Suppression of PI3Kp110ß Reduces Cell Viability and Induces Apoptosis in Human Esophageal Cancer.

OBJECTIVE: Activation of PI3K pathway has been reported to promote survival, tumorigenicity and metastasis in the esophageal cancer (EC), and the PI3Kp110ß (one of PI3K family) contributed to tumorigenesis in types of cancers. However, it is still unclear whether PI3Kp110ß effects the progression of EC. METHODS: RT-qPCR and western blot were used to detect the expression of PI3Kp110ß in the patients with EC and ECA-109 cells transfected with si-PI3Kp110ß. CCK-8 and clonogenic assays were performed to analyze the proliferation of ECA-109 cells. Flow cytometry was used to investigate cell cycle and apoptosis of ECA-109 cells. RESULTS: The expression of PI3Kp110ß was up-regulated in the patients with EC by online RNA Sep data and RT-qPCR assay. Compared with the ECA-109 cells with si-control, the proliferation was suppressed in the ECA-109 cells with si-PI3Kp110ß. The G1 phase of the cells with si-PI3Kp110ß was significantly higher than that of cells with si-control. The apoptosis of cells with si-PI3Kp110ß was accelerated, compared with that of cells with si-control. The expression of cyclinD1 and Bcl-2 was decreased, while the expression of Bax was increased in the ECA-109 cells with si-PI3Kp110ß. CONCLUSION: Inhibition of si-PI3Kp110ß attenuates cell viability and enhances apoptosis in esophageal cancer.

Ginsenoside compound K inhibits the proliferation, migration and invasion of Eca109 cell via VEGF-A/Pi3k/Akt pathway.

OBJECTIVE: Esophageal cancer, one of the most common cancers in the upper digestive tract and is one of the leading cancer-related mortality worldwide. Accumulating studies found that Ginsenoside compound K (CK) has significantly anti-tumor effects, especially in the suppression of proliferation, migration, as well as invasion in various human cancers. While the effects of Ginsenoside CK in esophageal cancer have not been well studied. In our present study, we aim to explore the functions and mechanisms of Ginsenoside CK in the progression of esophageal cancer cells (Eca109). METHODS: Cell Counting Kit-8 (CCK-8), wound healing, transwell and flow cytometry assays were applied to analyze the effects of Ginsenoside CK in the progression of Eca109 cell, western blot assay was used to investigate the potential downstream signaling pathway after Ginsenoside CK treatment. RESULTS: Our study found that Ginsenoside CK can suppress cell proliferation, migration and invasion of Eca109 cell. Furthermore, the flow cytometry showed that Ginsenoside CK increased of apoptosis rates in Eca109 cell. The western blot results indicated that Ginsenoside CK decreased the expression of VEGF-A, P-Pi3k and P-Akt proteins. Moreover, the knockdown of VEGF-A gene could suppress cell proliferation, migration, invasion and induce apoptosis in Eca109 cell, and the expression of P-Pi3k and P-Akt proteins were significantly downregulated. CONCLUSIONS: Our study suggests that Ginsenoside CK inhibits the proliferation, migration, invasion, and induced apoptosis of Eca109 cell by blocking VEGF-A/Pi3k/Akt signaling pathway.

An Immunogenic Cell Death-Related Classification Predicts Prognosis and Response to Immunotherapy in Head and Neck Squamous Cell Carcinoma.

Immunogenic cell death (ICD) has been classified as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response. Accumulating evidence has demonstrated the ability of ICD to reshape the tumor immune microenvironment through the emission of danger signals or DAMPs, which may contribute to the immunotherapy. Currently, identification of ICD-associated biomarkers that stratify patients according to their benefit from ICD immunotherapy would be of great advantage. Here, we identified two ICD-associated subtypes by consensus clustering. ICD-high subtype was associated with the favorable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signaling. Besides, we established and validated an ICD-related prognostic model that predicted the survival of HNSCC and was associated with tumor immune microenvironment. In conclusion, we established a new classification system of HNSCC based on ICD signatures. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of HNSCC patients.

Serum Inflammatory Biomarkers Contribute to the Prognosis Prediction in High-Grade Glioma.

BACKGROUND: To evaluate the prognostic value of serum inflammatory biomarkers and develop a risk stratification model for high-grade glioma (HGG) patients based on clinical, laboratory, radiological, and pathological factors. MATERIALS AND METHODS: A retrospective study of 199 patients with HGG was conducted. Patients were divided into a training cohort (n = 120) and a validation cohort (n = 79). The effects of potential associated factors on the overall survival (OS) time were investigated and the benefits of serum inflammatory biomarkers in improving predictive performance was assessed. Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, and support vector machines (SVM) were used to select variables for the final nomogram model. RESULTS: After multivariable Cox, LASSO, and SVM analysis, in addition to 3 other clinico-pathologic factors, platelet-to-lymphocyte ratio (PLR) >144.4 (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.25-3.38; P = 0.005) were left for constructing the predictive model. The model with PLR exhibited a better predictive performance than that without them in both cohorts. The nomogram based on the model showed an excellent ability of discrimination in the entire cohort (C-index, 0.747; 95%CI, 0.706-0.788). The calibration curves showed good consistency between the predicted and observed survival probability. CONCLUSION: Our study confirmed the prognostic value of serum inflammatory biomarkers including PLR and established a comprehensive scoring system for the OS prediction in HGG patients.

Clinical significance of the expression of EGFR signaling pathway-related proteins in esophageal squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) signaling is an important pathway that is not only involved in the determination of cellular development, but also has significant roles in tumor development and progression. The study aims to examine the expression of EGFR signaling pathway-related proteins (EGFR, c-Fos, and c-erb-B2) in esophageal squamous cell carcinoma and to investigate their relationships with clinical significance. Sixty esophageal squamous carcinoma specimens obtained by fiber esophagoscope were subjected to two-step immunohistochemistry to test the expression of EGFR, c-Fos, and c-erb-B2. EGFR expression was observed in 73.3% of tumors (44/60); positive EGFR expression was significantly correlated with tumor-node-metastasis (TNM) staging, lymph node metastasis, and distant metastasis (P < 0.05). c-Fos expression was found in 85% (51/60) of tumors, and its expression was significantly related to tumor depth and TNM staging (P < 0.05). c-erb-B2 expression was 75% (45/60) in esophageal squamous cell carcinoma (ESCC) specimens, and positive-erb-B2 expression had a significant association with the depth of tumor invasion (P < 0.05). c-Fos expression was significantly and positively correlated with c-erb-B2 (P < 0.05). Overexpression of EGFR, c-Fos, and c-erb-B2 was associated with tumor progression and development. EGFR and c-Fos expression can predict the tumor stage. c-Fos and c-erb-B2 expression can be used to determine the depth of tumor invasion and can also act as a combined prognostic indicator in ESCC.

Growth, clonability, and radiation resistance of esophageal carcinoma-derived stem-like cells.

OBJECTIVE: To separate/enrich tumor stem-like cells from the human esophageal carcinoma cell line OE-19 by using serum-free suspension culture and to identify their biological characteristics and radiation resistance. METHODS: OE-19 cells were cultivated using adherent and suspension culture methods. The tumor stem-like phenotype of CD44 expression was detected using flow cytometry. We examined growth characteristics, cloning capacity in soft agar, and radiation resistance of 2 groups of cells. RESULTS: Suspended cells in serum-free medium formed spheres that were enriched for CD44 expression. CD44 was expressed in 62.5% of suspended cells, but only in 11.7% of adherent cells. The suspended cells had greater capacity for proliferation and colony formation in soft agar than the adherent cells. When the suspended and adherent cells were irradiated at 5 Gy, 10 Gy, or 15 Gy, the proportion of CD44+ suspended cells strongly and weakly positive for CD44 was 77.8%, 66.5%, 57.5%; and 21.7%, 31.6%, 41.4%, respectively. In contrast, the proportion of CD44+ adherent cells strongly positive for CD44 was 18.9%, 14.%, and 9.95%, respectively. When the irradiation dose was increased to 30 Gy, the survival of the suspended and adherent cells was significantly reduced, and viable CD44+ cells were not detected. CONCLUSION: Suspended cell spheres generated from OE-19 esophageal carcinoma cells in serum-free stem medium are enriched in tumor stem-like cells. CD44 may be a marker for these cells.