Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

TNFα-senescence initiates a STAT-dependent positive feedback loop, leading to a sustained interferon signature, DNA damage, and cytokine secretion.

Abstract: Cellular senescence is a cell fate program that entails essentially irreversible proliferative arrest in response to damage signals. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some types of senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways linking TNFα-related inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that TNFα induces permanent growth arrest and increases p21CIP1, p16INK4A, and SA-β-gal, accompanied by persistent DNA damage and ROS production. By gene expression profiling, we identified the crucial involvement of inflammatory and JAK/STAT pathways in TNFα-mediated senescence. We found that TNFα activates a STAT-dependent autocrine loop that sustains cytokine secretion and an interferon signature to lock cells into senescence. Furthermore, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from proliferative arrest, but rather suppressed cell cycle regulatory genes and altered TNFα-induced senescence. Our findings suggest a positive feedback mechanism via the STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence.

RATIONALE 301 study: tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma.

Abstract: Advanced, unresectable hepatocellular carcinoma (HCC) has a poor prognosis with median life expectancy of approximately 1 year. Overexpression of PD-L1 in tumor cells and PD-1 on tumor-infiltrating T cells has been associated with poorer prognosis, more advanced disease and higher recurrence rates in HCC. Monoclonal antibodies against PD-1 have demonstrated antitumor activity in patients with solid tumors, including HCC. Tislelizumab, an investigational, humanized IgG4 monoclonal antibody with high affinity and binding specificity for PD-1, has demonstrated preliminary antitumor activity in HCC. Here we describe a head-to-head Phase III study comparing the efficacy, safety and tolerability of tislelizumab with sorafenib as first-line treatment in unresectable HCC.

Reduced survival and quality of life following return to dialysis after transplant failure: the Dialysis Outcomes and Practice Patterns Study.

Abstract: Although dialysis after kidney transplant failure (TF) is common, the outcomes of these patients remain unclear. We compared outcomes of TF patients with transplant-nave (TN) patients wait-listed for kidney transplantation. We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), including laboratory markers and health-related quality of life (HR-QOL). Mortality and hospitalization of participants with one prior TF versus TN patients were compared using the Cox regression analysis. HR-QOL physical and mental component summary scores (PCS and MCS) were examined using linear mixed models, and clinical practices were compared using logistic regression. Compared with TN patients (n 2806), TF patients (n 1856) were younger (48 versus 51 years, P 0.003), less likely to be diabetic (18 versus 27, P 0.0001) and to use a permanent surgical vascular access {adjusted odds ratio (AOR): 0.85 [95 confidence interval (CI): 0.701.03], P 0.10}, particularly within the first 3 months after TF [AOR 0.45 (0.320.62), P 0.0001]. TF patients also had lower PCS [mean difference 2.56 (3.36, 1.75), P 0.0001] but not MCS [0.42 (1.34, 0.50), P 0.37]. All-cause mortality [adjusted hazard ratio (AHR): 1.32 (95 CI: 1.051.66), P 0.02], especially infection-related [AHR 2.45 (95 CI: 1.364.41), P 0.01], was higher among TF patients. TF patients have reduced QOL and higher mortality, particularly due to infections, than TN patients. Interventions to optimize care before and after starting dialysis remain to be identified and applied in clinical practice.

Cytosolic 5'-Nucleotidase 1A As a Target of Circulating Autoantibodies in Autoimmune Diseases.

Abstract: Objective Prior investigations demonstrated that autoantibodies recognizing cytosolic 5′-nucleotidase 1A (NT5C1A) are found in 33–76% of patients with inclusion body myositis (IBM) but are observed only rarely in patients with polymyositis (PM). Thus, anti-NT5C1A may help distinguish IBM from PM. Although 4–21% of patients with dermatomyositis (DM) were shown to be anti-NT5C1A antibody positive, the clinical features of anti-NT5C1A–positive patients with DM have not been described. Furthermore, the prevalence of anti-NT5C1A antibodies in other rheumatic conditions has not been reported. This study was undertaken to define the prevalence and clinical features of anti-NT5C1A–positive patients with DM, PM, IBM, or other systemic autoimmune diseases. Methods We screened for anti-NT5C1A autoantibodies in patients with IBM, DM, PM, Sjogren's syndrome (SS), or systemic lupus erythematosus (SLE) and in healthy volunteers. Clinical characteristics were compared between patients who were anti-NT5C1A positive and those who were anti-NT5C1A negative. Results Anti-NT5C1A autoantibodies were detected in 71 (61%) of 117 patients with IBM, 2 (5%) of 42 patients with PM, 2 (5%) of 42 healthy volunteers, 24 (15%) of 159 patients with DM, 10 (23%) of 44 patients with SS, and 13 (14%) of 96 patients with SLE. No anti-NT5C1A antibody–positive patients with SS or SLE had muscle involvement. Anti-NT5C1A–positive patients with IBM had a lower prevalence of rimmed vacuoles (62% versus 83% of antibody-negative patients; P = 0.02). No differences in the clinical characteristics of antibody-positive and antibody-negative patients with DM, SS, or SLE were observed. Conclusion Anti-NT5C1A is a common target of circulating autoantibodies, especially in IBM but also in several different autoimmune diseases. In SLE and SS, anti-NT5C1A autoreactivity is not associated with muscle disease.