crossing96/oncoscreening huggingface dataset:
Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44(+) cancer stem cells.	Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation. Here, we report the identification and separation of CD44(+) cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44(±) cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry. Low concentration of ATRA (1μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44(±) cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1. We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.	esophagus
Spatial predisposition of dysplasia in Barrett's esophagus segments: a pooled analysis of the SURF and AIM dysplasia trials.	OBJECTIVES: Surveillance endoscopy detects dysplasia within Barrett's esophagus (BE) and dictates treatment. Current biopsy regimens recommend uniformly spaced random biopsies. We assessed the distribution of dysplasia in BE to develop evidence-based biopsy regimens. METHODS: We performed analysis of the distribution of dysplasia within BE using pretreatment biopsy data from two randomized controlled trials (RCTs) of radiofrequency ablation for dysplastic BE: the SURF (Surveillance vs. Radiofrequency Ablation) trial and the AIM Dysplasia (Ablation of Intestinal Metaplasia (AIM) Containing Dysplasia) trial. We used generalized linear models with generalized estimating equations (GEE) to estimate prevalence differences for dysplasia depending on the standardized location of biopsies. We performed Monte Carlo simulation of biopsy regimens to estimate their yield for any dysplasia within segments. RESULTS: Dysplasia preferentially resides in the proximal-most half of the BE segment that is almost twice as likely to demonstrate dysplasia as the distal-most quartile. In pooled analysis, compared with the distal-most quarter, the prevalence difference in the proximal-most quarter was 22.6%, in the second proximal-most quarter 23.1%, and in the second distal-most quarter 15.3%. The best performing biopsy regimen in simulation studies acquired 8 biopsies in the most proximal cm of BE, 8 biopsies in the second cm, and 2 biopsies in each cm thereafter (q1cm: 8, 8, 2, 2…). A slightly simpler q2cm (every 2 cm) regimen (q2cm: 12, 12, 4…) was nearly as effective. CONCLUSIONS: The post hoc analysis of two RCTs reveals a substantially increased prevalence of dysplasia proximally in BE segments. Our simulations suggest an altered biopsy regimen could increase sensitivity of biopsies in short-segment BE by >30%.	esophagus
Association of the p53 Arg72Pro polymorphism with esophageal cancer in Chinese populations: a meta-analysis.	Although many epidemiologic studies have investigated the p53 codon 72 polymorphism and its association with esophageal cancer (EC) in China, definite conclusions could not be drawn. To clarify the effects of p53 codon 72 polymorphism on the risk of EC, we performed a meta-analysis on the Chinese population. A total of 13 studies including 3308 patients and 5115 controls were involved in this meta-analysis. Our results suggested that the Pro/Pro genotype was associated with an increased risk of EC in the Chinese population (Pro vs Arg: odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.01-1.34; Pro/Pro vs Arg/Arg+Arg/Pro: OR = 1.32, 95%CI = 1.06-1.66; Pro/Pro vs Arg/Arg: OR = 1.35, 95%CI = 1.03-1.78; Pro/Pro vs Arg/Pro: OR = 1.32, 95%CI = 1.06-1.65). In subgroup analyses by geographical location and ethnicity, significant association was also found in south China in both the Han Chinese population and in the population group with no stated ethnicity. Sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies using the Egger test. In conclusion, this meta-analysis provides supporting evidence that the Pro/Pro genotype might contribute to the development of EC in the Chinese population, especially in Southern China.	esophagus
Development of a prediction model of adverse events after stent placement for esophageal cancer.	BACKGROUND AND AIMS: Self-expandable metal stent (SEMS) positioning is the recommended method for palliation of dysphagia from esophageal cancer, although it is not adverse event-free. The present study was aimed at identifying predictors for adverse events and at proposing a statistical model to predict them. METHODS: We performed a retrospective analysis of a prospectively collected database. All patients who underwent SEMS placement for stricture due to esophageal cancer between 2002 and 2011 in a tertiary-care center were identified. Multivariable regression analysis in the presence of competing risk events was used to identify factors associated with SEMS-related adverse events and to build a prediction model. RESULTS: A total of 267 patients were included. According to the competing risk regression analysis, only 2 variables were significantly associated with the risk of SEMS-related adverse events: prior chemoradiotherapy (CRT), yielding a hazard ratio (HR) of 1.687 (95% confidence interval [CI], 1.076-2.644), and the SEMS length (HR 0.884; 95% CI, 0.798-0.980) for every 10-mm length increase. Based on the estimated probability curves, after 4 months from SEMS placement, the probability of an adverse event in patients who did receive prior CRT was 50.9% compared with 34.4% in those who did not receive prior therapy, which was reduced to 9.2% and 15.1%, respectively, if a 180 mm-length stent was used. The ability of the predictive model to differentiate between patients who did and did not experience the adverse event was moderate (c-index: 0.617). CONCLUSION: The rate of SEMS-related adverse events was higher in patients with previous CRT and lower in patients receiving longer stents. Both factors were used to build an accurate predictive model.	esophagus
