Jean-François Bernaudin

Hôpital Tenon (Hôpitaux Universitaires Est Parisien), Lutetia Parisorum, Île-de-France, France

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Publications (33)127.19 Total impact

  • Dominique Valeyre, Hilario Nunes, Jean-François Bernaudin
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    ABSTRACT: To present an update on the most recent contributions in advanced pulmonary sarcoidosis (APS).
    Current opinion in pulmonary medicine. 07/2014;
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    ABSTRACT: Sarcoidosis is a systemic disease of unknown cause characterized by the formation of immune granulomas which most often involve the lung and the lymphatic system. Sarcoidosis may encompass numerous different clinical presentations. Typical presentations often prompt a rapid diagnosis while in 25 to 50% of cases, diverse and less typical presentations may lead to delayed diagnosis. The mediastinopulmonary sphere is involved in 85 to 95% of cases, associated with extrapulmonary localizations in half of cases while extrapulmonary localizations without lung involvement may be seen in 5 to 15% of cases. Bilateral hilar lymphadenopathy is the most typical sign at chest radiography. Computed tomography (CT) is essential face for atypical manifestations of the disease to avoid confusion with differential diagnoses and, sometimes, comorbidities. CT typically evidences diffuse pulmonary perilymphatic micronodules, with a perilobular and fissural distribution and upper and posterior predominance, even when an atypical CT pattern is predominant. CT allows deciphering pulmonary lesions in cases of pulmonary fibrosis, pulmonary hypertension, and airflow limitation. Pulmonary function tests generally correlate with the overall disease process. Forced vital capacity is the simplest and most accurate parameter to reflect the impact of pulmonary sarcoidosis. Cardiopulmonary exercise testing helps in understanding the mechanism behind dyspnea of uncertain origin. Endoscopic transbronchial needle aspiration is an extra tool to support diagnosis in addition to more classical biopsy means. Bronchoalveolar lavage (BAL) may be used for individual patients while it is not really decisive for the diagnosis of sarcoidosis for most patients. Diagnosis relies on compatible clinical and radiological presentation, evidence of noncaseating granulomas and exclusion of other diseases with a similar presentation or histology. The probability of diagnosis at presentation is variable from case to case and may often be reinforced with time. Some investigations are mandatory at diagnosis to assess organ involvement and disease activity. However, there are important variations in diagnostic work-up due to diverse expressions of sarcoidosis and differences in clinical practices among physicians.
    Seminars in Respiratory and Critical Care Medicine 06/2014; 35(3):336-351. · 2.75 Impact Factor
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    ABSTRACT: The goal of this study was CGH array profiling of breast cancer from Malian women in order to define differences with those from USA. CGH array was performed in 28 samples, 17 with a triple negative phenotype. The profiles were compared to those of 106 tumors from USA. 6 chromosomal regions (6p21, 9q34, 11q13, 12q24, 17q25 and 22q12.1-22q13.1) were identified with a significant higher rate of copy number alterations. These regions contain several genes of interest including BCR. FISH and IHC confirmed that BCR was amplified and overexpressed particularly in triple negative tumors. Finally, 5 regions presented a high level of amplification in two or more samples, including 2 regions located between 9p22.3-9p23 and 9p23-9p24.1. This study confirms that breast cancers from African women present biological differences with those from USA. Larger studies are needed to go further in the identification of therapeutic targets that would be specific to African women.
