Nicolas Magné

University of Lyon, Lyons, Rhône-Alpes, France

Are you Nicolas Magné?

Claim your profile

Publications (135)482.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: There is accumulating evidence that TrkA and its ligand Nerve Growth Factor (NGF) are involved in cancer development. Staurosporine derivatives such as K252a and lestaurtinib have been developed to block TrkA kinase signaling, but no clinical trial has fully demonstrated their therapeutic efficacy. Therapeutic failures are likely due to the existence of intrinsic signaling pathways in cancer cells that impede or bypass the effects of TrkA tyrosine kinase inhibitors. To verify this hypothesis, we combined different approaches including mass spectrometry proteomics, co-immunoprecipitation and proximity ligation assays. We found that NGF treatment induced CD44 binding to TrkA at the plasma membrane and subsequent activation of the p115RhoGEF/RhoA/ROCK1 pathway to stimulate breast cancer cell invasion. The NGF-induced CD44 signaling was independent of TrkA kinase activity. Moreover, both TrkA tyrosine kinase inhibition with lestaurtinib and CD44 silencing with siRNA inhibited cell growth in vitro as well as tumor development in mouse xenograft model; combined treatment significantly enhanced the antineoplastic effects of either treatment alone. Altogether, our results demonstrate that NGF-induced tyrosine kinase independent TrkA signaling through CD44 was sufficient to maintain tumor aggressiveness. Our findings provide an alternative mechanism of cancer resistance to lestaurtinib and indicate that dual inhibition of CD44 and TrkA tyrosine kinase activity may represent a novel therapeutic strategy.
    Oncotarget 01/2015; · 6.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nanoparticles have emerged in oncology as new therapeutic agents of distinct biochemical and physical properties, and pharmacokinetics. Current rationale and clinical applications in combination with radiation therapy were analyzed. A review of the literature was conducted on nanoparticles as radiosensitizers, with a focus on metallic nanoparticles and radiosensitization mechanisms. Nanoparticles are mainly used as vectors for drugs or to potentiate dose deposit selectively in irradiated tissues. Preclinical data suggest a predominating effect in the kilovoltage range through a photoelectric effect and a potential in the megavoltage range under a combination of physical and biochemical (diameter, concentration, site of infusion etc) conditions. Several clinical trials are ongoing with metallic/crystalline nanoparticles. Nanoparticles have shown a potential for better therapeutic index with radiation therapy, which is being increasingly investigated clinically. Copyright © 2014 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
    Bulletin du cancer. 01/2015;
  • [Show abstract] [Hide abstract]
    ABSTRACT: We retrospectively assessed the outcome of patients receiving emergency spinal radiation therapy (RT) concurrently with bevacizumab. Clinical records of 18 consecutive patients receiving emergency spinal RT for symptomatic vertebral metastases during the course of bevacizumab-based therapy were examined. Patients were receiving biweekly bevacizumab combined with paclitaxel (n=17) or with docetaxel/carboplatin (n=1) or as a single agent (n=1) for advanced metastatic carcinoma. RT was delivered at doses of 30 Gy in 10 fractions (n=8), 20 Gy in five fractions (n=9) or 18 Gy in nine fractions (n=1). In 10 patients (56%), irradiation field encompassed the thoracic vertebrae. The median time interval between the bevacizumab infusion and the RT course was 1.5 days (0-8 days). The median follow-up was 8.3 months (2 days-42 months). A clinical benefit of RT was reported in 13 patients (72%), including four patients with complete pain relief. Two of the three patients with neurological impairment at the time of RT experienced a partial improvement in their symptoms. No pain recrudescence was reported within the irradiated field after RT completion. All toxicities were mild to moderate, with no acute toxicity reported in 13 patients (72%). No RT disruption was necessary because of acute toxicity. No delayed toxicity was reported within RT fields among 11 patients with at least 6 months of follow-up. Spinal RT during the course of bevacizumab-based therapy was not associated with the occurrence of unexpected adverse effects. This suggests that emergency RT should not be contraindicated in these patients, provided that doses and treatment volumes are defined carefully.
