Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

BACKGROUND: One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. METHODS: The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. RESULTS: uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. CONCLUSION: These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients

Mise en évidence de la protéine de réparation de l'ADN 8-oxoguanine ADN Glycosylase 1, l'Ogg1, dans le système nerveux central du rat (étude de son expression après un stress par immobilisation)

La protéine 8-Oxoguanine ADN Glycosylase 1 (Ogg1) est une ADN glycosylase /AP lyase qui excise spécifiquement la 8-oxoguanine, une lésion de l'ADN. L'objectif de cette thèse consiste en l'étude descriptive et comparative de la protéine Ogg1 et du transcrit de son gène au sein du Système Nerveux Central des vertébrés ainsi qu'en l'étude de son expression fonctionnelle. Cette protéine présente une expression ubiquitaire dans les noyaux cellulaires des neurones et des astrocytes des cerveaux de mammifères. Après un stress par immobilisation, chez le rat dans les noyaux pontiques, la protéine Ogg1 et son métabolite 8-oxo-guanine sont augmentés et continuent à augmenter pendant la période de récupération fonctionnelle, 4 heures après le stress. 24 heures après stress, une image miroir est observée entre le niveau de protéine Ogg1 et la 8-oxoguanine. Aucune variation de l'ARN messager n'a été observée pendant cette période. En conclusion, Ogg1 représente un système de réparation des bases guanines oxydées de l'ADN au niveau du SNC et l'expression de cette protéine pourrait être régulée post-transcriptionnellement après un stress par immobilisationLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Human Endogenous Retrovirus K (HML-2) Elements in the Plasma of People with Lymphoma and Breast Cancer ▿ †

Actively replicating endogenous retroviruses entered the human genome millions of years ago and became a stable part of the inherited genetic material. They subsequently acquired multiple mutations, leading to the assumption that these viruses no longer replicate. However, certain human tumor cell lines have been shown to release endogenous retroviral particles. Here we show that RNA from human endogenous retrovirus K (HERV-K) (HML-2), a relatively recent entrant into the human genome, can be found in very high titers in the plasma of patients with lymphomas and breast cancer as measured by either reverse transcriptase PCR or nucleic acid sequence-based amplification. Further, these titers drop dramatically with cancer treatment. We also demonstrate the presence of reverse transcriptase and viral RNA in plasma fractions that contain both immature and correctly processed HERV-K (HML-2) Gag and envelope proteins. Finally, using immunoelectron microscopy, we show the presence of HERV-K (HML-2) virus-like particles in the plasma of lymphoma patients. Taken together, these findings demonstrate that elements of the endogenous retrovirus HERV-K (HML-2) can be found in the blood of modern-day humans with certain cancers

Correction for chromosome-17 is critical for the determination of true Her-2/neu gene amplification status in breast cancer

PURPOSE: Trastuzumab is the cornerstone for treatment of women with HER2-overexpressing breast cancer, both in the adjuvant and in the metastatic settings. The accurate assessment of HER2 is, therefore, critical to identifying patients who may benefit from trastuzumab-based therapy. This project aimed to determine the optimal scoring method for fluorescence in situ hybridization (FISH) assay. METHODS: FISH assay was done on 893 samples of breast cancer. Three scoring methods were evaluated: Her2/CEP17> or =2, Her2>4, or Her2>6. Protein and gene expression were evaluated by immunohistochemistry (n = 584) and mRNA/assay/nucleic acid sequence-based amplification (NASBA; n = 90). RESULTS: Samples were divided into five groups based on FISH results: disomic amplified and nonamplified, polysomic amplified, nonamplified, and discordant (10.8% of cases, mostly positive with Her2>4 scoring, but negative with the others). Her2/CEP17> or =2 and Her2>6 scoring methods showed the best association (a) with regard to FISH scoring (kappa = 0.906, P 0.650, P 0.536, P 6 scoring (68% and 58% perfect matches, respectively). No perfect matches were observed using the Her2>4 scoring method. CONCLUSION: Correction for chromosome-17 is the method of choice for clinical practice; Her-2>6, but not Her-2>4, could be used as an alternative.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe