Fluorescence Analysis of Vitamin D Receptor Status of Circulating Tumor Cells (CTCS) in Breast Cancer: From Cell Models to Metastatic Patients

The Vitamin D receptor (VDR) expressed in normal breast tissue and breast tumors has been suggested as a new prognostic biomarker in breast cancer (BC). Besides, increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcome in early and metastatic BC. Consequently, an evaluation of VDR expression in the CTCs of BC patients may allow optimization of their treatment. As an attempt to profile and subtype the CTCs of metastatic patients, we established an innovative fluorescence technique using nine BC cell lines to visualize, define, and compare their individual VDR status. Afterwards, we tested the CTC presence and VDR expression in blood samples (cytospins) collected from 23 metastatic BC patients. The results demonstrated major differences in the VDR levels among the nine cell lines, and VDR positive CTCs were detected in 46% of CTC-positive patients, with a total of 42 CTCs individually analyzed. Due to the limited number of patients in this study, no correlation between VDR expression and BC subtype classification (according to estrogen receptor (ER), progesterone receptor (PR) and HER2) could be determined, but our data support the view that VDR evaluation is a potential new prognostic biomarker to help in the optimization of therapy management for BC patients

Cytoplasmic LXR expression is an independent marker of poor prognosis for patients with early stage primary breast cancer

International audiencePurpose The aim of this study was to investigate the expression of liver X receptors α/β (LXR) in primary breast cancer (BC) tissues and to analyze its correlations with clinicopathological parameters including patient survival. Methods In a well-characterized cohort of 305 primary BC, subcellular distribution of LXR was evaluated by immunohistochemistry. Correlations with clinicopathological characteristics as well as with patient outcome were analyzed. Results LXR was frequently localized in both nuclei and cytoplasms of BC cells, with stronger staining in nuclei. Total and nuclear LXR expression was positively correlated with ER and PR status. Overall survival analysis demonstrated that cytoplasmic LXR was significantly correlated with poor survival and appeared as an independent marker of poor prognosis, in stage I but not in stage II–III tumors Conclusion Altogether, these data suggest that cytoplasmic LXR could be defined as a prognostic marker in early stage primary BC

Cytoplasmic colocalization of RXRα and PPARγ as an independent negative prognosticator for breast cancer patients

Retinoid X receptor α (RXRα) is a nuclear receptor (NR) which functions as the primary heterodimeric partner of other NRs including the peroxisome proliferator-activated receptor γ (PPARγ). We previously reported that, in breast cancers (BC), the subcellular localization of these two receptors was strongly associated with patient prognosis. In the present work, we investigated the prognosis value of the combined cytoplasmic expression of RXRα and PPARγ using a retrospective cohort of 250 BC samples. Patients with tumors expressing both NRs in tumor cell cytoplasm exhibited a significant shorter overall (OS) and disease-free survival (DFS). This was also observed for patients with stage 1 tumors. Cox univariate analysis indicated that patients with tumors coexpressing RXRα and PPARγ in the cytoplasm of tumor cells have a decreased 5 y OS rate. Cytoplasmic co-expression of the two NRs significantly correlated with HER2 positivity and with NCAD and CD133, two markers of tumor aggressiveness. Finally, in Cox multivariate analysis, the co-expression of RXRα and PPARγ in the cytoplasm appeared as an independent OS prognosticator. Altogether, this study demonstrates that the cytoplasmic co-expression of RXRα and PPARγ could be of relevance for clinicians by identifying high-risk BC patients, especially amongst those with early and node-negative disease

Contribution a la mise au point du ciblage de foyers inflammatoires ou infectieux a l'aide de molecules electrochargees dans es phagocytes

Available from INIST (FR), Document Supply Service, under shelf-number : TD 82099 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Les compléments alimentaires (usages, bénéfices et risques)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Interrelations entre les protéines Rho et le récepteur des oestrogènes alpha dans des modèles de cancers mammaires

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Prise en charge officinale du cancer du sein (traitements actuels, influence de l'obésité)

Le cancer du sein représente le premier rang des cancers féminins, avec plus de 50.000 nouveaux cas estimés par an en France. Grâce aux progrès de la recherche en matière de lutte contre le cancer, il existe aujourd'hui de nombreuses alternatives thérapeutiques, telles que la chirurgie, la radiothérapie, la chimiothérapie, l'hormonothérapie, la thérapie ciblée. En tant qu'acteur de santé publique, le pharmacien doit connaître l'évolution des traitements du cancer du sein, les facteurs de risques connus, les effets indésirables du traitement prescrit ; il a un rôle de conseil, d'information, d'orientation. Les dernières recherches épidémiologiques mettent en évidence le lien grandissant entre l'obésité et la prévalence des cancers du sein. Ainsi, le conseil diététique nécessite d'être bien maîtrisé par le pharmacien afin de prévenir l'obésité.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Utilisation clinique de l'association zarnestra® / novocaïne® dans le traitement des cancers du sein hormonodépendants

La survenue d'une résistance à l'hormonothérapie, et plus particulièrement au tamoxifène, constitue un problème majeur dans la prise en charge thérapeutique des carcinomes mammaires hormonodépendants. L'identification de mécanismes de résistance mettant en jeu les différentes voies oestrogéniques et d'autres voies de signalisation intracellulaires, a permis le développement de thérapies ciblées bloquant la transmission du signal à l'origine de la prolifération cellulaire tumorale. Ces thérapies ciblées, telles que les inhibiteurs des récepteurs à activité tyrosine kinase ou les inhibiteurs de farnésyltransférase, ont montré leur efficacité dans des travaux précliniques et les résultats obtenus lors des premiers essais cliniques laissent entrevoir l'espoir de nouvelles associations thérapeutiques. Une étude clinique de phase II combinant le tamoxifène à un inhibiteur de farnésyltransférase, le tipifarnib (Zarnestra®), dans les carcinomes mammaires hormonodépendants, illustre le bénéfice clinique attendu pour de telles associations.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Les compléments alimentaires (usages, bénéfices et risques)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF