Radical Cystectomy and Orthotopic Bladder Substitution Using Ileum

Over the past decade, continent urinary diversion, especially orthotopic bladder substitutions, has become increasingly popular following radical cystectomy for bladder cancer. The ultimate goal of orthotopic bladder substitution is to offer patients the best quality of life, similar to that of patients with native bladders. To achieve that purpose, surgeons should be familiar with the characteristics of good candidates for neobladders, the possible intraoperative and postoperative problems related to the surgery, and the solutions to these problems. Postoperative surveillance and instructions given to the patients also contribute to successful, functional results. Here, we reviewed the indications, pitfalls, and solutions for orthotopic bladder substitutions and the patients' quality of life after surgery. When performed properly, orthotopic continent diversion offers good quality of life with few long-term complications. Therefore, we believe it is the best option for the majority of patients requiring cystectomy

Functional Duality of Chondrocyte Hypertrophy and Biomedical Application Trends in Osteoarthritis

Chondrocyte hypertrophy is one of the key indicators in the progression of osteoarthritis (OA). However, compared with other OA indications, such as cartilage collapse, sclerosis, inflammation, and protease activation, the mechanisms by which chondrocyte hypertrophy contributes to OA remain elusive. As the pathological processes in the OA cartilage microenvironment, such as the alterations in the extracellular matrix, are initiated and dictated by the physiological state of the chondrocytes, in-depth knowledge of chondrocyte hypertrophy is necessary to enhance our understanding of the disease pathology and develop therapeutic agents. Chondrocyte hypertrophy is a factor that induces OA progression; it is also a crucial factor in the endochondral ossification. This review elaborates on this dual functionality of chondrocyte hypertrophy in OA progression and endochondral ossification through a description of the characteristics of various genes and signaling, their mechanism, and their distinguishable physiological effects. Chondrocyte hypertrophy in OA progression leads to a decrease in chondrogenic genes and destruction of cartilage tissue. However, in endochondral ossification, it represents an intermediate stage at the process of differentiation of chondrocytes into osteogenic cells. In addition, this review describes the current therapeutic strategies and their mechanisms, involving genes, proteins, cytokines, small molecules, three-dimensional environments, or exosomes, against the OA induced by chondrocyte hypertrophy. Finally, this review proposes that the contrasting roles of chondrocyte hypertrophy are essential for both OA progression and endochondral ossification, and that this cellular process may be targeted to develop OA therapeutics

Prognostic Significance of CREB-Binding Protein and CD81 Expression in Primary High Grade Non-Muscle Invasive Bladder Cancer: Identification of Novel Biomarkers for Bladder Cancer Using Antibody Microarray

<div><p>High-grade (HG) bladder cancers (BCs) are genetically unstable and have an unpredictable course. The identification of prognostic factors in HG non-muscle invasive BC (NMIBC) is crucial for improving patients’ quality of life and preventing BC-specific mortality. Here, we used an antibody microarray (AbM) to identify novel candidate biomarkers in primary HG NMIBC and validated the prognostic significance of the candidate biomarkers. Three pairs of tissue samples from primary HG NMIBC and normal urothelium were analyzed using an AbM kit containing 656 antibodies, and differentially expressed proteins were identified. Among the 42 upregulated and 14 downregulated proteins with statistical significance in BC tissues, CREB-binding protein and CD81 were selected as representative upregulated and downregulated candidate biomarkers, respectively. We then validated the expression of these candidate biomarkers in primary human urothelial cells and BC cell lines by western blotting and immunofluorescence assays, and the results were consistent with the AbM expression profiles. Additionally, Kaplan-Meier survival using immunohistochemical data from an independent primary HG NMIBC cohort comprising 113 patients showed that expression of the 2 biomarkers was significantly associated with recurrence-free and progression-free survival. In multivariate analysis, the 2 biomarkers remained significant predictors for recurrence-free survival. Taken together, our findings suggest that expression of CREB-binding protein and CD81 in BC tissue specimens may have prognostic value in patients with primary HG NMIBC.</p></div

Baseline characteristics of the validation cohort comprising 113 patients with primary high grade non-muscle invasive bladder cancer.

<p>^*Among patients undergoing intravesical therapy, 59 (93.7%) underwent bacillus Calmette-Guérin instillations.</p><p>Baseline characteristics of the validation cohort comprising 113 patients with primary high grade non-muscle invasive bladder cancer.</p

Protein expression of candidate biomarkers in human cell lines.

<p>(A) Total protein levels of CREB-binding protein (CREBBP) and CD81 were analyzed by western blotting. β-Tubulin was used as a calibration control. (B) The expression of CREBBP and CD81 were examined by immunofluorescence assay. CREBBP expression was mainly detected in the nucleus, and its expression was higher in T24 cells than in primary human urothelial cells. CD81 expression was prominent at the cell surface of primary human urothelial cells, but was only detected in a few T24 cells. Representative images from 3 independent experiments are shown. Nuclei and target proteins were detected using immunofluorescence staining and observed with a Nikon Eclipse E400 microscope at 400× magnification. UC, primary human urothelial cells.</p