crossing96/oncoscreening huggingface dataset:
ZSH-2208: A novel retinoid with potent anti-tumour effects on ESCC stem cells via RARγ-TNFAIP3 axis.	BACKGROUD: Oesophageal cancer ranks among the most prevalent malignant tumours globally, primarily consisting of oesophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSCs) accelerate the progression ESCC via their strong self-renewal and tumourigenic capabilities, presenting significant clinical challenges due to increased risks of recurrence and drug resistance. METHODS: Our previous study has reported WYC-209, which is capable of inducing apoptosis of CSCs in melanoma and hepatoma, but is ineffective against ESCC. Additionally, clinical studies in ESCC still lack drug candidates that effectively target CSCs. Therefore, our team developed a series of novel retinoids that target retinoic acid receptors (RARs), with enhanced potency, broader efficacy and minimised toxic side effects against CSCs. Following iterative optimisation and pharmacological validation, ZSH-2208 was identified as the most promising candidate for effectively targeting ESCC tumour-repopulating cells (TRCs). Mechanistic exploration revealed that ZSH-2208 inhibits the growth of ESCC-TRCs through modulation of the RARγ-TNFAIP3 axis. The clinical significance of the key molecule TNFAIP3 in ESCC has also been demonstrated. RESULTS: This study introduces ZSH-2208, a novel retinoid specifically targeting ESCC-TRCs, which holds significant potential for clinical application in ESCC. KEY POINTS: The ESCC-TRCs replicates the characteristics of ESCC stem cells, which are inhibited by ZSH-2208. In vivo and in vitro experiments demonstrated that ZSH-2208, a novel RA analogue, effectively inhibits the growth of ESCC-TRCs through the RARγ-TNFAIP3 axis. Low levels of TNFIP3 protein may be associated with improved survival probability in ESCC patients.	esophagus
Current status and perspectives of esophageal cancer: a comprehensive review.	Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in-depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.	esophagus
Closure of Ventricular Septal Rupture through a Left Thoracotomy in a Patient with a History of Esophageal Reconstruction.	A 73-year-old man who had undergone esophagectomy and retrosternal gastric tube reconstruction for esophageal cancer 8 years prior was transferred to our hospital for the treatment of an acute myocardial infarction. Emergent percutaneous coronary intervention for the left anterior descending artery (#7) was successfully performed. However, echocardiography revealed a ventricular septal rupture (25×27 mm). Seventeen days after admission, the rupture was successfully treated with a double-patch closure via a left anterolateral thoracotomy to avoid a surgical injury to his retrosternal gastric tube. Determining the best surgical approach to the heart is important for safe cardiac surgery in patients after esophageal reconstruction.	esophagus
Esophagectomy in patients with liver cirrhosis: systematic review and meta-analysis of short-term outcomes.	Patients with esophageal cancer and concomitant liver cirrhosis (LC) pose a surgical challenge because of the increased risk of postoperative complications and mortality. Purpose of this study was to review the existing literature and estimate perioperative short-term outcomes of esophagectomy in this patient population. Systematic review and meta-analysis. PubMed, MEDLINE, Scopus, Web of Science, Cochrane Central Library, and ClinicalTrials.gov were queried. The search was last updated on July 30th, 2024. Primary outcomes were anastomotic leak (AL) and 90 day mortality. Ten observational studies were included for a total of 387 patients with LC. The age of the included patients ranged from 35 to 85 years, 91.2% were males. The main causes of liver cirrhosis were alcoholic (75%) and viral hepatitis (20.4%). Esophageal squamous cell carcinoma was diagnosed in 58.7% of patients. Ivor-Lewis esophagectomy with intrathoracic anastomosis was reported in 69.9% of patients, while McKeown esophagectomy with cervical anastomosis was reported in 30.1% of patients. The estimated pooled prevalence of AL and 90-day mortality were 13% (95% CI = 6-24%; I(2) = 72%) and 17% (95% CI = 10-27%; I(2) = 72%), respectively. The estimated pooled prevalence of postoperative pulmonary complication, sepsis, and liver failure were 52% (95% CI = 39-65%), 30% (95% CI = 14-52%), and 9% (95% CI = 4-17%), respectively. Esophagectomy can be performed in properly selected patients with LC and concomitant esophageal cancer. Foregut surgeons should be aware of the not negligible postoperative complications rates and mortality. Risk stratification and attentive perioperative care are essential to minimize serious adverse events.	esophagus
