crossing96/oncoscreening huggingface dataset:
Suppression of MET Signaling Mediated by Pitavastatin and Capmatinib Inhibits Oral and Esophageal Cancer Cell Growth.	Despite increasing knowledge on oral and esophageal squamous cell carcinoma (OSCC and ESCC), specific medicines against both have not yet been developed. Here, we aimed to find novel anticancer drugs through functional cell-based screening of an FDA-approved drug library against OSCC and ESCC. Pitavastatin, an HMGCR inhibitor, emerged as an anticancer drug that inhibits tumor growth by downregulating AKT and ERK signals in OSCC and ESCC cells. One of the mechanisms by which pitavastatin inhibits cell growth might be the suppression of MET signaling through immature MET due to dysfunction of the Golgi apparatus. Moreover, the sensitivity of tumor growth to pitavastatin might be correlated with GGPS1 expression levels. In vivo therapeutic models revealed that the combination of pitavastatin with capmatinib, a MET-specific inhibitor, dramatically reduced tumor growth. Our findings suggest that GGPS1 expression could be a biomarker in cancer therapy with pitavastatin, and the combination of pitavastatin with capmatinib might be a promising therapeutic strategy in OSCC and ESCC. IMPLICATIONS: This study provides new insight into the mechanism of pitavastatin as an anticancer drug and suggests that the combination of pitavastatin with capmatinib is a useful therapeutic strategy in OSCC and ESCC.	esophagus
Predictors of Early and Late Mortality after Endoscopic Resection for Esophageal Squamous Cell Carcinoma.	In esophageal squamous cell carcinoma (ESCC) comprising 90% of cases with esophageal cancer, endoscopic resection (ER) is recommended for patients with negligible risk of ESCC-related mortality. In fact, a main cause of death in patients underwent ER is not ESCC. We thus aimed to clarify the predictors for early and late mortality among patients underwent ER of ESCC between 2005 and 2018 at our institution. In this retrospective cohort study, we investigated the prognosis and predictors of early and late mortality with the cut-off value of 3 years. We enrolled 407 patients with a median 69 months follow-up. The 5-year overall survival and disease-specific survival, an indicator of ESCC-related mortality, were 83.4% and 98.4%, respectively. In multivariate Cox analyses, Eastern Cooperative Oncology Group performance status (ECOG-PS), consisting of six grades by a patient's level of activity, ≥ 2 was a predictor for early and late morality [hazard ratio (HR), 7.21 (P = 0.007) and 15.62 (P = 0.021), respectively]. Charlson comorbidity index (CCI), which is an index for predicting mortality by comorbid conditions, ≥ 2 was also a predictor for both mortality [HR, 2.97 (P = 0.017) and 1.90 (P = 0.019), respectively]. However, age was a predictor only for late mortality [HR, 3.08 (P = 0.010) in 80-84 years and 8.38 (P < 0.001) in ≥ 85 years]. Considering the predictive ability for early mortality, we propose that ECOG-PS and/or CCI are better indices compared with age in deciding treatment strategy after ER for ESCC.	esophagus
The Predictive Value of Inflammatory Biomarkers in Esophageal Anastomotic Leaks.	BACKGROUND: This study investigated the role of the neutrophil-to-lymphocyte ratio (NLR) in predicting anastomotic leak (AL) after esophagectomy for esophageal adenocarcinoma. METHODS: This is a retrospective analysis of a prospectively collected database from the McGill University Health Center. Included were all patients with esophageal adenocarcinoma who underwent esophagectomy between 2005 and 2016. Patients with chronic infections, concurrent active malignancies, and autoimmune conditions were excluded. NLR values were obtained on postoperative days (POD) 0, 1, 2, and 3. Receiver operating characteristic curve study and multivariable logistic analysis were conducted to evaluate the diagnostic value of NLR. RESULTS: The study included 330 patients, and AL developed in 16%. Mean NLR values on POD1, 2, and 3 were higher in patients with leaks (20 vs 14 on POD1, P < .001; 20 vs 12 on POD2, P < .001; and 19 vs 10 on POD3, P < .001). The NLR value on POD3 was associated with an area under the curve of 70% and a negative predictive value of 92.4%. Multivariable analyses identified higher American Society of Anesthesiologists Physical Status Classification, increasing NLR trend (between POD1 and POD3), POD1 NLR, POD2 NLR, and POD3 NLR as independent factors associated with AL. CONCLUSIONS: Patients who developed AL demonstrate higher mean NLR values in the early postoperative period with rising trends. Conversely a low NLR is associated with a high negative predictive value for AL. This simple metric allows risk stratification that may guide treatment decisions in esophagectomy patients.	esophagus
