crossing96/oncoscreening huggingface dataset:
Multiparametric High-Content Cell Painting Identifies Copper Ionophores as Selective Modulators of Esophageal Cancer Phenotypes.	"Esophageal adenocarcinoma is of increasing global concern due to increasing incidence, a lack of effective treatments, and poor prognosis. Therapeutic target discovery and clinical trials have been hindered by the heterogeneity of the disease, the lack of ""druggable"" driver mutations, and the dominance of large-scale genomic rearrangements. We have previously undertaken a comprehensive small-molecule phenotypic screen using the high-content Cell Painting assay to quantify the morphological response to a total of 19,555 small molecules across a panel of genetically distinct human esophageal cell lines to identify new therapeutic targets and small molecules for the treatment of esophageal adenocarcinoma. In this current study, we report for the first time the dose-response validation studies for the 72 screening hits from the target-annotated LOPAC and Prestwick FDA-approved compound libraries and the full list of 51 validated esophageal adenocarcinoma-selective small molecules (71% validation rate). We then focus on the most potent and selective hit molecules, elesclomol, disulfiram, and ammonium pyrrolidinedithiocarbamate. Using a multipronged, multitechnology approach, we uncover a unified mechanism of action and a vulnerability in esophageal adenocarcinoma toward copper-dependent cell death that could be targeted in the future."	esophagus
Two- versus three-field lymphadenectomy for esophageal cancer. A systematic review and meta-analysis of early and late results.	This study aims to estimate whether prophylactic cervical lymphadenectomy for esophageal cancer influences the short- and long-term results through a systematic literature review and meta-analysis. Twenty-eight articles were selected in this systematic review, encompassing 9180 patients. Prophylactic neck lymphadenectomy for esophageal cancer should be performed with caution, as it is associated with worse short-term results compared to traditional two-field lymphadenectomy and does not improve long-term survival.	esophagus
Combined risk factors and risk of upper gastrointestinal cancer mortality in the Linxian general population.	We aimed to explore the association of combined risk factors with risk of death from upper gastrointestinal (UGI) cancer, including esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC) and gastric noncardia carcinoma (GNCC) in the Linxian Nutrition Intervention Trial (NIT) cohort. The NIT cohort included 29 584 healthy adults. A combined risk score (CRS) was calculated using a point system method based on 10 risk factors collected at baseline, including gender, smoking, alcohol drinking, body mass index, family history of UGI cancer, drinking tap water, tooth loss and consumption of fresh fruit, eggs and meat. Possible score ranged from 0 to 31, and higher score indicated as poorer health status. Subjects were divided into three groups by the CRS (<12 points, 12 to 20 points and >20 points). The group of CRS <12 points was considered as the reference. During the 30-year follow-up, we identified 4553 UGI cancer deaths. Compared to subjects with a CRS <12 points, the adjusted HRs for CRS of 12 to 20 points and >20 points were 1.69 (95% CI: 1.56-1.83) and 3.06 (95% CI: 2.82-3.33) for UGI cancer mortality, respectively (P(trend)  < .001). Comparable associations were also observed for ESCC, GCC and GNCC mortality. Results remained similar across different age groups (P(interaction)  > .05). All HRs observed in the second half follow-up period were stronger than that observed in the first half follow-up period. Our study indicated that higher CRS was associated with increased risk of UGI cancer mortality. Appropriate measures should be taken to reduce unhealthy lifestyles.	esophagus
