Additional clues for a protective role of vitamin D in neurodegenerative diseases: 1,25-dihydroxyvitamin D3 triggers an anti-inflammatory response in brain pericytes.

Epidemiological and experimental studies suggest that 1,25-dihydroxyvitamin D3 (1,25D) plays a neuroprotective role in neurodegenerative diseases including Alzheimer's disease. Most of the experimental data regarding the genes regulated by this hormone in brain cells have been obtained with neuron and glial cells. Pericytes play a critical role in brain function that encompasses their classical function in blood-brain barrier control and maintenance.

Brain mesenchymal stem cells: The other stem cells of the brain?

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist.

Rapid-Steady-State-T1 signal modeling during contrast agent extravasation: toward tumor blood volume quantification without requiring the arterial input function.

Purpose: This study demonstrates how to quantify the tumor blood volume fraction (BVf) using the dynamic Rapid-Steady-State-T1 (RSST1 )-MRI method despite contrast agent (CA) leakage and without arterial input function (AIF) determination.

Methods: For vasculature impermeable to CAs, the BVf is directly quantified from the RSST1 signal amplitude. In case of CA extravasation, we propose a two-compartment model to describe the dynamic RSST1 signal increase.

Imaging and histological characterization of a human brain xenograft in pig: the first induced glioma model in a large animal.

The prognosis of glioblastoma remains poor despite significant improvement in cytoreductive surgery, external irradiation and new approach of systemic treatment as antiangiogenic therapy. One of the issues is the low concentration in the infiltrated parenchyma of therapeutic agent administered intravenously mainly due to the blood-brain barrier. An intracerebral injection is advocated to overpass this barrier, this kind of administration need a low flow and continuous injection.

Hypoxia-induced expression of VE-cadherin and filamin B in glioma cell cultures and pseudopalisade structures.

Most of our knowledge regarding glioma cell biology comes from cell culture experiments. For many years the standards for glioma cell culture were the use of cell lines cultured in the presence of serum and 20 % O2. However, in vivo, normoxia in many brain areas is in close to 3 % O2.

The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.

Seasonal or chronic vitamin D deficiency and/or insufficiency is highly prevalent in the human population. Receptors for 1,25-dihydroxyvitamin D3, the hormonal metabolite of vitamin D, are found throughout the brain. To provide further information on the role of this hormone on brain function, we analyzed the transcriptomic profiles of mixed neuron-glial cell cultures in response to 1,25-dihydroxyvitamin D3.

Biodiversity as a barrier to glioma cell invasion.

Gliomas are extremely aggressive and lethal forms of brain cancer. Unlike many other cancer types, glioma cells rarely metastasize. They spread throughout the brain and invasiveness of glioma cells is a major cause of therapeutic failure.

Detection of antiendothelial cell antibodies by an enzyme-linked immunosorbent assay using antigens from cell lysate: minimal interference with antinuclear antibodies and rheumatoid factors.

The objective of the present work was to set up a routine test adapted to screening for antiendothelial cell antibodies (AECAs) in serum samples with minimal interference from antinuclear antibodies (ANAs) or rheumatoid factors (RFs). We compared the titers of AECAs titrated following two enzyme-linked immunosorbent assays (ELISAs): (i) an ELISA with ethanol-fixed EA.hy926 monolayers as the antigenic substrate and (ii) an ELISA with nucleus-depleted lysates prepared from EA.

6-hydroxydopamine-induced nuclear factor-kappa B activation in PC12 cells.

The involvement of nuclear Factor-kappa B (NF-kappa B) transcription factor in PC12 cell death triggered by the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) was investigated. Results show that oxidative stress generated by 6-OHDA activates NF-kappa B. When the NF-kappa B activation was inhibited by parthenolide, PC12 cell death induced by 6-OHDA was significantly increased, thus suggesting an involvement of this transcription factor in a protective mechanism against 6-OHDA toxicity.

Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a preferential loss of the dopaminergic neurons of the substantia nigra pars compacta. Although the etiology of PD is unknown, major biochemical processes such as oxidative stress and mitochondrial inhibition are largely described. However, despite these findings, the actual therapeutics are essentially symptomatical and are not able to block the degenerative process.

A cautionary note on the use of stable transformed cells.

Gene transfection and ectopic expression is a widely used method in experimental biology. In the present report, we would like to point out that this approach may, in certain circumstances, lead to a modification of the transfected cell phenotype. Indeed, we observed that after transfection of bcl-2 gene in the neuronal PC12 cell line some of the selected clones have lost their neuronal and catecholaminergic characteristics, i.

Extracellular toxicity of 6-hydroxydopamine on PC12 cells.

6-hydroxydopamine (6-OHDA) is usually thought to cross cell membrane through dopamine uptake transporters, to inhibit mitochondrial respiration and to generate intracellular reactive oxygen species. In this study, we show that the anti-oxidants catalase, glutathione and N-acetyl-cysteine are able to reverse the toxic effects of 6-OHDA. These two latter compounds considerably slow down 6-OHDA oxidation in a cell free system suggesting a direct chemical interaction with the neurotoxin.

Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study.

Contradictory experimental results and human trials have questioned the clinical relevance of the HSVtk/ganciclovir system. To bypass the problem of transfection efficiency, we used a glioma cell line stably expressing the HSVtk gene, which was also fully characterized from gene to protein. We also designed a more clinically relevant experimental protocol, consisting of late GCV delivery on large tumor formations.

Increased bax expression is associated with cell death induced by ganciclovir in a herpes thymidine kinase gene-expressing glioma cell line.

The herpes simplex virus thymidine kinase gene (HSV-tk) was stably transfected into rat C6 glioma cells (C6tk) in order to characterize the mechanisms underlying cell toxicity induced in vitro by the guanosine analog ganciclovir (GCV). The results demonstrate the efficiency of the HSV-tk/GCV system in ablating most of the tumoral cells within 7 to 8 days of treatment with 20 mivroM GCV; however, a few cells still survive. C6tk cells arrest in the S phase of the cell cycle after 2 days of drug treatment before undergoing cell death.

p53 and Bax activation in 6-hydroxydopamine-induced apoptosis in PC12 cells.

p53, Bax and Bcl-xL proteins have been implicated in apoptotic neuronal cell death. We have investigated whether those proteins are involved in 6-OHDA-induced PC12 cell death. After a 24-h exposure to the neurotoxin (100 microM), morphological evidence for apoptosis was observed in PC12 cells.

Unlike MPP+, apoptosis induced by 6-OHDA in PC12 cells is independent of mitochondrial inhibition.

The mechanisms of 6-hydroxydopamine (6-OHDA) cytotoxicity were studied in vitro using the PC12 cell line. Following a 24 h exposure, this neurotoxin induced apoptosis and a dose-dependent decrease in cell survival. The presence of monoamine oxidase inhibitors, tranylcypromine and clorgyline, together with 6-OHDA had neither synergistic nor protective effects.

Met-enkephalin receptors in human gliomas.

Endogenous opioid systems (opioid peptides and receptors) are involved in many functions including the regulation of cell growth. We investigated the presence of Met-enkephalin binding sites in gliomas by displacement assays. Results demonstrated that few gliomas exhibit Met-enkephalin binding sites and that the percentage of tumours which express these binding sites strongly decreases with increasing malignancy.

Infection with Toxoplasma gondii does not Alter TNFalpha and IL-6 Secretion by A human Astrocytoma Cell Line.

The secretion of tumour necrosis factor-alpha (TNFalpha), interleukin-1alpha (IL-alpha) and interleukin-6 (IL-6) by a human astrocytoma cell fine was studied 1 h, 3 h, 6 h and 24 h after infection with tachyzoites from three Toxoplasma gondii strains (virulent, RH; cystogentc, 76K and Prugniaud strains). The astrocytoma cell fine constitutively secreted TNFalpha and IL-6, but no IL-1alpha. A positive control was obtained by stimulation with phorbol esters inducing a significant increase (p < 0.

Identification and characterization of an anti-tyrosine kinase factor in cystic gliomas.

In view of the frequent activation of the epidermal growth factor receptor (EGF-R) in gliomas and autocrine hypothesis, we searched for 'EGF-like' factor(s) in cystic fluids (CFs) associated with gliomas. Membranes of A431 cells, which overexpress EGF-R, were used to explore such activity in 20 CFs. In all cases CFs induced inhibition of EGF-R phosphorylation.

A study of the expression of four chemoresistance-related genes in human primary and metastatic brain tumours.

We investigated four mechanisms of intrinsic chemoresistance in a series of 67 human brain tumours including 31 gliomas (one grade I ganglioglioma, nine grade II and 10 grade III astrocytomas, 11 glioblastomas), 13 cerebral metastases, one medulloblastoma, one malignant teratoma, three ependymomas and 18 meningiomas. We studied four genes by northern blotting: multidrug-resistance (MDR 1), glutathione-s transferase (GST pi), dihydrofolate reductase (DHFR), and topoisomerase II (Topo II). The Topo II gene was absent in the normal adult brain (100%) and in 64% of the tumour samples tested.

EGF receptor amplification and expression in human brain tumours.

Human epidermal growth factor receptor (EGFr) gene amplification, rearrangements and expression were studied in tumours of the human nervous system. EGFr gene amplification was studied in 46 brain tumours. Gene expression was analysed by northern blot in 37 tumours and binding of its protein to EGF in 27 tumours.

[The EGF receptor pathway in human cerebral tumors].

The epidermal growth factor receptor gene is the most frequently involved proto-oncogene in human glial brain tumors, in the present series in agreement with previous reports in literature. It is therefore important to study this gene from DNA to the protein product. The vicinity of cystic fluid (C.

[3 experimental models applied to the study of urothelial tumors of the bladder].

Three important models can be used in experimental carcinogenesis: Clonogenic assays which can be used to study tumor cells in vitro. This method is particularly useful in order to investigate biochemical markers and chromosomal spreads. Chemically-induced bladder tumors in various animals are used to analyse the mechanisms of induction and development of these cancers.

Expression of the preproenkephalin A gene in tumor cells and brain glioma: a northern and in situ hybridization study.

Preproenkephalin A (PPA) mRNA expression was studied by Northern blot and in situ hybridization in cell lines (rat glioma C6, rat hepatoma HTC, human neuroblastoma IMR32, mouse neuroblastoma NS20Y, rat fibroblast FR3T3, human bladder carcinoma EJ, human vulva carcinoma A431, myelocytic leukemia HL60, rat adrenal carcinoma Y1) and in brain tumours (implanted C6 cells). C6 glioma in cell culture, as well as in brain tumours, expressed high levels of PPA mRNA as compared to the caudate nucleus of the rat brain. EJ and FR3T3 cell lines also expressed the PPA mRNA, which was not detectable in A431, Y1, NS20Y, IMR32, HTC, HL60 cell lines as well as in the rat liver.