Marie-Pierre Chenard

University of Strasbourg, Strasburg, Alsace, France

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Publications (67)282.52 Total impact

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    ABSTRACT: Background: Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (mEGFR and mKRAS) are useful biomarkers in resected non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012. Results: mEGFR was observed in 103 patients (12.2%), and mKRAS in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for mKRAS (OS: 43 months; TTR: 19 months) compared with mEGFR (OS: 67 months; TTR: 24 months) and wild-type patients (OS: 55 months; disease-free survival (DFS): 24 months). Patients with KRAS G12V exhibited worse OS and TTR compared with the entire cohort (OS: KRAS G12V: 26 months vs Cohort: 60 months; DFS: KRAS G12V: 15 months vs Cohort: 24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR): 0.43 (confidence interval: 0.28-0.65), P<0.0001 for OS; HR: 0.67 (0.48-0.92), P=0.01 for TTR). Risk of recurrence was significantly lower for non-KRAS G12V (HR: 0.01, (0.001-0.08), P<0.0001). Conclusions: mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences.British Journal of Cancer advance online publication, 15 September 2015; doi:10.1038/bjc.2015.327 www.bjcancer.com.
    No preview · Article · Sep 2015 · British Journal of Cancer
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    ABSTRACT: Human epidermal growth factor receptor 2 (HER2) status in breast carcinomas serves as a predictor of benefit from anti-HER2 therapy. In providing clinicians with the information necessary to decide whether or not to treat with targeted therapy, it might be necessary to choose between methods assessing HER2 protein overexpression or gene amplification. A new diagnostic approach could be a combination of both tests on the same slide. If accurate and reproducible, this approach might optimize patient stratification for therapy. In this study, formalin-fixed paraffin-embedded tumor samples from 77 breast cancer patients were examined for HER2 by immunohistochemistry (IHC) and silver in situ hybridization (SISH) using HER2 IHC (clone 4B5), HER2/CEN17SISH, and combined IHC and SISH assay, called gene protein (GP). Cases were selected to ensure a sufficient number of borderline cases on the basis of IHC scores (0, 1+, 2+, 3+), obtained during diagnostic histopathological workup. The concordance between the HER2 IHC score obtained during diagnostic histopathological workup and GP was 93 %. Discordances had no influence on therapy decisions. The concordance between ISH results using dual ISH (DISH) and GP was 96 %. Of the 77 cases studied by GP, three cases with a ratio close to 2 would have been called amplified by DISH. The use of GP reduced the time for slide reading for a trained pathologist by up to 25 %, relative to sequential reading of IHC followed by SISH. For cases with an IHC score of 2+, the final result was obtained in 1 day, while the sequential technique would have required retesting by ISH on a second day. In conclusion, assessment of HER2 status by GP is an improvement for pathologists and facilitates clinical decision-making for breast cancer management.
    Full-text · Article · May 2015 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
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    ABSTRACT: MET pathway is a promising target in non-small cell lung cancers (NSCLC) requiring companion tests. The aim of this study was to compare MET expression/gene copy number in a Caucasian population of NSCLC patients.We analysed 201 NSCLC, with 141 adenocarcinomas classified according to 2011 IASLC recommendations, for MET expression by immunohistochemistry (IHC) and gene copy number (GCN) by silver in situ hybridisation (SISH) on tissue microarrays. Mutations in EGFR, KRAS, BRAF, HER2, PIK3CA genes and ALK rearrangements were determined.MET overexpression was observed in 44% and a high MET GCN (≥5 copies) in 14%. MET CGN was correlated with MET expression, regardless of IHC scores (p < 0.001) but only 31% of MET overexpressed cases were SISH positive. MET overexpression/GCN number was more frequent in ADC than the other types (p < 0.001), the highest in high grade (74%/34%) and sarcomatoid ADC (86%/43%). Mutations of current genes or ALK rearrangements were identified in overexpressed or amplified MET cases. MET overexpression was an independent prognostic factor for overall survival in non-smoker NSCLC in univariate (p = 0.01) and multivariate (p = 0.01) analyses.MET overexpression is more frequent than MET high GCN, particularly in high grade ADC, regardless of EGFR, KRAS, BRAF, HER2, PIK3CA and ALK status in NSCLC.