Mir-192 suppresses apoptosis and promotes proliferation in esophageal aquamous cell caicinoma by targeting Bim.	MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. However, the mechanisms by which miRNAs regulate esophageal squamous cell carcinoma (ESCC) development remain poorly understood. In the present study, we assayed expression level of miR-192 in ESCC tissues and cell lines by real-time PCR, and defined the target gene and biological function by luciferase reporter assay, Western blot and apoptosis assay. We first verified that the expression level of miR-192 was significantly increased in ESCC tissues and cancer cells. Moreover, miR-192 over-expression inhibited cells apoptosis and promoted ESCC cells proliferation. We further demonstrated that miR-192 directly targeted 3'-UTR of Bim gene, and inhibited its protein expression. Importantly, Bim could reduce ESCC cells apoptosis ability induced by miR-192. These data suggest an important role of miR-192 in the molecular etiology of ESCC and implicate the potential application of miR-192 in ESCC therapy.	esophagus
Salvage pharyngolaryngectomy with total esophagectomy following definitive chemoradiotherapy.	Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.	esophagus
Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma.	BACKGROUND: The epidermal growth factor receptor (EGFR) signaling pathway is important in regulating biological behaviors in many malignancies. We explored whether expression and activation of EGFR and several components on its downstream pathways have prognostic significance in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Expression of EGFR, phosphorylated (p)-EGFR, AKT1, p-AKT1, AKT2, p-AKT2, ERK1, ERK2, p-ERK1/2, STAT3, and p-STAT3 was assessed by immunohistochemical analysis of tissue microarrays for 275 ESCC patients who had undergone complete three-field lymphadenectomy. Spearman rank correlation tests were used to determine the relationships among protein expression, and Cox regression analyses were performed to determine the prognostic factors on overall survival (OS). RESULTS: p-EGFR expression was correlated statistically with all of the other phosphorylated markers. Gender, N stage, and p-AKT1 expression were found to be independent prognostic factors for OS. Increased expression of p-AKT1 was associated with decreased patient survival. EGFR and p-EGFR expression was not significantly associated with patient survival. CONCLUSION: Activation of AKT1 was associated with poor prognosis in ESCC.	esophagus
Accuracy of preoperative diagnosis of lymph node metastasis for thoracic esophageal cancer patients from JCOG9907 trial.	BACKGROUND: Accurate clinical evaluation of lymph nodes is crucial for selection of the optimum treatment strategy for individual esophageal cancer patients. This study investigated the accuracy of preoperative clinical diagnosis of lymph node metastasis for patients with clinical stage II/III esophageal squamous cell carcinoma. METHODS: Patients assigned to receive surgery and postoperative chemotherapy in JCOG9907 trial were studied to evaluate the concordance between clinical and pathological nodes. Preoperative diagnosis was based on computed tomography or magnetic resonance imaging. RESULTS: Among 166 patients in the postoperative group, 160 with sufficient pathological data were studied. The patient background characteristics were: male/female, 147/13; median age, 61 years (range 39-75 years); primary tumor site (upper/middle/lower), 15/76/69; cN0/cN1, 53/107. The sensitivity and specificity of clinical nodes for diagnosis of pathological nodes were 72.7 and 51.3 %, respectively; the positive and negative predictive values were 82.2 and 37.7 %, respectively. The lymph nodes overestimated in the preoperative diagnosis included thoracic paratracheal lymph nodes (#106) (n = 8), middle thoracic paraesophageal lymph nodes (#108) (n = 4), lymph nodes along the lesser curvature (#3) (n = 4), right cardiac lymph nodes (#1) (n = 3), and left cardiac lymph nodes (#2) (n = 2). CONCLUSION: Diagnosis of clinical nodes has low specificity and low negative predictive value for prediction of pathological node category in the preoperative diagnosis of lymph node metastasis for patients with locally advanced resectable esophageal cancer. Clinical staging techniques must therefore be improved for accurate preoperative diagnosis.	esophagus
