Anti-glomerular basement membrane disease, ulcerative colitis, and primary sclerosing cholangitis: link or co-incidence?

International audienceUlcerative colitis, primary sclerosing cholangitis, and anti-glomerular basement membrane disease (anti-GBM) are three rare immune diseases with incompletely under-stood pathogenic mechanisms. We describe here the case of a 29-year-old man with ulcer-ative colitis and primary sclerosing cholang -itis who, eight years later, developed anti-GBM disease with destruction of all glomeruli leading to end-stage kidney disease. Association of these three immune diseases in the same patient has never been described. Because HLA-mediated susceptibility cannot be incriminated completely in our case, we hypothesize that environmental factors or previous immunosuppressive treatment used might be the link

Système rénine-angiotensine et cancers urologiques / Renin-angiotensin system and urological cancers.

International audienceIntroduction: A controversy animates the literature on the potential role of the rennin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers. Material and Method: We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting. Results: Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers. Conclusion: Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings

Cytogénétique des carcinomes rénaux [Cytogenetics profiles of renal carcinoma]

National audienc

Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival.

International audienceClear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and several clinical and histolopathological factors are implicated in their prognosis. We recently demonstrated that the overexpression of PAR-3 protein encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of this work was to study the association of intratumoral PAR-3 expression with known prognostic parameters and clinical outcome. In this aim, PAR-3 expression was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to 2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly associated with worse histopathological and clinical prognostic factors: Fuhrman grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher tumor grade, lymph node involvement, metastasis, and worse clinical Eastern Cooperative Oncology Group and S classification scores. After multivariate analysis, 2 parameters were independently associated with cPAR-3: necrosis and eosinophilic components. In addition, cPAR-3 patients had shorter overall and progression-free survivals independently from strong prognostic validated factors like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in ccRCC and could be useful to identify patients with high-risk tumors

Wild-type VHL Clear Cell Renal Cell Carcinomas Are a Distinct Clinical and Histologic Entity: A 10-Year Follow-up

International audienceBackground: Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with 50% risk of metastases at initial diagnosis or at follow-up. An inactivation of the tumor-suppressor gene von Hippel-Lindau (VHL) is present in >70% of sporadic cases by two of three different mechanisms: locus deletion, gene mutation, or promoter hypermethylation. Objective: To correlate the complete status of the VHL gene with clinical and pathologic criteria. Design, setting, and participants We retrospectively included 98 patients with ccRCC who underwent surgery between 2002 and 2005. VHL gene deletions (71 of 98; 72.4%), mutations (68 of 98; 69.4%), and promoter hypermethylations (13 of 98; 13.3%) were screened by gene copy analysis, gene sequencing, and methylation-specific multiplex ligation-dependent probe amplification, respectively. Outcome measurements and statistical analysis Relationships between VHL subgroups and the studied criteria were analyzed using chi-square and Student t tests. Survival was analyzed with the log-rank test and Kaplan-Meier curves. Results and limitations: Compared with ccRCCs with two events (66.3%), tumors with no or one genetic event (33.6%) were associated with a higher nuclear grade IV (p = 0.02), metastases (p = 0.04), sarcomatoid component (p = 0.01), dense lymphocyte infiltrate (p = 0.013), and vascular endothelial growth factor overexpression (>30%) (p = 0.003), which was also an independent factor after multivariate analysis. Furthermore, wild-type VHL tumors (no inactivating event, 11.2%) were associated with nodal involvement (p = 0.019), and patients with this type of tumor had a specific survival of 33 mo compared with patients with ccRCCs having one or two VHL inactivating events (107 mo; p = 0.016). The retrospective design with small number of wild-type tumors was a limitation of this work. Conclusions: This long-term study (10-yr clinical follow-up) confirms that ccRCCs with wild-type VHL are highly aggressive tumors that need to be formally identified. Patient summary Among activated VHL tumors, the wild-type subgroup defines an aggressive phenotype with worse survival rates, suggesting that these tumors must be more thoroughly screene