External beam patient dose verification based on the integral quality monitor (IQM(®)) output signals.	BACKGROUND: The Integral Quality Monitor (IQM(®)) can essentially measure the integral fluence through a segment and provide real-time information about the accuracy of radiation delivery based on comparisons of measured segment signals and pre-calculated reference values. However, the present IQM chamber cannot calculate the dose in the patient. AIM: This study aims to make use of IQM field output signals to calculate the number of monitor units (MUs) delivered through an arbitrary treatment field in order to convert Monte Carlo (MC)-generated dose distributions in a patient model into absolute dose. METHODS: XiO and Monaco treatment planning systems (TPSs) were used to define treatment beam portals for cervix and esophagus conformal radiotherapy as well as prostate intensity-modulated radiotherapy for the translation of patient and beam setup information from DICOM to DOSXYZnrc. The planned beams were simulated in a patient model built from actual patient CT images and each simulated integral field/segment was weighted with its MUs before summation to get the total dose in the plan. The segment beam weights (MUs) were calculated as the ratio of the open-field IQM measured signal and the calculated signal per MU extracted from chamber sensitivity maps. These are the actual MUs delivered not just MUs set. The beam weighting method was evaluated by comparing weighted MC doses with original planned doses using profile and isodose comparisons, dose difference maps, γ analysis and dose-volume histogram (DVH) data. RESULTS: γ pass rates of up to 98% were found, except for the esophagus plan where the γ pass rate was below 45%. DVH comparisons showed good agreement for most organs, with the largest differences observed in low-density lung. However, these discrepancies can result from differences in dose calculation algorithms or differences in MUs used for dose weighting planned by the TPS and MUs calculated using IQM field output signals. To test this, a 4-field box DOSXYZnrc MC simulation weighted with planned (XiO) MUs was compared with the same simulation weighted with IQM-based MUs. Dose differences of up to 5% were found on the isocentre slice. For XiO versus MC, up to 7% dose differences were found, indicating additional error due to limitations of XiO's superposition algorithm. Dose differences between MC Monaco and MC EGSnrc were less than 3%. CONCLUSIONS: The most valuable comparison was MC versus MC as it eliminated algorithm discrepancies and evaluated dose differences precisely according to beam weighting. For XiO TPS, care must be taken as dose differences may also arise due to limitations in XiO's planning software, not merely due to differences in MUs. Overall, the IQM was successfully used to compute beam dose weights to accurately reconstruct the patient dose using unweighted MC beams. Our technique can be used for pre-treatment QA provided each segment output is known and an accurate linac source model is available.	esophagus
Inhibition of Growth of Esophageal Cancer by Alantolactone via Wnt/β- Catenin Signaling.	BACKGROUND: Alantolactone (AL) is a natural compound extracted from the roots of Inula Helenium L, which exerts an anti-tumor effect in a variety of cancer cell lines; however, its effect on esophageal cancer, a common malignancy with poor prognosis, remains unclear. Therefore, we aim to evaluate the effect of AL on esophageal cancer and to explore its underlying mechanism. OBJECTIVE: This study aims to determine whether AL has an anti-cancer effect on esophageal cancer cells and to explore its underlying mechanism. METHODS: The effect of AL on the proliferation and apoptosis of esophageal cancer cells was detected by MTT assay, colony formation assay, crystal violet assay, flow cytometry and hoechst apoptosis staining. The wound healing and Transwell invasion assay were performed to examine the effect of AL on the migration and invasion of esophageal cancer cells. Luciferase reporter system and Western blot were used to study the anti-tumor mechanism of AL on esophageal cancer cells. The subcutaneous murine xenograft model was employed to verify the effects of AL on esophageal cancer cells. RESULTS: MTT assay, colony formation assay and crystal violet assay found that AL inhibited the growth of esophageal cancer cells. Hoechst staining and flow cytometry analysis showed that AL induced apoptosis in esophageal cancer through mitochondrial pathway. Transwell assay and wound healing assays showed that AL inhibited the metastasis and invasion of esophageal cancer cells. Wnt/ β-catenin signaling may contribute to the mechanism of the inhibition. The anti-tumor effect of AL on esophageal cancer cells was validated on murine xenograft model. CONCLUSION: Our data indicate that AL inhibits proliferation, migration, and invasion of esophageal cancer cells, and promote apoptosis of esophageal cancer cells through the Wnt/β-catenin signaling pathway.	esophagus
