A French Cohort of Childhood Leukemia Survivors: Impact of Hematopoietic Stem Cell Transplantation on Health Status and Quality of Life

AbstractThe late effects and quality of life (QoL) in childhood acute leukemia survivors were compared between hematopoietic stem cell transplantation (HSCT) recipients and patients who underwent conventional therapy. The study included 943 patients, 256 of whom underwent HSCT (27.1%). Medical visits were conducted to detect the occurrence of physical late effects. Based on patient age, different questionnaires were used to assess QoL. To evaluate the association between HSCT and each type of late effect or QoL dimension, the appropriate multivariate regressions were performed. QoL mean scores were compared with those obtained for age- and sex-matched French control subjects. Of all the survivors, 674 (71.5%) had at least 1 late effect, with the risk being 5.0 CI95 (3.0-8.6) times higher for transplantation survivors. For child survivors, scoring of QoL showed no significant differences between the treatment groups. The adult HSCT survivors reported lower physical dimension QoL scores than chemotherapy survivors. Compared with French norms, the survivor group reported a significantly lower mental composite score; however, the physical composite score showed no significant difference. Thus, transplanted survivors have a high risk of developing late effects, resulting in a decreased physical well-being in adulthood. However, long after treatment completion, childhood leukemia survivors report that effects on psychological well-being are more important than they are in physical QoL dimensions

Specific Oncogenic Activity of the Src-Family Tyrosine Kinase c-Yes in Colon Carcinoma Cells

c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of β-catenin at cell membranes and a reduction of expression of β-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in β-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src

' i Dynarnics of the microbial community responsible for traditional sour cassava starch fermentation studied by denaturing gradient gel electrophoresis and quantitative rRNA hybridization

Abstract The microbial community developing during the spontaneous fermentation of sour cassava starch was investigated by cultivation-independent methods. Denaturing gradient gel electrophoresis (DGGE) of partially amplified 16s rDNA followed by sequencing of the most intense bands showed that the dominant organisms were all lactic acid bacteria (LAB), mainly close relatives of Bifdobacteriunt minintuin, Lactococcus lactis, Streptococcus sp., Enterococcus saccharolyticus and Lactobacillus plantarum. Close relatives of Lb. panis, Leuconostoc ïneseiiteroides and Ln. citreuni were also found. A complementary analysis using hybridization of 16s rRNA with phylogenetic probes was necessary to detect the presence of the recently discovered species Lb. iizaiiilzotivoraiis. Although it represented up to 13% of the total lactic acid bacteria of sour cassava starch, this species could not be detected by DGGE as the PCR product migrated to the same position as Lc. lactis. In addition, it was shown that a strong pH decrease in the time course of fermentation was most probably responsible for the competitive selection of acid-resistant LAB vs. both homo and heterofermentative acid-sensitive LAB. O 200 1 Elsevier Science B.V. All rights reserved

DDR1 inhibition as a new therapeutic strategy for colorectal cancer

The clinical management of metastatic colorectal cancer (mCRC) is still a major challenge. Recently, we discovered that nilotinib, an approved treatment for chronic myeloid leukaemia, inhibits invasive and metastatic properties of CRC cells by targeting the kinase activity of receptor for collagens DDR1 (Discoïdin Domain Receptor tyrosine kinase 1), suggesting that nilotinib could be an effective strategy to treat mCRC

Cytoplasmic signalling by the c-Abl tyrosine kinase in normal and cancer cells.

International audiencec-Abl is a non-receptor tyrosine kinase which is localized both in the nucleus and cytoplasm, and is involved in the regulation of cell growth, survival and morphogenesis. Although c-Abl nuclear function has been extensively studied, recent data also indicate an important role in cytoplasmic signalling through mitogenic and adhesive receptors. Here, we review the mechanisms by which growth factors promote cytoplasmic c-Abl activation and signalling and its function in the induction of DNA synthesis, changes in cell morphology and receptor endocytosis. The importance of de-regulated c-Abl cytoplasmic signalling in solid tumours is also discussed

Control of Tyrosine Kinase Signalling by Small Adaptors in Colorectal Cancer

Tyrosine kinases (TKs) phosphorylate proteins on tyrosine residues as an intracellular signalling mechanism to coordinate intestinal epithelial cell communication and fate decision. Deregulation of their activity is ultimately connected with carcinogenesis. In colorectal cancer (CRC), it is still unclear how aberrant TK activities contribute to tumour formation because TK-encoding genes are not frequently mutated in this cancer. In vertebrates, several TKs are under the control of small adaptor proteins with potential important physiopathological roles. For instance, they can exert tumour suppressor functions in human cancer by targeting several components of the oncogenic TK signalling cascades. Here, we review how the Src-like adaptor protein (SLAP) and the suppressor of cytokine signalling (SOCS) adaptor proteins regulate the SRC and the Janus kinase (JAK) oncogenic pathways, respectively, and how their loss of function in the intestinal epithelium may influence tumour formation. We also discuss the potential therapeutic value of these adaptors in CRC

Analyse

Les tyrosine-kinases (TK) régulent la signalisation intracellulaire induite par de nombreux stimulus extracellulaires et conduisent à la croissance ou à l’adhésion cellulaires. La dérégulation de leur activité leur confère des propriétés oncogéniques qui contribuent à la formation de cancers chez l’homme. Cependant, les voies de signalisation impliquées ne sont que partiellement élucidées. Dans ce contexte, l’analyse par spectrométrie de masse de type SILAC (stable isotope labelling with amino acids in cell culture) permet de caractériser l’ensemble des substrats et la dynamique de phosphorylation activée par ces TK. Cette approche a ainsi mis en évidence une complexité inattendue de la signalisation oncogénique induite par la TK Src dans les cellules de cancer colorectal (CCR). Dans cette revue, nous décrivons une nouvelle méthode de type SILAC appliquée à des modèles in vivo de tumeurs humaines xénogreffées chez la souris immunodéprimée. L’application de cette méthode aux tumeurs colorectales a révélé des différences importantes dans la signalisation dépendante de Src in vivo et in vitro. Enfin, nous discutons l’intérêt du SILAC par rapport à d’autres méthodes de protéomique in vivo, ainsi que dans ses applications en cancérologie