Epidermal growth factor receptor (EGFR) is expressed in various types of cancer and is associated with the malignant biological behavior of cancer cells. In the present study, the expression of EGFR in hepatocellular carcinoma (HCC) tissues and liver cancer cells was detected by immunohistochemical staining, western blotting and immunofluorescence. Furthermore, a lentivirus was transduced into HepG2 liver cancer cells to knock down EGFR expression. Cell proliferation and migration, and the expression levels of epithelial‑mesenchymal transition (EMT) markers were assessed by EdU staining, Cell Counting Kit‑8, colony formation, wound healing and Transwell assays, and western blotting. The results revealed that EGF/EGFR can mediate EMT through the Akt/glycogen synthase kinase‑3β (GSK-3β)/Snail signaling pathway to promote HepG2 cell proliferation and migration. Inhibition of the activation of the EGFR signaling pathway can help to partially reverse the EMT phenotype, and inhibit the proliferation and migration of HepG2 cells. In conclusion, the EGFR/Akt/GSK-3β/Snail signaling pathway serves an important role in HCC progression, and inhibition of the activation of the EGFR signaling pathway may be a valuable strategy in liver cancer treatment.

Background: Bladder cancer is often prone to recurrence and metastasis. We sought to construct nomogram models to predict the overall survival (OS) and cancer-specific survival (CSS) of bladder cancer patients. Methods: A reliable random split-sample approach was used to divide patients into two groups: modeling and validation cohorts. Uni-variate and multivariate survival analyses were used to obtain the independent prognostic risk factors based on the modeling cohort. A nomogram was constructed using the R package, “rms”. Harrell’s concordance index (C-index), calibration curves and receiver operating characteristic (ROC) curves were applied to evaluate the discrimination, sensitivity and specificity of the nomograms using the R packages “hmisc”, “rms” and “timeROC”. A decision curve analysis (DCA) was used to evaluate the clinical value of the nomograms via R package “stdca.R”. Results: 10,478 and 10,379 patients were assigned into nomogram modeling and validation cohorts, respectively (split ratio ≈ 1:1). For OS and CSS, the C-index values for internal validation were 0.738 and 0.780, respectively, and the C-index values for external validation were 0.739 and 0.784, respectively. The area under the ROC curve (AUC) values for 5- and 8-year OS and CSS were all greater than 0.7. The calibration curves show that the predicted probability values of 5- and 8-year OS and CSS are close to the actual OS and CSS. The decision curve analysis revealed that the two nomograms have a positive clinical benefit. Conclusion: We successfully constructed two nomograms to forecast OS and CSS for bladder cancer patients. This information can help clinicians conduct prognostic evaluations in an individualized manner and tailor personalized treatment plans.

Objective: This study explored the potential molecular mechanisms of ursolic acid (UA) in bladder cancer treatment using network pharmacology and molecular docking. Methods: The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were used to screen potential targets of UA. Relevant bladder cancer target genes were extracted using the GeneCards database. All data were pooled and intercrossed to obtain common target genes of UA and bladder cancer. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Molecular docking was conducted to verify the possible binding conformation between UA and bladder cancer cells. Then, in vitro experiments were performed to further validate the predicted results. Results: UA exerts anti-tumor effects on bladder cancer through multiple targets and pathways. Molecular docking indicated that UA undergoes stable binding with the proteins encoded by the top six core genes ( STAT3, VEGFA, CASP3, TP53, IL1B, and CCND1). The in vitro experiments verified that UA can induce bladder cancer cell apoptosis by regulating the PI3K/Akt signaling pathway. Conclusions: Our study illustrated the potential mechanism of UA in bladder cancer based on network pharmacology and molecular docking. The results will provide scientific references for follow-up studies and clinical treatment.

