H Loiseau

University of Bordeaux, Burdeos, Aquitaine, France

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Publications (134)381.35 Total impact

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    ABSTRACT: Although GH- and PRL-secreting pituitary adenomas are considered benign, in many patients, tumor growth and/or invasion constitute a particular challenge. In other tumors, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In this study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumor invasiveness. We have first established, by qPCR and immunohistochemistry, the expression profile of classical cadherins in normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, while N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumors: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalization of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalization of cadherin 18, beta-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumors. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumor invasion. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Journal of Neuroendocrinology
  • C. Pouchieu · I. Baldi · A. Gruber · E. Berteaud · C. Carles · H. Loiseau
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    ABSTRACT: Although comparisons are difficult due to differences in methodologies, the annual incidence rates of central nervous system (CNS) tumors range from 8.5 to 21.4/100,000 population according to cancer registries, with a predominance of neuroepithelial tumors in men and meningiomas in women. An increase in the incidence of CNS tumors has been observed during the past decades in several countries. It has been suggested that this trend could be due to aging of the population, and improvements in diagnostic imaging and healthcare access, but these factors do not explain differences in incidence by gender and histological subtypes. Several etiological hypotheses related to intrinsic (sociodemographic, anthropometric, hormonal, immunological, genetic) and exogenous (ionizing radiation, electromagnetic fields, diet, infections, pesticides, drugs) risk factors have led to analytical epidemiological studies to establish relationships with CNS tumors. The only established environmental risk factor for CNS tumors is ionizing radiation exposure. However, for other risk factors, studies have been inconsistent and inconclusive due to systematic differences in study design and difficulties in accurately measuring exposures. Thus, the etiology of CNS tumors is complex and may involve several genetic and/or environmental factors that may act differently according to histological subtype.
    No preview · Article · Dec 2015 · Revue Neurologique
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    Preview · Article · Nov 2015 · Neuro-Oncology
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    ABSTRACT: Objectives: We aimed to study the potential clinical relevance of 9p allelic loss, with or without copy number variation, in 1p/19q codeleted anaplastic oligodendroglial tumors (AOTs). Methods: This study enrolled 216 patients with 1p/19q codeleted AOT. The prognostic value of 9p allelic loss was investigated using a French nation-wide prospective registry, POLA (prise en charge des tumeurs oligodendrogliales anaplasiques) and high-density single nucleotide polymorphism arrays. We validated our results using the Repository of Molecular Brain Neoplasia Data (REMBRANDT) dataset. Results: The minimal common region of allelic loss in chromosome arm 9p was 9p21.3. Allelic loss of 9p21.3, detected in 41.7% of tumors, was associated with shorter progression-free and overall survival rates in univariate (p = 0.008 and p < 0.001, respectively) and multivariate analyses (p = 0.009 and p = 0.009, respectively). This finding was validated in the REMBRANDT dataset in univariate and multivariate analysis (p = 0.01 and p = 0.01, respectively). Conclusion: Our study highlights a novel potential prognostic biomarker in 1p/19q codeleted AOT. Further prospective studies are warranted to investigate our finding.
    No preview · Article · Sep 2015 · Neurology
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    ABSTRACT: This work describes the clinical epidemiology and pathology for patients undergoing surgery for newly diagnosed meningiomas in France between 2006 and 2010. The methodology is based on a multidisciplinary national network previously established by the French Brain Tumor DataBase (FBTDB) (in French: Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the scientific societies involved in neuro-oncology in France. From 2006 to 2010, 13,038 incident cases of meningioma with histological validation were identified and analyzed (9769 women, 3269 men, resection 98.2%, cryopreservation 20.5%). For each histological subtype of meningioma (meningothelial, fibrous, transitional, psammomatous, angiomatous, rare variety, microcystic, secretory, lymphoplasmacyte-rich, clear-cell, chordoid, rhabdoid, metaplastic, atypical, papillary, anaplastic and not otherwise specified), number of cases, sex, median age, cryopreservation and surgery were reported. Among the various histological subtypes, atypical meningioma (grade II) slightly, but significantly, increased after 2007. Headache, sensory-motor impairments and seizures were the most frequent clinical symptoms. Time between the first clinical symptom and surgery ranged from 0 to 314 months, and was <3 months in 37% of cases. At the time of surgery, 9% of patients were asymptomatic. Given the number of meningiomas not histologically-validated, we can estimate that the gross incidence rate for meningiomas operated in France is about 4.2 per 100,000 person/year. To our knowledge, this work is the most important study evaluating the different subtypes of meningiomas and it validates the relevance of histological databases for central nervous system tumors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    No preview · Article · Jun 2015 · Neurochirurgie
