315 research outputs found
Rare incidence of methotrexate-specific lesions in liver biopsy of patients with arthritis and elevated liver enzymes
PAX3-NCOA1 alveolar rhabdomyosarcoma of the tongue: A rare entity with challenging diagnosis and management.
AbstractAlveolar rhabdomyosarcoma (ARMS) is associated with PAX3/PAX7‐FOXO1 fusion, which confers specific clinic and biologic characteristics with inferior outcomes. A minority of tumors still histologically classified as "true" ARMS lack the canonical PAX‐FOXO1 fusion but have new molecular alterations. We present the first case of PAX3‐NCOA1 ARMS with clinical data and follow‐up in a two‐year‐old girl with ARMS of the tongue and nodal extension, treated with chemotherapy, hemi glossectomy, lymph node dissection, and brachytherapy to conserve oral function and limit long‐term sequelae. Given the rarity of such variant fusion in ARMS, international collaboration is required to evaluate its prognostic value
Identification and characterization of human Mex-3 proteins, a novel family of evolutionarily conserved RNA-binding proteins differentially localized to processing bodies
In Caenorhabditis elegans, the Mex-3 protein is a translational regulator that specifies the posterior blastomere identity in the early embryo and contributes to the maintenance of the germline totipotency. We have now identified a family of four homologous human Mex-3 genes, called hMex-3A to -3D that encode proteins containing two heterogeneous nuclear ribonucleoprotein K homology (KH) domains and one carboxy-terminal RING finger module. The hMex-3 are phosphoproteins that bind RNA through their KH domains and shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway. Our analysis further revealed that hMex-3A and hMex-3B, but not hMex-3C, colocalize with both the hDcp1a decapping factor and Argonaute (Ago) proteins in processing bodies (P bodies), recently characterized as centers of mRNA turnover. Taken together, these findings indicate that hMex-3 proteins constitute a novel family of evolutionarily conserved RNA-binding proteins, differentially recruited to P bodies and potentially involved in post-transcriptional regulatory mechanisms
A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors
Cancer models; Paediatric cancerModelos de cáncer; Cáncer pediátricoModels de càncer; Càncer pediàtricPediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies.This work was supported by grants from Fondation Gustave Roussy; Fédération Enfants Cancers et Santé, Société Française de lutte contre les Cancers et les leucémies de l’Enfant et l’adolescent (SFCE), Association AREMIG and Thibault BRIET; Parrainage médecin-chercheur of Gustave Roussy; INSERM; Canceropôle Ile-de-France; Ligue Nationale Contre le Cancer (Equipe labellisée); Fondation ARC for the European projects ERA-NET on Translational Cancer Research (TRANSCAN 2) Joint Transnational Call 2014 (JTC 2014) ‘Targeting Of Resistance in PEDiatric Oncology (TORPEDO)’, ERA-NET TRANSCAN JTC 2014 (TRAN201501238), and TRANSCAN JTC 2017 (TRANS201801292); Agence Nationale de la Recherche (ANR-10-EQPX-03, Institut Curie Génomique d’Excellence (ICGex); IMI ITCC-P4; The Child Cancer Research Foundation (CCRF), Cancer Council Western Australia (CCWA); PAIR-Pédiatrie/CONECT-AML (INCa-ARC-LIGUE_11905 and Association Laurette Fugain), Ligue contre le cancer (Equipe labellisée, since 2016), OPALE Carnot institute; Dell; Fondation Bristol-Myers Squibb; Association Imagine for Margo; Association Manon Hope; L’Etoile de Martin; La Course de l’Espoir; M la vie avec Lisa; ADAM; Couleur Jade; Dans les pas du Géant; Courir pour Mathieu; Marabout de Ficelle; Olivier Chape; Les Bagouz à Manon; Association Hubert Gouin Enfance et Cancer; Les Amis de Claire; Kurt-und Senta Hermann Stiftung; Holcim Stiftung Wissen; Gertrud-Hagmann-Stiftung für Malignom-Forschung; Heidi Ras Grant Forschungszentrum fürs Kind; Children’s Liver Tumor European Research Network (ChiLTERN) EU H2020 projet (668596); Fundación FERO and the Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Sassella-Stiftung, Berger-Janser Stiftung and Krebsliga Zürich, Deutschland Gemeindienst e.V. and others from Barcelona and province, and No Limits Contra el Cáncer Infantil Association
Hepatocellular Carcinoma Displays Distinct DNA Methylation Signatures with Potential as Clinical Predictors
BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption). Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis
Expression of VE-Cadherin in Peritubular Endothelial Cells during Acute Rejection after Human Renal Transplantation
Genes involved in acute rejection (AR) after organ transplantation remain to be further elucidated. In a previous work we have demonstrated the under-expression of VE-Cadherin by endothelial cells (EC) in AR following murine and human heart transplantation. Serial sections from 15 human kidney Banff-graded transplant biopsies were examined for the presence of VE-Cadherin and CD34 staining by immunohistochemistry (no AR (n = 5), AR grade IA (n = 5), or AR grade IIA (n = 5)).
Quantification of peritubular EC staining were evaluated and results were expressed by the percentage of stained cells per surface analysed. There was no difference in CD34 staining between the 3 groups. VE-Cadherin expression was significantly reduced in AR Grade IIA when compared to no AR (P = .01) and to AR grade IA (P = .02). This study demonstrates a reduced VE-Cadherin expression by EC in AR after renal transplantation. The down-regulation of VE-Cadherin may strongly participate in human AR
PPARγ contributes to PKM2 and HK2 expression in fatty liver
Rapidly proliferating cells promote glycolysis in aerobic conditions, to increase growth rate. Expression of specific glycolytic enzymes, namely pyruvate kinase M2 and hexokinase 2, concurs to this metabolic adaptation, as their kinetics and intracellular localization favour biosynthetic processes required for cell proliferation. Intracellular factors regulating their selective expression remain largely unknown. Here we show that the peroxisome proliferator-activated receptor gamma transcription factor and nuclear hormone receptor contributes to selective pyruvate kinase M2 and hexokinase 2 gene expression in PTEN-null fatty liver. Peroxisome proliferator-activated receptor gamma expression, liver steatosis, shift to aerobic glycolysis and tumorigenesis are under the control of the Akt2 kinase in PTEN-null mouse livers. Peroxisome proliferator-activated receptor gamma binds to hexokinase 2 and pyruvate kinase M promoters to activate transcription. In vivo rescue of peroxisome proliferator-activated receptor gamma activity causes liver steatosis, hypertrophy and hyperplasia. Our data suggest that therapies with the insulin-sensitizing agents and peroxisome proliferator-activated receptor gamma agonists, thiazolidinediones, may have opposite outcomes depending on the nutritional or genetic origins of liver steatosis
人型ロボットのための物理的制約に基づいた時間的ならびに空間的動作スタイルの模倣
学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 相澤 清晴, 東京大学教授 池内 克史, 東京大学教授 佐藤 洋一, 東京大学教授 苗村 健, 東京大学准教授 大石 岳史, 東京大学准教授 山崎 俊彦University of Tokyo(東京大学
Predictive and prognostic value of CT based radiomics signature in locally advanced head and neck cancers patients treated with concurrent chemoradiotherapy or bioradiotherapy and its added value to Human Papillomavirus status
- …