crossing96/oncoscreening huggingface dataset:
Comparison of two neoadjuvant chemoradiotherapy regimens in patients with potentially curable esophageal carcinoma.	The implementation of neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) patients has led to improved survival rates. Worldwide, different CRT regimens are applied. It is unknown how these regimens relate to each other regarding efficacy. Therefore, the aim of this study was to determine the preferred regimen regarding toxicity of, response to CRT, and long-term survival after esophagectomy in EC patients. EC patients in two centers who underwent CRT with different regimens prior to surgery were included in this study. CRT consisted of 50.4Gy combined with two cycles of cisplatin and 5-FU(center A), or 41.4Gy combined with five cycles of carboplatin and paclitaxel (center B). Toxicity, response to therapy and long-term survival were compared between groups. One hundred sisty-five patients were included. Forty-one percent of patients in center A developed ≥1 toxicity ≥ grade 3 versus 25% in center B (P = 0.025). CRT with a cisplatin-based regimen was an independent predictor for development of toxicity ≥ grade 3 (P = 0.043). There were no differences in response between both regimens (P = 0.904). Three-year survival was 61% (A) versus 57% (B) (P = 0.725). The carboplatin/paclitaxel/41.4Gy regimen causes less toxicity compared to the cisplatin/5-FU/50.4Gy regimen with nonsignificant differences in response rates and long-term survival; therefore our results support this regimen to be the preferred regimen for EC patients.	esophagus
Establishment and characterization of a paclitaxel‑resistant human esophageal carcinoma cell line.	The aim of this study was to establish a new paclitaxel (PTX)-resistant human esophageal squamous carcinoma (ESCC) cell line and investigate its biological characteristics. The resistant cell line (EC109/Taxol) was developed in vitro by intermittent exposure of the human ESCC cell line EC109 to a high concentration of PTX with time-stepwise increment over a period of 6 months. The MTT assay was performed to test the drug resistance of EC109 and EC109/Taxol cells. The morphological features were observed using inverted microscopy and apoptosis was measured by flow cytometry (FCM) and Hoechst 33258 fluorescence staining. Cell growth curves and colony formation of EC109 and EC109/Taxol cells were compared. FCM was also used to determine the distribution of the cell cycle. The protein levels of Bcl-2, Bax, Procaspase-3 and P-gp were detected by western blotting. P-gp activity was evaluated by Rh123 accumulation and efflux assay. In vivo resistance characterization was investigated. EC109/Taxol cells were 67.2-fold resistant to PTX in comparison with EC109 cells, and also exhibited cross-resistance to 5-fluorouracil (5-FU), cisplatin (CDDP) and epirubicin (EPI). FCM and Hoechst 33258 fluorescence staining confirmed that EC109 cells treated with PTX showed significantly higher percentage of apoptotic cells compared to EC109/Taxol cells. Simultaneously, EC109/Taxol cells exhibited changes in morphology, proliferation rate, doubling time, cell cycle distribution and colony formation rate were detected as compared with EC109 cells. The resistant cell line overexpressed Bcl-2, Procaspase-3 and P-gp protein, and showed decreased Bax expression. Further, EC109/Taxol cells did not change PTX resistance in vivo. This is the first report on the establishment of an EC109/Taxol cell line with higher resistance. Bcl-2, Bax, Procaspase-3 and P-gp are involved in the resistance of cell lines to PTX, which are invaluable tools to study the resistance of anticancer drugs and to identify the methods to overcome resistance.	esophagus
MiR-203 suppresses tumor growth and invasion and down-regulates MiR-21 expression through repressing Ran in esophageal cancer.	The expression of miR-203 has been reported to be significantly down-regulated in esophageal cancer. We showed here that overexpression of miR-203 in esophageal cancer cells dramatically increased cell apoptosis and inhibited cell proliferation, migration and invasion as well as tumor growth and down-regulated miR-21 expression. We subsequently identified that small GTPase Ran was a target gene of miR-203. Furthermore, Ran restoration partially counteracted the tumor suppressive effects of miR-203 and increased miR-21 expression. Taken together, our findings suggest that miR-203 may act as novel tumor suppressor in esophageal cancer through down-regulating the expression of Ran and miR-21.	esophagus
