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DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3DYRK1A is a serine/threonine kinase encoded on human chromosome 21 (HSA21) that has been implicated in several pathologies of Down syndrome (DS), including cognitive deficits and Alzheimer's disease. Although children with DS are predisposed to developing leukemia, especially B cell acute lymphoblastic leukemia (B-ALL), the HSA21 genes that contribute to malignancies remain largely undefined. Here, we report that DYRK1A is overexpressed and required for B-ALL. Genetic and pharmacologic inhibition of DYRK1A decreased leukemic cell expansion and suppressed B-ALL development in vitro and in vivo.
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Histological predictors of outcome for cutaneous squamous cell carcinoma in renal transplant patients: A case-control studyCutaneous squamous cell carcinoma is a significant cause of morbidity for immunosuppressed patients such as organ transplant recipients; however, histological parameters which predict the likelihood of tumor progression are typically based on general population studies in which immunosuppressed patients represent only a small fraction of cases.
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Home-based multidisciplinary interventions on skin adverse reactions in EGFR-The Kids-treated patients with lung cancer: a protocol for a randomised controlled trialHere, we provide a feasible, well-designed protocol of a randomised controlled trial for the assessment of the effects of a home-based multidisciplinary intervention on the severity of skin adverse drug reactions and health-related indicators in patients with non-small cell lung cancer (NSCLC) under epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-The Kids) therapy.
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Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemiaSymptomatic methotrexate-related central neurotoxicity (MTX neurotoxicity) is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study.
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Directing the future breakthroughs in immunotherapy: The importance of a holistic approach to the tumour microenvironmentImmunotherapy has revolutionised the treatment of cancers by exploiting the immune system to eliminate tumour cells. Despite the impressive response in a proportion of patients, clinical benefit has been limited thus far.
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Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymomaSupratentorial RELA fusion (ST-RELA) ependymomas (EPNs) are resistant tumors without an approved chemotherapeutic treatment. Unfortunately, the molecular mechanisms that lead to chemoresistance traits of ST-RELA remain elusive. The aim of this study was to assess RELA fusion-dependent signaling modules, specifically the role of the Hedgehog (Hh) pathway as a novel targetable vulnerability in ST-RELA.
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Glutamine Deprivation Synergizes the Anticancer Effects of Cold Atmospheric Plasma on Esophageal Cancer CellsEsophageal cancer is a highly aggressive malignancy with a low response to standard anti-cancer therapies. There is an unmet need to develop new therapeutic strategies to improve the clinical outcomes of current treatments. Cold atmospheric plasma (CAP) is a promising approach for cancer treatment, and has displayed anticancer efficacy in multiple preclinical models. Recent studies have shown that the efficacy of CAP is positively correlated with intracellular reactive oxygen species (ROS) levels.
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Type I interferon subtypes differentially activate the anti-leukaemic function of natural killer cellsNatural killer (NK) cells have an intrinsic ability to detect and eliminate leukaemic cells. Cellular therapies using cytokine-activated NK cells have emerged as promising treatments for patients with advanced leukaemia. However, not all patients respond to current NK cell therapies, and thus improvements in efficacy are required.
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The Bone Marrow Microenvironment in B-Cell Development and MalignancyB lymphopoiesis is characterized by progressive loss of multipotent potential in hematopoi-etic stem cells, followed by commitment to differentiate into B cells, which mediate the humoral response of the adaptive immune system.
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Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trialThere is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers.