BackgroundBreast cancer is a heterogeneous disease that is not totally eradicated by current therapies. The classification of breast tumors into distinct molecular subtypes by gene profiling and immunodetection of surrogate markers has proven useful for tumor prognosis and prediction of effective targeted treatments. The challenge now is to identify molecular biomarkers that may be of functional relevance for personalized therapy of breast tumors with poor outcome that do not respond to available treatments. The Mitochondrial Tumor Suppressor (MTUS1) gene is an interesting candidate whose expression is reduced in colon, pancreas, ovary and oral cancers. The present study investigates the expression and functional effects of MTUS1 gene products in breast cancer.Methods and FindingsBy means of gene array analysis, real-time RT-PCR and immunohistochemistry, we show here that MTUS1/ATIP3 is significantly down-regulated in a series of 151 infiltrating breast cancer carcinomas as compared to normal breast tissue. Low levels of ATIP3 correlate with high grade of the tumor and the occurrence of distant metastasis. ATIP3 levels are also significantly reduced in triple negative (ER- PR- HER2-) breast carcinomas, a subgroup of highly proliferative tumors with poor outcome and no available targeted therapy. Functional studies indicate that silencing ATIP3 expression by siRNA increases breast cancer cell proliferation. Conversely, restoring endogenous levels of ATIP3 expression leads to reduced cancer cell proliferation, clonogenicity, anchorage-independent growth, and reduces the incidence and size of xenografts grown in vivo. We provide evidence that ATIP3 associates with the microtubule cytoskeleton and localizes at the centrosomes, mitotic spindle and intercellular bridge during cell division. Accordingly, live cell imaging indicates that ATIP3 expression alters the progression of cell division by promoting prolonged metaphase, thereby leading to a reduced number of cells ungergoing active mitosis.ConclusionsOur results identify for the first time ATIP3 as a novel microtubule-associated protein whose expression is significantly reduced in highly proliferative breast carcinomas of poor clinical outcome. ATIP3 re-expression limits tumor cell proliferation in vitro and in vivo, suggesting that this protein may represent a novel useful biomarker and an interesting candidate for future targeted therapies of aggressive breast cancer.

International audienceWe report an exceptional case of multiple cutaneous and visceral neonatal pyogenic granuloma (PG) initially suggestive of a diffuse neonatal haemangiomatosis. CASE REPORT A full-term female newborn, with no significant past medical history, was referred to our department for treatment of an acute respiratory distress syndrome of neurological origin at day 8 of life. At birth, she presented with 3 small angiomatous papules and 4 subcutaneous nodules suggestive of neonatal hae-mangiomatosis (NH) (Fig. 1). A brain MRI revealed a highly vascularised brain stem tumour suggestive of glioma (Fig. 2), associated with 2 abnormal hepatic lesions consistent with infantile haemangiomas (IH) on ultrasound and CT scan. Methylprednisolone was started for the suspected glioma-associated oedema, and vincristine and propranolol were introduced for NH. After initial improvement, an acute intracranial hypertension related to cystic evolution of the disease necessitated surgical resection at the age of 2 months. Pathological examinations of the brain, cutaneous and subcutaneous lesions were similar, showing a vascular lobular proliferation of capillaries highly suggestive of PG. The misdiagnosis of glioma was eliminated. The GLUT-1 antigen marker was negative, ruling out the diagnosis of NH-like infantile haemangioma (Fig. 3). Lymphatic marker (D2-40) was also negative and eliminated a multifocal lymphangioendotheliomato-sis with thrombocytopaenia (MLT). Cutaneous and hepatic lesions gradually regressed. She is currently in complete remission after completing a treatment over 18 months with propranolol but a spontaneous improvement can not be excluded. DISCUSSIO

Oscillometric measurements of respiratory system resistance (Rrs) in infants are usually made via the nasal pathways, which not only significantly contribute to overall Rrs, but also introduce marked flow (V')-dependent changes. We employed intrabreath oscillometry in casts of the upper airways constructed from head CT images of 46 infants. We examined oscillometric nasal resistance (Rn) in upper airway casts with no respiratory flow (R0), and the effect of varying V' on Rn by simulating tidal breathing. A characteristic nonlinear relationship was found between Rn and V', exhibiting segmental linearity and a prominent breakpoint (V'bp) after log-log transformation. V'bp was linearly related to the preceeding value of end-expiratory volume acceleration (V"eE; on average r2=0.96, p<0.001). Rn depended on V', and R at end-expiration (ReE) and showed a strong dependence on V"eE in every cast (r2=0.994, p<001) with considerable inter-individual variability. The intercept of the linear regression of ReE vs. V"eE was found to be a close estimate of R0. These findings were utilised in re-analysed Rrs data acquired in vivo in a small group of infants (n=15). Using a graphical method to estimate R0 from ReE, we found a relative contribution of V'-dependent nonlinearity to total resistance of up to 33%. In conclusion, we propose a method for correcting the acceleration-dependent non-linearity error in ReE. This correction can be adapted to estimate R0 from a single intrabreath oscillometric measurement, which would reduce the masking effects of the upper airways on the changes in the intrathoracic resistance.

No abstract

New techniques have been developed in order to reduce the time of treatment, minimizing the cost and the psychological and surgical trauma of the patients, especially in regions with aesthetic involvement. The immediate placement of dental implants is a reality and clinical studies have shown that the success rate of immediate implant is similar to that placed after bone repair. The objective of this study is to present a clinical case of a immediate implant placement to substitute a central incisor after atraumatic extraction, through the use of Neodent root extractor. Immediate implant placement and immediate loading, when correctly indicated, are a quick and safe alternative for the rehabilitation of affected teeth , they also allow the preservation of bone architecture , and provides the patient a lower number of surgeries and consequently less morbidity. It also promotes psychological comfort, immediate aesthetic and functional satisfaction to the patient.