crossing96/oncoscreening huggingface dataset:
Thioridazine Sensitizes Esophageal Carcinoma Cell Lines to Radiotherapy-Induced Apoptosis In Vitro and In Vivo.	BACKGROUND Radiotherapy is one of the primary treatments for esophageal squamous cell carcinoma (ESCC). Identification of novel radio-sensitizing agents will improve the therapeutic outcome of radiotherapy. This study aimed to determine the radio-sensitizing effect of the antipsychotic agent thioridazine in ESCC and explored the underlying mechanisms. MATERIAL AND METHODS ECA-109 and TE-1 ESCC cells were treated with thioridazine and radiotherapy alone and in combination. Cell survival was measured by MTT assay. Cell cycle and apoptosis were monitored by flow cytometry. Western blot analysis was used to analyze the expression of phospho-PI3K, phosphor-AKT, phospho-mTOR, Caspase-3, Caspase-9, Bax, Bcl-2, Bal-xl, Bak, and p53. The xenograft mouse model was used to study the in vivo anticancer effect of thioridazine and irradiation. RESULTS Combined treatment with thioridazine and irradiation significantly reduced viability of ESCC cells compared with thioridazine or irradiation treatment alone. Thioridazine and irradiation treatment induced G0/G1 phases cell cycle arrest through down-regulation of CDK4 and cyclinD1. In addition, thioridazine and irradiation treatment induced apoptosis through up-regulation of cleaved capase-3 and 9, as well as an increase in the expression of Bax and Bak and a decrease in the expression of Bcl-2 and Bcl-xl. Furthermore, thioridazine and irradiation treatment inhibited the PI3K-AKT-mTOR pathway and up-regulated the expression of p53. In xenograft mice, thioridazine and irradiation reduced ESCC tumor growth. CONCLUSIONS Thioridazine sensitizes ESCC cells to radiotherapy. Thioridazine may play a role in ESCC radiation therapy as a promising radiosensitizer.	esophagus
Influence of body mass index on the long-term outcomes of patients with esophageal squamous cell carcinoma who underwent esophagectomy as a primary treatment: A 10-year medical experience.	We explored the influence of body mass index (BMI) on long-term outcomes in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy as a primary treatment. BMI is a risk factor for development of esophageal cancer. However, the details of the relationship between BMI and cancer prognosis remains unclear. Patients who underwent esophagectomy as an initial treatment in 2000 to 2009 period were included. The patients were divided into 3 groups according to Asian-specific BMI cut-offs. The associations between BMI and long-term outcomes were explored. This study included 1082 ESCC patients between 2000 and 2009; all the patients underwent esophagectomy. The median overall survival (OS) of the BMI <18.5, 18.5 ≤ BMI <23, and BMI ≥23 kg/m groups were 21, 24, and 29.5 months, respectively; they differed significantly (P = 0.005). The 5-year survival rates of the 3 groups were 24.6%, 30.4%, and 35.3%, respectively. Multivariate analysis showed that lower BMI was an independent risk factor for a shorter OS (18.5 ≤ BMI <23 kg/m vs. BMI ≥23 kg/m, hazard ratio [HR] = 1.18; 95% confidence interval [CI] = 1.00-1.40, P = 0.054, BMI <18.5 kg/m vs. BMI ≥23 kg/m, HR = 1.38; 95% CI = 1.09-1.75, P = 0.007). The better OS of the BMI ≥23 kg/m patients remained statistically significant in never-smoking patients (P < 0.05). In conclusion, patients with BMIs ≥23 kg/m experienced better OS, and multivariate analysis further indicated that BMI ≥23 kg/m was an independent predictor of survival. When stratified by smoking status, BMI ≥23 kg/m was still a factor in better OS among never smokers.	esophagus