    No preview · Article · May 2015 · Pathology
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    ABSTRACT: Abstract The extracellular matrix (ECM) molecule tenascin-C (TNC) promotes tumor progression. This has recently been demonstrated in the stochastic murine RIP1-Tag2 insulinoma model, engineered to either express TNC abundantly or to be devoid of TNC. However, our knowledge about organization of the TNC microenvironment is scant. Here we determined the spatial distribution of TNC together with other ECM molecules in murine RIP1-Tag2 insulinoma and human cancer tissue (insulinoma and colorectal carcinoma). We found that TNC is organized in matrix tracks together with other ECM molecules of the AngioMatrix signature, a previously described gene expression profile that characterizes the angiogenic switch. Moreover, stromal cells including endothelial cells, fibroblasts and leukocytes were enriched in the TNC tracks. Thus, TNC tracks may provide niches for stromal cells and regulate their behavior. Given similarities of TNC rich niches for stromal cells in human insulinoma and colon cancer, we propose that the RIP1-Tag2 model may be useful for providing insights into the contribution of the tumor stroma specific ECM as promoter of cancer progression.
    No preview · Article · Jan 2015 · Cell adhesion & migration
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    ABSTRACT: Background: The aim of this case-control study was to identify clinicopathological factors and test three relevant biomarkers for their ability to predict early intrahepatic recurrence after curative liver resection for colorectal liver metastases (CLM). Methods: Of the 184 patients with CLM undergoing hepatectomy between January 2007 and December 2009, thirty patients had intrahepatic disease recurrence within 6 months. The control group was randomly selected from a cohort of patients between April 1997 and December 2005 who have survived without disease recurrence after CLM resection for over 5 years. Both groups were matched for size of metastasis greater than 5.0 cm, the presence of multiple metastases, and synchronous versus metachronous CLM. The final study population consisted of 60 patients with CLM undergoing R0 hepatectomy, 30 of whom had early intrahepatic-only recurrences (study group) and 30 patients without recurrence for more than 5 years (control group). Both groups were analyzed and compared for the presence of clinical factors and expression levels of CD133, survivin, and Bcl-2 within tumor tissue. Results: Characteristics of patients were similar between the two groups except primary tumor location and administration of postoperative chemotherapy. Expression level of CD133 and survivin were significantly increased in tumors of patients with recurrence compared to patients without recurrence. On multivariate analysis high tumor expression levels of CD133 (odds ratio [OR] 14.7, confidence interval [CI] 1.8-121.3, p = 0.012) and survivin (OR 9.5, CI 2.1-44.3, p = 0.004) and postoperative chemotherapy (OR 4.8, CI 1.01-22.9, p = 0.049) were independent factors associated with early intrahepatic recurrence. Conclusions: Tumor expression levels of CD133 and survivin may be a useful predictor of early intrahepatic recurrence after hepatectomy for CLM. Administration of postoperative chemotherapy may prevent early intrahepatic recurrence.
    Full-text · Article · Jan 2015 · World Journal of Surgery
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    ABSTRACT: Background: The objective of our study is to provide predictive markers of locally advanced rectal tumour sensitivity to preoperative chemoradiotherapy in order to identify tumours that present a high risk of recurrence after standard total mesorectal excision surgery and preoperative chemoradiotherapy, according to histological response and microsatellite allelic imbalance (AI). Methods: Twenty-nine locally advanced tumours were included in the study and the genomic alterations and the tumour regression grade of paired rectal biopsies (before chemoradiotherapy) and carcinomas (after surgery) were assessed. Clinical and allelotyping data were analysed for local and distant recurrence. Results: The global AI frequency significantly decreased from 47.4 to 20.3% (p < 0.01) after preoperative treatment. Preoperative chemoradiotherapy significantly induced the loss of cells bearing AI at 8 microsatellites: D18S61, D8S264, D1S305, D10S191, D4S394, D14S65, D17S790 and D10S192. Among these, AI at the D8S264 locus was significantly associated with recurrence in our rectal tumour cohort (p = 0.039). Conclusion: Loss of AI at D8S264 is predictive of sensitivity to neoadjuvant treatment; thus, we concluded that the persistence of AI at D8S264 in rectal tumours after preoperative chemoradiotherapy could be considered a molecular marker of recurrence.
