crossing96/oncoscreening huggingface dataset:
Characterization of tumor-suppressive function of SOX6 in human esophageal squamous cell carcinoma.	PURPOSE: By using cDNA microarray analysis, we identified a transcriptional factor, SOX6, was frequently downregulated in esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the role of SOX6 in human esophageal cancer development, and to examine the prevalence and clinical significance of SOX6 downregulation in ESCC. EXPERIMENTAL DESIGN: Expressions of SOX6 mRNA in 50 ESCCs and SOX6 protein in 300 ESCCs were investigated by semiquantitative RT-PCR and immunohistochemistry, respectively. The tumor-suppressive function of SOX6 was characterized by cell growth, foci formation, wound-healing and cell invasive assays, and tumor xenograft experiment. Western blot analysis was applied to detect protein expression levels. RESULTS: SOX6 was frequently downregulated in primary ESCCs in both mRNA level (29/50, 58%) and protein level (149/219, 68.0%), which was significantly associated with the poor differentiation (P = 0.029), lymph node metastases (P = 0.014), advanced TNM stage (P = 0.000), and disease-specific survival (P < 0.001). Multivariate analysis indicated that the downregulation of SOX6 (P = 0.000) was a significant independent prognostic factors for ESCC. Functional studies showed that SOX6 was able to suppress both in vitro and in vivo tumorigenic ability of ESCC cells. The tumor-suppressive mechanism of SOX6 was associated with its role in G1/S cell-cycle arrest by upregulating expressions of p53 and p21(WAF1/CIP1) and downregulating expressions of cyclin D1/CDK4, cyclin A, and β-catenin. CONCLUSIONS: We provided the first evidence that SOX6 is a novel tumor-suppressor gene in ESCC development and is a potential prognostic marker in ESCC.	esophagus
Incidence of esophageal carcinoma among Malays in North-Eastern Peninsular Malaysia: an area with an exceptionally low prevalence of Helicobacter pylori infection.	BACKGROUND: Obesity, gastroesophageal reflux, and Barrett's esophagus have all been linked to esophageal adenocarcinoma. In addition, the decline in Helicobacter pylori (H. pylori) infection in affluent societies has also been suggested to be a major factor in the recent rise in the incidence of esophageal adenocarcinoma. If H. pylori infection has a protective role, populations with a naturally low prevalence of H. pylori infection such as the ethnic Malays of Northeastern Peninsular Malaysia should have high rates of esophageal adenocarcinoma. AIM: To test this hypothesis, we investigated the incidence of esophageal carcinoma among the ethnic Malays of the state of Kelantan in Northeastern Peninsular Malaysia. METHODS: The pathology services in the state of Kelantan are provided by two main hospitals. The histopathological records of both hospitals were systematically examined to retrieve all cases of esophageal carcinoma diagnosed between 2004 and 2008. Incidence rates were determined based on the most recent population census. RESULTS: The age-standardized incidence rates (per 100,000 population) of esophageal adenocarcinoma among Malay men and women were 0.75 and 0.69, respectively. The corresponding rates for squamous cell carcinoma of the esophagus were 0.66 and 1.34, respectively. CONCLUSIONS: The low rates of adenocarcinoma and squamous cell carcinoma of the esophagus in the study area, despite the fact that H. pylori infection is virtually absent, does not support the hypothesis that the absence of H. pylori infection is a pivotal factor in the pathogenesis of these cancers.	esophagus
Six-month postoperative quality of life predicts long-term survival after oesophageal cancer surgery.	BACKGROUND: Patients treated with curatively intended surgery for oesophageal cancer have an approximately 30% chance of 5-year survival. Little is known about associations between postoperative health-related quality of life (HRQL) and long-term survival. HYPOTHESIS: Poor postoperative HRQL after curatively intended oesophageal cancer surgery is associated with a reduced long-term survival. METHODS: A Swedish nationwide cohort of oesophageal cancer patients, treated surgically between 2001 and 2005, was followed up until death or end of August 2009. Nine HRQL aspects were selected for analyses from EORTC QLQ-C30 and QLQ-OES18 questionnaires answered 6 months postoperatively. The HRQL measures were categorised into two groups: 'good function' versus 'poor function' and 'no or minor symptoms' versus 'symptomatic'. Associations between HRQL and survival were analysed using Cox proportional hazard ratios (HR) and 95% confidence intervals (CIs), adjusted for potential confounding factors. FINDINGS: All 401 oesophageal cancer patients who survived at least 6 months postoperatively and responded to the questionnaires were included. For each of the nine selected outcomes, poor scores were associated with an increased hazard ratio of mortality: global HRQL (HR=1.55; 95% CI 1.19-2:02), physical function (HR=1.56; 95% CI 1.23-1.99), social function (HR=1.52; 95% CI 1.19-1.94), fatigue (HR=1.65; 95% CI 1.30-2.11), pain (HR=1.45; 95% CI 1.22-1.87), dyspnoea (HR=1.54; 95% CI 1.19-2.01), appetite loss (HR=1.69; 95% CI 1.32-2.14), dysphagia (HR=1.69; 95% CI 1.13-2.51) and oesophageal pain (HR=1.29; 95% CI 1.02-1.65). INTERPRETATIONS: HRQL assessed 6 months after oesophageal cancer surgery can be used as a clinically useful prognostic factor.	esophagus
Phase I study of concurrent selective lymph node late course accelerated hyper-fractionated radiotherapy and pemetrexed, cisplatin for locally advanced esophageal squamous cell carcinoma.	The optimized concurrent chemoradiotherapy has not been established for patients with advanced esophageal squamous cell carcinoma (SCC). The aim of the present study was to evaluate the safety and efficacy of concurrent chemotherapy and selective lymph node (SLN) late course accelerated hyperfractionated (LCAF) intensity modulated radiotherapy (IMRT) for the patients with thoracic SCC. Twelve patients with T3-4N0-1M0-1a thoracic esophageal SCC were included. The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy protocol was as following: cisplatin 10 mg/m(2) on days 1-5 and 22-26, pemetrexed in escalating doses, from the base level of 500 mg/m(2) once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLTs). Secondary end point included determination of preliminary radiographic response rates. As a result, three patients were enrolled in dose level 1 with pemetrexed 500 mg/m(2) and nine patients in dose level 0 with 400 mg/m(2) , respectively. At dose level 1, DLTs occurred in two of three patients. However, only two of nine patients in Level 0 developed DLTs. The complete response and partial response were observed in eight and four patients, respectively. Furthermore, no patient experienced cancer progression with a median follow-up of 9 months. In conclusion, the concurrent SLN LCAF IMRT and chemotherapy is feasible. The MTD of pemetrexed in this regimen was 500 mg/m(2) and RD was 400 mg/m(2) . Although toxicities were common, the protocol was safe, well tolerated, and achieved an encouraging outcome.	esophagus
[Three cases of squamous cell carcinoma of the esophagus who underwent argon plasma coagulation as salvage treatment for locoregional failure or remnant tumor after chemoradiotherapy].	We report 3 cases of locoregional failure or remnant esophageal squamous cell carcinoma after chemoradiotherapy that were successfully treated by argon plasma coagulation (APC) as a salvage treatment. Ablation was performed using argon plasma coagulation APC300 (ERBE). A power setting of 60W and an argon gas flow of 1.8L/min was used. APC is able to be repeated multiply without adverse reaction, and is an effective treatment to control the tumor growth.	esophagus
Impact of G₂ checkpoint defect on centromeric instability.	Centromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that G(2) checkpoint defect promotes centromeric instability. Our observations from multiple approaches consistently support this hypothesis. We found that overexpression of cyclin B1, one of the pivotal genes driving G(2) to M phase transition, impaired G(2) checkpoint and promoted the formation of centromeric aberrations in telomerase-immortalized cell lines. Conversely, centromeric instability in cancer cells was ameliorated through reinforcement of G(2) checkpoint by cyclin B1 knockdown. Remarkably, treatment with KU55933 for only 2.5 h, which abrogated G(2) checkpoint, was sufficient to produce centromeric aberrations. Moreover, centromeric aberrations constituted the major form of structural abnormalities in G(2) checkpoint-defective ataxia telangiectasia cells. Statistical analysis showed that the frequencies of centromeric aberrations in G(2) checkpoint-defective cells were always significantly overrepresented compared with random assumption. As there are multiple pathways leading to G(2) checkpoint defect, our finding offers a broad explanation for the common occurrence of centromeric aberrations in cancer cells.	esophagus