Markers of sarcopenia quantified by computed tomography predict adverse long-term outcome in patients with resected oesophageal or gastro-oesophageal junction cancer.	OBJECTIVES: To assess the impact of sarcopenia and alterations in body composition parameters (BCPs) on survival after surgery for oesophageal and gastro-oesophageal junction cancer (OC). METHODS: 200 consecutive patients who underwent resection for OC between 2006 and 2013 were selected. Preoperative CTs were used to assess markers of sarcopenia and body composition (total muscle area [TMA], fat-free mass index [FFMi], fat mass index [FMi], subcutaneous, visceral and retrorenal fat [RRF], muscle attenuation). Cox regression was used to assess the primary outcome parameter of overall survival (OS) after surgery. RESULTS: 130 patients (65%) had sarcopenia based on preoperative CT examinations. Sarcopenic patients showed impaired survival compared to non-sarcopenic individuals (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.15-3.03, p = 0.011). Furthermore, low skeletal muscle attenuation (HR 1.91, 95% CI 1.12-3.28, p = 0.019) and increased FMi (HR 3.47, 95% CI 1.27-9.50, p = 0.016) were associated with impaired outcome. In the multivariate analysis, including a composite score (CSS) of those three parameters and clinical variables, only CSS, T-stage and surgical resection margin remained significant predictors of OS. CONCLUSION: Patients who show signs of sarcopenia and alterations in BCPs on preoperative CT images have impaired long-term outcome after surgery for OC. KEY POINTS: • Sarcopenia is associated with impaired OS after surgery for oesophageal cancer. • Other body composition parameters are also associated with impaired survival. • This influence on survival is independent of established clinical parameters. • Sarcopenia provides a better estimation of cachexia than BMI. • Sarcopenia assessment could be considered in risk/benefit stratification before oesophagectomy.	esophagus
From Barrett metaplasia to esophageal adenocarcinoma: the molecular background.	The molecular landscape of Barrett's esophagus and Barrett-related neoplastic lesions is still far from being completely elucidated. Both in vitro and in vivo studies pinpointed the pathogenetic role of different morphogenic pathways (the para-homeobox, the Notch and the Sonic Hedgehog families in particular) implicated in the acquisition of the metaplastic phenotype of the esophageal mucosa. On the other hand, the most common genetic alterations observed during Barrett's carcinogenesis include disorders of major regulators of the cell cycle, as well as deregulation of the TGF-β/Smad and receptor tyrosine kinases signalling pathways. Recent comprehensive mutational profiling studies identified that the inactivation of the TP53 and of the SMAD4 tumour suppressor genes occurred in a stage-specific manner, confined to (high grade) dysplastic and neoplastic lesions, respectively. The next step will be the correlation of these findings into multidisciplinary diagnostic approaches integrating endoscopy, histology, molecular profiling and liquid biopsies. This will allow the introduction of innovative strategies for secondary prevention of esophageal adenocarcinoma based on biological rationales, and the implementation of potential novel therapeutic targets.	esophagus
Extent of Lymphadenectomy and Prognosis After Esophageal Cancer Surgery.	IMPORTANCE: The prognostic role of the extent of lymphadenectomy during surgery for esophageal cancer is uncertain and requires clarification. OBJECTIVE: To clarify whether the number of removed lymph nodes influences mortality following surgery for esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: Conducted from January 1, 2000, to January 31, 2014, this was a cohort study of patients who underwent esophagectomy for cancer in 2000-2012 at a high-volume hospital for esophageal cancer surgery, with follow-up until 2014. EXPOSURES: The main exposure was the number of resected lymph nodes. Secondary exposures were the number of metastatic lymph nodes and positive to negative lymph node ratio. MAIN OUTCOMES AND MEASURES: The independent role of the extent of lymphadenectomy in relation to all-cause and disease-specific 5-year mortality was analyzed using Cox proportional hazard regression models, providing hazard ratios (HRs) with 95% CIs. The HRs were adjusted for age, pathological T category, tumor differentiation, margin status, calendar period of surgery, and response to preoperative chemotherapy. RESULTS: Among 606 included patients, 506 (83.5%) had adenocarcinoma of the esophagus, 323 (53%) died within 5 years of surgery, and 235 (39%) died of tumor recurrence. The extent of lymphadenectomy was not statistically significantly associated with all-cause or disease-specific mortality, independent of the categorization of lymphadenectomy or stratification for T category, calendar period, or chemotherapy. Patients in the fourth quartile of the number of removed nodes (21-52 nodes) did not demonstrate a statistically significant reduction in all-cause 5-year mortality compared with those in the lowest quartile (0-10 nodes) (HR, 0.86; 95% CI, 0.63-1.17), particularly not in the most recent calendar period (HR, 0.98; 95% CI, 0.57-1.66 for years 2007-2012). A greater number of metastatic nodes and a higher positive to negative node ratio was associated with increased mortality rates, and these associations showed dose-response associations. CONCLUSIONS AND RELEVANCE: This study indicated that the extent of lymphadenectomy during surgery for esophageal cancer might not influence 5-year all-cause or disease-specific survival. These results challenge current clinical guidelines.	esophagus
