Presence of iron catalytic for free radical reactions in patients undergoing chemotherapy: implications for therapeutic management.

We investigated the kinetics of generation of iron 'catalytic' for free radical reactions in children with diagnosed acute lymphoblastic leukaemia (ALL) who received high-dose methotrexate infusions. In 76% of the chemotherapy courses studied, 'catalytic' iron appeared in plasma in the concentration range from 0.1 to 3 mumol/l.

Autologous transplantation with peripheral blood stem cells in children and young adults after myeloablative treatment: nonrandomized comparison between GM-CSF and G-CSF for mobilization.

Recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF) was compared with recombinant granulocyte colony-stimulating factor (rhG-CSF) in 34 patients for mobilization of peripheral blood stem cells (PBSC) and for posttransplantation use. Peripheral blood stem cell mobilization was initiated by a single 1 h infusion of cyclophosphamide (4 g/m2) in all patients, followed by either a continuous infusion of rhGM-CSF (250 micrograms/m2/day) in 17 patients (group A) or a daily subcutaneous injection of rhG-CSF (10 micrograms/kg/day) in 17 patients (group B). PBSC were collected using a Fenwal CS 3000 continuous flow blood cell separator in one to three sessions.

Comparative analysis of the immunophenotypes of decidual and peripheral blood large granular lymphocytes and T cells during early human pregnancy.

Problem: The functional role of the leukocytes in the decidual is not clear. They may regulate the maternal immune response to the fetal allograft. However, the factors controlling maternal and fetal communication have not yet been identified.

Evidence for a lymphotropic nature of circulating plasmacytoid monocytes: findings from a case of CD56+ chronic myelomonocytic leukemia.

Because the cells previously designated plasmacytoid T cells share major immunophenotypic features with cells of the mononuclear-phagocyte system, they have been re-named and are now known as plasmacytoid monocytes (PM). We describe a unique case of chronic myelomonocytic leukemia with circulating PM. The patient, a 48-year-old man, presented initially with refractory anemia.

Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma.

Amplification of the MYCN gene is a well documented genetic alteration of aggressively growing human neuroblastomas. Through cytogenetic studies we have identified neuroblastoma cell lines which, in addition to amplified MYCN, carry amplified DNA not harbouring MYCN. In situ hybridization of biotinylated total genomic DNA to metaphase chromosomes of normal human lymphocytes by reverse genomic hybridization revealed the amplified DNA to be derived from chromosome 12 band q13-14.

Expression of mdr1, mrp, topoisomerase II alpha/beta, and cyclin A in primary or relapsed states of acute lymphoblastic leukaemias.

In a series of 60 ALL samples drawn during different stages of the disease we used a cDNA-PCR approach to analyse the relative mRNA levels of the MDR-associated genes encoding mdr1/P-glycoprotein, mrp, and the topoisomerase II isozymes alpha and beta. Expression analysis of the cyclin A gene was included to examine cellular proliferation activity. The expression of gapdh served as an internal standard.

[Functional significance of CD56 large granular lymphocytes in the decidua in early pregnancy in the human].

Objective: The study was undertaken to characterize the large granular lymphocytes (LGL) found in large numbers in the decidua of early pregnancy, in order to investigate their functional significance in placentation.

Methods: The LGL were investigated by immunohistochemical, flow cytometric and molecular biological techniques.

Results And Conclusions: The LGL resemble a small subpopulation of Natural Killer cells (NK-cells) in the peripheral blood, express activation antigens and produce cytokines that may have a regulatory/modulatory influence on trophoblast growth.

A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma.

9 patients with stage IV neuroblastoma were treated with 19 courses of human/mouse chimeric monoclonal antiganglioside GD2 antibody ch14.18 at dose levels of 30, 40 and 50 mg/m2/day for 5 days per course. The maximum tolerated dose (MTD) per injection was 50 mg/m2/day.

Clinical strategies for the treatment of neuroblastoma.

Neuroblastoma is the most common solid extracranial tumour in childhood. In spite of intensive efforts of clinicians and scientists the prognosis for advanced disease is still poor. This paper presents a short review of the state-of-the-art in conventional treatment including surgery, chemotherapy, and radiation.

Cytogenetic evolution of MYCN and MDM2 amplification in the neuroblastoma LS tumour and its cell line.

Amplification of the MYCN gene is frequently seen either in extrachromosomal double minutes (DMs) or in homogeneously staining regions (HSRs) of aggressively growing neuroblastomas. Total genomic DNA from cell line LS, from early passages of the same line and from original tumour material was biotinylated and hybridised to metaphase chromosomes of normal human lymphocytes. The reverse genomic hybridisation revealed the amplified DNA to be derived both from chromosome 2p23-24, which is the position of MYCN, and from chromosome 12 band q13-14.

[Autologous bone marrow transplantation].

Autologous bone marrow transplantation (ABMT) is a treatment modality increasingly used to treat a growing number of malignancies both in children and in adults. The theoretical rationale is the transfer of dose-action relationship from pharmacological theory to clinical practice. The basic principles, the important indications and the problems of this particular approach are discussed.

