Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma cell lines are commonly used as a model to study neuronal differentiation as they retain the capacity to differentiate into a neuronal-like phenotype. It is of great medical interest to understand the signalling pathways biasing differentiation versus proliferation. Neuroblastoma cells differentiate in response to serum reduction or addition of the cholesterol synthesis inhibitor mevastatin. The responsible pathways are not well characterized. In Neuro2a neuroblastoma cells, we found that mevastatin and serum withdrawal triggered the production of nitric oxide (NO). In addition, the differentiation of Neuro2a cells and the activation of Akt/PKB triggered by serum withdrawal could be blocked by addition of the NO synthetase (NOS) inhibitor l-NAME. Moreover, mevastatin and serum withdrawal rapidly increased the expression of the neuronal NOS isoform nNOS. However, addition of an NO donor SNP per se did not trigger neurite outgrowth. Taken together, we report for the first time a role of NO in neurite outgrowth of neuroblastoma cells triggered by mevastatin or serum reduction.
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PMID:A role of nitric oxide in neurite outgrowth of neuroblastoma cells triggered by mevastatin or serum reduction. 1985 42

For adoptive T-cell therapy to be effective against solid tumors, tumor-specific T cells must be able to migrate to the tumor site. One requirement for efficient migration is that the effector cells express chemokine receptors that match the chemokines produced either by tumor or tumor-associated cells. In this study, we investigated whether the tumor trafficking of activated T cells (ATCs) bearing a chimeric antigen receptor specific for the tumor antigen GD2 (GD2-CAR) could be enhanced by forced coexpression of the chemokine receptor CCR2b, as this receptor directs migration toward CCL2, a chemokine produced by many tumors, including neuroblastoma. Neuroblastoma cell lines (SK-N-SH and SK-N-AS) and primary tumor cells isolated from 6 patients all secreted high levels of CCL2, but GD2-CAR transduced ATCs lacked expression of CCR2 (<5%) and migrated poorly to recombinant CCL2 or tumor supernatants. After retroviral transduction, however, ATCs expressed high levels of CCR2b (>60%) and migrated well in vitro. We expressed firefly luciferase in CCR2b-expressing ATCs and observed improved homing (>10-fold) to CCL2-secreting neuroblastoma compared with CCR2-negative ATCs. As a result, ATCs co-modified with both CCR2b and GD2-CAR had greater antitumor activity in vivo.
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PMID:Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. 2084 59