    Breast (Edinburgh, Scotland) 06/2013; 22(3):295–300. · 2.09 Impact Factor
  • Journal of Histochemistry and Cytochemistry 05/2013; · 2.26 Impact Factor
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    ABSTRACT: We have previously reported an association between ABCB1 C3435T polymorphism and docetaxel pharmacokinetics in breast cancer patients. We therefore investigated whether these parameters could account for variations in pathological response. Five ABCB1 polymorphisms including C3435T polymorphism were analyzed in breast cancer patients receiving neoadjuvant chemotherapy with doxorubicin and docetaxel (n = 101). Pathological response was assessed using the Sataloff classification. Pharmacokinetic analysis was performed for the first course of docetaxel (n = 84). No significant association was found between ABCB1 polymorphisms or docetaxel pharmacokinetics and pathological complete response. C3435T genotype was an independent predictive factor of good response in breast (response >50 %, i.e., Sataloff T-A and T-B): OR: 4.6 (95 % CI: 1.3-16.1), p = 0.015, for TT patients versus CT and CC patients. Area under the plasma concentration-time curve (AUC) of docetaxel was the only independent predictive factor of the total absence of response in breast (Sataloff T-D): OR: 14.3, (95 % CI: 1.7-118), p = 0.015, for AUC of docetaxel <3,500 μg h/L versus ≥3,500 μg h/L. These results suggest that C3435T polymorphism and docetaxel exposure are involved in the response to neoadjuvant chemotherapy in breast cancer patients and may be useful to optimize individualized therapy.
    Breast Cancer Research and Treatment 05/2013; · 4.47 Impact Factor
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    ABSTRACT: Objective: Few studies have been conducted on breast cancer in Sub-Saharan Africa and their results have been suspected to be impaired by artefacts. This prospective study was designed to determine tumor and patient characteristics in Mali with control of each methodological step. These data are necessary to define breast cancer treatment guidelines in this country. Methods: Clinical and tumor characteristics and known risk factors were obtained in a consecutive series of 114 patients. Each technical step for the determination of tumor characteristics [histology, TNM, grade, estrogen (ER) and progesterone receptors (PR), HER2, and Ki67] was controlled. Results: Patients had a mean age of 46 years. Most tumors were invasive ductal carcinomas (94%), T3-T4 (90%) with positive nodes (91%), grade III (78%), and ER (61%) and PR (72%) negative. HER2 was overexpressed in 18% of cases. The triple-negative subgroup represented 46%, displaying a particularly aggressive pattern (90% grade III; 88% Ki67 >20%). Conclusion: This study demonstrates the high incidence of aggressive triple-negative tumors in Mali. Apart from a higher prevalence of premenopausal women, no significant difference in risk factors was observed between triple-negative tumors and other tumors. The hormonal therapy systematically prescribed therefore needs to be revised in light of this study.
    Oncology 09/2012; 83(5):257-263. · 2.17 Impact Factor
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    ABSTRACT: How is the expression of nectins and nectin-like molecules (Necls) detected by immunostaining altered by endometriosis? SUMMARY ANSWER: Our results suggest that Nectin-1, -3, -4 and Necl-2 may contribute to the pathogenesis of endometriosis. Immunostaining of nectins and Necls varies according to the anatomical location of endometriosis. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Nectin and Necl molecules are immunoglobulin-like cell adhesion molecules involved in apoptosis, cell proliferation and in metastases. Previous studies have demonstrated the involvement of adhesion molecules in the development of endometriotic lesions but no data exist on immunostaining of nectins and Necls molecules in endometriosis. This retrospective study was conducted in a tertiary-care hospital (Tenon Hospital, Paris, France). Samples were collected from 55 women undergoing endometrial biopsy or surgery for endometriosis and 20 controls having hysterectomy or endometrial biopsy for other reasons; multiple samples were collected from 15 women. We studied the immunostaining of Nectin-1, -3, -4 and Necl-2 in secretory and proliferative endometrium from women with (n = 20) or without endometriosis (i.e. control group, n = 20), and in peritoneal (n = 20), ovarian (n = 20) and colorectal endometriosis (n = 20). Semi-quantitative immunostaining demonstrated that (1) Necl-2 staining was stronger in all types of endometriotic lesions than in the eutopic endometrium from patients with endometriosis (P < 0.0125) and in ovarian endometriotic cysts compared with other locations (P < 0.001); (2) Nectin-3 staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.03) and in all endometriotic lesions compared with the eutopic endometrium from patients with endometriosis (P < 0.0125); (3) Nectin-4, staining was stronger in the eutopic endometrium of patients with endometriosis compared with controls (P = 0.04) and (4) Nectin-1 staining was significantly increased in colorectal endometriosis compared with other locations (P = 0.004). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: We did not assess the pattern of expression in endometriosis of all nectins and Necl molecules. Indeed, Necl-5 is implicated in many pathophysiological processes such as cell movement and proliferation with potential relevance to endometriosis. GENERALISABILITY TO OTHER POPULATIONS: At present, few data on implication of nectins and Necl molecules in endometriosis exist. Hence, our results should be confirmed by further quantitative studies at protein or RNA levels. STUDY FUNDING/COMPETING INTEREST(S): No funding source. All the authors declare no conflict of interest.