Endoscopic resection and ablation versus esophagectomy for high-grade dysplasia and intramucosal adenocarcinoma.	BACKGROUND: Esophagectomy has been the traditional therapy for high-grade dysplasia and intramucosal adenocarcinoma. New endoscopic approaches allow treatment of these lesions with esophageal preservation. The aim of this study was to compare the outcome of endoscopic therapy with esophagectomy for high-grade dysplasia and intramucosal cancer. METHODS: A retrospective review was performed of all patients treated for high-grade dysplasia or intramucosal adenocarcinoma from 2001 to April 2010. RESULTS: Endoscopic therapy was performed in 40 patients (high-grade dysplasia = 22, intramucosal cancer = 18) and esophagectomy in 61 patients (high-grade dysplasia = 13, intramucosal cancer = 48). Endotherapy consisted of 102 endoscopic resections and 79 mucosal ablations (median 3 interventions per patient). In the endotherapy group, intramucosal cancer was completely resected in all patients. At last assessment, 10 patients have been converted to intestinal metaplasia without dysplasia and 21 to no residual intestinal metaplasia. Five patients have follow-up biopsy procedures pending after recent ablation, and esophagectomy was performed in 3 patients for failed endotherapy. A laparoscopic Nissen fundoplication has been performed in 8 patients after eradication of intestinal metaplasia. Esophagectomy resected the mucosal disease with negative margins in all patients. Compared with esophagectomy, endotherapy was associated with significantly lower morbidity (39% vs 0; P < .0001) and similar survival (94% at 3 years in both groups; median follow-up 34 months after esophagectomy vs 17 months after endotherapy; P = .0026). CONCLUSIONS: Endoscopic therapy for high-grade dysplasia or intramucosal cancer has lower morbidity than an esophagectomy and similar survival during short-term follow-up, but required multiple procedures in most patients. Both therapies are appropriate options, but preservation of the esophagus allows the option of a fundoplication for reflux control, perhaps further improving long-term quality of life.	esophagus
Prognostic relevance of β-catenin expression in T2-3N0M0 esophageal squamous cell carcinoma.	AIM: To study the expression of β-catenin in esophageal squamous cell carcinoma (ESCC) at stage T2-3N0M0 and its relation with the prognosis of ESCC patients. METHODS: Expression of β-catenin in 227 ESCC specimens was detected by immunohistochemistry (IHC). A reproducible semi-quantitative method which takes both staining percentage and intensity into account was applied in IHC scoring, and receiver operating characteristic curve analysis was used to select the cut-off score for high or low IHC reactivity. Then, correlation of β-catenin expression with clinicopathological features and prognosis of ESCC patients was determined. RESULTS: No significant correlation was observed between β-catenin expression and clinicopathological parameters in terms of gender, age, tumor size, tumor grade, tumor location, depth of invasion and pathological stage. The Kaplan-Meier survival curve showed that the up-regulated expression of β-catenin indicated a poorer post-operative survival rate of ESCC patients at stage T2-3N0M0 (P = 0.004), especially of those with T3 lesions (P = 0.014) or with stage IIB diseases (P = 0.007). Multivariate analysis also confirmed that β-catenin was an independent prognostic factor for the overall survival rate of ESCC patients at stage T2-3N0M0 (relative risk = 1.642, 95% CI: 1.159-2.327, P = 0.005). CONCLUSION: Elevated β-catenin expression level may be an adverse indicator for the prognosis of ESCC patients at stage T2-3N0M0, especially for those with T3 lesions or stage IIB diseases.	esophagus
ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.	"BACKGROUND AND OBJECTIVES: Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the ""Asian esophageal cancer belt"" along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. METHODS: A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. RESULTS: The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR) being 1.62 (95% CI: 1.49-1.76) and 3.86 (2.96-5.03) for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13). Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR = 13.46, 95% CI: 2.32-78.07). CONCLUSION: Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled with alcohol drinking or the ALDH2*504Lys allele."	esophagus
Microsatellite instability analysis and its correlation with hMLH1 repair gene hypermethylation status in esophageal pathologies including cancers.	Cancer development is associated with genetic instability. Identification of specific loci altered during carcinogenesis in a particular tissue gives scope for early detection and predicting the progressive nature of the tissue pathology. Instability at microsatellite loci is widely attributed to mismatch repair errors due to epigenetic alterations. Using three dinucleotide markers, D3S1313, D9S171, D17S250 and two mononucleotide markers BAT25, BATRII, we evaluated MSI in 97 cases enrolled for endoscopy of upper GI tract with symptoms of dyspepsia, reflux or dysphagia. We aimed at evaluating markers that reflect instability in esophageal malignancies, examine the prevalence of MSI in cancers and other pathologies of the esophagus, and determine the methylation status of hMLH1 gene in relation to MSI. 42% (21/50) cancers and 15.4%(2/13) precancers exhibited MSI where 85.7% cancers and 50% precancers with MSI, showed a hypermethylated hMLH1 promoter. Increased number of cases with repair gene methylation were seen with increasing severity of the esophageal pathology suggesting epigenetic progression parallels histologic changes. BAT25 and D3S1313 markers exhibited instability frequently and cases with MSI using these markers showed an abnormal hMLH1 promoter. Thus these markers were useful in identifying the mismatch repair phenotype. These two markers may be useful to screen cases for early cancer related changes, after validation on a larger sample.	esophagus
Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery.	The inability to repair DNA double-strand breaks (DSB) leads to radiosensitization, such that ionizing radiation combined with molecular inhibition of cellular DSB processing may greatly affect treatment of human cancer. As a variety of viral products interact with the DNA repair machinery, oncolytic virotherapy may improve the therapeutic window of conventional radiotherapy. Here, we describe the mechanistic basis for synergy of irradiation and OBP-301 (Telomelysin), an attenuated type-5 adenovirus with oncolytic potency that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 infection led to E1B55kDa viral protein expression that degraded the complex formed by Mre11, Rad50, and NBS1, which senses DSBs. Subsequently, the phosphorylation of cellular ataxia-telangiectasia mutated protein was inhibited, disrupting the signaling pathway controlling DNA repair. Thus, tumor cells infected with OBP-301 could be rendered sensitive to ionizing radiation. Moreover, by using noninvasive whole-body imaging, we showed that intratumoral injection of OBP-301 followed by regional irradiation induces a substantial antitumor effect, resulting from tumor cell-specific radiosensitization, in an orthotopic human esophageal cancer xenograft model. These results illustrate the potential of combining oncolytic virotherapy and ionizing radiation as a promising strategy in the management of human cancer.	esophagus
Molecular cloning and characterization of a novel esophageal cancer related gene.	We previously identified four novel cDNA fragments related to human esophageal cancer. One of the fragments was named esophageal cancer related gene 2 (ECRG2). We report here the molecular cloning, sequencing, and expression of the ECRG2 gene. The ECRG2 cDNA comprises a 258 bp nucleotide sequence which encodes for 85 amino acids with a predicted molecular weight of 9.2 kDa. Analysis of the protein sequence reveals the presence at the N terminus of a signal peptide followed by 56 amino acids with a significant degree of sequence similarity with the conserved Kazal domain which characterizes the serine protease inhibitor family. Pulse-chase experiments showed that ECRG2 protein was detected in both cell lysates and culture medium, indicating that the ECRG2 protein was extracellularly secreted after the post-translational cleavage. In vitro uPA/plasmin activity analysis showed the secreted ECRG2 protein inhibited the uPA/plasmin activity, indicating that ECRG2 may be a novel serine protease inhibitor. Northern blot analysis revealed the presence of the major band corresponding to a size of 569 kb throughout the fetal skin, thymus, esophagus, brain, lung, heart, stomach, liver, spleen, colon, kidney, testis, muscle, cholecyst tissues and adult esophageal mucosa, brain, thyroid tissue and mouth epithelia. However, ECRG2 gene was significantly down-regulated in primary esophageal cancer tissues. Taken together, these results indicate that ECRG2 is a novel member of the Kazal-type serine protease inhibitor family and may function as a tumor suppressor gene regulating the protease cascades during carcinogenesis and migration/invasion of esophageal cancer.	esophagus
Immunochemical staining of MT2-MMP correlates positively to angiogenesis of human esophageal cancer.	Matrix metalloproteinases (MMPs) play an important role in the pathological processes of degradation of extracellular matrix and destruction of basement membrane, which leads to tumor invasion and metastasis. In the present study, we investigated membrane-type 2 MMP (MT2-MMP) expression pattern in esophageal cancer tissues collected from 103 patients, and explored MT2-MMP expression pattern in correlation to patients' clinicopathological features, intratumoral angiogenesis and postoperative prognoses. The intensity of immunochemical staining of MT2-MMP was significantly positively correlated to the intratumoral angiogenesis of esophageal cancer tissues. Positive MT2-MMP immunoreactions were found in 85.4% of total tumor sections, whereas none or very weak MT2-MMP staining occurred in normal esophageal tissues. In addition, MT2-MMP immunochemical intensities were significantly correlated to tumor size, but not to patient's gender, age, invasion depth, lymph node metastasis and distant metastasis. Moreover, MT2-MMP levels could not be applied for predicting patients' survival rate although the H-score cut-off value showed the overall survival rate of patients with low MT2-MMP protein level to be better than those with high MT2-MMP protein level.	esophagus
Orthotopic fluorescent peritoneal carcinomatosis model of esophageal cancer.	AIM: Orthotopic models utilizing orthotopic implantation have been used for developing cancer models of multiple tumor entities. The aim of this study was to evaluate the role of orthotopic injection in establishing a model of esophageal cancer using a human green fluorescent protein (GFP) cell line of human esophageal carcinoma. MATERIALS AND METHODS: Nude mice were orthotopically injected in the abdominal esophagus with stably transfected GFP-PT1590 cells. Tumor progression was examined by fluorescence imaging. RESULTS: Fifty percent of animals developed extensive peritoneal spread without a distinct primary tumor at the injection site. Continuous and metastatic spread to the liver, lungs, and lymph nodes was also observed. Fluorescence imaging enabled fast and specific visualization of tumor progression without the need for anesthesia. Intraperitoneal and metastatic tumor spread of GFP-PT1590 esophageal carcinoma demonstrated a highly aggressive but heterogeneous behaviour. Although injection of the esophageal carcinoma cell line GFP-PT1590 did not lead to primary esophageal tumor development at the site of injection, 50% of the mice developed extensive peritoneal spread, as well as lymph node and organ metastasis. CONCLUSION: The orthotopic cell injection model resulted in peritoneal carcinomatosis of esophageal adenocarcinoma, which could be visualized in real time using fluorescence imaging.	esophagus