    No preview · Article · Dec 2014 · Digestive surgery
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    ABSTRACT: Diffuse adult high grade gliomas (HGG) with necrosis encompass anaplastic oligodendrogliomas (AO) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO", restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were done. 1p/19q codeletion characterized AO whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of PFS and OS (p<10(-4) ). Diffuse adult HGG with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q codeleted AO, IDH1 R132H- GBM, and 1p19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO. This article is protected by copyright. All rights reserved.
    Full-text · Article · Nov 2014 · Brain Pathology
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    ABSTRACT: Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS' update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Oct 2014 · Annales de Pathologie
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    ABSTRACT: De nouvelles recommandations internationales pour l’évaluation du statut HER2 dans les cancers du sein, basées sur plus de dix ans d’expérience et sur les résultats d’études cliniques et de concordance entre les différentes techniques de détection, viennent tout juste de voir le jour. Le présent article a pour objet de faire le point sur ces nouvelles recommandations, à la lumière de la publication récente du groupe de travail de l’American Society of Clinical Oncology (ASCO) et du Collège des pathologistes américains (CAP), adaptées à la pratique de la pathologie en France et revues par le groupe GEFPICS. À l’ère de la médecine personnalisée, la détermination du statut HER2 reste un élément phare dans le panel des biomarqueurs théranostiques des cancers du sein. Si l’interprétation du statut HER2 dans les cancers du sein est aisée dans la majorité des cas, un certain nombre de situations anatomocliniques est d’interprétation plus délicate, telles que la possibilité rare mais réelle de l’hétérogénéité intra-tumorale du statut de HER2, les formes à différenciation micropapillaire ou la ré-évaluation du statut des biomarqueurs lors de la rechute métastatique. Ces nouvelles recommandations abordent ces différentes questions, reprécisent les conditions pré-analytiques optimales et les critères d’interprétation (notamment des cas 2+), afin de réduire au maximum le risque de faux négatifs. Plus que jamais, la mobilisation de la spécialité d’anatomo-cytopathologie autour de la qualité des tests théranostiques témoigne de son implication dans la chaîne des soins en cancérologie.
    No preview · Article · Oct 2014 · Annales de Pathologie
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    ABSTRACT: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P < 10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(-4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023). The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.
    Full-text · Article · Apr 2014 · Neuro-Oncology
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    ABSTRACT: While a variety of registered therapies exist for Cutaneous T Cell Lymphoma, no such therapy is available for Cutaneous B Cell Therapy. In this context we performed a phase II, open label, multicenter, non-comparative study to evaluate the efficacy and safety of repeated intra-lesional administrations of TG1042 (adenovirus-interferon-γ) in patients with relapsing primary cutaneous B-cell lymphomas (CBCL). Thirteen patients have been enrolled and received intralesional injections of TG1042 containing 5×10(10) viral particles into up to six lesions simultaneously. Injections were performed on days 1, 8 and 15 of each of four consecutive 28 day cycles. Eleven (85%) out of 13 enrolled patients showed an objective response after injections of TG1042. Seven patients (54%) exhibited complete and four (31%) displayed partial response. The median time to disease progression in the study population was 23.5 months (range 6.25 to 26+). Most commonly observed adverse events were minor to moderate flu-like symptoms, fatigue and injection site reactions. Our study showed that treatment with TG1042 was associated with a clinical benefit in the majority of the patients with relapsing CBCL, including tumor regression, a clinically meaningful duration of response and a good treatment tolerance. www.clinicaltrials.govNCT00394693.
    Full-text · Article · Feb 2014 · PLoS ONE

