Endocrine disruptor chlorpyrifos promotes migration, invasion, and stemness phenotype in 3D cultures of breast cancer cells and induces a wide range of pathways involved in cancer progression.

Organophosphorus chlorpyrifos (CPF) is currently considered an endocrine disruptor (ED), as it can imitate hormone actions both in vitro and in vivo. We recently reported that CPF induces migration and invasion in 2D cultures and changes the expression of key molecular markers involved in epithelial mesenchymal transition in MCF-7 and MDA-MB-231 cell lines. In this study, we investigated whether CPF could behave as a predisposing factor for tumors to become more metastatic and aggressive using 3D culture models. In MCF-7 cells, 0.05 µM CPF induced an increase in the number and size of mammospheres via estrogen receptor alpha (ERα) and c-SRC. Furthermore, 0.05 µM CPF increased the area of spheroids generated from MCF-7 cells, induced invasion using both Matrigel® and type 1 collagen matrices, and increased cell migration capacity via ERα in this 3D model. In turn, 50 µM CPF increased cell migration capacity and invasion using type 1 collagen matrix. In monolayers, CPF increased the phosphorylation and membrane translocation of c-SRC at both concentrations assayed. CPF at 0.05 µM boosted p-AKT, p-GSK-3ß and p-P38. While p-AKT rose in a ERα-dependent way, p-GSK-3ß was dependent on ERα- and c-SRC, and p-P38 was only dependent on c-SRC. On the other hand, the increase in p-AKT and p-P38 induced by 50 µM CPF was dependent on the c-SRC pathway. We also observed that 0.05 µM CPF increased IGF-1R and IRS-1 expression and that 50 µM CPF induced IGF-1Rß phosphorylation. In the MDA-MB-231 cell line, 0.05 and 50 µM CPF increased p-c-SRC. Finally, p-AKT and p-GSK-3ß were also induced by CPF at 0.05 and 50 µM, and an increase in p-P38 was observed at 50 µM. Taken together, these data provide support for the notion that CPF may represent a risk factor for breast cancer development and progression.

Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells.

Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 µM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 µM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 µM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and ß-Catenin expression diminishing their membrane location. Furthermore, 50 µM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 µM CPF increase MMP2 gelatinolytic activity and expression, decrease ß-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.

Hexachlorobenzene alters cell cycle by regulating p27-cyclin E-CDK2 and c-Src-p27 protein complexes.

Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea-induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7. Here, we show that HCB alters cell cycle in a concentration-dependent way. The lowest assessed concentration (0.005µM) promotes the cell cycle progression, enhances cyclin D1 expression, and reduces the nuclear localization of p27 accompanied by an increased interaction between p27 and c-Src kinase. On the other hand, 5µM HCB delays the cell cycle progression and promotes the formation of the cyclin E-CDK2-p27 protein complex. Our results show that HCB stimulates cell proliferation through cell cycle modulation and c-Src involvement in MCF-7 cells. Here, we report for the first time that differential mechanisms of action of HCB on mammary cell cycle progression are triggered at different concentrations of this pollutant.

[Anti-Ri paraneoplastic syndrome associated with ophtalmoplegia, blepharospasm and palilalia]. / Ophtalmoplégie, blépharospasme et palilalie associés à des anticorps anti-Ri.

INTRODUCTION: Anti-Hu and anti-Yo are the most well-known anti-neuronal antibodies. The anti-Ri antibodies, which are less common, are generally found in subjects with opsoclonus-myoclonus, often associated with breast cancer. CASE REPORT: A 54-year-old woman presented anti-Ri antibodies associated with a paraneoplastic syndrome and unusual symptoms of ophthalmoplegia, blepharospasm, palilalia and ataxia. Adenocarcinoma of the breast was also found. After chemotherapy, radiotherapy, and several immunoglobulin infusions, the patient did not improve ten months after tumor surgery. CONCLUSION: Anti-Ri antibodies associated with paraneoplastic syndrome can be observed in patients who develop a rapidly progressive brainstem tumor. Breast or lung cancer and conduct to search a breast or pulmonary cancer.

[Therapeutic efficacy during active phases of multiple sclerosis: gait analysis and comparison with the EDSS score]. / Mesure de l'efficacité thérapeutique au cours d'une poussée de sclérose en plaques par l'analyse de la marche: comparaison avec le score EDSS.

Fifteen patients experiencing a flare-up of multiple sclerosis were given 1 g methylprednosolone per day for 5 days. The EDSS score and gait analysis using spatio-temporal variables were recorded for these patients on days 0, 5 and 45. Both methods evidenced significant improvement but the significance was observed between day 0 and day 5 for the EDSS and between day 5 and 45 for gait speed and between day 0 and 45 for step rate. Gait speed was correlated with the pyramidal scale but not with the other functional scales of the EDSS. These results suggest that EDSS and spatio-temporal gait analysis are different tools for the assessment of therapeutic effect. Gait analysis can provide a precise quantitative assessment of the locomotor handicap as a function of the proposed treatment.

[Naming impairment for man-made objects in a case of herpes encephalitis]. / Trouble de la dénomination pour les objets manufacturés dans un cas d'encéphalite herpétique.

We report the naming performances of a 25 year-old woman with a left internal and inferior temporal lesion caused by herpes encephalitis who showed a preferential impairment for naming man-made objects. Evidence for category-specific effect was provided by a stepwise logistic regression using 171 pictures characterized by several parameters (words frequency, diversity of responses, length, name agreement, majoritary response, familiarity, visual complexity and canonicity). Analyses were realized over a 5 month period. Methodological considerations, anatomic correlations and arguments suggesting lexical access or semantic storage disturbance are discussed.

[Palinopsia associated with partial seizures secondary to right parietal hemorrhage]. / Palinopsie associée à des crises partielles secondaires à une hémorragie pariétale droite.

Palinopsia and motor partial seizures were associated in a 51-year-old man. The manifestation appeared six months after a right parietal hemorrhage. The relationship between the hallucinatory phenomena and epilepsy is discussed.

[The evolution of the migratory flows in South Catalonia, 1950-1975]. / L'evolution du panorama migratoire en Catalogne Sud, 1950-1975.

PIP: "This paper retraces the history and the geography of the substitution in the migratory flows to Catalonia...during the last 30 years. After the huge movement of internal migration during the first half of the twentieth century, the first flow of foreign migrants appeared in the [1970s]. This substitution of migratory origin is related to a reconfiguration of the immigrants' geographic polarity of settlements and in their economic role. Based on various statistical indicators and bibliographic references, this paper provides some essential elements for the understanding of the migratory complexity of this space." (EXCERPT)^ieng

[Brachial diplegia caused by cervical spinal cord ischemia. A case]. / Diplégie brachiale par ischémie médullaire cervicale. Un cas.

We report one case of acute cervical spinal cord infarction characterized by motor impairment of the upper limbs with respect of the lower limbs. It occurs infrequently. The purpose of this paper is to discuss the clinical, neurophysiological and magnetic resonance imaging findings, and to review the presumed mechanisms of spinal cord infarction.