[Technical aspects of autologous bone marrow transplantation].

Autologous bone marrow transplantation has become an established procedure in the treatment of malignancies. Especially in patients with hematological malignant diseases, who have no compatible allogeneic bone marrow donor or in patients with solid tumors, in whom the threshold of irreversible bone marrow toxicity is reached by the intensified chemotherapy, this procedure allows the use of a myeloablative therapy. As stem cell sources, bone marrow (BM), peripheral blood-derived stem cells (PBSC), and umbilical cord blood can be used.

Distribution of cell adhesion molecules in decidua of early human pregnancy. An immunohistochemical study.

Background: The aim of the study was to investigate human decidua for cell adhesion molecules involved in interactions between the various different maternal and fetal cell populations, homing of the unusual intradecidual population of CD56+ lymphocytes, and organization of the decidual extracellular matrix.

Experimental Design: First trimester human decidua from normal pregnancies was investigated immunohistochemically with antibodies against integrin subunits (alpha 1-6, alpha L, alpha M, alpha X, alpha IIb, alpha V, beta 1, beta 3, and beta 4), platelet-endothelial cell adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and L-selectin.

Results: Endometrial glands stained for alpha 1, alpha 2, alpha 3, alpha 5, alpha 6, alpha V, beta 1, beta 3, and beta 4, and stromal cells for alpha 1, alpha 3, alpha 5, alpha 6, alpha V, beta 1, beta 3, ICAM-1, and VCAM-1.

Chemotactic activity of substances derived from antibody-loaded tumor cells on granulocytes.

Chemotactic activity of granulocytes attracted by tumor cells loaded either with anti-ganglioside monoclonal antibodies (mAb) or with antibody-glucose oxidase conjugates (mAb-GO) was investigated. The melanoma cell line SK-Mel-28 which expresses the ganglioside GD3 at high density as well as the neuroectodermal cell line SK-N-LO which expresses GD2 were used for the experiments. In the presence of 50% human AB-serum, antibody-loaded tumor cells induced chemotactic activity on granulocytes, probably due to the generation of C3a/C5a which could be detected in serum incubated with anti-GD3 loaded SK-Mel-28 cells.

Activation of cellular cytotoxicity and complement-mediated lysis of melanoma and neuroblastoma cells in vitro by murine antiganglioside antibodies MB 3.6 and 14.G2a.

Mouse monoclonal antibodies against tumour-associated gangliosides GD2 (14.G2a) and GD3 (MB 3.6) were tested to mediate antibody-dependent cellular cytotoxicity (ADCC) with various effector cells or complement-dependent cytolysis (CDC).

Differential responses of fetal, neonatal, and adult myelopoietic progenitors to interferon and tumor necrosis factor.

Human fetal liver (FL) and neonatal cord blood (CB) granulocyte-monocyte colony-forming progenitor cells (GM-CFC) are unique in their physiological environment and in certain proliferative and differentiative capacities. Tumor necrosis factor (TNF) and interferon (IFN) may inhibit or stimulate the growth of human bone marrow GM-CFC in vitro. The effects of recombinant human (rh) TNF-alpha, rhIFN-alpha, and rhIFN-tau on recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)-stimulated clonogenic cultures of day 7 GM-CFC from FL and umbilical CB were compared with rhGM-CSF-stimulated GM-CFC from normal human bone marrow (BM).

Drug-induced changes in the expression of MDR-associated genes: investigations on cultured cell lines and chemotherapeutically treated leukemias.

The induced expression of multiple drug resistance (MDR)-associated genes as a direct response of tumor cells to antineoplastic drugs could be an important factor influencing the success of cancer chemotherapy. We investigated the effects of such compounds on mdr1/P-glycoprotein (P-gp) gene expression and drug sensitivities in the T-lymphoblastoid human cell line CCRF-CEM and MDR sublines. Thereby, we observed that actinomycin D or adriamycin administered at sublethal concentrations induced increases of mdr1 mRNA levels and resistance within 72 h.

Rapid method for purification of CD56+ natural killer cells with preferential enrichment of the CD56bright+ subset.

A rapid method for the purification of CD56+ natural killer (NK) cells with the preferential enrichment of the CD56bright+ subset is described. The method is based on the adsorption of CD56+ cells indirectly stained with a biotinylated antibody on an avidin-coated column. The adsorbed CD56+ cells can then be squeezed out mechanically without damaging the viability or the function of the cells.

Distribution of cell adhesion molecules on CD56++, CD3-, CD16- large granular lymphocytes and endothelial cells in first-trimester human decidua.

Human decidua exhibits a unique infiltrate of large granular lymphocytes (LGL) with a natural killer (NK) cell phenotype (CD56++, CD16-, CD3-). The mechanisms underlying the binding of circulating LGL to vascular endothelium in the decidua and their migration into the decidual stroma were investigated immunohistochemically in first-trimester decidua with antibodies against endothelial adhesion molecules and their counter-receptors on leukocytes. Decidual and peripheral blood LGL were also investigated by flow cytometry.