Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression

<p>Abstract</p> <p>Background</p> <p>Cimetidine, a histamine type-2 receptor antagonist, has been reported to inhibit the growth of glandular tumors such as colorectal cancer, however the mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma is well known as a malignant salivary gland tumor which preferentially invades neural tissues. We demonstrated previously that human salivary gland tumor (HSG) cells spontaneously express neural cell adhesion molecule (NCAM), that HSG cell proliferation may be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. We further demonstrated that cimetidine inhibited NCAM expression and induced apoptosis in HSG cells. Here, we investigated the effects of cimetidine on growth and perineural/neural invasion of salivary gland tumor cells.</p> <p>Methods</p> <p>In this study, we have examined the effect of cimetidine on cancer cell adhesion to neural cells <it>in vitro</it>, one of the critical steps of cancer invasion and metastasis. We have also used an <it>in vivo </it>carcinogenesis model to confirm the effect of cimetidine.</p> <p>Results</p> <p>We have demonstrated for the first time that cimetidine can block the adhesion of HSG cells to neural cell monolayers and that it can also induce significant apoptosis in the tumor mass in a nude mouse model. We also demonstrated that these apoptotic effects of cimetidine might occur through down-regulation of the cell surface expression of NCAM on HSG cells. Cimetidine-mediated down-regulation of NCAM involved suppression of the nuclear translocation of NF-κB, a transcriptional activator of NCAM gene expression.</p> <p>Conclusion</p> <p>These findings suggest that growth and perineural/neural invasion of salivary gland tumors can be blocked by administration of cimetidine via induction of apoptosis and in which NCAM plays a role.</p

Peer substance use overestimation among French university students: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Normative misperceptions have been widely documented for alcohol use among U.S. college students. There is less research on other substances or European cultural contexts. This study explores which factors are associated with alcohol, tobacco and cannabis use misperceptions among French college students, focusing on substance use.</p> <p>Methods</p> <p>12 classes of second-year college students (n = 731) in sociology, medicine, nursing or foreign language estimated the proportion of tobacco, cannabis, alcohol use and heavy episodic drinking among their peers and reported their own use.</p> <p>Results</p> <p>Peer substance use overestimation frequency was 84% for tobacco, 55% for cannabis, 37% for alcohol and 56% for heavy episodic drinking. Cannabis users (p = 0.006), alcohol (p = 0.003) and heavy episodic drinkers (p = 0.002), are more likely to overestimate the prevalence of use of these consumptions. Tobacco users are less likely to overestimate peer prevalence of smoking (p = 0.044). Women are more likely to overestimate tobacco (p < 0.001) and heavy episodic drinking (p = 0.007) prevalence. Students having already completed another substance use questionnaire were more likely to overestimate alcohol use prevalence (p = 0.012). Students exposed to cannabis prevention campaigns were more likely to overestimate cannabis (p = 0.018) and tobacco use (p = 0.022) prevalence. Other identified factors are class-level use prevalences and academic discipline.</p> <p>Conclusions</p> <p>Local interventions that focus on creating realistic perceptions of substance use prevalence could be considered for cannabis and alcohol prevention in French campuses.</p

Babassu aqueous extract (BAE) as an adjuvant for T helper (Th)1-dependent immune responses in mice of a Th2 immune response-prone strain

<p>Abstract</p> <p>Background</p> <p>The aqueous extract of a Brazilian palm-tree fruit - the babassu - (BAE) exerts a clear immunostimulative activity <it>in vivo</it>. In the present work, the possibility that BAE can promote Th1 immune responses in mice of a Th2 immune response-prone strain - the BALB/c was investigated. BAE itself, and preparations consisting of <it>Leishmania amazonensis </it>promastigote extract (LE), adsorbed or not to Al(OH)₃, and in the presence or not of BAE, were used as immunogens. LE and Al(OH)₃have been shown to preferentially elicit Th2 immune responses.</p> <p>Results</p> <p>The addition of BAE to LE-containing immunogenic preparations, adsorbed or not to Al(OH)₃, clearly promoted the <it>in vitro </it>production of interferon γ (IFN-γ), a major Th1-dependent cytokine, and not of interleukin (IL-)4 (a Th2-dependent cytokine), by LE-stimulated splenocytes of immunized BALB/c mice. It also promoted the <it>in vivo </it>formation of IgG2a anti-LE antibodies. However, immunization with LE by itself led to an increased production of IL-4 by LE-stimulated splenocytes, and this production, albeit not enhanced, was not reduced by the addition of BAE to the immunogen. On the other hand, the IL-4 production by LE-stimulated splenocytes was significantly lower in mice immunized with a preparation containing Al(OH)₃-adsorbed LE and BAE than in mice immunized with the control preparation of Al(OH)₃-adsorbed LE without BAE. Moreover, an increased production of IFN-γ, and not of IL-4, was observed in the culture supernatants of splenocytes, from BAE-immunized mice, which were <it>in vitro </it>stimulated with BAE or which received no specific <it>in vitro </it>stimulus. No differences in IL-10 (an immunoregulatory cytokine) levels in the supernatants of splenocytes from mice that were injected with BAE, in relation to splenocytes from control mice, were observed. The spontaneous <it>ex vivo </it>production of NO by splenocytes of mice that had been injected with BAE was significantly higher than the production of NO by splenocytes of control mice.</p> <p>Conclusions</p> <p>Based on the results described above, BAE, or biologically active molecules purified from it, should be further investigated as a possible adjuvant, in association or not with aluminium compounds, for the preferential induction of Th1-dependent immune responses against different antigens in distinct murine strains and animal species.</p