Activity

05). Staphylococcus was the most common Gram-positive organism in both EOP and LOP groups. The multivariate logistic regression analysis showed that factors associated with EOP included a higher CCI score (OR 1.285, p=0.011), lower serum albumin level (OR 0.924, p=0.016) and lower Kt/V (OR 0.600, p=0.018) at start of PD. In the Cox proportional-hazards model, EOP was more likely a predictor of technique failure (HR 1.801, p=0.051). There was no difference between EOP and LOP for all-cause mortality. CONCLUSION A higher CCI score and lower serum albumin level and Kt/V at PD initiation were significantly associated with EOP. EOP also predicted a high peritonitis rate and poor clinical outcome. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.The success story of hemophilia care first began in the 1970s, when the availability of plasma-derived concentrates of coagulation factor VIII (FVIII) and factor IX (FIX) provided efficacious treatment of bleeding in patients with hemophilia A and B. This positive scenario was consolidated in terms of greater safety and availability in the 1990s, when the first recombinant coagulation factors were produced. This meant that, instead of only treating episodic bleeding events, prophylaxis regimens could be implemented as a preventive measure. Following the demonstration of its superiority in the frame of two randomized clinical trials, prophylaxis became evidence-based standard of care. In high-income countries, these achievements have led to a patients’ life expectancy being extended to close to that of the general male population. Alongside this, the last decade has witnessed further spectacular therapeutic progress, such as the availability of coagulation factors with a longer plasma half-life that allow for wider intervals between treatment. Moreover, new therapeutic products based on new mechanisms other than the replacement of the deficient factor, have become available (emicizumab) or are at an advanced stage of development. This review celebrates the success story of hemophilia care, while also discussing current limitations, issues and as yet unmet needs. The prospects of cure by means of gene therapy are also outlined. Copyright© 2020 Ferrata Storti Foundation.Tumor-associated macrophages (TAMs) play an indispensable role in the modulation of the cancer immune microenvironment. Despite the fact that TAMs may exert both anti-tumor and pro-tumor activities, the molecular mechanisms involved remain poorly understood. Here, we characterized a subpopulation of TAMs expressing DC-specific C-type lectin (DC-SIGN) and investigated its relevance to the prognosis and immune microenvironment of muscle-invasive bladder cancer (MIBC). DC-SIGN+ TAMs were abundant in a significant proportion of human MIBC specimens. High levels of DC-SIGN+ TAMs were associated with dismal prognosis and unresponsiveness to adjuvant chemotherapy in MIBC. Notably, multiple anti-inflammatory cytokines were enriched in DC-SIGN+ TAMs. RNA-seq analysis revealed that multiple M2-like signaling pathways were significantly upregulated in DC-SIGN+ TAMs. High infiltration of DC-SIGN+ TAMs was associated with CD8+ T cell tolerance in MIBC. Moreover, abrogating DC-SIGN function using a neutralizing antibody led to impaired expression of anti-inflammatory cytokines and augmented PD-1 inhibitor pembrolizumab-mediated cytotoxic effects of CD8+T cells towards MIBC cells. In summary, these results suggest that DC-SIGN+ TAM infiltration is closely linked to a pro-tumor immune microenvironment, and may serve as a promising therapeutic target in the immunotherapy of MIBC. Copyright ©2020, American Association for Cancer Research.Nasopharyngeal carcinoma (NPC) is an EBV-related malignancy. Recently, we found that the EBV-encoded microRNA BART2-5p was increased in the serum of preclinical NPC patients and that the copy number positively correlated with disease progression. In this study, we established its role in NPC progression, and explored underlying mechanisms and clinical significance. BART2-5p was an independent unfavorable prognostic factor for progression-free survival and its circulating abundance positively associated with distant metastasis. Ectopic expression of BART2-5p promoted migration and invasion of EBV-negative NPC cells, whereas genetic downregulation of BART2-5p in EBV-positive NPC cells decreased aggressiveness. Mechanistically, BART2-5p targeted RND3, a negative regulator of Rho signaling. Downregulation of RND3 phenocopied the effect of BART2-5p and reconstitution of RND3 rescued the phenotype. By suppressing RND3, BART2-5p activated Rho signaling to enhance cell motility. These findings suggest a novel role for EBV microRNA BART2-5p in promoting NPC metastasis and its potential value as a prognostic indicator or therapeutic target. NMS-873 in vivo Copyright ©2020, American Association for Cancer Research.Invasive lobular carcinoma (ILC) accounts for 8-14% of all breast cancer cases. The main hallmark of ILCs is the functional loss of the cell-cell adhesion protein E-cadherin. Nonetheless, loss of E-cadherin alone does not predispose mice to mammary tumor development indicating that additional perturbations are required for ILC formation. Previously, we identified an N-terminal truncation variant of ASPP2 (t-ASPP2) as a driver of ILC in mice with mammary-specific loss of E-cadherin. Here we showed that expression of t-ASPP2 induced actomyosin relaxation, enabling adhesion and survival of E-cadherin-deficient murine mammary epithelial cells on stiff matrices like fibrillar collagen. The induction of actomyosin relaxation by t-ASPP2 was dependent on its interaction with protein phosphatase 1 (PP1) but not on t-ASPP2-induced YAP activation. Truncated ASPP2 collaborated with both E-cadherin loss and PI3K pathway activation via PTEN loss in ILC development. t-ASPP2-induced actomyosin relaxation was required for ILC initiation but not progression. Conversely, YAP1 activation induced by t-ASPP2 contributed to tumor growth and progression while being dispensable for tumor initiation. Together these findings highlight two distinct mechanisms through which t-ASPP2 promotes ILC initiation and progression. Copyright ©2020, American Association for Cancer Research.