MiR-429 up-regulation induces apoptosis and suppresses invasion by targeting Bcl-2 and SP-1 in esophageal carcinoma.	PURPOSE: MicroRNAs (miRNAs) may act as oncogenes or tumor suppressor genes and, as such, they may play a role in cancer development. We investigated miR-429 expression levels in a cohort of esophageal carcinomas (EC) to assess its impact on EC cell growth, apoptosis and invasion. METHODS: qRT-PCR assays were used to quantify miR-429 expression levels in 32 paired EC samples and adjacent non-neoplastic tissues. Assays for cell growth, apoptosis, caspase activity and trans-well invasion were used to evaluate the effects of miR-429 expression on EC cells. Luciferase reporter and Western blotting assays were used to test whether the Bcl-2 and specificity protein 1 (SP1) mRNAs serve as major targets of miR-429. RESULTS: The expression levels of miR-429 in EC tissues were found to be lower than those in adjacent non-neoplastic tissues (P < 0.05). This relatively low expression was found to be significantly associated with the occurrence of lymph node metastases (P < 0.05). Apoptosis and migration rates were found to be significantly higher in two EC-derived cell lines (EC9706 and KYSE30) transfected with a miR-429 agomir (P < 0.05). Subsequent Western blotting and luciferase reporter assays showed that miR-429 can bind to putative binding sites within the Bcl-2 and SP1 mRNA 3' untranslated regions (UTRs) to reduce their expression. CONCLUSIONS: In primary EC tissues miR-429 is expressed at low levels. Up-regulation of miR-429 inhibits invasion and promotes apoptosis in EC cells by targeting Bcl-2 and SP1. Our findings suggest that Bcl-2 and SP1 may serve as major targets of miR-429. This study paves the way for a better understanding of the mechanism underlying EC pathogenesis and the development of novel, targeted therapies.	esophagus
Complications of gastro-oesophageal reflux disease.	Gastro-oesophageal reflux disease (GORD) is on the rise with more than 20% of the western population reporting symptoms and is the most common gastrointestinal disorder in the United States. This increase in GORD is not exactly clear but has been attributed to the increasing prevalence of obesity, changing diet, and perhaps the decreasing prevalence of H. pylori infection. Complications of GORD could be either benign or malignant. Benign complications include erosive oesophagitis, bleeding and peptic strictures. Premalignant and malignant lesions include Barrett's metaplasia, and oesophageal cancer. Management of both the benign and malignant complications can be challenging. With the use of proton-pump inhibitors, peptic strictures (i.e., strictures related to reflux) have significantly declined. Several aspects of Barrett's management remain controversial including the stage in the disease process which needs to be intervened, type of the intervention and surveillance of these lesions to prevent development of high grade dysplasia and oesophageal adenocarcinoma.	esophagus
Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma.	Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina's Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC.	esophagus
The esophagitis to adenocarcinoma sequence; the role of inflammation.	Esophageal adenocarcinoma (EAC) is the eighth most common cancer worldwide, and approximately 15% of patients survive 5years. Reflux disease (GERD) and Barrett's esophagus (BE) are major risk factors for the development of EAC, and epidemiologic studies highlight a strong association with obesity. The immune, inflammatory and intracellular signaling changes resulting from chronic inflammation of the esophageal squamous epithelium are increasingly well characterized. In GERD and Barrett's, an essential role for T-cells in the initiation of inflammation in the esophagus has been identified, and a balance between T-cell responses and phenotype may play an important role in disease progression. Obesity is a chronic low-grade inflammatory state, fueled by adipose tissue derived- inflammatory mediators such as IL-6, TNF-α and leptin, representing a novel area for targeted research. Additionally, reactive oxygen species (ROS) and receptor tyrosine kinase (RTK) activation may drive progression from esophagitis to EAC, and downstream signaling pathways employed by these molecules may be important. This review will explain the diverse range of mechanisms potentially driving and maintaining inflammation within the esophagus and explore both existing and future therapeutic strategies targeting the process.	esophagus
Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B.	Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia and these metabolic abnormalities may contribute to the progression of several obesity-associated cancers including oesophageal adenocarcinoma (OAC). We have examined the effects of leptin and adiponectin on OE33 OAC cells. Leptin stimulated proliferation, invasion and migration and inhibited apoptosis in a STAT3-dependant manner. Leptin-stimulated MMP-2 secretion in a partly STAT3-dependent manner and MMP-9 secretion via a STAT3-independent pathway. Adiponectin inhibited leptin-induced proliferation, migration, invasion, MMP secretion and reduced the anti-apoptotic effects: these effects of adiponectin were ameliorated by both a non-specific tyrosine phosphatase inhibitor and a specific PTP1B inhibitor. Adiponectin reduced leptin-stimulated JAK2 activation and STAT3 transcriptional activity in a PTP1B-sensitive manner and adiponectin increased both PTP1B protein and activity. We conclude that adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B. Relative adiponectin deficiency in obesity may contribute to the promotion of OAC.	esophagus
Personalized assessment of radiation risks from the one-stop-shop myocardial 256-slice CT examination.	BACKGROUND: This study provides data on the cumulative life attributable risk (LAR) of radiation-induced cancer from the combination of coronary CT angiography (CCTA), dynamic CT perfusion (CTP) and delayed enhancement (DE) CT scans, required for reliable risk-benefit analysis of the one-stop-shop CCTA + CTP + DECT cardiac examination. METHODS: Monte Carlo simulation of the dynamic CTP and DECT exposures on 62 adult individuals was employed to determine radiation absorbed dose to exposed radiosensitive organs. Corresponding data for CCTA were derived using patient chest circumference and previously published data. Individual-specific LARs of cancer were estimated using organ/tissue-specific radiogenic cancer risk factors. Total LAR from CCTA + CTP + DECT scans' sequence were estimated and compared to nominal intrinsic risk of cancer. RESULTS: The main contribution, up to 80%, to cumulative radiation burden from CCTA + CTP + DECT scan-sequence was found to originate from the CTP scan. The total LAR from CCTA + CTP + DECT for females was found 4-6 times higher, compared to males. The mean cumulative risk of radiogenic cancer associated with the complete CCTA + CTP + DECT scan sequence was found to marginally increase the intrinsic risk for cancer induction by less than 0.6% and 0.1% for females and males, respectively. CONCLUSIONS: The radiation risk from the 256-slice CCTA + CTP + DECT scan sequence may be considered low and should not constitute an obstacle for the clinical endorsement of the one-stop-shop cardiac CT examination, given that its clinical value has been well verified. Nevertheless, every effort should be made towards optimization of the dynamic CTP component which is the main contributor to patient radiation burden.	esophagus
Prevalence of lymph node metastases in superficial esophageal squamous cell carcinoma.	"OBJECTIVE: Endoscopic treatment of superficial esophageal carcinoma has been increasingly conducted around the world. Because no lymph nodes are removed in such a procedure, the risk of lymph node metastases (LNMs) should be clearly understood. The aim of the present study was to accurately clarify the pattern of lymphatic spread in patients with superficial esophageal squamous cell carcinoma and analyze the factors potentially related to LNMs. METHODS: The pattern of lymphatic spread was studied in 189 patients who had undergone radical lymphadenectomy from 2006 to 2011. The risk factors associated with LNMs were determined by multivariate logistic regression analysis. According to the depth of tumor invasion, mucosal tumors were classified as M1, M2, and M3 and submucosal tumors as SM1, SM2, and SM3. RESULTS: A total of 4252 lymph nodes were resected (average, 23 ± 9; range, 12-68). LNMs occurred in 49 patients (25.9%). The frequency of LNMs was 4.3% in those with mucosal and 33.1% in those with submucosal cancer. LNMs were found in 0%, 0%, 11.8%, 24.0%, 20.5%, and 43.8% of the M1, M2, M3, SM1, SM2, and SM3 cancer, respectively. For submucosal cancer, SM3 cancer (P = .006) and lymphovascular invasion (P = .001) were significant independent risk factors for LNMs. Paratracheal nodes were the most frequently involved. ""Skip"" metastases occurred in 20 of 49 patients (40.8%). CONCLUSIONS: Endoscopic treatment can be attempted when the tumor is limited to the lamina propria mucosa. However, 2-field radical lymphadenectomy with careful upper mediastinal lymph node resection should be conducted for submucosal squamous cell carcinoma."	esophagus
[Molecular biological review of esophageal cancer].	Esophageal squamous cell carcinoma accounts for most esophageal cancers in East Asia. Esophageal adenocarcinoma arises from Barrett's esophagus. However, patients with advanced disease remain poor prognosis. Therefore, it is needed to clarify the carcinogenic mechanism and cancer metastatic process in esophageal cancer. Here, we described the recent research approaches of microarray and next generation sequence in esophageal squamous cell carcinoma and esophageal adenocarcinoma.	esophagus
[Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport].	OBJECTIVE: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. RESULTS: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. CONCLUSIONS: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.	esophagus
[Clinical characteristics of lymph node metastasis in Siewert type II adenocarcinoma of the gastroesophageal junction].	OBJECTIVE: To explore the pattern of lymph node metastasis (LNM) in advanced Siewert type II adenocarcinoma of the gastroesophageal junction (AGEJ) in order to properly guide lymphadenectomy. METHODS: From January 2009 to Jun 2011, a total of 86 patients with advanced Siewert type II AGEJ underwent radical esophagogastrectomy by thoracic-abdominal incision and two-field lymphadenectomy. The clinical characteristics, pathologic features, LNM, and influence factor of thoracic metastasis were retrospectively analyzed. RESULTS: LNM was observed in 65 of the 86 cases (75.6%). Simple abdominal lymph node metastasis was observed in 49 of the 86 cases (57.0%), simple thoracic lymph node metastasis was 2.3%, and thoracic-abdominal metastasis was 16.3%, with a significant difference between the abdominal and thoracic metastatic patterns. LNM frequency was found in the lymph node groups No. 3, No. 1, No. 7, No. 110, No. 2 and No. 9 (from the highest to the lowest). The incidences of those lymph node metastases were 46.5%, 41.9%, 17.4%, 14.0%, 10.5%, and 5.8%, respectively. Vascular tumor embolus was the only independent factor for thoracic lymph node metastasis. CONCLUSIONS: Abdominal lymph node metastases of advanced Siewert type II AGEJ mainly occur around the proximal stomach and the coeliac trunk. The metastatic rate of distal stomach and splenic perihilar lymph nodes is low, but metastatic rate of the group No.110 lymph nodes is high. The thoracic lymph node metastasis is only correlated with vascular tumor embolus.	esophagus
Primary mucosa-associated lymphoid tissue lymphoma of the esophagus, manifesting as a submucosal tumor.	We report a case of primary mucosa-associated lymphoid tissue (MALT) lymphoma in the esophagus that manifested as a large submucosal tumor (SMT). Primary esophageal lymphoma is very rare, occurring in less than 1% of all patients with gastrointestinal lymphoma. Only a few cases of MALT lymphoma in the esophagus have been reported in the English literature. A 53-year-old man was referred to Dongguk University Ilsan Hospital (Goyang, Korea) in July 2012 for further evaluation and treatment of an esophageal SMT. Endoscopy showed a cylindrically elongated submucosal mass with normal overlying mucosa in the mid esophagus, 25-30 cm from the incisor teeth. He underwent surgery to confirm the diagnosis. Pathologic findings showed diffuse small atypical lymphoid cells which were stained with Bcl-2, CD20, but not with CD3, CD5, CD23, Bcl-6, or cyclin D1. These cells showed a positive monoclonal band for immunoglobulin heavy chain gene rearrangement. Based on the pathological, immunohistochemical, and molecular biological features, the esophageal mass was diagnosed as extranodal marginal zone B-cell lymphoma of the MALT type.	esophagus
Multiple polymorphisms within the PLCE1 are associated with esophageal cancer via promoting the gene expression in a Chinese Kazakh population.	Although recent genome-wide association studies of esophageal squamous cell carcinoma (ESCC) identified a susceptibility locus in phospholipase C epsilon 1 (PLCE1) in Chinese Han populations, few studies further confirmed these findings in pure Kazakh population in which there are higher incidence and mortality of ESCC. Here, we investigated the potential associations between 19 SNPs of PLCE1 and susceptibility to ESCC in 222 cases and 326 controls from a pure ethnic population of Kazakh. Real-time PCR and immunohistochemistry were performed to detect the PLCE1 expression levels and evaluate their association with PLCE1 polymorphism. We found that only 4 SNPs (rs753724, rs11187842, rs2274223, and rs12263737) with moderate linkage disequilibrium (LD) confer significantly increased risk of ESCC, with the ORs ranging from 1.43 to 2.04, and there was a risk allele dose-dependent increase in ESCC risk (P-trend=0.043). Especially, the risk effects of rs2274223 were more evident in poor differentiation and advanced clinical stages of Kazakh ESCC. Additionally, the significantly lowest PLCE1 mRNA expression was found in the KYSE-150 cell line having no risk alleles compared with other three cell lines having risk alleles, and the normal tissues of both homozygous mutant type of PLCE1 rs12263737 and rs2274223 had a higher PLCE1 staining score than that of homozygous wild type. Our findings suggested that genetic variants in PLCE1 might serve as candidate markers for Kazakh ESCC susceptibility, and these LD variants might influence ESCC risk individually and jointly by promoting the messenger RNA and protein expression of the gene.	esophagus