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    ABSTRACT: Surgical excision of brain metastases has been well evaluated in unique metastases. Two randomized phase III trial have shown that combined with adjuvant whole brain radiotherapy, it significantly improves overall survival. However, even in the presence of multiple brain metastases, surgery may be useful. Also, even in lesions amenable to radiosurgery, surgical resection is preferred when tumors displayed cystic or necrotic aspect with important edema or when located in highly eloquent areas or cortico-subcortically. Furthermore, surgery may have a diagnostic role, in the absence of histological documentation of the primary disease, to rule out a differential diagnosis (brain abscess, lymphoma, primary tumor of the central nervous system or radionecrosis). Finally, the biological documentation of brain metastatic disease might be useful in situations where a specific targeted therapy can be proposed. Selection of patients who will really benefit from surgery should take into account three factors, clinical and functional status of the patient, systemic disease status and characteristics of intracranial metastases. Given the improved overall survival of cancer patients partially due to the advent of effective targeted therapies on systemic disease, a renewed interest has been given to the local treatment of brain metastases. Surgical resection currently represents a valuable tool in the armamentarium of brain metastases but has also become a diagnostic and decision tool that can affect therapeutic strategies in these patients.
    Full-text · Article · Jan 2015 · Cancer/Radiothérapie
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    ABSTRACT: Bien que représentant plus d’un tiers des tumeurs primitives du système nerveux central (SNC), les données épidémiologiques concernant les méningiomes (chiffres d’incidence et facteurs de causalité) demeurent réduites comparativement à celles disponibles dans les gliomes. Un nombre limité de registres de cancers, à travers le monde, enregistrent non seulement les tumeurs malignes mais aussi les méningiomes. Leur pertinence et la qualité du recueil ont été l’objet de discussions importantes. Même si les comparaisons sont difficiles à cause des différences méthodologiques, les données disponibles, d’incidence annuelles des méningiomes (standardisée selon le sexe et l’âge en utilisant soit la population Nord-Américaine, soit la population mondiale) sont compris entre 1,3/100 000 et 7,8/100 000. Une augmentation de l’incidence des tumeurs primitives du SNC, en général, et des méningiomes, en particulier, a été observée au cours des dernières décennies dans plusieurs pays. Il a été suggéré que ces tendances pouvaient être artéfactuelles et seraient la ou les résultantes de tout ou partie du vieillissement de la population, de l’amélioration non seulement de son accès mais aussi de la qualité de l’imagerie diagnostique, et des modifications des prises en charge chirurgicale y compris chez les sujets les plus âgés induisant une augmentation des confirmations histologiques et, enfin, des modifications des classifications histologiques. Tous ces facteurs ont un rôle indéniable, mais ne permettent pas d’expliquer l’augmentation de l’incidence qui a été observée, pour les méningiomes, dans toutes les tranches d’âge. Au-delà des facteurs intrinsèques (groupes ethniques, sexe, terrain allergique, antécédents personnels et familiaux, polymorphismes et syndromes de prédisposition génétiques), un certain nombre de facteurs extrinsèques sont suspectés de jouer un rôle dans la survenue des méningiomes, et leurs changements au cours du temps est à même d’impacter les tendances en termes d’incidence. Une relation de causalité a été définie seulement pour les radiations ionisantes mais l’impact de nombreux autres est suspecté: champs électromagnétiques, facteurs nutritionnels, pesticides, traitements facteurs hormonaux. Dans la mesure où, d’une part, les méningiomes représentent une menace fonctionnelle et/ou vitale, et que, d’autre part, ils voient leur incidence augmenter, les différents acteurs de la communauté neuro-oncologique doivent se sentir concernés par ces affections, non seulement au niveau de leurs prises en charge mais aussi par les données épidémiologiques afférentes.
    No preview · Article · Sep 2014 · Neurochirurgie
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    ABSTRACT: The carcinogenic effect of radiofrequency electromagnetic fields in humans remains controversial. However, it has been suggested that they could be involved in the aetiology of some types of brain tumours. The objective was to analyse the association between mobile phone exposure and primary central nervous system tumours (gliomas and meningiomas) in adults. CERENAT is a multicenter case-control study carried out in four areas in France in 2004-2006. Data about mobile phone use were collected through a detailed questionnaire delivered in a face-to-face manner. Conditional logistic regression for matched sets was used to estimate adjusted ORs and 95% CIs. A total of 253 gliomas, 194 meningiomas and 892 matched controls selected from the local electoral rolls were analysed. No association with brain tumours was observed when comparing regular mobile phone users with non-users (OR=1.24; 95% CI 0.86 to 1.77 for gliomas, OR=0.90; 95% CI 0.61 to 1.34 for meningiomas). However, the positive association was statistically significant in the heaviest users when considering life-long cumulative duration (≥896 h, OR=2.89; 95% CI 1.41 to 5.93 for gliomas; OR=2.57; 95% CI 1.02 to 6.44 for meningiomas) and number of calls for gliomas (≥18 360 calls, OR=2.10, 95% CI 1.03 to 4.31). Risks were higher for gliomas, temporal tumours, occupational and urban mobile phone use. These additional data support previous findings concerning a possible association between heavy mobile phone use and brain tumours.
    No preview · Article · May 2014 · Occupational and environmental medicine

