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Accueil Nota Bene Cancer V2 Numéro 128 du 20 March 2012 Dépistage, diagnostic et pronostic

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Nota Bene Cancer Numéro 128 du 20 March 2012 RSS

Dépistage, diagnostic et pronostic

Découverte de technologies et de biomarqueurs

Menée sur 101 cas de gliome astrocytaire diffus de bas grade, cette étude montre que, en association avec des caractéristiques du développement névroglique, des mutations du gène IDH permettent d'identifier des sous-types de la maladie

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    Menée sur 101 cas de gliome astrocytaire diffus de bas grade, cette étude montre que, en association avec des caractéristiques du développement névroglique, des mutations du gène IDH permettent d'identifier des sous-types de la maladie

    “IDH Mutation and Neuroglial Developmental Features Define Clinically Distinct Subclasses of Lower-Grade Diffuse Astrocytic Glioma”

    • Gorovets, Daniel;Kannan, Kasthuri;Shen, Ronglai;Kastenhuber, Edward;Islamdoust, Nasrin;Campos, Carl;Pentsova, Elena;Jhanwar, Suresh C.;Heguy, Adriana;Mellinghoff, Ingo K.;Chan, Timothy A.;Huse, Jason T.

    Purpose: Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notable clinical heterogeneity. Accordingly, we sought to identify and characterize clinically relevant molecular subclasses of lower-grade diffuse astrocytic gliomas. Experimental Design: We performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. Results: We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and ...


Mots clés : Système nerveux central; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Cette étude montre la faisabilité d'une approche faisant appel à des souris génétiquement modifiées, en parallèle à un essai clinique évaluant l'ajout de selumetinib au docetaxel dans le cancer du poumon avec mutations KRAS, pour identifier des biomarqueurs génétiques associés à la réponse thérapeutique

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    Cette étude montre la faisabilité d'une approche faisant appel à des souris génétiquement modifiées, en parallèle à un essai clinique évaluant l'ajout de selumetinib au docetaxel dans le cancer du poumon avec mutations KRAS, pour identifier des biomarqueurs génétiques associés à la réponse thérapeutique

    “A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response”

    • Chen, Zhao;Cheng, Katherine;Walton, Zandra;Wang, Yuchuan;Ebi, Hiromichi;Shimamura, Takeshi;Liu, Yan;Tupper, Tanya;Ouyang, Jing;Li, Jie;Gao, Peng;Woo, Michele S.;Xu, Chunxiao;Yanagita, Masahiko;Altabef, Abigail;Wang, Shumei;Lee, Charles;Nakada, Yuji;Pena, Christopher G.;Sun, Yanping;Franchetti, Yoko;Yao, Catherine;Saur, Amy;Cameron, Michael D.;Nishino, Mizuki;Hayes, D. Neil;Wilkerson, Matthew D.;Roberts, Patrick J.;Lee, Carrie B.;Bardeesy, Nabeel;Butaney, Mohit;Chirieac, Lucian R.;Costa, Daniel B.;Jackman, David;Sharpless, Norman E.;Castrillon, Diego H.;Demetri, George D.;Janne, Pasi A.;Pandolfi, Pier Paolo;Cantley, Lewis C.;Kung, Andrew L.;Engelman, Jeffrey A.;Wong, Kwok-Kin

    Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a ‘co-clinical’ trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244)10 increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly ...


Mots clés : Poumon; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Cette étude évalue l'intérêt de diverses nanoparticules d'or pour l'imagerie fonctionnelle à haute résolution du réseau vasculaire tumoral

  • Gold nanoparticles as high-resolution X-ray imaging contrast agents for the analysis of tumor-related micro-vasculature
    Journal of Nanobiotechnology, Vol. 10 (1), pp. 10, 2012 (article en libre accès)
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    Cette étude évalue l'intérêt de diverses nanoparticules d'or pour l'imagerie fonctionnelle à haute résolution du réseau vasculaire tumoral

    “Gold nanoparticles as high-resolution X-ray imaging contrast agents for the analysis of tumor-related micro-vasculature”

    • Chien, Chia-Chi;Chen, H.;Lai, S.;Wu, Kang-Chao;Cai, Xiaoqing;Hwu, Y.;Petibois, Cyril;Chu, Y. s.;Margaritondo, G.

    BACKGROUND:Angiogenesis is widely investigated in conjunction with cancer development, in particular because of the possibility of early stage detection and of new therapeutic strategies. However, such studies are negatively affected by the limitations of imaging techniques in the detection of microscopic blood vessels (diameter 3-5 micron) grown under angiogenic stress. We report that synchrotron-based X-ray imaging techniques with very high spatial resolution can overcome this obstacle, provided that suitable contrast agents are used.RESULTS:We tested different contrast agents based on gold nanoparticles (AuNPs) for the detection of cancer-related angiogenesis by synchrotron microradiology, microtomography and high resolution X-ray microscopy. Among them only bare-AuNPs in conjunction with heparin injection provided sufficient contrast to allow in vivo detection of small capillary species (the smallest measured lumen diameters were 3-5 micron). The detected vessel density was 3-7 ...


Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Evaluation des technologies et des biomarqueurs

Cet article passe en revue les travaux récents sur les diverses modalités d'imagerie moléculaire pour la détection et le diagnostic du cancer du sein

  • Advances in molecular imaging for breast cancer detection and characterization
    Breast Cancer Research, Vol. 14 (2), pp. 206, 2012 (article en libre accès)
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    Cet article passe en revue les travaux récents sur les diverses modalités d'imagerie moléculaire pour la détection et le diagnostic du cancer du sein

    “Advances in molecular imaging for breast cancer detection and characterization”

    • Specht, Jennifer;Mankoff, David

    Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have lead to identification of new treatments for breast cancer patients. The ability to measure biologic processes without perturbing them in vivo allows for the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessing therapeutic targets, and evaluating responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer, focusing primarily on radionuclide-based methods.


Mots clés : Sein; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur des échantillons tumoraux prélevés sur 151 patientes atteintes d'un cancer du sein ER+ de stade I ou II, cette étude compare les performances de deux outils, PAM50 et Oncotype DX, pour estimer le pronostic de la maladie

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    Menée sur des échantillons tumoraux prélevés sur 151 patientes atteintes d'un cancer du sein ER+ de stade I ou II, cette étude compare les performances de deux outils, PAM50 et Oncotype DX, pour estimer le pronostic de la maladie

    “Agreement in Risk Prediction Between the 21-Gene Recurrence Score Assay (Oncotype DX®) and the PAM50 Breast Cancer Intrinsic Classifier™ in Early-Stage Estrogen Receptor–Positive Breast Cancer”

    • Kelly, Catherine M.;Bernard, Philip S.;Krishnamurthy, Savitri;Wang, Bailiang;Ebbert, Mark T.W.;Bastien, Roy R.L.;Boucher, Kenneth M.;Young, Elliana;Iwamoto, Takayuki;Pusztai, Lajos

    Abstract Purpose. To compare risk assignment by PAM50 Breast Cancer Intrinsic Classifier™ and Oncotype DX_Recurrence Score (RS) in the same population.Methods. RNA was extracted from 151 estrogen receptor (ER)+ stage I–II breast cancers and gene expression profiled using PAM50 “intrinsic” subtyping test.Results. One hundred eight cases had complete molecular information; 103 (95%) were classified as luminal A (n = 76) or luminal B (n = 27). Ninety-two percent (n = 98) had a low (n = 59) or intermediate (n = 39) RS. Among luminal A cancers, 70% had low (n = 53) and the remainder (n = 23) had an intermediate RS. Among luminal B cancers, nine were high (33%) and 13 were intermediate (48%) by the RS. Almost all cancers with a high RS were classified as luminal B (90%, n = 9). One high RS cancer was identified as basal-like and had low ER/ESR1 and low human epidermal growth factor receptor 2 (HER2) expression by quantitative polymerase chain reaction in both assays. The majority of ...


