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Barriere G.,Astralab Clinical Laboratory | Riouallon A.,Clinique du Colombier | Renaudie J.,Clinique du Colombier | Tartary M.,Astralab Clinical Laboratory | Rigaud M.,Astralab Clinical Laboratory
Anticancer Research | Year: 2012

Background: Breast cancer is one of the most common malignancies in women. Approximately 25% of patients with early-stage disease will develop metastatic recurrence. Two clinical trials were undertaken in order to detect circulating tumor cells (CTCs) in primary breast cancer. Patients and Methods: Four-hundred patients with early breast cancer were enrolled in the trial. After enrichment from their peripheral blood, their CTCs were characterized by gene expression of cancer cell markers. Results: CTCs had a predominant epithelial phenotype in 8.75% of patients and dedifferentiated characteristics (mesenchymal, stem phenotypes alone or both) in 37.6%. Conclusion: Tumor epithelial cells undergoing epithelial-mesenchymal transition give rise to cells with mesenchymal aggressive phenotype. Detection of mesenchymal and cancer stem cells, which are tumorinitiating cells, is more relevant than simple counting of CTCs to assess their presence in the blood of patients with breast cancer. This study will be the basis for future evaluation of the outcome of the disease and the prognostic value of early-detected CTCs. Source

Barriere G.,Astralab Clinical Laboratory | Riouallon A.,Clinique du Colombier | Renaudie J.,Clinique du Colombier | Tartary M.,Astralab Clinical Laboratory | Rigaud M.,Astralab Clinical Laboratory
BMC Cancer | Year: 2012

Background: Epithelial mesenchymal transition (EMT) is a crucial event likely involved in dissemination of epithelial cancer cells. This process enables them to acquire migratory/invasive properties, contributing to tumor and metastatic spread. To know if this event is an early one in breast cancer, we developed a clinical trial. The aim of this protocol was to detect circulating tumor cells endowed with mesenchymal and/or stemness characteristics, at the time of initial diagnosis. Breast cancer patients (n = 61), without visceral or bone metastasis were enrolled and analysis of these dedifferentiated circulating tumor cells (ddCTC) was realized.Methods: AdnaGen method was used for enrichment cell selection. Then, ddCTC were characterized by RT-PCR study of the following genes: PI3Kα, Akt-2, Twist1 (EMT markers) and ALDH1, Bmi1 and CD44 (stemness indicators).Results: Among the studied primary breast cancer cohort, presence of ddCTC was detected in 39% of cases. This positivity is independant from tumor clinicopathological factors apart from the lymph node status.Conclusions: Our data uniquely demonstrated that in vivo EMT occurs in the primary tumors and is associated with an enhanced ability of tumor cells to intravasate in the early phase of cancer disease. These results suggest that analysis of circulating tumor cells focused on cells showing mesenchymal or stemness characteristics might facilitate assessment of new drugs in clinical trials. © 2012 Barrière et al; licensee BioMed Central Ltd. Source

Tabaraud F.,Clinical Center | Leman J.P.,Clinical Center | Milor A.M.,Clinical Center | Roussie J.M.,Astralab Clinical Laboratory | And 4 more authors.
Acta Neurologica Scandinavica | Year: 2012

Objectives- Our work was aimed to evaluate Alzheimer's disease diagnosis improvement using cerebrospinal fluid biomarkers (CSF) in neurological daily practice. Materials and Methods- For this purpose, 150 patients clinically and neurochemically classified as having AD or cognitive impairment with or without other dementia type were included in the study. The following CSF peptides were studied, blindly to the clinical diagnosis: beta-amyloid 1-42 peptide (Aβ 1-42), Tau (T-tau), threonine-181 hyperphosphorylated tau protein (P-tau 181), and beta-amyloid 1-40 peptide (Aβ 1-40). From these measurements, Innotest® Amyloid Tau Index (IATI) was calculated for each patient. Results- This assessment allowed to separate 83 biochemical profiles of AD and 67 non-Alzheimer's disease (non-AD), both AD and non-AD categories match with clinical data amounting to 73% and 90%, respectively. Among mild cognitive impairment (MCI) patients, CSF biomarkers led to discriminate those who are likely to be AD. We devoted a special section to Aβ 1-40 which is not a routine parameter but can help to confirm a pathological amyloid process as Aβ 1-42/Aβ 1-40 ratio underlining the real decline of the Aβ 1-42. Conclusions- The interest of biomarkers and their ability to solve awkward cases were carefully noticed all the more when a discrepancy between clinical and CSF biological data was involved. The final proposed algorithm allowed to identify pathogenic forms of AD according to the prevailing role of hyperphosphorylated tau or amyloid beta peptide. © 2011 John Wiley & Sons A/S. Source

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