PubMed · 13289369
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C PELOSIO. 1955-11-07. [The breast; development and function].. https://pubmed.ncbi.nlm.nih.gov/13289369/
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Microarrays have been extensively used to investigate genome-wide expression patterns. Although this technology has been tremendously successful, it has suffered from suboptimal individual measurement precision. Significant improvements in this respect have been recently made. In an effort to further explore the underlying variability, we have attempted to globally assess the accuracy of individual probe sequences used to query gene expression. For mammalian Affymetrix microarrays, we identify an unexpectedly large number of probes (greater than 19% of the probes on each platform) that do not correspond to their appropriate mRNA reference sequence (RefSeq). Compared with data derived from inaccurate probes, we find that data derived from sequence-verified probes show 1) increased precision in technical replicates, 2) increased accuracy translating data from one generation microarray to another, 3) increased accuracy translating data from oligonucleotide to cDNA microarrays, and 4) improved capture of biological information in human clinical specimens. The logical conclusion of this work is that probes containing the most reliable sequence information provide the most accurate results. Our data reveal that the identification and removal of inaccurate probes can significantly improve this technology.
In the present study, we showed that a single-dose treatment of normal breast epithelial cell line, MCF10A, for 72 h with cigarette smoke condensate (CSC) resulted in a transformed phenotype. The anchorage-dependent growth of these cells was decreased due to increased cell cycle arrest in S-G2/M phase; however, the surviving cells developed resistance due to an increased Bcl-xL to Bax ratio. Levels of PCNA and gadd45 proteins--involved in DNA repair in response to genomic damage--were increased, suggesting that the cells were responding to CSC-induced genomic damage. The transformation of MCF10A cells was determined by their colony-forming efficiency in soft-agar in an anchorage-independent manner. CSC-treated MCF10A cells efficiently formed colonies in soft-agar. We then re-established cell lines from the soft-agar colonies and further examined the persistence of their transforming characteristics. The re-established cell lines, when plated after 17 passages without CSC treatment, still formed colonies in the soft-agar. An increased staining of neuropilin-1 (NRP-1) further showed a transformation characteristic of MCF10A cells treated with CSC. In summary, our results suggest that CSC is capable of transforming the MCF10A cells in vitro, supporting the role of cigarette smoking and increased risk for breast cancer.
UNLABELLED: Hormone replacement therapy (HRT) is widely used with a large variety of regimens and medications. For each of these regimens the goal is the same but there is always a fear about side effects, especially on breast. Mammographic screening is a standard tool for all women receiving hormone replacement therapy. Breast density is very important, because it interferes with the sensitivity of the evaluation and it is also a predictor of malignity. OBJECTIVE: We planned a study to investigate the effects of tibolone on mammographic breast density. DESIGN AND METHODS: We studied 70 postmenopausal women who started tibolone therapy (2.5 mg per day) after initial mammography and blood samples taken for biochemical examinations. None of the women used any hormone replacement therapy before. Eleven of them either discontinued the therapy or lost contact. After 1 year, we evaluated 59 women by mammographic status, using Wolfe classification. Mammographies were analyzed by two independent radiologists. RESULTS: Mammographies of 59 women were compared with the initial ones. While in the low density patterns, there was a slight increase (15%; P < 0.05); in the higher density groups, there was a decrease of 25% as observed by one radiologist, and 16% according to the other (P < 0.05). None of the women had a diffuse, high density pattern. There was no statistically significant inter-observer variation between two radiologists (P < 0.05). CONCLUSIONS: Wolfe classification allows easy interpretation of mammographic evaluation and the results are reproducible. Tibolone, as a tissue-specific steroid, does not have an estrogenic effect on breast cells. We found that it might limit, even reverse breast density increase, especially in postmenopausal women with high breast density.