Epithelial mesenchymal transitions are a remarkable example of cellular plasticity. These transitions are the hallmark of embryo development, are pivotal in cancer progression, and seem to occur infrequently in adult organisms. The reduced incidence of transitions in the adult could result from restrictive functions of the microenvironment that stabilizes adult cell phenotypes and prevents plastic behavior. Multipotential progenitor cells exhibiting a mesenchymal phenotype have been derived from various adult tissues. The ability of these cells to differentiate into all germ layer cell types, raises the question as to whether mesenchymal epithelial transitions occur in the adult organism more frequently than presently appreciated. A series of cytokines are known to promote the transitions between epithelium and mesenchyme. Moreover, several transcription factors and other intracellular regulator molecules have been conclusively shown to mediate these transitions. However, the exact molecular basis of these transitions is yet to be resolved. The identification of the restrictive mechanisms that prevent cellular transitions in adult organisms, which seem to be unleashed in cancerous tissues, may lead to the development of tools for therapeutic tissue repair and effective tumor

L-asparaginase is an effective antileukaemic drug and a potent inhibitor of hepatic protein synthesis. Its effect on lipid metabolism was studied in two cohorts of children with ALL, one of whom received L-asparaginase concomitantly with three other drugs (protocol BFM 79). In the second protocol (BFM 83) administration of L-asparaginase was arranged to follow the other three drugs in time sequence. The two major findings of this study were elevated serum levels of total cholesterol and a strong increase in serum triglycerides. The former change was due to an increase in alpha-cholesterol and could not be attributed to L-asparaginase because it was also found following protocol BFM 83 before the administration of the drug. Elevations of total triglycerides were due to high levels of exogenous chylomicron bound triglycerides and were limited in occurrence almost exclusively to the period of L-asparaginase monotherapy. Hypothyroidism was excluded as a possible pathogenetic mechanism. These changes in lipid metabolism induced by L-asparaginase during intensive remission induction chemotherapy are fully reversible.

Colony forming units (CFUc) giving rise to myelocytic colonies in methylcellulose cultures were found among non-adherent mononuclear cells of human cord blood with a frequency of one in 1678. The number decreased makredly during the first 8 to 10 days of life. They were rarely detected in adult blood by this technique.

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99 children with non-Hodgkin's lymphoma entered the prospective, multicenter BFM study 81/83. They were treated with a four-fold stratified therapy according to clinical stage and origin of the lymphoma from B- or non-B-lymphocytes. In the BFM study 75/81, these criteria had been proven to be most relevant for prognosis. Therapy of non-B-NHL was very similar to the therapeutic concept as applied in acute lymphoblastic leukemias by the BFM group. For the NHL of B-type, a new therapeutic regimen was developed. Cytostatic drugs applied in this group were: medium dose methotrexate, cyclophosphamide in a fractionated manner of application, adriamycin, cytarabine, VM 26 and prednisone. The probability of disease-free survival was 80% after nearly 3 years for all patients. In non-B-NHL it was 89% in localized, and 79% in disseminated disease. All patients with localized B-NHL are surviving without relapse, while the probability of disease-free survival in patients with disseminated B-NHL was 67%. Thus, the therapy result in the latter group was doubled as compared to the result of the BFM study 75/81.