Τετάρτη 11 Μαρτίου 2020

BRD4 levels determine the response of human lung cancer cells to BET degraders that potently induce apoptosis through suppression of Mcl-1
Lung cancer consists of approximately 80% non-small cell lung cancer (NSCLC) and 20% small cell lung cancer (SCLC) and remains the leading cause of cancer deaths worldwide despite advances in early diagnosis, targeted therapy, and immunotherapy. Thus, novel therapies are still urgently needed. Bromodomain and extra terminal (BET) proteins, primarily comprised of BRD2, BRD3, and BRD4 proteins, function as epigenetic readers and master transcription coactivators and are now recognized cancer therapeutic...
Cancer Research Online First Articles
6h
Blockade of {beta}-catenin-induced CCL28 suppresses gastric cancer progression via inhibition of Treg cell infiltration
Dysregulation of Wnt/β-catenin signaling is frequently observed in human gastric cancer. Elucidation of the tumor immune microenvironment is essential for understanding tumorigenesis and for the development of immunotherapeutic strategies. However, it remains unclear how β-catenin signaling regulates the tumor immune microenvironment in the stomach. Here we identify CCL28 as a direct transcriptional target gene of β-catenin/T cell factor (TCF). Protein levels of β-catenin and CCL28 positively correlated...
Cancer Research Online First Articles
6h
RUNX1 is a driver of renal cell carcinoma correlating with clinical outcome
The recurring association of specific genetic lesions with particular types of cancer is a fascinating, and largely unexplained area of cancer biology. This is particularly true of clear cell renal cell carcinoma (ccRCC) where although key mutations such as loss of VHL is an almost ubiquitous finding, there remains a conspicuous lack of targetable genetic drivers. In this study, we have identified a previously unknown pro-tumorigenic role for the RUNX genes in this disease setting. Analysis of patient...
Cancer Research Online First Articles
6h
Targeting glycosylated PD-1 induces potent anti-tumor immunity
Immunotherapies targeting programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) immune checkpoints represent a major breakthrough in cancer treatment. PD-1 is an inhibitory receptor expressed on the surface of activated T-cells that dampens T-cell receptor (TCR)/CD28 signaling by engaging with its ligand PD-L1 expressed on cancer cells. Despite the clinical success of PD-1 blockade using monoclonal antibodies, most patients do not respond to the treatment, and the underlying...
Cancer Research Online First Articles
6h
ICOS is an indicator of T cell-mediated response to cancer immunotherapy
Immunotherapy is innovating clinical cancer management. Nevertheless, only a small fraction of patients benefit from current immunotherapies. To improve clinical management of cancer immunotherapy, it is critical to develop strategies for response monitoring and prediction. In this study, we describe Inducible T cell Costimulator (ICOS) as a conserved mediator of immune response across multiple therapy strategies. ICOS expression was evaluated by flow cytometry, 89Zr-DFO-ICOS mAb PET/CT imaging was...
Cancer Research Online First Articles
6h
IL33 is a key driver of treatment resistance of cancer
Recurrence and treatment resistance are major causes of cancer-associated death. There has been a growing interest in better understanding epithelial-mesenchymal transition (EMT), stemness of cancer cells, and exhaustion and dysfunction of the immune system for which numerous genomic, proteomic, microenvironmental, and immunological mechanisms have been demonstrated. However, practical treatments for such patients have not yet been established. Here we identified interleukin-33 (IL33) as a key driver...
Cancer Research Online First Articles
6h
TAp63-regulated microRNAs suppress cutaneous squamous cell carcinoma through inhibition of a network of cell cycle genes
TAp63 is a p53 family member and potent tumor and metastasis suppressor. Here, we show that TAp63-/- mice exhibit an increased susceptibility to UVR-induced cutaneous squamous cell carcinoma (cuSCC). A human-to-mouse comparison of cuSCC tumors identified miR-30c-2* and miR-497 as underexpressed in TAp63-deficient cuSCC. Reintroduction of these microRNAs significantly inhibited the growth of cuSCC cell lines and tumors. Proteomic profiling of cells expressing either microRNA showed downregulation...
Cancer Research Online First Articles
6h
Targeting chromosomal architectural HMGB proteins could be the next frontier in cancer therapy
Chromatin-associated architectural proteins are part of a fundamental support system for cellular DNA-dependent processes and can maintain/modulate the efficiency of DNA replication, transcription, and DNA repair. Interestingly, prognostic outcomes of many cancer types have been linked with the expression levels of several of these architectural proteins. The High Mobility Group Box (HMGB) architectural protein family has been well studied in this regard. The differential expression levels of HMGB...
Cancer Research Online First Articles
1d
Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis
Patient-Derived Xenografts (PDXs) are tumor-in-mouse models for cancer. PDX collections, such as the NCI PDXNet, are powerful resources for preclinical therapeutic testing. However, variations in experimental and analysis procedures have limited interpretability. To determine the robustness of PDX studies, the PDXNet tested temozolomide drug response for three pre-validated PDX models (sensitive, resistant, and intermediate) across four blinded PDX Development and Trial Centers (PDTCs) using independently...
Cancer Research Online First Articles
1d

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