  • No preview · Article · Jan 2014 · Revue des Maladies Respiratoires
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    ABSTRACT: Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL). For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patient's objective response at the end of the study. Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit. These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response.Trial registrationThe phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693.
    Full-text · Article · Sep 2013 · Journal of Translational Medicine

  • No preview · Conference Paper · Feb 2013

  • No preview · Article · Nov 2012 · Annales de Pathologie
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    ABSTRACT: Portal triad clamping (PTC) has been widely adopted in an attempt to decrease bleeding during liver parenchymal transection. As a larger proportion of patients are treated with chemotherapy prior to liver resection, the safety of PTC in patients with chemotherapy-associated liver injury remains poorly investigated. This study aims to evaluate the influence of PTC on early postoperative outcomes in patients with chemotherapy-associated liver injury undergoing major hepatectomy for colorectal liver metastases (CLM). From January 2000 to October 2010, 53 patients with histologically proven chemotherapy-associated liver injuries [sinusoidal obstruction syndrome (SOS; n = 41), steatohepatitis (n = 5), and both SOS and steatohepatitis (n = 7)] who underwent major hepatectomy for CLM were divided into two groups; patients undergoing intermittent TPC (n = 20) and those who did not undergo TPC (n = 33). Perioperative clinicobiological factors, morbidity including septic complications, and mortality were analyzed and compared between the two groups. Intraoperative blood transfusions and postoperative liver function were comparable between the two groups. Sepsis and biloma occurred more often in patients undergoing PTC longer than 30 min than in those undergoing PTC ≤ 30 min (66.7 % versus 17.1 %, p = 0.002, and 33.3 versus 0 %, p = 0.002, respectively). A multiple logistic regression analysis showed that prolonged PTC (>30 min) and the ratio of future liver remnant volume to total liver volume ≤ 43 % were independent factors for predicting postoperative sepsis [odds ratio (OR): 32.68; 95 % confidence interval (95 % CI): 2.86-372.82; p = 0.005--and odds ratio: 9.70; 95 % CI: 1.04-90.86; p = 0.047, respectively]. Portal triad clamping can be safely used in patients with chemotherapy-associated liver injury who require major liver resection. Prolonged PTC can increase the occurrence of postoperative biliary and septic complications.
    Full-text · Article · Mar 2012 · World Journal of Surgery
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    ABSTRACT: Aluminium hydroxide is used as an effective adjuvant in a wide range of vaccines for enhancing immune response to the antigen. The pathogenic role of aluminium hydroxide is now recognized by the presence of chronic fatigue syndrome, macrophagic myofasciitis and subcutaneous pseudolymphoma, linked to intramuscular injection of aluminium hydroxide-containing vaccines. The aim of this study is to verify if the subcutaneous pseudolymphoma observed in this patient in the site of vaccine injection is linked to an aluminium overload. Many years after vaccination, a subcutaneous nodule was discovered in a 45-year-old woman with subcutaneous pseudolymphoma. In skin biopsy at the injection site for vaccines, aluminium (Al) deposits are assessed by Morin stain and quantification of Al is performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry. Morin stain shows Al deposits in the macrophages, and Al assays (in μg/g, dry weight) were 768.10±18 for the patient compared with the two control patients, 5.61±0.59 and 9.13±0.057. Given the pathology of this patient and the high Al concentration in skin biopsy, the authors wish to draw attention when using the Al salts known to be particularly effective as adjuvants in single or repeated vaccinations. The possible release of Al may induce other pathologies ascribed to the well-known toxicity of this metal.
    Full-text · Article · Mar 2012 · Journal of Trace Elements in Medicine and Biology
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    ABSTRACT: Indocyanine green (ICG) retention is a validated test of hepatic function in patients with chronic liver disease. The underlying mechanism for the impairment of ICG retention in patients undergoing chemotherapy for colorectal liver metastases (CLM) remains unclear. We sought to elucidate the mechanism for impairment of ICG retention in patients with CLM. Clinicopathologic data of 98 patients with CLM undergoing hepatectomy were analyzed. The archived nontumoral liver parenchyma bearing no CLM were immunostained with CD34 antibody to determine the sinusoidal capillarization. Of 98 patients, 80 received preoperative chemotherapy. Sinusoidal obstruction syndrome (SOS) occurred in 39 patients (39.8%). The development of SOS in patients receiving oxaliplatin-based chemotherapy was