Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.45M | Year: 2012
The greatest challenge for radiation therapy is to reach the highest probability of cure with the least morbidity. In practice, some difficulties remain to identify cancer cells, target them with radiation and minimize collateral damage. Over the last decades, remarkable progress has been made thanks to modern advances in computer and imaging technologies. Currently, the radiotherapy has reached a point where, besides 3D tumour morphology, time variations and biological variability within the tumour can also be taken into account. The SUMMER project is devised to produce unique software using several imaging sources (CT, MRI, PET, MR spectroscopy, fMRI, 4D PET-CT) for biological target volume delineation, based on spatial co-registration of multimodal morphologic and functional images. Furthermore, it will make additional biological information concerning tumour extension and tumour response available to radiotherapy, essential for patient treatment follow-up. Finally, radiation area will be more focused leading to less side-effect for the patient. Radiation oncology is now more dependent on medical imaging than it has ever been - and that dependence is only going to become greater. Therefore, convergence and collaboration of radiation oncology, nuclear medicine, diagnostic imaging and also computer science is the underlying driver to integrate efficiently and cost-effectively all information coming from various imaging technologies into the radiation therapy workflow. The design challenge is to combine the different level and kind of information into one interface, while currently doctors need to mentally do this operation. SUMMER will contribute to renew and strengthen this relationship through cross-disciplinary research, common workshops, and collaboration on training and education.
French National Center for Scientific Research, Institute Claudius Regaud and University Paul Sabatier | Date: 2011-05-18
The present invention relates to a method for diagnosing aggressiveness and/or genetic instability of a cancer in a patient from a cancer sample of said patient, comprising: a) measuring in vitro the expression level of the POLQ gene and the expression level of a control gene in said patient cancer sample; b) calculating for said POLQ gene an expression level ratio of the expression level of POLQ to the expression of the said control gene in said patient cancer sample; c) comparing the said POLQ expression level ratio to a corresponding threshold value, and d) diagnosing cancer aggressiveness and genetic instability if the said POLQ expression level ratio is superior to a corresponding threshold values. Dedicated microarrays and kits are also described, as well as a method of selecting a suitable treatment.
French National Center for Scientific Research and Institute Claudius Regaud | Date: 2011-05-18
The present invention relates to a method for diagnosing aggressiveness and/or genetic instability of a breast cancer in a patient from a breast cancer sample of said patient, comprising: a) measuring in vitro the expression level of the POLQ gene and the expression level of a control gene in said patient breast cancer sample; b) calculating for said POLQ gene an expression level ratio of the expression level of POLQ to the expression of the said control gene in said patient breast cancer sample; c) comparing the said POLQ expression level ratio to a corresponding threshold value, and d) diagnosing breast cancer aggressiveness and genetic instability if the said POLQ expression level ratio is superior to a corresponding threshold values. Dedicated microarrays and kits are also described, as well as a method of selecting a suitable treatment.
Cortes J.,University of Barcelona |
Roche H.,Institute Claudius Regaud
Cancer Treatment Reviews | Year: 2012
The treatment of metastatic breast cancer (MBC) is essentially palliative and should be based on hormone therapy or optimized chemotherapy designed to delay disease progression and maximize survival with good quality of life. Novel chemotherapeutic agents introduced in the 1990s include the taxanes (notably docetaxel), which are among the most potent of current anticancer drugs. Current research is also focusing on molecular targeted agents including those against the HER family of transmembrane receptors and vascular endothelial growth factor. Optimal effects are obtained when these compounds are used in combination with chemotherapy, as shown in preclinical models and more recently in clinical trials. Results of a large randomized trial have demonstrated a significant survival advantage for trastuzumab plus docetaxel compared with docetaxel monotherapy. Docetaxel plus bevacizumab combinations have recently been shown to significantly improve progression-free survival and objective response rate compared with docetaxel monotherapy. Overall, docetaxel in combination with novel targeted agents in MBC appears to be highly active in patients with MBC, and such combinations represent promising treatment regimens for clinical investigation. © 2011 Elsevier Ltd.