CXCL12 expression promotes esophageal squamous cell carcinoma proliferation and worsens the prognosis.	BACKGROUND: The chemokine CXCL12 and its corresponding receptor CXCR4 are key players in the development of several cancers. Therefore, we hypothesized that there is a functional causality between CXCL12 expression and tumor progression in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We performed an immunohistochemical analysis in 79 consecutive patients with ESCC. We performed in vitro and in vivo cell proliferation assays using ESCC cell lines and a newly established transfectant stably overexpressing CXCL12. RESULTS: Immunohistochemistry revealed positive CXCR4 and CXCL12 expression in 48 (61 %) and 62 (78 %) patients, respectively. Additionally, the expression levels did not significantly correlate with any clinicopathological factors. The MIB-1 proliferation index was markedly higher in ESCC with a positive expression of CXCR4 or CXCL12. Positive CXCL12 expression was significantly correlated with lower recurrence-free survival (RFS, p = 0.02). Cox's hazard models revealed CXCL12 expression as an independent predictive factor for recurrence. In vitro, CXCL12 exposure or overexpression enhanced ESCC proliferation; and AMD3100, a specific inhibitor of CXCR4, equally decreased proliferation irrespective of CXCL12 exposure or overexpression. In the mouse model, AMD3100 significantly decreased ESCC tumor size (p = 0.03). CONCLUSIONS: CXCL12 stimulates ESCC proliferation, and its expression levels are related to lower RFS in patients with ESCC. Our findings indicate that positive CXCL12 expression may be a useful marker for predicting the outcome in patients with ESCC and is a potentially new therapeutic target for ESCC.	esophagus
Plasma matrix metalloproteinase 1 improves the detection and survival prediction of esophageal squamous cell carcinoma.	This study aimed to identify noninvasive protein markers capable of detecting the presence and prognosis of esophageal squamous-cell carcinoma (ESCC). Analyzing microarray expression data collected from 17-pair ESCC specimens, we identified one protein, matrix metalloproteinase-1 (MMP1), as a possibly useful marker. Plasma MMP1 was then measured by enzyme-linked immunosorbent assay (ELISA) in 210 ESCC patients and 197 healthy controls. ESCC patients had higher mean levels of MMP1 than controls (8.7 ± 7.5 vs. 6.7 ± 4.9 ng/mL, p < 0.0001). Using the highest quartile level (9.67 ng/mL) as cut-off, we found a 9.0-fold risk of ESCC in those with higher plasma MMP1 after adjusting for covariates (95% confidence interval = 2.2, 36.0). Heavy smokers and heavy drinkers with higher plasma MMP1 had 61.4- and 31.0 times the risk, respectively, than non-users with lower MMP1. In the survival analysis, compared to those with MMP1 ≤ 9.67 ng/mL, ESCC patients with MMP1 > 9.67 ng/mL had a 48% increase in the risk of ESCC death (adjusted hazard ratio = 1.48; 95% CI = 1.04-2.10). In conclusion, plasma MMP1 may serve as a noninvasive marker of detecting the presence and predicting the survival of ESCC.	esophagus
Barrett's oesophagus and associated dysplasia are not equally distributed within the esophageal circumference.	BACKGROUND: A careful endoscopic surveillance of Barrett's oesophagus is warranted to prevent esophageal cancer. AIM: To identify the preferred location of non-circumferential Barrett's oesophagus and associated dysplasia within the esophageal circumference. METHODS: We retrospectively reviewed a prospectively maintained database of patients with non-circumferential lesions. The location of metaplastic lesions and dysplastic lesions within the esophageal circumference was identified as on a clock face, and their distribution in the 4 quadrants was compared. RESULTS: Of overall 443 patients with Barrett's oesophagus, 192 (43%) were eligible for our study. Multiple lesions were diagnosed in 110 (57%) of them, for a total amount of 352 metaplastic areas. Barrett's oesophagus lesions were located significantly more in the posterior wall of the oesophagus (38.4%), rather than in the right wall (28.8%), the anterior wall (22.6%), or the left wall (10.2%) (P<0.0001). Among all metaplastic lesions, 28 were associated with dysplasia (7.9%), and one with adenocarcinoma (0.3%). Dysplastic lesions were significantly more common in the posterior wall (39.3%) than, respectively, in the anterior wall (35.8%), the right wall (21.4%) or the left wall (3.5%) (P=0.03). CONCLUSION: Our results show that the posterior wall of the oesophagus is the preferential location of both Barrett's oesophagus and associated dysplasia.	esophagus
