Potentiation of neuroblastoma metastasis by loss of caspase-8

Neuroblastoma, the most common paediatric solid tumour, arises from defective neural crest cells. Genetic alterations occur frequently in the most aggressive neuroblastomas. In particular, deletion or suppression of the proapoptotic enzyme caspase-8 is common in malignant, disseminated disease, although the effect of this loss on disease progression is unclear. Here we show that suppression of caspase-8 expression occurs during the establishment of neuroblastoma metastases in vivo, and that reconstitution of caspase-8 expression in deficient neuroblastoma cells suppressed their metastases. Caspase-8 status was not a predictor of primary tumour growth; rather, caspase-8 selectively potentiated apoptosis in neuroblastoma cells invading the collagenous stroma at the tumour margin. Apoptosis was initiated by unligated integrins by means of a process known as integrin-mediated death. Loss of caspase-8 or integrin rendered these cells refractory to integrin-mediated death, allowed cellular survival in the stromal microenvironment, and promoted metastases. These findings define caspase-8 as a metastasis suppressor gene that, together with integrins, regulates the survival and invasive capacity of neuroblastoma cells.     

The mitotic chromosomes of the lampreyMordacia mordax (agnatha: Petromyzonidae)

Résumé L'étude des chromosomes somatiques de la lamproie de l'hémisphère sud,Mordacia mordax (Richardson), montre que l'équipement chromosomique diploïde de cette espèce est composé de 76 chromosomes très petits. La plupart des chromosomes sont métacentrique ou bien submétacentrique. Ces chromosomes sont différents en nombre de ceux décrits pour les lamproies de l'hémisphère nord.     

Hormone binding globulins undergo serpin conformational change in inflammation

A surprising recent finding is that thyroxine binding globulin (TBG) and cortisol binding globulin (CBG), are members of the serine protease inhibitor (serpin) superfamily. Apparently evolution has completely adapted the serpin structure for its new role in these proteins as a transport agent, as there is no evidence of any retained protease inhibitory activity. This drastic change in function raises the question as to why such a complex molecular framework has been selected for the relatively simple task of hormone transport? To function as inhibitors the serpins have a native stressed (S) conformation that makes them vulnerable to proteolytic cleavage, the cleavage being accompanied by an irreversible transition to a stable relaxed (R) form. We demonstrate here that TBG and CBG have retained the stressed native structure typical of the inhibitor members of the family and we provide evidence that the S-R transition has been adapted to allow altered hormone delivery at inflammatory sites.     

Comparative effects of sulfhydryl inhibitors on melanosome movements within vertebrate melanophores

Résumé Dans les mélanophores des grenouilles et des lézards examinés in vitro, les inhibiteurs du groupe sulfhydryl (thiol) tels que le mérsalyle et les maléimides N-substitutés bloquent irrévocablement la dispersion des mélanosomes soumis à l'action de la MSH et provoquent même leur retrait. On étudie les conditions structurales de l'action inhibitrice d'un certain nombre de maléimides N-substitués, étroitement apparentés.     

Rabbit and human insulins: Similar cross-reactivities with antibodies to porcine insulin

Résumé L'insuline du lapin diffère de l'insuline de l'homme et du porc par l'acide aminé C-terminal de la B-chaîne. Les expériences démontrent que les insulines humaine et cuniculine réagissent de la même manière envers l'anticorps du cobaye et l'insuline du porc. Par conséquent, l'acide aminé en quéstion ne paraît pas être déterminant pour la production des anticorps contre les insulines de l'homme et du lapin.     

Evaluation of the maternal role in survival of suckling mice

Zusammenfassung Das Überleben der von der eigenen Mutter und von stammesfremden «Ammen» gesäugten Jungen wurde untersucht an Mäusen der Stämme AKR/Sp, PL/Sp und C57BL/Sp. Die Ergebnisse zeigen, dass die genetische Herkunft der Säuglinge wie auch andere, nicht genetisch bedingte Einflüsse der Mutter auf die Jungen in utero für das Überleben der Jungen ausschlaggebend ist.

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This investigation was supported in part by Public Health Service Research Grants Nos. CA 02151, CA 02903 and CA 02624 from the National Cancer Institute, and in part by an institutional grant to the Detroit Institute of Cancer Research from the United Foundation of Greater Detroit allocated through the Michigan Cancer Foundation.