crossing96/oncoscreening huggingface dataset:
A novel human interleukin-24 peptide created by computer-guided design contributes to suppression of proliferation in esophageal squamous cell carcinoma Eca-109 cells.	Based on the three-dimensional modeling structure of human interleukin-24 (hIL-24) and its most likely active position predicted by solvent accessibility and apparent electrostatic properties, a novel hIL-24 peptide M1 was created by computer-guided molecular design. The cytotoxicity and cell selectivity of M1 were examined in three human carcinoma cell lines and one normal human embryo lung fibroblast cell line (HEL). MTT assay showed that M1 induced growth arrest in two IL-20 receptor complex-positive cancer cell lines (the esophageal squamous cell carcinoma cell line Eca-109 and the melanoma cell line A375), and antibodies against IL-24 or IL-20 receptor complexes significantly neutralized the inhibitory activity. Moreover, M1 had almost no cytotoxicity on the lung cancer A549 cell line, which lacks a full complement of the IL-20 receptor complexes, or on HEL cells that express the IL-20 receptor complexes. These findings demonstrate that M1 could act as an excellent candidate for the induction of growth arrest on receptor complex-positive cancer cells. In summary, the M1 peptide may represent a novel anticancer agent for esophageal squamous cell carcinoma therapy due to its cancer cell selectivity and its relatively low cytotoxicity to normal cells.	esophagus
Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia.	PURPOSE: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls. EXPERIMENTAL DESIGN: An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography-pyrolysis-isotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown. RESULTS: Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03). CONCLUSION: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.	esophagus
Long-term outcome after endoscopic submucosal dissection in patients with superficial esophageal squamous cell carcinoma: a single-center study.	BACKGROUND/AIMS: Superficial esophageal squamous cell carcinoma (SESCC) is being increasingly detected during screening endoscopy. Endoscopic submucosal dissection (ESD) allows for en bloc and histologically complete resection of lesions. This study assessed the technical feasibility and long-term outcomes of ESD for SESCCs. METHODS: Between January 2005 and August 2012, 27 patients with 28 SESCCs underwent ESD at Pusan National University Hospital. The en bloc and pathologically complete resection rates, complication (perforation and bleeding) rate, incidence of esophageal stricture after ESD, and overall and disease-specific survival rates were evaluated. RESULTS: The en bloc and pathologically complete resection rates were 93% and 83%, respectively. No significant bleeding occurred, and perforation with mediastinal emphysema was observed in two patients (7%). Post-ESD stricture occurred in two patients (7%) who had mucosal defects involving more than three-fourths of the esophageal circumference. During a mean follow-up of 23 months, local tumor recurrence was seen in two of four lesions with pathologically incomplete resection; one was treated by re-ESD, and the other was treated by surgical esophagectomy. The 5-year overall and disease-specific survival rates were 84% and 100%, respectively. CONCLUSIONS: ESD seems to be a feasible, effective curative treatment for SESCCs. All patients should be closely followed after ESD.	esophagus
Transthoracic approach is associated with increased incidence of atrial fibrillation after esophageal resection.	AIM: Atrial fibrillation (AF) has been associated with higher morbidity after esophagectomy. The objective of this study is to identify the surgical risk factors associated with new-onset atrial fibrillation after esophagectomy. METHODS: After Institutional Review Board approval, a prospectively maintained database was retrospectively queried to identify patients who underwent esophagectomy between 2003 and 2013. Data variables collected include pre-operative, intra-operative, and post-operative factors. Appropriate statistical analysis is performed utilizing Sigmaplot(®) version 12.3. RESULTS: From 2003 to 2013, 245 esophagectomies were performed at our institution, of these, 192 (147 males, mean age of 62 ± 11.12 years) were included in the final analysis and 53 were excluded [25 Roux-en-Y reconstruction (including three