation and CRT sensitivity. High CD24 and KRT4 mRNA expression was associated with a favorable prognosis following CRT. Multivariate analyses revealed that high CD24 and CK4 protein expression, as determined by immunohistochemistry, and differentiated type were independent factors for predicting a favorable prognosis in response to CRT. Notably, in cases with low CD24 or CK4, surgery was suggested to be a good therapeutic modality compared with CRT. CD24 and KRT4 were expressed preferentially in differentiated layers of the normal esophageal mucosa, and their mRNA expression in 3D cultured ESCC cells was induced by SIM2 transfection, thus suggesting that CD24 and KRT4 were downstream differentiation markers of SIM2. Furthermore, CD24 small interfering RNA increased the mRNA expression levels of superoxide dismutase 2 and enhanced H2O2 resistance, thus indicating the involvement of CD24 in the radiosensitivity of patients with ESCC; however, it had no effect on cisplatin sensitivity. In conclusion, the two markers CD24 and CK4 may be considered predictive biomarkers for definitive CRT.	esophagus
Preoperative Low Vital Capacity Influences Survival After Esophagectomy for Patients with Esophageal Carcinoma.	BACKGROUND: Assessment of preoperative physiological status is crucial for optimizing clinical outcomes in patients undergoing surgery for esophageal carcinoma (EC). We aimed to evaluate the prognostic impact of pulmonary dysfunctions and their relationships with other physiological factors, especially sarcopenia, in EC patients receiving esophagectomy. METHODS: In total, 411 EC patients who underwent esophagectomy between 2006 and 2016 were retrospectively reviewed. Preoperative pulmonary functions were evaluated based on %vital capacity (%VC) and forced expiratory volume (FEV) 1.0%. The thresholds were set as the lowest quartile (99% for %VC and 68.6% for FEV1.0%) in this cohort. RESULTS: One hundred and two patients (24.8%) had low %VC (%VC < 99%), which was significantly associated with age, comorbidity, sarcopenia and postoperative complications, while not correlating with pathological variables. The overall survival (OS) of patients in the low %VC group was significantly poorer than that of those in the high %VC group (P < 0.001), especially in those with pStage 0-II diseases (P < 0.001). In contrast, survival was not stratified by FEV1.0% (P = 0.80). Notably, patients with both low %VC and sarcopenia showed very poor 5-year OS (30.3%). Multivariate analysis revealed low %VC to be independently associated with poor OS (P = 0.03). In the cause-specific survival analyses, low %VC was an independent predictor of deaths from non-EC-related causes (P = 0.03). CONCLUSIONS: Preoperative low %VC was independently associated with poor survival outcomes, especially when present in combination with sarcopenia, due to an increased risk of death from non-EC-related causes. Preoperative spirometry testing is useful for predicting long-term outcomes in EC patients undergoing esophagectomy.	esophagus
Validation and Comparison of Tools for Selecting Individuals to Screen for Barrett's Esophagus and Early Neoplasia.	BACKGROUND & AIMS: Guidelines suggest endoscopic screening of individuals who are at increased risk for Barrett's esophagus (BE) and esophageal adenocarcinoma. Tools based on clinical factors are available for identifying patients at risk, but only some have been validated. We aimed to compare and validate available tools. METHODS: We performed a prospective study of 1241 patients, ages 40 to 79 years, presenting either for their first esophagogastroduodenoscopy (EGD) or their first endoscopic therapy of early neoplastic BE, from April 2015 through June 2018. We calculated risk scores for 6 previously published tools (the Gerson, Locke, Thrift, Michigan BE pREdiction Tool [M-BERET], Nord-Trøndelag Health Study [HUNT], and Kunzmann tools). We also investigated the accuracy of frequency and duration of gastroesophageal reflux disease (GERD), using data from a randomly selected 50% of patients undergoing their first EGD. We compared the ability of all these tools to discriminate patients with BE and early neoplasia from patients without BE, using findings from endoscopy as the reference standard. RESULTS: BE was detected in 81 of 1152 patients during their first EGD (7.0%). GERD symptoms alone identified patients with BE with an area under the receiver operating characteristic curve (AuROC) of 0.579. All of the tools were more accurate in identifying patients with BE than the frequency and duration of GERD (AuROC for GERD, 0.579 vs range for other tools, 0.660-0.695), and predicted risk correlated well with observed risk (calibration). The AUROCs of the HUNT tool (0.796), the M-BERET (0.773), and the Kunzmann tool (0.763) were comparable in discriminating between patients with early neoplasia (n = 94) vs no BE. Each tool was more accurate in discriminating BE with early neoplasia than GERD frequency and duration alone (AuROC, 0.667; P < .01). CONCLUSIONS: The HUNT, M-BERET, and Kunzmann tools identify patients with BE with AuROC values ranging from 0.665 to 0.695, and discriminate patients with early neoplasia from patients without BE with AuROC values ranging from 0.763 to 0.796. These tools are more accurate than frequency and duration of GERD in identifying individuals at risk for neoplastic BE.	esophagus
