Wnt/β-Catenin Signaling Contributes to Paclitaxel Resistance in Bladder Cancer Cells with Cancer Stem Cell-Like Properties

The Wnt/β-catenin pathway plays an important role in tumor progression and chemotherapy resistance and seems to be essential for the maintenance of cancer stem cells (CSC) in several tumor types. However, the interplay of these factors has not been fully addressed in bladder cancer. Here, our goal was to analyze the role of the Wnt/β-catenin pathway in paclitaxel resistance and to study the therapeutic efficacy of its inhibition in bladder cancer cells, as well as to determine its influence in the maintenance of the CSC-like phenotype in bladder cancer. Our results show that paclitaxel-resistant HT1197 cells have hyperactivation of the Wnt/β-catenin pathway and increased CSC-like properties compared with paclitaxel-sensitive 5637 cells. Paclitaxel sensitivity diminishes in 5637 cells after β-catenin overexpression or when they are grown as tumorspheres, enriched for the CSC-like phenotype. Additionally, downregulation of β-catenin or inhibition with XAV939 sensitizes HT1197 cells to paclitaxel. Moreover, a subset of muscle-invasive bladder carcinomas shows aberrant expression of β-catenin that associates with positive expression of the CSC marker ALDH1A1. In conclusion, we demonstrate that Wnt/β-catenin signaling contributes to paclitaxel resistance in bladder cancer cells with CSC-like properties.

Validation of grading of non-invasive urothelial carcinoma by digital pathology for routine diagnosis

Background Pathological grading of non-invasive urothelial carcinoma has a direct impact upon management. This study evaluates the reproducibility of grading these tumours on glass slides and digital pathology. Methods Forty eight non-invasive urothelial bladder carcinomas were graded by three uropathologists on glass and on a digital platform using the 1973 WHO and 2004 ISUP/WHO systems. Results Consensus grades for glass and digital grading gave Cohen’s kappa scores of 0.78 (2004) and 0.82 (1973). Of 142 decisions made on the key therapeutic borderline of low grade versus high grade urothelial carcinoma (2004) by the three pathologists, 85% were in agreement. For the 1973 grading system, agreement overall was 90%. Conclusions Agreement on grading on glass slide and digital screen assessment is similar or in some cases improved, suggesting at least non-inferiority of DP for grading of non-invasive urothelial carcinoma.

Osteoclastic giant cell variant of urothelial carcinoma in a COVID- positive patient: A rare variant in an unusual circumstances

Bladder carcinomas have a great propensity for divergent differentiation with more that 90% being Transitional cell carcinoma. Several histological variants have been have described so far; they are not only morphologically unique but also have significant prognostic and therapeutic differences making their timely identification of paramount importance. Osteoclastic giant cell variant of urothelial carcinoma is very rare type with controversial management. Studies from China have documented higher incidence and severity of illness in COVID-19 positive cancer patients. We report an unusual case of Osteoclastic giant cell variant of urothelial carcinoma in a 63 yrs old male patient associated with simultaneous COVID-19 infection.

4,6,4′-Trimethylangelicin Photoactivated by Blue Light Might Represent an Interesting Option for Photochemotherapy of Non-Invasive Bladder Carcinoma: An In Vitro Study on T24 Cells

Photodynamic therapy (PDT) is frequently used to treat non-muscle invasive bladder cancer due its low toxicity and high selectivity. Since recurrence often occurs, alternative approaches and/or designs of combined therapies to improve PDT effectiveness are needed. This work aimed to evaluate the cytotoxicity of 4,6,4′-trimethylangelicin (TMA) photoactivated by blue light (BL) on human bladder cancer T24 cells and investigate the mechanisms underlying its biological effects. TMA/BL exerted antiproliferative activity through the induction of apoptosis without genotoxicity, as demonstrated by the expression levels of phospho-H2AX, an indicator of DNA double-stranded breaks. It also modulated the Wnt canonical signal pathway by increasing the phospho-β-catenin and decreasing the nuclear levels of β-catenin. The inhibition of this pathway was due to the modulation of the GSK3β phosphorylation state (Tyr 216) that induces a proteasomal degradation of β-catenin. Indeed, a partial recovery of nuclear β-catenin expression and reduction of its phosphorylated form after treatment with LiCl were detected. As demonstrated by RT-PCR and cytofluorimetric analysis, TMA/BL also decreased the expression of CD44v6, a marker of cancer stem cells. Taken together, our data suggest that TMA photoactivated by BL may represent an interesting option for the photochemotherapy of noninvasive bladder carcinomas, since this treatment is able to inhibit key pathways for tumour growth and progression in the absence of genotoxic effects.

Evidence of BK Polyomavirus Infection in Urothelial but not Renal Tumors from a Single Center Cohort of Kidney Transplant Recipients

Emerging evidence indicates that reactivation of BK polyomavirus (BKPyV) in the kidney and urothelial tract of kidney transplant recipients (KTRs) may be associated with cancer in these sites. In this retrospective study of a single center cohort of KTRs (n = 1307), 10 clear cell renal cell carcinomas and 5 urinary bladder carcinomas were analyzed from 15 KTRs for the presence of BKPyV infection through immunohistochemistry and fluorescent in situ hybridization (FISH). Three of these patients had already exhibited biopsy-proven polyomavirus-associated nephropathies (PyVAN). Although the presence of BKPyV large-T antigen was evident in the urothelium from a kidney removed soon after PyVAN diagnosis, it was undetectable in all the formalin-fixed and paraffin-embedded (FFPE) blocks obtained from the 10 kidney tumors. By contrast, large-T antigen (LT) labeling of tumor cells was detected in two out of five bladder carcinomas. Lastly, the proportion of BKPyV DNA-FISH-positive bladder carcinoma nuclei was much lower than that of LT-positive cells. Taken together, our findings further strengthen the association between BKPyV reactivation and cancer development in KTRs, especially bladder carcinoma.

Histopathology of bladder carcinomas: an eight year retrospective study at Lagos state university teaching hospital, Ikeja, Nigeria

Background: This study was undertaken to evaluate the histological types, frequency, age and sex distribution of bladder carcinoma in Lagos State University Teaching Hospital (LASUTH), Ikeja, Lagos state. This study aims to classify bladder carcinoma in this centre according to the World Health Organisation/ International Society of Urological Pathology.Methods: An eight-year retrospective study of all bladder carcinomas specimens that were sent to the department of Pathology and Forensic Medicine, LASUTH between 1st January, 2011 and 31st December, 2018 was done. Relevant data consisting of the age and sex distributions as well as histopathological types were extracted from the departmental information system and filed documents. The data was analysed using the IBM-SPSS version 25.0.Results: There were 87 cases of bladder tumours, out of which 55 (63.2%) were bladder carcinomas. The mean age at diagnosis of bladder carcinomas was 56.9±13.9 years. Sex distribution has male to female ratio of 1: 1. Urothelial carcinoma predominates as the most common histological type.Conclusions: Bladder carcinoma presents most frequently at the 5th decade of life, with a slight male preponderance.