Insulin receptor substrate 1(IRS1) is related with lymph node metastases and prognosis in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related mortality globally with a high risk of lymph node metastasis (LNM). In this study, weighted gene co-expression network analysis (WGCNA) showed the identification of 10 modules among which the significant module (turquoise), including 1352 genes, was correlated with LNM. A group 52 overlapping differentially expressed genes (DEGs) was identified based on the comparison of turquoise module with GSE23400 and GSE20347 datasets. Using Ctyohubba plugin, we identified 7 hub genes (ACTG2, SORBS1, MYH11, CXCL12, CNN1, IRS1 and CXCL8). IRS1 displayed significant correlation with metastasis. The decreased expression of IRS1 was also a predictor of poor OS of ESCC patients whereas the hub genes namely ACTG2, MYH11, CXCL8, CXCL12, IRS1 and CNN1 were associated with RFS of ESCC patients. These findings suggest that the altered expression of these hub genes are associated with prognosis and thus can be used as potential biomarkers for ESCC. Moreover, immunohistochemical staining and cell functional experiments displayed that the overexpression of IRS1 was negatively associated with metastasis in ESCC. In general, our research revealed several novel genes in ESCC especially the association of IRS1 with LNM in ESCC, which could provide novel insights into the initiation and progression of ESCC.	esophagus
Paclitaxel and cisplatin combined with concurrent involved-field irradiation in definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: a phase II clinical trial.	PURPOSE: This trial aims to explore the efficacy and safety of involved-field irradiation (IFI) combined with paclitaxel plus cisplatin as concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT). METHODS: Enrolled patients with locally advanced ESCC were treated with definitive concurrent chemoradiotherapy. IFI was administered adopting IMRT and the total dose was 61.2 Gy delivered in 34 fractions. On the first day of radiotherapy, the patients were treated with paclitaxel and cisplatin one cycle per month for 2 cycles followed by the same regimen in consolidation chemotherapy for two cycles. The primary endpoint of the study was the 2-year locoregional recurrence-free survival (LRFS) rate, and secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. RESULTS: Between January 2018 and September 2020, 108 patients participated in the trial. 78.7% (85/108) of patients completed all 4 cycles of chemotherapy. The median follow-up of the surviving patients was 33.9 months (interquartile range, 29.2-41.1). The 2-year LRFS rate, as the primary endpoint, was 64.2%. In addition, the median PFS was 39.2 months, and 1-year and 3-year OS rates of 88.0% and 63.3%, respectively. Among the patients, out-of-field regional failure was seen in only 7 (6.5%) patients. Neutropenia grade 3 and 4 occurred in 21.3% and 37.0% of the patients, respectively. CONCLUSIONS: IFI using IMRT combined with paclitaxel and cisplatin concurrent chemotherapy for locally advanced ESCC yields encouraging local control and overall survival, but high hematological toxicity. Trial registration Clinical Trials ChiCTR1800017039.	esophagus
Transhiatal versus transthoracic esophagectomy for esophageal SCC: outcomes and complications.	BACKGROUND: Transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) are both accepted procedures for esophageal cancer but still the most effective surgical approach continues to be controversial. This study aimed to determine post-operative complications and outcomes of TTE compared with THE. METHODS: A retrospective analysis was performed on data of 243 adult patients with resectable esophageal cancer who underwent THE or TTE between December 2016 and October 2018. Demographic data, consisting of preoperative co-morbidities, disease stage, and perioperative morbidity and mortality were collected. RESULTS: Among the patients, 99 individuals (40.7%) had a transhiatal resection and 144 (59.3%) had a transthoracic resection. Most patients (83.1%) were above 50 years old with no significant difference between groups (p = 0.297). The frequency distribution of comorbidities was similar in both groups. The most common site of the tumor in TTE group was middle esophagus and in THE group was lower esophagus. The most common complication was recurrence of dysphagia which was more common in THE group without significant difference. The other complications including pulmonary and cardiac events, tracheal and recurrent laryngeal nerve injury, chylothorax and anastomosis stricture did not differ between the groups. The operative mortality within 30 days after the operation was 2.8% with significant difference favored the THE group (THE 0%, TTE 5.2%, p = 0.033). CONCLUSION: Because of the controversies, the decision on the type of surgical technique in esophageal cancer treatment hinges on patient's co-morbidities, cancer stage, tumor location and surgeon's experience.	esophagus
