100 research outputs found
Classification of current anticancer immunotherapies
During the past decades, anticancer immunotherapy has evolved from a promising
therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are
now approved by the US Food and Drug Administration and the European Medicines
Agency for use in cancer patients, and many others are being investigated as standalone
therapeutic interventions or combined with conventional treatments in clinical
studies. Immunotherapies may be subdivided into “passive” and “active” based on
their ability to engage the host immune system against cancer. Since the anticancer
activity of most passive immunotherapeutics (including tumor-targeting monoclonal
antibodies) also relies on the host immune system, this classification does not properly
reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer
immunotherapeutics can be classified according to their antigen specificity. While some
immunotherapies specifically target one (or a few) defined tumor-associated antigen(s),
others operate in a relatively non-specific manner and boost natural or therapy-elicited
anticancer immune responses of unknown and often broad specificity. Here, we propose
a critical, integrated classification of anticancer immunotherapies and discuss the clinical
relevance of these approaches
Meccanismi di neurotossicita' dell'etanolo durante lo sviluppo: interferenze nella neurotrasmissione
Dottorato di ricerca in tossicologia dell'ambiente e dell'alimentazione. 9 ciclo. A.a. 1996-97Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal
Methylmercury interaction with lymphocyte cholinergic muscarinic receptors in developing rats
Cerebral cholinergic muscarinic receptors (MR) have been suggested as one of the sensitive biochemical endpoints of the central nervous system altered by developmental exposure to the widespread seafood contaminant methylmercury (MeHg). In adult rats, MeHg has been shown to alter MR binding both in the brain and lymphocytes, supporting the use of MR in blood cells as a surrogate marker of
CNS changes. The effects of MeHg have been evaluated on rat lymphocyte MR binding (using [3H]QNB as specific muscarinic ligand) in vivo (after perinatal exposure) and in vitro. For comparison, in vitro studies were also performed on human lymphocytes. Exposure to 1mg MeHg/kg/day during pregnancy and lactation (from GD7 to PND7) significantly enhanced lymphocyte MR density in both adult and young rats 21 days after delivery, with a more pronounced effect in the mothers (Bmax increase of 139%) than in the male offspring (+49%) and female offspring (+73%) as compared with their respective controls (3374, 4178, and 3774 fmol/million cells), in accordance with the higher Hg levels detected in the adult blood (11.372.2 mg/mL) than in pups (1.370.4 mg/L in both genders).
A lower MeHg dose (0.5 mg/kg/day) was without any effect on lymphocyte MRs. In in vitro studies, MeHg was an almost equipotent
inhibitor of 3H-QNB binding to rat and human lymphocyte MRs (IC50 values were 4.170.29, 5.270.51, and 5.070.9 mM for total rat
lymphocytes, rat T lymphocytes, and total human lymphocytes, respectively). Notably, the IC50 values for MeHg to lymphocyte MRs
were comparable to the Hg levels reached in blood (5–50 mM) of the PND21 rats exposed to MeHg.
The finding that the MR binding is a target for the effects of MeHg in peripheral blood cells is in accordance with our previous data in
brain [Coccini et al., 2006. Effects of developmental co-exposure to methylmercury and 2,20,4,40,5,50-hexachlorobiphenyl (PCB153) on
cholinergic muscarinic receptors in rat brain. Neurotoxicology, in press], and supports the use of this peripheral endpoint as a biomarker of MeHg-induced cerebral muscarinic alterations. The similarity of MeHg IC50 binding data between human and rat in peripheral tissues suggests the possible application of such biomarker to humans exposed to environmental chemical
Effects of developmental co-exposure to methylmercury and PCB153 on brain cholinergic muscarinic receptors in the rat
Values of peripheral blood lymphocyte muscarinic receptors and platelet monoamine oxidase B activity in healthy humans
Developmental co-exposure to methylmercury and PCB153 or PCB126 affects cerebral cholinergic muscarinic receptors at weaning and puberty in rats
Enhancement of the susceptibility of cerebellar granule neurons to apoptosis by low concentrations of methylmercury.
Neurobehavioural and molecular changes induced by methylmercury exposure during development.
none6There is an increasing body of evidence on the possible environmental influence on neurodevelopmental and neurodegenerative disorders.
Both experimental and epidemiological studies have demonstrated the distinctive susceptibility of the developing brain to environmental
factors such as lead, mercury and polychlorinated biphenyls at levels of exposure that have no detectable effects in adults. Methylmercury
(MeHg) has long been known to affect neurodevelopment in both humans and experimental animals.
Neurobehavioural effects reported include altered motoric function and memory and learning disabilities. In addition, there is evidence
from recent experimental neurodevelopmental studies that MeHg can induce depression-like behaviour. Several mechanisms have been suggested from in vivo- and in vitro-studies, such as effects on neurotransmitter systems, induction of oxidative stress and disruption of microtubules and intracellular calcium homeostasis.
Recent in vitro data show that very low levels of MeHg can inhibit neuronal differentiation of neural stem cells. This review summarises what is currently known about the neurodevelopmental
effects of MeHg and consider the strength of different experimental approaches to study the effects of environmentally relevant exposure in vivo and in vitro.JOHANSSON C; CASTOLDI AF; ONISHCHENKO N; L. MANZO; VAHTER M; CECCATELLI SJohansson, C; Castoldi, Af; Onishchenko, N; Manzo, Luigi; Vahter, M; Ceccatelli, S
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