crossing96/oncoscreening huggingface dataset:
Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma.	BACKGROUND: Dysregulation of miRNAs is associated with cancer development by coordinately suppressing abundant target genes. Emerging evidence indicates that miR-31 plays a dual role in tumorigenicity. However, whether miR-31 plays as an oncogene in esophageal squamous cell carcinoma (ESCC) and the potential target molecules are still unclear. MiR-31 role in ESCC was investigated and an association of the target molecules with EMT was identified in the progression of ESCC. METHODS: Western blot assays and qRT-PCR was performed to detect the protein and mRNA levels. We investigated the role of miR-31 in the regulation of LATS2 expression in ESCC cell lines via functional assays both in vivo and in vitro. The luciferase reporter assays was conducted to confirm LATS2 is a potential target of miR-31. Immunohistochemistry was used to measure LATS2 and TAZ expression in normal and ESCC tissue. RESULTS: LATS2 is a component of the Hippo tumor-suppressive signaling pathway. Frequent loss of heterozygosity of LATS2 has been reported in esophageal cancer. We analyzed the reciprocal expression regulation of miR-31 and LATS2 and demonstrated that LATS2 expression was elevated by down-regulation of miR-31 at the post-transcriptional level in ESCC. Moreover, miR-31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3'-UTR, a key molecule in the Hippo pathway. Then, LATS2 consequently promoted the translocation of TAZ, which was examined using immunohistochemistry. Silencing of miR-31 significantly inhibited the cell proliferation, induced apoptosis and decreased the ability of migration/invasion in vitro. LATS2 impedes ESCC cell proliferation and invasion by suppressing miR-31, as well as mice xenograft model in vivo. Meanwhile, the nuclear localization of LATS2 constrained the phosphorylation of TAZ. Then, the expression level of TAZ was notably heightened with a high risk of recurrence compared to that observed in the low-risk patients, as well as, the higher expression associated with a poor survival. CONCLUSIONS: Our study demonstrated that overexpression of miR-31 undertook an oncogenic role in ESCC by repressing expression of LATS2 via the Hippo Pathway and activating epithelial-mesenchymal transition. LATS2 and TAZ could be potential novel molecular markers for predicting the risk of recurrence and prognosis of ESCC.	esophagus
Clinical Significance of New Magnetic Resonance Thoracic Ductography Before Thoracoscopic Esophagectomy for Esophageal Cancer.	BACKGROUND: Preoperative simulation of the thoracic duct using magnetic resonance thoracic ductography (MRTD) would enable a safe lymph node dissection near the thoracic duct and the prevention of chylothorax after an esophagectomy. The aim of this study was to determine whether MRTD is useful for preventing injury to the thoracic duct during surgery and for reducing the incidence of chylothorax after surgery. METHODS: We evaluated 130 patients who underwent preoperative MRTD followed by a thoracoscopic esophagectomy for the treatment of thoracic esophageal cancer between August 2014 and April 2017 (MRTD group). These patients were then compared with 160 patients with esophageal cancer who underwent a thoracoscopic esophagectomy without preoperative MRTD (non-MRTD group). RESULTS: Four patients in the non-MRTD group developed Type IIIB chylothorax (International Consensus on Standardization), while none of the patients in the MRTD group developed Type III chylothorax. Some type of abnormal finding was found during MRTD in 24 patients (18.5%). Among them, 13 patients (10.0%) exhibited abnormal divergence, which was the most frequent finding, followed by 5 patients (3.8%) with window formation and 2 patients (1.5%) with stitch formation. CONCLUSIONS: The present study revealed the frequencies of abnormal findings of the thoracic duct and of patients with false-negative MRTD findings. Injury to the thoracic duct can be avoided through the use of appropriate care during procedures performed in patients with abnormal findings on preoperative MRTD.	esophagus
