Letrozole sensitizes breast cancer cells to ionizing radiation

INTRODUCTION: Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. We determined the effects of the combination of RT and letrozole in the aromatase-expressing breast tumour cell line MCF-7CA, stably transfected with the CYP19 gene. METHODS: Irradiations were performed using a cobalt-60 source with doses ranging from 0 to 4 Gy. Cells were incubated with androstenedione in the presence or absence of letrozole. Effects of treatment were evaluated using clonogenic assays, tetrazolium salt colorimetric (MTT) assays, and cell number determinations. Cell-cycle analyses were conducted using flow cytometry. RESULTS: The survival fraction at 2 Gy was 0.66 for RT alone and was 0.44 for RT plus letrozole (P = 0.02). Growth of MCF-7CA cells as measured by the cell number 6 days after radiotherapy (2 and 4 Gy) was decreased by 76% in those cells treated additionally with letrozole (0.7 μM) compared with those receiving radiotherapy alone (P = 0.009). Growth inhibition, assessed either by cell number (P = 0.009) or by the MTT assay (P = 0.02), was increased after 12 days of the combination treatment. Compared with radiation alone, the combination of radiation and letrozole produced a significant decrease in radiation-induced G(2 )phase arrest and a decrease of cells in the S phase, with cell redistribution in the G(1 )phase. CONCLUSIONS: These radiobiological results may form the basis for concurrent use of letrozole and radiation as postsurgical adjuvant therapy for breast cancer

Added value of hepcidin quantification for the diagnosis and follow-up of anemia-related diseases.

International audienceIron homeostasis is based on a strict control of both intestinal iron absorption and iron recycling through reticulo-endothelial system. Hepcidin controls the iron fluxes in order to maintain sufficient iron levels for erythropoietic activities, hemoproteins synthesis or enzymes function, but also to limit its toxic accumulation throughout the body. Hepcidin expression is regulated by various stimuli: inflammation and iron stimulate the production of the peptide, while anemia, erythropoiesis and hypoxia repress its production. Regulation of hepcidin expression is not so simple in complex pathological situations such as hemolytic anemia, cancer or chronic inflammation. Serum hepcidin quantification in association with the diagnostic tests currently available is quite promising for the diagnosis or the follow-up of anemia in those conditions. This study is part of the working group « Clinical interests of hepcidin quantification » of the Société française de biologie clinique

Hepcidin: immunoanalytic characteristics

International audienceHepcidin has progressively become essential in clinical practice for the diagnosis and follow-up of a large spectrum of diseases. Anyway, its own biochemical and structural characteristics have complicated and delayed the acquisition of a standardized quantifying tool of the peptide

Variable age of onset and clinical severity in transferrin receptor 2 related haemochromatosis: novel observations

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The role of genetic factors in patients with hepatocellular carcinoma and iron overload - a prospective series of 234 patients

International audienceBACKGROUND & AIMS:Iron overload (IO) in HFE-related hereditary haemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC).METHODS:Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/L (females) and/or transferrin saturation ≥50% (males) or ≥45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC.RESULTS:A total of 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, three were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. Thirteen patients with a LIC>70 μmol/g were enrolled in further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe haemochromatosis. Specific haplotypes of SLC40A1 were also studied.CONCLUSIONS:Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and the associated at-risk genotypes in patients who have developed HCC, is useful for both determining etiologic diagnosis and enabling family screening and possibly primary prevention in relatives

Potentiation of radiation-induced growth inhibition by letrozole measured by the MTT assay

<p><b>Copyright information:</b></p><p>Taken from "Letrozole sensitizes breast cancer cells to ionizing radiation"</p><p>Breast Cancer Research 2004;7(1):R156-R163.</p><p>Published online 7 Dec 2004</p><p>PMCID:PMC1064115.</p><p>Copyright © 2004 Azria et al., licensee BioMed Central Ltd.</p> Growth of MCF-7CA cells, measured 6 days after treatment, was inhibited to a 40% greater extent with letrozole plus 2 Gy radiation, and to a 76% greater extent with letrozole plus 4 Gy radiation, compared with radiation alone

Potentiation of radiation-induced growth inhibition by letrozole measured by cell-count assay

<p><b>Copyright information:</b></p><p>Taken from "Letrozole sensitizes breast cancer cells to ionizing radiation"</p><p>Breast Cancer Research 2004;7(1):R156-R163.</p><p>Published online 7 Dec 2004</p><p>PMCID:PMC1064115.</p><p>Copyright © 2004 Azria et al., licensee BioMed Central Ltd.</p> Growth of MCF-7CA cells, measured for 18 days after treatment, was inhibited to a 76% greater extent with letrozole plus 4 Gy radiation after 12 days, and to an 85% greater extent after 18 days, compared with radiation alone. Solid lines, ■ and ◆ represent radiation alone at 2 Gy and 4 Gy, respectively; dotted lines, ■ and ◆ represent combination of radiation plus letrozole (0.7 μM) at 2 Gy and 4 Gy, respectively

Potentiation of radiation-induced growth inhibition by letrozole measured by clonogenic assay

<p><b>Copyright information:</b></p><p>Taken from "Letrozole sensitizes breast cancer cells to ionizing radiation"</p><p>Breast Cancer Research 2004;7(1):R156-R163.</p><p>Published online 7 Dec 2004</p><p>PMCID:PMC1064115.</p><p>Copyright © 2004 Azria et al., licensee BioMed Central Ltd.</p> With radiation alone the MCF-7CA cell survival fraction decreased in a dose-dependent manner, which was significantly potentiated by the addition of 0.7 μM letrozole. For 2 Gy radiation, the surviving fraction was 0.66 with radiation alone and was 0.46 with the addition of letrozole (= 0.02). For 3 Gy radiation, the corresponding surviving fractions were 0.4 and 0.18, respectively (= 0.02)