Merendino procedures), 20 had AF before surgery, and eight with staged esophagectomy]. Of 192 esophagectomies, 160 had malignancy (138 adenocarcinoma and 22 squamous cell carcinoma) and 106 (66.25%) received neo-adjuvant therapy. Esophagectomies were performed with Ivor Lewis Mckeown approach in 78 patients [34 Minimally Invasive (MIE), 37 open, and 7 Hybrid], Ivor Lewis approach in 56 patients (31 MIE, 10 Open, 15 Hybrid) and Transhiatal approach in 58 patients (16 MIE and 42 Open). Gastric conduit was used in 185 patients and colonic conduit in seven patients. Overall 30-day or in-hospital mortality was 3.6% (7/192). Forty-five (23.4%) patients with esophagectomy developed new-onset AF. Median onset of AF was post-op day 3 (0-32). They were older (65.7 vs. 61.3, p = 0.021), with medical comorbidities (thyroid disorder, hyperlipidemia, and coronary artery disease; p < 0.05) and lower diffusion capacity on Pulmonary function test (80.16 vs. 87.74%, p = 0.02) and stayed longer in hospital (19 vs. 14 days, p < 0.001) with severe post-operative complications (Clavien score ≥ III) (69 vs. 35.3%, p < 0.001). Multiple logistic regression analysis showed transthoracic approach (OR = 3.71, CI = 1.23-11.17, p = 0.02) and thyroid disorder (OR = 6.29, CI = 1.54-25.65, p = 0.01), and severe post-op complications (OR = 3.34, CI = 1.20-9.28, p = 0.02) were significantly associated with the development of new-onset AF. CONCLUSIONS: Transthoracic approach is an independent risk factor for the development of new-onset AF after esophagectomy. New-onset AF is associated with severe post-operative complications and longer hospital stay. Minimally invasive approach does not decrease the incidence of new-onset AF.	esophagus
p16 hypermethylation: a biomarker for increased esophageal cancer susceptibility in high incidence region of North East India.	Esophageal cancer is one of the most common cancers in North East India. The molecular mechanisms of esophageal cancer susceptibility in North East India have not been fully understood. There is a need for identification of biomarkers to identify people at risk of esophageal cancer. p16 is an essential G1 cell cycle regulatory gene whose loss of function is associated with carcinogenesis. Therefore, we conducted this study to determine the prevalence of p16 gene methylation in patients with esophageal cancer to assess the feasibility of using gene methylation as a biomarker. A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex, and ethnicity-matched controls were included in this study. Methylation-specific PCR was used to determine the p16 methylation status. Aberrant promoter methylation of the p16 gene was detected in 81 of 100 (81%) esophageal cancer cases. Hypermethylation of p16 gene was found to be influenced by lifestyle factors. Betel quid and tobacco chewing habit synergistically with p16 methylation elevated the risk for esophageal cancer development (adjusted odds ratio (OR) = 6.88, 95% confidence interval (CI) = 1.64-28.81, p = 0.003 for betel quid chewing and adjusted OR = 7.02, 95% CI = 1.87-26.38, p = 0.001 for tobacco chewing). Further, intake of green leafy vegetables and fruits lowered the risk of esophageal cancer (adjusted OR = 0.16, 95 % CI = 0.04-0.58, p = 0.05 for green leafy vegetables and adjusted OR = 0.15, 95% CI = 0.04-0.64, p = 0.01 for fruits). Thus, p16 hypermethylation may aid as a biomarker in identifying habitués at greater risk for esophageal cancer susceptibility in high incidence region of North East India.	esophagus
Antitumor effects and molecular mechanisms of figitumumab, a humanized monoclonal antibody to IGF-1 receptor, in esophageal carcinoma.	The insulin-like growth factor type 1 receptor (IGF-1R) plays an essential role in the development of numerous cancers. Figitumumab (CP) is not only a monoclonal antibody, it also has agonist activity on IGF-1R. The antitumor activity of CP in esophageal squamous cell carcinoma (ESCC) is still unclear. In our study, we identified IGF-1R as an independent prognostic factor in ESCC patients, and investigated the antitumor effects of CP in ESCC cell lines. CP suppressed tumor growth and sensitized cells to chemotherapeutic drugs. In addition, CP inhibited cell proliferation, migration, colony forming activity and anti-apoptosis induced by IGF-1. Our results showed that CP not only inhibited IGF-1 induced receptor autophosphorylation and downstream signaling, but also triggered β-arrestin1 and G protein-coupled receptor kinases (GRKs) mediated ERK1/2 activation, indicating CP as a biased agonist for IGF-1R. Inhibition of ERK1/2 enhanced the antitumor activity of CP. Furthermore, CP was a more powerful agonist for IGF-1R down-regulation than IGF-1, and dysregulation of β-arrestin1 and GRKs affected this down-regulation. Thus, we demonstrated antitumor activities of CP on ESCC, and as a biased agonist, CP induced ERK1/2 activation and receptor down-regulation required β-arrestin1 and GRKs, suggesting a promising role for targeting IGF-1R in ESCC.	esophagus