Mots clés : Sein; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Ces deux études évaluent l'association entre des mutations somatiques et le risque d'évolution d'un syndrome myélodysplasique en leucémie myéloïde aiguë, pour l'une, et la réponse thérapeutique à une chimiothérapie d'induction à haute dose dans la leucémie myéloïde aiguë, pour l'autre

  • Clonal Architecture of Secondary Acute Myeloid Leukemia
    New England Journal of Medicine, sous presse, 2012 (résumé)
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    Ces deux études évaluent l'association entre des mutations somatiques et le risque d'évolution d'un syndrome myélodysplasique en leucémie myéloïde aiguë, pour l'une, et la réponse thérapeutique à une chimiothérapie d'induction à haute dose dans la leucémie myéloïde aiguë, pour l'autre

    “Clonal Architecture of Secondary Acute Myeloid Leukemia”

    • Walter, Matthew J.;Shen, Dong;Ding, Li;Shao, Jin;Koboldt, Daniel C.;Chen, Ken;Larson, David E.;McLellan, Michael D.;Dooling, David;Abbott, Rachel;Fulton, Robert;Magrini, Vincent;Schmidt, Heather;Kalicki-Veizer, Joelle;O'Laughlin, Michelle;Fan, Xian;Grillot, Marcus;Witowski, Sarah;Heath, Sharon;Frater, John L.;Eades, William;Tomasson, Michael;Westervelt, Peter;DiPersio, John F.;Link, Daniel C.;Mardis, Elaine R.;Ley, Timothy J.;Wilson, Richard K.;Graubert, Timothy A.

    Background: The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic syndromes to secondary AML are not well understood. Methods: We performed whole-genome sequencing of seven paired samples of skin and bone marrow in seven subjects with secondary AML to identify somatic mutations specific to secondary AML. We then genotyped a bone marrow sample obtained during the antecedent myelodysplastic-syndrome stage from each subject to determine the presence or absence of the specific somatic mutations. We identified recurrent mutations in coding genes and defined the clonal architecture of each pair of samples from the myelodysplastic-syndrome stage and the secondary-AML stage, using the allele burden of hundreds of mutations. Results: Approximately 85% of bone marrow cells were clonal in the myelodysplastic-syndrome and secondary-AML samples, ...


  • Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia
    New England Journal of Medicine, sous presse, 2012 (résumé)
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    Ces deux études évaluent l'association entre des mutations somatiques et le risque d'évolution d'un syndrome myélodysplasique en leucémie myéloïde aiguë, pour l'une, et la réponse thérapeutique à une chimiothérapie d'induction à haute dose dans la leucémie myéloïde aiguë, pour l'autre

    “Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia”

    • Patel, Jay P. ; Gönen, Mithat ; Figueroa, Maria E. ; Fernandez, Hugo ; Sun, Zhuoxin ; Racevskis, Janis ; Van Vlierberghe, Pieter ; Dolgalev, Igor ; Thomas, Sabrena ; Aminova, Olga ; Huberman, Kety ; Cheng, Janice ; Viale, Agnes ; Socci, Nicholas D. ; Heguy, Adriana ; Cherry, Athena ; Vance, Gail ; Higgins, Rodney R. ; Ketterling, Rhett P. ; Gallagher, Robert E. ; Litzow, Mark ; van den Brink, Marcel R.M. ; Lazarus, Hillard M. ; Rowe, Jacob M. ; Luger, Selina ; Ferrando, Adolfo ; Paietta, Elisabeth ; Tallman, Martin S. ; Melnick, Ari ; Abdel-Wahab, Omar ; Levine, Ross L.

    Background: Acute myeloid leukemia (AML) is a heterogeneous disease with respect to presentation and clinical outcome. The prognostic value of recently identified somatic mutations has not been systematically evaluated in a phase 3 trial of treatment for AML. Methods: We performed a mutational analysis of 18 genes in 398 patients younger than 60 years of age who had AML and who were randomly assigned to receive induction therapy with high-dose or standard-dose daunorubicin. We validated our prognostic findings in an independent set of 104 patients. Results: We identified at least one somatic alteration in 97.3% of the patients. We found that internal tandem duplication in FLT3 (FLT3-ITD), partial tandem duplication in MLL (MLL-PTD), and mutations in ASXL1 and PHF6 were associated with reduced overall survival (P=0.001 for FLT3-ITD, P=0.009 for MLL-PTD, P=0.05 for ASXL1, and P=0.006 for PHF6); CEBPA and IDH2 mutations were associated with improved overall survival (P=0.05 for CEBPA ...


  • Profiles in Leukemia
    New England Journal of Medicine, sous presse, 2012 (éditorial en libre accès)
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    Ces deux études évaluent l'association entre des mutations somatiques et le risque d'évolution d'un syndrome myélodysplasique en leucémie myéloïde aiguë, pour l'une, et la réponse thérapeutique à une chimiothérapie d'induction à haute dose dans la leucémie myéloïde aiguë, pour l'autre

    “Profiles in Leukemia”

    • Godley, Lucy A.

