A new murine esophageal organoid culture method and organoid-based model of esophageal squamous cell neoplasia.
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ABSTRACT:
SUBMITTER: Zheng B
PROVIDER: S-EPMC8633967 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We sought to develop esophageal minimum essential organoid culture medium (E-MEOM) for culturing murine esophageal organoids (EOs) and establishing an early ESCC model. We formulated E-MEOM that is sufficient to grow EOs from a single cell with clonal expansion, maintenance, and passage. From the IHC and single cell RNA sequencing of EOs results, we found that EOs cultured in E-MEOM were histologically and functionally equivalent to the esophageal epithelium.
2021-11-17 | GSE174577 | GEO
Project description:A New Murine Esophageal Organoid Culture Method and Organoid-Driven Model of Esophageal Squamous Cell Neoplasia
| PRJNA730569 | ENA
Project description:Neonatal mouse cochlear duct cells can proliferate and grow in vitro into inner ear organoids. Distinctive cochlear duct cell types have different organoid formation capacities. Here, we provide a flow cytometric cell-sorting method that allows the subsequent culture of individual cochlear cell populations. For the efficient culture of the sorted cells, we provide protocols for growing free-floating inner ear organoids, the adherence of organoids to a substrate, and the expansion of organoid-derived inner ear colonies. For complete details on the use and execution of this protocol, please refer to Kubota et al. (2021).
| S-EPMC8271165 | biostudies-literature
Project description:BackgroundEndocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS.MethodsThis study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions.ResultsESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7-99.7%), specificity (95% CI) was 100% (92.7-100%), diagnostic accuracy (95% CI) was 98.9% (94.0-99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4-100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5-99.7%).ConclusionsECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.
| S-EPMC9123668 | biostudies-literature
Project description:BackgroundIn view of the low accuracy of the prognosis model of esophageal squamous cell carcinoma (ESCC), this study aimed to optimize the least squares support vector machine (LSSVM) algorithm to determine the uncertain prognostic factors using a Cloud model, and consequently, to establish a new high-precision prognosis model of ESCC.MethodsWe studied 4,771 ESCC patients(training samples) from the Surveillance, Epidemiology, and End Results (SEER) database and 635 ESCC patients(validation samples) from the Henan Provincial Center for Disease Control and Prevention (HCDC) database, with the same exclusion criteria and inclusion criteria for both databases, and obtained permission to obtain a research data file in the SEER database from the National Cancer Institute. The independent risk factors were analyzed using the log-rank method, survival curves, univariate and multivariate Cox analysis. Finally, the independent prognostic factors were used to construct the nomogram, random forest and Cloud-LSSVM prognostic models were utilized for validation.ResultsThe overall median survival time of the SEER database was 14 months (HCDC samples was 46 months), the mean survival time was 26.5 months (HCDC samples was 36.8 months), and the 3-year survival rate was 65.8%. This is because most of the patients with Henan samples are early ESCC, and most of the Seer patients are T3 and T4 people. The multivariate Cox analysis showed that age at diagnosis (P<0.001), sex (P=0.001), race (P=0.002), differentiation grade (P<0.001), pathologic T category (P<0.001), and pathologic M category (P<0.001) were the factors affecting the prognosis of ESCC patients. The SEER data and HCDC database results showed that the accuracy of the Cloud-LSSVM (C-index =0.71, 0.689) model is higher than the differentiation grade (C-index =0.548, 0.506), random forest (C-index =0.649, 0.498), and nomogram (C-index =0.659, 0.563). This new model can realize the unity of the randomness and fuzziness of the Cloud model and utilize the powerful learning and non-linear mapping abilities of LSSVM.ConclusionsDue to the difference of clans between training samples and test samples, the accuracy of prediction is generally not high, but the accuracy of Cloud-LSSVM model is much higher than other models. The new model provides a clear prognostic superiority over the random forest, nomogram, and other models.
| S-EPMC10586994 | biostudies-literature
Project description:AimTo evaluate the diagnostic potential of Lugol's chromoendoscopy-guided confocal laser endomicroscopy (CLE) in detecting superficial esophageal squamous cell neoplasia (ESCN).MethodsBetween December 2008 and September 2010, a total of 52 patients were enrolled at the Chinese PLA General Hospital in Beijing, China. First, Lugol's chromoendoscopy-guided CLE was performed in these patients and the CLE in vivo histological diagnosis was recorded. Then, chromoendoscopy-guided biopsy was performed in the same patients by another endoscopist who was blinded to the CLE findings. Based on the biopsy and CLE diagnosis, en bloc endoscopic resection was performed. The CLE in vivo diagnosis and the histological diagnosis of biopsy of ESCN were compared, using a histological examination of the endoscopic resection specimens as the standard reference.ResultsA total of 152 chromoendoscopy-guided biopsies were obtained from 56 lesions. In the 56 lesions of 52 patients, a total of 679 CLE images were obtained vs 152 corresponding biopsies. The sensitivity, specificity, negative predictive value and positive predictive value of chromoendoscopy-guided CLE compared with biopsy were 95.7% vs 82% (P < 0.05), 90% vs 70% (P < 0.05), 81.8% vs 46.7% (P < 0.05), and 97.8% vs 92.7% (P > 0.05), respectively. There was a significant improvement in sensitivity, specificity, negative predictive value, and accuracy when comparing chromoendoscopy-guided CLE with biopsy.ConclusionLugol's chromoendoscopy-guided CLE is a real-time, non-invasive endoscopic diagnostic technology; the accuracy of the detection of superficial ESCN is equivalent to or may be superior to biopsy histology.
| S-EPMC4462739 | biostudies-literature
Project description:Smoking and alcohol consumption are major risk factors for the development of esophageal squamous cell carcinoma (ESCC). Recent studies have demonstrated that smoking and alcohol consumption may be associated with altered DNA methylation in human cancer development. The aim of the present study was to evaluate methylation-modulated protein expression of tumor-related genes (TRGs) in the early stages of esophageal squamous neoplasia (ESN). ESN tissue samples (n=141) comprising 19 cases of low-grade intraepithelial neoplasia (LGIN), 70 of high-grade intraepithelial neoplasia/carcinoma in situ (HGIN/CIS) and 52 of invasive cancer, were endoscopically resected. The methylation-modulated protein expression of 5 TRGs [fragile histidine triad (FHIT), E-cadherin, MutL homolog 1 (MLH1) /MutS homolog 2 (MSH2) and cyclooxygenase-2 (COX-2)] as well as p53 was examined with immunohistochemistry, and their expression was compared with patient clinicopathological characteristics. Reduced or loss of FHIT, E-cadherin, MLH1/MSH2 and COX-2 expression was detected in 26.3 (5/19), 5.3 (1/19), 0 (0/19) and 63.2% (12/19) of LGIN cases, 61.4 (43/70), 18.6 (13/70), 7.1 (5/70) and 65.7% (46/70) of HGIN/CIS cases, and 78.8 (41/52), 50.0 (26/52), 11.5 (6/52) and 59.6% (31/52) of invasive cancer cases, respectively. Reduced or absent expression of FHIT and E-cadherin was significantly associated with neoplastic progression (FHIT, P=0.0007; E-cadherin, P=0.00014). The mean number of TRGs (FHIT, E-cadherin, MLH1/MSH2, and COX-2) that exhibited reduced or absent expression in LGIN, HGIN/CIS and invasive cancer specimens was 1.12±0.61, 1.66±0.93 and 2.09±0.96, respectively, demonstrating a significant stepwise increment from LGIN to HGIN/CIS and then to invasive cancer (P<0.05). p53 overexpression was frequently detected in ESN with head and neck carcinomas. However p53 overexpression was not significantly associated with ESN progression. An increase in the number of the 5 TRG proteins with reduced or loss of expression in the early stages of esophageal tumorigenesis was demonstrated, and their decreased expression was observed to be associated with tumor progression. Therefore, smoking and alcohol drinking may be associated with not only carcinogenesis but also the progression of ESN.
