Data management for prospective research studies using SAS® software

<p>Abstract</p> <p>Background</p> <p>Maintaining data quality and integrity is important for research studies involving prospective data collection. Data must be entered, erroneous or missing data must be identified and corrected if possible, and an audit trail created.</p> <p>Methods</p> <p>Using as an example a large prospective study, the Missouri Lower Respiratory Infection (LRI) Project, we present an approach to data management predominantly using SAS software. The Missouri LRI Project was a prospective cohort study of nursing home residents who developed an LRI. Subjects were enrolled, data collected, and follow-ups occurred for over three years. Data were collected on twenty different forms. Forms were inspected visually and sent off-site for data entry. SAS software was used to read the entered data files, check for potential errors, apply corrections to data sets, and combine batches into analytic data sets. The data management procedures are described.</p> <p>Results</p> <p>Study data collection resulted in over 20,000 completed forms. Data management was successful, resulting in clean, internally consistent data sets for analysis. The amount of time required for data management was substantially underestimated.</p> <p>Conclusion</p> <p>Data management for prospective studies should be planned well in advance of data collection. An ongoing process with data entered and checked as they become available allows timely recovery of errors and missing data.</p

Atonal homolog 1 Is a Tumor Suppressor Gene

Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation

Matrix Metalloproteinase-Induced Epithelial-Mesenchymal Transition in Breast Cancer

Matrix metalloproteinases (MMPs) degrade and modify the extracellular matrix (ECM) as well as cell-ECM and cell-cell contacts, facilitating detachment of epithelial cells from the surrounding tissue. MMPs play key functions in embryonic development and mammary gland branching morphogenesis, but they are also upregulated in breast cancer, where they stimulate tumorigenesis, cancer cell invasion and metastasis. MMPs have been investigated as potential targets for cancer therapy, but clinical trials using broad-spectrum MMP inhibitors yielded disappointing results, due in part to lack of specificity toward individual MMPs and specific stages of tumor development. Epithelial-mesenchymal transition (EMT) is a developmental process in which epithelial cells take on the characteristics of invasive mesenchymal cells, and activation of EMT has been implicated in tumor progression. Recent findings have implicated MMPs as promoters and mediators of developmental and pathogenic EMT processes in the breast. In this review, we will summarize recent studies showing how MMPs activate EMT in mammary gland development and in breast cancer, and how MMPs mediate breast cancer cell motility, invasion, and EMT-driven breast cancer progression. We also suggest approaches to inhibit these MMP-mediated malignant processes for therapeutic benefit