Endoscopic Submucosal Dissection for Superficial Proximal Esophageal Neoplasia is Highly Successful.	OBJECTIVE: The aim of this study was to evaluate the outcomes of endoscopic submucosal dissection (ESD) for superficial proximal esophageal neoplasia. SUMMARY OF BACKGROUND DATA: The surgery for a tumor located in proximal esophagus is relatively difficult and leads to a high morbidity and mortality. ESD is a minimally invasive endoscopic treatment of superficial neoplasia of the gastrointestinal tract allowing en block resection with low recurrence rates; however, ESD for superficial proximal esophageal neoplasia is little known. METHODS: We retrospectively analyzed 102 consecutive patients who fit the inclusion criteria with 106 lesions who underwent ESD from February 2009 to July 2015 at the Zhongshan Hospital, Fudan University in Shanghai, China. During the study, the en bloc and pathologically complete resection rates, complication rate, incidence of esophageal stricture after ESD, disease-specific, and overall survival rates were evaluated. RESULTS: The mean age was 62 (45-84) years with 100% en bloc resection rate. The mean operation time was 48 (10-144) minutes. The mean diameter of the resected tumors was 2.9 (1.2-6.5) cm. The pathological diagnoses were high-grade intraepithelial dysplasia in 45 (42.5%) lesions, and the rest were squamous cell carcinoma with staging of intraepithelial in 18 (17.0%), lamina propria in 13 (12.3%), muscularis mucosa in 16 (15.1%), SM1 in 10 (9.4%), and SM2 or deeper in 4 (3.8%) of the lesions. The R0 resection rates were 94.3% (100/106). There was no delayed bleeding. Two small perforations observed were closed successfully with clips. Symptomatic esophageal strictures in 17 (16.7%) patients were treated by endoscopic balloon dilation with a mean of 4 (1-14) times and 88.2% (15/17) success. Additional treatments of esophagectomy or chemoradiotherapy were recommended to patients with SM1 or deeper neoplasia or incomplete resection. Local recurrence was observed in 3 (2.9%) cases. Fifteen patients were lost to follow-up. Five-year overall survival rate was 98% and disease-specific survival rate was 100%. The mean follow-up time was 33.6 months. CONCLUSIONS: ESD for the superficial proximal esophageal neoplasia is a safe and a very effective treatment method with a 100% 5-year disease-specific survival rate.	esophagus
Treatment utilization and outcomes in elderly patients with locally advanced esophageal carcinoma: a review of the National Cancer Database.	For elderly patients with locally advanced esophageal cancer, therapeutic approaches and outcomes in a modern cohort are not well characterized. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment type. Variables associated with treatment utilization were evaluated using logistic regression and survival evaluated using Cox proportional hazards analysis. Propensity matching (1:1) was performed to help account for selection bias. A total of 21,593 patients were identified. Median and maximum ages were 77 and 90, respectively. Treatment included palliative therapy (24.3%), chemoradiation (37.1%), trimodality therapy (10.0%), esophagectomy alone (5.6%), or no therapy (12.9%). Age ≥80 (OR 0.73), female gender (OR 0.81), Charlson-Deyo comorbidity score ≥2 (OR 0.82), and high-volume centers (OR 0.83) were associated with a decreased likelihood of palliative therapy versus no treatment. Age ≥80 (OR 0.79) and Clinical Stage III (OR 0.33) were associated with a decreased likelihood, while adenocarcinoma histology (OR 1.33) and nonacademic cancer centers (OR 3.9), an increased likelihood of esophagectomy alone compared to definitive chemoradiation. Age ≥80 (OR 0.15), female gender (OR 0.80), and non-Caucasian race (OR 0.63) were associated with a decreased likelihood, while adenocarcinoma histology (OR 2.10) and high-volume centers (OR 2.34), an increased likelihood of trimodality therapy compared to definitive chemoradiation. Each treatment type demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49) to trimodality therapy (HR 0.25) with significance between all groups. Any therapy, including palliative care, was associated with improved survival; however, subsets of elderly patients with locally advanced esophageal cancer are less likely to receive aggressive therapy. Care should be taken to not unnecessarily deprive these individuals of treatment that may improve survival.	esophagus
