Accumulation of exogenous histone in rat brain parenchyma

2000 ◽  
Vol 130 (1) ◽  
pp. 665-668
Author(s):  
O. A. Gorukhina ◽  
R. D. Ilyuk ◽  
I. V. Mishchenko
Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 123 ◽  
Author(s):  
Souheyla Bensalma ◽  
Soumaya Turpault ◽  
Annie-Claire Balandre ◽  
Madryssa De Boisvilliers ◽  
Afsaneh Gaillard ◽  
...  

Glioblastoma (GBM) remains an incurable disease, mainly due to the high migration and invasion potency of GBM cells inside the brain. PI3K/Akt, Sonic Hedgehog (SHH), and PKA pathways play major regulatory roles in the progression of GBM. The vasoactive intestinal peptide (VIP) family of neuropeptides and their receptors, referred in this article as the “VIP-receptor system”, has been reported to regulate proliferation, differentiation, and migration in a number of tumor cell types and more particularly in GBM cells. These neuropeptides are potent activators of the cAMP/PKA pathway. The present study aimed to investigate the cross-talks between the above cited signaling cascades. Regulation by VIP-related neuropeptides of GBM migration and invasion was evaluated ex vivo in rat brain slices explanted in culture. Effects of different combinations of VIP-related neuropeptides and of pharmacological and siRNA inhibitors of PKA, Akt, and of the SHH/GLI1 pathways were tested on GBM migration rat C6 and human U87 GBM cell lines using the wound-healing technique. Quantification of nuclear GLI1, phospho-Akt, and phospho-PTEN was assessed by western-immunoblotting. The VIP-receptor system agonists VIP and PACAP-38 significantly reduced C6 cells invasion in the rat brain parenchyma ex vivo, and C6 and U87 migration in vitro. A VIP-receptor system antagonist, VIP10-28 increased C6 cell invasion in the rat brain parenchyma ex vivo, and C6 and migration in vitro. These effects on cell migration were abolished by selective inhibitors of the PI3K/Akt and of the SHH pathways. Furthermore, VIP and PACAP-38 reduced the expression of nuclear GLI1 while VIP10-28 increased this expression. Selective inhibitors of Akt and PKA abolished VIP, PACAP-38, and VIP10-28 effects on nuclear GLI1 expression in C6 cells. PACAP-38 induced a time-dependent inhibition of phospho-Akt expression and an increased phosphorylation of PTEN in C6 cells. All together, these data indicate that triggering the VIP-receptor system reduces migration and invasion in GBM cells through a PKA-dependent blockade of the PI3K/Akt and of the SHH/GLI1 pathways. Therefore, the VIP-receptor system displays anti-oncogenic properties in GBM cells and PKA is a central core in this process.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 2066-2066
Author(s):  
Sadhana Jackson ◽  
Nicole Anders ◽  
Antonella Mangraviti ◽  
Teresia Wanjiku ◽  
Henry Brem ◽  
...  

2013 ◽  
Vol 1527 ◽  
pp. 1-14 ◽  
Author(s):  
Sarah M. Clinton ◽  
Matthew E. Glover ◽  
Astha Maltare ◽  
Ann M. Laszczyk ◽  
Stephen J. Mehi ◽  
...  

2008 ◽  
Vol 109 (5) ◽  
pp. 867-873 ◽  
Author(s):  
Toshio Kikuchi ◽  
Ryuta Saito ◽  
Shin-ichirou Sugiyama ◽  
Yoji Yamashita ◽  
Toshihiro Kumabe ◽  
...  

Object The characteristics of polyethylene glycol–coated liposomal doxorubicin (PLD), the only liposomal drug now clinically available for intravenous injection, were investigated after convection-enhanced delivery (CED) into the rat brain parenchyma. Methods The distribution, tissue retention, and toxicity profile were evaluated after CED into the rat brain parenchyma. The antitumor efficacy was also determined in rodent intracranial U-251MG and U-87MG glioma models. Results Convection-enhanced delivery of PLD achieved wider distributions and delayed onset of toxicity in the brain parenchyma compared with CED of free doxorubicin infusion. Fluorescence generated from doxorubicin infused as PLD was detected until at least 30 days after infusion. Local toxicity was not observed when a 10% dilution of the commercially available PLD solution was used (0.2 mg/ml doxorubicin), but was significant at higher concentrations. Results after 10% PLD was delivered locally with CED demonstrated significant survival prolongation in both intracranial U-251MG and U-87MG xenograft models. Conclusions Convection-enhanced delivery of PLD achieved extensive tissue distribution and sustained drug release. Convection-enhanced delivery of PLD is a promising chemotherapy for the treatment of malignant gliomas.


2015 ◽  
Vol 17 (suppl 3) ◽  
pp. iii38-iii38
Author(s):  
S. Jackson ◽  
N. Anders ◽  
A. Mangraviti ◽  
H. Brem ◽  
B. Tyler ◽  
...  

Endocrinology ◽  
2001 ◽  
Vol 142 (2) ◽  
pp. 812-822 ◽  
Author(s):  
Patricia Crisanti ◽  
Boubaker Omri ◽  
Eleanor J. Hughes ◽  
Geri Meduri ◽  
Christiane Hery ◽  
...  

Abstract The regulation of the thyroid gland by TSH is mediated by a heterotrimeric G protein-coupled receptor. Nonthyroid effects of TSH have been reported, and expression of its receptor has been described in adipocytes and lymphocytes. We have previously reported the existence of specific and saturable binding sites of TSH and specific TSH effects in primary cultured rat brain astroglial cells. We now report expression of the TSH receptor gene in these cells; the coding sequence of the corresponding complementary DNA is identical to that previously established in thyroid. Using specific antisense RNA probe, expression of this gene was detected in some isolated or clustered glial fibrillary acidic protein-positive primary cultured cells by in situ hybridization. With this technique, we further detected TSH receptor messenger RNA (mRNA) expression in rat brain cryoslices in both neuronal cells and astrocytes. Its presence predominated in neuron-rich areas (pyriform and postcingulate cortex, hippocampus, and hypothalamic nuclei) and was mostly colocalized with neuron-specific enolase. In astrocytes, this mRNA was detected in the ependymal cell layer and the subependymal zone, and several isolated cells were also found in the brain parenchyma. We also detected TSH receptor mRNA and protein in primary cultured human astrocytes. The protein was detected as well in both rat and human brain cryoslices. Together, these findings clearly demonstrate the expression of the TSH receptor gene in the brain in both neuronal cells and astrocytes.


Author(s):  
Yuji MIURA ◽  
Yusuke MIYAZAKI ◽  
Shihori HAYASHI ◽  
Motoki INAJI ◽  
Katsushige SATO

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