PI3K inhibition as a novel therapeutic strategy for neoadjuvant chemoradiotherapy resistant oesophageal adenocarcinoma.	OBJECTIVE: Neoadjuvant chemoradiotherapy (neo-CRT) prior to surgery is the standard of care for oesophageal adenocarcinoma (OAC) patients. Unfortunately, most patients fail to respond to treatment. MiR-187 was previously shown to be downregulated in neo-CRT non-responders, whist in vitro miR-187 overexpression enhanced radiosensitivity and upregulated PTEN. This study evaluates the role of miR-187 and downstream PI3K signalling in radiation response in OAC. METHODS: The effect of miR-187 overexpression on downstream PI3K signalling was evaluated in OAC cell lines by qPCR and Western blotting. PTEN expression was analysed in OAC pre-treatment biopsies of neo-CRT responders and non-responders. Pharmacological inhibition of PI3K using GDC-0941 was evaluated in combination with radiotherapy in two-dimensional and three-dimensional OAC models in vitro and as a single agent in vivo. Radiation response in vitro was assessed via clonogenic assay. RESULTS: PTEN expression was significantly decreased in neo-CRT non-responders. MiR-187 overexpression significantly upregulated PTEN expression and inhibited downstream PI3K signalling in vitro. GDC-0941 significantly reduced viability and enhanced radiation response in vitro and led to tumour growth inhibition as a single agent in vivo. CONCLUSION: Targeting of PI3K signalling is a promising therapeutic strategy for OAC patients who have repressed miR-187 expression and do not respond to conventional neo-CRT. ADVANCES IN KNOWLEDGE: This is the first study evaluating the effect of PI3K inhibition on radiosensitivity in OAC, with a particular focus on patients that do not respond to neo-CRT. We have shown for the first time that targeting of PI3K signalling is a promising alternative therapeutic strategy for OAC patients who do not respond to conventional neo-CRT.	esophagus
A study of Human Epidermal Growth factor receptor-2 [HER-2] in Carcinoma Oesophagus [Single Institutional Tertiary cancer centre study from North-East part of India].	BACKGROUND: Oesophageal cancer both squamous cell [SCC] and adenocarcinoma have poor outcomes with high morbidity and mortality. Our hospital-based registry for year 2017-2018 showed that oesophageal cancer constituted 22.7% of annual case load. The main objective of this study was to determine the presence of HER-2 receptors in patients with oesophageal carcinoma in our region. METHODOLOGY: From September 2018 to September 2019, data regarding expression of HER-2 receptors was analysed in 133 patients of oesophageal carcinoma. Data were statistically described as frequencies (number of cases) and percentages where appropriate. Chi-square and Fischer's exact test was used to find out the association between categorical variables. A P value less than 0.05 was considered as statistical significant at 95% confidence interval. The statistical analysis was performed using SSPS [statistical package for the social sciences] software version 17.0. RESULTS: A total of 133 patients were taken into study. Majority of patients were males (96) with mean age of 52 years. Squamous cell carcinoma was predominant histology. HER-2 receptor positivity was seen in 6.01% of patients. Patients with HER-2 receptor positivity presented in advanced stage with poor functional status and poor grades of differentiation. Statistically significant correlation of Her-2 expression was seen with stage (p = 0.001) and pathology of tumour (p = 0.0001). CONCLUSION: Squamous cell carcinoma of oesophagus still predominates in North-eastern part of India. For studying the role of effective targeted therapies knowledge of frequency of HER-2 receptor positivity is of utmost importance in our population, and our study aims to answer this question. The present study shows low prevalence of HER-2 neu overexpression in our community, probably due to disproportionately high incidence of SCC compared to adenocarcinoma. Patients with HER-2 receptor positivity presented in advanced stage with poor functional status and poor grades of differentiation.	esophagus
