Therapeutic targeting of RBPJ, an upstream regulator of ETV6 gene, abrogates ETV6-NTRK3 fusion gene transformations in glioblastoma.

Fusion genes are abnormal genes resulting from chromosomal translocation, insertion, deletion, inversion, etc. ETV6, a rather promiscuous partner forms fusions with several other genes, most commonly, the NTRK3 gene. This fusion leads to the formation of a constitutively activated tyrosine kinase which activates the Ras-Raf-MEK and PI3K/AKT/MAPK pathways, leading the cells through cycles of uncontrolled division and ultimately resulting in cancer.

TGF-β1 induced autophagy in cancer associated fibroblasts during hypoxia contributes EMT and glycolysis via MCT4 upregulation.

The Transforming growth factor-β1 (TGF- β1) in the tumor microenvironment (TME) is the major cytokine that acts as a mediator of tumor-stroma crosstalk, which in fact has a dual role in either promoting or suppressing tumor development. The cancer-associated fibroblasts (CAFs) are the major cell types in the TME, and the interaction with most of the epithelial cancers is the prime reason for cancer survival. However, the molecular mechanisms, associated with the TGF- β1 induced tumor promotion through tumor-CAF crosstalk are not well understood.

An insight into the ubiquitin-proteasomal axis and related therapeutic approaches towards central nervous system malignancies.

The Ubiquitin-Protease system (UPS) is a major destruction system responsible for eliminating dysfunctional/misfolded proteins, thus acting as a pivotal regulator of protein homeostasis in eukaryotic cells. In this review, the UPS system and its various functions in the cell and their detailed impact such as cell cycle control, DNA damage response, apoptosis, and cellular stress regulations have been elucidated with a focus on the central nervous system. Since the Ubiquitin-Protease pathway(UPP) plays a prominent role in the sculpting of the CNS cells and their maintenance, it is naturally deeply involved in many malignancies that develop due to dysregulation of the UPS.

ETV6 gene aberrations in non-haematological malignancies: A review highlighting ETV6 associated fusion genes in solid tumors.

ETV6 (translocation-Ets-leukemia virus) gene is a transcriptional repressor mainly involved in haematopoiesis and maintenance of vascular networks and has developed to be a major oncogene with the potential ability of forming fusion partners with many other genes with carcinogenic consequences. ETV6 fusions function primarily by constitutive activation of kinase activity of the fusion partners, modifications in the normal functions of ETV6 transcription factor, loss of function of ETV6 or the partner gene and activation of a proto-oncogene near the site of translocation. The role of ETV6 fusion gene in tumorigenesis has been well-documented and more variedly found in haematological malignancies.

Lumefantrine, an antimalarial drug, reverses radiation and temozolomide resistance in glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive cancer without currently effective therapies. Radiation and temozolomide (radio/TMZ) resistance are major contributors to cancer recurrence and failed GBM therapy. Heat shock proteins (HSPs), through regulation of extracellular matrix (ECM) remodeling and epithelial mesenchymal transition (EMT), provide mechanistic pathways contributing to the development of GBM and radio/TMZ-resistant GBM.

Transcriptional regulation of HSPB1 by Friend leukemia integration-1 factor modulates radiation and temozolomide resistance in glioblastoma.

Glioblastoma (GBM) is the most common primary brain tumor and is invariably fatal. Heat shock proteins (HSPs) provide protein signatures/biomarkers for GBM that afford potential as targets for developing anti-GBM drugs. In GBM, elevated expression of hypoxia inducible factors under the influence of Ets family proteins significantly promotes the expression of HSPs.

Delineation of crosstalk between HSP27 and MMP-2/MMP-9: A synergistic therapeutic avenue for glioblastoma management.

Background: Epithelial to mesenchymal transition (EMT) and extracellular matrix (ECM) remodeling, are the two elemental processes promoting glioblastoma (GBM). In the present work we propose a mechanistic modelling of GBM and in process establish a hypothesis elucidating critical crosstalk between heat shock proteins (HSPs) and matrix metalloproteinases (MMPs) with synergistic upregulation of EMT-like process and ECM remodeling.

Methods: The interaction and the precise binding site between the HSP and MMP proteins was assayed computationally, in-vitro and in GBM clinical samples.

Push-Pull Stilbene: Visible Light Activated Photoremovable Protecting Group for Alcohols and Carboxylic Acids with Fluorescence Reporting Employed for Drug Delivery.

For the first time we have utilized push-pull stilbene as a visible light activated photoremovable protecting group (PRPG) for the uncaging of alcohols and carboxylic acids. The PRPG efficiently release caged molecules with good photochemical quantum yield. It is capable of monitoring the release in real time owing to its fluorescence "turn on" phenomenon upon photorelease in polar medium.

Targeting NFE2L2, a transcription factor upstream of MMP-2: A potential therapeutic strategy for temozolomide resistant glioblastoma.

Glioblastoma (GBM) is the most malignant form of brain tumor posing a major threat to cancer amelioration. Temozolomide (TMZ) resistance is one of the major hurdles towards GBM prognosis. Oxidative stress and ECM remodeling are the two important processes involved in gaining chemo-resistance.

Glioma progression through the prism of heat shock protein mediated extracellular matrix remodeling and epithelial to mesenchymal transition.

Glial tumor is one of the intrinsic brain tumors with high migratory and infiltrative potential. This essentially contributes to the overall poor prognosis by circumvention of conventional treatment regimen in glioma. The underlying mechanism in gliomagenesis is bestowed by two processes- Extracellular matrix (ECM) Remodeling and Epithelial to mesenchymal transition (EMT).