    For years, scientists have postulated the evolution of a cancer as a series of acquired mutations and epigenetic alterations that accumulate in a progressive way, beginning with a single transformed cell. Within this process, subclones of cells develop that acquire new properties, giving cells advantages, such as the ability to resist chemotherapy or to metastasize. Two articles now provide experimental evidence for this model of cancer and a glimpse of how we may evaluate patients with cancer in the near future...


Mots clés : Leucémie; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Essais de technologies et de biomarqueurs dans un contexte clinique

Menée à partir d'échantillons tumoraux prélevés sur 3 992 patientes atteintes d'un cancer du sein de stade précoce et de type basal-like, cette étude montre qu'une infiltration tumorale par des lymphocytes T CD8+ est associée à un pronostic favorable

  • CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer
    Breast Cancer Research, Vol. 14 (2), pp. R48, 2012 (article en libre accès)
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    Menée à partir d'échantillons tumoraux prélevés sur 3 992 patientes atteintes d'un cancer du sein de stade précoce et de type basal-like, cette étude montre qu'une infiltration tumorale par des lymphocytes T CD8+ est associée à un pronostic favorable

    “CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer”

    • Liu, Shuzhen;Lachapelle, Jonathan;Leung, Samuel;Gao, Dongxia;Foulkes, William;Nielsen, Torsten

    INTRODUCTION:Tumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes.METHODS:Immunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival.RESULTS:Among 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and ...


Mots clés : Sein; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 29 patients atteints d'un cancer primitif ou récidivant de la prostate, cette étude compare la sensibilité et la spécificité d'une tomographie numérique par émission de positions à l'aide de choline C-11 et d'une lymphographie par résonance magnétique utilisant le ferumoxtran-10 pour détecter des micro-métastases ganglionnaires et individualiser le traitement

  • Value of PET/CT and MR Lymphography in Treatment of Prostate Cancer Patients with Lymph Node Metastases
    International journal of radiation oncology, biology, physics, sous presse, 2012 (résumé)
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    Menée sur 29 patients atteints d'un cancer primitif ou récidivant de la prostate, cette étude compare la sensibilité et la spécificité d'une tomographie numérique par émission de positions à l'aide de choline C-11 et d'une lymphographie par résonance magnétique utilisant le ferumoxtran-10 pour détecter des micro-métastases ganglionnaires et individualiser le traitement

    “Value of PET/CT and MR Lymphography in Treatment of Prostate Cancer Patients with Lymph Node Metastases”

    • Fortuin, Ansje S.;Deserno, Willem M. L. L. G.;Meijer, Hanneke J. M.;Jager, Gerrit J.;Takahashi, Satoru;Debats, Oscar A.;Reske, Sven N.;Schick, Christian;Krause, Bernd J.;van Oort, Inge;Witjes, Alfred J.;Hoogeveen, Yvonne L.;Th. van Lin, Emile N. J.;Barentsz, Jelle O.

    To determine the clinical value of two novel molecular imaging techniques: 11C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined. The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were ...


Mots clés : Prostate; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 110 patients atteints d'un adénocarcinome du poumon traité par résection, cette étude montre une association entre l'expression tumorale de la napsine A, une protéase à acide aspartique, et la survie globale des patients

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    Menée sur 110 patients atteints d'un adénocarcinome du poumon traité par résection, cette étude montre une association entre l'expression tumorale de la napsine A, une protéase à acide aspartique, et la survie globale des patients

    “Napsin A is an independent prognostic factor in surgically resected adenocarcinoma of the lung”

    • Lee, Jin Gu;Kim, Sewha;Shim, Hyo Sup

    Introduction : Napsin A is regarded as a marker of lung adenocarcinoma. However, no comprehensive analyses of napsin A-positive lung ADCs or the prognostic significance of napsin A expression have been reported to date. Methods : 110 primary lung adenocarcinoma cases were analyzed for clinicopathologic parameters, including overall survival, stage, histology, napsin A and TTF-1 expression, EGFR mutation, and ALK rearrangement. Results : Napsin A-positive adenocarcinomas were significantly more prevalent among tumors characterized as relatively small (p = 0.023), non-solid predominant (p < 0.001), non-mucinous/enteric (p < 0.001), positive for TTF-1 expression (p < 0.001), and positive for EGFR mutation (p = 0.001). Multivariate analysis of overall survival demonstrated that the absence of napsin A was an independent prognostic factor for reduced survival time (p = 0.002). Conclusion : Clinicopathologic characteristics associated with napsin A-positive lung ADC are similar to and ...