    Human Reproduction 08/2012; 27(11):3179-86. · 4.67 Impact Factor
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    ABSTRACT: The role of DNA ploidy in genomic instability of cancer cells and prognosis has been described in a number of studies. The role of the centrosome in cell cycle has also been reported. In this study, we aimed to investigate the correlation between the centrosome and DNA ploidy in breast cancer in a search for a cytologic predictive and prognostic marker. Cell prints were prepared from cell culture of mesothelial cells, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Indirect immunofluorescence was used with anti-γ-tubulin and centrosomes were quantified using a fluorescence microscope. DNA ploidy was scored with the DNA index analyzed by flow cytometry. The normal mesothelial cells (94% of the cells with one detected centrosome) and MRC5 diploid cells (68% with two centrosomes) were used as quality controls. A correlation between the number of centrosomes and DNA ploidy was found in MCF7 cell lines (64% of the cells with a number of centrosomes ≥ 3). It was not observed in invasive breast cancer samples; however, the frequency of cells with centrosomes ≥ 3 was found to be slightly higher in DNA aneuploid samples than in DNA diploid samples (15% vs 13.3%). Quantification of centrosome appears to be correlated to DNA ploidy in breast cancer cell lines and slightly associated to DNA aneuploidy in invasive breast cancer. Studies analyzing a larger number of samples as well as morphological abnormalities of the centrosome are needed.
    Journal of Cytology 04/2012; 29(2):111-5. · 0.31 Impact Factor
  • Chest 12/2011; 140(6):1664; author reply 1664-5. · 7.13 Impact Factor
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    ABSTRACT: Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.
    Experimental Cell Research 10/2011; 317(16):2321-32. · 3.56 Impact Factor
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    ABSTRACT: Breast cancer is the second most frequent cancer in Sub-Saharan African women with an incidence of 15-53 per 100,000 women. Using PubMed, we reviewed all the articles published on this topic between 1989 and 2009. Breast cancer is usually diagnosed in women younger than in developed countries (mean age: 42-53 years), with later stages (III or IV, i.e. with axillary nodes and distant metastases). Reported tumors are mostly invasive ductal carcinomas with aggressive characteristics: grade III histoprognosis, absence of hormonal receptors or HER2 expression. According to the new breast cancer classification, nearly half of these tumors should be classified as triple negative. However, studies are rare and require confirmation. In conclusion, data on epidemiology and biology of breast cancer in Sub-Saharan African women are still scarce and need more extensive studies. In these countries, the pattern of breast cancer will likely change in the future, according to the evolution of lifestyle namely urbanisation. There is a great need for commitment of research and clinical resources in Sub-Saharan Africa in order to develop specific strategies.
