III.

Breast cancer is a malignancy whose dependence on estrogen exposure has long been recognized even though the mechanisms whereby estrogens cause cancer are not clearly understood. This work was performed to determine whether 17beta-estradiol (E2), the predominant circulating ovarian steroid, is carcinogenic in human breast epithelial cells and whether nonreceptor mechanisms are involved in the initiation of breast cancer. For this purpose, the effect of four 24 h alternate periods of 70 nM E2 treatment of the estrogen receptor alpha (ER-alpha) negative MCF-10F cell line on the in vitro expression of neoplastic transformation was evaluated. E2 treatment induced the expression of anchorage-independent growth, loss of ductulogenesis in collagen, invasiveness in Matrigel, and loss of 9p11-13. Only invasive cells that exhibited a 4p15.3-16 deletion were tumorigenic. Tumors were poorly differentiated ER-alpha and progesterone receptor-negative adenocarcinomas that expressed keratins, EMA, and E-cadherin. Tumors and tumor-derived cell lines exhibited loss of chromosome 4, deletions in chromosomes 3p12.3-13, 8p11.1-21, 9p21-qter, and 18q, and gains in 1p, and 5q15-qter. The induction of complete transformation of MCF-10F cells in vitro confirms the carcinogenicity of E2, supporting the concept that this hormone could act as an initiator of breast cancer in women. This model provides a unique system for understanding the genomic changes that intervene for leading normal cells to tumorigenesis and for testing the functional role of specific genomic events taking place during neoplastic transformation.

There's something in the air … A nanocomposite consisting of well-dispersed SnO(2) and Pt nanoparticles on reduced graphene oxide (see the high-resolution TEM image) exhibited very high responses to hydrogen at concentrations between 0.5 and 3% in air, with response times of 3-7 s and recovery times of 2-6 s. The sensor was prepared by a straightforward microwave-assisted non-aqueous sol-gel approach.

Introduction Sexual distress is an important component of diagnostic criteria for sexual dysfunctions, but little is known about the factors associated with sexual distress in women with low sexual desire. Aim To investigate the correlates of sexual distress in women with self-reported low sexual desire. Methods The Prevalence of Female Sexual Problems Associated with Distress and Determinants of Treatment Seeking study was a cross-sectional, nationally representative, mailed survey of U.S. adult women. There were 31,581 respondents (response rate 63.2%) to the 42-item questionnaire that measured sexual function, sexual distress, demographic, and health-related factors. Multivariable logistic regression was used to explore the correlates of distress. Main Outcome Measures Low sexual desire was defined as a response of “never” or “rarely” to the question, “How often do you desire to engage in sexual activity?” Sexual distress was measured with the Female Sexual Distress Scale (range 0–48), with a score of 15 or higher indicating presence of distress. Results Of 10,429 women with low desire, 2,868 (27.5%) had sexual distress (mean age 48.6 years, 81% with a current partner). Women without distress were 10 years older on average, and 44% had a current partner. Having a partner was strongly related to distress (odds ratio 4.6, 95% confidence interval 4.1–5.2). Other correlates were age, race, current depression, anxiety, lower social functioning, hormonal medication use, urinary incontinence, and concurrent sexual problems (arousal or orgasm). Dissatisfaction with sex life was more common in women with low desire and distress (65%) than in those without distress (20%). Conclusions Age has a curvilinear relationship with distress, and the strongest correlate of sexual distress was having a current partner. Sexual distress and dissatisfaction with sex life are strongly correlated. Distress is higher in women with low sexual desire in a partner relationship; further research on this factor is needed.

Early pregnancy and multiparity are known to reduce the risk of women to develop breast cancer at menopause. The knowledge that the differentiation of the breast induced by the hormones of pregnancy plays a major role in this protection, the present work was performed with the purpose of identifying what differentiation-associated molecular changes persist in the breast until menopause. Core needle biopsies (CNB) obtained from the breast of 42 nulliparous (NP) and 71 parous (P) postmenopausal women were analyzed in morphology, immunocytochemistry and gene expression. Whereas in the NP breast nuclei of epithelial cells were large and euchromatic, in the P breast they were small and hypercromatic, showing strong methylation of istone 3 at lysine 9 and 27. Transcriptomic analysis performed using Affymetrix HG_U133 oligonucleotide arrays revealed that in CNB of the P breast there were 267 upregulated probesets that comprised genes controlling chromatin organization, transcription regulation, splicing machinery, mRNA processing, and noncoding elements including XIST. We concluded that the differentiation process induced by pregnancy is centered in chromatin remodeling and in the mRNA processing reactome, both of which emerge as important regulatory pathways. These are indicative of a safeguard step that maintains the fidelity of the transcription process, becoming the ultimate mechanism mediating the protection of the breast conferred by full term pregnancy.