Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.

Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44(+)/CD24(-/low) human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP.

Epithelial-mesenchymal transition induces similar metabolic alterations in two independent breast cancer cell lines.

Epithelial-mesenchymal transition (EMT) induces invasive properties in epithelial tumors and promotes metastasis. Although EMT-mediated cellular and molecular changes are well understood, very little is known about EMT-induced metabolic changes. HER2-positive BT-474 breast cancer cells were induced to undergo a stable EMT using mammosphere culture, as previously described by us for the ERα-positive MCF-7 breast cancer cells.

ERα, microRNAs, and the epithelial-mesenchymal transition in breast cancer.

The most common form of breast cancer, luminal A, is estrogen receptor α (ERα)-positive and epithelial, but nevertheless can metastasize. The process of epithelial-mesenchymal transition (EMT) is probably the first step in the metastasis of epithelial cancers. We discuss the characteristics of EMT, including factors that induce EMT, and the relationship of EMT to cancer stem cells (CSCs).

Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells.

The FOXO1 transcription factor orchestrates the regulation of genes involved in the apoptotic response, cell cycle checkpoints, and cellular metabolism. FOXO1 is a putative tumor suppressor, and the expression of this gene is dysregulated in some cancers, including prostate and endometrial cancers. However, the molecular mechanism resulting in aberrant expression of human FOXO1 in cancer cells is poorly understood.

The role of miR-206 in the epidermal growth factor (EGF) induced repression of estrogen receptor-alpha (ERalpha) signaling and a luminal phenotype in MCF-7 breast cancer cells.

Epidermal growth factor (EGF) receptor (EGFR)/MAPK signaling can induce a switch in MCF-7 breast cancer cells, from an estrogen receptor (ER)alpha-positive, Luminal-A phenotype, to an ERalpha-negative, Basal-like phenotype. Although mechanisms for this switch remain obscure, Basal-like cancers are typically high grade and confer a poorer clinical prognosis. We previously reported that miR-206 and ERalpha repress each other's expression in MCF-7 cells in a double-negative feedback loop.

Healthcare IT and connecticut's acute-care hospitals. An analysis of trends, barriers, impacts and perspectives.

In recent years there has been much discussion in regards to the uses of information technology in healthcare. This paper presents a snapshot and analysis of the current information technology outlook in Connecticut's acute-care hospitals. Seventy-seven percent of the state's acute-care hospitals participated in the study.

Involvement of microRNAs in breast cancer.

MicroRNAs regulate numerous aspects of normal and pathologic cellular processes, including cancer. Breast cancer is a heterogeneous form of cancer that is derived from mammary epithelial cells. This review discusses the involvement of microRNAs in the regulation of normal mammary epithelial stem cells, their differentiation into basal and luminal phenotypes, and their control of breast cancer stem cells, also referred to as tumor-initiating cells.

Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogen-activated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells.

Argonaute (Ago) 2 is the catalytic engine of mammalian RNA interference, but little is known concerning the regulation of Ago2 by cell-signaling pathways. In this study we show that expression of Ago2, but not Ago1, Ago3, or Ago4, is elevated in estrogen receptor (ER) alpha-negative (ERalpha(-)) vs. ERalpha-positive (ERalpha+) breast cancer cell lines, and in ERalpha(-) breast tumors.

The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines.

Micro-RNAs are small noncoding RNAs, which diminish the stability and/or translation of mRNAs. This study examined whether miR-206, previously shown to be elevated in estrogen receptor (ER)alpha-negative breast cancer, regulates the expression of ERalpha. Two putative miR-206 sites, (hERalpha1 and hERalpha2), were found in silico within the 3'-untranslated region of human ERalpha mRNA.

The low-density lipoprotein receptor is regulated by estrogen and forms a functional complex with the estrogen-regulated protein ezrin in pituitary GH3 somatolactotropes.

Estrogen regulates the function, growth, and proliferation of lactotropes in the pituitary. We report here that low-density lipoprotein (LDL) receptor (LDLR) gene expression and LDL uptake are strongly up-regulated by estrogen in pituitary somatolactotropic GH(3) cells. The uptake of LDL was significantly inhibited by the F-actin-severing drug, swinholide A, indicating that LDL uptake is dependent on the integrity of the cortical actin cytoskeleton in GH(3) cells.

Tissue-specific regulation by estrogen of ezrin and ezrin/radixin/moesin-binding protein 50.

The morphology and function of rat GH3 pituitary cells are profoundly affected by estradiol-17beta (E2), presumably due to changes in the profile of gene expression. We recently reported that a major target of E2 in these cells is the ezrin gene, which encodes a cytoskeletal linker protein that forms a complex with ezrin/radixin/ moesin-binding protein 50 (EBP50) in some cell types. Other studies have shown that EBP50 levels are increased by E2 in human breast and uterine tissue.

Reciprocal regulation by estradiol 17-beta of ezrin and cadherin-catenin complexes in pituitary GH3 cells.

The antiestrogen, ICI 182780, and estradiol-17beta (E2) regulate cadherin-mediated cell adhesion in pituitary GH3 cells. Using a cDNA expression array to screen for E2-regulated genes that are associated with the cytoskeleton, we observed that E2 stimulated ezrin gene expression and confirmed that ezrin gene expression is regulated pretranslationally by ICI 182780 versus E2. E2 increased ezrin protein levels in whole-cell lysates and in the cytoskeletal-associated, detergent-insoluble fraction.