significantly higher compared to those receiving non-oxaliplatin-based chemotherapy (P=0.003). SOS was independently associated with abnormal ICG retention rate at 15 minutes (ICG-R15) (odds ratio 3.45, 95% confidence interval 1.31-9.04, P=0.012) and CD 34 overexpression (odds ratio 18.76, 95% confidence interval 4.58-76.81, P<0.001). ICG-R15 correlated with CD34 expression within the nontumoral liver parenchyma (r=0.707, P<0.001) and severity of SOS (r=0.423, P<0.001). CD34 positive areas were likely situated at the peripheral area of SOS, and both SOS score and number of cycles of oxaliplatin-based chemotherapy significantly correlated with CD34 expression (r=0.629, P<0.001 and r=0.522, P<0.001, respectively). These results suggest that the deterioration of hepatic functional reserve due to SOS is associated with sinusoidal capillarization, indicated by CD34 overexpression within nontumoral liver parenchyma adjacent to SOS.
    Full-text · Article · Mar 2012 · Annals of Surgical Oncology
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    ABSTRACT: A multidisciplinary approach involving preoperative chemotherapy has become common practice in patients with colorectal liver metastases (CLM). The definition of a safe future liver remnant (FLR) volume based on preoperative clinical data in these patients is lacking. Our aim was to identify predictors of postoperative morbidities in patients undergoing major hepatectomy after intensive preoperative chemotherapy for CLM. Between January 2000 and August 2010, a total of 101 consecutive patients with CLM underwent major hepatectomy after preoperative chemotherapy (≥6 cycles of oxaliplatin or irinotecan regimen with or without targeted therapies). The FLR ratio was calculated by two formulas: actual FLR (aFLR) ratio, and standardized FLR (sFLR) ratio. Predictors of postoperative overall morbidity, sepsis, and liver failure were identified by univariate and multivariate analyses. Fifty-eight patients (57.4%) had 95 postoperative complications. Sepsis and postoperative liver failure occurred in 23 (22.8%) and 16 patients (15.8%), respectively. On univariate analysis, small aFLR ratio was significantly associated with all complications, and sFLR ratio was associated with sepsis and liver failure. In receiver-operating characteristic analysis, the cutoff of aFLR ratio in predicting overall morbidity, sepsis, and liver failure was 44.8, 43.1, and 37.7%, respectively, and that of sFLR ratio in predicting sepsis and liver failure was 43.6 and 48.5%, respectively. On multivariate analysis, these aFLR and sFLR ratio cutoffs were independent predictors of all complications and of sepsis and liver failure, respectively. This study provides a cutoff FLR ratio for safe postoperative outcome after major hepatectomy in CLM patients receiving six or more cycles of preoperative chemotherapy.
    Full-text · Article · Mar 2012 · Annals of Surgical Oncology
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    ABSTRACT: Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal transducers for the TNF and interleukin-1/Toll-like receptor superfamilies. However, TRAF4 does not fit the paradigm of TRAF function in immune and inflammatory responses. Its physiological and molecular functions remain poorly understood. Behavorial analyses show that TRAF4-deficient mice (TRAF4-KO) exhibit altered locomotion coordination typical of ataxia. TRAF4-KO central nervous system (CNS) ultrastructure shows strong myelin perturbation including disorganized layers and disturbances in paranode organization. TRAF4 was previously reported to be expressed by CNS neurons. Using primary cell culture, we now show that TRAF4 is also expressed by oligodendrocytes, at all stages of their differentiation. Moreover, histology and electron microscopy show degeneration of a high number of Purkinje cells in TRAF4-KO mice, that was confirmed by increased expression of the Bax pro-apoptotic marker (immunofluorescence), TUNEL analysis, and caspase-3 activation and PARP1 cleavage (western blotting). Consistent with this phenotype, MAG and NogoA, two myelin-induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR were overexpressed (Q-RT-PCR and western blotting). The strong increased phosphorylation of Rock2, a RhoA downstream target, indicated that the NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton rearrangement that favors axon regeneration inhibition and neuron apoptosis, is activated in the absence of TRAF4 (western blotting). Altogether, these results provide conclusive evidence for the pivotal contribution of TRAF4 to myelination and to cerebellar homeostasis, and link the loss of TRAF4 function to demyelinating or neurodegenerative diseases.
    Full-text · Article · Feb 2012 · PLoS ONE

Publication Stats

2k Citations
282.52 Total Impact Points

Institutions

  • 2005-2015
    • University of Strasbourg
      • • Faculty of Medicine
      • • Institut de Bactériologie
      Strasburg, Alsace, France
  • 2002-2012
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 1997
    • Centre Hospitalier Universitaire de Brest
      Brest, Brittany, France