  • No preview · Article · Apr 2014 · Neurosurgery
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    ABSTRACT: The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155-280]; B-CRC n = 21, 318[166-480]; B-RT n = 37, 149[130-214]; RS-CT n = 11, 245[211-na]; RS-CRC n = 18, 372[349-593]; RS-RT n = 39, 269[218-343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.
    No preview · Article · Feb 2014 · Neurosurgical Review
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    ABSTRACT: Background The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs).Methods The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays.ResultsMost of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2.Conclusion In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.
    Preview · Article · Dec 2013 · Neuro-Oncology

  • No preview · Article · Oct 2013 · Revue d Épidémiologie et de Santé Publique
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    ABSTRACT: Growing evidence supports a role for the Unfolded Protein Response (UPR) in carcinogenesis, however the precise molecular mechanisms underlying this phenomenon remain elusive. Herein, we identified the circadian clock PER1 mRNA as a novel substrate of the endoribonuclease activity of the UPR sensor IRE1α. Analysis of the mechanism demonstrates that IRE1α endoribonuclease activity decreased PER1 mRNA in tumor cells without affecting PER1 gene transcription. Inhibition of IRE1α signaling using either siRNA-mediated silencing or a dominant-negative strategy prevented PER1 mRNA decay, reduced tumorigenesis, and increased survival, features that were reversed upon PER1 silencing. Further analysis also identifies the chemokine CXCL3 as an IRE1α/PER1 target mediating these cellular effects. Clinically, patients showing reduced survival have lower levels of PER1 mRNA expression and increase splicing of XBP1, a known IRE1α substrate, thereby pointing towards an increase IRE1α activity in these patients. Hence, we describe a novel mechanism connecting the UPR and circadian clock components in tumor cells, thereby highlighting the importance of this interplay in tumor development.
    Full-text · Article · Jun 2013 · Cancer Research
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    ABSTRACT: Background: Brain metastases (BM) from differentiated thyroid carcinoma (DTC) are uncommon, and many questions about their management remain unsolved. The objective of this retrospective study was to analyze the characteristics, treatments, and outcomes of patients with BM from DTC. Methods: Among the 1523 patients with a DTC prospectively recorded in institutional databases between 1989 and 2012, 21 patients (1.4%) with BM were retrospectively retrieved. Patient characteristics, histological findings on initial thyroidectomy specimen, treatments, and time to death were reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method. Survival curves for various subgroups of patients according to baseline characteristics and treatment received were compared. Results: The mean age at initial and BM diagnosis was, respectively, 52.7 and 63.2 years. World Health Organization performance status (PS) at BM diagnosis was good (<2) for 12 patients and poor (≥2) for 9. The initial carcinoma was papillary for 12 patients, follicular for 5, and poorly differentiated for 4. Eighteen patients had other previous and/or synchronous distant metastases: lung (11), bone (10), and others (2 peritoneum, 1 liver, 1 adrenal gland, and 1 uterine cervix). The average interval between the first metastasis and the BM was 3 years (range 0-35.6 years). The mean number and the mean size of BM were, respectively, 2.8 (range 1-10) and 22.5 mm (range 3-44 mm). Surgery was performed for 10 patients and radiotherapy (RT) for 18, with 2 stereotactic radiosurgery (SRS), 2 conformal RT limited to the metastasis, and 15 whole-brain RT. The median OS after BM was 7.1 months. OS at 1 and 2 years were 41.6% and 35.6%. PS and realization of surgery or SRS had an impact on survival, with OS of 27 months when PS <2 versus 3 months when PS ≥2 (p=0.0009), and OS of 11.9 months after surgery or SRS versus 3.6 months in their absence (p=0.04). Conclusions: BM from thyroid cancer may have an indolent evolution with survival of one to two years or longer for specific groups of patients. Therefore, aggressive treatment options such as neurosurgery and RT should be strongly considered in patients with good PS.
    No preview · Article · Jun 2013 · Thyroid: official journal of the American Thyroid Association

