Publications by authors named "Alice Aarnink"

15 Publications

  • Page 1 of 1

[Biobanking in a histocompatibility laboratory. Guidelines from the Francophone Society of Histocompatibility and Immunogenetics (SFHI)].

Ann Biol Clin (Paris) 2021 Aug;79(4):371-378

Department of Histocompatibility, Amiens University Medical Center, Amiens, France, Société francophone d'histocompatibililité et d'immunogénétique (SFHI), France.

Histocompatibility laboratories perform the biological analyses linked related to organ transplant, hematopoietic stem cells transplant, some immune dysfunction diseases and immuno-allergy after therapeutic treatment. Most of these analyses are prospectively or retrospectively performed on sera and DNA. The Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI) has made some recommendations in order to define storage conditions and storage lifetime of the samples required in a histocompatibility laboratory. These recommendations have been drawn up by a working group of ten biologists. They have been established on literature review and data from method validation, which has been already performed within French laboratories (collected through a national questionnaire sent to participant laboratories). The recommendations made by the SFHI for the storage of samples for immunogenetics analyses facilitate the harmonization of practices among histocompatibility laboratories.
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http://dx.doi.org/10.1684/abc.2021.1661DOI Listing
August 2021

Prognostic value for long-term graft survival of estimated glomerular filtration rate and proteinuria quantified at 3 months after kidney transplantation.

Clin Kidney J 2020 Oct 26;13(5):791-802. Epub 2020 Apr 26.

Department of Nephrology and Kidney Transplantation, Nancy University Hospital, Vandoeuvre-lès-Nancy, France.

Background: The estimated glomerular filtration rate (eGFR) measured at 1 year is the usual benchmark applied in kidney transplantation (KT). However, acting on earlier eGFR values could help in managing KT during the first post-operative year. We aimed to assess the prognostic value for long-term graft survival of the early (3 months) quantification of eGFR and proteinuria following KT.

Methods: The 3-, 6- and 12-month eGFR using the Modified Diet in Renal Disease equation (eGFR) was determined and proteinuria was measured in 754 patients who underwent their first KT between 2000 and 2010 (with a mean follow-up of 8.3 years) in our centre. Adjusted associations with graft survival were estimated using a multivariable Cox model. The predictive accuracy was estimated using the C-index and net reclassification index. These same analyses were measured in a multicentre validation cohort of 1936 patients.

Results: Both 3-month eGFR and proteinuria were independent predictors of return to dialysis (all P < 0.05) and there was a strong correlation between eGFR at 3 and 12 months (Spearman's ρ = 0.76). The predictive accuracy of the 3-month eGFR was within a similar range and did not differ significantly from the 12-month eGFR in either the derivation cohort [C-index 62.6 (range 57.2-68.1) versus 66.0 (range 60.1-71.9), P = 0.41] or the validation cohort [C-index 69.3 (range 66.4-72.1) versus 71.7 (range 68.7-74.6), P = 0.25].

Conclusion: The 3-month eGFR was a valuable predictor of the long-term return to dialysis whose predictive accuracy was not significantly less than that of the 12-month eGFR in multicentre cohorts totalling >2500 patients. Three-month outcomes may be useful in randomized controlled trials targeting early therapeutic interventions.
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http://dx.doi.org/10.1093/ckj/sfaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577768PMC
October 2020

Cynomolgus macaque IL37 polymorphism and control of SIV infection.

Sci Rep 2019 05 28;9(1):7981. Epub 2019 May 28.

Laboratoire d'immunogénétique moléculaire (LIMT, EA 3034, Faculté de médecine Purpan, Université Toulouse 3, Paul Sabatier, UPS), Toulouse, France.