    Anti-cancer drugs. 01/2015;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rare cancers represent about a quarter of all cancers diagnosed in Europe, and their incidence is increasing. Meanwhile, scientific advances provide techniques, which become more and more sophisticated in the domain of radiotherapy. Treatment options for radiotherapy rare cancers are increasing, but are not yet evaluated. The question of the appropriateness of treatment by modern radiotherapy techniques in rare cancers remains. There are a lot of cases reported in the literature for treating rare cancers by modern technology. These techniques are often used when anatomical and dosimetric constraints do not achieve optimal treatment by surgery or standard radiotherapy. In contrast, standard radiotherapy techniques also provide good results in terms of overall survival and tolerance. They are also less expensive and less complex in terms of dosimetry. The establishment of specialized centers in rare cancers seems essential to evaluate the appropriateness of the use of modern techniques in these cases. Currently, data from the literature does not provide an answer to this question. Copyright © 2014 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
    Bulletin du cancer. 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the study was to analyze the medical and economic interest of OSNA molecular technique, compared to conventional postoperative histopathologic evaluation for sentinel lymph node exploration in breast cancer patients. This retrospective cost-benefit study was conducted in the French Universitary Hospital of Saint Etienne on patients who received sentinel lymph node exploration between July 1, 2007 and December 31, 2009. Lymph nodes were analyzed by conventional postoperative histological evaluation in group 1 (82 patients) and OSNA in group 2 (86 patients). Costs were analyzed in three different ways: surgery cost, hospitalization cost and histopathologic cost. Average operating time was slightly shorter for group 1 (histology) [71.9 vs. 76.8 min for group 2 (OSNA)]. Time and operating costs were not significantly different (p = 0.293). The average cost of pathological examination was significantly higher in group 2 (35.04 euros per node in group 1 vs. 291.84 euros per node in group 2 p < 10(-3)). The average length of hospital stay was significantly longer in group 1 (5.4 days in group 1 vs. 4.2 days in group 2, p = 0.0065). The total costs were not significantly different between both groups (3,774.6 euros in group 1 vs. 3,393.9 euros in group 2 p = 0.055). The sentinel lymph node analysis with OSNA technique does not lead to higher expenses. It also avoids another surgery for 20 % of patients. A prospective multicentric medico-economic study made with a larger effective would probably confirm these results.
    Medical Oncology 12/2014; 31(12):322. · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radiation therapy is a keystone treatment in cancer. Photon radiation has proved its benefits in overall survival in many clinical studies. However, some patients present local recurrences or metastases when cancer cells survive to treatment. Metastasis is a process which includes adhesion of the cell to the extracellular matrix, degradation of the matrix by proteases, cell motility, intravasation in blood or lymphatic vessels, extravasation in distant parenchyma and development of cell colonies. Several studies demonstrated that ionizing radiation might promote migration and invasion of tumor cells by intricate implications in the micro-environment, cell-cell junctions, extracellular matrix junctions, proteases secretion, and induction of epithelial-mesenchymal transition. This review reports various cellular pathways involved in the photon-enhanced cell invasion process for which potential therapeutic target may be employed for enhancing antitumor effectiveness. Understanding these mechanisms could lead to therapeutic strategies to counter the highly invasive cell lines via specific inhibitors or carbon-ion therapy.
    Critical Reviews in Oncology/Hematology 11/2014; · 4.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Invasive fungal infections (IFIs) remain one of the worrying complications in patients with acute myeloid leukemia (AML) due to their incidence and high level of attributable mortality. In light of these risks, antifungal prophylaxis has always been debated. We conducted a single-center retrospective study of two prophylactic antifungal agents (fluconazole/posaconazole) in 91 consecutive patients receiving induction chemotherapy for AML between 2005 and 2009, in order to evaluate the impact on the incidence of IFI and on the mycological flora of the patients. Methods: In total, 39 patients received prophylactic fluconazole versus 52 who received posaconazole. The baseline characteristics of the two groups were comparable. Results: Overall, 17 patients developed an IFI, with no difference in frequency between the two groups. Utilization of empirical or pre-emptive therapy was similar irrespective of the type of prophylaxis used. Mycological examination of stools revealed an increase in non-albicans Candida colonization in the fluconazole group during hospitalization and the appearance of Saccharomyces cerevisiae colonization in patients receiving posaconazole. Conclusion: The present study does not distinguish between fluconazole and posaconazole as a primary effective prevention against fungal infections. More prospective studies and meta-analyses are warranted.
    Biomedical journal. 10/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glioblastoma multiform is the most common and aggressive brain tumor with a worse prognostic. Ionizing radiation is a cornerstone in the treatment of glioblastome with chemo-radiation association being the actual standard. As a paradoxal effect, it has been suggested that radiotherapy could have a deleterious effect on local recurrence of cancer. In vivo studies have studied the effect of radiotherapy on biological modification and pathogenous effect of cancer cells. It seems that ionizing radiations with photon could activate oncogenic pathways in glioblastoma cell lines. We realized a review of the literature of photon-enhanced effect on invasion and migration of glioblastoma cells by radiotherapy.
