crossing96/oncoscreening huggingface dataset:
Current and future treatment options for esophageal cancer in the elderly.	Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years). Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer. Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.	esophagus
Aberrant Methylation-Mediated Silencing of lncRNA MEG3 Functions as a ceRNA in Esophageal Cancer.	Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), has tumor-suppressor properties and its expression is lost in several human tumors. However, its biological role in esophageal squamous cell carcinoma (ESCC) tumorigenesis is poorly defined. The present study determined the role and methylation status of MEG3 in esophageal cancer cells and ESCC clinical specimens, and further observed the competing endogenous RNA (ceRNA) activity of MEG3 in the pathogenesis and development of ESCC. Significant downregulation of MEG3 was detected in esophageal cancer cells and ESCC tissues and the expression level of MEG3 was significantly increased in cancer cells after treated with the DNA methyltransferase inhibitor 5-Aza-dC. Upregulation of MEG3 led to the inhibition of proliferation and invasiveness of the cancer cells. The aberrant promoter hypermethylation of MEG3 indicates silencing of its expression. Furthermore, MEG3 acts as a ceRNA to regulate the expression of E-cadherin and FOXO1 by binding hsa-miR-9. Upregulation of miR-9 was detected in esophageal cancer cell lines and ESCC tissues, and miR-9 promoted esophageal cancer cell proliferation and invasion. Finally, downregulation and hypermethylation of MEG3 was associated with ESCC patients' survival.Implications: MEG3 functions as a tumor-suppressive lncRNA and aberrant promoter hypermethylation is critical for MEG3 gene silencing in ESCC. In addition, MEG3 acts as a ceRNA to regulate expression of E-cadherin and FOXO1 by competitively binding miR-9 and may be used as a potential biomarker in predicting ESCC patients' progression and prognosis. Mol Cancer Res; 15(7); 800-10. ©2017 AACR.	esophagus
Inflammatory cytokines are associated with response and prognosis in patients with esophageal cancer.	BACKGROUND: Esophageal cancer is often marked by aggressive tumor growth and poor prognosis. Patient groups who benefit from perioperative therapy are not yet defined. The tumor microenvironment and circulating factors as possible predictors of response and prognosis gain interest. This study aimed to investigate cytokines in patients' serum and tumor tissue with regard to response and prognosis. RESULTS: Median survival between SCC and AC was not different (published previously). Lower levels of CCL11 (Eotaxin-1) and CXCL10 (IP-10) in the tumor tissue were associated with a better prognosis (p = 0.022; p = 0.002). In the AC subgroup higher concentrations of TGF-β3 in serum and corresponding tumor tissue were associated with adverse prognosis (p = 0.035; p = 0.006). An association with histopathological response was found for IL-12(p70) and CXCL10 in patients' sera (p = 0.041; p = 0.032). The tissue levels of TGF-β1 and TGF-β2 were significantly lower in histopathological responders than in nonresponders (p = 0.033; p = 0.007). A similar trend was seen for TGF-β3, without statistical significance (p = 0.097). MATERIALS AND METHODS: Preoperative serum samples and corresponding tumor tissue (n = 54), only serum (n = 20) or only tissue (n = 4) were collected from patients undergoing surgery for cT3/4 esophageal squamous cell cancer (SCC) (n = 34) and adenocarcinoma (AC) (n = 44). All samples were taken after neoadjuvant treatment. All patients received perioperative chemo(radio)therapy. Cytokine levels of 17 different cytokines were measured by multiplex immunoassay and correlated with clinicopathological factors. CONCLUSIONS: Two chemokines (CCL11 and CXCL10) in posttherapeutic tumor tissue were associated with prognosis in patients with esophageal cancer, lower levels indicating a better prognosis. Lower levels of TGF-β were associated with better response and prognosis in patients with AC.	esophagus
A meta-analysis of CXCL12 expression for cancer prognosis.	BACKGROUND: CXCL12 (SDF1) is reported to promote cancer progression in several preclinical models and this is corroborated by the analysis of human tissue specimens. However, the relationship between CXCL12 expression and cancer survival has not been systematically assessed. METHODS: We conducted a systematic review and meta-analysis of studies that evaluated the association between CXCL12 expression and cancer survival. RESULTS: Thirty-eight studies inclusive of 5807 patients were included in the analysis of overall, recurrence-free or cancer-specific survival, the majority of which were retrospective. The pooled hazard ratios (HRs) for overall and recurrence-free survival in patients with high CXCL12 expression were 1.39 (95% CI: 1.17-1.65, P=0.0002) and 1.12 (95% CI: 0.82-1.53, P=0.48) respectively, but with significant heterogeneity between studies. On subgroup analysis by cancer type, high CXCL12 expression was associated with reduced overall survival in patients with oesophagogastric (HR 2.08; 95% CI: 1.31-3.33, P=0.002), pancreatic (HR 1.54; 95% CI: 1.21-1.97, P=0.0005) and lung cancer (HR 1.37; 95% CI: 1.08-1.75, P=0.01), whereas in breast cancer patients high CXCL12 expression conferred an overall survival advantage (HR 0.5; 95% CI: 0.38-0.66, P<0.00001). CONCLUSIONS: Determination of CXCL12 expression has the potential to be of use as a cancer biomarker and adds prognostic information in various cancer types. Prospective or prospective-retrospective analyses of CXCL12 expression in clearly defined cancer cohorts are now required to advance our understanding of the relationship between CXCL12 expression and cancer outcome.	esophagus
RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer.	Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3 Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals.	esophagus
Subsequent thoracic cancers among patients diagnosed with lung cancer: a SEER database analysis.	BACKGROUND: Population-based data on the development of subsequent thoracic cancers following the initial diagnosis of lung cancer are scarce. We evaluated this clinical scenario in lung cancer patients registered within the Surveillance, Epidemiology and End Results (SEER) database. METHODS: The SEER database (1988-2013) was queried using the SEER*Stat program to determine the clinico-pathological features of lung cancer patients who develop subsequent thoracic cancers as well as the characteristics of these subsequent cancers. Associations were ascertained with chi-squared tests and survival analysis was performed using Kaplan-Meier methods. Standardized incidence ratios (SIRs) were calculated to determine the risk of each type of subsequent cancer. RESULTS: A total of 223,274 lung cancer patients were identified and included in the current study. In this cohort, 6387 patients developed subsequent thoracic cancers. The following were associated with a higher likelihood of second cancers: female gender, younger age, white race, adenocarcinoma histology, married, lower AJCC stage, earlier year of diagnosis and local treatment with surgery rather than radiotherapy (p < .0001 for all parameters). In the subset of patients with subsequent thoracic cancers, survival was best for patients with second primary breast cancer followed by patients with lung or esophageal cancer (p < .0001). SIR analyses showed an excess risk for the development of esophageal cancer and second primary lung cancer following an initial diagnosis of lung cancer. This risk persists regardless of gender or receipt of radiotherapy (p < .05 for all scenarios). CONCLUSION: There is an excess risk for the development of esophageal cancer and second primary lung cancer following an initial lung cancer diagnosis. This risk is present irrespective of gender or receipt of radiotherapy.	esophagus
Impact of mutations in Toll-like receptor pathway genes on esophageal carcinogenesis.	Esophageal adenocarcinoma (EAC) develops in an inflammatory microenvironment with reduced microbial diversity, but mechanisms for these influences remain poorly characterized. We hypothesized that mutations targeting the Toll-like receptor (TLR) pathway could disrupt innate immune signaling and promote a microenvironment that favors tumorigenesis. Through interrogating whole genome sequencing data from 171 EAC patients, we showed that non-synonymous mutations collectively affect the TLR pathway in 25/171 (14.6%, PathScan p = 8.7x10-5) tumors. TLR mutant cases were associated with more proximal tumors and metastatic disease, indicating possible clinical significance of these mutations. Only rare mutations were identified in adjacent Barrett's esophagus samples. We validated our findings in an external EAC dataset with non-synonymous TLR pathway mutations in 33/149 (22.1%, PathScan p = 0.05) tumors, and in other solid tumor types exposed to microbiomes in the COSMIC database (10,318 samples), including uterine endometrioid carcinoma (188/320, 58.8%), cutaneous melanoma (377/988, 38.2%), colorectal adenocarcinoma (402/1519, 26.5%), and stomach adenocarcinoma (151/579, 26.1%). TLR4 was the most frequently mutated gene with eleven mutations in 10/171 (5.8%) of EAC tumors. The TLR4 mutants E439G, S570I, F703C and R787H were confirmed to have impaired reactivity to bacterial lipopolysaccharide with marked reductions in signaling by luciferase reporter assays. Overall, our findings show that TLR pathway genes are recurrently mutated in EAC, and TLR4 mutations have decreased responsiveness to bacterial lipopolysaccharide and may play a role in disease pathogenesis in a subset of patients.	esophagus