The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma.	The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial-to-mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters. Immunohistochemical staining for Notch intracellular domain (NICD) was performed on 60 consecutive cases of esophageal squamous cell carcinoma, 42 cases of benign esophageal squamous epithelium, and 13 cases of eosinophilic esophagitis diagnosed in our department from 2007 through 2015, and exact nuclear staining and nuclear characteristics were graded using the Vectra imaging system. Clinicopathologic data (gender, age at diagnosis, smoking status, tumor grade, tumor stage, tumor location, and survival) were collected for each SCC case and these were correlated with NICD staining. Cases of esophageal SCC demonstrated significantly higher NICD staining compared to cases of benign and reactive esophageal epithelium (P=.003 and .005, respectively). Among cases of esophageal SCC, nuclear NICD staining was significantly correlated with both tumor grade and stage. Following classification and regression tree analysis, esophageal SCC patients with increased NICD expression were found to be more likely to die from their disease than those with lower levels of expression. Taken together, the findings suggest that increased Notch 1 may contribute to the development and aggressiveness of esophageal SCC.	esophagus
A 17-molecule set as a predictor of complete response to neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer.	"BACKGROUND: Recently, neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (NAC-DCF) was identified as a novel strong regimen with a high rate of pathological complete response (pCR) in advanced esophageal cancer in Japan. Predicting pCR will contribute to the therapeutic strategy and the prevention of surgical invasion. However, a predictor of pCR after NAC-DCF has not yet been developed. The aim of this study was to identify a novel predictor of pCR in locally advanced esophageal cancer treated with NAC-DCF. PATIENTS AND METHODS: A total of 32 patients who received NAC-DCF followed by esophagectomy between June 2013 and March 2016 were enrolled in this study. We divided the patients into the following 2 groups: pCR group (9 cases) and non-pCR group (23 cases), and compared gene expressions between these groups using DNA microarray data and KeyMolnet. Subsequently, a validation study of candidate molecular expression was performed in 7 additional cases. RESULTS: Seventeen molecules, including transcription factor E2F, T-cell-specific transcription factor, Src (known as ""proto-oncogene tyrosine-protein kinase of sarcoma""), interferon regulatory factor 1, thymidylate synthase, cyclin B, cyclin-dependent kinase (CDK) 4, CDK, caspase-1, vitamin D receptor, histone deacetylase, MAPK/ERK kinase, bcl-2-associated X protein, runt-related transcription factor 1, PR domain zinc finger protein 1, platelet-derived growth factor receptor, and interleukin 1, were identified as candidate molecules. The molecules were mainly associated with pathways, such as transcriptional regulation by SMAD, RB/E2F, and STAT. The validation study indicated that 12 of the 17 molecules (71%) matched the trends of molecular expression. CONCLUSIONS: A 17-molecule set that predicts pCR after NAC-DCF for locally advanced esophageal cancer was identified."	esophagus
Solitary Orbital Metastasis in Carcinoma Esophagus: Findings on Serial 18F-FDG PET/CT Scans.	Orbital metastasis is an uncommon and atypical presentation of recurrent esophageal cancer that has been only seldom reported in literature. F-FDG PET/CT is routinely performed for staging and response assessment in patients with esophageal carcinoma. This case demonstrates use of follow-up FDG PET/CT scans in characterizing solitary metastatic disease in orbit and in evaluating response to therapy. It also highlights a key teaching point that postradiation-related inflammatory/infective changes may interfere in accurate assessment of PET/CT scan; however, frequently used clinical and radiological correlation may not be entirely sufficient to rule out pathological involvement.	esophagus