    Bulletin du cancer 06/2011; 98(7):797-806. · 0.61 Impact Factor
  • Joseph Gligorov, Anne Fajac, Jean-François Bernaudin
    Journal of Clinical Oncology 05/2011; 29(15):e454-5; author reply e456-7. · 18.04 Impact Factor
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    ABSTRACT: ADN ploidy was shown to play a role in genomic instability of cancer cells and prognosis. The implication of the centrosome in the cell cycle was also described. Therefore, new prognostic factors could be suggested for a better-tailored therapy. The purpose of this study is to search for correlation between centrosomal abnormality and ADN ploidy in breast cancer. Cell prints were prepared from cell culture of mesothelial ascitis, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Fresh cell prints were also obtained from cases with invasive carcinoma. The centrosome was labelled by an indirect immunofluorescence assay using anti-γ-tubulin antibody and F(ab')(2) FITC before quantification with fluorescence microscopy. ADN ploidy was scored with DNA index obtained by means of flux cytometry. The normal mesothelial cells (94% of cells with only one centrosome) and the diploid cell line MRC5 (68% of cells with two centrosomes) were used as controls. DNA ploidy was found to be correlated with centrosomal abnormality in MCF7 cell line (64% of cells had more than three centrosomes) but not in the 10 cases of invasive ductal carcinoma analysed in this study. The absence of correlation between DNA ploidy and centrosomal abnormality in breast cancer samples may be due to the small numbers of cases, the cell prints or tumorigenesis. Correlation analysis of a larger number of cases and types of breast lesions to numerical and morphological abnormalities of the centrosome are ongoing.
    Annales de biologie clinique 04/2011; 69(2):181-9. · 0.30 Impact Factor
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    Marianne Kambouchner, Jean-François Bernaudin
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    ABSTRACT: It has been assumed for a long time that except for limited areas close to respiratory bronchioles or their satellite arteries, there is no evidence of lymphatic vessels deep in the pulmonary lobule. An immunohistochemical study using the D2-40 monoclonal antibody was performed on normal pulmonary samples obtained from surgical specimens, with particular attention to the intralobular distribution of lymphatic vessels. This study demonstrated the presence of lymphatics not only in the connective tissue surrounding the respiratory bronchioles but also associated with intralobular arterioles and/or small veins even less than 50 mum in diameter. A few interlobular lymphatic vessels with a diameter ranging from 10 mum to 20 mum were also observed further away, in interalveolar walls. In conclusion, this study, using the D2-40 monoclonal antibody, demonstrated the presence of small lymphatic channels within the normal human pulmonary lobules, emerging from interalveolar interstitium, and around small blood vessels constituting the paraalveolar lymphatics. This thin intralobular lymphatic network may play a key pathophysiological role in a wide variety of alveolar and interstitial lung diseases and requires further investigation.
    Journal of Histochemistry and Cytochemistry 04/2009; 57(7):643-8. · 2.26 Impact Factor
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    ABSTRACT: Bronchial typical carcinoid tumors are low-grade malignancies. However, metastases are diagnosed in some patients. Predicting the individual risk of these metastases to determine patients eligible for a radical lymphadenectomy and patients to be followed-up because of distant metastasis risk is relevant. Our objective was to screen for predictive criteria of bronchial typical carcinoid tumor aggressiveness based on a logistic regression model using clinical, pathological and biomolecular data. A multicenter retrospective cohort study, including 330 consecutive patients operated on for bronchial typical carcinoid tumors and followed-up during a period more than 10 years in two university hospitals was performed. Selected data to predict the individual risk for both nodal and distant metastasis were: age, gender, TNM staging, tumor diameter and location (central/peripheral), tumor immunostaining index of p53 and Ki67, Bcl2 and the extracellular density of neoformed microvessels and of collagen/elastic extracellular fibers. Nodal and distant metastasis incidence was 11% and 5%, respectively. Univariate analysis identified all the studied biomarkers as related to nodal metastasis. Multivariate analysis identified a predictive variable for nodal metastasis: neo angiogenesis, quantified by the neoformed pathological microvessels density. Distant metastasis was related to male gender. Discussion: Predictive models based on clinical and biomolecular data could be used to predict individual risk for metastasis. Patients under a high individual risk for lymph node metastasis should be considered as candidates to mediastinal lymphadenectomy. Those under a high risk of distant metastasis should be followed-up as having an aggressive disease. Individual risk prediction of bronchial typical carcinoid tumor metastasis for patients operated on can be calculated in function of biomolecular data. Prediction models can detect high-risk patients and help surgeons to identify patients requiring radical lymphadenectomy and help oncologists to identify those as having an aggressive disease requiring prolonged follow-up.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 10/2008; 34(3):473-7; discussion 477-8. · 2.40 Impact Factor
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    ABSTRACT: Study the clinical relevance of micrometastases in head and neck squamous cell carcinoma (HNSCC). We reviewed the outcome of 31 patients who underwent neck dissection for HNSCC with lymph node analysis by cytokeratin 19 real-time Taqman polymerase chain reaction (CK19RT-PCR) for detection of micrometastasis. Fifteen patients were N+ on histopathology (group 1) and 16 were N-; nine of these 16 patients were CK19RT-PCR positive (group 2), whereas seven were negative (group 3). Local and neck recurrences, metastases, and other tumour sites were recorded during follow-up. Five patients in group 1, eight patients in group 2, and one patient in group 3 experienced a tumor-related event. N- patients in groups 2 and 3 had a different outcome (P<0.01). It is suggested that CK19RTPCR detection of micrometastasis in lymph nodes could be of significant prognostic value in HNSCC, because more aggressive treatment could be indicated in these patients.
    Otolaryngology Head and Neck Surgery 10/2008; 139(3):436-41. · 1.73 Impact Factor
  • Koami Dagnon, Didier Heudes, Jean-François Bernaudin, Patrice Callard
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    ABSTRACT: Interactions between tumor cells and microvasculature are particularly critical. This computerized morphometric study was designed to analyze the distance between cancer cells and blood vessels and microvasculature organization in non-small cell lung carcinoma (NSCLC) comparing squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Seventy nine nests of tumor cells, located less than or more than 3 mm from the invading edge, with a similar surface area, and their surrounding stroma were analyzed. After immunolabeling with an antihuman CD34 monoclonal antibody, computerized morphometric analyses of microvascular density (MVD), distribution of microvessels within stroma, and fractions of carcinomatous cells over various distances from microvessels were performed. This analysis showed a significantly higher MVD score in ADC than in SCC, particularly close to the invading edge (382+/-57 in ADC <3 mm; 242+/-28 in SCC <3 mm, p=0.015). Moreover, a significantly higher proportion of cancer cells was situated more than 75 microm from microvessels in SCC than in ADC, regardless of their site in relation to the invading edge (for example, 25+/-5% in ADC <3 mm; 52+/-3% in SCC <3 mm, p=0.001).
    Microvascular Research 01/2008; 75(1):112-8. · 2.93 Impact Factor
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    ABSTRACT: Investigation of the role of vascular endothelial growth factor-C (VEGF-C) and VEGF receptor-3 (VEGFR-3) in non-small-cell lung cancer (NSCLC) has mainly focused on lymph node (LN) metastasis related to lymphangiogenesis. However, the coexpression of VEGF-C/VEGFR-3 by tumour cells can independently play an important role. The present study was therefore designed to evaluate VEGF-C/VEGFR-3 coexpression in tumour cells from the primary tumour and corresponding LN metastases. VEGF-C and VEGFR-3 expression in cancer cells were evaluated by immunohistochemistry in 92 NSCLC samples and 45 metastatic LNs. Ki67 expression and mitotic index (MI) in tumours and clinicopathological data were analysed concurrently. VEGFR-3 and VEGF-C expression were observed in 42% and 74% of tumours, respectively. Concurrent expression of VEGF-C and VEGFR-3, observed in 39% of tumours, was significantly associated with a higher proliferation rate and a higher incidence of LN metastases. VEGF-C expression in tumour cells was observed in 100% of metastatic LN and VEGF-C/VEGFR-3 coexpression was observed in 71% of metastatic LN. Finally, concurrent expression of VEGF-C/VEGFR-3 in the primary tumour was associated with poor disease-free survival on univariate analysis. In NSCLC cancer cells, VEGF-C/VEGFR-3 coexpression suggests an autocrine/paracrine loop responsible for a high proliferation rate in tumour cells. As VEGF-C/VEGFR-3 coexpression is very frequent in metastatic LN tumour cells, it can be hypothesised that this coexpression participates in the growth of LN metastasis.