  • No preview · Article · Dec 2012 · Neurochirurgie

  • No preview · Article · Nov 2012 · International Journal of Radiation OncologyBiologyPhysics
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    ABSTRACT: The human matrix metalloprotease 9 (hMMP-9) is involved in many physiological processes such as tissue remodeling. Its overexpression in tumors promotes the release of cancer cells thus contributing to tumor metastasis. It is a relevant marker of malignant tumors. We selected an RNA aptamer containing 2'fluoro, pyrimidine ribonucleosides, that exhibits a strong affinity for hMMP-9 (Kd = 20 nM) and that discriminates other human MMPs: no binding was detected to either hMMP-2 or -7. Investigating the binding properties of different MMP-9 aptamer variants by surface plasmon resonance allowed the determination of recognition elements. As a result, a truncated aptamer, 36 nucleotide long was made fully resistant to nuclease following the substitution of every purine ribonucleoside residue by 2'-O-methyl analogues and was conjugated to S-acetylmercaptoacetyltriglycine for imaging purposes. The resulting modified aptamer retained the binding properties of the originally selected sequence. Following 99mTc labelling this aptamer was used for ex vivo imaging slices of human brain tumors. We were able to specifically detect the presence of hMMP-9 in such tissues.
    No preview · Article · Oct 2012 · Bioconjugate Chemistry
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    ABSTRACT: Cancer registries cover 18% of the French population. A national surveillance might be warranted for some potentially environment-related cancers such as tumors of the central nervous system (CNS) to detect abnormal incidence variations. The PMSI database provides an interesting source of comprehensive, standardized and mandatory data collected from all health facilities. The aim of this work was to develop methods to identify incident CNS tumors using the PMSI database. A selection of patients living in Gironde was made in the 2004 PMSI database of the hospital of Bordeaux, using the CNS tumors codification. Cases were validated via the CNS primary tumor registry of Gironde taken as the reference, or medical records. Various combinations of criteria were defined and tested. The first selection based on diagnoses identified patients with a sensitivity of 84% and a positive predictive value (PPV) of 34%. Patients wrongly identified by the PMSI were non-incident cases (49%) or patients without a CNS tumor (45%). Patients with a tumor not identified by the PMSI had been hospitalized in 2005 (44%) or had no code for CNS tumor (42%). According to the algorithms, the sensitivity ranged from 64% to 84%, and the PPV from 34% to 69%. The best combination had a sensitivity of 67% and a PPV of 69% and was obtained with codes for CNS tumor in 2004 associated with a diagnostic or therapeutic code for persons under 70 years without code for CNS tumor in previous years or code for metastasis in 2004. According to these results, the PMSI database cannot be used alone to calculate the incidence of these complex tumors. However the PMSI database plays an important role in cancer surveillance, in combination with other information sources and the expertise of cancer registries. This role could increase with further reflection and improvement of data quality.
    No preview · Article · Jun 2012 · Revue d Épidémiologie et de Santé Publique
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    Full-text · Article · Feb 2012 · International Journal of Cancer
  • Isabelle Baldi · Hugues Loiseau
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    ABSTRACT: Epidemiology of primary brain tumors includes a descriptive approach (determination of prevalence and incidence) and an analytical approach (identification of risk factors). Among risk factors, some are intrinsic to the person and others are external causes that are more easily preventable. Descriptive epidemiological data have concluded an increase of annual incidence of primary brain tumor in most industrialized countries. Main explanations for this increase are the ageing of the population and a better access to the diagnostic imaging, albeit it is not possible to exclude changes in risks factors. Comparing incidences between registries is difficult. Spatial and temporal variations constitute one explanation for the discrepancies and evolutions of coding methods another one. Intrinsic factors likely to modify the risk are age, genetic predisposition and susceptibility, gender, race, birth weight, and allergy. Extrinsic factors likely to modify the risk are mainly radiation exposures. Many studies concerning, among others, electro magnetic fields, and especially cellular phones, pesticides, substitutive hormonal therapy, and diet have been published. Until now, results remain globally inconclusive. Weak incidence of primary brain tumors constitutes a huge limiting factor in the progress of knowledge, both on incidence and risk factors. Important mobilization of the neuro-oncological community is mandatory to obtain consistent and valuable data that will lead to a significant improvement in our knowledge of brain tumor epidemiology.
    No preview · Chapter · Jan 2012

Publication Stats

2k Citations
381.35 Total Impact Points

Institutions

  • 1987-2013
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2007-2011
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
    • Académie de Bordeaux
      Burdeos, Aquitaine, France
  • 2000-2011
    • Université Victor Segalen Bordeaux 2
      • • Institut de Santé Publique d'Epidémiologie et de Développement (ISPED)
      • • Centre de Résonance Magnétique des Systèmes Biologiques
      Burdeos, Aquitaine, France
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 2001-2010
    • Institut Bergonié
      Burdeos, Aquitaine, France
  • 2005
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
  • 2004
    • Centre Hospitalier Universitaire de Toulouse
      • Service de Neurochirurgie
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 1988
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France