Germline variant in MSX1 identified in a Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma.	The vast majority of esophageal adenocarcinoma cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of Barrett's esophagus and esophageal adenocarcinoma. This observation suggests that one or more hereditary factors may play a role in the initiation of Barrett's esophagus and esophageal adenocarcinoma in these families. A Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma was identified. Normal DNA obtained from the proband diagnosed with Barrett's esophagus was analyzed with SNP array and exome sequencing. A custom-made panel consisting of potential germline variants was verified in the normal DNA of the affected family members. In addition, the respective tumors were analyzed for somatic loss of the wild type allele or the presence of an inactivating somatic mutation in the wild type allele. Exome sequencing revealed 244 candidate variants in the normal DNA of the proband, of which 212 variants were verified successfully. After the normal DNA of the affected family members was analyzed for the presence of the 212 potential germline variants and subsequently the respective tumors, only one potential germline variant in MSX1 (chr4: 4861985 T > G, c.359T > G, p.V120G, NM_002448) showed loss of the wild type allele in the tumor DNAs of the affected family members. A germline variant in MSX1 was identified in a Dutch family with clustering of Barrett's esophagus and esophageal adenocarcinoma. This finding indicates that the germline defect in MSX1 may be associated with Barrett's esophagus and cancer in this particular family.	esophagus
Comparative Analysis of Clinical, Treatment, and Survival Characteristics of Basaloid and Squamous Cell Carcinoma of the Esophagus.	BACKGROUND: Basaloid squamous cell carcinoma (BSC) is a rare variant of squamous cell carcinoma (SqCC) of the esophagus. Even though pathologically thought to be more aggressive than SqCC, there is discrepancy in the literature regarding the outcomes of BSC compared with those of SqCC. STUDY DESIGN: We conducted a retrospective cohort study using the Surveillance Epidemiology and End Results (SEER) database. All patients with a histologic diagnosis of BSC and SqCC between 2004 and 2013 were included. We compared treatment and survival characteristics of patients with BSC and SqCC. RESULTS: There were 16,158 patients included in this study; 173 patients (1.1%) had BSC. There were no significant differences between the 2 groups based on age, sex, marital status, insurance, or geographic region of diagnosis, but patients with BSC were more likely to be Caucasian (73.4% vs 64.7%; p = 0.017). Among staged patients, baseline tumor stage was similar in both groups. However, BSC tumors were more likely to be of high pathologic grade (56.8% vs 38.2%; p < 0.001). Patients with SqCC were more likely to receive radiation therapy (36.9% vs 53.9%; p < 0.001), while patients with BSC were more likely to undergo resection (32.4% vs 17.0%; p < 0.001). Median overall survival was similar in both groups (14 vs 9 months; log rank = 0.144), and this relationship persisted after stratification by treatment. CONCLUSIONS: Even though more likely to be poorly differentiated at presentation, BSC of the esophagus seems to have similar clinical features and survival outcomes when compared with SqCC. Patients with BSC and SqCC should undergo stage-specific treatment to achieve optimal outcomes.	esophagus
Gastrointestinal Malignancies.	This article reviews esophageal, gastric, and colon cancers for the primary care physician. Risk factors, demographics, and screening are discussed. The rise of Western lifestyle has been a mixed blessing for these cancers. Our modern world has led to the decline of gastric cancer from the leading cause of cancer death before the 1930s to the 13th leading cause of cancer death now. Conversely, esophageal cancer is increasing faster than any other cancer. Screening for esophageal and gastric cancer is not practical in the West, but screening for colon cancer is gratifying for the patient and physician.	esophagus
Deguelin, an Aurora B Kinase Inhibitor, Exhibits Potent Anti-Tumor Effect in Human Esophageal Squamous Cell Carcinoma.	Aurora B kinase has emerged as a key regulator of mitosis and deregulation of Aurora B activity is closely related to the development and progression of human cancers. In the present study, we found that Aurora B is overexpressed in human esophageal squamous cell carcinoma (ESCC), high levels of Aurora B protein were associated with a worse overall survival rate in ESCC patients. Depleting of Aurora B blunted the malignant phenotypes in ESCC cells. Importantly, we demonstrated that a natural compound, deguelin, has a profound anti-tumor effect on ESCC via inhibiting Aurora B activity. Deguelin potently inhibited in vitro Aurora B kinase activity. The in silico docking study further indicated that deguelin was docked into the ATP-binding pocket of Aurora B. Inhibition of Aurora B activity attenuated growth of ESCC cells, resulted in G2/M cell cycle arrest, polyploidy cells formation, and apoptosis induction. Knocking down of Aurora B decreased the sensitivity of ESCC cells to deguelin. The in vivo results showed that deguelin blocked the phosphorylation of histone H3 and inhibited the growth of ESCC tumor xenografts. Overall, we identified deguelin as an effective Aurora B inhibitor, which deserves further studies in other animal models and ESCC treatment.	esophagus
