Halle, Universiẗat, Diss., 2000.

Note:

Bcl10 is one of the apoptosis regulatory protein. It is located at 1p22,one site harbor tumor suppressor tumor gene. We screen Bcl10 expression in different tumor cell lines by reverse transcription-polymerase chain reaction(RT-PCR), western blot(WB) and immunohistochemistry(IHC). The results showed Bcl10 genomic expression was found in U87, Astrocytoma and no expression in glioma , glioblastoma. There were cell lines with expressions in Bcl10 protein and NF-£eB including hepatocellular carcinoma, glioblastoma, and breast cancer, but increased in lung cancer cell line. In immunohistochemistry,we found the Bcl10 protein has positive finding in glioma U373, U251; oral cancer CA922, SAS, clinical patient VGH283; Lung cancer PC14, PC13; Hepatoma Huh7; Colon cancer SW 480; Cervical cancer HeLa. The Bcl10 gene, unlike other tumor suppressor genes such as p53, may be selectively targeted by different human tumors. In our study, Bcl10 play a role in brain tumor, oral cancer and some tumor cell line had not been reported before.

Wilms Tumour (WT) is one of the commonest tumours in children. Hepatic Sinusoidal Obstruction Syndrome (HSOS) is a documented complication following treatment of WT. The role of malnutrition in the development of HSOS has not been studied. Malnutrition reduces tolerance to chemotherapy and shows increased risk for toxicity. Purpose of study To determine the prevalence of HSOS in children with WT, as well as its predisposing factors and outcomes. Method A descriptive retrospective analysis of medical records of children treated for WT, who developed HSOS, at the Paediatric Haematology/Oncology Unit, Chris Hani Baragwanath Hospital. Results 82 patients were evaluated. 19 (23%) showed features compatible with HSOS. Younger age, irradiation and a right-sided WT predicted the development of HSOS but were not statistically significant. Serum albumin levels were lower in the affected group (P = 0.02). Apart from 2 deaths, outcomes were good, with patients showing full resolution of symptoms. Conclusion A higher prevalence of HSOS was shown than previously reported. Low serum albumin levels points to the role of malnutrition. Effort needs to be put into the various methods of identifying malnutrition. Long term follow-up is needed.

aranza801@hotmail.com / Cartas al editor / Revisión por pares

Malgré les progrès dans les traitements contre le cancer, cette maladie demeure difficile à contrôler au stade métastatique. La migration des cellules tumorales est une étape majeure du processus métastatique qui implique la réorganisation du cytosquelette. Dans ce contexte, notre équipe a caractérisé une voie de signalisation par laquelle le récepteur oncogénique ErbB2 régule la migration cellulaire via le contrôle de la dynamique des microtubules (MT). La protéine EB1, qui s’associe aux extrémités + des MT, est un acteur majeur du réseau de protéines favorisant la capture des microtubules. Dans l’objectif de mieux définir les mécanismes qui régulent la capture des MT, nous avons caractérisé l’interactome d’EB1. J’ai ainsi identifié iASPP, un inhibiteur du suppresseur de tumeur p53, comme un nouveau partenaire d’EB1. Mes résultats montrent qu’iASPP participe à la capture des MT au cortex cellulaire lors de la migration. De manière intéressante, la déplétion de iASPP a aussi des conséquences sur la mitose, induisant un défaut du positionnement du fuseau, dû à un ancrage asymétrique des microtubules astraux au cortex. Ces fonctions de iASPP dépendent de son interaction spécifique avec EB1 via un motif SxIP, mais sont indépendantes de son association à p53. iASPP interagit aussi avec des protéines associées au cortex cellulaire dont la Myosine 1c, qui participe également au bon positionnement du fuseau mitotique. Nous proposons que le complexe EB1-iASPP-Myo1c contribue à la capture des MT lors de la division et de la migration des cellules tumorales et pourrait constituer à terme une cible thérapeutique. / Despite significant progress in the treatments of cancer, this disease is still difficult to manage at the metastatic grade. Tumor cell migration is a major step in the metastatic process which involves cytoskeleton reorganization. In this context, our group has characterized a signal transduction pathway driven by the oncogenic receptor ErbB2 which controls microtubule dynamics and cell migration. EB1, a protein associating with the +end of MT, is a key actor of proteins network promoting MT capture. In order to characterize mechanisms that regulate MT dynamics, we have defined EB1 interactome. I identified iASPP, an inhibitor of the p53 tumor suppressor as a partner of EB1. My results show that iASPP contributes to MT capture at the cell cortex during cell migration. Interestingly, iASPP depletion has consequences on mitosis, inducing a defect in mitotic spindle positioning most likely due to asymmetric astral MT anchoring at the cell cortex. iASPP functions are dependent on its specific interaction with EB1 via a « SxIP » motif, but are independent of its interaction with p53. iASPP interacts also with proteins associated to the cell cortex of which Myosin 1C participates, as well, to the correct positioning of the mitotic spindle. We propose that EB1-iASPP-Myo1c complex contribute to MT capture during division and migration of tumoral cells and could represent a therapeutic target.

No description available.

Thesis (doctoral)--München, 1983. / Box 5698.

Thesis (doctoral)--Köln, 1986.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1983. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 129-140).