Perioperative outcomes of esophageal cancer surgery in a mid-volume institution in the era of centralization.	BACKGROUND: Centralization of esophageal cancer surgery to high-volume institutions has been shown to improve perioperative outcomes in several studies. However, there is an ongoing debate, whether defined minimal annual hospital volumes for esophagectomies are required for quality assurance. The aim of the study was to assess perioperative outcomes of esophagectomies in a single institution in Switzerland. METHODS: Data from a database of esophagectomies performed between 2004 and 2013 was analyzed. Perioperative morbidity of esophagectomies due to cancer was assessed according to the Clavien-Dindo classification. Postoperative mortality was defined as death from any cause within the same hospital stay. RESULTS: A total of 143 operations (125 transthoracic esophagectomies, 18 extended transhiatal gastrectomies) were performed in the surveyed 10-year period. Two surgeons performed 91 % of all procedures. Postoperative morbidity was 43.4 %. Complications with a Clavien-Dindo score of III/IV (requiring surgical, endoscopic, or radiological intervention) occurred in 19 cases (13.4 %). The overall anastomotic leak rate was 3.5 %. Pulmonary complications were the most frequent postoperative problems involving 21 % of patients. In-hospital mortality was 0.7 %. Mean length of hospital stay was 17 days in patients with no complications and 22 days if there were any complications (p < 0.001). CONCLUSION: Esophageal cancer surgery is complex and has a significant risk of morbidity. The most common postoperative problems are pulmonary complications, usually responding well to non-invasive treatment. Appropriate patient selection and preparation, high surgeon volume, and a comprehensive multidisciplinary care pathway can provide a low perioperative mortality rate in a mid-volume institution.	esophagus
[Modified (Wu's) esophagectomy for a huge thoracic esophageal squamous cell carcinoma 18.3 cm in length].	An esophageal squamous cell carcinoma measuring 18.3 cm in length and 5 cm in diameter was found in the mediastinum of a 53-year man. The patient underwent a modified 3-stage esophagectomy and an esophagogastrostomy at the cervical level (Wu's method). The operation was performed smoothly and the patient recovered uneventfully after the operation. The patient was followed up for 6 months after discharge and reported no difficulties in eating with improved quality of life. This case represents the world's longest esophageal cancer that had been surgically removed. Local advanced esophageal cancer should be removed immediately to prevent potential occurrence of esophageal obstruction, tracheoesophageal fistula or aorto-esophageal fistula.	esophagus
The long noncoding RNA CASC9 regulates migration and invasion in esophageal cancer.	The objective of the study was to investigate the expression and functions of CASC9 in esophageal squamous cell carcinoma (ESCC). Long noncoding RNAs (lncRNAs) upregulated in ESCC tissues were detected by RNA sequencing. Expression of CASC9 was determined from clinical samples and cell lines by qRT-PCR. The effects of CASC9 knockdown on migration and invasion were evaluated by wound healing assay, cell migration and invasion assays in vitro. We found that the lncRNA, CASC9, was markedly upregulated in ESCC tissues. Furthermore, knockdown of CASC9 significantly suppressed cell migration and invasion in vitro. Furthermore, enhanced CASC9 expression level was correlated with differentiation. The results indicated that CASC9 is significantly upregulated in ESCC tissues and may represent a new marker of poor prognosis and a potential therapeutic target for esophageal cancer intervention.	esophagus
Transglutaminase 3 protein modulates human esophageal cancer cell growth by targeting the NF-κB signaling pathway.	It has recently been found that the expression of the transglutaminase 3 (TGM3) is significantly reduced in esophageal cancer (EC). However, the potential of TGM3 as a useful biomarker or as a molecular target for EC diagnosis and treatment is unclear. The aim of the present study was to explore the role of the TGM3 in EC. The expression level of TGM3 were measured by real-time polymerase chain reaction and western blot analysis in EC cell lines, including SKGT-4, KYSE-510, OE33, OE21 and the normal esophageal epithelial cell line HEEC; fifty-eight pairs of tissues samples were also measured. through exogenous expression of TGM3 in EC cells it was found that the expression of TGM3 is closely associated with tumor cell growth and apoptosis. TGM3 was found downregulated in EC and closely associated with tumor proliferation and migration. In addition, overexpression of TGM3 apparently induces EC cell proliferation, migration, invasion and promotes cell apoptosis in vitro. Subsequent experiments identified the NF-κB signaling pathway as direct target of TGM3. Our data collectively demonstrate that TGM3 can be a candidate tumor suppressor that is able to induce EC cell proliferation and migration by downregulating the NF-κB signaling pathway, indicating that TGM3 may serve as a useful biomarker and therapeutic target for EC treatment.	esophagus