Mots clés : Poumon; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

A partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 289 patientes atteintes d'un cancer primitif de l'ovaire, cette étude montre que le niveau d'expression tumorale de la chimiokine CXCL12 est associé à un pronostic défavorable

  • The chemokine, CXCL12, is an independent predictor of poor survival in ovarian cancer
    British Journal of Cancer, sous presse, 2012 (résumé)
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    A partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 289 patientes atteintes d'un cancer primitif de l'ovaire, cette étude montre que le niveau d'expression tumorale de la chimiokine CXCL12 est associé à un pronostic défavorable

    “The chemokine, CXCL12, is an independent predictor of poor survival in ovarian cancer”

    • Popple, A.;Durrant, L. G.;Spendlove, I.;Rolland, P.;Scott, I. V.;Deen, S.;Ramage, J. M.

    Background : The chemokine CXCL12 and its cognate receptor, CXCR4, have been implicated in numerous tumour types where expression promotes tumour growth, angiogenesis, metastasis and suppresses tumour immunity. Methods : Using a tissue microarray of 289 primary ovarian cancers coupled to a comprehensive database of clinicopathological variables, the expression of CXCL12 and CXCR4 was assessed by immunohistochemistry and its impact in terms of survival and clinicopathological variables was determined. Results :Patients whose tumours expressed high levels of CXCL12 had significantly poorer survival (P=0.026) than patients whose tumours failed to produce this chemokine. Lack of CXCL12 expression within tumours was associated with a 51-month survival advantage for patients when compared with patients whose tumours expressed high levels of CXCL12. FIGO stage, adjuvant chemotherapy and the absence of macroscopic disease after surgery were all shown to predict prognosis independently of each ...


Mots clés : Ovaire; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 1 064 patients atteints d'un cancer colorectal et sur 1 064 témoins, cette étude de cohorte, couplée à l'étude EPIC, évalue l'association entre le niveau sérique prédiagnostique de biomarqueurs du stress oxydant (métabolites de l'oxygène réactif) et le risque de développer la maladie

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    Menée sur 1 064 patients atteints d'un cancer colorectal et sur 1 064 témoins, cette étude de cohorte, couplée à l'étude EPIC, évalue l'association entre le niveau sérique prédiagnostique de biomarqueurs du stress oxydant (métabolites de l'oxygène réactif) et le risque de développer la maladie

    “Biomarkers of Oxidative Stress and Risk of Developing Colorectal Cancer: A Cohort-nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition”

    • Leufkens, Anke M.;van Duijnhoven, Fränzel J. B.;Woudt, Sjoukje H. S.;Siersema, Peter D.;Jenab, Mazda;Jansen, Eugene H. J. M.;Pischon, Tobias;Tjønneland, Anne;Olsen, Anja;Overvad, Kim;Boutron-Ruault, Marie Christine;Clavel-Chapelon, Françoise;Morois, Sophie;Palli, Domenico;Pala, Valeria;Tumino, Rosario;Vineis, Paolo;Panico, Salvatore;Kaaks, Rudolf;Lukanova, Annekatrin;Boeing, Heiner;Aleksandrova, Krasimira;Trichopoulou, Antonia;Trichopoulos, Dimitrios;Dilis, Vardis;Peeters, Petra H.;Skeie, Guri;González, Carlos A.;Argüelles, Marcial;Sánchez, María-José;Dorronsoro, Miren;Huerta, José María;Ardanaz, Eva;Hallmans, Göran;Palmqvist, Richard;Khaw, Kay-Tee;Wareham, Nick;Allen, Naomi E.;Crowe, Francesca L.;Fedirko, Veronika;Norat, Teresa;Riboli, Elio;Bueno-de-Mesquita, H. Bas

    Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992–2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRRadj) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRRadj = 1.89, 95% CI: 1.06, 3.36) and distal (IRRadj = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer ...


Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Ressources et infrastructures (Dépistage)

Menée sur 162 388 hommes d'âge compris entre 55 et 69 ans à leur inclusion dans un essai européen de dépistage du cancer de la prostate à l'aide du dosage du PSA, cette étude évalue l'effet du dépistage sur la mortalité par cancer de la prostate et la mortalité globale après une durée médiane de suivi de 11 ans

  • Prostate-Cancer Mortality at 11 Years of Follow-up
    New England Journal of Medicine, Vol. 366 (11), pp. 981-990, 2012 (résumé)
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    Menée sur 162 388 hommes d'âge compris entre 55 et 69 ans à leur inclusion dans un essai européen de dépistage du cancer de la prostate à l'aide du dosage du PSA, cette étude évalue l'effet du dépistage sur la mortalité par cancer de la prostate et la mortalité globale après une durée médiane de suivi de 11 ans

    “Prostate-Cancer Mortality at 11 Years of Follow-up”

    • Schröder, Fritz H.;Hugosson, Jonas;Roobol, Monique J.;Tammela, Teuvo L.J.;Ciatto, Stefano;Nelen, Vera;Kwiatkowski, Maciej;Lujan, Marcos;Lilja, Hans;Zappa, Marco;Denis, Louis J.;Recker, Franz;Páez, Alvaro;Määttänen, Liisa;Bangma, Chris H.;Aus, Gunnar;Carlsson, Sigrid;Villers, Arnauld;Rebillard, Xavier;van der Kwast, Theodorus;Kujala, Paula M.;Blijenberg, Bert G.;Stenman, Ulf-Hakan;Huber, Andreas;Taari, Kimmo;Hakama, Matti;Moss, Sue M.;de Koning, Harry J.;Auvinen, Anssi

    Background: Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up. Methods: The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer. Results: After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. ...


  • New Data on Prostate-Cancer Mortality after PSA Screening
    New England Journal of Medicine, Vol. 366 (11), pp. 1047-1048, 2012 (éditorial)
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    Menée sur 162 388 hommes d'âge compris entre 55 et 69 ans à leur inclusion dans un essai européen de dépistage du cancer de la prostate à l'aide du dosage du PSA, cette étude évalue l'effet du dépistage sur la mortalité par cancer de la prostate et la mortalité globale après une durée médiane de suivi de 11 ans

    “New Data on Prostate-Cancer Mortality after PSA Screening”

    • Miller, Anthony B.

    After 11 years of follow-up in the European Randomized Study of Screening for Prostate Cancer (ERSPC), Schröder et al.1 report in this issue of the Journal that there has been little change in the apparent benefit of screening men for levels of prostate-specific antigen (PSA), as compared with an earlier report.2 Both studies showed a relative reduction of 21% in the rate of death from prostate cancer in the screening group, as compared with the control group. This reduction was achieved after considerable use of resources: in order to prevent one death from prostate cancer at 11 years of follow-up, . . .


Mots clés : Prostate; Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

Cet article présente la mise à jour des recommandations de l'American Cancer Society en matière de dépistage du cancer du col de l'utérus

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    Cet article présente la mise à jour des recommandations de l'American Cancer Society en matière de dépistage du cancer du col de l'utérus

    “American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer”

    • Saslow, Debbie;Solomon, Diane;Lawson, Herschel W.;Killackey, Maureen;Kulasingam, Shalini L.;Cain, Joanna;Garcia, Francisco A. R.;Moriarty, Ann T.;Waxman, Alan G.;Wilbur, David C.;Wentzensen, Nicolas;Downs, Levi S.;Spitzer, Mark;Moscicki, Anna-Barbara;Franco, Eduardo L.;Stoler, Mark H.;Schiffman, Mark;Castle, Philip E.;Myers, Evan R.

    An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012. © 2012 American Cancer Society.


  • Testing for cervical cancer
    CA: A Cancer Journal for Clinicians, sous presse, 2012 (communiqué de presse)
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    Cet article présente la mise à jour des recommandations de l'American Cancer Society en matière de dépistage du cancer du col de l'utérus

    “Testing for cervical cancer”


Mots clés : Col de l'utérus; Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

Cet article présente la mise à jour des recommandations d'un groupe d'experts américains, l'U.S. Preventive Services Task Force, en matière de dépistage du cancer du col de l'utérus

  • Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement
    Annals of Internal Medicine, sous presse, 2012 (article en libre accès)
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    Cet article présente la mise à jour des recommandations d'un groupe d'experts américains, l'U.S. Preventive Services Task Force, en matière de dépistage du cancer du col de l'utérus

    “Screening for Cervical Cancer: U.S. Preventive Services Task Force Recommendation Statement”

    • Moyer, Virginia A.