The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.	BACKGROUND: Loss of STAT1 (Signal Transducer and Activator of Transcription-1) has been implicated in the pathobiology of a number of cancer types. Nonetheless, the biological and clinical significance of STAT1 in esophageal squamous cell carcinomas (ESCC) has not been comprehensively studied. METHODS: Using immunohistochemistry, we detected the STAT1 expression in a cohort of ESCC patients; In-vitro experiments, we used enforced gene transfection of STAT1C into two STAT1- weak/negative ESCC cell lines and siRNA knockdown of STAT1 in two STAT1-strong ESCC cell lines to detect STAT1 function in ESCC. RESULTS: We found that the expression of STAT1 was heterogeneous in ESCC, with 64 (49.0%) strongly positive cases, 59 (45.0%) weakly positive cases and 8 (6.1%) negative cases. STAT1 expression inversely correlated with the depth of tumor invasion and tumor size (p=0.047 and p=0.029, respectively, Chi square). Furthermore, patients with STAT1-strong/weak tumors had a significantly longer survival compared to those with STAT1-negative tumors (33.6 months versus 13.1 months, p=0.019). In patients carrying tumors of aggressive cytology (n=50), those with STAT1-strong tumors survived significantly longer than those with STAT1-weak/negative tumors (34.6 months versus 20.5 months, p=0.011). Our in-vitro experiments revealed that STAT1 is proapoptotic and inhibitory to cell-cycle progression and colony formation. Lastly, we found evidence that STAT1 signaling in ESCC cells down-regulated the expression and/or activity of NF-κB and STAT3, both of which are known to have oncogenic potential. CONCLUSION: To conclude, our findings suggest that STAT1 is a tumor suppressor in ESCC. Loss of STAT1, which is frequent in ESCC, contributes to the pathogenesis of these tumors.	esophagus
Downregulation of VGLL4 in the progression of esophageal squamous cell carcinoma.	VGLL4, a member of the Vestigial-like (VGLL) proteins, has been reported to be dysregulated in several cancer types. However, its function in esophageal squamous cell carcinoma (ESCC) remains poorly understood. Here, it was found that the expression level of VGLL4 was decreased in ESCC tissues. Moreover, forced expression of VGLL4 in ESCC cells inhibited cell growth and migration, while knockdown of VGLL4 expression promoted the tumorigenecity of ESCC cells. Mechanistically, VGLL4 regulated the growth and motility of ESCC cells through downregulating the expression of connective tissue growth factor (CTGF), a known oncogene in the progression of ESCC. Taken together, our study suggested that downregulation of VGLL4 was very important in the progression of ESCC, and restoring the function of VGLL4 might be a promising therapeutic strategy for ESCC.	esophagus
Off-pump coronary artery bypass grafting via median sternotomy in a patient with a history of esophagectomy with substernal gastric tube reconstruction: report of a case.	We performed successful off-pump coronary artery bypass grafting (OPCAB) in a patient with unstable angina caused by triple-vessel disease, who had undergone esophagectomy with substernal gastric tube reconstruction for esophageal cancer 40 years earlier. Preoperative multidetector-row computed tomography was done to evaluate the course of the gastric tube and also that of the gastroepiploic artery, which feeds the gastric tube. Following careful sternal re-entry and adequate dissection, OPCAB was performed safely via a median sternotomy without injuring the gastric tube or causing hemodynamic instability. The patient had an uneventful early postoperative course.	esophagus
Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis.	Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.	esophagus
