Defining new criteria for selection of cell-based intestinal models using publicly available databases.

BACKGROUND: The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies. RESULTS: We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. CONCLUSIONS: This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question.

Audit report on the Disaster Grants – Public Assistance program of the Green Bay Levee and Drainage District in Lee County, Iowa for the year ended June 30, 2009

Audit report on the Disaster Grants – Public Assistance program of the Green Bay Levee and Drainage District in Lee County, Iowa for the year ended June 30, 2009

Report on a special investigation of the Food Service Department of the Springville Community School District for the period July 1, 2005 through March 31, 2009

Report on a special investigation of the Food Service Department of the Springville Community School District for the period July 1, 2005 through March 31, 2009

Audit report on the Xenia Rural Water District for the year ended December 31, 2009

Audit report on the Xenia Rural Water District for the year ended December 31, 2009

Iowa Supreme Court Improvement Project for Child in Need of Assistance Cases: Annual Report and Proposed Policy Revisions.

The first part of a three year plan to evaluate and recommend improvements to Iowa's Juvenile Courts.

Combined report on the eight Judicial District Departments of Correctional Services for the year ended June 30, 2009

Combined report on the eight Judicial District Departments of Correctional Services for the year ended June 30, 2009

Audit report on the Disaster Grants – Public Assistance program of the Iowa River - Flint Creek Levee District in Des Moines County and Louisa County, Iowa for the year ended June 30, 2009

Audit report on the Disaster Grants – Public Assistance program of the Iowa River - Flint Creek Levee District in Des Moines County and Louisa County, Iowa for the year ended June 30, 2009

Audit report on the Disaster Grants – Public Assistance program of Louisa – Des Moines County Drainage District in Des Moines County and Louisa County, Iowa for the year ended June 30, 2009

Audit report on the Disaster Grants – Public Assistance program of Louisa – Des Moines County Drainage District in Des Moines County and Louisa County, Iowa for the year ended June 30, 2009

Report on a special investigation of the Clinton Community School District for the period July 1, 2005 through February 28, 2010

Report on a special investigation of the Clinton Community School District for the period July 1, 2005 through February 28, 2010

Report on the Iowa Judicial Branch – County Clerks of District Courts, a part of the State of Iowa, for the year ended June 30, 2009

Report on the Iowa Judicial Branch – County Clerks of District Courts, a part of the State of Iowa, for the year ended June 30, 2009

ß-Catenin Regulation during the Cell Cycle: Implications in G2/M and Apoptosis

ß-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. ß-Catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems ß-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of ß-Catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous ß-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase¿synchronized epithelial cells. ß-Catenin levels increase in S phase, reaching maximum accumulation at late G2/M and then abruptly decreasing as the cells enter into a new G1 phase. In parallel, an increased cytoplasmic and nuclear localization of ß-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not ß-catenin, is detected in M phase. Interestingly, overexpression of a stable form of ß-catenin, or inhibition of endogenous ß-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for ß-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes.

Letter to the Colo-Nesco Community School District as a result of reaudit procedures performed at the request of the Superintendent pursuant to Chapter 11.6(4)(a)(2) of the Code of Iowa for the period July 1, 2007 through June 30, 2008

Letter to the Colo-Nesco Community School District as a result of reaudit procedures performed at the request of the Superintendent pursuant to Chapter 11.6(4)(a)(2) of the Code of Iowa for the period July 1, 2007 through June 30, 2008