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For decades, the treatment of advanced prostate cancer was mainly based on the manipulation of the androgen receptor-controlled proliferation pathway. Chemotherapy only played an additional important role with the advent of taxanes. The progress in translational research in recent years has led to innovations in the therapeutic environment. With the decoding of the homologous repair deficiency (HRD) machinery and its ability to be influenced by PARP inhibitors, targeted therapies moved into the therapeutic focus for selected patients. The first positive phase III study for PARP inhibitors is already available. In addition, immunotherapy for the treatment of prostate cancer, which is now widely used in oncology, is also making progress; both checkpoint inhibitors and bispecific antibodies have shown clinically useful activities. Cellular therapies such as CAR T cells, which are directed against prostate-specific membrane antigen (PSMA), are still at an early stage of development. In this review, the authors provide a summary of the basic principles and clinical development of these new therapies.

Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs)-which are critical regulators of signaling cascades-to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface. We identified and validated the transcription factor cAMP-responsive element binding protein (Creb1) and its transcriptional co-Activators (Crtc1-3) as targets of miR-17, miR-144, and miR-21. Sec14-like 3 (Sec14l3)-a putative target of Creb1-was down-regulated in both asthma models and in NHBE cells upon IL13 treatment, while it's expression correlated with ciliated cell development and decreased along with increasing goblet cell metaplasia. Finally, we propose that Creb1/Crtc1-3 and Sec14l3 could be important for early responses of the bronchial epithelium to Th2-stimuli. This study shows that miRNA profiles can be used to identify novel targets that would be overlooked in mRNA based strategies.

Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells that act as master regulators of acquired and innate immune responses. While descriptions of cells with dendritic morphology in rodent kidneys date back to the early 1970s, a network of DCs in the mouse kidney has only recently been described. DCs acquire distinct phenotypic and functional characteristics depending on the microenvironment and the disease stages. Concomitantly, their communication with cells of the adaptive immunity might have tissue-protective or tissue-deleterious consequences. This review summarizes results from recent studies on the role of DCs in experimental renal inflammation. Copyright © 2011 S. Karger AG, Basel.

Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells that act as master regulators of acquired and innate immune responses. Here, we review the available information on their role in human renal inflammation. In the 1980s and early 1990s, major histocompatibility complex class II antigen- (HLA-DR) positive DCs were first described in normal human kidneys and in the interstitium of kidneys from patients with glomerulonephritis. Several DC subtypes were subsequently distinguished based on their expression of CD1c/BDCA-1, CD141/BDCA-3 and CD209/DC-SIGN (in combination with HLA-DR). These cells were almost exclusively found in the tubulointerstitium, with increased numbers seen during glomerulonephritis. It appears that the human renal tubulointerstitium harbors different DC types which allow the collection of both exogenous as well as endogenous antigens. Plasmacytoid DCs have a plasma cell-like morphology and were commonly found within nodular tubulointerstitial infiltrates. Follicular DCs are rarely seen, but show a predominant localization in organized infiltrates. CD207/langerin is a marker for Langerhans cells. Langerin-positive cells have been found in association with the collecting ducts and urothelium. A functional characterization of these subtypes has been hampered by the difficulty of obtaining samples for analysis. However, these studies are clearly required to define the role of DCs and DC subsets in the pathophysiology of renal disease.