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Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors. [ABSTRACT FROM AUTHOR]

Trefoil Factor 1 (TFF1), the first member of the trefoil factor family, is normally expressed in the stomach mucosa. Ectopic expression is also observed in various human pathological conditions, notably in numerous carcinomas and gastrointestinal acute inflammatory disorders. In vivo experimental data using TFF1-deficient mice highlight the pleiotropic functions of TFF1: (i) it is a gastric tumor suppressor gene involved in gastric ontogenesis and homeostasis; (ii) it protects gut mucosa from aggression; (iii) it participates in folding secreted proteins inside the endoplasmic reticulum. At the cellular level, it limits cell proliferation and apoptosis, and favors cell differentiation. Collectively, these data suggest that TFF1 may provide an alternative pharmacological tool for the prevention and treatment of human gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Expression of pS2 (an estrogen-induced gene isolated from breast carcinoma MCF7 cells) and of the human spasmolytic peptide (hSP) gene was analyzed in 21 human biliary tract and gallbladder carcinomas and 16 non-neoplastic gallbladders at the protein level (immunochemistry) and, in a series of these cases, at the RNA level (Northern blots). Eighteen carcinomas and 14 nonneoplastic mucosae with inflammatory alterations showed pS2 activity by immunostaining or Northern blotting. In addition, in samples with pS2 expression, hSP RNA was demonstrated. In the corresponding nonneoplastic and healthy mucosae, pS2 was negative, as judged by immunostaining. Northern blots showed weak (basal) level of activity for pS2 and hSP. The genes' increased expression in correlation to inflammatory and neoplastic processes, by now observed in several carcinomas and idiopathic inflammatory bowel disease, hints to their essential role in such diseases. [ABSTRACT FROM AUTHOR]

The 1993 Spanish National Health Survey data were used to estimate how frequently both medication and alcohol were used among 21084 people over 16 years of age. A total of 47.1% of the population, especially women and an increasingly older section, had taken some kind of medication during the previous fortnight. A total of 9.8% of the population took medication and alcohol together. This was more frequently observed among men than among women, and especially so among the older age groups. These data reveal that concomitant alcohol and medication use is frequent among the Spanish population, and suggest a need to devote much more attention to this potential problem. [ABSTRACT FROM AUTHOR]

Introduction Des études cliniques rétrospectives ont suggéré l’effet protecteur de l’anesthésie loco-régionale contre les récidives locales et les métastases dans la chirurgie carcinologique [1] . Peu d’études se sont intéressées à l’impact de l’anesthésie dans le cancer du sein. Notre travail a consisté à évaluer in vitro le possible effet inhibiteur direct de la lidocaïne sur la prolifération et la migration cellulaires dans le cancer du sein. Matériel et méthodes La prolifération d’une lignée cellulaire épithéliale mammaire non-tumorale (MCF-10A) et de 3 lignées malignes (MCF-7, SKBr3 et MDA-MB-231) a été étudiée par test colorimétrique MTT. La migration cellulaire a été étudiée par test de blessure sur les cellules MCF-10A, SKBr3 et MDA-MB-231. Les cellules étaient exposées à de la lidocaïne (LIDO) à concentrations croissantes ou au contrôle éthanol (CTL). Résultats La prolifération cellulaire de toutes les lignées cellulaires après exposition à la LIDO (de 5 × 10 −4 à 10 −3 M) pendant 4 heures a permis une inhibition significative par rapport au CTL. À la concentration de 10 −4 M, l’inhibition est plus importante pour les cellules MDA-MB-231 (–10,38 ± 9,87 %, moyenne ± écart-type) que pour les cellules MCF-10A (+14,69 ± 12,9 %, p < 0,001). Pour la migration cellulaire, après 24 heures, pour les cellules SKBr3, la blessure s’est refermée de 5,327 ± 7,504 % pour le groupe LIDO à la dose de 10 −4 M contre 13,34 ± 2,618 % pour le groupe CTL ( p < 0,01). Pour les cellules MDA-MB-231, les résultats étaient respectivement de 12,82 ± 11,49 % contre 29,31 ± 11,68 %, p < 0,01. Cet effet inhibiteur de la migration cellulaire n’est pas retrouvé pour les cellules non-tumorales MCF-10A, avec une fermeture de 39,36 ± 12,55 % (LIDO) contre 51,02 ± 15,04 % (CTL), p = 0,0931. Lorsque l’on compare les 3 lignées entre elles, l’effet inhibiteur de la LIDO est plus important pour les 2 lignées cancéreuses (Anova : p < 0,001, Fig. 1 ). Discussion La lidocaïne, aux concentrations cliniques d’infiltration péricicatricielle, a un effet inhibiteur direct sur la prolifération et la migration de cellules cancéreuses de sein in vitro . Ces résultats devront faire l’objet d’une étude clinique prospective randomisée évaluant la survie sans récidive après chirurgie carcinologique mammaire. [ABSTRACT FROM AUTHOR]