    Bulletin du cancer. 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: In France, there is an important interregional disparity concerning participation to cancer screening programs. The aim of this study was to assess oncologic screening practices in Loire, a French rural department, in women and in the elderly (over age 74 years). For this, two surveys were conducted. The first one was regarding screening for breast, cervical and colorectal cancer in women over age 18 years living in Loire. The second survey was regarding onco-geriatric screening through two questionnaires : one for the elderly and the other for general practitioner (GP) of the department, evaluating screening for breast, colorectal, prostate, cervical and lung cancer. One hundred sixty six women were included in the first investigation mean age of 47.6 years. Ninety three point six per cent were screening for breast cancer, 19% received Human Papilloma virus vaccine, 83.1% were screening by Papanicolau smear for cervical cancer and finally, 51.7% were screening for colorectal cancer, among the one entering screening program criteria. In the second survey, 44 patients and 28 GP were included. Thirty-eight point six per cent of patients over 74 years continue screening. Only 11.4% were reluctant to screening and in 80% because of anxiety du to the results. Among GP, 50 % continued screening on two major criteria : life expectancy and performans status. The present study shows heterogeneity of screening in this department both rural and working class and gives us a societo-medical photography.
    Bulletin du cancer. 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is an increasing number of therapeutic options in breast cancer management. While prognosis improves, the cardiac toxicity related to treatments remains a significant issue. This toxicity has several clinical presentations and can be explained by complex and diverse molecular mechanisms. Systemic treatments (anthracyclines, inhibitors of HER2 signaling pathway, hormone therapy, antiangiogenic agents) and radiotherapy have their own cardiac toxicity. However, the toxicities associated with these treatments may potentiate together and the existence of pre-existing cardiovascular risk factors should be taken into account. The assessment of cardiac hazard evolves toward a multifactorial approach. Several possibilities exist to minimize the incidence of cardiac complications. Those include pharmacological and technological innovations, but also a more accurate selection of patients and a growing involvement of practitioners in the field of cardiac toxicity, which is prerequisite for an early management of cardiac events.
    Bulletin du cancer. 08/2014; 101(7-8):730-740.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Carcinosarcoma, also known as mixed mesodermal tumor or malignant mixed Mullerian tumor (MMMT) is a pathological entity combining a sarcomatous and a carcinomatous component. Found in thoracic, digestive, genitourinary, liver or skin locations, the most common location is the female genital tract. In gynecological tumors, carcinosarcoma accounts for about 2-5% of endometrial cancers, and 1% of ovarian cancers. To date, there is no consensus on the therapeutic strategy. It relies mostly on maximum cytoreductive surgery. Adjuvant therapy remains controversial, and few prospective studies investigating its interest. Retrospective studies show the benefits of adjuvant chemotherapy based on platinum in most cases. Radiation therapy has a place in the adjuvant situations of endometrial and cervical carcinosarcoma. A more detailed pathological knowledge, and the use of targeted therapies may be promising in this histological subtype whose prognosis remains very poor. The objective of this study is to present the main principles of carcinosarcoma management in female genital tracts, describing pathological and prognostic features at the same time.
    Bulletin du cancer. 08/2014; 101(7-8):760-764.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of the present study is to report the pilot experience at the « Loire cardiorespiratory readaptation center » of re-entrainment of physical activity for patients suffering from breast cancer. Between January 2012 and February 2013, 63 patients took the program at the readaptation center. The program is composed of three sessions a week during seven weeks. During the care, a medical team intervenes. It is composed of a cardiologist, a physiotherapist, a sophrologist, a psychologist and a dietician who take part in turns and/or together. During the first session of the program, the warm-up power chosen on the exercise bike was on average of 14.72 watts (min = 5; max = 30), and it went up to 44.84 watts (min = 15; max = 85) on average during the last session. The maximal power used by the patient was on average of 39.08 watts (min = 10; max = 70) during the first session. On the last day of training, the average maximal power between the patients was of 76.03 watts (min = 30; max = 110). The tests used into practice tend to confirm a physical progression between the beginning and the end of the re-training program. This study particularly shows that it is possible today to propose this type of program to the patients in daily practice.
