49 research outputs found
The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival
Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ.ARC -Fondation ARC pour la Recherche sur le Cancer(EML20120904843
L'amylose en Nouvelle-Calédonie (une premiÚre approche)
L'amylose est une maladie rare dans les pays occidentaux comme la France mĂ©tropolitaine mais reste relativement frĂ©quente - particuliĂšrement dans sa forme AA - dans les pays en voie de dĂ©veloppement. C'est aussi le cas dans les territoires français du Pacifique Sud que sont la Nouvelle-CalĂ©donie et Wallis et Futuna, comme le dĂ©montre cette Ă©tude rĂ©trospective recensant tous les cas diagnostiquĂ©s dans ces territoires entre janvier 2001 et dĂ©cembre 2006 inclus, chez des adultes. En effet, l'incidence calĂ©donienne se rĂ©vĂšle ĂȘtre 5 fois supĂ©rieure Ă celle de mĂ©tropole, et plus de 85% des cas sont des amyloses de type AA. Cette Ă©tude a permis de dresser un Ă©tat des lieux de l'Ă©pidĂ©miologie de l'amylose dans ces territoires en prĂ©cisant le profil de la population concernĂ©e, les types d'amyloses retrouvĂ©s, leur Ă©tiologie, les modalitĂ©s de diagnostic, l'Ă©volution et la survie ainsi que la cause des dĂ©cĂšs. Un accent particulier a Ă©tĂ© mis sur la population des patients porteurs de bronchectasies puisqu'ils reprĂ©sentent la moitiĂ© des 59 patients inclus dans l'Ă©tude ; nous avons ainsi essayĂ© de dĂ©terminer des facteurs pronostiques de survenue d'amylose au cours de l'Ă©volution des dilatations des bronches. Notre attention s'est finalement portĂ©e plus particuliĂšrement sur les patients qui ont nĂ©cessitĂ© une prise en charge en dialyse chronique, cette derniĂšre reprĂ©sentant une des complications les plus lourdes de l'amylose en terme de pĂ©nibilitĂ© et de coĂ»t.CLERMONT FD-BCIU-SantĂ© (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Apport de l'immunohistochimie dans le diagnostic des adénomes atypiques de la thyroïde (étude rétrospective comparative de 138 cas dont 30 adénomes atypiques (Centre Anticancéreux J. Perrin et CHU de Clermont-Ferrand)
CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Ischemia reperfusion injury in kidney transplantation
International audienceAbstract Rationale: Kidney transplantation is considered the best treatment for patients with end stage renal disease. Ischemia- reperfusion injury (IRI) is an evitable event after deceased donor transplantation and influences short term and long term graft outcome. Few data on IRI's histology in the setting of kidney transplantation are available in the literature despite its frequency and its severity. Patient concerns: A 64-year-old patient was admitted for his 1st kidney transplantation. There were no pre-existing immunization. The surgery proceeded without complications; with cold ischemia estimated at 37âh 50âmin and warm ischemia at 44âmin. The immunosuppression protocol was as follows: induction by thymoglobulins, mycophelonate mofetil, corticosteroids. Few hours after transplantation, the patient remained anuric and the biological assessment highlighted in addition to renal failure, hyperlactatemia at 5âmmol/L and a high increase in lactate deshydrogenase (LDH) at 5239âU/L. An abdominopelvic angio-scanner was performed urgently to eliminate the hypothesis of thrombosis of the artery or vein of the graft. A kidney biopsy was performed the day after the transplant and revealed massive lesions of acute tubular necrosis including apoptosis, autophagy-associated cell death, and necrosis. Microvascular dysfunction with increased vascular permeability and endothelial cell inflammation were also present. Activation of coagulation is represented by thrombi in the lumens of the glomerular capillaries. Diagnosis: The diagnosis was ischemia reperfusion injury responsible for delayed graft function (DGF). Interventions: Immunosuppressive regimen was delayed use of calcineurin inhibitors, mycophenolate mofetil, and corticosteroids. Outcomes: At 1 year post transplant, the patient has a renal autonomy with a graft function stable and physiological proteinuria. Lessons: The main clinical consequences of IRI in kidney transplant are DGF, acute and chronic graft rejection, and chronic graft dysfunction. Reducing IRI is one of the most relevant challenge in kidney transplantation