Duration of Smoking Cessation and Postoperative Morbidity After Esophagectomy for Esophageal Cancer: How Long Should Patients Stop Smoking Before Surgery?	BACKGROUND: Smoking is one of the risk factors for postoperative morbidity. There were no studies on the correlation between the duration of smoking cessation and the incidence of morbidities after esophagectomy. METHODS: A total of 246 patients undergoing elective esophagectomy with 2- or 3-field lymphadenectomy for esophageal cancer between April 2005 and February 2015 were retrospectively analyzed. Patients were divided into five groups according to the duration of smoking cessation [no smoking cessation (including cessation for a few days), cessation for 7-30, 31-90, ≥91 days, never smoker]. RESULTS: Any morbidity of Clavien-Dindo classification (CDc) ≥II, pneumonia, any pulmonary morbidity, surgical site infection, cardiovascular morbidity, and severe morbidities of CDc ≥IIIb frequently occurred in patients with no smoking cessation. The incidence of pneumonia and severe morbidities decreased as the duration of smoking cessation became longer. Logistic regression analysis suggested that no smoking cessation was the independent risk factor for any pulmonary morbidity (HR 3.68, 95% CI 1.152-11.74; p = 0.028). Smoking cessation ≤30 days was also the independent risk factor for pneumonia (HR 2.89, 95% CI 1.141-7.301; p = 0.025). Smoking cessation ≤90 days was the independent risk factor for severe morbidities of CDc ≥IIIb (HR 2.82, 95% CI 1.072-7.427; p = 0.036). CONCLUSIONS: Preoperative smoking cessation more than 90 days is ideal to reduce morbidities after esophagectomy. When patients with insufficient smoking cessation undergo esophagectomy, careful perioperative management is required.	esophagus
Inhibition of Rho-associated kinases disturbs the collective cell migration of stratified TE-10 cells.	BACKGROUND: The collective cell migration of stratified epithelial cells is considered to be an important phenomenon in wound healing, development, and cancer invasion; however, little is known about the mechanisms involved. Furthermore, whereas Rho family proteins, including RhoA, play important roles in cell migration, the exact role of Rho-associated coiled coil-containing protein kinases (ROCKs) in cell migration is controversial and might be cell-type dependent. Here, we report the development of a novel modified scratch assay that was used to observe the collective cell migration of stratified TE-10 cells derived from a human esophageal cancer specimen. RESULTS: Desmosomes were found between the TE-10 cells and microvilli of the surface of the cell sheet. The leading edge of cells in the cell sheet formed a simple layer and moved forward regularly; these rows were followed by the stratified epithelium. ROCK inhibitors and ROCK small interfering RNAs (siRNAs) disturbed not only the collective migration of the leading edge of this cell sheet, but also the stratified layer in the rear. In contrast, RhoA siRNA treatment resulted in more rapid migration of the leading rows and disturbed movement of the stratified portion. CONCLUSIONS: The data presented in this study suggest that ROCKs play an important role in mediating the collective migration of TE-10 cell sheets. In addition, differences between the effects of siRNAs targeting either RhoA or ROCKs suggested that distinct mechanisms regulate the collective cell migration in the simple epithelium of the wound edge versus the stratified layer of the epithelium.	esophagus
The impact of adjuvant radiotherapy on radically resected T3 esophageal squamous cell carcinoma.	PURPOSE: The role of adjuvant radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. This retrospective study was designed to analyze the impact of adjuvant radiotherapy in patients with T3 stage ESCC after radical resection. METHODS: Data of a single-center cohort of 692 patients with T3 stage ESCC who underwent radical resection, with or without adjuvant radiotherapy, were reviewed. Univariate and multivariate analyses were performed to compare overall survival (OS) and locoregional recurrence-free survival (LRFS). RESULTS: Two hundred and forty-six patients received adjuvant radiotherapy (S + R group), and 446 patients underwent surgery alone (S group). The median survival time and 5-year OS rate were 40.0 months and 40.9 % for the entire population, 50.0 months and 45.6 % for the S + R group and 38.0 months and 38.3 % for the S group (P = 0.114 for S + R group vs. S group). The 5-year LRFS rate for the S + R group was significantly higher than that for S group (50.8 vs. 35.9 %, P < 0.001). In subgroup analyses, adjuvant radiotherapy was found to improve the 5-year OS in the subgroups of tumor length >5 cm, pN0 and pN1 categories, pTNM stage IIa, IIb and IIIa (P < 0.005). CONCLUSIONS: Adjuvant radiotherapy is effective in local control of radically resected T3 stage ESCC and may improve the overall survival in certain subgroups, such as the patients with tumor length >5 cm, pN0 and pN1 categories, pTNM stage IIa, IIb and IIIa. Further studies are required to confirm our results.	esophagus