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Search Results: 1 - 10 of 4014 matches for " Jacques Barbet "
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Different ways to improve the clinical effectiveness of radioimmunotherapy in solid tumors
Chatal Jean-Francois,Davodeau Francois,Cherel Michel,Barbet Jacques
Journal of Cancer Research and Therapeutics , 2009,
Abstract: Radioimmunotherapy (RIT) has been proven effective in the treatment of radiosensitive non-Hodgkin lymphoma but, for radioresistant solid tumors, new approaches are necessary to improve the clinical effectiveness. A real improvement has been the introduction of the pretargeting technology which appeared to be able to significantly increase tumor-to-normal organ uptake ratios.Another very promising approach consists in associating RIT with other treatment modalities. Finally the use of alpha particle-emitting radionuclides such as astatin-211 or bismuth-213 (alpha-RIT) should allow to efficiently eradicate disseminated microscopic clusters of tumor cells or isolated tumor cells which fit well with the short path length of alpha particles.
Challenges in nuclear medicine: innovative theranostic tools for personalized medicine
Fran?oise Kraeber-Bodéré,Jacques Barbet
Frontiers in Medicine , 2014, DOI: 10.3389/fmed.2014.00016
Abstract: Over the past few years, nuclear medicine has undergone impressive growth with the development of positron emission tomography (PET), especially using 18F-fluoro-deoxy-glucose (18FDG), and new approaches in targeted radionuclide therapy. These developments pave the way for personalized medicine by offering practical solutions, especially in oncology, neurology and cardiology. Novel radiopharmaceuticals targeting relevant biomarkers are powerful patient selection tools for patients who may benefit from targeted therapies, and for early therapeutic response assessment. Moreover, once labeled with beta– or alpha emitters, radiopharmaceuticals targeting relevant molecular markers expressed by different solid tumors and hemopathies can be used for radionuclide therapy. The final objective here is to eradicate residual cancer disease by using cytotoxic mechanisms complementary to those of "non-radioactive” therapies. PET imaging and targeted radionuclide therapy then come together in the context of the theranostic approach to adapt injected activity for personalized therapy. 18FDG-PET demonstrates the high accuracy and the clinical benefits of non-invasive whole-body imaging. It is used in clinical practice for initial staging and therapy evaluation in several solid tumors and hemopathies. 18FDG-PET is also applied outside oncology to explore dementia, assess myocardial viability, or detect infectious and inflammatory processes. However, 18FDG is not a specific tracer. For example, in solid tumor or lymphoma assessment, 18FDG-PET does not distinguish tumors from inflammation, inducing false positive results, especially after therapies inducing inflammatory or immune reactions. New radiopharmaceuticals are needed to better characterize pathologic processes and to predict and assess response to therapy (Zhao et al., 2009). In oncology, the development of 18FDG-PET is ongoing, particularly for therapy response assessment. Image acquisition and analysis protocols are being further standardized to improve diagnostic accuracy (Wahl et al., 2009). For example, specific criteria have been elaborated to assess lymphoma or solid tumor response to therapy (Wahl et al., 2009; Juweid et al., 2007; Meignan et al., 2012). For tumors with low avidity for 18FDG, other 18F-labeled compounds are being proposed (e.g. 18F-choline in prostate cancer or hepatocellular carcinoma) (Apolo et al., 2008). In addition, phenotype-specific tracers are needed for theranostic applications: 68Ga-labelled somatostatin analogues improve image quality in neuroendocrine tumors in comparison to
Comparison of Gene Expression in Human Embryonic Stem Cells, hESC-Derived Mesenchymal Stem Cells and Human Mesenchymal Stem Cells
Romain Barbet,Isabelle Peiffer,Antoinette Hatzfeld,Pierre Charbord,Jacques A. Hatzfeld
Stem Cells International , 2011, DOI: 10.4061/2011/368192
Abstract: We present a strategy to identify developmental/differentiation and plasma membrane marker genes of the most primitive human Mesenchymal Stem Cells (hMSCs). Using sensitive and quantitative TaqMan Low Density Arrays (TLDA) methodology, we compared the expression of 381 genes in human Embryonic Stem Cells (hESCs), hESC-derived MSCs (hES-MSCs), and hMSCs. Analysis of differentiation genes indicated that hES-MSCs express the sarcomeric muscle lineage in addition to the classical mesenchymal lineages, suggesting they are more primitive than hMSCs. Transcript analysis of membrane antigens suggests that , , , , and CD34 may be good candidates for the detection and isolation of the most primitive hMSCs. The expression in hMSCs of cytokine genes, such as IL6, IL8, or FLT3LG, without expression of the corresponding receptor, suggests a role for these cytokines in the paracrine control of stem cell niches. Our database may be shared with other laboratories in order to explore the considerable clinical potential of hES-MSCs, which appear to represent an intermediate developmental stage between hESCs and hMSCs. 1. Introduction A major challenge in developmental biology is to decipher gene expression controlling stemness and differentiation networks. A more practical goal is to identify among these genes those encoding membrane antigens such as receptors, which could be used as markers to track or select stem cells from the earliest pluripotent cells to the latest adult progenitor cells. In this study, we analyzed gene expression in pluripotent human Embryonic Stem Cell lines (hESCs), in human multipotent bone marrow Mesenchymal Stem Cells (hMSCs), and in hESC-derived MSCs (hES-MSCs). It is well known that hMSCs constitute a heterogeneous population that may include a subset of more primitive cells [1–3]. Although many antibodies directed at cell membrane antigens have been used to select specific hMSC populations [4–6], there is no cogent evidence that some of these antibodies may select for a more primitive population with enlarged differentiation potential and robust self-renewal capacity. Even in the mouse, where such a primitive population has been recently characterized by the expression of the cytoskeletal protein nestin [7], separation according to membrane phenotype is not yet feasible. In a previous study [8], we observed that a 24?h pretreatment of Stro1+/GlycoA? or CD45?/GlycoA? hMSCs with a monoclonal antibody blocking the human type I interferon-alpha (IFNα) receptor, or with a polyclonal anti-IFNα antibody, resulted in a marked increase in the number
dAcquisition setting optimization and quantitative imaging for 124I studies with the Inveon microPET-CT system
Nadège Anizan, Thomas Carlier, Cecilia Hindorf, Jacques Barbet, Manuel Bardiès
EJNMMI Research , 2012, DOI: 10.1186/2191-219x-2-7
Abstract: The noise equivalent count rate [NECR], the scatter fraction [SF], and the gamma-prompt fraction [GF] were used to determine the best acquisition parameters for mouse- and rat-sized phantoms filled with 124I. An image-quality phantom as specified by the National Electrical Manufacturers Association NU 4-2008 protocol was acquired and reconstructed with two-dimensional filtered back projection, 2D ordered-subset expectation maximization [2DOSEM], and 3DOSEM with maximum a posteriori [3DOSEM/MAP] algorithms, with and without attenuation correction, scatter correction, and gamma-prompt correction (weighted uniform distribution subtraction).Optimal energy windows were established for the rat phantom (390 to 550 keV) and the mouse phantom (400 to 590 keV) by combining the NECR, SF, and GF results. The coincidence time window had no significant impact regarding the NECR curve variation. Activity concentration of 124I measured in the uniform region of an image-quality phantom was underestimated by 9.9% for the 3DOSEM/MAP algorithm with attenuation and scatter corrections, and by 23% with the gamma-prompt correction. Attenuation, scatter, and gamma-prompt corrections decreased the residual signal in the cold insert.The optimal energy windows were chosen with the NECR, SF, and GF evaluation. Nevertheless, an image quality and an activity quantification assessment were required to establish the most suitable reconstruction algorithm and corrections for 124I small animal imaging.Small animal imaging is an active area of research for the investigation of new pharmaceuticals and treatment regimens. In vivo imaging permits longitudinal studies to be performed [1]. Quantitative imaging also provides a basis for the calculation of the absorbed dose for radioimmunotherapy applications since it yields both the pharmacokinetics (SPECT or positron-emission tomography [PET]) and the anatomy and density of the tissues (computed tomography [CT]) [2]. Most PET studies are performed with 18
Improvement of Radioimmunotherapy Using Pretargeting
Eric Frampas,Caroline Bodet-Milin,Jacques Barbet,Jean-Francois Chatal
Frontiers in Oncology , 2013, DOI: 10.3389/fonc.2013.00159
Abstract: During the past two decades, considerable research has been devoted to radionuclide therapy using radiolabeled monoclonal antibodies and receptor binding agents. Conventional radioimmunotherapy (RIT) is now an established and important tool in the treatment of hematologic malignancies such as Non-Hodgkin lymphoma. For solid malignancies, the efficacy of RIT has not been as successful due to lower radiosensitivity, difficult penetration of the antibody into the tumor, and potential excessive radiation to normal tissues. Innovative approaches have been developed in order to enhance tumor absorbed dose while limiting toxicity to overcome the different limitations due to the tumor and host characteristics. Pretargeting techniques (pRIT) are a promising approach that consists of decoupling the delivery of a tumor monoclonal antibody (mAb) from the delivery of the radionuclide. This results in a much higher tumor-to-normal tissue ratio and is favorable for therapy as well and imaging. This includes various strategies based on avidin/streptavidin-biotin, DNA-complementary DNA, and bispecific antibody-hapten bindings. pRIT continuously evolves with the investigation of new molecular constructs and the development of radiochemistry. Pharmacokinetics improve dosimetry depending on the radionuclides used (alpha, beta, and Auger emitters) with prediction of tumor response and host toxicities. New constructs such as the Dock and Lock technology allow production of a variety of mABs directed against tumor-associated antigens. Survival benefit has already been shown in medullary thyroid carcinoma. Improvement in delivery of radioactivity to tumors with these pretargeting procedures associated with reduced hematologic toxicity will become the next generation of RIT. The following review addresses actual technical and clinical considerations and future development of pRIT.
Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery
Eliot. P. Botosoa,Mike Maillasson,Marie Mougin-Degraef,Patricia Remaud-Le Sa c,Jean-Fran ois Gestin,Yannick Jacques,Jacques Barbet,Alain Faivre-Chauvet
Journal of Drug Delivery , 2011, DOI: 10.1155/2011/368535
Abstract: Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex) and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR). Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy.
Evaluation of Protocol Biopsy Utility 12 Months after Renal Transplantation: A Multicenter Observational Analysis
Bruno Moulin,Pierre Merville,Karine Renaudin,David Buob,Sophie Ferlicot,Michel Delahousse,Jacques Dantal,Laetitia Albano,Christelle Barbet,Georges Mourad,Laure-Hélène Noel
Journal of Transplantation , 2012, DOI: 10.1155/2012/781263
Abstract: The clinical merit of surveillance kidney graft biopsies remains controversial. A retrospective, multicenter analysis evaluated 12-month surveillance biopsies (SB, 154 patients) versus no SB (NSB, 138 patients (11 with diagnostic biopsy)) in patients >18 months posttransplant with estimated GFR (eGFR) ≥30 mL/min. The primary objective was to describe renal function at 18 months post-transplant in patients with or without SB at month 12. Globally, most recipients in both cohorts were at low immunological risk (<10% of patients with PRA ≥30%). The immunosuppressive regimen remained unchanged following more than half of SB that exhibited chronic lesions (18/33, 54.5%). Mean (SD) eGFR at month 18 (primary endpoint) was 56 (19) mL/min/1.73 m² with SB and 54 (15) mL/min/1.73 m² with NSB (=0.48). In the SB group, slight nonspecific changes were observed in 51 cases, rejection (acute or chronic) in 6 cases, CNI-related toxicity in 15 cases, recurrence of initial disease in two cases, and interstitial fibrosis/tubular atrophy (IF/TA) in 83 cases (71.6%), of which 35 cases (30.2%) were grade II/III lesions. eGFR <50 mL/min/1.73 m² at month 6 predicted IF/TA grade II or III (OR 3.85, 95% CI 1.64, 9.05, <0.002). SB at 12 months posttransplant did not prompt significant modification of immunosuppression, and no renal benefit was observed.
Persistence mechanisms in tick-borne diseases : tick-borne diseases
A.F. Barbet
Onderstepoort Journal of Veterinary Research , 2010, DOI: 10.4102/ojvr.v76i1.65
Abstract: The use of new, highly sensitive diagnostic methods has revealed persistent infections to be a common feature of different tick-borne diseases, such as babesiosis, anaplasmosis and heartwater. Antigenic variation can contribute to disease persistence through the continual elaboration of new surface structures, and we know in several instances how this is achieved. Known or suspected mechanisms of persistence in babesial parasites include cytoadhesion and rapid variation of the adhesive ligand in Babesia bovis and genetic diversity in several merozoite stage proteins of different Babesia spp. In Anaplasma, extensive variation in the pfam01617 gene family accompanies cycling of organism levels in chronic infection. One result from the pioneering research at Onderstepoort is the definition of a related polymorphic gene family that is likely involved in immunity against heartwater disease. We are beginning to understand the sizes of the antigenic repertoires and full definition is close, with the possibility of applying simultaneous high-throughput sequencing to the order of 1 000 small genomes. We also, for the first time, can consider modifying these genomes and looking at effects on persistence and virulence. However, important biological questions remain unanswered; for example, why we are seeing a new emerging Anaplasma infection of humans and is infection of endothelial cells by Anaplasma significant to persistence in vivo.
