14-3-3ζ negatively regulates mitochondrial biogenesis in GBM residual cells.

Glioblastoma (GBM) is the most lethal primary brain tumour with a median survival of only 15 months. We have previously demonstrated the generation of an therapy resistance model that captures the residual resistant (RR) disease cells of GBM post-radiation. We also reported the proteomic landscape of parent, residual, and relapse cells using iTRAQ based quantitative proteomics of glioma cells.

Nuclear localization of p65 reverses therapy-induced senescence.

Senescence is the arrest of cell proliferation and is a tumor suppressor phenomenon. In a previous study, we have shown that therapy-induced senescence of glioblastoma multiforme (GBM) cells can prevent relapse of GBM tumors. Here, we demonstrate that ciprofloxacin-induced senescence in glioma-derived cell lines and primary glioma cultures is defined by SA-β-gal positivity, a senescence-associated secretory phenotype (SASP), a giant cell (GC) phenotype, increased levels of reactive oxygen species (ROS), γ-H2AX and a senescence-associated gene expression signature, and has three stages of senescence -initiation, pseudo-senescence and permanent senescence.

Inhibition of SETMAR-H3K36me2-NHEJ repair axis in residual disease cells prevents glioblastoma recurrence.

Background: Residual disease of glioblastoma (GBM) causes recurrence. However, targeting residual cells has failed, due to their inaccessibility and our lack of understanding of their survival mechanisms to radiation therapy. Here we deciphered a residual cell-specific survival mechanism essential for GBM relapse.

HER2 borderline is a negative prognostic factor for primary malignant breast cancer.

Background: HER-(human epidermal growth factor receptor 2) gene amplification and protein overexpression are important predictive, prognosis markers, and therapeutic target for breast cancer, emphasizing the importance of categorizing patients into HER2 positive and negative. However, from immunohistochemistry scores, 2% patients are neither HER2 + nor -ve, but borderline called HER2B. To make informed treatment decisions of these patients, it is important to know how different this group is compared to HER-2 positive/negative.

Effect of Glucosamine Conjugate-Functionalized Liposomes on Glioma Cell and Healthy Brain: An Insight for Future Application in Brain Infusion.

Conjugation of D-glucosamine with lipophilic moiety can ease its application in surface modification of liposomes. Interestingly, although D-glucosamine is safe, studies have shed light on "toxic effect" of its conjugates on cancer cells and highlighted its application in targeting glioma. However, understanding the safety of such conjugates for local delivery to the brain is unavailable.

Enhanced proteasomal activity is essential for long term survival and recurrence of innately radiation resistant residual glioblastoma cells.

Therapy resistance and recurrence in Glioblastoma is due to the presence of residual radiation resistant cells. However, because of their inaccessibility from patient biopsies, the molecular mechanisms driving their survival remain unexplored. Residual Radiation Resistant (RR) and Relapse (R) cells were captured using cellular radiation resistant model generated from patient derived primary cultures and cell lines.

Unique spectral markers discern recurrent Glioblastoma cells from heterogeneous parent population.

An inability to discern resistant cells from bulk tumour cell population contributes to poor prognosis in Glioblastoma. Here, we compared parent and recurrent cells generated from patient derived primary cultures and cell lines to identify their unique molecular hallmarks. Although morphologically similar, parent and recurrent cells from different samples showed variable biological properties like proliferation and radiation resistance.

Radiation-induced homotypic cell fusions of innately resistant glioblastoma cells mediate their sustained survival and recurrence.

Understanding of molecular events underlying resistance and relapse in glioblastoma (GBM) is hampered due to lack of accessibility to resistant cells from patients undergone therapy. Therefore, we mimicked clinical scenario in an in vitro cellular model developed from five GBM grade IV primary patient samples and two cell lines. We show that upon exposure to lethal dose of radiation, a subpopulation of GBM cells, innately resistant to radiation, survive and transiently arrest in G2/M phase via inhibitory pCdk1(Y15).