crossing96/oncoscreening huggingface dataset:
Identification of candidate genes involved in the radiosensitivity of esophageal cancer cells by microarray analysis.	Radiotherapy plays a key role in the control of tumor growth in esophageal cancer patients. To identify the patients who will benefit most from radiation therapy, it is important to know the genes that are involved in the radiosensitivity of esophageal cancer cells. Hence, we examined the global gene expression in radiosensitive and radioresistant esophageal squamous cell carcinoma cell lines. Radiosensitivities of 13 esophageal cancer cell lines were measured. RNA was extracted from each esophageal cancer cell line and a normal esophageal epithelial cell line, and the global gene expression profiles were analyzed using a 34 594-spot oligonucleotide microarray. In the clonogenic assay, one cell line (TE-11) was identified to be highly sensitive to radiation, while the other cell lines were found to be relatively radioresistant. We identified 71 candidate genes that were differentially expressed in TE-11 by microarray analysis. The up-regulated genes included CABPR, FABP5, DSC2, GPX2, NME, CBR3, DOCK8, and ABCC5, while the down-regulated genes included RPA1, LDOC1, NDN, and SKP1A. Our investigation provided comprehensive information on genes related to radiosensitivity of esophageal cancer cells; this information can serve as a basis for further functional studies.	esophagus
Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy.	The zinc finger protein glioma-associated oncogene homologue 1 (Gli-1) is a critical component of the Hedgehog (Hh) signalling pathway, which is essential for morphogenesis and stem-cell renewal, and is dysregulated in many cancer types. As data were not available on the role of Gli-1 expression in oesophageal cancer progression, we analysed whether it could be used to predict disease progression and prognosis in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Among 69 patients with histologically confirmed oesophageal squamous cell carcinomas (ESCCs), 25 showed a pathological complete response after preoperative CRT. Overall survival (OS) was significantly associated with lymph-node metastasis, distant metastasis, and CRT, and was further correlated with the absence of both Gli-1 nuclear expression and residual tumour. All patients with Gli-1 nuclear expression (10.1%) had distant or lymph-node metastasis, and six out of seven died within 13 months. Furthermore, patients with Gli-1 nuclear-positive cancers showed significantly poorer prognoses than those without (disease-free survival: mean DFS time 250 vs 1738 months, 2-year DFS 0 vs 54.9%, P=0.009; OS: mean OS time 386 vs 1742 months, 2-year OS 16.7 vs 54.9%, P=0.001). Our study provides the first evidence that Gli-1 nuclear expression is a strong and independent predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that Hh signal activation might promote cancer regrowth and progression after CRT.	esophagus
Oesophageal cancer: caregiver mental health and strain.	OBJECTIVE: To investigate strain and mental health among family caregivers of oesophageal cancer patients and possible factors associated with caregiver mental health and strain. METHODS: Patients with oesophageal adenocarcinoma in Ireland were recruited into the FINBAR study (the main aim of which was to investigate factors influencing the Barrett's adenocarcinoma relationship). Carers completed the 13-item Caregiver Strain Index and the General Health Questionnaire-30 (GHQ) in the context of a brief interview with trained research staff that was undertaken separately from the interview with each cancer patient. RESULTS: Two hundred and twenty-seven patients participated in the FINBAR study. A total of 39 patients did not have a family carer or the carer could not be identified. Fifty percent (94/188) of carers completed the questionnaires. Mean (SD) scores for strain (6.65, SD=3.63) and mental health status (10.21, SD=7.30) were high and 71% of carers scored >5 on the GHQ indicating psychological distress. There was a statistically significant positive relationship between level of strain experienced by caregivers and the severity of their mental health status and whether or not carers scored >5 on the GHQ. Relatives were 1.70 (95% CI 1.34-2.15) times more likely to be defined as high scorers with each unit increase in the CSI score. CONCLUSIONS: A significant proportion of caregivers experienced high levels of strain and psychological distress. There is a need to provide appropriate support and services targeted specifically at reducing the considerable strain of caring for patients with oesophageal cancer, particularly for carers of patients from lower socioeconomic groups.	esophagus