What is known and objective First-line and second-line immunotherapy with programmed death-1 (PD-1) inhibitors both improve overall survival in patients with advanced oesophageal squamous cell cancer (ESCC). This study explored survival differences between first-line and second-line PD-1 inhibition in advanced ESCC. Methods This registry study included 167 patients with advanced ESCC who were exposed to PD-1 inhibitors in either a first-line or a second-line setting between 15 January 2019 and 31 October 2020. The primary endpoint was overall survival, and secondary endpoints included overall tumour response, progression-free survival (PFS) and PFS2. A propensity score-matching (PSM) analysis was performed using the nearest-neighbour method. Results and discussion Sixty-one patients started first-line treatment with chemotherapy and a PD-1 inhibitor (Group 1), while 106 started chemotherapy as the first-line choice and received a PD-1 inhibitor as the second-line choice (Group 2). The median PFS was 7.1 months in Group 1 and 4.1 months in Group 2 (log-rank p = 0.001). The median PFS2 was 7.1 months in Group 1 and 7.4 months in Group 2 (log-rank p = 0.4). Before PSM, the median overall survival was 13.5 months in Group 1 and 14.1 months in Group 2 (log-rank p = 0.9), and the sensitivity analysis showed consistent results (14.0 vs. 14.1 months). After PSM, the median overall survival rates for Group 1 (n = 61) and Group 2 (n = 61) were 13.5 and 13.1 months (log-rank p = 0.7) respectively. What is new and conclusion In this study, patients with advanced ESCC who received first-line or second-line PD-1 inhibitors seemed to have comparable overall survival.

Ursolic acid (UA) is a natural compound that exists in a number of Chinese medicinal herbs, which has been demonstrated to enhance the efficacy of chemotherapy in multiple types of cancer. The present study aimed to observe whether UA enhances the antitumor effects of gemcitabine (GEM) in human bladder cancer (BCa) cell lines, and to investigate the possible underlying mechanisms. The human BCa cell lines, T24 and 5637, were treated with GEM and/or UA in vitro. Cell viability was measured by the Cell Counting Kit-8 assay. Apoptosis was detected using Hoechst 33258 staining, western blot analysis and flow cytometry. The expression levels of signaling pathway-related proteins were detected using western blot analysis. UA and GEM synergistically inhibited the proliferation of human BCa cells. Compared with GEM treatment alone, the combination of GEM and UA led to enhanced the antitumor effects, which were associated with the induction of apoptosis. The PI3K/AKT and JNK signaling pathways were involved in human BCa cells treated with GEM and UA. Both the AKT activator, SC79, and the JNK inhibitor, SP600125, reduced the expression of cleaved PARP and cleaved caspase-3. On the whole, the results of the present study demonstrate that UA enhances GEM-induced apoptosis by inactivating the PI3K/AKT signaling pathway and activating the JNK signaling pathway in human BCa cells.

Rationale: The giant cystic pheochromocytomas (>10 cm) are exceedingly rare. Due to the massive size of tumor, traditional laparoscopic minimally invasive surgery poses significant technical challenges. Patient concerns: We present the case of a 53-year-old male patient who was admitted due to poorly controlled hypertension and an ultrasound-detected right adrenal mass. Diagnoses: Abdomen computed tomography scans revealed a cystic mass (11 cm × 9 cm) in the right adrenal gland, highly suggestive of pheochromocytoma. The laboratory findings demonstrate significantly elevated levels of catecholamines and their metabolites. Histopathological examination confirmed the diagnosis of cystic pheochromocytoma. Interventions: After 2 weeks of preoperative α-blockade preparation, the patient successfully underwent robot-assisted laparoscopic resection of the right adrenal tumor. Outcomes: At the 6-week postoperative evaluation, catecholamine levels had normalized. Blood pressure has returned to normal range in the absence of antihypertensive therapy and there are no more symptoms of dizziness and palpitations. The patient remained disease-free with no evidence of recurrence or metastasis during 1 year of surveillance. Lessons: In this case, we demonstrate the successful resection of a giant cystic pheochromocytoma in the right adrenal gland using robotic-assisted laparoscopy. This approach overcomes the technical limitations of conventional laparoscopy for large-volume adrenal pheochromocytomas and provides a novel therapeutic alternative for these challenging tumors.