The association between gene polymorphisms and plasma virus load at the set point (SP-PVL) was investigated in Mauritian macaques inoculated with SIV. Among 44 macaques inoculated with 50 AID50, six individuals were selected: three with SP-PVL among the highest and three with SP-PVL among the lowest. The exons of 390 candidate genes of these six animals were sequenced. Twelve non-synonymous single nucleotide polymorphisms (NS-SNPs) lying in nine genes potentially associated with PVL were genotyped in 23 animals. Three NS-SNPs with probabilities of association with PVL less than 0.05 were genotyped in a total of 44 animals. One NS-SNP lying in exon 1 of the IL37 gene displayed a significant association (p = 3.33 × 10) and a strong odds ratio (19.52). Multiple linear regression modeling revealed three significant predictors of SP-PVL, including the IL37 exon 1 NS-SNP (p = 0.0004) and the MHC Class IB haplotypes M2 (p = 0.0007) and M6 (p = 0.0013). These three factors in conjunction explained 48% of the PVL variance (p = 4.8 × 10). The potential role of IL37 in the control of SIV infection is discussed.
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http://dx.doi.org/10.1038/s41598-019-44235-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538695PMC
May 2019

Which is the best predictor of de novo donor-specific antibodies in a cohort of non-sensitized first kidney transplantation: Antigenic, allelic, epitope, or physiochemical HLA mismatches?

Clin Transplant 2019 04 22;33(4):e13508. Epub 2019 Mar 22.

Laboratoire d'Histocompatibilité, CHRU Nancy Brabois, Vandœuvre-lès-Nancy, France.

Background: Assessment of human leukocyte antigen (HLA) matching by using high-resolution allele typing and knowledge of HLA molecule structure may lead to better prediction of de novo donor-specific antibody (dnDSA) development.

Methods: We conducted a single-center cohort study among 150 non-sensitized first kidney transplant recipients to compare the association between antigenic (Ag), allelic (Al), eplet (Ep), amino acid (AAMS) HLA matching and electrostatic (EMS) and hydrophobic (HMS) mismatch scores, and the development of dnDSA.

Results: After a mean follow-up time of 49.3 ± 17.7 months, 18 patients (12%) developed dnDSA. The number of HLA mismatches (MM) was significantly associated with the development of dnDSA. The optimal threshold, determined by Harrell's C-index, varied according to the method (5 MM for Ag, P = 0.006; 6 for Al, P = 0.009; 22 for Ep, P = 0.005; 42 for AAMS, P = 0.0007; 45 for EMS, P = 0.009 and 44 for HMS, P = 0.026). C-indices were similar for all matching approaches, suggesting a similar prediction of dnDSA development.

Conclusion: In this cohort of low immunological risk transplant patients, the use of Al or Ep matching did not improve the prediction of dnDSA development in comparison with the traditional approach.
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http://dx.doi.org/10.1111/ctr.13508DOI Listing
April 2019

Whole genome sequencing in the search for genes associated with the control of SIV infection in the Mauritian macaque model.

Sci Rep 2018 05 8;8(1):7131. Epub 2018 May 8.

Laboratoire d'immunogénétique moléculaire (LIMT, EA 3034, Faculté de médecine Purpan, Université Toulouse 3 (Université Paul Sabatier, UPS), Toulouse, France.

In the Mauritian macaque experimentally inoculated with SIV, gene polymorphisms potentially associated with the plasma virus load at a set point, approximately 100 days post inoculation, were investigated. Among the 42 animals inoculated with 50 AID of the same strain of SIV, none of which received any preventive or curative treatment, nine individuals were selected: three with a plasma virus load (PVL) among the lowest, three with intermediate PVL values and three among the highest PVL values. The complete genomes of these nine animals were then analyzed. Initially, attention was focused on variants with a potential functional impact on protein encoding genes (non-synonymous SNPs (NS-SNPs) and splicing variants). Thus, 424 NS-SNPs possibly associated with PVL were detected. The 424 candidates SNPs were genotyped in these 42 SIV experimentally infected animals (including the nine animals subjected to whole genome sequencing). The genes containing variants most probably associated with PVL at a set time point are analyzed herein.
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http://dx.doi.org/10.1038/s41598-018-25071-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940699PMC
May 2018

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

Immunogenetics 2015 Oct 8;67(10):563-78. Epub 2015 Sep 8.

Laboratoire d'Immunogénétique moléculaire, Université Toulouse III, Faculte de Medecine Purpan, Laboratoire d'immunologie, 1 Avenue Jean Poulhes, Hôpital Rangueil, TSA50032, 31059, Toulouse, Cedex 9, France.