Lower esophageal palisade vessels and the definition of Barrett's esophagus.	The designated area of the columnar-lined esophagus (CLE) is anatomically defined by the distal limit of the lower esophageal palisade vessels (LEPV) and the term 'Barrett's esophagus' is equally used along with the name CLE in Japan. The aim of this study was to investigate the actual prevalence of CLE based on the Japanese criteria and to evaluate the criteria per se. A total of 42 esophagi consecutively resected at this institute were included. All subjects underwent a surgical resection for squamous cell carcinoma of the esophagus. The position of the LEPV, squamocolumnar junction, the prevalence of CLE and intestinal metaplasia were investigated both pre- and postoperatively. Preoperative endoscopy revealed CLE based on the Japanese criteria in half of all patients. In the resected specimens the distal limit of LEPV was lower than the squamocolumnar junction in 95.2%. In other words, almost all cases had CLE (equivalent to Barrett's mucosa in Japanese criteria). However, most of the CLE areas were very short and their average maximum length was only about 5 mm. In addition, no intestinal metaplasia was observed in any of the CLE cases. Almost all individuals might therefore be diagnosed to have CLE or Barrett's mucosa based on precise endoscopic observations in Japan. The CLE located in a small area, e.g. less than 5 mm, defined according to the LEPV criteria without any other factor concerning typical Barrett's esophagus such as signs of gastroesophageal reflux should therefore be excluded from consideration as a high-risk mucosa.	esophagus
Does systematic 2-field lymphadenectomy for esophageal malignancy offer a survival advantage? Results from 178 consecutive patients.	More extensive resection for esophageal cancer has been reported to improve survival in several series. We compared results from an unselected consecutive cohort of patients undergoing radical esophagectomy, including removal of all periesophageal tissue with a 2-field abdominal and mediastinal lymphadenectomy for esophageal and gastroesophageal malignancy. A prospective electronic database was reviewed for patients with esophageal malignancy undergoing an open esophagectomy between 1991 and 2004. Data were analyzed on an SPSS file (version 12.0, Chicago, IL, USA) using chi(2) or Fisher's exact test; odds ratio and 95% confidence interval; and the Kaplan-Meier method, log-rank test and Cox's proportional hazards regression for survival analysis. There were 178 patients with a median age of 65 years and a 70/30 male to female ratio. Median follow-up was 20.4 months. Pathology comprised adenocarcinoma in 64% of patients, squamous cell carcinoma 30%, and other malignancies 6%. Seventeen patients had neoadjuvant therapy. Hospital mortality was 3.3%. Complete resection was achieved in 87%. Local recurrence occurred at a median of 13 months in 6.7% of patients. Overall 5-year survival was 42%. For patients with invasive squamous cell carcinoma and adenocarcinoma the 5-year survival was 47% and 40.3%, respectively, and for patients without nodal involvement it was 71.5%, with one to four nodes involved, 23.5% and with >4 nodes, 5% (P < 0.001). Survival decreased with increasing direct tumor spread (P < 0.001) and pathological stage (P < 0.001). Esophageal resection with systematic 2-field lymphadenectomy can be performed with acceptable operative mortality and favorable survival.	esophagus
Enteral immuno-enhanced diets with arginine are safe and beneficial for patients early after esophageal cancer surgery.	We previously reported that provision of immediate enteral nutrition (EN) with a certain amount of omega (omega)-3 fatty acids (FAs) in patients after esophageal cancer surgery resulted in reduced platelet aggregation, coagulation activity, and cytokine production. We investigated whether EN using immuno-enhanced diet (IED) containing a large amount of omega-3 FAs as well as arginine and RNA affected the above-described responses. We also attempted to reveal whether arginine in the IED can potentially harm patients who undergo esophageal cancer surgery. Twenty-nine patients with esophageal cancer who underwent similar surgical procedures were selected. All patients received EN starting immediately after surgery. Fourteen patients received the formula with fewer omega-3 FAs, and fifteen patients received the IED. Administration of the IED tended