Poirot M.,Institute Claudius Regaud
International Journal of Developmental Biology | Year: 2011
V. Craig Jordan is a pioneer in the molecular pharmacology and therapeutics of breast cancer. As a teenager, he wanted to develop drugs to treat cancer, but at the time in the 1960s, this was unfashionable. Nevertheless, he saw an opportunity and through his mentors, trained himself to re-invent a failed "morning-after pill" to become tamoxifen, the gold standard for the treatment and prevention of breast cancer. It is estimated that at least a million women worldwide are alive today because of the clinical application of Jordan's laboratory research. Throughout his career, he has always looked at "the good, the bad and the ugly" of tamoxifen. He was the first to raise concerns about the possibility of tamoxifen increasing endometrial cancer. He described selective estrogen receptor modulation (SERM) and he was the first to describe both the bone protective effects and the breast chemopreventive effects of raloxifene. Raloxifene did not increase endometrial cancer and is now used to prevent breast cancer and osteoporosis. The scientific strategy he introduced of using long term therapy for treatment and prevention caused him to study acquired drug resistance to SERMs. He made the paradoxical discovery that physiological estrogen can be used to treat and to prevent breast cancer once exhaustive antihormone resistance develops. His philosophy for his four decades of discovery has been to use the conversation between the laboratory and the clinic to improve women's health. © 2011 UBC Press.
Bousquet E.,Institute Claudius Regaud
Oncogene | Year: 2015
Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, which is mainly due to its high risk of metastatic dissemination. One critical point of this process is the ability of cancer cells to detach from the primary tumor and migrate through the extracellular matrix; however, the underlying molecular mechanisms are not yet fully understood. In the present study, we identified the small GTPase RhoB as a key regulator of bronchial cell morphology in a three-dimensional (3D) matrix. RhoB loss, which is frequently observed during lung cancer progression, induced an epithelial–mesenchymal transition (EMT) characterized by an increased proportion of invasive elongated cells in 3D. The process was mediated by Slug induction and E-cadherin repression. In addition, downregulation of RhoB induced Akt1 activation, which in turn activated Rac1 through the guanine-exchange factor Trio to control cell shape rearrangement. Further, we provide evidence that RhoB interacted with and positively regulates phosphatase PP2A through the recruitment of its regulatory subunit B55, which was found to be crucial for Akt dephosphorylation. B55 inhibition completely suppressed RhoB-mediated PP2A regulation. Finally, we show that PP2A inactivation, by targeting either its catalytic or its regulatory B55 subunit, completely reversed RhoB-dependent morphological changes and also fully prevented the ability of RhoB to decrease the invasiveness of bronchial cells. Altogether, these results highlight a novel signaling axis and describe new molecular mechanisms that could explain the tumor suppressor role of RhoB in lung cancer. Therefore, we propose that RhoB could be responsible for early metastatic prevention by inhibiting the EMT-derived invasiveness of lung cells through the control of PP2A activity.Oncogene advance online publication, 6 July 2015; doi:10.1038/onc.2015.240. © 2015 Macmillan Publishers Limited
Pierre S.,Institute Claudius Regaud
European Journal of Anaesthesiology | Year: 2011
Despite the recent publication of international guidelines, post-operative nausea and vomiting (PONV) remains unacceptably frequent. Some authors have suggested a shift from the recommended risk-adaptive approach to ultra-liberal administration of antiemetics irrespective of the patient's risk of PONV. We review briefly the arguments in favour of measured utilisation of a simplified risk score to predict PONV. © 2011 Copyright European Society of Anaesthesiology.
Record M.,French Institute of Health and Medical Research |
Record M.,Institute Claudius Regaud |
Record M.,University Paul Sabatier
Placenta | Year: 2014
Exosomes are nanovesicles released from viable cells and have attracted increasing interest due to their role in intercellular communication and biological functions. More recently exosomes have been shown to be released by trophoblasts and to carry molecules involved in placental physiology. This involves proteins such as fibronectin, syncytin, Wnt/βcatenin-related molecules, galectin-3, and HLA-G, but also bioactive lipids such as the immunosuppressive PGE2, the PPARγ ligand 15d-PGJ2, or microRNAs that appear as immunomodulators in pregnancy and are able to confer viral resistance. Exosome trafficking within the placental micro-environment potentially links these nanovesicles to the organization of the placental interface, fetal tolerance, viral protection, and possibly mother-fetus communication. Because of the presence of immunocompetent exosomes in breast-milk, they appear as an essential component in reproduction. Several aspects of the "exosome pathway" are described in the review, from general aspects related to their origin, their characteristics and their ability to vectorize material between cells, to more specific functions involved in placental physiology such as their putative role in triggering cell fusion required for syncytiotrophoblast formation. © 2014 Elsevier Ltd. All rights reserved.
Poirot M.,Institute Claudius Regaud |
Silvente-Poirot S.,Institute Claudius Regaud
Biochimie | Year: 2013
In the nineteen sixties it was proposed that cholesterol might be involved in the etiology of cancers and cholesterol oxidation products were suspected of being causative agents. Researchers had focused their attention on cholesterol-5,6-epoxides (5,6-ECs) based on several lines of evidence: 1) 5,6-ECs contained an oxirane group that was supposed to confer alkylating properties such as those observed for aliphatic and aromatic epoxides. 2) cholesterol-5,6-epoxide hydrolase (ChEH) was induced in pre-neoplastic lesions of skin from rats exposed to ultraviolet irradiations and ChEH was proposed to be involved in detoxification processes like other epoxide hydrolases. However, 5,6-ECs failed to induce carcinogenicity in rodents which ruled out a potent carcinogenic potential for 5,6-ECs. Meanwhile, clinical studies revealed an anomalous increase in the concentrations of 5,6β-EC in the nipple fluids of patients with pre-neoplastic breast lesions and in the blood of patients with endometrious cancers, suggesting that 5,6-ECs metabolism could be linked with cancer. Paradoxically, ChEH has been recently shown to be totally inhibited by therapeutic concentrations of tamoxifen (Tam), which is one of the main drugs used in the hormonotherapy and the chemoprevention of breast cancers. These data would suggest that the accumulation of 5,6-ECs could represent a risk factor, but we found that 5,6-ECs were involved in the induction of breast cancer cell differentiation and death induced by Tam suggesting a positive role of 5,6-ECs. These observations meant that the biochemistry and the metabolism of 5,6-ECs needed to be extensively studied. We will review the current knowledge and the future direction of 5,6-ECs chemistry, biochemistry, metabolism, and relationship with cancer.
Roche H.,Institute Claudius Regaud |
Vahdat L.T.,Weill Cornell Breast Cancer Center
Annals of Oncology | Year: 2011
Increasing use of standard chemotherapy, especially anthracycline- and taxane-based therapies, in early-stage breast cancer has led to a corresponding increase in heavily pretreated and/or treatment-resistant cases of metastatic breast cancer (MBC). Thus, second and later lines of MBC therapy frequently involve the clinically challenging picture of progressive disease and limited treatment options. While several prognostic factors have been identified to aid treatment selection in MBC patients, treatment is palliative and aimed at prolonging survival, controlling symptoms, and maximizing patients' quality of life. No globally accepted standard exists for meeting these goals, and treatment patterns vary according to region. The list of available agents for the treatment of MBC is increasing with newer chemotherapeutic agents and molecular-targeted therapies. Within recent years, several single-agent and combination chemotherapy regimens have been shown to improve progression-free survival and reduce symptoms of disease in clinical studies in patients with resistant and/or heavily pretreated MBC. However, at present, the demonstrated benefits of these medical interventions have usually not included extension of overall survival times. It is hoped that in the near future, ongoing refinements to treatment approaches used in second-line settings and beyond will allow meaningful improvements in symptom control and survival in MBC. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.