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    ABSTRACT: Breast cancer is the second-most prevalent cancer in the United States. Although overall outcomes are promising for early-stage (I/II) disease, prognosis is poor for those with metastatic or recurrent disease. Skeletal recurrence occurs frequently in breast cancer and is associated with significant morbidity. However, the mechanisms underlying the development of skeletal metastases in breast cancer are poorly understood. Cox et. al. recently reported their discovery that lysyl oxidase (LOX) induces skeletal metastases in estrogen receptor-negative (ER-negative) breast adenocarcinoma. They first uncovered differential expression of LOX in samples of tumoral tissue from ER-negative breast cancers. Using a murine syngeneic model of spontaneously-metastasizing ERnegative breast adenocarcinoma, they demonstrated increased formation of pre-metastatic osteolytic lesions in mice harboring tumors with high levels of LOX expression and in those treated with tumorconditioned media from tumor cell lines with high levels of LOX expression. These findings were reproducible with colorectal adenocarcinoma cell lines overexpressing LOX. Perhaps most notably, they demonstrated that the pre-metastatic lesions observed form when LOX stimulates osteoclast activity in a RANK-independent manner. Although further work is needed to elicit why LOX is associated with skeletal metastases in ER-negative breast cancer alone, this work supports a role for novel, LOX-specific inhibitors in treating skeletal recurrence of ER-negative breast adenocarcinoma.
    09/2015; DOI:10.1016/j.gendis.2015.08.004
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    ABSTRACT: The Hippo signaling pathway was first discovered in Drosophila as a conserved regulator of organ size. Genetic inactivation in mice demonstrates that the Hippo pathway functions as a fundamental inhibitor of organ growth during development, and as a critical tumor suppressor in epithelial tissues.
    12/2014; 1(2). DOI:10.1016/j.gendis.2014.09.001
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    ABSTRACT: Background: In patients with heart disease, the presence of a fragmented QRS complex (fQRS) on the surface electrocardiogram (ECG) is associated with an increased risk of mortality. We sought to evaluate the prevalence and location of fQRS before and after left ventricular assist device (LVAD) implantation and any associated risk of mortality. Methods and results: Twelve-lead surface ECGs before (pre-LVAD, n. =. 98) and after (early [<. 7. days], n. =. 96, and late [≥. 30. days], n. =. 85, post-LVAD) LVAD implantation were evaluated for fQRS. Mortality data were gathered via review of medical records. The prevalence of fQRS increased significantly following LVAD implantation on early post-LVAD ECGs (31% to 47%, p. <. 0.01). Patients with fQRS in the anterior territory (precordial leads V1 to V5) on late post-LVAD ECGs had decreased survival or survival to cardiac transplantation over a 30. month follow-up period compared with patients who did not exhibit anterior fQRS (30% and 59%, respectively, p. <. 0.01). Conclusions: The prevalence of fragmented QRS on 12-lead ECG increases significantly in the anterior territory following LVAD implantation and is associated with decreased survival.
    11/2014; 357. DOI:10.1016/j.ijcha.2014.10.017


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