Membranous Nephropathy and Intrarenal Extramedullary Hematopoiesis in a Patient With Myelofibrosis
International audienc
Le taux prĂ©opĂ©ratoire dâIL-6 sĂ©rique comme marqueur prĂ©dictif dâatteinte mĂ©diastinale dans le cancer bronchique non Ă petites cellules de stage Ic
Session ThoraciqueObjectif : Le cancer bronchique non Ă petites cellules (CBNPC) est la premiĂšre cause de mortalitĂ© par cancer dans le monde. Son pronostic dĂ©pend de son stade TNM. Une atteinte ganglionnaire mĂ©diastinale est un critĂšre de mauvais pronostic et les patients cN2 ne tirent que rarement bĂ©nĂ©fice dâune exĂ©rĂšse chirurgicale. Le but de cette Ă©tude Ă©tait dâĂ©valuer la pertinence de marqueurs biologiques qui pourraient traduire lâagressivitĂ© tumorale.MĂ©thode : Nous avons effectuĂ© une Ă©tude monocentrique prospective sur 42 patients cT1N0 qui ont bĂ©nĂ©ficiĂ© dâune lobectomie avec curage ganglionnaire mĂ©diastinal radical entre mai 2001 et juillet 2003 pour CBNPC. Avant lâintervention, nous avons dosĂ© 4 cytokines dans le sang : IL-6, IL-10, TGFB et VEGF. Le stade clinique Ă©tait Ă©valuĂ© par scanner thoracique injectĂ©, le TEP-scanner nâĂ©tait pas disponible en routine. Nous avons comparĂ© ces taux de cytokines Ă ceux de 38 sujets contrĂŽles.RĂ©sultat : Le taux dâIL-6 sĂ©rique Ă©tait significativement plus Ă©levĂ© dans le groupe des opĂ©rĂ©s comparĂ©s aux sujets sains (33,45 ± 92,9 pg/ml vs 2,10 ± 3,2 pg/ml, p 9 pg/ml (p = 0,0039) et la lymphopĂ©nie (p = 0,026). En analyse multivariĂ©e, le taux dâIL-6 Ă©tait un facteur pronostic indĂ©pendant (p = 0,0063, HR = 3,7 [1,45-9,44]). Ce taux dâIL-6 nâĂ©tait pas corrĂ©lĂ© Ă la taille de la tumeur (p = 0,98), mais clairement associĂ© Ă lâatteinte ganglionnaire (p = 0,002).Conclusion : LâIL-6 est une cytokine plĂ©iotrope impliquĂ©e dans la rĂ©ponse immunitaire, lâangiogenĂšse et lâinflammation. Elle est connue comme Ă©tant un marqueur dâagressivitĂ© tumorale dans certaines hĂ©mopathies malignes ou dâautres cancers solides. Nos rĂ©sultats suggĂšrent clairement que le taux dâIL-6 peut ĂȘtre considĂ©rĂ© comme un marqueur dâatteinte ganglionnaire dans les stades prĂ©coces de CBNPC indĂ©pendamment de la taille tumorale. La corrĂ©lation de ce taux dâIL-6 au TEP-scanner doit ĂȘtre Ă©valuĂ©e
Role of STAT3 in Genesis and Progression of Human Malignant Gliomas
International audienceSignal Transducer and Activator of Transcription 3 (STAT3) is aberrantly activated in glioblastoma and has been identified as a relevant therapeutic target in this disease and many other human cancers. After two decades of intensive research, there is not yet any approved STAT3-based glioma therapy. In addition to the canonical activation by tyrosine 705 phosphorylation, concordant reports described a potential therapeutic relevance of other post-translational modifications including mainly serine 727 phosphorylation. Such reports reinforce the need to refine the strategy of targeting STAT3 in each concerned disease. This review focuses on the role of serine 727 and tyrosine 705 phosphorylation of STAT3 in glioma. It explores their contribution to glial cell transformation and to the mechanisms that make glioma escape to both immune control and standard treatment
Hyalinose segmentaire et focale collapsante secondaire au cytomĂ©galovirus : Ă Â propos dâun cas
International audienc