TIM-3 promotes the metastasis of esophageal squamous cell carcinoma by targeting epithelial-mesenchymal transition via the Akt/GSK-3β/Snail signaling pathway.	T-cell immunoglobulin and mucin domain-con-taining protein-3 (TIM-3), a negative regulator of antitumor immune response, has been demonstrated to be involved in the onset and progression of several types of malignancies. The present study aimed to determine whether and how TIM‑3 plays such a role in esophageal squamous cell carcinoma (ESCC). TIM-3 expression was analyzed by immunohistochemistry and real‑time fluorescence quantitative PCR (qRT‑PCR) in ESCC and matched adjacent normal tissues. Functional experiments in vitro were performed to elucidate the effect of TIM‑3 knockdown on the proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT) in Eca109 and TE‑1 cell lines. Our data revealed that TIM‑3 expression was significantly elevated at both the mRNA and protein levels in ESCC tissues compared with the levels in the matched adjacent normal tissues (both P<0.001). TIM‑3 expression was significantly associated with lymph node metastasis (P=0.008), tumor‑node‑metastasis (TNM) stage (P=0.042) and depth of tumor invasion (P=0.042). In addition, we observed a strong correlation between high TIM‑3 expression and a worse overall survival of ESCC patients (P=0.001). Functional study demonstrated that TIM‑3 knockdown markedly inhibited proliferation, migration and invasion of ESCC cell lines without affecting apoptosis. In addition, TIM‑3 depletion was associated with downregulation of matrix metalloproteinase (MMP)-9 and upregulation of tissue inhibitor of metalloproteinase (TIMP)-1, and with reversion of EMT, as reflected by higher levels of the epithelial marker E‑cadherin and lower levels of the mesenchymal markers N‑cadherin and vimentin. Further study found that TIM‑3 depletion suppressed the signaling pathway involving p‑Akt, p‑GSK‑3β and Snail. Taken together, these results suggest that TIM‑3 is a novel therapeutic target and prognostic biomarker for ESCC and promotes metastasis of ESCC by inducing EMT via, at least partially, the Akt/GSK-3β/Snail signaling pathway.	esophagus
Survival After Neoadjuvant and Adjuvant Treatments Compared to Surgery Alone for Resectable Esophageal Carcinoma: A Network Meta-analysis.	OBJECTIVE: This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. SUMMARY BACKGROUND DATA: The optimal treatment for resectable esophageal cancer is unknown. METHODS: A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. RESULTS: In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). CONCLUSIONS: This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.	esophagus
Development of a novel handheld intra-operative laparoscopic Compton camera for (18)F-Fluoro-2-deoxy-2-D-glucose-guided surgery.	As well as pre-operative roadmapping by (18)F-Fluoro-2-deoxy-2-D-glucose (FDG) positron emission tomography, intra-operative localization of the tracer is important to identify local margins for less-invasive surgery, especially FDG-guided surgery. The objective of this paper is to develop a laparoscopic Compton camera and system aimed at use for intra-operative FDG imaging for accurate and less-invasive dissections. The laparoscopic Compton camera consists of four layers of a 12-pixel cross-shaped array of GFAG crystals ([Formula: see text] mm(3)) and through silicon via multi-pixel photon counters and dedicated individual readout electronics based on a dynamic time-over-threshold method. Experimental results yielded a spatial resolution of 4 mm (FWHM) for a 10 mm working distance and an absolute detection efficiency of 0.11 cps kBq(-1), corresponding to an intrinsic detection efficiency of  ∼0.18%. In an experiment using a NEMA-like well-shaped FDG phantom, a [Formula: see text] mm cylindrical hot spot was clearly obtained even in the presence of a background distribution surrounding the Compton camera and the hot spot. We successfully obtained reconstructed images of a resected lymph node and primary tumor ex vivo after FDG administration to a patient having esophageal cancer. These performance characteristics indicate a new possibility of FDG-directed surgery by using a Compton camera intra-operatively.	esophagus