A Monoclonal Antibody to O-Acetyl-GD2 Ganglioside and Not to GD2 Shows Potent Anti-Tumor Activity without Peripheral Nervous System Cross-Reactivity
Nidia Alvarez-Rueda, Ariane Desselle, Denis Cochonneau, Tanguy Chaumette, Béatrice Clemenceau, Stéphanie Leprieur, Gwenola Bougras, Stéphane Supiot, Jean-Marie Mussini, Jacques Barbet, Julie Saba, Fran?ois Paris, Jacques Aubry, Stéphane Birklé
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025220
Abstract: Background Monoclonal antibodies (mAb) against GD2 ganglioside have been shown to be effective for the treatment of neuroblastoma. Beneficial actions are, however, associated with generalized pain due to the binding of anti- GD2 mAbs to peripheral nerve fibers followed by complement activation. Neuroblastoma cells that express GD2 also express its O-acetyl derivative, O-acetyl- GD2 ganglioside (OAcGD2). Hence, we investigated the distribution of OAcGD2 in human tissues using mAb 8B6 to study the cross-reactivity of mAb 8B6 with human tissues. Methodology/Principal Findings The distribution of OAcGD2 was performed in normal and malignant tissues using an immunoperoxydase technique. Anti-tumor properties of mAb 8B6 were studied in vitro and in vivo in a transplanted tumor model in mice. We found that OAcGD2 is not expressed by peripheral nerve fibers. Furthermore, we demonstrated that mAb 8B6 was very effective in the in vitro and in vivo suppression of the growth of tumor cells. Importantly, mAb 8B6 anti-tumor efficacy was comparable to that of mAb 14G2a specific to GD2. Conclusion/Significance Development of therapeutic antibodies specific to OAcGD2 may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of antibodies.
Syndecan-1 antigen, a promising new target for triple-negative breast cancer immuno-PET and radioimmunotherapy. A preclinical study on MDA-MB-468 xenograft tumors
Caroline Rousseau, Anne Ruellan, Karine Bernardeau, Fran?oise Kraeber-Bodéré, Sebastien Gouard, Delphine Loussouarn, Catherine Sa?-Maurel, Alain Faivre-Chauvet, John Wijdenes, Jacques Barbet, Jo?lle Gaschet, Michel Chérel, Fran?ois Davodeau
EJNMMI Research , 2011, DOI: 10.1186/2191-219x-1-20
Abstract: The immunoreactivity of 125I-B-B4 (80%) was determined, and the affinity of 125I-B-B4 and the expression of CD138 on MDA-MB-468 was measured in vitro by Scatchard analysis. CD138 expression on established tumors was confirmed by immunohistochemistry. A biodistribution study was performed in mice with subcutaneous MDA-MB-468 and 125I-B-B4 at 4, 24, 48, 72, and 96 h after injection and compared with an isotype-matched control. Tumor uptake of B-B4 was evaluated in vivo by immuno-PET imaging using the 124I-B-B4 mAb. The maximum tolerated dose (MTD) was determined from mice treated with 131I-B-B4 and the RIT efficacy evaluated.125I-B-B4 affinity was in the nanomolar range (Kd = 4.39 ± 1.10 nM). CD138 expression on MDA-MB-468 cells was quite low (Bmax = 1.19 × 104 ± 9.27 × 102 epitopes/cell) but all expressed CD138 in vivo as determined by immunohistochemistry. The tumor uptake of 125I-B-B4 peaked at 14% injected dose (ID) per gram at 24 h and was higher than that of the isotype-matched control mAb (5% ID per gram at 24 h). Immuno-PET performed with 124I-B-B4 on tumor-bearing mice confirmed the specificity of B-B4 uptake and its retention within the tumor. The MTD was reached at 22.2 MBq. All mice treated with RIT (n = 8) as a single treatment at the MTD experienced a partial (n = 3) or complete (n = 5) response, with three of them remaining tumor-free 95 days after treatment.These results demonstrate that RIT with 131I-B-B4 could be considered for the treatment of metastatic triple-negative breast cancer that cannot benefit from hormone therapy or anti-Her2/neu immunotherapy. Immuno-PET for visualizing CD138-expressing tumors with 124I-B-B4 reinforces the interest of this mAb for diagnosis and quantitative imaging.The expression of syndecan-1 in breast cancer is described as a poor prognostic factor. However, the potential of targeting this antigen for immuno-PET or radioimmunotherapy has not yet been investigated. Syndecans represent a four-member family of transmembra
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