Minimally Invasive Versus open AbdominoThoracic Esophagectomy for esophageal carcinoma (MIVATE) - study protocol for a randomized controlled trial DRKS00016773.	BACKGROUND: The only curative treatment for most esophageal cancers is radical esophagectomy. Minimally invasive esophagectomy (MIE) aims to reduce postoperative morbidity, but is not yet widely established. Linear stapled anastomosis is a promising technique for MIE because it is quite feasible even without robotic assistance. The aim of the present study is to compare total MIE with linear stapled anastomosis to open esophagectomy (OE) with circular stapled anastomosis with special regard to postoperative morbidity in an expertise-based randomized controlled trial (RCT). METHODS/DESIGN: This superiority RCT compares MIE with linear stapled anastomosis (intervention) to OE with circular stapled anastomosis (control) for Ivor-Lewis esophagectomy. It was initiated in February 2019, and recruitment is expected to last for 3 years. For inclusion, patients must be 18 years of age or more with a resectable primary malignancy in the distal esophagus. Participants with tumor localizations above the azygos vein, metastasis, or infiltration into adjacent tissue will be excluded. In an expertise-based approach, the allocated treatment will only be carried out by the single most experienced surgeon of the surgical center for each respective technique. The sample size was calculated with 20 participants per group for the primary endpoint postoperative morbidity according to comprehensive complication index (CCI) within 30 postoperative days. Secondary endpoints include anastomotic insufficiency, pulmonary complications, other intra- and postoperative outcome parameters such as estimated blood loss, operative time, length of stay, short-term oncologic endpoints, adherence to a standardized fast-track protocol, postoperative pain, and postoperative recovery (QoR-15). Quality of life (SF-36, CAT EORTC QLQ-C30, CAT EORTC QLQ-OES18) and oncological outcomes are evaluated with 60 months follow-up. DISCUSSION: MIVATE is the first RCT to compare OE with circular stapled anastomosis to total MIE with linear stapled anastomosis exclusively for intrathoracic anastomosis. The expertise-based approach limits bias due to heterogeneity of surgical expertise. The use of a dedicated fast-track protocol in both OE and MIE will shed light on the role of the access strategy alone in this setting. The findings of this study will serve to define which approach has the best perioperative outcome for patients requiring esophagectomy. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016773 . Registered on 18 February 2019.	esophagus
The Impact of Pretherapeutic Naples Prognostic Score on Survival in Patients with Locally Advanced Esophageal Cancer.	BACKGROUND: Naples prognostic score (NPS) is a scoring system based on albumin, cholesterol concentration, lymphocyte-to-monocyte ratio, and neutrophil-to-lymphocyte ratio reflecting host systemic inflammation, malnutrition, and survival for several malignancies. This study was designed to assess the prognostic significance of NPS in patients with locally advanced esophageal squamous cell carcinoma (ESCC) and to compare its prognostic accuracy with that of other systemic inflammatory and nutritional index. METHODS: We retrospectively examined 165 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by curative resection between January 2011 and September 2019. Patients were divided into three groups based on their NPS before neoadjuvant therapy (Group 0: NPS = 0; Group 1: NPS = 1-2; Group 2: NPS = 3-4). We compared the clinicopathological characteristics and survival rates among the groups. RESULTS: The 5-year recurrence-free survival (RFS) and overall survival (OS) rates were significantly different between the groups (P < 0.001). The NPS was superior to other systemic inflammatory and nutritional index for predicting prognoses, as determined using area under the curves (P < 0.05). Multivariate analysis demonstrated that the NPS was a significant predictor of poor RFS (Group 1: hazard ratio [HR] 1.897, P = 0.049; Group 2: HR 3.979, P < 0.001) and OS (Group 1: HR 2.152, P = 0.033; Group 2: HR 3.239, P = 0.006). CONCLUSIONS: The present study demonstrated that NPS was an independent prognostic factor in patients with locally advanced ESCC and more reliable and accurate than the other systemic inflammatory and nutritional index.	esophagus
SOX12 contributes to the activation of the JAK2/STAT3 pathway and malignant transformation of esophageal squamous cell carcinoma.	As a crucial transcription factor, sex‑determining region Y box 12 (SOX12) is closely related with tumorigenesis and malignant transformation in various malignant tumor types. To date, the specific function of SOX12 in esophageal squamous cell carcinoma (ESCC) has remained largely elusive and requires further investigation. The present study aimed to determine whether aberrant expression of SOX12 is associated with malignant development of ESCC. The expression level of SOX12 in ESCC cells and tissues was analyzed by RT‑qPCR and western blotting. Short hairpin RNA (shRNA) targeting SOX12 was transfected into ESCC cells to knock down the expression of SOX12. Colony formation and Transwell assays were used to detect viability and mobility of ESCC