Androgen deprivation therapy (ADT) is a cornerstone treatment for locally advanced or metastatic prostate cancer (PCa). However, its potential effects on the tumor immune microenvironment (TIM) of PCa patients and the underlying mechanism remain largely unclear. To explore the effects of ADT on PCa TIM, RNA sequencing was performed on six paired pre-ADT biopsy and post-ADT PCa lesions, and five paired paracancerous benign tissues from patients receiving neoadjuvant ADT with locally advanced PCa. Bioinformatics methods including ESTIMATE and ssGSEA were used to evaluate the stromal immune score and immune cell infiltration in PCa and paracancerous tissues. Weighted correlation network analysis was used to screen hub genes in the ADT-induced immune remodeling process. The results showed differences exist between PCa and paracancerous tissues in response to ADT. Compared with paracancerous tissues, the immune remodeling effect of ADT in PCa was more intense. ZFP36, JUNB, and SOCS3 served as hub genes in the ADT-induced immune remodeling process and were associated with PSA recurrent-free survival in the TCGA and our neoadjuvant ADT cohort. To investigate the joint action of the above three hub genes, an immune signature score was constructed. The results showed that immune signature score-based immune subtypes reveal the heterogeneity of the immune microenvironment of PCa and showed significant differences in patient prognosis, tumor immune infiltration, mutation burden, and landscape.

To obtain high tumor-specific accumulation, strong tumor penetration and low off-target uptake, we developed a series of polymer therapeutics with different architectures, including random, block, and brush-like structure, based on the classic N-(2-hydroxypropyl) methacrylamide polymers. The influence of polymer architecture on biological properties such as cellular uptake, blood clearance, and biodistribution have been investigated. Besides small micelles whose sizes were determined by polymer architectures, large aggregates formed by micelle aggregation could also be observed. Although they had different architectures, the drug release rate, endocytic pathways and cellular uptake level of various conjugates have been proved to be identical. The polymer architecture of various conjugates lay great impact on the blood clearance, biodistribution and tumor growth inhibition. We assumed that the differences in in vivo biological properties were coordinately caused by the different size of the small aggregates and the formation and stability of large aggregates for different conjugates. Even though the reason was still unclear, the results inspired us that only by diblock conjugates with improved cellular uptake can we realize tumor specific accumulation, deep penetration, and efficient tumor inhibition.

No abstract

ObjectiveTo assess the efficacy and safety of green-light laser photoselective vaporisation of the prostate (PVP) compared with transurethral resection of the prostate (TURP) for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).DesignSystematic review and meta-analysis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.Data sourcesPubMed, EMBASE, the Cochrane Library until October 2018.Eligibility criteriaRandomised controlled trials and prospective studies comparing the safety and efficacy of PVP versus TURP for LUTS manifesting through BPH.Data extraction and synthesisPerioperative parameters, complications rates and functional outcomes including treatment-related adverse events such as International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), postvoid residual (PVR), quality of life (QoL) and International Index of Erectile Function (IIEF).Results22 publications consisting of 2665 patients were analysed. Pooled analysis revealed PVP is associated with reduced blood loss, transfusion, clot retention, TUR syndrome, capsular perforation, catheterisation time and hospitalisation, but also with a higher reintervention rate and longer intervention duration (all p<0.05). No significant difference in IPSS, Qmax, QoL, PVR or IIEF at 3, 24, 36 or 60 months was identified. There was a significant difference in QoL at 6 months (MD=−0.08; 95% CI −0.13 to −0.02; p=0.007), and IPSS (MD = −0.10; 95% CI −0.15 to −0.05; p<0.0001) and Qmax (MD=0.62; 95% CI 0.06 to 1.19; p=0.03) at 12 months, although these differences were not clinically relevant.ConclusionPVP is an effective alternative, holding additional safety benefits. PVP has equivalent long-term IPSS, Qmax, QoL, PVR, IIEF efficacy and fewer complications. The main drawbacks are dysuria and reintervention, although both can be managed with non-invasive techniques. The additional shortcoming is that PVP does not acquire histological tissue examination which removes an opportunity to identify prostate cancer.