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.
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http://dx.doi.org/10.1007/s00251-015-0867-9DOI Listing
October 2015

Efficacy of immunoadsorption to reduce donor-specific alloantibodies in kidney-transplant candidates.

Exp Clin Transplant 2015 Apr;13 Suppl 1:201-6

From the Department of Nephrology and Organ Transplantation, Toulouse, France; Laboratory of Histocompatibility, University Hospital; Toulouse, France; and the Université Paul Sabatier, Toulouse, France.

Objectives: We implemented a desensitization program at our center to enable transplant in kidney-transplant candidates who have a living human-leukocyte antigen-incompatible (HLAi) donor. We report on the efficacy of semispecific immunoadsorption to allow HLAi kidney transplant in 6 highly sensitized patients.

Materials And Methods: We chose immunoadsorption as the apheresis technique coupled to hemodialysis as a means to decrease donor-specific alloantibodies in kidney transplant candidates submitted to a pretransplant desensitization program to remove detrimental antibodies.

Results: Six highly sensitized kidney-transplant patients (5 females), awaiting their first (n = 1) or second (n = 5) kidney transplant from a living donor, were enrolled in this desensitization program. They had 1 (n = 2), 2 (n = 1), 3 (n = 2), or 4 (n = 1) donor-specific alloantibodies; their mean fluorescent intensities at predesensitization ranged from 1200 to 19 000. Each patient underwent between 10 and 16 immunoadsorption sessions. At the time of transplant, donor-specific alloantibodies were undetectable in 2 patients (A24, DR3); donorspecific alloantibodies decreased by > 50% in 8 patients (A11, B44, DR3, DR11, DQ3 thrice, DQ5); donor-specific alloantibodies remained unchanged in 2 patients (B50, DR13); and mean fluorescent intensities were slightly increased in 2 patients (Cw6, DQ8). In the analysis of final outcomes, 2 patients experienced no rejection (1 experienced donor-specific alloantibody elimination, and 1 experienced a > 50% decrease in donor-specific alloantibodies). One patient presented with acute antibody-mediated rejection, which required immunoadsorption sessions and eculizumab therapy (donor-specific alloantibodies between 5000 and 19 000). Two patients presented with subacute antibody-mediated rejection; 1 was treated by plasmapheresis/rituximab therapy, and the other was treated with plasmapheresis/ methylprednisolone pulses. Another patient presented with chronic antibody-mediated rejection, which was treated unsuccessfully with plasmapheresis/rituximab; a tentative of rescue therapy with eculizumab was attempted without success.

Conclusions: Desensitization of the humanleukocyte antigen using this immunoadsorption procedure effectively reduced or eliminated donorspecific alloantibodies in 71% of patients undergoing kidney transplant, at the time of transplant.
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April 2015

Deleterious impact of feto-maternal MHC compatibility on the success of pregnancy in a macaque model.

Immunogenetics 2014 Feb 28;66(2):105-13. Epub 2013 Dec 28.

Laboratoire d'Immunogénétique Moléculaire, EA 3034, Faculté de Médecine Purpan, Université Paul Sabatier, Toulouse 3, CHU de Toulouse, Toulouse, France.

The impact of feto-maternal histocompatibility on reproduction has inspired long-lasting debates. However, after the review of numerous articles, the impact of HLA allele sharing within couples on fecundity remains questionable. We decided to explore the impact of major histocompatibility complex (MHC) feto-maternal compatibility on reproduction in a cynomolgus macaque facility composed of animals of Mauritian descent. The Mauritian-derived macaque population presents a very restricted MHC polymorphism (only seven founding haplotypes) due to a strong founding bottleneck effect. The MHC polymorphism was investigated in 237 trios (male, female and offspring) using 17 microsatellite markers distributed across the MHC. Haplotypes were confirmed by segregation analysis. We evaluated the relative frequencies of MHC-compatible and MHC-semi-compatible offspring with the mothers. Among the 237 trios, we selected 42 trios for which the identity of the father is certain and for which the theoretical probabilities of fully compatible and semi-compatible offspring were equal. We found 11 offspring fully compatible and 31 offspring semi-compatible with their respective mother. The observed proportions were clearly outside the interval of confidence of 99 % and therefore most probably resulted from a selection of the semi-compatible offspring during pregnancy. We concluded that MHC fully compatible cynomolgus macaque offspring have a selective survival disadvantage in comparison with offspring inheriting a paternal MHC haplotype differing from maternal haplotypes.
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http://dx.doi.org/10.1007/s00251-013-0752-3DOI Listing
February 2014

