crossing96/oncoscreening huggingface dataset:
Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and is highly resistant to current treatments. ESCC harbors a subpopulation of cells exhibiting cancer stem-like cell (CSC) properties that contribute to therapeutic resistance including radioresistance, but the molecular mechanisms in ESCC CSCs are currently unknown. Here, we report that ribosomal S6 protein kinase 4 (RSK4) plays a pivotal role in promoting CSC properties and radioresistance in ESCC. RSK4 was highly expressed in ESCC CSCs and associated with radioresistance and poor survival in patients with ESCC. RSK4 was found to be a direct downstream transcriptional target of ΔNp63α, the main p63 isoform, which is frequently amplified in ESCC. RSK4 activated the β-catenin signaling pathway through direct phosphorylation of GSK-3β at Ser9. Pharmacologic inhibition of RSK4 effectively reduced CSC properties and improved radiosensitivity in both nude mouse and patient-derived xenograft models. Collectively, our results strongly suggest that the ΔNp63α/RSK4/GSK-3β axis plays a key role in driving CSC properties and radioresistance in ESCC, indicating that RSK4 is a promising therapeutic target for ESCC treatment.	esophagus
The integration of proportion and cell counts of stromal, not intratumoral, PD-1+ tumor-infiltrating lymphocytes has prognostic significance in esophageal squamous cell carcinoma.	The present study aimed to investigate the prognostic effect of intratumoral and stromal exhausted tumor-infiltrating lymphocytes (TILs) on operable esophageal cancer patients. We performed a retrospective cohort study by consecutively recruiting 142 patients with esophageal cancer. The proportion and cell counts of intratumoral and stromal PD-1+ TILs in tumor microenvironment were independently evaluated by two pathologists. Neither proportion nor cell counts of intratumoral PD-1+ TILs was associated with prognosis (p > 0.05). However, patients with the proportion of stromal PD1+ TILs >20% had the median overall survival (OS) at 19 months, significantly longer than those with the proportion = 20%. The adjusted hazard ratio (HR) was 1.49 (95%CI 0.82, 2.69). Patients with cell counts of stromal PD1+ TILs = 18/ high-power field (HPF) had the median disease-free survival (DFS) at 10 months. However, patients with cell counts>18/HPF had the median DFS at 48 months (p = 0.037), and the adjusted HR was 0.59 (95%CI 0.35, 1.01). Compared with patients with proportion = 20% and cell counts >18/HPF of stromal PD1+ TILs, patients with proportion = 20% and cell counts = 18/HPF, proportion >20% and cell counts >18/HPF, and proportion >20% and cell counts = 18/HPF, had the adjusted HRs increased to 3.73, 3.36 and 3.99 for DFS (p for trend being 0.030) and the adjusted HRs increased to 2.95, 3.64 and 3.82 (p for trend being 0.015) for OS, respectively. The integration of proportion and cell counts of PD-1+ stromal TILs has a significant association with the relapse and overall survival of esophageal cancer patients. Further prospective studies are warranted.	esophagus
MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma.	Gastroesophageal cancers are a major cause of death worldwide and treatment outcomes remain poor. Adequate predictive biomarkers have not been identified. Microsatellite instability (MSI) as a result of mismatch repair deficiency is present in four to twenty percent of gastroesophageal cancers and has been associated with favorable survival outcomes compared to microsatellite stable tumors. This prognostic advantage may be related to immunosurveillance, which may also explain the favorable response to immune checkpoint inhibition observed in MSI high (MSI-H) tumors. The value of conventional cytotoxic treatment in MSI-H tumors is unclear and results on its efficacy range from detrimental to beneficial effects. Here the recent data on MSI as a predictive factor for outcome of gastroesophageal cancer treatment is reviewed.	esophagus
Radiofrequency Ablation of Barrett's Esophagus: Have We Gone Too Far, or Not Far Enough?	PURPOSE OF REVIEW: Barrett's esophagus (BE) is a premalignant condition of the esophagus associated with an increased risk for esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) is a safe and effective first-line treatment for dysplastic BE and early stage EAC. This report reviews clinically relevant evidence published over the last 3 years regarding RFA for BE. RECENT FINDINGS: Our use of this technology has simultaneously gone too far, in that many patients who may not derive a benefit from these treatments are receiving them, and not far enough, in that many patients who would be eligible for ablative therapy never undergo screening exams to assess them for dysplastic BE, or do not have endoscopic therapy considered part of the treatment of superficial invasive cancer. Research to better identify patients with BE, risk stratify those patients, improve the quality of RFA treatment, and inform surveillance practices has the potential to optimize the benefit of RFA, and minimize the harms, costs, and risks.	esophagus