p53 and Ki-67 combined with periodic acid-Schiff staining for the diagnosis of early stage esophageal squamous cell carcinoma lesions in biopsy specimens.	BACKGROUND: Esophageal cancer is highly prevalent in China, predominantly represented by squamous cell carcinoma. This retrospective study sought to evaluate the diagnostic efficacy of four staining protocols in identifying early stage esophageal squamous cell carcinoma (ESCC). METHODS: A consecutive series of ninety biopsy samples of esophageal mucosa, collected retrospectively from March 2016 to December 2019, were obtained at Beijing Chao-Yang Hospital, a tertiary care facility in Beijing, China. These samples were categorized into four groups: non-neoplastic squamous lesions (Non-NSL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and early stage ESCC. Baseline, molecular analyses (p53 by immunohistochemistry and Ki-67 by immunohistochemistry), and staining analyses (hematoxylin & eosin (HE) and periodic acid-Schiff (PAS) were conducted across the categories. The staining protocols included HE, HE + p53 + Ki-67, HE + p53 + Ki-67 + PAS, and HE + p53/PAS + Ki-67/PAS. RESULTS: Patients with HGD and ESCC were significantly older and had larger lesions. Elevated p53 and Ki-67 mutation rates were observed in HGD and ESCC, while increased PAS positivity was noted in RE and LGD. The p53, Ki-67, and PAS staining results showed mostly no correlation among the four groups. Abnormal Ki-67 basal layer distribution pattern correlated with histological grades, with higher proportions in HGD and ESCC. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS demonstrated complete consistency with the reference standard, with weighted κ values of 1. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS protocols exhibited 100% accuracy, sensitivity, and specificity for diagnosing ESCC or ESCC combined with HGD, outperforming the other protocols. CONCLUSIONS: Incorporating specific staining protocols, particularly HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS, enhances the diagnostic accuracy for early stage ESCC, showing promise in advancing the pathology diagnostic pathway.	esophagus
Changes in PD-1 expression on T lymphocyte subsets and related immune indicators before and after definitive chemoradiotherapy for esophageal squamous cell carcinoma.	OBJECTIVE: This study aimed to observe the dynamic changes in the expression of T lymphocytes, natural killer (NK) cells, and PD-1 in patients with first-diagnosed esophageal squamous cell carcinoma (ESCC) before and after chemoradiotherapy (CRT) and evaluate the impact of PD-1 expression in peripheral blood on the short-term outcome of patients with ESCC. PATIENTS AND METHODS: Seventy-three patients with ESCC who were treated with definitive CRT were enrolled. Before and after CRT, flow cytometry was used to detect thePD-1 expression in the peripheral blood and related immune indicators. Peripheral blood from 10 healthy individuals was used as control. RESULTS: The percentages of CD3(+) (p = 0.018), CD4(+) (p < 0.001), and CD8(+) T cells (p < 0.001); NK cells (p = 0.009); and the CD4(+)/CD8(+) ratio (p < 0.001), as well as PD-1(+)CD3(+) (p < 0.001), PD-1(+)CD4(+) (p < 0.001), and PD-1(+)CD8(+) (p < 0.001) T cells, before CRT significantly differed from those in the post-CRT group. The percentages of PD-1(+)CD8(+) T cells differed significantly between the radiotherapy alone and CRT groups (p < 0.05). PD-1 expression in CD3(+), CD4(+), and CD8(+) T cells significantly decreased in patients achieving overall response rate (all p < 0.05). Compared with those in the incomplete response group, PD-1(+)CD8(+) T cells significantly decreased in the CR group (p < 0.05). CONCLUSION: CRT aggravated immunosuppression and increased PD-1 expression in T lymphocyte subsets in patients with ESCC, possibly related to the radiation field. PD-1 expression in T lymphocyte subsets can predict short-term outcomes in patients and provide a theoretical basis for the sequential application of PD-1 immunosuppressants after radiotherapy and chemotherapy.	esophagus
Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses.	BACKGROUND: Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications. METHODS: Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients. Mutations and rearrangements in clinically relevant cancer genes were investigated and correlated with OncoKB, a knowledge-based precision oncology database, to identify treatment implications. Genome-wide signatures and manually curated molecular profiles were also determined. RESULTS: The analyses revealed 90 targetable oncogenic mutations and fusions in 63 % of the patients, including novel NTRK, NRG1, ALK, and MET fusions, and structural variants in cancer genes like RAD51B. Also, molecular signatures associated with mismatch repair and homologous recombination deficiency were elucidated. Notably, we identified CDK12-type genomic instability associated with CDK12 fusions. CONCLUSIONS: Our findings support the potential of whole genome and transcriptome sequencing analyses as a comprehensive approach to identify treatment targets in adenocarcinoma of the stomach and the esophagus, and their application in precision oncology.	esophagus
METTL3-mediated CEP170 m6A modifications in spindle orientation and esophageal cancer cell proliferation.	Esophageal cancer is a major malignancy with a high incidence and poor prognosis. To elucidate the mechanisms underlying its progression, particularly with respect to cell division and spindle orientation, we investigated the role of m6A modifications and the centrosomal protein CEP170. Using m6A-seq and RNA-seq of esophageal cancer tissues and adjacent normal tissues, we identified significant alterations in m6A modifications and gene expression, highlighting the upregulation and m6A enrichment of CEP170 in tumor tissues. Functional assays, including cell cycle synchronization, qPCR, immunoblotting, immunofluorescence, coimmunoprecipitation, methylated RNA immunoprecipitation, and cell proliferation assays, demonstrated that CEP170 plays a critical role in mitotic progression and spindle orientation. m6A-seq and RNA-seq revealed significant alterations in m6A modifications and gene expression in esophageal cancer. CEP170 was upregulated and highly enriched in m6A modifications in tumor tissues. Functional assays revealed that CEP170 plays a critical role in proper mitotic progression and spindle orientation. Knockdown of CEP170 led to spindle misorientation and impaired the stability of astral microtubules. Additionally, CEP170 affected the localization of the dynein/dynactin motor complex in the cell cortex. METTL3 was upregulated in tumor tissues and regulated CEP170 expression. RNA-seq upon CEP170 depletion revealed that ASPM was significantly downregulated, indicating its involvement as a downstream target of CEP170 in regulating cell proliferation and mitosis. Our findings provide novel insights into the molecular mechanisms by which CEP170 and m6A modifications regulate esophageal cancer progression, revealing that CEP170 is a potential therapeutic target.	esophagus
Preoperative management of patients with oesophageal cancer: Expert recommendations.	The aim of this work is to establish recommendations for the preoperative evaluation and selection of patients with malignant oesophageal neoplasms, who are candidates for surgical resection with curative intent, based on the consensus established by a group of experts. Using the Delphi methodology and after 2 rounds of evaluation, responses were obtained from 37 experts to 47 questions about the preoperative management of oesophageal cancer, considering consensus if there was a mean score greater than 8 (range between 0-10). Of the respondents, 54% were women, with a mean age of 50.2 years, with more than 15 years of average experience in oesophageal surgery. In the preoperative evaluation, agreement was obtained on most of the recommendations, with the indication of a staging laparoscopy being the only one where it was not reached. In the preoperative optimisation, agreement was reached on nutritional, anaemia, physical status, respiratory and comorbidities evaluation, but no agreement was reached on recommending immunonutrition or echocardiography routinely. In the inoperability criteria were included ECOG greater than 1, impaired lung function, and/or Child B or C liver cirrhosis. Agreement was reached on considering unresectable tumours with invasion of the tracheobronchial tract, large vessels, and spinal column, multivisceral metastases, and/or peritoneal carcinomatosis. Therefore, the recommendations established in this manuscript may be useful to support decision-making in daily clinical practice, with a high degree of consensus that decisions regarding the management of these patients should be made on an individual basis and within a multidisciplinary committee of experts.	esophagus