Study of cynomolgus monkey (Macaca fascicularis) Mhc DRB gene polymorphism in four populations.

Immunogenetics 2012 Aug 4;64(8):605-14. Epub 2012 Apr 4.

Laboratoire d'Immunogénétique moléculaire, EA 3034, Faculté de Médecine Purpan, Université Paul Sabatier, Toulouse 3, CHU de Toulouse, Toulouse, France.

The cynomolgus macaque (Macaca fascicularis) is currently used as an animal model in various fields of immunology especially in the development of innovative vaccines for the prevention and treatment of infectious diseases. The polymorphism of the major histocompatibility complex (MHC) influences the development of adaptive immune responses, and it is crucial to characterize the polymorphism of cynomolgus MHC genes. Among all macaque species, the cynomolgus macaque has the most diversified geographical area encompassing continental and insular populations. By the study of a large sample of animals from the Philippines (N = 359), we have characterized 20 DRB haplotypes. The DRB genotyping was performed by denaturing gradient gel electrophoresis (DGGE) sequencing of exon 2 and was confirmed by polymerase chain reaction-sequence-specific oligonucleotide. The DRB and DRA cDNA of 126 animals were characterized by cloning and sequencing. By means of DGGE sequencing, we characterized the polymorphism of genomic DRB exon 2 in three other cynomolgus macaque population samples (Java, Vietnam, and Mauritius), and we discuss about the origin of the founders of the Mauritian and the Filipino cynomolgus macaque populations.
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http://dx.doi.org/10.1007/s00251-012-0613-5DOI Listing
August 2012

Use of Cumulative Poisson Probability Distribution as an Estimator of the Recombination Rate in an Expanding Population: Example of the Macaca fascicularis Major Histocompatibility Complex.

G3 (Bethesda) 2012 Jan 1;2(1):123-30. Epub 2012 Jan 1.

We describe a method to estimate the rate of recombination per generation from the genotypes of a large individual sample of an expanding population, for which the founding event is dated. The approach is illustrated with an application to estimating the major histocompatibility complex (MHC) recombination rate in the Mauritian macaque population. We genotyped 750 macaques by means of 17 microsatellites across the MHC region and reconstructed the seven most frequent haplotypes assumed to represent the founding haplotypes (H(rec(0))) as well as the 31% recombinant haplotypes (H(rec(h))) resulting from a variable number "h" of recombinations between the founding haplotypes. The relative frequencies of the various classes of haplotypes (H(rec(0)) and H(rec(h))) follow a Poisson distribution. By using a maximum likelihood method, we calculated the mean of the Poisson distribution that best fits the data. By dividing this mean by the number of generations (50-100) from the date of the population founding, we deduced that rate of recombination in the MHC is approximately 0.004 to 0.008 in the Mauritian macaque population. When the founding date of the population is precisely known, our method presents a useful alternative to the coalescent method.
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http://dx.doi.org/10.1534/g3.111.001248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276188PMC
January 2012

Characterization of MHC class I transcripts of a Malaysian cynomolgus macaque by high-throughput pyrosequencing and EST libraries.

Immunogenetics 2011 Nov 28;63(11):703-13. Epub 2011 Jun 28.

Laboratoire d'Immunogénétique moléculaire, EA 3034, Faculté de Médecine Purpan, Université Paul Sabatier, Toulouse 3, France.