Partition-Defective 3 (PARD3) Regulates Proliferation, Apoptosis, Migration, and Invasion in Esophageal Squamous Cell Carcinoma Cells.	BACKGROUND Altered expression of partition-defective 3 (PARD3), a polarity-related gene associated with oncogenesis, has been identified in some cancers, but the role of PARD3 in esophageal squamous cell carcinoma (ESCC) remains unclear. MATERIAL AND METHODS PARD3 expression in Eca109 cells was silenced using siRNA and overexpressed using an expression vector. We investigated the role of PARD3 in ESCC growth and motility to evaluate its potential role in ESCC. Transwell assay was used to evaluated cell migration and invasion. PARD3 protein expression was assessed by Western blot. RESULTS PARD3 overexpression promoted apoptosis, impaired proliferation, and inhibited cell migration and invasion in Eca109 cells, while PARD3 silencing promoted proliferation and increased migration and invasion. Overexpression of PARD3 exerted its antitumor activity in vitro by impairing cell proliferation, inducing apoptosis, and inhibiting migration and invasion of Eca109 cells, suggesting that PARD3 might play a tumor suppressor role in ESCC. CONCLUSIONS Overexpression of PARD3 could be a promising new therapeutic intervention against ESCC.	esophagus
Esophageal Cancer Diagnosed by Thyroid Scintigraphy.	We report a 34-year-old man referred because of increasing dysphagia secondary to goiter. Thyroid scintigraphy and SPECT/CT images helped to recognize an unsuspected esophageal dilation due to a poorly differentiated adenocarcinoma arising at the lower end of the esophagus. Further examinations are mandatory when abnormal activities are observed during thyroid scintigraphy.	esophagus
Protective Effect of Dietary Calcium Intake on Esophageal Cancer Risk: A Meta-Analysis of Observational Studies.	Although several epidemiological studies have investigated the association between dietary calcium intake and the risk of esophageal cancer, the results are inconsistent. This study aimed to make a comprehensive evaluation regarding the association between calcium intake and risk of esophageal cancer through a meta-analysis approach. We searched for all relevant articles from the inception to April 2017, using PUBMED, EMBASE, and Web of Knowledge. The pooled odds ratio (ORs) with the 95% confidence interval (95% CI) for the highest versus the lowest categories of calcium intake was calculated using a Mantel-Haenszel fixed-effect model. In total, 15 articles reporting 17 studies including 3396 esophageal cancer cases and 346,815 controls were selected for the meta-analysis. By comparing the highest vs. the lowest levels of dietary calcium intake, we found that dietary calcium intake was inversely associated with the risk of esophageal cancer (OR = 0.80, 95% CI: 0.71-0.91, I² = 33.6%). The subgroup analysis indicated that the protective function of dietary calcium intake were observed in esophageal squamous cell cancer, but not in esophageal adenocarcinoma in the studies conducted in Asia, but not those in Europe and America. In conclusion, our results suggest that higher dietary calcium intake is associated with a lower risk of esophageal cancer-especially esophageal squamous cell cancer-in Asian populations, though more data from prospective cohort studies are needed.	esophagus
Can oesophagectomy be performed for patients with oesophageal carcinoma and concomitant liver cirrhosis? A retrospective study based on a propensity-matched cohort.	OBJECTIVES: For patients with oesophageal carcinoma and concomitant liver cirrhosis, the safety profile and postoperative prognosis of oesophagectomy are not clearly established due to the lack of relevant studies with large sample sizes. Our objective was to explore the surgical indications and postoperative prognosis in patients with oesophageal carcinoma and liver cirrhosis. METHODS: A total of 2226 patients with oesophageal carcinoma underwent curative oesophagectomy (37 with liver cirrhosis and 2189 without) in our department from April 2008 to September 2013. Overall, 37 patients with liver cirrhosis (30 Child-Pugh Grade A and 7 Child-Pugh Grade B) and a propensity-matched cohort of 74 patients without cirrhosis were analysed. We compared the rates of postoperative complications and 5-year survival in these 2 groups. In addition, we performed an analysis of any potential risk factors for death, including patient demographic information and of operation performed. RESULTS: A higher operative mortality rate was observed in patients with oesophageal carcinoma and liver cirrhosis compared to patients with oesophageal carcinoma but without cirrhosis (11 vs 1%, P = 0.042). Patients with cirrhosis included those with Child-Pugh Grade B (43%), preoperative moderate ascites (100%), a prothrombin time of ≥ 4 s (75%) and greater weight loss. Although the rates of surgical death and postoperative hydrothorax were significantly higher in patients with liver cirrhosis, the rates of other major complications and 5-year overall survival were not significantly different compared to patients without cirrhosis. CONCLUSIONS: Curative oesophagectomy is a feasible, beneficial treatment option for patients with oesophageal carcinoma and liver cirrhosis, with a higher perioperative risk but reasonable longer term survival compared to patients without cirrhosis.	esophagus