to inhibit postoperative decrease in platelet count. Prothrombin activity and thrombin-antithrombin III complex levels were significantly reduced in the IED group. Plasma IL-8 levels were significantly lower (P < 0.05) in patients without the IED on the fifth postoperative day (POD). The proportion of T-cells was significantly higher (P < 0.05) in the IED group on PODs 1 and 7. Nitrate/nitrite levels did not differ significantly between the two groups. Early EN with an IED may enhance the inhibitory effects on postoperative platelet aggregation and hypercoagulation, and appeared to be advantageous to T-cell proliferation. These effects are expected to be beneficial in patients at risk of developing infectious complications. This study also showed that the IED could be safely used without any adverse effects for patients early after a radical surgery for the esophageal cancer.	esophagus
Reduced membranous beta-catenin protein expression is associated with metastasis and poor prognosis in squamous cell carcinoma of the esophagus.	OBJECTIVES: The aim of this study was to evaluate, by immunohistochemical analysis, the protein expression of beta-catenin and p53 in resected esophageal squamous cell carcinoma specimens. The clinical relevance and prognostic significance of the expression of these proteins were also analyzed. METHODS: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 68 resected esophageal squamous cell carcinoma tumor specimens to detect the expression of beta-catenin and p53. The correlation between the results of immunoexpression and the clinicopathologic parameters and patient survival was processed statistically. RESULTS: Reduced membranous beta-catenin expression was noted in 43 (63.2%) of 68 tumor specimens. Increased expression of p53 was observed in 43 (63.2%) of 68 specimens. Reduced membranous beta-catenin protein expression was associated with the presence of distant metastasis (P = .006). Patients with reduced membranous beta-catenin expression had a worse prognosis than patients with normal membranous beta-catenin expression (P = .005). Patients with combined increased p53 and reduced membranous beta-catenin protein expression had the worst prognosis (P = .012). In a multivariate survival analysis, reduced membranous beta-catenin expression and nodal involvement were independent prognostic factors (P = .004 and .019, respectively). CONCLUSIONS: Immunohistochemical analysis revealed that reduced membranous beta-catenin protein expression was associated with the presence of distant metastasis and a poor prognosis in patients with esophageal squamous cell carcinoma. Combined increased p53 and reduced membranous beta-catenin protein expression indicated a very poor prognosis in patients with esophageal squamous cell carcinoma. Further investigation is needed to understand the roles of beta-catenin and p53 in the tumorigenesis and metastasis of esophageal squamous cell carcinoma.	esophagus
Influence of cell proportions and proliferation rates on FDG uptake in squamous-cell esophageal carcinoma: a PET study.	PURPOSE: We investigated the influence of cell proportions and proliferation activities on tumor maximum standard uptake value (SUV(max)) in patients with squamous-cell esophageal cancer (SCEC). METHODS: Sixteen (16) patients with untreated SCEC were examined with (18)F-flourodeoxyglucose positron emission tomography (FDG-PET). The tumor SUV(max) were calculated. Tumors were resected by transthoracic esophagectomy. Tissues were stained with hematoxylin and eosin for the measurement of cell proportions and MIB-1 for measurement of proliferation indices (PIs). Tumor SUV and histologic data were related by using multiple linear regression analysis. RESULTS: The mean proportion of tumor cells in the tumor site was 58.1% (+/-12.1%); the proportion of inflammatory cells was 34.2% (+/-14.2%); the PI of tumor cells was 70.5% (+/-11.8%); and the PI of inflammatory cells was 22.2% (+/-7.6%). The tumor PI was the only variable that was significantly associated with the FDG uptake in the tumor site (p = 0.04). The correlation was low (Pearson-coefficient Gamma = 0.51). The Pearson-correlation-coefficient between tumor SUV and the fraction of inflammatory cells was Gamma = 0.37 and between tumor SUV and PI of inflammatory cells Gamma = 0.13. CONCLUSIONS: In untreated SCEC-patients, the tumor maximum FDG uptake is weakly associated with the proliferation rate of tumor cells. In contrast, neither the proportion nor the PI of inflammatory cells in the tumor site significantly correlates with the maximum SUV and should not profoundly affect PET interpretations.	esophagus