    Description: Update of the 2003 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for cervical cancer.Methods: The USPSTF reviewed new evidence on the comparative test performance of liquid-based cytology and the benefits and harms of human papillomavirus (HPV) testing as a stand-alone test or in combination with cytology. In addition to the systematic evidence review, the USPSTF commissioned a decision analysis to help clarify the age at which to begin and end screening, the optimal interval for screening, and the relative benefits and harms of different strategies for screening (such as cytology and co-testing).Recommendations: This recommendation statement applies to women who have a cervix, regardless of sexual history. This recommendation statement does not apply to women who have received a diagnosis of a high-grade precancerous cervical lesion or cervical cancer, women with in utero exposure to diethylstilbestrol, or women who are ...


  • Cervical Cancer Screening: Primum Non Nocere
    Annals of Internal Medicine, sous presse, 2012 (éditorial en libre accès)
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    Cet article présente la mise à jour des recommandations d'un groupe d'experts américains, l'U.S. Preventive Services Task Force, en matière de dépistage du cancer du col de l'utérus

    “Cervical Cancer Screening: Primum Non Nocere”

    • Kizer, Nora ; Peipert, Jeffrey F.


Mots clés : Col de l'utérus; Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

Cet article passe en revue les travaux récents sur l'importance de la prise en compte de l'hétérogénéité du microenvironnement tumoral pour la prise en charge personnalisée des cancers

  • Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy
    Cancer Research, sous presse, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur l'importance de la prise en compte de l'hétérogénéité du microenvironnement tumoral pour la prise en charge personnalisée des cancers

    “Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy”

    • Swartz, Melody A;Iida, Noriho;Roberts, Edward W;Sangaletti, Sabina;Wong, Melissa H;Yull, Fiona E;Coussens, Lisa M;DeClerck, Yves A.

    The tumor microenvironment (TME) consists of cells, soluble factors, signaling molecules, extracellular matrix and mechanical cues that can promote neoplastic transformation, support tumor growth and invasion, protect the tumor from host immunity, foster therapeutic resistance, and provide niches for dormant metastases to thrive. An AACR special conference held on November 3-6, 2011, addressed five emerging concepts in our understanding of the TME: its dynamic evolution, how it is educated by tumor cells, pathways of communication between stromal and tumor cells, immunomodulatory roles of the lymphatic system, and contribution of the intestinal microbiota. These discussions raised critical questions on how to include the analysis of the TME in personalized cancer diagnosis and treatment.


Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

Cet article démontre la faisabilité d'une analyse intégrée de différentes données génomiques, transcriptomiques, protéomiques et métaboliques recueillies sur un individu en bonne santé pendant une période de 14 mois

  • Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes
    Cell, Vol. 148 (6), pp. 1293-1307, 2012 (article en libre accès)
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    Cet article démontre la faisabilité d'une analyse intégrée de différentes données génomiques, transcriptomiques, protéomiques et métaboliques recueillies sur un individu en bonne santé pendant une période de 14 mois

    “Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes”

    • Chen, Rui;Mias, George I;Li-Pook-Than, Jennifer;Jiang, Lihua;Lam, Hugo Y K.;Chen, Rong;Miriami, Elana;Karczewski, Konrad J;Hariharan, Manoj;Dewey, Frederick E;Cheng, Yong;Clark, Michael J;Im, Hogune;Habegger, Lukas;Balasubramanian, Suganthi;O'Huallachain, Maeve;Dudley, Joel T;Hillenmeyer, Sara;Haraksingh, Rajini;Sharon, Donald;Euskirchen, Ghia;Lacroute, Phil;Bettinger, Keith;Boyle, Alan P;Kasowski, Maya;Grubert, Fabian;Seki, Scott;Garcia, Marco;Whirl-Carrillo, Michelle;Gallardo, Mercedes;Blasco, Maria A;Greenberg, Peter L;Snyder, Phyllis;Klein, Teri E;Altman, Russ B;Butte, Atul J.;Ashley, Euan A;Gerstein, Mark;Nadeau, Kari C;Tang, Hua;Snyder, Michael

    Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity. º ...


Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

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