Low Risk of Progression of Barrett's Esophagus to Neoplasia in Women.	BACKGROUND AND AIMS: Men are at a higher risk for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but little is known about BE progression to dysplasia and EAC in women. We performed a retrospective, multicenter cohort study to assess risk of BE progression to dysplasia and EAC in women compared with men. We also investigated comorbidities, medication use, and endoscopic features that contribute to sex differences in risk of BE progression. METHODS: We collected data from large cohort of patients with BE seen at 6 centers in the United States and Europe, followed for a median 5.7 years. We obtained demographic information (age, sex, ethnicity), clinical history (tobacco use, body mass index, comorbidities), endoscopy results (procedure date, BE segment length), and histopathology findings. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Rates of disease progression between women and men were compared using χ2 analysis and the Student t test. Multivariable logistic regression was used to assess the association between sex and disease progression after adjusting for possible confounding variables. RESULTS: Of the total 4263 patients in the cohort, 2145 met the inclusion criteria, including 324 (15%) women. There was a total of 34 (1.6%) incident EACs, with an overall annual incidence of 0.3% (95% confidence interval: 0.2%-0.4%). We found significant differences between women and men in annual incidence rates of EAC (0.05% for women vs. 0.3% in men; P=0.04) and in the combined endpoint of HGD or EAC (0.1% for women vs. 1.1% for men; P<0.001). Female gender was an independent predictor for reduced progression to HGD or EAC when rates of progression were adjusted for body mass index, smoking history, race, use of aspirin, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, or statins, hypertriglyceridemia, BE length, and histology findings at baseline (hazard ratio: 0.11; 95% confidence interval: 0.03-0.45; P=0.002). CONCLUSIONS: In a multicenter study of men versus women with BE, we found a significantly lower risk of disease progression to cancer and HGD in women. The extremely low risk of EAC in women with BE (0.05%/y) indicates that surveillance endoscopy may not be necessary for this subgroup of patients with BE.	esophagus
WAVE3 upregulation in esophageal squamous cell carcinoma and its effect on the migration of human esophageal cancer cell lines in vitro.	The present study aimed to investigate the role of Wiskott‑Aldrich syndrome verprolin‑homologous protein 3 (WAVE3) in the progression of esophageal squamous cell carcinoma (ESCC), and to explore its effect on the migration of esophageal cancer cell lines in vitro. The expression level of WAVE3 in ESCC tissues was determined via immunohistochemistry, and the relative levels of WAVE3 mRNA and micro (mi)RNA200b were assessed in the serum of patients with ESCC using reverse transcription‑quantitative PCR (RT‑qPCR). Following cell transfection, the levels of miRNA200b and WAVE3 protein were determined via RT‑qPCR and western blot analysis, and cell migration was examined using a Transwell assay. Subsequently, the clinical parameters were used to analyze whether the expression of WAVE3 in tissues and serum was associated with the occurrence and development of ESCC. The results demonstrated that the expression of WAVE3 was increased in ESCC tissues compared with normal tissues. The results also revealed increased expression levels of WAVE3 and decreased expression levels of miRNA200b in the serum of patients with ESCC, compared with healthy volunteers. High expression of WAVE3 was significantly associated with tumor TNM stage, invasion depth and lymphatic invasion of ESCC. In cells transfected with miRNA200b mimic, the miRNA200b was overexpressed, WAVE3 protein was downregulated and cell migration ability was decreased. The results of the present study suggest that WAVE3 may serve as an oncogene in ESCC, and its inhibition via miRNA200b decreased tumor cell migration. Therefore, WAVE3 may serve as a novel biological marker and therapeutic target for ESCC.	esophagus
Integrated analysis of genome-wide miRNAs and targeted gene expression in esophageal squamous cell carcinoma (ESCC) and relation to prognosis.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide and in China. We know miRNAs influence gene expression in tumorigenesis, but it is unclear how miRNAs affect gene expression or influence survival at the genome-wide level in ESCC. METHODS: We performed miRNA and mRNA expression arrays in 113 ESCC cases with tumor/normal matched tissues to identify dysregulated miRNAs, to correlate miRNA and mRNA expressions, and to relate miRNA and mRNA expression changes to survival and clinical characteristics. RESULTS: Thirty-nine miRNAs were identified whose tumor/normal tissue expression ratios showed dysregulation (28 down- and 11 up-regulated by at least two-fold with P < 1.92E-04), including several not previously reported in ESCC (miR-885-5p, miR-140-3p, miR-708, miR-639, miR-596). Expressions of 16 miRNAs were highly correlated with expressions of 195 genes (P < 8.42E-09; absolute rho values 0.51-0.64). Increased expressions of miRNA in tumor tissue for both miR-30e* and miR-124 were associated with increased survival (P < 0.05). Similarly, nine probes in eight of 818 dysregulated genes had RNA expression levels that were nominally associated with survival, including NF1, ASXL1, HSPA4, TGOLN2, BAIAP2, EZH2, CHAF1A, SUPT7L. CONCLUSIONS: Our characterization and integrated analysis of genome-wide miRNA and gene expression in ESCC provides insights into the expression of miRNAs and their relation to regulation of RNA targets in ESCC tumorigenesis, and suggest opportunities for the future development of miRs and mRNAs as biomarkers for early detection, diagnosis, and prognosis in ESCC.	esophagus