    Bulletin du cancer. 08/2014; 101(7-8):698-702.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gadolinium based nanoparticles (GBNs, diameter 2.9±0.2nm), have promising biodistribution properties for theranostic use in-vivo. We aimed at demonstrating the radiosensitizing effect of these GBNs in experimental radioresistant human Head and Neck Squamous Cell Carcinoma (SQ20B, FaDu and Cal33 cell lines). Combining 0.6mM GBNs with 250kV photon irradiation significantly decreased SQ20B cell survival, associated with the increase in non-reparable DNA double-strand breaks, the shortening of G2/M phase blockage, the inhibition of cell proliferation, each contributing to the commitment of late apoptosis. Similarly, radiation resistance was overcome for SQ20B stem-like cells, as well as for FaDu and Cal33 cell lines. Using a SQ20B tumor-bearing mouse model, combination of GBNs with 10Gy irradiation significantly delayed tumor growth with an increase in late apoptosis and a decrease in cell proliferation. These results suggest that GBNs could be envisioned as adjuvant to radiotherapy for HNSCC tumors.
    Nanomedicine Nanotechnology Biology and Medicine 06/2014; · 5.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gadolinium based nanoparticles (GBNs, diameter 2.9±0.2nm), have promising biodistribution properties for theranostic use in-vivo. We aimed at demonstrating the radiosensitizing effect of these GBNs in experimental radioresistant human Head and Neck Squamous Cell Carcinoma (SQ20B, FaDu and Cal33 cell lines). Combining 0.6mM GBNs with 250kV photon irradiation significantly decreased SQ20B cell survival, associated with the increase in non-reparable DNA double-strand breaks, the shortening of G2/M phase blockage, the inhibition of cell proliferation, each contributing to the commitment of late apoptosis. Similarly, radiation resistance was overcome for SQ20B stem-like cells, as well as for FaDu and Cal33 cell lines. Using a SQ20B tumor-bearing mouse model, combination of GBNs with 10Gy irradiation significantly delayed tumor growth with an increase in late apoptosis and a decrease in cell proliferation. These results suggest that GBNs could be envisioned as adjuvant to radiotherapy for HNSCC tumors.
    Nanomedicine 06/2014; · 5.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In clinical practice and the literature, malignant melanoma usually appears in typical sites where melanocytes can be found: skin, eyes meninges and anal region. Malignant melanomas of the esophagus-gastrointestinal (EGI) tract are usually metastatic. Primary and diffuse EGI tract melanoma is rare and only a few descriptions of this presentation have been found in the literature. The prognosis of EGI tract melanoma is frightening because of late diagnosis and high malignancy potential. Treatment is based essentially on surgery. The objective of the present study is to specify the clinical and therapeutic aspects of primary digestive melanoma.
    Bulletin du cancer. 06/2014; 101(6):637-640.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Radiotherapy for epithelioid hemangioendothelioma (EHE) using volumetric intensity-modulated arc radiotherapy (VMAT). A 48-year-old woman was referred for curative irradiation of a vertebral EHE after failure of surgery. A comparison between VMAT and conventional conformal tridimensional (3D) dosimetry was performed and potential advantage of VMAT for sparing critical organs from irradiation׳s side effects was discussed. The total delivered dose on the planning target volume was 54Gy in 27 fractions. The patient was finally treated with VMAT. The tolerance was excellent. There was no acute toxicity, including no increase in pain. With a follow-up of 18 months, no delayed toxicity was reported. The clinical response consisted of a decrease in the dorsal pain. The Dmax for the spinal cord was reduced from 55Gy (3D-radiotherapy [RT]) (which would be an unacceptable dose to the spine because of the risk of myelopathy) to 42.8Gy (VMAT), which remains below the recommended dose threshold (45Gy). The dose delivered to 20% of organ volume (D20) was reduced from 47Gy (3D-RT) to 3Gy (VMAT) for the spinal cord. The study shows that VMAT allows the delivery of curative treatment for vertebral EHEs because of critical organ sparing.
    Medical dosimetry: official journal of the American Association of Medical Dosimetrists 05/2014; · 1.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background There are only scarce data on the management of patients aged 90 years or older with cancer, and more particularly on the place of radiation therapy (RT). We report the first large study on patients (pts) aged 90 years or older receiving RT. Methods and materials Records from RT departments from five institutions were reviewed to identify pts 90 years of age and older who underwent RT for various malignant tumours treated between 2003 and 2012. Tumours’ characteristics were examined, as well as treatment specificities and treatment intent. Results 308 pts receiving 318 RT courses were identified, mean age was 93.2 years (standard deviation 2.8). Treatment was given with curative and palliative intent in 44% and 56%, respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery and tumour stage. Median total prescribed dose was 36 Gy (4–76 Gy). Hypofractionation and split course were used in 88% and 7.3%, respectively. Most toxicities were mild to moderate. RT could not be completed in 23 pts (7.5%). No long-term toxicity was reported. Median overall survival was 22.9 months (95CI: 15.5–42.7 months). Cancer was the cause of death in 8.7% and 46% of pts treated with curative and palliative intent, respectively. Conclusion This study shows that RT is feasible for patients aged 90 years or more. PS, place of life and tumour stage were factors of the therapeutic decision. There is no reason to withdraw pts with good general health condition from potentially curative RT, provided that careful attention is paid to factors of toxicity and to geriatric vulnerabilities.