Post-recurrence survival analysis in patients with oligo-recurrence after curative esophagectomy.	BACKGROUND: Recurrent esophageal cancer is associated with dismal prognosis. There is no consensus about the role of surgical treatments in patients with limited recurrences. This study aimed to evaluate the role of surgical resection in patients with resectable recurrences after curative esophagectomy and to identify their prognostic factors. METHODS: We retrospectively reviewed patients with recurrent esophageal cancer after curative esophagectomy between 2004 and 2017 and included those with oligo-recurrence that was amenable for surgical intent. The prognostic factors of overall survival (OS) and post-recurrence survival (PRS), as well as the survival impact of surgical resection, were analyzed. RESULTS: Among 654 patients after curative esophagectomies reviewed, 284 (43.4%) had disease recurrences. The recurrences were found resectable in 63 (9.6%) patients, and 30 (4.6%) patients received surgery. The significant prognostic factors of PRS with poor outcome included mediastinum lymph node (LN) recurrence and pathologic T3 stage. In patients with and without surgical resection for recurrence cancer, the 3-year OS rates were 65.6 and 47.6% (p = 0.108), while the 3-year PRS rates were 42.9 and 23.5% (p = 0.100). In the subgroup analysis, surgery for resectable recurrence, compared with non-surgery, could achieve better PRS for patients without any comorbidities (hazard ratio 0.36, 95% CI: 0.14 to 0.94, p = 0.038). CONCLUSIONS: Mediastinum LN recurrence or pathologic T3 was associated with worse OS and PRS in patients with oligo-recurrences after curative esophagectomies. No definite survival benefit was noted in patients undergoing surgery for resectable recurrence, except in those without comorbidities.	esophagus
Urolithins increased anticancer effects of chemical drugs, ionizing radiation and hyperthermia on human esophageal carcinoma cells in vitro.	Despite progress in diagnosis and treatment of esophageal cancer (EC), it is still considered as a serious malignancy with very poor prognosis. Urolithins are colonic microbiota metabolites with a wide range of pharmacological properties including chemopreventive, anti-inflammatory and anticancer activities. In this study, we hypothesized that urolithins might possess the potential to improve the efficacy of chemical drugs, ionizing radiation (IR) and/or hyperthermia on EC cells. After synthesis of urolithin A (UA), methylurolithin A (mUA) and urolithin B (UB), KYSE30 esophageal cancer cells were treated with urolithins + paclitaxel (PTX), + cisplatin (DDP), + different doses of IR or + heat-shock. Viability of cells was then determined by alamarBlue assay. To further elucidate the effects of UA, we used flow cytometry for investigation of induced apoptosis, and qRT-PCR for evaluating changes in the expression of HSP27, CCND1 and BCL2. Assessment of cell viability demonstrated that mUA increased the toxicity of PTX and DDP (up to 22.4 % and 20 %, respectively) and improved the effects of 6 Gy IR (26.5 %). Our main results achieved after UA treatment were improved toxicity of PTX and 6 Gy IR, beside enhanced effects of hyperthermia (37.3 %), which was confirmed by flow cytometry analysis and downregulation of HSP27, CCND1 and BCL2 expression. Taken together, our findings suggest that UA and mUA could be used as promising agents in combination with therapeutic modalities to improve the clinical outcomes of EC treatment.	esophagus
Implementation of the Esophagectomy Complication Consensus Group definitions: the benefits of speaking the same language.	In 2015 the Esophagectomy Complication Consensus Group (ECCG) reported consensus definitions for complications after esophagectomy. This aimed to reduce variation in complication reporting, attributed to heterogeneous definitions. This systematic review aimed to describe the implementation of this definition set, including the effect on complication frequency and variation. A systematic literature review was performed, identifying all observational and randomized studies reporting complication frequencies after esophagectomy since the ECCG publication. Recruitment periods before and subsequent to the index ECCG publication date were included. Coefficients of variance were calculated to assess outcome heterogeneity. Of 144 studies which met inclusion criteria, 70 (48.6%) used ECCG definitions. The median number of separately reported complication types was five per study; only one study reported all ECCG complications. The coefficients of variance of the reported frequencies of eight of the 10 most common complications were reduced in studies which used the ECCG definitions compared with those that did not (P = 0.036). Among ECCG studies, the frequencies of postoperative pneumothorax, reintubation, and pulmonary emboli were significantly reduced in 2020-2021, compared with 2015-2019 (P = 0.006, 0.034, and 0.037 respectively). The ECCG definition set has reduced variation in esophagectomy morbidity reporting. This adds greater confidence to the observed gradual improvement in outcomes with time, and its ongoing use and wider dissemination should be encouraged. However, only a handful of outcomes are widely reported, and only rarely is it used in its entirety.	esophagus
Esophageal spindle cell lipoma.	Symptomatic ordinary esophageal lipomas are rare tumors. Spindle cell lipomas (SCLs) of this location are even more infrequent. To our knowledge, only a previous esophageal SCL case has been reported. We describe herein the case of a 62-year-old woman with a long history of heartburn and feeling of abdominal distension. Preoperative investigations, including a Barium meal, gastroscopy, and echoendoscopy revealed a lipomatous polypoid mass attached to the middle esophageal segment. The lesion (3.5×2×1 cm) was excised endoscopically under deep sedation. The final histopathology diagnosis was pedunculated SCL. An accurate diagnosis of esophageal SCL is crucial to rule out malignant lesions, relieve symptoms, and undertake suitable treatment. The main differential diagnosis includes well-differentiated sclerosing liposarcoma, atypical spindle cell∕pleomorphic lipomatous tumor, giant fibrovascular polyp, and fat-forming solitary fibrous tumor. Although rare, SCL should be added to the list of lipomatous tumors that can affect the esophagus. Complete excision is the appropriate treatment.	esophagus
The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020.	BACKGROUND & AIMS: The aim of this study was to provide an overview of the burden of esophageal cancer in 185 countries in 2020 and projections for the year 2040. METHODS: Estimates of esophageal cancer cases and deaths were extracted from the GLOBOCAN database for 2020. Age-standardized incidence and mortality rates were calculated overall, by sex, histologic subtype (adenocarcinoma [AC] and squamous cell carcinoma [SCC]), country, and level of human development for 185 countries. The predicted burden of incidence and mortality in 2040 was calculated based on global demographic projections. RESULTS: Globally, there were an estimated 604,100 new cases of, and 544,100 deaths from, esophageal cancer in 2020, corresponding to age-standardized incidence and mortality rates of 6.3 and 5.6 per 100,000, respectively. Most cases were SCCs (85% [512,500 cases]) and 14% (85,700 cases) were ACs. Incidence and mortality rates were 2- to 3-fold higher in male (9.3 and 8.2, respectively) compared with female (3.6 and 3.2, respectively) individuals. Global variations in incidence and mortality were observed across countries and world regions; the highest rates occurred in Eastern Asia and Southern and Eastern Africa and the lowest occurred in Western Africa and Central America regions. If rates remain stable, 957,000 new cases (141,300 AC cases and 806,000 SCC cases) and 880,000 deaths from esophageal cancer are expected in 2040. CONCLUSIONS: These updated estimates of the global burden of esophageal cancer represent an important baseline for setting priorities in policy making and developing and accelerating cancer control initiatives to reduce the current and projected burden. Although primary prevention remains key, screening and early detection represent important components of esophageal cancer control in high-risk populations.	esophagus
Right video-assisted thoracoscopic enucleation of an upper thoracic esophageal leiomyoma.	Leiomyomas are rare benign tumors of the esophagus that account for about 4% of all esophageal tumors. Recently, the great improvements in minimally invasive techniques have made the resection of mediastinal and pulmonary neoplasms more feasible through video-assisted thoracoscopic or robotic surgery. Our video tutorial describes our approach for a right-sided 3-port thoracoscopic resection of an upper esophageal leiomyoma.	esophagus
Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol-related disorder and cancer.	BACKGROUND: ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly associated with alcohol-related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol-related disorder and cancer. METHODS: This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression. RESULTS: Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol-related disorders and was related to an increased risk of alcohol-related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities [odds ratio (OR) = 1.56, p = 0.0009], cancer of the pancreas (OR = 1.66, p = 0.018), and cancer of the esophagus (OR = 4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR = 3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR = 4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes. CONCLUSION: rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol-related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high-risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.	esophagus
Bite-on-bite biopsies for the detection of residual esophageal cancer after neoadjuvant chemoradiotherapy.	BACKGROUND: Active surveillance after neoadjuvant treatment is increasingly implemented. The success of this strategy relies on the accurate detection of residual cancer. This study aimed to assess the diagnostic value of a second (bite-on-bite) biopsy for the detection of residual esophageal cancer and to correlate outcomes to the distribution of residual cancer found in the resection specimen. METHODS: A multicenter prospective study of esophageal cancer patients undergoing active surveillance after neoadjuvant chemoradiotherapy was performed. At clinical response evaluations, an upper gastrointestinal (GI) endoscopy was performed with at least four bite-on-bite biopsies of the primary tumor site. First and second biopsies were analyzed separately. Patients with histopathological evidence of residual cancer were included in the primary analysis. Two pathologists blinded for biopsy outcome examined all resection specimens. RESULTS: Between October 2017 and July 2020, 626 upper GI endoscopies were performed in 367 patients. Of 138 patients with residual cancer, 112 patients (81 %) had at least one positive biopsy. In 14 patients (10 %) only the first biopsy was positive and in 25 patients (18 %) only the second biopsy (P = 0.11). Remarkably, the rates of patients with tumor-free mucosa and deeper located tumors were higher in patients detected by the first biopsy. The second biopsy increased the false-positive rate by 3 percentage points. No adverse events occurred. CONCLUSIONS: A second (bite-on-bite) biopsy improves the detection of residual esophageal cancer by almost 20 percentage points, at the expense of increasing the false-positive rate by 3 percentage points. The higher detection rate is explained by the higher number of biopsies obtained rather than by the penetration depth.	esophagus
Potential Role of Silencing Ribonucleic Acid for Esophageal Cancer Treatment.	"INTRODUCTION: Esophageal cancer is an aggressive malignancy with high mortality. Optimal treatment of esophageal cancer remains an elusive goal. Ribonucleic acid (RNA) interference is a novel potential targeted approach to treat esophageal cancer. Targeting oncogenes that can alter critical cellular functions with silencing RNA molecules is a promising approach. The silencing of specific oncogenes in esophageal cancer cells in the experimental setting has been shown to decrease the expression of oncogenic proteins. This has resulted in cell apoptosis, reduction in cell proliferation, reduced invasion, migration, epithelial-mesenchymal transition, decrease in tumor angiogenesis and metastasis, and overcoming drug resistance. The Hedgehog (Hh) signaling pathway has been shown to be involved in esophageal adenocarcinoma formation in a reflux animal model. In addition to Hh, we will focus on other targets with clinical potential in the treatment of esophageal cancer. MATERIALS AND METHODS: We searched for articles published from 2005 to August 2020 that studied the siRNA effects on inhibiting esophageal cancer formation in experimental settings. We used combinations of the following terms for searching: ""esophageal cancer,"" ""RNA interference,"" ""small interfering RNA,"" ""siRNA,"" ""silencing RNA,"" ""Smoothened (Smo),"" ""Gli,"" ""Bcl-2,"" ""Bcl-XL,"" ""Bcl-W,″ ""Mcl-1,"" ""Bfl-1,"" ""STAT3,""and ""Hypoxia inducible factor (HIF)"". A total of 21 relevant articles were found. RESULTS AND CONCLUSIONS: Several proto-oncogenes/oncogenes including Hh pathway mediators, glioma-associated oncogene homolog 1 (Gli-1), Smoothened (Smo), and antiapoptotic Bcl-2 have potential as targets for silencing RNA in the treatment of esophageal cancer."	esophagus