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Background: Abiraterone acetate (ABI) and Enzalutamide (ENZA) are second-generation hormone drugs that show breakthrough activity in post-chemotherapy, metastatic castration-resistant prostate cancer (mCRPC). The leading oncological and urological guidelines indicate both drugs with the same strong recommendation. There is a lack of randomized trials which compare the efficacy of ABI and ENZA. The current study aimed to compare the effectiveness of the drugs with an analysis of prognostic factors related to those drugs. Patients and methods: The study included 420 patients with docetaxel (DXL) pretreated mCRPC from seven Polish cancer centers. Patients were treated according to inclusion and exclusion criteria in the Polish national drug program (1000 mg ABI and 10 mg prednisone, n=76.2%; ENZA, 160 mg; n=23.8%). The study retrospectively analyzed the overall survival (OS), time to treatment failure (TTF), PSA 50% decline rate (PSA 50%) and selected clinic-pathological data. Results: In the study group, the median OS was 17 months (95% CI: 15.6-18.3). The median OS (26.1 vs. 15.7 mo.; p<0.001), TTF (14.2 vs. 7.6 mo.; p<0.001) and PSA 50% (87.5 vs. 56%; p<0.001) were higher in ENZA than in ABI treatment. Multivariate analysis shows that ENZA treatment and PSA nadir <17.35 ng/mL during or after DXL treatment were related to longer TTF. ENZA treatment, DXL dose ≥750 mg, PSA nadir <17.35 ng/mL during or after DXL treatment was related to longer OS. Conclusions: ENZA treatment may be related to more favorable oncological outcomes than ABI treatment in the studied Polish population of patients. A 50% decline in PSA is an indicator of longer TTF and OS. Due to the non-randomized and retrospective nature of the analysis, the current results require prospective validation.
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Interleukin 22 (IL-22) is critically involved in gut immunity and host defense and primarily produced by activated T cells. In different circumstances IL-22 may contribute to pathological conditions or act as a cancer promoting cytokine secreted by infiltrating immune cells. Here we show that bone marrow-derived macrophages (BMM) express and produce IL-22 after activation of the aryl hydrocarbon receptor (AhR) when cells are activated through the Toll-like receptor (TLR) family. The additional activation of AhR triggered a significant induction of IL-22 in TLR-activated BMM. Deletion and mutation constructs of the IL-22 promoter revealed that a consensus DRE and RelBAhRE binding element are necessary to mediate the synergistic effects of AhR and TLR ligands. Inhibitor studies and analysis of BMM derived from knockout mice confirmed that the synergistic induction of IL-22 by AhR and TLR ligands depend on the expression of AhR and Nuclear Factor-kappa B (NF-κB) member RelB. The exposure to particulate matter (PM) collected from traffic related air pollution (TRAP) and wildfires activated AhR as well as NF-κB signaling and significantly induced the expression of IL-22. In summary this study shows that simultaneous activation of the AhR and NF-κB signaling pathways leads to synergistic and prolonged induction of IL-22 by integrating signals of the canonical and non-canonical AhR pathway.
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Recently developed COVID-19 vaccines significantly reduce the risk of severe coronavirus disease, which is essential in the particularly vulnerable cancer patient population. There is a growing anti-vaccine concern that may affect the success of the fight against the SARS-CoV2 pandemic. To evaluate opinions and attitudes toward vaccination, we conducted an anonymous online survey among Polish patients diagnosed with cancer. We analyzed how socio-demographic factors, type of cancer, comorbidities, previous influenza vaccinations, and information sources affect the general willingness and opinions about vaccinations, emphasizing vaccination against COVID-19. Six hundred thirty-five patients (80.2% female) participated in the study. A positive attitude towards vaccination was presented by 73.7%, neutral by 17.8%, while negative by 8.5%. Willingness to get vaccinated was declared by 60.3%, 23.5% were unwilling, and 16.2% were undecided. Significant predictors of willingness were education, marital status, active anti-cancer treatment, previous influenza vaccination, and positive attitude towards vaccinations. Patients with cancer have concerns regarding safety, effectiveness, and the process of development of the COVID-19 vaccine. Overall, patients with cancer present positive attitudes towards COVID-19 vaccination but required sufficient information on its efficacy and side effects.