We characterized the repertoire of MHC class I transcripts of a Malaysian cynomolgus macaque by the study of EST libraries derived from the mRNA extracted from six tissues (thymus, spleen, bone marrow, liver, heart and pancreas). The MHC class I transcripts present in a lymph node of the same animal were characterized by pyrosequencing of amplified cDNA fragments (515 bp from exon 2 to the beginning of exon 4). All pyrosequence consensus sequences, but three corresponding to rare transcripts, were identical to those obtained from EST libraries. In total, we characterized 19 classical class I transcripts in the Malaysian macaque studied here. By means of high-throughput sequencing of exon 2 amplified from the genomic DNA (190 bp), we characterized 38 classical class I genes in the genome of this animal. By comparison, using the same method, we found 23 classical class I genes in the genome of a MHC homozygous Mauritian animal (H2/H2). All these results suggested that the Malaysian animal was most probably heterozygous. This study reveals that the high-throughput pyrosequencing allows not only to characterize the MHC class I transcripts but also to estimate the number of MHC class I genes in the genome of cynomolgus macaque.
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http://dx.doi.org/10.1007/s00251-011-0550-8DOI Listing
November 2011

Influence of the MHC genotype on the progression of experimental SIV infection in the Mauritian cynomolgus macaque.

Immunogenetics 2011 May 14;63(5):267-74. Epub 2011 Jan 14.

Laboratoire d'Immunogénétique moléculaire, EA 3034, Faculté de Médecine Purpan, Université Paul Sabatier, CHU de Toulouse, 1 avenue Jean Poulhes, Toulouse cedex 9, France.

Experimental infection of Mauritian cynomolgus macaques by simian immunodeficiency virus is a representative model of HIV infection, currently in favour for evaluating the efficacy of new preventive or curative treatments. Extensive studies of major histocompatibility complex (MHC) polymorphism by microsatellites revealed seven haplotypes (H1-H7). We present statistical evidence of the influence of MHC polymorphism on the set-point plasma viral load (PVL). Our analysis was based on the study of 45 Mauritian cynomolgus macaques inoculated by intravenous or intrarectal injection of a 50 AID50 dose of the SIVmac251 virus. The animals received no treatment before or after the inoculation. MHC polymorphism was investigated by means of 20 microsatellites distributed across the MHC and by DRB genotyping using the DGGE sequencing method. Statistical analysis with UNPHASED: software revealed that two markers located in the class IB region significantly influenced the Log PVL and that three class IB haplotypes were significantly associated with lower (H2 or H6) or higher (H4) set-point Log PVL values. Although the impact of MHC on Log PVL was found to be low (around one Log10), it is important to dispose of animals paired for their MHC genotypes, each animal tested for a given treatment and its untreated control, to minimize the influence of the MHC and clearly reveal the effect of the treatment.
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http://dx.doi.org/10.1007/s00251-010-0504-6DOI Listing
May 2011

Impact of MHC class II polymorphism on blood counts of CD4+ T lymphocytes in macaque.

Immunogenetics 2011 Feb 18;63(2):95-102. Epub 2010 Nov 18.

Laboratoire d'Immunogénétique Moléculaire, EA 3034, Faculté de Médecine Purpan, Université Paul Sabatier, Toulouse 3, IFR150 (INSERM), CHU de Toulouse, 1 avenue Jean Poulhes, TSA 50032, 31059, Toulouse cedex 9, France.

While the number of peripheral blood T lymphocytes and of their two main subsets (CD4+CD8- and CD4-CD8+) varies little in a given healthy individual, substantial variation is observed between individuals. It was proposed that these counts could be influenced by MHC polymorphisms because of the well-established role of MHC molecules in thymic T lymphocyte maturation and presentation of antigenic peptides to peripheral T lymphocytes. To test this hypothesis, we have chosen the crab-eating macaque (Macaca fascicularis), an animal model phylogenetically close to man. We selected the Philippine macaque population because of a restriction of the MHC polymorphism in this islander population. Peripheral blood lymphocytes were counted with an automated analyzer and T lymphocyte subsets were assessed by immunolabeling and flow cytometry. The MHC polymorphism was investigated in 200 unrelated subjects using 14 microsatellites markers distributed across the MHC and the DRB locus that was genotyped by denaturing gradient gel electrophoresis and sequencing. All markers were in Hardy-Weinberg equilibrium. Allelic associations were tested with the UNPHASED software. We revealed a significant influence of the MHC class II region on CD4+ T lymphocyte blood count with the largest effect associated with a two-locus haplotypes combining the DRACA allele 274 and the DRB haplotype #8a (p < 8 × 10(-7)). Our data should stimulate a similar association study of the CD4+ T cell counts in humans.
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http://dx.doi.org/10.1007/s00251-010-0492-6DOI Listing
February 2011

