Institute Of Recherche En Cancerologie Of Montpellier Ircm
Institute Of Recherche En Cancerologie Of Montpellier Ircm
Nougaret S.,Institute Of Recherche En Cancerologie Of Montpellier Ircm |
Nougaret S.,French Institute of Health and Medical Research |
Nougaret S.,Montpellier University |
Nougaret S.,Institute Regional Du Cancer Of Montpellier |
And 4 more authors.
Imagerie de la Femme | Year: 2017
Endometrial cancer is the first diagnosed gynecologic malignancy in France with rising incidence due to obesity. Preoperative magnetic resonance imaging is nowadays critical to evaluate endometrial cancer risk of recurrence. The combination of morphological and functional MRI provides a perfectly accurate approach for patient staging (i.e. evaluation of the depth of myometrial invasion, cervical stromal invasion, extrauterine extension, and lymph node status). © 2017 Elsevier Masson SAS.
Lakhman Y.,Sloan Kettering Cancer Center |
D'Anastasi M.,Sloan Kettering Cancer Center |
D'Anastasi M.,Ludwig Maximilians University of Munich |
Micco M.,Catholic University melli Hospital |
And 9 more authors.
European Radiology | Year: 2016
Purpose: To determine if second-opinion review of gynaecologic oncologic (GynOnc) magnetic resonance imaging (MRI) by sub-specialized radiologists impacts patient care. Methods: 469 second-opinion MRI interpretations rendered by GynOnc radiologists were retrospectively compared to the initial outside reports. Two gynaecologic surgeons, blinded to the reports’ origins, reviewed all cases with discrepancies between initial and second-opinion MRI reports and recorded whether these discrepancies would have led to a change in patient management defined as a change in treatment approach, counselling, or referral. Histopathology or minimum 6-month imaging follow-up were used to establish the diagnosis. Results: Second-opinion review of GynOnc MRIs would theoretically have affected management in 94/469 (20 %) and 101/469 (21.5 %) patients for surgeons 1 and 2, respectively. Specifically, second-opinion review would have theoretically altered treatment approach in 71/469 (15.1 %) and 60/469 (12.8 %) patients for surgeons 1 and 2, respectively. According to surgeons 1 and 2, these treatment changes would have prevented unnecessary surgery in 35 (7.5 %) and 31 (6.6 %) patients, respectively, and changed surgical procedure type/extent in 19 (4.1 %) and 12 (2.5 %) patients, respectively. Second-opinion interpretations were correct in 103 (83 %) of 124 cases with clinically relevant discrepancies between initial and second-opinion reports. Conclusions: Expert second-opinion review of GynOnc MRI influences patient care. Key points: • Outside gynaecologic oncologic MRI examinations are often submitted for a second-opinion review. • One-fifth of MRIs had important discrepancies between initialand second-opinion interpretations. • Second-opinion review of gynaecologic oncologic MRI is a valuable clinical service. © 2015, European Society of Radiology.
PubMed | Birkbeck, University of London, Paris-Sorbonne University, Umeå University, Mayo Medical School and 8 more.
Type: | Journal: Nature communications | Year: 2016
Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients.
Bossard C.,Montpellier University |
Busson M.,Montpellier University |
Vindrieux D.,Montpellier University |
Gaudin F.,University Paris - Sud |
And 7 more authors.
PLoS ONE | Year: 2012
Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients. © 2012 Bossard et al.
Paillas S.,Institute Of Recherche En Cancerologie Of Montpellier Ircm |
Paillas S.,French Institute of Health and Medical Research |
Causse A.,Institute Of Recherche En Cancerologie Of Montpellier Ircm |
Causse A.,French Institute of Health and Medical Research |
And 21 more authors.
Autophagy | Year: 2012
Recently we have shown that the mitogen-activated protein kinase (MAPK) MAPK14/p38α is involved in resistance of colon cancer cells to camptothecin-related drugs. Here we further investigated the cellular mechanisms involved in such drug resistance and showed that, in HCT116 human colorectal adenocarcinoma cells in which TP53 was genetically ablated (HCT116-TP53KO), overexpression of constitutively active MAPK14/p38α decreases cell sensitivity to SN-38 (the active metabolite of irinotecan), inhibits cell proliferation and induces survival-autophagy. Since autophagy is known to facilitate cancer cell resistance to chemotherapy and radiation treatment, we then investigated the relationship between MAPK14/p38α, autophagy and resistance to irinotecan. We demonstrated that induction of autophagy by SN38 is dependent on MAPK14/p38α activation. Finally, we showed that inhibition of MAPK14/p38α or autophagy both sensitizes HCT116-TP53KO cells to drug therapy. Our data proved that the two effects are interrelated, since the role of autophagy in drug resistance required the MAPK14/p38α. Our results highlight the existence of a new mechanism of resistance to camptothecin-related drugs: upon SN38 induction, MAPK14/p38α is activated and triggers survival-promoting autophagy to protect tumor cells against the cytotoxic effects of the drug. Colon cancer cells could thus be sensitized to drug therapy by inhibiting either MAPK14/p38 or autophagy. © 2012 Landes Bioscience.
Rodier G.,French National Center for Scientific Research |
Rodier G.,Institute Of Recherche En Cancerologie Of Montpellier Ircm |
Rodier G.,French Institute of Health and Medical Research |
Rodier G.,Montpellier University |
And 48 more authors.
Cell Reports | Year: 2015
Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, includingMYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1- dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells.
Le Maire A.,French Institute of Health and Medical Research |
Le Maire A.,French National Center for Scientific Research |
Bourguet W.,French Institute of Health and Medical Research |
Bourguet W.,French National Center for Scientific Research |
And 3 more authors.
Cellular and Molecular Life Sciences | Year: 2010
Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system by interfering with hormone biosynthesis, metabolism, or action. The molecular mechanisms of EDCs involve different pathways including interactions with nuclear hormone receptors (NHRs) which are primary targets of a large variety of environmental contaminants. Here, based on the crystal structures currently available in the Protein Data Bank, we review recent studies showing the many ways in which EDCs interact with NHRs and impact their signaling pathways. Like the estrogenic chemical diethylstilbestrol, some EDCs mimic the natural hormones through conserved protein-ligand contacts, while others, such as organotins, employ radically different binding mechanisms. Such structure-based knowledge, in addition to providing a better understanding of EDC activities, can be used to predict the endocrine-disrupting potential of environmental pollutants and may have applications in drug discovery. © Birkhäuser Verlag.
Teyssier C.,French Institute of Health and Medical Research |
Teyssier C.,French National Center for Scientific Research |
Le Romancer M.,University of Lyon |
Le Romancer M.,Center Leon Berard |
And 12 more authors.
Trends in Endocrinology and Metabolism | Year: 2010
Estrogen signaling pathways regulate multiple cellular processes including proliferation and differentiation, and dysregulation of these pathways underlies several human pathologies. Post-translational modifications (PTMs) play an important role in estrogen signaling. This review focuses on recent findings pertinent to arginine methylation of non-histone proteins and their implications in estrogen signaling. We describe protein arginine methyltransferases and demethylases, the role of methylarginine proteins in estrogen action and crosstalk with other PTMs such as phosphorylation and lysine methylation. The relationships between various PTMs form a specific code that is likely to play an important role in hormone signaling. In addition, dysregulation of arginine methylation or of enzymes responsible for these modifications could be key events in estrogen-dependent cancers such as breast cancer. © 2009 Elsevier Ltd.
PubMed | Institute Of Recherche En Cancerologie Of Montpellier Ircm
Type: Journal Article | Journal: Bulletin du cancer | Year: 2011
VitaminB6 is well-known for its role as a cofactor in many enzymatic reactions and recently, several epidemiological studies have highlighted the importance of this vitamin as a protective agent against various cancers: elevated vitaminB6 plasma levels were associated with a lower risk of colorectal cancer development, for example. Invivo studies have shown that vitaminB6 decreased cell proliferation and enhanced the immune response. At the cellular level, antioxidant, pro-apoptotic and anti-angiogenic effects have been identified. At the molecular level, vitaminB6 is able to inhibit the transactivation potential of various nuclear receptors. Interestingly, a recent paper has described the conjugation of vitaminB6 to RIP140 (receptor interacting protein of 140kDa), a protein that acts as a transcriptional corepressor of nuclear receptors. This post-translational modification increases the transcriptional repression of RIP140 and regulates its subcellular localization and its ability to interact with different protein partners. Finally, vitaminB6 is involved in the methyl donor cycle ant thus, some of the antitumor properties of vitaminB6 may involve an indirect effect on the level of DNA or histone methylation. All of these mechanistic and clinical data justify further studies to decipher the mechanism of action of vitaminB6 and its clinical interest in combination with molecules typically used in chemotherapy or hormonal therapy.
PubMed | Institute Of Recherche En Cancerologie Of Montpellier Ircm
Type: | Journal: Methods in molecular biology (Clifton, N.J.) | Year: 2016
Circulating cell-free DNA (cfDNA) is a valuable source of tumor material available with a simple blood sampling enabling a noninvasive quantitative and qualitative analysis of the tumor genome. cfDNA is released by tumor cells and exhibits the genetic and epigenetic alterations of the tumor of origin. Circulating cell-free DNA (cfDNA) analysis constitutes a hopeful approach to provide a noninvasive tumor molecular test for cancer patients. Based upon basic research on the origin and structure of cfDNA, new information on circulating cell-free DNA (cfDNA) structure, and specific determination of cfDNA fragmentation and size, we revisited Q-PCR-based method and recently developed a the allele-specific-Q-PCR-based method with blocker (termed as Intplex) which is the first multiplexed test for cfDNA. This technique, named Intplex() and based on a refined Q-PCR method, derived from critical observations made on the specific structure and size of cfDNA. It enables the simultaneous determination of five parameters: the cfDNA total concentration, the presence of a previously known point mutation, the mutant (tumor) cfDNA concentration (ctDNA), the proportion of mutant cfDNA, and the cfDNA fragmentation index. Intplex() has enabled the first clinical validation of ctDNA analysis in oncology by detecting KRAS and BRAF point mutations in mCRC patients and has demonstrated that a blood test could replace tumor section analysis for the detection of KRAS and BRAF mutations. The Intplex() test can be adapted to all mutations, genes, or cancers and enables rapid, highly sensitive, cost-effective, and repetitive analysis. As regards to the determination of mutations on cfDNA Intplex() is limited to the mutational status of known hotspot mutation; it is a targeted approach. However, it offers the opportunity in detecting quantitatively and dynamically mutation and could constitute a noninvasive attractive tool potentially allowing diagnosis, prognosis, theranostics, therapeutic monitoring, and follow-up of cancer patients expanding the scope of personalized cancer medicine.