L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia.

The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute lymphoblastic leukemia (T-ALL)/lymphoma (T-LL) cells. We show here that a potent and LAT1 selective inhibitor (JPH203) decreased leukemic cell viability and proliferation, and induced transient autophagy followed by apoptosis. JPH203 could also alter the in vivo growth of luciferase-expressing-tPTEN-/- cells xenografted into nude mice. In contrast, JPH203 was nontoxic to normal murine thymocytes and human peripheral blood lymphocytes. JPH203 interfered with constitutive activation of mTORC1 and Akt, decreased expression of c-myc and triggered an unfolded protein response mediated by the C/EBP homologous protein (CHOP) transcription factor associated with cell death. A JPH203-resistant tPTEN-/-clone appeared CHOP induction deficient. We also demonstrate that targeting LAT1 may be an efficient broad spectrum adjuvant approach to treat deadly T-cell malignancies as the molecule synergized with rapamycin, dexamethasone, doxorubicin, velcade and l-asparaginase to alter leukemic cell viability.

[Social adjustment in French adults from who had undergone standardised treatment of complete unilateral cleft lip and palate]. / Impact social sur de jeunes adultes du traitement standardisé de fentes labiomaxillopalatines unilatérales complètes traitées dans l'enfance.

France has a population of about 60 million peoples and each ten years data about the standard of living are collected by the central bureau of statistics, we considered the collection of data on 5000 households in 1999 in our geographical area would afford a unique opportunity to compare the equivalent status of French adults with repaired cleft of the lip and palate (CLP). Aspects of social adjustment were investigated in a sample of 82 French adults 18-35 years old with repaired complete unilateral cleft of the lip and palate (CLP). All subjects received a standardized regimen of care from the Burgundy cleft palate team of Dijon. The investigation, based on response to a questionnaire, partly replicated a national survey of social and economic life in the population (Standard of living survey Burgundy, INSEE France 1999), so that adults with complete clefts could be compared with a large control sample of the same age. The control group was constituted by subjects between 18 and 35 years in the standard of living survey Burgundy 1999, INSEE France, they were taken from a regional probability sample of households. This report covers education, employment, and marriage. The significant difference between groups was assessed by: Student's t-test or analysis of variance for continuous variables and chi2 test for categorical variables. The results demonstrated that there are significant differences in educational attainment and employment between adults with cleft of the lip and palate and other people. Fewer with cleft of the lip and palate marry, and when they marry they do so later in life, scholarship history showed significant delay in the cleft of the lip and palate group, independence regarding housing was lower in the cleft of the lip and palate group. If cleft of the lip and palate adults functioned within normal limits with regard to employment. However, levels of income were substantively lower than control groups. It would appear that cleft subjects experience some limitation in their ability to secure vocational and economic rewards from society. As a conclusion we can say regarding our results that the cleft of the lip and palate group, even with the smallest degree of malformation (unilateral without associated malformation), showed a significant delay in the independence process.