Issues in the management of esophageal cancer and geriatric patients.	Esophageal cancer is a disease occurring in older adults and given the aging population, the incidence of cancer in the elderly will continue to rise. However, older patients are less likely to receive treatment for their cancers based on age alone. There are limited data and guidelines for how to manage the older patient population but elderly patients can derive benefit from treatment. This review will describe issues specific to older patients with esophageal cancer with a focus on the utilization of geriatric assessment (GA) tools and how to apply geriatric principles to this cancer patients.	esophagus
Screening and prevention strategies and endoscopic management of early esophageal cancer.	Esophageal cancer is the 8th most common cancer worldwide and the 6th most common cause of cancer-related death. Its two main subtypes, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), have varying incidences globally, but recent decades have seen a demonstrated rise of EAC in Western countries whereas ESCC remains highly prevalent in Eastern Africa, Central Asia, and China. Screening interventions have focused on using endoscopy to identify Barrett's esophagus (BE) as a precursor to EAC, and squamous cell dysplasia prior to onset of ESCC. However, additional cost-effective screening interventions that can be applied to larger populations at risk for esophageal cancer are needed. Advances in endoscopic ablative techniques and endoscopic resection via endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have proven to be effective in eradicating dysplasia and early stage cancer. Preventive strategies involving reduction in tobacco and alcohol consumption as well as regular use of proton pump inhibitors and nonsteroidal anti-inflammatory drugs are aimed at reducing the incidence of dysplasia and esophageal cancer, but require further study before being recommended for widespread use.	esophagus
Surgical management of esophageal cancer.	Esophageal cancer (EC) is an aggressive malignancy associated with an overall poor prognosis. The specific risk factors for EC vary by histologic type as well as geographic distribution but there is no widely applicable screening strategy to date. Patients can present with vague symptoms which can prove to be a diagnostic challenge. Furthermore, cases tend to present at a late stage, making therapeutic approach difficult. Despite ongoing changes in management strategy, surgery remains the only viable option for cure in early stage malignancy. Advances in operative and peri-operative management have led to a relatively safe and efficacious procedure that provides durable therapy. Additionally, careful consideration of procedure specific factors can help maximize patient benefit. This review focuses on the surgical approaches to the management of EC and highlights select current trends and recent advances.	esophagus
Radiation techniques for esophageal cancer.	Radiotherapy plays a crucial role in the curative management of localized esophageal cancer, both as definitive and preoperative therapy. For definitive therapy, the standard radiation dose is 50.4 Gy in 28 fractions and should be delivered with concurrent chemotherapy. Chemoradiotherapy also has a wellestablished benefit in the preoperative setting, as established in the CROSS randomized trial. Radiation fields are typically generous, to account for subclinical extension of disease along the esophagus and to regional nodes. Three-dimensional conformal radiation is the current standard technique for esophageal cancer, though intensity-modulated radiation therapy is increasingly utilized and may improve the outcomes of esophageal radiotherapy by reducing radiation dose to critical normal tissues.	esophagus