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Tumor microtubes convey resistance to surgical lesions and chemotherapy in gliomas | Neuro-Oncology | Oxford Academic
Primary and adaptive resistance against chemo- and radiotherapy and local recurrence after surgery limit the benefits from these standard treatments in glioma patients. Recently we found that glioma cells can extend ultra-long membrane protrusions, “tumor microtubes” (TMs), for brain invasion, proliferation, and interconnection of single cells to a syncytium that is resistant to radiotherapy. We wondered whether TMs also convey resistance to the other 2 standard treatment modalities.

Patient-derived glioblastoma stemlike cell (GBMSC) lines were implanted under a cranial window in mice. Longitudinal in vivo two-photon laser scanning microscopy was used to follow tumor growth, including the fate of single glioma cells over months.

After a cylindrical surgical lesion, GBMSCs increasingly extended TMs toward the lesion area, which contributed to the repopulation of this area over many weeks. In fact, an excessive “healing response” was observed in which tumor cell densities significantly exceeded those of unlesioned brain regions over time. Inhibition of TM formation and function by genetic targeting of growth associated protein-43 robustly suppressed this surgery-induced tumor growth reaction, in contrast to standard postsurgical anti-inflammatory treatment with dexamethasone. After one cycle of temozolomide chemotherapy, intra- and intertumoral heterogeneity of TM formation and interconnection was strongly associated with therapy response: when tumor cells were integrated in TM networks, they were more likely to resist chemotherapy.

TMs can contribute to the resistance against standard treatment modalities in gliomas. Specific inhibition of TMs is a promising approach to reduce local recurrence after surgery and lower resistance to chemotherapy.
TNTs  Glioma  GBM 
march 2019 by Segalllab
EGFR-Phosphorylated Platelet Isoform of Phosphofructokinase 1 Promotes PI3K Activation: Molecular Cell
Interesting mech for egfr activation of pi3k in glioma through both gab1 and pfkp.

EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent translocation of PFKP to the plasma membrane, where the PFKP was phosphorylated at Y64 by EGFR. Phosphorylated PFKP binds to the N-terminal SH2 domain of p85α, which is distinct from binding of Gab1 to the C-terminal SH2 domain of p85α, and recruited p85α to the plasma membrane resulting in PI3K activation. PI3K-dependent AKT activation results in enhanced phosphofructokinase 2 (PFK2) phosphorylation and production of fructose-2,6-bisphosphate, which in turn promotes PFK1 activation. PFKP Y64 phosphorylation–enhanced PI3K/AKT-dependent PFK1 activation and GLUT1 expression promoted the Warburg effect, tumor cell proliferation, and brain tumorigenesis. These findings underscore the instrumental role of PFKP in PI3K activation and enhanced glycolysis through PI3K/AKT-dependent positive-feedback regulation.
EGFR  PI3K  Glioma 
august 2018 by Segalllab
Bratislava Medical Journal Vol.119, No.1, p.17-21, 2018
Pretty weak paper in terms of methods but still indicates that mir375 is reduced in GBM and increased expression inU87 reduces invasion/proliferation possibly through CTGF and EGFR
Ctgf  EGFR  miR-375  Glioma  invasion 
june 2018 by Segalllab
Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells | Cancer Research
Tenascin C (TNC) in matrix binding to a2b1 induces jag1 in glioma cells to stimulate notch signaling/stemness in the tumor cells. Not clear how a2b1 stimulates JAG1.