Single disease entity for both chromosomal instable subtype gastric adenocarcinoma and esophageal adenocarcinoma.	Gastric cardiac carcinoma (GCC) was and is considered as a part of esophageal adenocarcinoma (EAC) and staged with the rules for EAC. This may change. Recent comprehensive integrated genomic investigations on gastric and esophageal carcinomas discovered similar chromosomal instability profiles in these two groups of carcinomas with a gradual increasing gradient from the lowest percentage in the distal gastric antrum to a high level in the proximal gastric cardia, and to the peak of almost 100% in EAC. Therefore, most GCCs and EAC share similar chromosomal instable features of gastric carcinoma and should be grouped as a single disease entity because EAC may be the proximal extension of chromosomal instable GCCs. This breakthrough discovery in genomic characteristics of GCC and EAC would dramatically change the strategy on how patients should be appropriately managed clinically and also greatly help future investigation on detailed molecular pathogenetic mechanisms of GCC, leading to cure this fatal cancer.	esophagus
Improved xenograft efficiency of esophageal adenocarcinoma cell lines through in vivo selection.	The present study aimed to investigate the orthotopic growth potential of two generally available esophageal adenocarcinoma cell lines, OE33 and OACM5 1.C, and a third in vivo selected subpopulation, OACM5 1.C SC1. One group of mice was subcutaneously injected in the hind legs. Tumor growth was measured with calipers. Another group was injected orthotopically in the distal esophageal wall through median laparotomy. Tumor development was evaluated macroscopically and confirmed microscopically. A subset of mice was evaluated with magnetic resonance imaging (MRI) to follow tumor progression. Additionally, functional cell line characteristics were evaluated in vitro (clonogenic, collagen invasion and sphere formation assays, and protein analysis of cell-cell adhesion and cytoskeletal proteins) to better understand xenograft behavior. OE33 cells were shown to be epithelial‑like, whereas OACM5 1.C and OACM5 1.C SC1 were more mesenchymal-like. The three cell lines were non‑invasive into native type I collagen gels. In vivo, OE33 cells led to 63.6 and 100% tumor nodules after orthotopic (n=12) and subcutaneous (n=8) injection, respectively. Adversely, OACM5 1.C cells did not lead to tumor formation after orthotopic injection (n=6) and only 50% of subcutaneous injections led to tumor nodules (n=8). However, the newly established cell line OACM5 1.C SC1 resulted in 33% tumor formation when orthotopically injected (n=6) and in 100% tumors when injected subcutaneously (n=8). The higher xenograft rate of OACM5 1.C SC1 (P<0.05) corresponded with a higher clonogenic potential compared to its parental cell line (P<0.0001). All models showed local tumor growth without metastasis formation. In conclusion, OACM5 1.C has a poor tumor take rate at an orthotopic and ectopic site. A subpopulation obtained through in vivo selection, OACM5 1.C SC1, gives a significant higher take rate, ectopically. Furthermore, OE33 establishes orthotopic (and subcutaneous) xenografts in mice. These models can be of interest for future studies, and their slow growth rates are a challenge for therapeutic intervention.	esophagus
A Single Intercostal Space Thoracoscopic Approach for Minimally Invasive Ivor Lewis Esophagectomy.	OBJECTIVE: We present a laparoscopic and single intercostal space thoracoscopic approach (SICS group) for Ivor Lewis minimally invasive esophagectomy (MIE) and provide postoperative analgesia with a continuous multiple intercostal nerve blocking technique. The characters of this technique are evaluated. MATERIALS AND METHODS: From October 2015 to April 2016, 18 consecutive patients with esophageal cancer were treated with Ivor Lewis MIE by a SICS group. Moreover, from July 2014 to September 2015, 48 patients with esophageal cancer received Ivor Lewis MIE by four-port video-assisted thoracic surgery (VATS) approach. Among those patients, by using propensity-score matching, 18 matched patients who underwent four-port VATS MIE (four-port group) were retrospectively selected for further statistical analysis. Patient demographics, short-term postoperative outcomes were recorded. RESULTS: None of the patients in the SICS group required conversion to an open procedure. No failure of the intrathoracic esophagogastrostomy occurred. No perioperative mortality or readmission was observed in this series. No patient suffered from anastomotic leak or complained remarkable dysphasia during follow-up. SICS group had a shorter duration of both docking procedure and closure of chest incisions compared with four-port group. The visual analog scale (VAS) pain scores on 24 hours after surgery was significantly lower in SICS group than in four-port group, while the values on 6 hours were comparable. The level of creatine kinase on postoperative day (POD) 1 was significantly lower in SICS group than in four-port group. CONCLUSION: Single intercostal space thoracoscopic procedure is safe and technically feasible and can therefore be viewed as an attractive alternative approach for performing Ivor Lewis MIE.	esophagus