Epinephrine stimulates esophageal squamous-cell carcinoma cell proliferation via beta-adrenoceptor-dependent transactivation of extracellular signal-regulated kinase/cyclooxygenase-2 pathway.	Esophageal cancer is the sixth leading causes of cancer-related death in the world. It is suggested that beta-adrenoceptor is involved in the control of cell proliferation, but its role in the pathogenesis of esophageal cancer remains unknown. We therefore studied the role of beta-adrenergic signaling in the regulation of growth of an esophageal squamous-cell carcinoma cell line HKESC-1. Results showed that both beta(1)- and beta(2)-adrenoceptors were expressed in HKESC-1 cells. Stimulation of beta-adrenoceptors with epinephrine significantly increased HKESC-1 cell proliferation accompanied by elevation of intracellular cyclic AMP levels, which were abolished by beta(1)- or beta(2)-selective antagonists. Epinephrine also increased extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation as well as cyclooxygenase-2 (COX-2) and cytosolic phospholipase A(2) expression, which were blocked by beta(1)- or beta(2)-selective antagonists. Moreover, epinephrine increased cyclin D(1), cyclin E(2), cyclin-dependent kinase (CDK)-4, CDK-6, and E(2)F-1 expression and retinoblastoma protein phosphorylation at Ser807/811, all of which were abrogated by beta(1)-adrenoceptor antagonist. Furthermore, epinephrine increased the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1 and -2 in a beta(2)-adrenoceptor-, mitogen-activated protein kinase/ERK kinase (MEK)-, and COX-2-dependent manner. MEK or COX-2 inhibitor also significantly inhibited HKESC-1 cell proliferation induced by epinephrine. Collectively, we demonstrate that epinephrine stimulates esophageal squamous-cell carcinoma cell proliferation via beta-adrenoceptor-dependent transactivation of ERK/COX-2 pathway. Stimulation of beta(1)- and beta(2)-adrenoceptors also elicits a differential response on the expression of cell cycle regulators. These novel findings may shed new light on the understanding of beta-adrenergic signaling in the control of esophageal cancer cell growth.	esophagus
Treatment of radioresistant stem-like esophageal cancer cells by an apoptotic gene-armed, telomerase-specific oncolytic adenovirus.	PURPOSE: Radioresistance may be caused by cancer stem cells (CSC). Because CSCs require telomerase to proliferate, a telomerase-specific oncolytic adenoviral vector carrying apoptotic tumor necrosis factor-related apoptosis-inducing ligand and E1A gene (Ad/TRAIL-E1) may preferentially target CSCs. EXPERIMENTAL DESIGN: We established two pairs of parental and radioresistant (R) esophageal carcinoma cell lines (Seg-1, Seg-1R and TE-2, TE-2R) by fractionated irradiation. Stem cell markers were measured by Western blotting and flow cytometry. Serial sorting was used to enrich stem-like side population cells. Telomerase activity, transgene expression, antitumor activity, apoptosis induction, and viral replication were determined in vitro and/or in vivo. RESULTS: Expression of the stem cell markers beta-catenin, Oct3/4, and beta(1) integrin in Seg-1R cells was 29.4%, 27.5%, and 97.3%, respectively, compared with 4.8%, 14.9%, and 45.3% in Seg-1 cells (P < 0.05). SP levels in Seg-1R and TE-2R cells were 14.6% and 2.7%, respectively, compared with 3.4% and 0.3% in Seg-1 and TE-2 cells. Serial sorting of Seg-1R SP cells showed enrichment of the SP cells. Telomerase activities in Seg-1R, Seg-1R SP, and TE-2R cells were significantly higher than in Seg-1, Seg-1R non-SP, and TE-2 cells, respectively (P < 0.05). Seg-1R and TE-2R cells were more sensitive to Ad/TRAIL-E1 than parental cells. Increased Coxsackie-adenovirus receptor and elevated transgene expressions were found in the radioresistant cells. Ad/TRAIL-E1 resulted in significant tumor growth suppression and longer survival in Seg-1R-bearing mice (P < 0.05) with no significant toxicity. CONCLUSION: Radioresistant cells established by fractionated irradiation display CSC-like cell properties. Ad/TRAIL-E1 preferentially targets radioresistant CSC-like cells.	esophagus