| S-EPMC5494775 | biostudies-other
Project description:BackgroundThe prognostic role of lactate dehydrogenase (LDH) has been confirmed in many malignant tumors, but it has not been widely discussed in esophageal squamous cell cancer (ESCC). This study aimed to assess the prognostic value of LDH in patients with ESCC and to generate a risk score model to predict prognosis in patients who were treated with chemoradiotherapy.MethodsA total of 614 patients with ESCC who received chemoradiotherapy from 2012 to 2016 were examined in this single-center retrospective study. The optimal cutoff points for age, cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), carcinoembryonic antigen (CEA), tumor length, total dose, and LDH were calculated by the X-tile software. We analyzed the association between the level of LDH and clinicopathological characteristics, and a 1:3 propensity score matching analysis was used to compensate for differences in baseline characteristics. Kaplan-Meier and Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). Based on the results, we developed a corresponding risk score model and established a nomogram to assess its predictive capacity.ResultsThe optimal cutoff point of LDH was 134 U/L. Patients in the high-LDH group had significantly shorter PFS and worse OS than did those in the low-LDH group (all P values <0.05). Multivariate survival analysis indicated that pretreatment serum LDH level (P=0.039), Cyfra21-1 level (P=0.003), tumor length (P=0.013), clinical N stage (P=0.047), and clinical M stage (P=0.011) were independent predictors for OS in patients with ESCC who underwent chemoradiotherapy. Furthermore, a risk score model based on these 5 prognostic factors was established to divide patients into 3 prognostic groups to identify those patients with ESCC who were most likely to benefit from chemoradiotherapy (χ2=20.53; P<0.0001). However, the prediction nomogram that integrated the significant independent factors for OS is not performed very well in predicting survival (C-index =0.599).ConclusionsPretreatment serum LDH level may be a reliable factor in predicting the therapeutic effect of chemoradiotherapy in ESCC. Further validation is needed before this model can be widely used in clinical practice.
| S-EPMC10183543 | biostudies-literature
Project description:Background: The aim of this study was to identify prognostic markers for esophageal squamous cell carcinoma (ESCC) and build an effective prognostic nomogram for ESCC. Methods: A total of 365 patients with ESCC from three medical centers were divided into four cohorts. In the discovery phase of the study, we analyzed transcriptional data from 179 cancer tissue samples and identified nine marker genes using edgeR and rbsurv packages. In the training phase, penalized Cox regression was used to select the best marker genes and clinical characteristics in the 179 samples. In the verification phase, these marker genes and clinical characteristics were verified by internal validation cohort (n = 58) and two external cohorts (n = 81, n = 105). Results: We constructed and verified a nomogram model based on multiple clinicopathologic characteristics and gene expression of a patient cohort undergoing esophagectomy and adjuvant radiochemotherapy. The predictive accuracy for 4-year overall survival (OS) indicated by the C-index was 0.75 (95% CI, 0.72-0.78), which was statistically significantly higher than that of the American Joint Committee on Cancer (AJCC) seventh edition (0.65). Furthermore, we found two marker genes (TM9SF1, PDZK1IP) directly related to the OS of esophageal cancer. Conclusion: The nomogram presented in this study can accurately and impersonally predict the prognosis of ESCC patients after partial resection of the esophagus. More research is required to determine whether it can be applied to other patient populations. Moreover, we found two marker genes directly related to the prognosis of ESCC, which will provide a basis for future research.
| S-EPMC8921680 | biostudies-literature
Project description:Salivary glands that produce and secrete saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we establish long-term murine and human salivary gland organoid cultures. Murine and human salivary gland organoids express gland-specific genes and proteins of acinar, myoepithelial, and duct cells, and exhibit gland functions when stimulated with neurotransmitters. Furthermore, human salivary gland organoids are established from isolated basal or luminal cells, retaining their characteristics. Single-cell RNA sequencing also indicates that human salivary gland organoids contain heterogeneous cell types and replicate glandular diversity. Our protocol also enables the generation of tumoroid cultures from benign and malignant salivary gland tumor types, in which tumor-specific gene signatures are well-conserved. In this study, we provide an experimental platform for the exploration of precision medicine in the era of tissue regeneration and anticancer treatment.
| S-EPMC9174290 | biostudies-literature