"In breast cancer, tumor cells that metastasize to the lungs support their metastatic capacity by expressing TNC that enhances the expression of a stem cell signaling component, musashi homolog 1, a positive regulator of NOTCH signaling (34)."
JAG1  Notch1  Glioma  tenascin_C  a2b1  Integrins 
september 2017 by Segalllab
Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma : Nature : Nature Research
> Here we show that HGG growth depends on microenvironmental NLGN3, identify signalling cascades downstream of NLGN3 binding in glioma, and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of paediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. NLGN3 stimulates several oncogenic pathways, such as early focal adhesion kinase activation upstream of PI3K–mTOR, and induces transcriptional changes that include upregulation of several synapse-related genes in glioma cells. NLGN3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase.
glioma  OPC  NLGN3  cancer 
september 2017 by porejide
Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease | SpringerLink
Nice evaluation of extracellular vesicles/exosomes from glioma lines including U87. Mention of invadopodia mainly from network analysis.
" Cathepsin D (CTSD) was also increased in EVs from more invasive cells, its release and activity is linked to glioma invasion [55], and may act directly by degrading local ECM structures or indirectly through activation of cysteine proteinases [56]. Interestingly, elevated CTSD serum levels correlate with glioma grade [57] and high CTSD transcript levels in GBM tumours is associated with reduced survival [58]. CTSD levels in circulating EVs might offer valuable, non-invasive prognostic information. "
glioma  invasion  exosomes  extracellular_vesicles  cathepsins 
june 2017 by Segalllab
Cellular and Molecular Identity of Tumor-Associated Macrophages in Glioblastoma | Cancer Research
excellent detailed analysis of BMDM vs microglia in glioma. CD45 expression maybe is the best marker...?
microglia  macrophage  glioma  CCL2  cx3cr 
june 2017 by Segalllab
glioma  MRI  operation 
october 2016 by incep
Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells
NO can activate NOTCH signaling through stimulation of production (presumably) of ligands Dll1 and Dll4.
NO  notch  glioma  stem_cells 
august 2016 by Segalllab
Control of glioblastoma tumorigenesis by feed-forward cytokine signaling : Nature Neuroscience : Nature Research
EGFR vIII is constitutively associated with OSMR, probably because of higher autophosphorylaiton levels. Stimulation with OSM can trigger binding of OSMR to WT EGFR, also phosphorylation dependent, though EGF did stimulate the binding. Also OSMR seemed to stabilize the expression of EGFR vIII "Our findings reveal that the interaction of OSMR with wild-type EGFR is triggered by the ligand OSM in non-tumorigenic cells, suggesting that OSMR forms a co-receptor with wild-type EGFR in response to environmental cues. "
EGFRvIII  egfr  osm  osmr  stat3  glioma 
august 2016 by Segalllab
Propentofylline inhibits glioblastoma cell invasion and survival by targeting the TROY signaling pathway - Springer
"Increased TROY expression in GBM enhances resistance to both radiation and TMZ via activation of the AKT and NF-κB signaling pathways [6, 13]. Our data show that PPF treatment decreased TROY expression and concomitantly decreased the phosphorylation of AKT and NF-κB, demonstrating that PPF inhibits TROY survival signaling.
glioma  invasion  drug_resistance 
may 2016 by Segalllab
seizures, mri scan, op 90% removed, biopsy - grade 4 glioblastoma. 26 years old. [... + life extension treatments that will reduce quality of life significantly ] Nadia started chemotherapy and radiotherapy to treat the tumour this week. She said: “The idea is to try and shrink it – hopefully holding it off a little bit and give me a longer life expectancy.”
brain  tumor  brain  cancer  glioma  cancer  chemotherapy  radiotherapy  health  care  demand  health  care  budget  health  care  cost  health  care  spending  sick  population  diabetes  diet-related  disease  chronic  disease  obesity  epidemic  chronic  low-grade  inflammation  health  crisis  overweight  obesity  heart  disease  high  blood  pressure  Statin  Statins  NHS  austerity  rationing  ethics 
april 2016 by asterisk2a
PLOS ONE: A Role for Fibrillar Collagen Deposition and the Collagen Internalization Receptor Endo180 in Glioma Invasion
indicating the presence of collagen I in~30% of the glioblastoma cases they evaluated. Also summarizing other evidence for collagen I in glioblastoma:
"First, interrogation of the ONCOMINE™ microarray data revealed that within the 100 most highly upregulated genes in GBM compared to grade III tumors were fibrillar collagen genes and genes encoding collagen processing enzymes (Table S2). Second…., COL1A1, COL1A2 and Endo180 (MRC2) expression in GBM lines was comparable to that in normal human fibroblasts, which are known to produce high levels of collagen 1 and Endo180 protein. Third, the high-grade glioma samples arrayed in the TMA (Table 1) and available as whole tissue sections (see Figure 1) were also subjected to Masson's trichrome staining to visualize collagen fibers. …. Analysis of the tumors in the TMA revealed that 21/69 (30.4%) of GBM samples and 1/10 grade III tumors also showed extensive collagen fibers present within the tumor mass. … Finally, to confirm that the tumor-associated collagen detected by Masson's trichrome staining truly represented the deposition of fibrillar collagens, consecutive formalin-fixed paraffin-embedded (FFPE) glioma whole tissue sections were subject to Masson's trichrome staining and triple immunofluorescent labeling with antibodies against collagen I, collagen IV, Endo180 and GFAP (Figure 5B). Collagen I depositions were observed in three separate areas: intimately associated with high Endo180 expressing, GFAP-positive tumor cells, in GFAP-negative stromal regions, and, to a lesser extent, adjacent to vascular proliferations."
Collagen  glioma 
march 2016 by Segalllab
Novel Drugs Seek Cure for Cancer That Killed Ted Kennedy
[CTFxC Charles Trippy had a not so invasive one, grade 2 glioma if I remember well. Currently stable. No talk about remission. Likely to mutate into a more aggressive one late in life. See below. ] &!// &! - Wall Street billionaire Ted Forstmann is fighting for his life -- reportedly against the same virulent form of brain cancer that felled Sen. Edward Kennedy in 2009 [...] Among people aged 15 to 44, such tumors are the second most common cause of cancer-related death. [...] Patients with the least aggressive type can live 10 years. //&! - every patient can get 2nd and 3rd opinions and approaches/arguments for and against what treatment &! //&! - Gliomas are a broad category, [...] They include grade 1 and 2 tumors that are regarded as precancerous, although about 70% of these go on to become malignant, and also include grade 3 anaplastic astrocytomas and grade 4 glioblastomas.
brain  cancer  gioblastoma  malignant  glioma  cancer  medical  profession 
march 2016 by asterisk2a

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