Characterization of MCF-12A cell phenotype, response to estrogens, and growth in 3D.

Background: Three-dimensional cultures of mammary epithelial cells allow for biologically-relevant studies of the development of the mammary gland in rodents and humans under normal and pathological conditions, like carcinogenesis. Under these conditions, mammotropic hormones play significant roles in tissue morphogenesis. Therefore, a system that recreates the normal, hormonally responsive epithelium would be a valuable tool to study the normal state and its transition to carcinogenesis.

A Hormone-responsive 3D Culture Model of the Human Mammary Gland Epithelium.

The process of mammary epithelial morphogenesis is influenced by hormones. The study of hormone action on the breast epithelium using 2D cultures is limited to cell proliferation and gene expression endpoints. However, in the organism, mammary morphogenesis occurs in a 3D environment.

TAK1 inhibition promotes apoptosis in KRAS-dependent colon cancers.

Colon cancers frequently harbor KRAS mutations, yet only a subset of KRAS mutant colon cancer cell lines are dependent upon KRAS signaling for survival. In a screen for kinases that promote survival of KRAS-dependent colon cancer cells, we found that the TAK1 kinase (MAP3K7) is required for tumor cell viability. The induction of apoptosis by RNAi-mediated depletion or pharmacologic inhibition of TAK1 is linked to its suppression of hyperactivated Wnt signaling, evident in both endogenous and genetically reconstituted cells.

Microinjection of zebrafish embryos to analyze gene function.

One of the advantages of studying zebrafish is the ease and speed of manipulating protein levels in the embryo. Morpholinos, which are synthetic oligonucleotides with antisense complementarity to target RNAs, can be added to the embryo to reduce the expression of a particular gene product. Conversely, processed mRNA can be added to the embryo to increase levels of a gene product.

Acute left atrial thrombus after recombinant factor VIIa administration during left ventricular assist device implantation in a patient with heparin-induced thrombocytopenia.

We present a patient with end-stage heart failure and heparin-induced thrombocytopenia Type II, who required cardiopulmonary bypass (CPB) during a repeat implantation of a left ventricular assist device for long-term circulatory support. Bivalirudin was selected for anticoagulation during CPB, with concomitant infusion of aprotinin, in an effort to ameliorate blood loss. Nonetheless, profuse bleeding after CPB required massive transfusion of packed red blood cells, multiple coagulation factors, and platelets.