EZH2 elicits CD8(+) T-cell desert in esophageal squamous cell carcinoma via suppressing CXCL9 and dendritic cells.	"CD8(+) T cell spatial distribution in the context of tumor microenvironment (TME) dictates the immunophenotypes of tumors, comprised of immune-infiltrated, immune-excluded and immune-desert, discriminating ""hot"" from ""cold"" tumors. The infiltration of cytotoxic CD8(+) T cells is associated with favorable therapeutic response. Hitherto, the immunophenotypes of esophageal squamous cell carcinoma (ESCC) have not yet been comprehensively delineated. Herein, we comprehensively characterized the immunophenotypes of ESCC and identified a subset of ESCC, which was defined as cold tumor and characterized with CD8(+) T cell-desert TME. However, the mechanism underlying the defect of CD8(+) T cells in TME is still pending. Herein, we uncovered that tumor cell-intrinsic EZH2 with high expression was associated with the immunophenotype of immune-desert tumors. Targeted tumor cell-intrinsic EZH2 rewired the transcriptional activation of CXCL9 mediated by NF-κB and concomitantly reinvigorated DC maturation differentiation via inducing the reduction of VEGFC secretion, thereby enhancing the infiltration of cytotoxic CD8(+) T cells into TME and inhibiting tumor immune evasion. Our findings identify EZH2 as a potential therapeutic target and point to avenues for targeted therapy applied to patients with ESCC characterized by CD8(+) T cell-desert tumors."	esophagus
Patterns of recurrence after esophagectomy following neoadjuvant immunochemotherapy in patients with thoracic esophageal squamous cell carcinoma.	PURPOSE: To explore the recurrence pattern and risk factors associated with the relapse of thoracic esophageal squamous cell carcinoma (TESCC) among patients who received esophagectomy following neoadjuvant immunochemotherapy (NICT). METHODS: A total of 191 TESCC patients who received esophagectomy following NICT were retrospectively reviewed from 2019 to 2022. The first recurrence patterns were assessed. The postoperative recurrence-free survival (RFS) was determined using the Kaplan-Meier method. Multivariate recurrence risk factor analysis was performed using the logistic regression model. RESULTS: As of the December 31, 2023 follow-up, 66 patients experienced recurrence, with a median time to recurrence of 10.8 months (1.2-37.3 months). The recurrence pattern included locoregional recurrence (LR), distant recurrence (DR), and LR + DR, accounting for 69.7 %, 16.7 %, and 13.6 %, respectively. Locoregional lymph node (LN) predominated the pattern of postoperative recurrence (40/66), particularly in the mediastinal station 2R (17.5 %) and 4R (16.5 %). The 2-year RFS rates for groups with dissected LN stations of ≤6, 7-9, and 10-14 were 50.5 %, 72.3 %, and 63.5 %, respectively (P = 0.04). Similarly, the 2-year RFS rates for groups with dissected LNs of <15, 15-29, and ≥30 were 49.7 %, 61.6 %, and 71.6 %, respectively (P = 0.28). Furthermore, tumor length >5 cm, the T-stage evaluation as clinically stable disease, dissected LN stations ≤6, and the ypN2-3 stage were unfavorable factors for postoperative failure in patients. CONCLUSIONS: The major pattern of LR may be LN recurrence after NICT in TESCC patients, particularly in the station 2R and 4R. In addition, less than 6 LN dissection stations or less than 15 LNs are not recommended.	esophagus
Spatial transcriptome profiling identifies DTX3L and BST2 as key biomarkers in esophageal squamous cell carcinoma tumorigenesis.	BACKGROUND: Understanding the stepwise progression of esophageal squamous cell carcinoma (ESCC) is crucial for developing customized strategies for early detection and optimal clinical management. Herein, we aimed to unravel the transcriptional and immunologic alterations occurring during malignant transformation and identify clinically significant biomarkers of ESCC. METHODS: Digital spatial profiling (DSP) was performed on 11 patients with early-stage ESCC (pT1) to explore the transcriptional alterations in epithelial, immune cell, and non-immune cell stromal compartments across regions of distinct histology, including normal tissues, low- and high-grade dysplasia, and cancerous tissues. Furthermore, single-cell spatial