Impact of phase I metabolism on uptake, oxidative stress and genotoxicity of the emerging mycotoxin alternariol and its monomethyl ether in esophageal cells.	Studies on the genotoxicity of Alternaria mycotoxins focus primarily on the native compounds. Alternariol (AOH) and its methyl ether (AME) have been reported to represent substrates for cytochrome P450 enzymes, generating hydroxylated metabolites. The impact of these phase I metabolites on genotoxicity remains unknown. In the present study, the synthesis and the toxicological effects of the metabolites 4-hydroxy alternariol (4-OH-AOH) and 4-hydroxy alternariol monomethyl ether (4-OH-AME) are presented and compared to the effects of the parent molecules. Although the two phase I metabolites contain a catecholic structure, which is expected to be involved in redox cycling, only 4-OH-AOH increased reactive oxygen species (ROS) in human esophageal cells (KYSE510), 4 times more pronounced than AOH. No ROS induction was observed for 4-OH-AME, although the parent compound showed some minor impact. Under cell-free conditions, both metabolites inhibited topoisomerase II activity comparable to their parent compounds. In KYSE510 cells, both metabolites were found to enhance the level of transient DNA-topoisomerase complexes in the ICE assay. Although the level of ROS was significantly increased by 4-OH-AOH, neither DNA strand breaks nor enhanced levels of formamidopyrimidine-DNA-glycosylase (FPG)-sensitive sites were observed. In contrast, AOH induced significant DNA damage in KYSE510 cells. Less pronounced or even absent effects of hydroxylated metabolites compared to the parent compounds might at least partly be explained by their poor cellular uptake. Glucuronidation as well as sulfation appear to have only a minor influence. Instead, methylation of 4-OH-AOH seems to be the preferred way of metabolism in KYSE510 cells, whereby the toxicological relevance of the methylation product remains to be clarified.	esophagus
The Prevalence of Overall and Initial Lymph Node Metastases in Clinical T1N0 Thoracic Esophageal Cancer: From the Results of JCOG0502, a Prospective Multicenter Study.	OBJECTIVE: To evaluate the sites and frequencies of overall and initial lymph node (LN) metastases (LNMs) of clinical T1N0 esophageal cancer. BACKGROUND: The sites and frequencies of initial LNMs and sentinel LNs (SLNs) of esophageal cancer remain unclear. METHODS: The Japan Clinical Oncology Group JCOG0502 trial was a 4-arm prospective study that compared esophagectomy with chemoradiotherapy for clinical T1N0 esophageal cancer in both randomized and patient-preference arms. The preoperative diagnostic accuracy was evaluated for patients assigned to the surgery arm. Patients who withdrew consent and who were not treated were excluded. All patients underwent esophagectomy with D2 or greater LN dissection. From the pathologic findings, sites and frequencies of LNMs and SLNs were assessed and the frequency of skip LNMs was calculated. RESULTS: In total, 211 patients underwent LNM and SLN analysis. Regarding N-factor accuracy, 57 (27.0%) of 211 clinical N0 cases had pathologic LNMs. The upper mediastinal and mediastinal/abdominal regions were frequent sites of LNMs in upper and lower thoracic cases, respectively. However, in middle thoracic cases, LNMs were observed in the neck, mediastinal, and abdominal regions, and pathologic SLN spread to all 3 fields. The frequency of skip LNMs was 36.7%. CONCLUSIONS: A clinical diagnosis of T1N0 is not sufficiently accurate, and therefore, it is unacceptable to omit LN dissection or minimize the prophylactic radiation field. SLNs, which are not location restricted, should be surveyed in all 3 fields.	esophagus