Clinical Factors and Outcomes of Octogenarians Receiving Curative Surgery for Esophageal Cancer.	BACKGROUND: The incidence of esophageal cancer is increasing in the United States. Although neoadjuvant therapy (NAT) for locally advanced cancers followed by surgical resection is the standard of care, there are no clearly defined guidelines for patients aged ≥79 y. METHODS: Query of an institutional review board-approved database of 1031 esophagectomies at our institution revealed 35 patients aged ≥79 y from 1999 to 2017 who underwent esophagectomy. Age, gender, tumor location, histology, clinical stage, Charlson Comorbidity Index (CCI), NAT administration, pathologic response rate to NAT, surgery type, negative margin resection status, postoperative complications, postoperative death, length of stay, 30- and 90-d mortality, and disease status parameters were analyzed in association with clinical outcome. RESULTS: The median age of the octogenarian cohort was 82.1 y with a male preponderance (91.4%). American Joint Committee on Cancer clinical staging was stage I for 20% of patients, stage II for 27% of patients, and stage III for 50% of patients, which was not statistically significant compared with the younger cohort (P = 0.576). Within the octogenarian group, 54% received NAT compared with 67% in the younger group (P = 0.098). There was no difference in postoperative complications (P = 0.424), postoperative death (P = 0.312), and recurrence rate (P = 0.434) between the groups. However, CCI was significantly different between the octogenarian and nonoctogenarian cohort (P = 0.008), and octogenarians had shorter overall survival (18 versus 62 mo, P<0.001). None of the other parameters assessed were associated with clinical outcomes. CONCLUSIONS: Curative surgery is viable and safe for octogenarians with esophageal cancer. Long-term survival was significantly shorter in the octogenarian group, suggesting the need for better clinical selection criteria for esophagectomy after chemoradiation and that identification of complete responders for nonoperative management is warranted.	esophagus
High thromboembolic event rate in patients with locally advanced oesophageal cancer during neoadjuvant therapy. An exploratory analysis of the prospective, randomised intergroup phase III trial SAKK 75/08.	BACKGROUND: High rates of venous thromboembolic events (VTEs), mainly in advanced disease, are reported for patients with cancer of the upper gastrointestinal tract (stomach, pancreas) and for treatment with cisplatin. METHODS: Exploratory analysis of VTEs reported as adverse events and serious adverse events in a prospective, randomised, multicentre, multimodal phase III trial according to VTEs reported as adverse events and severe adverse events. Patients with resectable oesophageal cancer (T2N1-3, T3-4aNx) were randomized to 2 cycles of chemotherapy with docetaxel 75 mg/m(2), cisplatin 75 mg/m(2) followed by chemo-radiotherapy (CRT) and subsequent surgery (control arm) or the same treatment with addition of cetuximab (investigational arm). RESULTS: VTEs occurred in 26 of 300 patients included in the trial, resulting in an incidence rate (IR) of 8.7% [95% CI 5.7-12.4%]. A total of 29 VTEs were reported:13 (45%) VTEs were grade 2, 13 (45%) grade 3 and three (10%) fatal grade 5 events. 72% (21/29) of all VTEs occurred preoperatively (IR 6.7%): 14% (4/29) during chemotherapy and 59% (17/29) during CRT. In multivariable logistic regression only adenocarcinoma (IR 11.1%, 21/189 patients) compared to squamous cell cancer (IR 4.5%, 5/111 patients) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.0-8.4], p = 0.046. Baseline Khorana risk score was 0 in 73% (19/26), 1-2 in 23% (6/26) and 3 in only 4% (1/26) of patients with VTEs. CONCLUSION: A high incidence of VTEs during preoperative therapy of resectable oesophageal cancer is observed in this analysis, especially in patients with adenocarcinoma. The role of prophylactic anticoagulation during neoadjuvant therapy in resectable esophageal cancer should be further evaluated in prospective clinical trials. According to our data, which are in line with other analysis of VTE-risk in patients with oesophageal cancer patients treated with neoadjuvant cisplatin-based chemotherapy and CRT, prophylactic anticoagluation could be considered balanced against individual bleeding risks, especially in patients with adenocarcinoma. In addition to the established risk factors, oesophageal adenocarcinoma treated with neoadjuvant cisplatin-based therapy may be regarded as a high-risk situation for VTEs. TRIAL REGISTRATION: Registered at clinicaltrials.gov, NCT01107639, on 21 April 2010.	esophagus