transcriptomics was performed using the CosMx Spatial Molecular Imaging (SMI) system on 4 additional patients with pT1 ESCC. Immunohistochemical (IHC) analysis was performed on consecutive histological sections of 20 pT1 ESCCs. Additionally, public bulk and single-cell RNA-sequencing (scRNA-seq) datasets were analyzed, and in vitro and in vivo functional studies were conducted. RESULTS: Spatial transcriptional reprogramming and dynamic cell signaling pathways that determined ESCC progression were delineated. Increased infiltration of macrophages from normal tissues through dysplasia to cancerous tissues occurred. Macrophage subtypes were characterized using the scRNA-seq dataset. Cell-cell communication analysis of scRNA-seq and SMI data indicated that the migration inhibitory factor (MIF)-CD74 axis may exhibit pro-tumor interactions between macrophages and epithelial cells. DSP, SMI, and IHC data demonstrated that DTX3L expression in epithelial cells and BST2 expression in stromal cells increased gradually with ESCC progression. Functional studies demonstrated that DTX3L or BST2 knockdown inhibited ESCC proliferation and migration and decreased M2 polarization of tumor-associated macrophages. CONCLUSIONS: Spatial profiling comprehensively characterized the molecular and immunological hallmarks from normal tissue to ESCC, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease and contributing to the prevention of ESCC. Within this exploration, we uncovered biomarkers that exhibit a robust correlation with ESCC progression, offering potential new avenues for insightful therapeutic approaches.	esophagus
Dose to cardiac substructures and cardiovascular events in esophageal cancer patients treated with definitive radiotherapy.	INTRODUCTION: While there is a growing amount of data on the cardiac toxicity of radiotherapy (RT) in relation to its impact on cardiac sub-structures (CSS), there are only few studies addressing this issue in patients followed for esophageal cancer (ESOC). We aimed to evaluate the association between independent parameters of dose received by CSS and major cardiac events (MACEs) in this population. MATERIALS AND METHODS: We retrospectively analyzed 122 patients treated with exclusive RT or chemo-RT for ESOC. Heart and CSS i.e. right atrium, left atrium (LA), right ventricle, left ventricle and myocardium, have been automatically segmented, and dose volume histogram were extracted. Cardiac events were collected focusing on the occurrence of MACEs of grade 3 or higher (G3+) and grade 4 or higher (G4+) according to the CTCAE v5.0. RESULTS: With a median follow-up of 21.9 months and in a population of high to very high cardiovascular risk (95.5%), 21 (17.2%) and 9 (7.4%) patients had G3 + and G4 + MACEs with a respective median time to event of 13.05 and 9.8 months. After multivariate analysis and among all heart and CSS-based dosimetric features, only the volume of LA receiving 15 Gy or more (V15LA) remained significantly associated with the G3 + and G4 + MACEs. The use of volumetric modulated arctherapy significantly reduced V15LA compared with 3D conformal RT. CONCLUSION: In a cohort of ESOC patients treated with exclusive RT, incidence of MACEs was associated with V15LA, underlining the importance of CSS. These high cardiovascular (CV) risk patients should benefit from standard CV assessment and strict control of their risk factors.	esophagus
Impact of Fusobacterium nucleatum in the treatment of cancer, including radiotherapy and its future potential in esophageal cancer.	Despite advances in multimodality therapy, including surgery, chemotherapy, radiation therapy and chemoradiation, the fatality rate for esophageal cancer remains high. Specifically, Fusobacterium nucleatum, due to its aggregation capacity, has shown a tendency to form biofilms. The biofilm-forming capabilities of microbial communities are of utmost importance in the context of cancer treatment, as they have been shown to drive significant losses in the efficaciousness of various cancer treatments. Therefore, elucidating the dynamics of F. nucleatum will be important for the development of effective treatments for esophageal cancer. Therefore, this review summarizes the current knowledge of F. nucleatum, its involvement in cancer and its impact on chemotherapy and radiation therapy. In conclusion, further research on the role of F. nucleatum is essential for the continued advancement of the treatment of esophageal cancer and patient care.	esophagus