WNT/beta-catenin pathway status was investigated by immunohistochemical analysis of CTNNB1 and the pathway target cyclin D1 (CCND1) in 49 CNS PNETs and 46 medulloblastomas.
WNT-activated MDB is associated to monosomy 6, CTNNB1, DDX3X and TP53 mutations, beta-catenin nuclear immunoexpression, and a better prognosis than SHH-activated MDB.
Within this review, we summarize the main preclinical studies regarding epigenetic targets (such as HDAC, SIRT, BET, EZH2, G9a, LSD1, and DNMT) inhibitors in medulloblastoma.
With respect to clinical efficacy, the reduced expression of TR on DAOY medulloblastoma in vivo may be less significant than expected because of the extreme potency of immunotoxins observed in central nervous system tumors.
With regard to tumors of central nervous system origin, bcl2 expression was absent from most medulloblastomas but was detected at moderate to low levels in a retinoblastoma and some glioblastoma multiforme cell lines.
Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines.
Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines.
Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines.
While most medulloblastoma samples expressed CD133 and LIN28, OCT4 expression was found to be more sporadic, with detectable levels occurring in 48% of tumors.
While all strains replicated at low levels in the medulloblastoma cell line DAOY from a cerebellar neuronal tumour, JCV(Mad1) replicated better in astroglial SVG cells than JCV(Mad1D) or JCV(GCN1) and all strains replicated at higher levels in COS-7 kidney cells, suggesting that the GCN1-deletion confers a disadvantage for viral growth in central nervous system white matter.
While all strains replicated at low levels in the medulloblastoma cell line DAOY from a cerebellar neuronal tumour, JCV(Mad1) replicated better in astroglial SVG cells than JCV(Mad1D) or JCV(GCN1) and all strains replicated at higher levels in COS-7 kidney cells, suggesting that the GCN1-deletion confers a disadvantage for viral growth in central nervous system white matter.
While all strains replicated at low levels in the medulloblastoma cell line DAOY from a cerebellar neuronal tumour, JCV(Mad1) replicated better in astroglial SVG cells than JCV(Mad1D) or JCV(GCN1) and all strains replicated at higher levels in COS-7 kidney cells, suggesting that the GCN1-deletion confers a disadvantage for viral growth in central nervous system white matter.
While Msi1 is barely detected in normal adult tissue, it has been observed to be highly expressed in numerous tumor types (e.g. breast, colon, medulloblastoma, glioblastoma, and et cetera).
Whereas high HDAC1 and low REN expression in neural progenitors and medulloblastomas correlates with active Hedgehog signalling, loss of HDAC activity suppresses Hedgehog-dependent growth of neural progenitors and tumour cells.
Whereas high HDAC1 and low REN expression in neural progenitors and medulloblastomas correlates with active Hedgehog signalling, loss of HDAC activity suppresses Hedgehog-dependent growth of neural progenitors and tumour cells.
Whereas high HDAC1 and low REN expression in neural progenitors and medulloblastomas correlates with active Hedgehog signalling, loss of HDAC activity suppresses Hedgehog-dependent growth of neural progenitors and tumour cells.
Whereas genetic mutations in PTCH1 have previously been shown to lead to medulloblastoma, our study indicates that epigenetic silencing of PTCH1, and other critical developmental loci, by DNA methylation is a fundamental process of pediatric medulloblastoma formation.
When using RNAi and a pharmacological inhibitor selective for PCTK1, we could show that this kinase plays a crucial role in the proliferation of MB cell lines and the activation of the mammalian target of rapamycin (mTOR) pathway.