Neuroblastomas

USP (Oncovin) vindesine sulfate [59917-39 ] C43H55N5O7 -H2S0 852.01 (50) chil-dren lymphocytic leukemia Hodgkin s disease non-Hodg-kin s lymphomas Wilm s tumor neuroblastoma rhabdomyosarcoma, investigational dmg (paresthesias, foot drop, double vision, etc) constipation ileus alopecia leu-kopenia (occasional) ... 

Sensitive to toxins, in this case means that the assay presents no false negative results. Primary hepatocytes can elucidate hepatotoxins, and mouse neuroblastoma cells can elucidate sodium channel-blocking neurotoxins therefore these assays can be used to screen for the appropriate toxins. 

Cancer Neuroblastoma, leukemia, brain tumors and prostate cancer (A) ... 

Reports of ChE abnormalities in tumours, e.g., meningioma, glioma, acoustic neurinomas and lung cancers, megakaryocytopoietic disorders and leukemias, ovarian tumours and neuroblastomas, suggest cell proliferation and differentiation activities. 

Rat Neuroblastoma N1E115 cell line Coupling to Gi, inhibition of cAMP production ... 

Sympathetic, parasympathetic and sensory neurones, chromaffin, neuroblastoma and PC 12 cells (ganglionic nAChR, typically comprised of a3,a5,(32,(34 or al subunits)... 

Extrahypothalamic OX-B-like immunoreactivity, reminiscent to that of CRF, has been described in clustered GABAergic neuronal populations, in the lateral division of central nucleus ofthe amygdala, the bednucleus of the stria terminalis, and in the hippocampus. Moreover, ectopic expression of preproorexin mRNA in the gut, ependymal cells, neuroblastomas, and of orexin receptors in adrenal gland, cancer and hematopietic stem cells suggests yet unexplored roles of orexins as paracrine factors controlling blood-brain barrier, and tumor or stem cell function. 

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

Figure 4. Neurite outgrowth by LA-N-1 human neuroblastoma cells in culture. LA-N-1 human PNS neuroblastoma cells were grown for five days in N2 medium (as described by Bottenstein and Sato, 1979) on a polylysine and fibronectin-modified surface. The cells were plated in clumps, rather than as a single cell suspension, which enhances neurite extension. Very long processes result, and exhibit varicosities along their length. Most of the cells have migrated from the central clump. (Photo courtesy of Dr. jane Bottenstein.)...

Bottenstein, J.E. Sato, G.H. (1979). Growth of a rat neuroblastoma cell line in senan-ffee supplemented medium. Proc. Natl. Acad. Sci. USA 76,514-517. 

Lonart G, Johnson KM Inhibitory effects of nitric oxide on the uptake of [3H]dopamine and [3H]glutamate by striatal synaptosomes. J Neurochem 63 2108—2117, 1994 Lovinger DM, White G Ethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in neuroblastoma cells and isolated adult mammalian neurons. Mol Pharmacol 40 263—270, 1991... 

Sun L., Fuselier J.A., Murphy W.A., Coy D.H. Antisense peptide nucleic acids conjugated to somatostatin analogs and targeted at the n-myc oncogene display enhanced cytotoxity to human neuroblastoma 1M.R.32 cells expressing somatostatin receptors. Peptides 2002 23 1557-1565. 

Tissue Culture Assay. Kogure et al. (48) report a novel tissue culture assay for detecting several types of sodium channel blockers. The mouse neuroblastoma cell line ATCC CCL 131 is grown in RPMI 1640 supplemented with 13.5% fetal bovine serum and 100 pg/ml gentamycin, in an atmosphere of 5% C0 95% air at 37 C. Ninety-six well plates are seeded with 1 x 10 cells in 200 pi of medium containing 1 mM ouabain and 0.075 mM veratridine. Veratridine and ouabain cause neuroblastoma cells to round-up and die. In the presence of sodium channel blockers (e.g., TTXs or STXs), the lethal action of veratridine is obviated and cells retain normal morphology and viability. An important feature of this assay is that a positive test for sodium channel blockers results in normal cell viability. Since bacterial extracts can contain cytotoxic components, this assay offers an advantage over tests that use cell death as an endpoint. The minimum detectable level of TTX is approximately 3 nM, or approximately 1/1000 mouse unit. 

Tamplin et. al. (54) observed that V. cholerae and A. hydrophila cell extracts contained substances with TTX-like biological activity in tissue culture assay, counteracting the lethal effect of veratridine on ouabain-treated mouse neuroblastoma cells. Concentrations of TTX-like activity ranged from 5 to 100 ng/L of culture when compared to standard TTX. The same bacterial extracts also displaced radiolabelled STX from rat brain membrane sodium channel receptors and inhibited the compound action potential of frog sciatic nerve. However, the same extracts did not show TTX-like blocking events of sodium current when applied to rat sarcolemmal sodium channels in planar lipid bilayers. 

CTx that has been purified from muscles of Gymnothorax javanicus stimulates the release of neurotransmitters such as 7-aminobutyric acid and dopamine from rat brain nerve terminals. It causes a membrane depolarization of mouse neuroblastoma cells and, under appropriate conditions, it creates spontaneous oscillations of... 

In addition to the pre-synaptic effects, CX3CL1 modulates the functional properties of ligand-gated channels at post-synaptic sites. In SK-N-SH cells, a human neuroblastoma cell line, CX3CL1 reduces the amplitude of NMDA-induced calcium transients (Deiva et al. 2004). In these cells, CX3CL1 application causes a PTX insensitive transient increase in the intracellular Ca " concentration dependent on... 

Sommerburg, O. et al.. Oxidation derived metabolites of 3-carotene are able to initiate apoptosis in S-type SHEP neuroblastoma cells. Free Rad. Biol. Med., 33, S332, 2002. 

Graham, D.G. Tiffany, S.M. Bell, W.R., Jr. and Gutknecht, W.F. Autooxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine and related compounds toward C1300 neuroblastoma cells in vitro. Mol Pharmacol 14 644-653, 1978. 

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