[Factors influencing platelets labelling with indium-111 oxine]. / Facteurs influençant le marquage des plaquettes à l'oxinate d'indium-111.

Autologous indium-111 labelled platelets can be used for kinetic studies in patients with autoimmune thrombocytopenic purpura [AITP]. The objective of this study was to evaluate some biological and clinical factors influencing the labeling efficiency. METHODS: We studied incubation media (Plasma media [MP] or dry media [MS]), platelet concentration [NP], mean platelet volume [VPM], hemoglobin level and pathology associated with AITP. RESULTS: This was a retrospective study of 93 platelets labelling (43 in MS and 50 in MP), 38 primary AITP (41%) and 55 secondary AITP (59%). The labeling efficiency was 72% (78% in MS versus 53% in MP; p < 0.0001). The labeling efficiency was correlated with VPM (p = 0.0004), NP (p = 0.03), hemoglobin level (p = 0.037) and type of AITP (p = 0.0036). The incubation medium, hemoglobin level and type of the AITP have an independent predictive value on the labeling efficiency. CONCLUSION: These data confirm the influence of the incubation medium on the labeling efficiency and identify two other predictive criteria, hemoglobin level and type of AITP.

[Effect of obesity, age and gender on glomerular filtration rate measured in normal adults]. / Influence de l'obésité, de l'âge et du sexe sur le débit de filtration glomérulaire mesuré chez l'adulte normal.

The aims of this study were to assess the dependence of glomerular filtration rate (GFR) on age and gender and to produce reference data for the interpretation of 51Cr-EDTA GFR measurements in adults. METHODS: This was a retrospective study of 120 live kidney donors (75 females, 45 males). GFR was evaluated from 51Cr-EDTA plasma clearance using blood samples taken at 3, 4 and 5 hours. The slope-intercept GFR was corrected for body surface area using the Dubois & Dubois and for the fast exponential using the Brochner-Mortensen equation. Scatter plot of DFG against age in live kidney donors was plotted and the 98% range limits have been defined. RESULTS: The median GFR obtained for kidney donors was 88 mL/min/1.73 m2 [68-130]. No significant difference with gender was found. 51Cr-EDTA clearance was strongly correlated with patient age (r = - 0.62, P < 0,0001). GFR decreased by approximately 8 mL/min/1.73 m2 per decade. Based on these results, a nomogram for GFR is presented. CONCLUSION: The interpretation of GFR requires age-adjusted normal values. These standards need not be adjusted to the patient's sex or BMI.

[Effect of 99mTc elution in vivo from red cells on red cell volumes measured using autologous 99mTc-labeled red cells: comparison with 51Cr method]. / Effet de l'élution in vivo du technétium sur les volumes globulaires mesurés à l'aide d'hématies autologues marquées au 99mTc : comparaison avec la technique au 51Cr.

The purpose of this work was to compare the measured red-cell volume (RCV) using sodium pertechnétate [RCV-99mTc] compared to the reference technique using sodium radiochromate [RCV-51Cr] and to assess the influence of technetium-99 elution on the RCV-99mTc value. Ten patients had simultaneous measurements of RCV-99mTc and RCV-51Cr. Elution of Tc-99m from red blood cells was 2.9% and led to an average overestimation of RCV-99mTc of 3.7%. The introduction of individual tracer elution rates in the RCV-99mTc calculation corrects this overestimation.

Dendritic cell-tumor cell hybrids and immunotherapy: what's next?

Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, this approach has now been evaluated in clinical trials, although with limited success. We summarize and discuss the results from the animal studies and first clinical trials. We also present a new approach to inducing hybrid formation by expression of viral fusogenic membrane glycoproteins.

Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism.

Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-gamma-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-alpha, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.

The inhibition of TNF-alpha anti-tumoral properties by blocking antibodies promotes tumor growth in a rat model.

Tumor necrosis factor (TNF) antagonists represent a milestone in the therapy of autoimmune conditions. Anti-TNF antibodies have been approved for clinical use and during the last eight years thousands of patients have been treated. However, the long-term sequelae of anti-TNF agents in promoting carcinogenesis remain unclear. This study sought to define the role of intra-tumor TNF-alpha production on cancer cell progression and to determine whether TNF-alpha antibodies can suppress anti-tumoral immunity. Using an experimental animal tumor model we demonstrate that anti-TNF-alpha antibodies hinder anti-tumor immune responses and promote growth of immunogenic rat colon tumors (REG) that are always rejected by immunocompetent untreated rats. The major role of TNF-alpha in the anti-tumoral immune response was confirmed by transfecting progressive and tolerogenic rat colon tumor cells (PRO) with the TNF-alpha gene. PRO tumor cells secreting TNF-alpha induce tumor-infiltrating dendritic cell (DC) activation. This triggers a potent immune response leading to tumor rejection and long-lasting immunity. Therefore, the prominent role of TNF-alpha in anti-tumoral immune responses underscores the need for caution and close surveillance following the administration of TNF inhibitors.

Apoptotic, necrotic, or fused tumor cells: an equivalent source of antigen for dendritic cell loading.

The identification of the most efficient strategy for tumor antigen loading of dendritic cells (DCs) remains a challenge in cancer immunotherapy protocols. Autologous dead tumor cells have been demonstrated to constitute an acceptable source of multiple tumor-associated antigens (TAA) to pulse DCs. However the optimal approach for inducing cell death that would lead to effective endocytosis and activation of DCs remains controversial. In this study we have induced and defined 3 distinct mechanisms of tumor cell death (apoptosis, necrosis and fusion-mediated cell death), and investigated their differential effects on DCs. Bone marrow-derived DCs demonstrated comparable uptake of primary apoptotic, necrotic, or fused dead tumor cells. Furthermore, the distinct modes of cancer cell death had analogous potential in activating the transcription factors NF-kappaB and STAT1 and in maturing DCs, resulting in an equally effective stimulation of immune T cells. The current study therefore provides further informations on the use of dead whole tumor cells as antigen sources for effective active anti-cancer immunotherapy.