Study of cynomolgus monkey (Macaca fascicularis) DRA polymorphism in four populations.

Immunogenetics 2010 Mar 22;62(3):123-36. Epub 2010 Jan 22.

Laboratoire d'immunogénétique moléculaire, EA3034, Faculté de Médecine Purpan, Toulouse 3, France.

To describe the polymorphism of the DRA gene in Macaca fascicularis, we have studied 141 animals either at cDNA level (78 animals from Mauritius, the Philippines, and Vietnam) or genomic level (63 animals from the Philippines, Indonesia, and Vietnam). In total, we characterized 22 cDNA DRA alleles, 13 of which had not been described until now. In the Mauritius population, we confirmed the presence of three DRA alleles. In the Philippine and Vietnam populations, we observed 11 and 14 DRA alleles, respectively. Only two alleles were present in all three populations. All DRA alleles but one differ from the consensus sequence by one to three mutations, most being synonymous; so, only seven DR alpha proteins were deduced from the 22 cDNA alleles. One DRA cDNA allele, Mafa-DRA*02010101, differs from all other alleles by 11 to 14 mutations of which only four are non-synonymous. The two amino acid changes inside the peptide groove of Mafa-DRA*02010101 are highly conservative. The very low proportion of non-synonymous/synonymous mutations is compatible with a purifying selection which is comparable to all previous observations concerning the evolution of the DRA gene in mammals. Homologues of the allele Mafa-DRA*02010101 are also found in two other Asian macaques (Macaca mulatta and Macaca nemestrina). The forces able to maintain this highly divergent allele in three different macaque species remain hypothetical.
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http://dx.doi.org/10.1007/s00251-009-0421-8DOI Listing
March 2010

Interest of liposomal doxorubicin as a radiosensitizer in malignant glioma xenografts.

Anticancer Drugs 2008 Nov;19(10):991-8

EA 4001 Radiopotentialisation: de la préclinique à la clinique, Faculté de Médecine, Nancy Université, 9 avenue de la Forêt de Haye-BP 184, Vandoeuvre-les-Nancy, Nancy, France.

Malignant glioma patients have a life expectancy reduced to about 15 months despite aggressive surgery, radiotherapy (RT), and chemotherapy. Doxorubicin has shown a marked cytotoxic effect against malignant glioma cells in vitro. The brain exposure to this drug is, however, hindered by the blood-brain barrier. Encapsulation of doxorubicin in liposomal carriers has been shown to reduce toxicities and to improve brain tumors exposure to doxorubicin. In this study, we evaluated the radiosensitizing properties of a nonpegylated liposomal doxorubicin (Myocet, MYO) on two subcutaneous (U87 and TCG4) and one intracranial (U87) malignant glioma models xenografted on nude mice. Doxorubicin biodistribution was assessed by a high-performance liquid chromatography method. Antitumor efficacy was investigated by tumor volume measurements and mice survival determination. We showed that (i) encapsulation of doxorubicin ensured a preferential deposition of doxorubicin in tumoral tissue in comparison with free doxorubicin; (ii) doxorubicin accumulated in both subcutaneous and intracranial tumors during repeated injections of MYO and this accumulation was linked to the potentiation of RT efficacy on two subcutaneous models; (iii) MYO was unable to improve the antitumoral efficacy of RT on an intracranial glioma model. Finally, this study emphasizes the importance of performing preclinical studies on models closer as possible of human tumors and localization to be more predictive of therapeutic effects observed in humans.
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http://dx.doi.org/10.1097/CAD.0b013e328313e172DOI Listing
November 2008
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