Genomic Alterations of Signaling and DNA Damage Repair Pathways in Non-Muscle Invasive Bladder Cancer.

The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.

A candidate antineoplastic herbal agent for bladder cancer: Ankaferd Blood Stopper.

BACKGROUND AND AIMS: Ankaferd Blood Stopper (ABS) was used for in vitro studies of osteosarcoma and colon carcinoma cancer cell lines to reveal the apoptotic and antineoplastic effects. The aim of this study is to evaluate the antineoplastic effect of ABS on bladder cancer cell cultures. METHODS: We prospectively collected minimum 0.5 cm parts of fresh frozen tumour samples from patients with bladder tumour from 2015 to 2017. Primary bladder cancer cultures were produced from the frozen tumour samples. Two different doses of ABS were used on cancer cell cultures. Viability tests of each cell cultures were performed. Flow cytometry was used for the determination of apoptosis and necroptosis. We also checked the effect of ABS on different stages, grade and variant histology of bladder cancer cells. The results of all cancer cell cultures were compared with their own controls. RESULTS: This study included 24 patients. Mean age of patients was 66.2 ± 11.7 years (34-83 years), where 19 of them (79.5%) were males and five (20.5%) were females. When we compared the data, we found decreased cancer cell viability ratio in each ABS group compared with their own controls. Necroptosis was observed in the great majority of ABS groups, and necroptosis and apoptosis were observed in some cell cultures. CONCLUSIONS: In this study, we demonstrated the cytotoxic effect of ABS on bladder cancer cells. The results of this study suggests planning of animal model of bladder cancer for ABS with intravesical application as an antineoplastic agent. In the future, ABS may be a candidate intravesical treatment agent for bladder cancer.

Prognostic value of intraductal carcinoma for adjuvant radiotherapy candidates after radical prostatectomy.

OBJECTIVE: To investigate the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens and predictive value of IDC-P for biochemical recurrence and adjuvant therapy decision. METHOD: We retrospectively evaluated patients who were performed RP between 2000 and 2014. Among, 67 patients who had stage pT3a tumour with negative surgical margin (Group 1, n = 35) and who had stage pT2 tumour with positive surgical margin (Group 2, n = 32) were included in the study. RP specimens were re-evaluated for the presence of IDC-P component and other prognostic factors. In both the groups, prognostic factors were compared according to the presence of IDC-P and biochemical recurrence status. RESULTS: In Group 1, IDC-P was detected in five cases and biochemical recurrence was detected in three cases. Patients with IDC-P showed significantly higher biochemical recurrence than those without IDC-P (P = .002). In univariate analysis, IDC-P was found to be significantly associated with worse progression-free survival (P < .001). In Group 2, IDC-P was detected in four cases and biochemical recurrence was detected in 10 cases. Also, tumour volume was significantly higher in patients with IDC-P than those without IDC-P (P = .02). IDC-P was also significantly associated with worse progression-free survival in Group 2 (P = .033). CONCLUSIONS: In both the groups, IDC-P was a prognostic factor for progression-free survival and/or biochemical recurrence. Especially in these patients, the presence of IDC-P might be helpful for postoperative adjuvant therapy management decision.

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

Aim: To evaluate the ex vivo efficacy of chemotherapy, immunotherapy and targeted agents with the oncogram method in patients with bladder cancer and determine the most appropriate personalized treatment agent using immune markers. Materials & methods: Bladder cancer tissues were obtained from each patient. After cultivation, cell cultures were divided into 12 groups for each patient and 11 drugs were administered. Cell viability and immunohistochemistry expression were examined. Results: A good response rate was determined to be a 23% viability drop. The nivolumab good response rate was slightly better in PD-L1-positive patients and the ipilimumab good response rate was slightly better in tumoral CTLA-4-positive cases. Interestingly, the cetuximab response was worse in EGFR-positive cases. Conclusion: Although good responses of drug groups after their ex vivo application by using oncogram were found to be higher than control group, this outcome differed on a per patient basis.

Bladder cancer primary cell cultures were shown to be effective for drug sensitivity and also able to be used ex vivo in the process of determining personalized treatment. The ex vivo efficacy of 11 different agents was evaluated with oncogram in bladder cancer cell cultures obtained from patients. Together with clinicopathological features, evaluation of drug responses detected by oncogram can provide important information for pretreatment drug selection when deciding on individualized treatment.