    European journal of cancer (Oxford, England: 1990) 05/2014; · 4.12 Impact Factor
  • The American journal of cardiology 04/2014; 113(8):1447-8. · 3.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are only scarce data on the management of nonagenarians with breast cancer, and more particularly on the place of radiation therapy (RT). We report a retrospective study on patients aged 90 years old or older, with breast cancer, receiving RT. Records from RT departments from five institutions were reviewed to identify patients 90 years old of age and older undergoing RT over past decade for breast cancer. Tumors' characteristics were examined, as well treatment specificities and treatment intent. 44 patients receiving RT courses were identified, mean age 92 years. Treatment was given with curative and palliative intent in 72.7% and 27.3% respectively. Factors associated with a curative treatment were performance status (PS), place of life, previous surgery, and tumor stage. Median total prescribed dose was 40 Gy (23-66). Hypo fractionation was used in 77%. Most toxicities were mild to moderate. RT could not be completed in 1 patient (2.3%). No long-term toxicity was reported. Among 31 patients analyzable for effectiveness, 24 patients (77.4%) had their diseased controlled until last follow-up, including 17 patients (54.8%) experiencing complete response. At last follow-up, 4 patients (12.9%) were deceased, cancer being cause of death for two of them. The study shows that breast/chest RT is feasible in nonagenarians. Although the definitive benefit of RT could not be addressed here, hypofractionated therapy allowed a good local control with acceptable side effects.
    Breast (Edinburgh, Scotland) 04/2014; · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the field of radiotherapy, there is very little scientific data on the management of nonagenarians, especially in patients aged 90 years or more and with head and neck cancer (HNC). We made one of the first retrospective study of the feasibility and safety of radiotherapy in this population with HNC. Records of radiotherapy coming from four health facilities were studied to include all nonagenarian patients with HNC in the last 10 years and who received radiation therapy. We analyzed patient characteristics and primary cancers, as well as objective of the treatment (curative or palliative), efficacy and toxicity. Twenty patients receiving radiotherapy were identified; mean age was 93.2 years (standard deviation 2.8). Treatment was given with curative and palliative intent in 40 and 60 % of cases, respectively. The most common primary tumors were tumors of the salivary glands (30 % of cases), oral cavity tumors (25 % of cases) and thyroid tumors (15 % of cases). Median total prescribed dose was 47.5 Gy (12-70 Gy). Median number of delivered fractions was 18.5 (2-35 fractions). All patients received intensive supportive care during radiotherapy. Toxicities were mild to moderate. Radiotherapy could not be completed for four patients (20 % of cases). One patient developed grade 1-2 delayed toxicities. At the last follow-up, only four patients (20 % of cases) were alive. Cancer was cause of death in most cases. Radiotherapy may be performed for the nonagenarians with HNC. The total dose and fractionation must be adjusted to optimize the tolerance. However, the prognosis remains very poor, cancer being the main cause of death. Research of geriatric vulnerabilities prior to any treatment, in the context of a comprehensive geriatric assessment, is still recommended to select patients for radiotherapy.
    Archives of Oto-Rhino-Laryngology 04/2014; · 1.61 Impact Factor

Publication Stats

1k Citations
482.99 Total Impact Points

Institutions

  • 2013–2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
    • Institut National d'Oncologie, Rabat
      Rabat, Rabat-Salé-Zemmour-Zaër, Morocco
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2012–2014
    • Institut de cancérologie Lucien-Neuwirth
      La Fouillouse, Rhône-Alpes, France
  • 2007–2012
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Ile-de-France, France
  • 2006–2011
    • Institut Jules Bordet
      Bruxelles, Brussels Capital Region, Belgium
    • Université Libre de Bruxelles
      • Bordet Institute
      Bruxelles, Brussels Capital Region, Belgium
  • 2009–2010
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
  • 2002–2006
    • Centre Antoine-Lacassagne
      Nice, Provence-Alpes-Côte d'Azur, France
    • Centre Hospitalier Universitaire de Nice
      Nice, Provence-Alpes-Côte d'Azur, France