High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma.	BACKGROUND: Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). METHODS: A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. RESULTS: Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17). CONCLUSIONS: CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.	esophagus
A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer.	Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case-control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95% CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0.05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0.24 (95% CI 0.12, 0.49) for OAC, 0.31 (95% CI 0.15, 0.65) for OSCC, and 0.49 (95% CI 0.28, 0.84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population.	esophagus
Prognostic value of C-reactive protein in esophageal cancer: a meta-analysis.	"BACKGROUND: The classical inflammatory biomarker, C-reactive protein (CRP), has been identified to be related to progression of esophageal cancer. Some research showed that elevated pretreatment serum CRP indicated a poor prognosis, but results have been inconsistent. MATERIALS AND METHODS: We searched the Medline, Embase and the Cochrane Central Search Library for suitable studies and a meta-analysis of eleven (1,886 patients) was conducted to examine the relationship between elevated serum CRP level and overall survival (OS) in esophageal cancer cases. Moreover, correlation analyses were conducted to assess links between pretreatment serum CRP level and tumor node metastasis (TNM) stage as well as T, N, M grade, respectively. RESULTS: The pooled analysis showed that elevated pretreatment serum CRP level was significantly associated with poorer overall survival (HR 2.09, 95%CI 1.52-2.87, p<0.01). Subgroup analyses were conducted by ""country"", ""cut-off value"", ""treatment"" and ""number of patients"", and no single factor could alter the result. Elevated pretreatment serum CRP was significantly correlated with more advanced TNM stage and T, N, M grade respectively. CONCLUSIONS: Elevated pretreatment serum CRP levels are associated with poorer prognosis in esophageal cancer patients, and could serve as a useful biomarker for outcome prediction."	esophagus
A panel of overexpressed proteins for prognosis in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. In order to identify useful biomarkers for accurately classifying prognostic risks for ESCC patients, we examined the expression of six proteins by immunohistochemistry (IHC) in 590 paraffin-embedded ESCC samples. The candidate proteins include p53, EGFR, c-KIT, TIMP1 and PI3K-p110α reported to be altered in ESCC tissues as well as another important component of PI3K, PI3K-p85α. Of the six proteins tested, p53, EGFR, c-KIT, TIMP1 and PI3K-p85α were detected with high expression in 43.0%, 36.6%, 55.9%, 70.7% and 57.1% of tumors, respectively. Significant associations were found between high expression of PI3K-p85α, EGFR and p53 and poor prognosis (P = 0.00111; 0.00001; 0.00426). Applying these three proteins as an IHC panel could divide patients into different subgroups (P<0.000001). Multivariate cox regression analysis indicated that the three-protein panel was an independent prognostic factor with very high statistical significance (HR = 2.090, 95% CI: 1.621-2.696, P = 0.00000001). The data suggest that the three-protein panel of PI3K-p85α, EGFR and p53 is an important candidate biomarker for the prognosis of patients with ESCC.	esophagus
[Esophageal sarcomatoid squamous carcinoma: report of one case].	Sarcomatoid squamous carcinoma (ESC) is a rare esophageal neoplasm, with a clinical, etiological and pathological behavior that differs from squamous cancer. From the histological point of view it has a dual configuration. The squamous epithelial component is usually limited to small areas, while the major part is constituted by mesenchymatous (sarcomatoid) polypoid tissue. Treatment is esophagectomy or total esophagogastrectomy depending on the tumor location. Early detection is critical in terms of survival. For large lesions, preoperative chemo-radiotherapy can be considered. We report a 78-year-old male presenting with dysphagia. An upper gastrointestinal endoscopy showed a tumor located below the cardia. The patient was subjected to a total esophageal and gastric resection. In a second operation, the digestive transit was reconstituted in 2 steps. The pathology report informed a sarcomatoid squamous carcinoma. After 18 months of follow up, the patient is ambulatory.	esophagus