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Research

Incidence and survival for childhood central nervous system tumours in Australia, 1983–2016

To investigate incidence and survival of childhood tumours of the central nervous system (CNS) by histological subtype, tumour behaviour and tumour grade. Methods: National, population-based data on all children under 15 years old diagnosed with a CNS tumour between 1983 and 2016 were sourced from the Australian Childhood Cancer Registry. Incidence rate trends were calculated using Joinpoint regression.

Research

Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements

Infant MLL-AF4-driven acute lymphoblastic leukemia (ALL) is a devastating disease with dismal prognosis. A lack of understanding of the unique biology of this disease, particularly its prenatal origin, has hindered improvement of survival. We perform multiple RNA sequencing experiments on fetal, neonatal, and adult hematopoietic stem and progenitor cells from human and mouse.

Research

Viridans Group Streptococci in Pediatric Leukemia and Stem Cell Transplant: Review of a Risk-stratified Guideline for Empiric Vancomycin in Febrile Neutropenia

Viridans group streptococci (VGS) are an important cause of sepsis in immunosuppressed children. We reviewed the effectiveness of risk-stratified addition of vancomycin to empiric febrile neutropenia therapy among 107 children with leukemia or undergoing an allogeneic transplant.

Research

What matters for people with brain cancer? Selecting clinical quality indicators for an Australian Brain Cancer Registry

The goal of a clinical quality registry is to deliver immediate gains in survival and quality of life by delivering timely feedback to practitioners, thereby ensuring every patient receives the best existing treatment. We are developing an Australian Brain Cancer Registry (ABCR) to identify, describe, and measure the impact of the variation and gaps in brain cancer care from the time of diagnosis to the end of life.

Research

Therapeutic targeting of the leukaemia microenvironment

In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells.

Research

Conduct of neuro-oncology multidisciplinary team meetings and closing the "gaps" in the clinical management of childhood central nervous system tumors in a middle-income country

Multidisciplinary team meetings (MDTMs) are essential in the clinical management of pediatric central nervous system (CNS) tumors. Evaluations of the impact of MDTMs on childhood CNS tumors and clinicians' perspectives on their effectiveness are scarce.

Research

Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia

Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL.

Research

Malignant Melanoma in Children and Adolescents Treated in Pediatric Oncology Centers: An Australian and New Zealand Children’s Oncology Group (ANZCHOG) Study

Unlike adults, malignant melanoma in children and adolescents is rare. In adult melanoma, significant progress in understanding tumor biology and new treatments, including targeted therapies and immunotherapy have markedly improved overall survival. In sharp contrast, there is a paucity of data on the biology and clinical behavior of pediatric melanoma. We report a national case series of all pediatric and adolescent malignant melanoma presenting to ANZCHOG Childhood Cancer Centers in Australia and New Zealand.

Research

Preclinical Evaluation of Carfilzomib for Infant KMT2A-Rearranged Acute Lymphoblastic Leukemia

Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL.

Research

Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells

Both tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins.