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2 results on '"Meyniel, Jean-Philippe"'

1. miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response

Author

Mateescu, Bogdan, Batista, Luciana, Cardon, Melissa, Gruosso, Tina, de Feraudy, Yvan, Mariani, Odette, Nicolas, Andre, Meyniel, Jean-Philippe, Cottu, Paul, Sastre-Garau, Xavier, and Mechta-Grigoriou, Fatima

Subjects
Ovarian tumors -- Research -- Physiological aspects, MicroRNA -- Research -- Physiological aspects, Oxidative stress -- Research -- Physiological aspects, Biological sciences, Health
Abstract

Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38a and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38a deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials., Epithelial ovarian cancer is the most lethal form of gynecologic malignancy. The clinical prognosis factors for this type of cancer are based on the state of the disease at diagnosis, [...]

Published
2011
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2. High-resolution mapping of DNA breakpoints to define true recurrences among ipsilateral breast cancers

Author

Bollet, Marc A., Servant, Nicolas, Neuvial, Pierre, Decraene, Charles, Lebigot, Ingrid, Meyniel, Jean-Philippe, De Rycke, Yann, Savignoni, Alexia, Rigaill, Guillem, Hupe, Philippe, Fourquet, Alain, Sigal-Zafrani, Brigitte, Barillot, Emmanuel, and Thiery, Jean-Paul

Subjects
Breast cancer -- Diagnosis, Breast cancer -- Genetic aspects, DNA microarrays -- Usage, Single nucleotide polymorphisms -- Identification and classification, Health
Abstract

Background To distinguish new primary breast cancers from true recurrences, pangenomic analyses of DNA copy number alterations (CNAs) using single-nucleotide polymorphism arrays have proven useful. Methods The pangenomic profiles of 22 pairs of primary breast carcinoma (ductal or Iobular) and ipsilateral breast cancers from the same patients were analyzed. Hierarchical clustering was performed using CNAs and DNA breakpoint information. A partial identity score developed using DNA breakpoint information was used to quantify partial identities between two tumors. The nature of ipsilateral breast cancers (true recurrence vs new primary tumor) as defined using the clustering methods and the partial identity score was compared with that based on clinical characteristics. Metastasis-free survival was compared among patients with primary tumors and true recurrences as defined using the partial identity score and by clinical characteristics. All statistical tests were two-sided. Results All methods agreed on the nature of ipsilateral breast cancers for 14 pairs of samples. For tive pairs, the clinical definition disagreed with both clustering methods. For three pairs, the two clustering methods were discordant and the one using DNA breakpoints agreed with the clinical definition. The partial identity score confirmed the nature of ipsilateral breast cancers as defined by clustering of DNA breakpoints in 21 of 22 pairs. The difference in metastasis-free survival of patients with new primary tumors and those with true recurrences was not statistically significant when tumors were defined based on clinical and histologic characteristics (5-year metastasis-free survival: 76%, 95% confidence interval [CI] = 52% to 100% for new primary tumors and 38%, 95% CI = 17% to 83% for true recurrences; P = .18; new primary tumor vs true recurrence, hazard ratio = 2.8, 95% CI = 0.6 to 13.7), but the difference was statistically significant when tumors were defined using the partial identity score (5-year metastasis-free survival: 100% for new primary tumors and 29%, 95% CI = 11% to 78% for true recurrences; P= .01). Conclusions DNA breakpoint information more often agreed with the clinical determination than CNAs in this population. The partial identity score, which was calculated based on DNA breakpoints, allows statistical discrimination between new primary tumors and true recurrences that could outperform the clinical determination in terms of prognosis.

Published
2008

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