Intravesical delivery of rapamycin via folate-modified liposomes dispersed in thermo-reversible hydrogel

Two-dimensional (2D) cell culture is a valuable method for cell-based research but can provide unpredictable, misleading data about in vivo responses. In this study, we created a three-dimensional (3D) cell culture environment to mimic tumor characteristics and cell-cell interactions to better characterize the tumor formation response to chemotherapy. We fabricated the 3D cell culture samples using a 3D cell bio printer and the bladder cancer cell line 5637. T24 cells were used for 2D cell culture. Then, rapamycin and Bacillus Calmette-Guérin (BCG) were used to examine their cancer inhibition effects using the two bladder cancer cell lines. Cell-cell interaction was measured by measuring e-cadherin and n-cadherin secreted via the epithelial-mesenchymal transition (EMT). We constructed a 3D cell scaffold using gelatin methacryloyl (GelMA) and compared cell survival in 3D and 2D cell cultures. 3D cell cultures showed higher cancer cell proliferation rates than 2D cell cultures, and the 3D cell culture environment showed higher cell-to-cell interactions through the secretion of E-cadherin and N-cadherin. Assessment of the effects of drugs for bladder cancer such as rapamycin and BCG showed that the effect in the 2D cell culture environment was more exaggerated than that in the 3D cell culture environment. We fabricated 3D scaffolds with bladder cancer cells using a 3D bio printer, and the 3D scaffolds were similar to bladder cancer tissue. This technique can be used to create a cancer cell-like environment for a drug screening platform.

We investigated the prognostic significance of macroscopic tumor necrosis in renal cell carcinoma. We retrospectively analyzed the records of 485 patients who underwent surgical treatment for organ confined or metastatic renal cell carcinoma. The presence or absence of tumor necrosis was evaluated based on macroscopic description of the tumor, and tumors were considered necrotic only if they exhibited more than 10% macroscopic necrosis. Macroscopic tumor necrosis was identified in 27% of total patients. Patients with macroscopic necrotic renal cell carcinoma were more likely to have larger tumor, metastatic disease, higher local stage and higher tumor grade (all p < 0.001). Pathological features of microvascular invasion (p = 0.026) and sarcomatoid differentiation (p = 0.002) along with several laboratory findings were also observed to be associated with macroscopic tumor necrosis. Among the total subjects those without macroscopic tumor necrosis had significantly higher progression-free (p < 0.0001) and disease specific survival (p < 0.0001). When survival analysis was limited to nonmetastatic tumors only, the same logic applied, which was not the case for the patients with metastatic disease (p > 0.05). Among the different histological subtypes of renal cell carcinoma, macroscopic tumor necrosis was observed to have a significant impact only for the clear cell subtype. In patients with nonmetastatic RCC multivariate analysis revealed that macroscopic tumor necrosis (p = 0.004) was an independent prognostic predictor of disease specific survival along with pathological T stage, tumor grade and tumor size. Our results suggest that macroscopic tumor necrosis may be a reliable prognostic indicator for nonmetastatic clear cell renal cell carcinoma which should routinely be examined for during pathological analysis.