Crosstalk between MEIS1 and markers of different cell signaling pathways in esophageal squamous cell carcinoma.	The homeobox transcription factor MEIS1 is involved in cell fate decision, stem cells properties, gastrointestinal (GI) tract development, and progression of several malignancies such as esophageal squamous cell carcinoma (ESCC). Increasing evidences suggest the crosstalk between MEIS1 and cell signaling pathways. Therefore, our aim in present study was to investigate the probable linkage of MEIS1 expression with key genes of different cell signaling pathways in ESCC tumorigenesis, and their correlation with clinicopathological feature of the patients. The gene expression profiling of MEIS1 and different cell signaling genes including SALL4, SIZN1, and HEY1 (stemness state, BMP, and NOTCH signaling pathways, respectively) was performed using quantitative real-time reverse transcription polymerase chain reaction (PCR) in fresh tumoral compared to margin normal tissues of 50 treatment-naive ESCC samples. The mRNA expression of MEIS1/SIZN1, SIZN1/HEY1, and SIZN1/SALL4 were significantly associated to each other (P < 0.05). There were remarkable correlations between concomitant mRNA expression of MEIS1 and SIZN1 in tumors with invasion to adventitia, early stages of tumor progression and poorly differentiated tumors. Moreover, expression of MEIS1 and HEY1 was correlated to each other in primary stages of tumor progression and non-invaded tumors. Expression of MEIS1 was significantly associated with SALL4 in poorly differentiated tumors. Our results indicated that correlation between different cell signaling pathway-related genes may lead to esophageal tumorigenesis. It is illustrated that MEIS1 as a HOX gene has a significant correlation with stemness state, BMP, and NOTCH signaling pathways via the SIZN1.	esophagus
A Right Video-Assisted Thoracoscopic Enucleation of a Calcified Esophageal Leiomyoma: A Case Report.	BACKGROUND Benign esophageal tumors are considered rare, and most commonly are leiomyomas with the incidence of 0.005%. They arise intramurally in the distal two-thirds of the esophagus and are multiple in about 5% of patients. Leiomyoma lesions can mimic esophageal cancer making the diagnosis more challenging. Many cases are asymptomatic, up to 15%-50%, and most cases are discovered incidentally during esophagogastroduodenoscopy (EGD) and other procedures. The treatment of choice for symptomatic leiomyomas to relieve the compression is surgical enucleation with either an open thoracotomy, submucosal tunneling endoscopic resection, a video-assisted thoracoscopic approach (VATS), or with robotic techniques. CASE REPORT Here we report a case of a 53-year-old Saudi female patient who presented with dysphagia which had been ongoing for a long time. There were no other associated symptoms such as dyspepsia, nausea, or vomiting. She was diagnosed with a calcified leiomyoma of the esophagus based on a computed tomography (CT) scan and an endoscopic ultrasound (EUS) finding. After thorough investigations and workups, the management plan was taken at King Faisal Specialist Hospital and Research Centre by preforming a right video-assisted thoracoscopic enucleation. CONCLUSIONS The aim of this case report was to add to the literature by reporting the satisfactory outcomes of right video-assisted enucleation contrary to other surgical approaches that have been discussed in the literature.	esophagus
Synthetic Lethality with Trifluridine/Tipiracil and Checkpoint Kinase 1 Inhibitor for Esophageal Squamous Cell Carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a disease characterized by a high mutation rate of the TP53 gene, which plays pivotal roles in the DNA damage response (DDR) and is regulated by checkpoint kinase (CHK) 2. CHK1 is another key DDR-related protein, and its selective inhibition is suggested to be particularly sensitive to TP53-mutated cancers, because a loss of both pathways (CHK1 and/or CHK2-p53) is lethal due to the serious impairment of DDR. Such a therapeutic strategy is termed synthetic lethality. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and prexasertib (CHK1 inhibitor) as a treatment for ESCC. Trifluridine is a key component of the antitumor drug combination with trifluridine/tipiracil (an inhibitor of trifluridine degradation), also known as TAS-102. In this study, we demonstrate that trifluridine increases CHK1 phosphorylation in ESCC cells combined with a reduction of the S-phase ratio as well as the induction of ssDNA damage. Because CHK1 phosphorylation is considered to be induced as DDR for trifluridine-mediated DNA damage, we examined the effects of CHK1 inhibition on trifluridine treatment. Consequently, CHK1 inhibition by short hairpin RNA or treatment with the CHK1 inhibitor, prexasertib, markedly enhanced trifluridine-mediated DNA damage, represented by an increase of γH2AX expression. Moreover, the combination of trifluridine/tipiracil and CHK1 inhibition significantly suppressed tumor growth of ESCC-derived xenograft tumors. Furthermore, the combination of trifluridine and prexasertib enhanced radiosensitivity both in vitro and in vivo Thus, the combination of trifluridine/tipiracil and a CHK1 inhibitor exhibits effective antitumor effects, suggesting a novel therapeutic strategy for ESCC.	esophagus
Esophageal microbiome signature in patients with Barrett's esophagus and esophageal adenocarcinoma.	Preliminary studies suggested a possible correlation of microbiota with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), where the need for tools to ameliorate its poor prognosis is mandatory. We explored the potential signature of esophageal microbiota and its predicted functional profile along the continuous spectrum from BE to EAC. We analyzed through 16S-based amplicon sequencing the mucosal microbiota and the microbiota-related functional predictions in 10 BE and 6 EAC patients compared with 10 controls, exploring also potential differences between the metaplastic mucosa (BEM) and the adjacent normal areas of BE patients (BEU). BEM and EAC showed a higher level of α and β-diversity. BEM evidenced a decrease of Streptococcus and an increase of Prevotella, Actinobacillus, Veillonella, and Leptotrichia. EAC displayed a striking reduction of Streptococcus, with an increase of Prevotella, Veillonella and Leptotrichia. LefSe analysis identified Leptotrichia as the main taxa distinguishing EAC. BEM showed a decreased α-diversity compared with BEU and a reduction of Bacteroidetes, Prevotella and Fusobacterium. Functional predictions identified peculiar profiles for each group with a high potential for replication and repair in BEM; an upregulated energy, replication and signaling metabolisms, with the fatty-acids biosynthesis and nitrogen and D-alanine pathways down-regulated in EAC. Our pilot study identifies a unique microbial structure and function profile for BE and EAC, as well as for metaplastic and near-normal areas. It proposes a new concept for BE, which could be intended not only as the histological, but, also, as the microbial closest precursor of EAC. This requires further larger follow-up studies, but opens intriguing horizons towards innovative diagnostic and therapeutic options for EAC.	esophagus
Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells.	PURPOSE: Chemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor's acquired drug resistance, the related action mechanism is still not explored specifically. METHODS: To elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin. RESULTS: Small RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-sensitive cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine-cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin's inhibition of the cell cycle of sensitive cells. CONCLUSION: Sensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.	esophagus
The usefulness of intraoperative neurological monitoring for esophageal cancer with double aortic arch; a case report.	BACKGROUND: Double aortic arch (DAA) is a congenital anomaly of the aorta. Esophageal cancer with DAA is rare, and consequently, the appropriate surgical approach has not been standardized. Herein, we report the utilization of intraoperative neurological monitoring (IONM) system to preserve the function of the recurrent laryngeal nerve. CASE PRESENTATION: A 79-year-old man with esophageal cancer was diagnosed with DAA incidentally. The descending aorta was located on the right side of the thoracic vertebrae. Safe dissection of the mediastinal lymph nodes was difficult using the right transthoracic approach because of the anatomical abnormalities. During surgery, we used cervical mediastinoscopy combined with the IONM system to preserve the bilateral recurrent laryngeal nerves. Severe complications, including recurrent nerve palsy, were not observed postoperatively. CONCLUSION: IONM may be useful for evaluation of the function of the recurrent laryngeal nerve, and it would be suitable for atypical cases of esophageal cancer.	esophagus
Survival outcomes of resection for pulmonary malignancies including non-small cell lung cancer and pulmonary metastasis after esophagectomy for esophageal carcinoma.	OBJECTIVES: This study investigated survival outcomes of resection for pulmonary malignancies after esophagectomy for esophageal carcinoma, comparing non-small cell lung cancer and pulmonary metastases. METHODS: We retrospectively reviewed consecutive patients who underwent resection for pulmonary malignancies after esophagectomy for esophageal carcinoma between 2009 and 2018. The overall survival and relapse-free survival rate were assessed using Kaplan-Meier analysis. RESULTS: Eleven patients had non-small cell lung cancer and eight patients had pulmonary metastases from esophageal carcinoma. The 5-year overall survival rate was 92.9% in all patients with a median follow-up period of 50.4 (range: 9.1-130.2) months. While the 5-year overall survival rate was 100.0% in patients with non-small cell lung cancer, it was 85.7% in patients with pulmonary metastases from esophageal carcinoma. The 5-year relapse-free survival rate was 85.7% in patients with non-small cell lung cancer. CONCLUSIONS: Our data suggest that resection for pulmonary malignancies after esophagectomy for esophageal carcinoma is associated with favorable survival outcomes and should be considered in selected patients.	esophagus