Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.

Purpose: ALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single-agent treatment has been reported and therapies that improve the response duration are urgently required.

Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead.

The constitutive and dysregulated expression of the transcription factor MYCN has a central role in the pathogenesis of the paediatric brain tumour medulloblastoma, with an increased expression of this oncogene correlating with a worse prognosis. Consequently, the genomic and functional alterations of MYCN represent a major therapeutic target to attenuate tumour growth in medulloblastoma. This review will provide a comprehensive synopsis of the biological role of MYCN and its family components, their interaction with distinct signalling pathways, and the implications of this network in medulloblastoma development.

Extreme climate projections under representative concentration pathways in the Lower Songkhram River Basin, Thailand.

This paper aims to assess changes in the extreme climate indices of the Lower Songkhram River Basin of Thailand under Representative Concentration Pathways (RCPs) scenarios. A linear scaling method was used to correct climate data bias in three Regional Climate Models (RCMs) under RCP 4.5 and RCP 8.

Designing topographically textured microparticles for induction and modulation of osteogenesis in mesenchymal stem cell engineering.

Mesenchymal stem cells are the focus of intense research in bone development and regeneration. The potential of microparticles as modulating moieties of osteogenic response by utilizing their architectural features is demonstrated herein. Topographically textured microparticles of varying microscale features are produced by exploiting phase-separation of a readily soluble sacrificial component from polylactic acid.