Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis.

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape. Mechanistically, CCL5 binds to the receptor CCR5 on prostate cancer cells and activates the AKT signaling pathway, leading to the upregulation of AR and PD-L1. The CCR5 antagonist maraviroc to inhibit the CAFs mediated CCL5 signaling pathway can effectively reduce the expression of AR and PD-L1, and improve the efficacy of enzalutamide. This study highlights a promising therapeutic approach targeting the CCL5-CCR5 signaling pathway to improve the effectiveness of enzalutamide.

Sulfide Oxidation on Ladder-Type Heteroarenes to Construct All-Acceptor Copolymers for Visible-Light-Driven Hydrogen Evolution.

Conjugated polymers (CPs) have recently gained increasing attention as photocatalysts for sunlight-driven hydrogen evolution. However, they suffer from insufficient electron output sites and poor solubility in organic solvents, severely limiting their photocatalytic performance and applicability. Herein, solution-processable all-acceptor (A1 -A2 )-type CPs based on sulfide-oxidized ladder-type heteroarene are synthesized. A1 -A2 -type CPs showed upsurging efficiency improvements by two to three orders of magnitude, compared to their donor-acceptor -type CP counterparts. Furthermore, by seawater splitting, PBDTTTSOS exhibited an apparent quantum yield of 18.9% to 14.8% at 500 to 550 nm. More importantly, PBDTTTSOS achieved an excellent hydrogen evolution rate of 35.7 mmol h-1  g-1 and 150.7 mmol h-1  m-2 in the thin-film state, which is among the highest efficiencies in thin film polymer photocatalysts to date. This work provides a novel strategy for designing polymer photocatalysts with high efficiency and broad applicability.

[Family-centered psychological support helps improve illness cognition and quality of life in patients with advanced prostate cancer].

OBJECTIVE: To explore the effect of family-centered psychological support (FCPS) on illness cognition and quality of life in patients with advanced prostate cancer (PCa). METHODS: Using a randomized controlled study design, we divided 84 advanced PCa patients into an intervention group and a control group, all provided with PCa-related knowledge and answers to their questions, while the former group with FCPS in addition. Before, immediately after and at 1 and 3 months after intervention, we evaluated the effectiveness using the Illness Cognition Questionnaire (ICQ) and Functional Assessment of Cancer Therapy － Prostate (FACT-P). RESULTS: Totally, 78 of the patients completed the whole intervention procedure, 38 in the intervention and 40 in the control group. There were statistically significant differences between the intervention and control groups in the scores on the three factors of ICQ acceptance (17.89 ± 3.86 vs 15.20 ± 2.83, t = 3.528, P < 0.05), perceived benefits (18.68 ± 3.02 vs 17.08 ± 2.74, t = 2.465, P < 0.05) and helplessness (13.37 ± 3.00 vs 15.63 ± 3.11, t = －3.259, P < 0.05) immediately after intervention, and so were there at 1 and 3 months after intervention (P < 0.05). The patients in the intervention group showed remarkably higher quality of life scores than the controls immediately after (100.59 ± 11.66 vs 92.20 ± 9.54, t = 7.943, P < 0.05) and at 1 month (93.03 ± 13.33 vs83.55 ± 14.29, t = 3.481, P < 0.05) and 3 months after intervention (85.66 ± 17.39 vs 75.95 ± 16.66, t = 3.025, P < 0.05). The covariance analysis found that, excluding the time effect, FCPS significantly improved the positive illness cognition of the patients (P < 0.05). CONCLUSIONS: Family-centered psychological support contributes to the positive illness cognition of the patients with advanced PCa and helps improve their quality of life, and therefore deserves to be popularized in clinical practice.

Combination Therapy of Prostate Cancer by Oncolytic Adenovirus Harboring Interleukin 24 and Ionizing Radiation.

Prostate cancer is a common malignant tumor and the second leading cause of cancer-related death in men. Radiation therapy is a curative treatment for localized prostate cancer and has a limited effect for castration-resistant prostate cancer (CRPC). Interleukin 24 (IL-24) has a radiosensitizing effect in cancer cells. Our previous studies showed that ZD55-IL-24, an oncolytic adenovirus harboring IL-24, had better anti-tumor effect with no toxicity to normal cells. In this study, we evaluated the synergistic anti-tumor effect of oncolytic adenovirus ZD55-IL-24 combined with radiotherapy in prostate cancer. In Vitro and In Vivo experiments showed that the combined therapy significantly inhibited the growth of prostate cancer and provoked apoptosis of prostate cancer cells. In conclusion, the combination of ionizing radiation and oncolytic adenovirus expressing IL24 could achieve synergistic anti-tumor effect on prostate cancer, and is a promising strategy for prostate cancer therapy.