Viability of meta-populations of wetland birds in a fragmented landscape: Testing the key-patch approach

The key patch approach assumes that metapopulations in fragmented landscapes are likely to be viable with at least one "key" sub-population that is sufficiently large to ensure re-colonization of surrounding minor habitat patches. It is based on a minimum viable number of breeding pairs and within-breeding season dispersal distance, linked to size of the animal and longevity. It was tested using census data of 15 wetland bird species (bearded tit, bluethroat, great reed warbler, sedge warbler, Savi's warbler, grasshopper warbler, spotted crake, water rail, common snipe, common teal, garganey, little bittern, night heron, great bittern and marsh harrier) in 14 wetland complexes of variable size (3-55 k

Potentiality of close-range hyperspectral imaging as a tool for phenotyping : applying to wheat nitrogen concentration

Le phénotypage consiste à caractériser les plantes et leur comportement en vue de la sélection génétique. Cette étude a évalué le potentiel de l'imagerie hyperspectrale de proximité pour répondre à ces besoins. Elle s'appuie sur le lien existant entre la physiologie des plantes et leurs propriétés optiques. Cette étude a montré qu'il est possible de retrouver la réflectance des feuilles en dépit d'un éclairage naturel variable. La procédure de correction mise en place permet de retrouver la réflectance vraie de feuilles à plat et introduit un effet additif (dû à la réflexion spéculaire), un effet multiplicatif (dû au niveau d'éclairement) et un effet non linéaire (dû aux réflexions multiples) sur les feuilles inclinées des plantes au champ. Cependant, nous avons montré également que, grâce à des pré-traitements des spectres adéquats et à la PLS (Partial Least Square regression), la concentration en azote est accessible à partir de la réflectance (400-1000~nm) de feuilles fraîches sur pied. L'étude de spectres simulés a montré que la non prise en compte des réflexions multiples dans l'étalonnage d'un modèle conduisait à une surestimation de la concentration en azote des feuilles subissant des réflexions multiples. Enfin, cette étude a illustré l'intérêt de l'imagerie hyperspectrale de proximité par rapport à la spectrométrie ponctuelle. Le fait d'avoir une image, combiné à la haute résolution spatiale permet d'obtenir des données plus représentatives de la parcelle et de calculer une vitesse de fermeture de couvert. La réalisation de cartographies d'azote permet de suivre la concentration en azote dans différents étages foliaires ou parties d'une même feuille.Henotyping consists in characterising plants and their behavior with the aim of the genetic selection. This study estimated the potential of the close-range hyperspectral imaging to meet these needs. It leans on the link existing between plant physiology and their optical properties. This study showed that it is possible to find leaf reflectance in spite of a variable natural lighting. The developed correction procedure allows finding the true reflectance of flat leaves and introduces an additive effect (due to specular reflection), a multiplicative effect (due to illumination level) and a not linear effect (due to the multiple reflections) on inclinated leaves of plants in the field. However, we also showed that, thanks to adequate preprocessing of the spectra and to PLS (Partial Least Square regression), the nitrogen concentration is accessible from the reflectance (400-1000~nm) of fresh leaves on standing plants. The study of simulated spectra showed that the not consideration of the multiple reflections in the calibration of a model lead to an overestimation of the nitrogen concentration leaves undergoing multiple reflections. Finally, this study illustrated the interest of close-range hyperspectral imaging with regard to the punctual spectrometry. The fact of having an image, combined with the high spatial resolution allows to obtain more representative data of the plot and to calculate a speed of cover closure. Nitrogen mappings allow following the nitrogen concentration in various leaf level or parts of the same leaf

Potentiel de l'imagerie hyperspectrale de proximité comme outil de phénotypage (application à la concentration en azote du blé)

