@article {8355,
	title = {Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes.},
	journal = {Mol Med Rep},
	volume = {14},
	year = {2016},
	month = {2016 Jul},
	pages = {574-82},
	abstract = {<p>Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in~vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in~vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti-rheumatic effect. These findings are notable and must be accounted for, as bystander-activated cells in~vivo could contribute to the spread of autoimmune activation and disease progression.</p>},
	issn = {1791-3004},
	doi = {10.3892/mmr.2016.5263},
	author = {Piscianz, Elisa and Candilera, Vanessa and Valencic, Erica and Loganes, Claudia and Paron, Greta and De Iudicibus, Sara and Decorti, Giuliana and Tommasini, Alberto}
}
@article {7694,
	title = {Alendronate, a double-edged sword acting in the mevalonate pathway.},
	journal = {Mol Med Rep},
	volume = {12},
	year = {2015},
	month = {2015 Sep},
	pages = {4238-42},
	abstract = {<p>Aminobisphosphonate aledronate is a compound commonly used clinically for the treatment of osteoporosis and other bone diseases, as a result of it preventing bone resorption. However, in previous years it has also been used to obtain cellular and animal models of a rare genetic disorder termed Mevalonate Kinase Deficiency (MKD). MKD is caused by mutations affecting the mevalonate kinase enzyme, in the cholesterol pathway and alendronate can be used to biochemically mimic the genetic defect as it inhibits farnesyl pyrophosphate synthase in the same pathway. Despite evidence in favor of the inhibition exerted on the mevalonate pathway, there is at least one clinical case of MKD in which alendronate improved not only skeletal and bone fractures, as expected, but also MKD clinical features. Based on this finding, the present study assessed the anti-inflammatory properties of this aminobisphosphonate in vitro. No anti-inflammatory effects of alendronate were observed in the in vitro experiments. Since MKD lacks specific treatments, these results may assist scientists and physicians in making the decision as to the most suitable choice of therapeutic compounds for this neglected disease.</p>},
	issn = {1791-3004},
	doi = {10.3892/mmr.2015.3957},
	author = {Tricarico, Paola Maura and Girardelli, Martina and Kleiner, Giulio and Knowles, Alessandra and Valencic, Erica and Crovella, Sergio and Marcuzzi, Annalisa}
}
@article {7787,
	title = {Altered germinal center reaction and abnormal B cell peripheral maturation in PI3KR1-mutated patients presenting with HIGM-like phenotype.},
	journal = {Clin Immunol},
	volume = {159},
	year = {2015},
	month = {2015 Jul},
	pages = {33-6},
	keywords = {B-Lymphocytes, Child, Preschool, Female, Germinal Center, Humans, Hyper-IgM Immunodeficiency Syndrome, Infant, Male, Mutation, Phenotype, Phosphatidylinositol 3-Kinases, RNA Splice Sites, Sequence Analysis, DNA},
	issn = {1521-7035},
	doi = {10.1016/j.clim.2015.04.014},
	author = {Lougaris, Vassilios and Faletra, Flavio and Lanzi, Gaetana and Vozzi, Diego and Marcuzzi, Annalisa and Valencic, Erica and Piscianz, Elisa and Bianco, AnnaMonica and Girardelli, Martina and Baronio, Manuela and Loganes, Claudia and Fasth, Anders and Salvini, Filippo and Trizzino, Antonino and Moratto, Daniele and Facchetti, Fabio and Giliani, Silvia and Plebani, Alessandro and Tommasini, Alberto}
}