cells. Signaling pathway‑related proteins were assessed using western blot analysis and cellular immunofluorescence. Clinical prognosis data was analyzed by Kaplan‑Meier and Cox logistic regression. The present results revealed that SOX12 was overexpressed in ESCC cells and tissues. Knockdown of the expression of SOX12 by shRNA inhibited the colony forming efficiency, migration and invasion capacities of ESCC cells in vitro. Recombinant protein of SOX12 could restore the aggressive phenotype of ESCC cells. Furthermore, knockdown of the expression of SOX12 inhibited the activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by decreasing the expression of the JAK2/STAT3 signaling pathway. Recombinant protein of SOX12 could recover the activation of the JAK2/STAT3 signaling pathway. Analysis of the clinical data revealed that overexpression of SOX12 indicated shorter overall survival time (OS; P=0.0341) and disease‑free survival time (DFS; P=0.04). Univariate and multivariate analysis revealed that overexpression of SOX12 was an independent factor for ESCC. In conclusion, SOX12 was revealed to serve a crucial function in sustaining the viability, as well as enhancing the motility of ESCC cells via activating the JAK2/STAT3 signaling pathway. Thus, SOX12 may potentially serve as a novel biomarker and candidate for the targeted treatment of ESCC.	esophagus
Upregulation of miR-1269 Contributes to the Progression of Esophageal Squamous Cell Cancer Cells and Is Associated With Poor Prognosis.	BACKGROUND: MicroRNA-1269 (miR-1269) has been identified upregulated in several cancers, as well as in esophageal cancer. In the present study, we investigated the clinical prognostic significance and potential functional role of miR-1269 in esophageal squamous cell carcinoma (ESCC). METHODS: A total of 107 ESCC patients who underwent surgical resection were enrolled in this study. miR-1269 expression was measured using quantitative real-time PCR (qRT-PCR). Kaplan-Meier method and multivariate Cox regression analysis were used to explore the prognostic significance of miR-1269. CCK-8 assays and Transwell assays were used to investigate the effects of miR-1269 on cell proliferation, migration, and invasion. The direct association between miR-1269 and SOX6 was evaluated using a dual-luciferase reporter assay. RESULTS: The expression of miR-1269 was significantly upregulated in ESCC tissues and cell lines compared with adjacent normal tissues and esophageal epithelial cell line, respectively. What's more, the upregulation of miR-1269 was associated with positive lymph node metastasis and advanced TNM stage. ESCC patients with high miR-1269 expression had shorter overall survival than those with low miR-1269 expression levels. Compared with the control group, overexpression of miR-1269 promoted cell proliferation, migration, and invasion, while knockdown of miR-1269 inhibited cell proliferation, migration, and invasion. SOX6 was a direct target of miR-1269. CONCLUSION: These results suggest that miR-1269 plays an important role in the progression of ESCC by targeting SOX6 and may be a potential prognostic biomarker and the miR-1269/SOX6 axis may be a therapeutic target for the patient with ESCC.	esophagus
Intraoperative neuromonitoring during prone thoracoscopic esophagectomy for esophageal cancer reduces the incidence of recurrent laryngeal nerve palsy: a single-center study.	The incidence of recurrent laryngeal nerve palsy (RLNP) following minimally invasive esophagectomy has yet to be satisfactorily reduced. Use of intraoperative neuromonitoring (IONM), specifically of the RLN, during thyroidectomy has been reported to reduce the incidence of RLN injury. We now apply IONM during curative prone thoracoscopic esophagectomy, and we conducted a retrospective study to evaluate the feasibility and efficacy of intermittent monitoring of the RLN during the surgery. The study involved 32 consecutive patients who underwent esophagectomy with radical lymph node dissection for esophageal cancer. The patients were of two groups: an IONM group (n = 17) and a non-IONM group (n = 15). We chiefly strip around the esophagus preserving the membranous structure, which contains the tracheoesophageal artery, lymph nodes, and RLN. In the IONM group patients, we stimulated the RLN and measured the electromyography (EMG) amplitude after dissection, at the dissection starting point and dissection end point on both sides. For the purpose of the study, we compared outcomes between the two groups of patients. IONM was carried out successfully in all 17 patients in the IONM group. The incidence of RLNP was significantly reduced in this group. We found that both RLNs can be identified by mean of IONM easily, immediately, and safely and that the EMG amplitude attenuation rate is particularly useful for predicting RLNP.	esophagus