Exploratory factor analysis of squamous cell carcinoma of the esophagus in Uruguay.	In the period 1996--2004, a hospital-based, case-control study on diet and risk of squamous cell carcinoma of the esophagus was conducted in Montevideo, Uruguay. The study included 234 cases and 468 controls, frequency matched on age, sex, and residence. Factor analysis (principal components) was used to identify the major food patterns associated with esophageal cancer. The analysis of food groups led to the identification of four patterns, arbitrarily labeled as traditional, healthy, high-fat, and drinker. The traditional pattern was not associated with risk of esophageal carcinoma, whereas the healthy pattern displayed a strong inverse association with this malignancy [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.17-0.48, P value for trend < 0.0001]. Unexpectedly, the high-fat foods diet was also marginally protective (OR 0.60, 95% CI 0.36-1.01, P value for trend = 0.07). On the other hand, the drinker pattern displayed a twofold increase in risk of esophageal carcinoma (OR 2.03, 95% CI 1.17-3.51, P value for trend = 0.01). The present study suggests that factor analysis might contribute to the elucidation of the contribution of diet on human cancer. Because diet represents a complex set of highly correlated exposures, dietary patterns could be more explicative of the etiology of squamous cell carcinoma of the esophagus than the traditional reductionist approach.	esophagus
Mechanism of growth inhibitory effects of cyclooxygenase-2 inhibitor-NS398 on cancer cells.	Cyclooxygenase (COX)-2 appears to play an important role in gastrointestinal carcinogenesis, and COX-2 overexpression has been demonstrated both in esophageal adenocarcinomas and lymph nodes metastasis. The aim of our study was to investigate the mechanism of growth inhibitory effect of selective inhibition of COX-2 by NS-398 on human cancer cells. The esophageal cancer cell lines (EC9706) that express COX-2 permanently and hepatocellular carcinoma cell lines (SMMC7721) while no expression of COX-2 were studied. Two kinds of cell lines were treated with various concentrations of NS-398 (selective for COX-2 inhibition) at 0.01-0.1 mM for 24 h, 48 h and 72 h. Antiproliferation effect was measured by 3H-TdR incorporation. The cell apoptosis were determined by flow cytometry (FCM) and DNA fragmentation analysis. Survivin was detected by immunocytochemical technique. The growth inhibition could be induced by NS398 in a dose- and time-dependent manner in two kinds of cell lines. FCM analysis revealed a high sub-G1 cell peak in EC9706 group. Agarose electrophroesis showed marked apoptosis ladder pattern, but no apoptosis by NS-398 in SMMC7721. The difference of apoptosis percentage in EC9706 and SMMC7721 was (45.23 +/- 1.08)% and (3.05 +/- 0.15)% (p < 0.001). After 24 h incubation with NS-398 at concentration of 0.1 dmM, the expression of survivin was markedly reduced in EC9706, but not in SMMC7721. We conclude that the administration of a selective inhibitor of COX-2 significantly decreases cell growth in cancer cell lines by different mechanism. NS-398 could inhibit cell proliferation in cancer cells whether or no COX-2 expression. Nevertheless, apoptosis in the cancer cells expressing COX-2 protein increase more than those lacking COX-2.	esophagus
Modulating effects of fumonisin B1 and ochratoxin A on leukocytes and messenger cytokines of the human immune system.	Fumonisin B1 and ochratoxin A are mycotoxins of importance to public health and agro-economics. Although much is known about their cellular toxicity and carcinogenesis in animals, there are no reports of adverse effects on immune cells (leukocytes) or on the immune modulation of the molecular messengers (cytokines) in humans. This study was designed, therefore, to determine and compare the morphological effects of fumonisin B1 and ochratoxin A on lymphocytes and neutrophils harvested from the circulation of healthy volunteer subjects and patients with oesophageal and breast carcinomas. Both fumonisin B1 and ochratoxin A reduced the number of viable lymphocytes and neutrophils harvested from the circulation of volunteer subjects carcinoma patients in a dose-dependent manner. Leukocyte secretion of cytokines on exposure to the mycotoxins was evaluated by immunocytochemical methods. Expression of granulocyte-colony stimulating factor (G-CSF), tumour necrosis factor (TNF-alpha) and chemokine (CX3CR1) receptors were determined on the circulating leukocytes and the immunolabelling visualized by brightfield-and electron-microscopy. Cytokine levels were determined in the circulation of healthy volunteer subjects and in patients with oesophageal and breast carcinomas since they reflect the status of the immune system in humans. The findings of this study on immunocytes (leukocytes) and the immune molecular messengers (cytokines) suggest that fumonisin B1 and ochratoxin A have an immuno-suppressive effect in humans, in particular patients with cancer by impairing immune surveillance.	esophagus