Le phénotypage consiste à caractériser les plantes et leur comportement en vue de la sélection génétique. Cette étude a évalué le potentiel de l'imagerie hyperspectrale de proximité pour répondre à ces besoins. Elle s'appuie sur le lien existant entre la physiologie des plantes et leurs propriétés optiques. Cette étude a montré qu'il est possible de retrouver la réflectance des feuilles en dépit d'un éclairage naturel variable. La procédure de correction mise en place permet de retrouver la réflectance vraie de feuilles à plat et introduit un effet additif (dû à la réflexion spéculaire), un effet multiplicatif (dû au niveau d'éclairement) et un effet non linéaire (dû aux réflexions multiples) sur les feuilles inclinées des plantes au champ. Cependant, nous avons montré également que, grâce à des pré-traitements des spectres adéquats et à la PLS (Partial Least Square regression), la concentration en azote est accessible à partir de la réflectance (400-1000~nm) de feuilles fraîches sur pied. L'étude de spectres simulés a montré que la non prise en compte des réflexions multiples dans l'étalonnage d'un modèle conduisait à une surestimation de la concentration en azote des feuilles subissant des réflexions multiples. Enfin, cette étude a illustré l'intérêt de l'imagerie hyperspectrale de proximité par rapport à la spectrométrie ponctuelle. Le fait d'avoir une image, combiné à la haute résolution spatiale permet d'obtenir des données plus représentatives de la parcelle et de calculer une vitesse de fermeture de couvert. La réalisation de cartographies d'azote permet de suivre la concentration en azote dans différents étages foliaires ou parties d'une même feuille.Henotyping consists in characterising plants and their behavior with the aim of the genetic selection. This study estimated the potential of the close-range hyperspectral imaging to meet these needs. It leans on the link existing between plant physiology and their optical properties. This study showed that it is possible to find leaf reflectance in spite of a variable natural lighting. The developed correction procedure allows finding the true reflectance of flat leaves and introduces an additive effect (due to specular reflection), a multiplicative effect (due to illumination level) and a not linear effect (due to the multiple reflections) on inclinated leaves of plants in the field. However, we also showed that, thanks to adequate preprocessing of the spectra and to PLS (Partial Least Square regression), the nitrogen concentration is accessible from the reflectance (400-1000~nm) of fresh leaves on standing plants. The study of simulated spectra showed that the not consideration of the multiple reflections in the calibration of a model lead to an overestimation of the nitrogen concentration leaves undergoing multiple reflections. Finally, this study illustrated the interest of close-range hyperspectral imaging with regard to the punctual spectrometry. The fact of having an image, combined with the high spatial resolution allows to obtain more representative data of the plot and to calculate a speed of cover closure. Nitrogen mappings allow following the nitrogen concentration in various leaf level or parts of the same leaf.MONTPELLIER-SupAgro La Gaillarde (341722306) / SudocSudocFranceF

Neuroanatomie du langage (les réseaux de la lecture)

CAEN-BU Sciences et STAPS (141182103) / SudocSudocFranceF

Toxicité rénale des antiangiogéniques [Renal toxicity of anti-VEGF (corrected) targeted therapies].

International audienceFor a few years, new targeted therapies have been used for metastatic cancers, targeting VEGF and its receptors and improving patients' survival for metastatic carcinoma (kidney, GIST, breast, colorectal). The objective of these treatments is to block either circulating VEGF (bevacizumab; VEGF-Trap), or tyrosine kinase receptors (especially the VEGF receptor) (sorafenib, sunitinib, brivanib, imatinib, etc.). Indeed, VEGF stimulates endothelial cell proliferation and then tumour growth and metastasis. However, all these antiangiogenic drugs share similar side effects, most frequently gastrointestinal disturbance, skin toxicity and hypertension. Hypertension seems to be especially frequent in case of good response. Renal side effects have probably been underestimated in the first place and their exact frequency is not known, needing some specific trials and registries. Proteinuria, thrombotic microangiopathies and acute renal failures have been reported: renal biopsies might be necessary for precise evaluation of renal damages. Physiopathology seems very close to preeclampsia. Good collaboration between oncologists, nephrologists and cardiologists is therefore crucial in order to continue these targeted therapies safely for the patients