    Lung Cancer 12/2007; 58(2):205-13. · 3.39 Impact Factor
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    ABSTRACT: Lung resistance-related protein (LRP) is an integral part of the multidrug resistance (MDR) phenotype involved in cell resistance toward xenobiotics or chemotherapy. The aim of this study was to compare the intracellular localization and cell expression of LRP in normal bronchial cells and their tumoral counterparts from non-small cell lung cancer (NSCLC). LRP expression was also investigated concurrently with DNA ploidy and chromosome 16 (lrp gene locus) aberrations. Confocal microscopy showed that LRP localization was exclusively intracytoplasmic regardless of the cell type and was never observed in the nuclear pore complex. Flow cytometry demonstrated a similar level of LRP expression in normal bronchial cells and in cancer cells from NSCLC samples. FISH analysis, performed to evaluate the number of chromosome 16 and lrp loci, demonstrated a significant gain of chromosome 16 in DNA aneuploid tumors. Furthermore, we did not find any link between LRP expression and DNA ploidy status or chromosome 16 number. These results suggest that LRP expression observed in NSCLC, maintained through the carcinogenesis process of respiratory cells, is not altered by the increased number of copies of chromosome 16 and probably controlled by mechanisms different from those of MRP1 expression, whereas both proteins are associated with the MDR phenotype.
    Journal of Histochemistry and Cytochemistry 09/2007; 55(8):773-82. · 2.26 Impact Factor
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    ABSTRACT: This study was designed to evaluate the prognostic effect of erythropoietin (EPO) and EPO receptor (EPO-R) expression in stage I non-small cell lung cancer (NSCLC) patients. EPO and EPO-R expression in 158 tumor samples from resected stage I NSCLC was evaluated using immunohistochemistry and tissue array technology. EPO-R and EPO were highly expressed in 20.9% and 35.4% of tumors, respectively. High EPO-R expression compared with negative or low-level expression was associated with a poor 5-year disease-specific survival (60.6% versus 80.8%; P = 0.01, log-rank test). High EPO expression compared with negative and low-level expression was associated with a trend toward a poor 5-year disease-specific survival (69.6% versus 80.4%; P = 0.13, log-rank test). A high level of EPO-R and EPO coexpression was associated with a poor 5-year disease-specific survival compared with other groups of patients (50.0% versus 80.0% survival at the end of follow-up; P = 0.005, log-rank test). In multivariate analysis for disease-specific survival, high-level EPO-R and EPO coexpression was an independent prognostic factor for disease-specific survival (hazard ratio, 2.214; 95% confidence interval, 1.012-4.848; P = 0.046). These results establish the pejorative prognostic value of EPO and EPO-R expression in early-stage resected NSCLC and suggest a potential paracrine and/or autocrine role of endogenous EPO in NSCLC aggressiveness.
    Clinical Cancer Research 09/2007; 13(16):4825-31. · 7.84 Impact Factor

Publication Stats

333 Citations
127.19 Total Impact Points

Institutions

  • 2011
    • Hôpital Tenon (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2002–2008
    • Pierre and Marie Curie University - Paris 6
      • Laboratoire d'histopathologie
      Lutetia Parisorum, Île-de-France, France
  • 2007
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1990
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      Créteil, Île-de-France, France
    • Centre Hospitalier Intercommunal Creteil
      Créteil, Île-de-France, France