RESUMEN
BACKGROUND: Growth differentiation factor 15 (GDF15), a member of the transforming growth factor beta (TGF-ß) superfamily, is involved in various pathophysiological processes such as anorexia, obesity, inflammation, and tumorigenesis. However, the role of GDF15 in clear cell renal cell carcinoma (ccRCC) remains poorly understood. METHODS: Clinical significance of GDF15 in ccRCC as well as other types of human cancers was analyzed using the TCGA PANCAN dataset. Gene Set Enrichment Analysis (GSEA) was used to study the significantly enriched pathways associated with GDF15 expression. qRT-PCR was used to quantitatively assess relative mRNA expression level. Flow cytometry was used to detect cell cycle. CCK-8 assay, colony formation assay, wound healing assay, Transwell migration/invasion assay, and EdU assay were used to comprehensively examine tumor viability and aggressiveness. MDA and iron assays were used to determine ferroptosis-related intracellular changes. RESULTS: We found that GDF15 expression is decreased in renal carcinoma tissue. In 769-p and Caki-1 cells, GDF15 knockdown significantly promoted tumor viability, proliferation, and migration. Conversely, overexpression of GDF15 suppressed cell proliferation and invasion. Results from GSEA suggested that GDF15 might play a crucial role in ferroptosis. We further demonstrated that GDF15 is correlated with intracellular iron and lipid peroxidation MDA in 769-p and Caki-1 cells. In summary, we conclude that GDF15 inhibits migration and invasion of ccRCC cells by regulating ferroptosis. CONCLUSION: Our study demonstrates that GDF15 downexpression promotes viability and aggressiveness of ccRCC cells by abolishing ferroptosis, which confers unfavorable patient survival outcomes.
RESUMEN
OBJECTIVE: To investigate the efficacy and safety of transurethral holmium laser resection (THOLR) and transurethral electrocision (TUR) combined with intravesical epirubicin within 24 hours postoperatively for treatment of non-muscular invasive bladder cancer. METHODS: A total of 218 consecutive patients who were newly diagnosed with bladder cancer were enrolled in this prospective study from July 2014 to December 2017. The patients were randomly divided into THOLR and TUR groups. All patients received intravesical epirubicin (30 mg dissolved in 5% glucose solution) within 24 hours postoperatively. The operation time, blood loss, rate of obturator reflex, hospitalization time, catheterization time, complications, and recurrence were analyzed. RESULTS: Operation, hospitalization, and catheterization times were significantly greater in the TUR group than in the THOLR group. The rates of blood loss and intraoperative obturator reflex were also significantly greater in the TUR group. There were no significant differences in complications, recurrence rate survival, or recurrence-free survival between the two groups, with the exception of bladder perforation rate. CONCLUSIONS: THOLR and TUR combined with intravesical epirubicin within 24 hours postoperatively were both safe and effective for treatment of bladder tumor; however, patients who undergo THOLR might experience more rapid recovery.
