Amplification of loci present on band q13 of human chromosome 11 is a feature of a subset of estrogen receptor positive breast carcinomas prone to metastasis. As many as five distinct amplification units have been described on 11q13. They include particularly a genomic area encompassing the GARP gene at 11q13.5→q14.1. We have reassessed our current knowledge of this region, located telomeric to CCND1 and EMS1, which is amplified in 7–10% of mammary tumors. The loose definition of the driving forces of these amplification events led us to map accurately the boundaries of the amplifiable region, and thus to contribute a physical and transcriptional map of a 3-Mb region of chromosome 11. Four new genes were placed on the regional map, namely CBP2, CLNSIA, UVRAG, and PAKl. We have narrowed the core of the 11q13→q14 amplicon to a 350-kb area encompassing D11S533, mostly on its telomeric side. The map reported here represents an indispensable step toward sequencing the entire region, and thus toward uncovering gene(s) which play(s) a critical role in breast cancer progression.
We explored, by cDNA mini-arrays, gene expression measurements of MVLN, a human breast carcinoma cell line derived from MCF-7, after 4 days of exposure to 17 -estradiol (E 2 ) treatment, in order to extend our understanding of the mechanism of the pharmacological action of estrogens. We focused on 22 genes involved in estrogen metabolism, cell proliferation regulation and cell transformation. genes. The temporal response of these gene expression regulations was then investigated after 6 and 18 h of E 2 treatment and this allowed the identification of different time-course patterns. Cycloheximide treatment studies indicated first that estrogen affected the transcript levels of ABCC3 and ABCC5 through dissimilar pathways, and secondly that protein synthesis was needed for modulation of the expression of the CCNA2 and TACC1 genes by estrogens. Western blot analysis performed on TFF1, IRS1, IGFBP4, amphiregulin, PCNA, cyclin A2, TACC1 and ABCC5 proteins confirmed the mini-array and RTQ-PCR data, even for genes harboring low variations of mRNA expression. Our findings should enhance the understanding of changes induced by E 2 on the transcriptional program of human E 2 -responsive cells and permit the identification of new potential diagnostic/prognostic tools for the monitoring of estrogen-related disease conditions such as breast cancer.
The initial experience with this simple technique of antegrade cerebral perfusion avoiding profound systemic hypothermia and the possible disadvantages of femoral artery cannulation appears promising.
To evaluate the potential of centrifugal blood pumps for saving blood, 120 patients scheduled for elective coronary artery bypass grafting were entered into a prospective randomized trial. A standard roller pump (group I) was compared with a centrifugal blood pump (group II) and roller pump plus aprotinin (group III). There was no significant difference between groups I and II with respect to free haemoglobin, lactic dehydrogenase, serum bilirubin, platelet surface glycoprotein IIb-IIIa and granule membrane protein 140, chest-tube drainage, use of blood products, length of stay in intensive care, time on ventilator and postoperative mortality. Aprotinin reduced chest-tube drainage and use of blood products significantly. Three cases of graft occlusions were noted in group III. Centrifugal blood pumps offer no advantage in routine heart surgery over conventional roller pumps. Aprotinin reduces blood loss, but does not influence GP IIb-IIIa and GMP 140 expression on blood platelets.
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