The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer.

Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program "epithelial-mesenchymal transition" (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity.

Breakdown of the endothelial barrier function in tumor cell transmigration.

The ability of tumor cells to metastasize is associated with a poor prognosis for cancer. During the process of metastasis, tumor cells circulating in the blood or lymph vessels can adhere to, and potentially transmigrate through, the endothelium and invade the connective tissue. We studied the effectiveness of the endothelium as a barrier against the invasion of 51 tumor cell lines into a three-dimensional collagen matrix.

CD24 induces localization of beta1 integrin to lipid raft domains.

The expression of the glycosyl phosphatidylinositol (GPI)-anchored protein CD24 correlates with poor prognosis in a variety of carcinomas. However, little is known about the cellular mechanisms of the CD24-mediated effects. In this study, we present evidence that CD24 affects the lateral localization of beta1 integrin.

AMER1 regulates the distribution of the tumor suppressor APC between microtubules and the plasma membrane.

APC is a multifunctional tumor suppressor protein that negatively controls Wnt signaling, but also regulates cell adhesion and migration by interacting with the plasma membrane and the microtubule cytoskeleton. Although the molecular basis for the microtubule association of APC is well understood, molecular mechanisms that underlie its plasma membrane localization have remained elusive. We show here that APC is recruited to the plasma membrane by binding to APC membrane recruitment 1 (AMER1), a novel membrane-associated protein that interacts with the ARM repeat domain of APC.

[Company centredness in the rehabilitation system of the German Democratic Republic, GDR].

This article describes major aspects of the rehabilitation system of the former German Democratic Republic, GDR. Based on presentation of the actors in the medical and occupational rehabilitation system, differences are pointed out in comparison to the notion of rehabilitation in the former Federal Republic of Germany, FRG. The article focuses on the system of rehabilitation after stroke, which is outlined with relevant scientific literature.

Expression profiling reveals genes associated with transendothelial migration of tumor cells: a functional role for alphavbeta3 integrin.

Transendothelial migration is a key step in the extravasation of tumor cells during metastasis formation. Here, we have classified 45 human tumor cell lines derived from various tissues according to their capacity for transendothelial migration in vitro. We could distinguish cell lines showing strong transmigration (TEM+ cell lines) from others that did not transmigrate (TEM- cell lines).

Sugar-induced premature aging and altered differentiation in human epidermal keratinocytes.

Normal human epidermal keratinocytes (NHEK) show both the Hayflick phenomenon and differentiation in vitro. The aim of this study was to induce senescence in keratinocytes using two sugars, glucose and glyoxal. Induction of senescence in early-passage NHEK was characterized by monitoring cell morphology, short-term growth characteristics, cell proliferation, and viability assay.

Mutations of the Wnt antagonist AXIN2 (Conductin) result in TCF-dependent transcription in medulloblastomas.

Medulloblastomas (MBs) represent the most common malignant brain tumors in children. Most MBs develop sporadically in the cerebellum, but their incidence is highly elevated in patients with familial adenomatous polyposis coli. These patients carry germline mutations in the APC tumor suppressor gene.

Oxygen dynamics around buried lesser sandeels Ammodytes tobianus (Linnaeus 1785): mode of ventilation and oxygen requirements.

The oxygen environment around buried sandeels (Ammodytes tobianus) was monitored by planar optodes. The oxygen penetration depth at the sediment interface was only a few mm. Thus fish, typically buried at 1-4 cm depth, were generally in anoxic sediment.

Truncated APC regulates the transcriptional activity of beta-catenin in a cell cycle dependent manner.

Most colon cancer cells express truncated versions of the tumour suppressor Adenomatous Polyposis Coli (APC). These molecules are selected during tumourigenesis for impaired beta-catenin degrading activity. In this study, we describe that truncated APC can still control the activity of beta-catenin in colon cancer cell lines via its first 20 amino acid repeat.

In-home behavioral health case management: an integrated model for high-risk populations.

The escalating health care costs attributed to high-risk populations have fueled a need for a proactive approach to deal with people affected by complex mental health issues that often coexist with chronic medical conditions. Through an in-home behavioral health case management (CM) program, patients with mental illnesses (some with coexisting medical conditions) receive integrated medical and mental health services through a disease-management approach that has proven effective in treating high-risk patients.

A distinct PAR complex associates physically with VE-cadherin in vertebrate endothelial cells.

A cell polarity complex consisting of partitioning defective 3 (PAR-3), atypical protein kinase C (aPKC) and PAR-6 has a central role in the development of cell polarity in epithelial cells. In vertebrate epithelial cells, this complex localizes to tight junctions. Here, we provide evidence for the existence of a distinct PAR protein complex in endothelial cells.

Nursing home staff training in dementia care: a systematic review of evaluated programs.

Background: We reviewed studies of in-service interventions for caregivers of persons with dementia in nursing homes published between 1990 and 2004. The aim was to obtain an overview of the evaluated interventions and to characterize their methodological quality.

Methods: A thorough literature search was conducted, including searching electronic databases for selected intervention studies and previous reviews.

CIN By WNT: growth pathways, mitotic control and chromosomal instability in cancer.

There is mounting evidence suggesting that an instable genome is directly involved in the development of cancer. The predominant form of genomic instability in most cancers presents itself as an increased rate of loss or gain in chromosome number and parts, referred to as chromosomal instability (CIN). Indeed, mutations in components of mitotic checkpoints have been described in human cancers, albeit in low numbers, suggesting that although CIN principally arises due to defective surveillance of mitosis, its molecular causes remain largely unclear.

Aberrant Wnt/beta-catenin signaling can induce chromosomal instability in colon cancer.

Chromosomal instability (CIN), a hallmark of most colon tumors, may promote tumor progression by increasing the rate of genetic aberrations. CIN is thought to arise as a consequence of improper mitosis and spindle checkpoint activity, but its molecular basis remains largely elusive. The majority of colon tumors develop because of mutations in the tumor suppressor APC that lead to Wnt/beta-catenin signaling activation and subsequent transcription of target genes, including conductin/AXIN2.

[The need for autonomy in the process of care-conceptual framework and research perspectives].

The article reflects the difference between independence and self-determination or autonomy in care relations. We consider that independence is only a fiction even for people with no functional limitations. Compared with this are people in need of care always confronted with professional interventions in their daily life which limit their self-determination.

Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention.

beta-catenin is the central signalling molecule of the canonical Wnt pathway, where it activates target genes in a complex with LEF/TCF transcription factors in the nucleus. The regulation of beta-catenin activity is thought to occur mainly on the level of protein degradation, but it has been suggested that beta-catenin nuclear localization and hence its transcriptional activity may additionally be regulated via nuclear import by TCF4 and BCL9 and via nuclear export by APC and axin. Using live-cell microscopy and fluorescence recovery after photobleaching (FRAP), we have directly analysed the impact of these factors on the subcellular localization of beta-catenin, its nucleo-cytoplasmic shuttling and its mobility within the nucleus and the cytoplasm.

Truncated APC is required for cell proliferation and DNA replication.

The tumour suppressor APC is truncated in most colon cancers, which leads to the stabilization of beta-catenin and to the constitutive activation of Wnt signalling. However, it is not clear why colon cancer cells retain the truncated APC fragment. Here, we show that a decrease of APC levels achieved by RNA interference impairs cell proliferation and DNA replication, not only in 293 cells that express a wild-type protein, but also in SW480 colon cancer cells that express exclusively a truncated APC fragment.

E-cadherin modulates Wnt-dependent transcription in colorectal cancer cells but does not alter Wnt-independent gene expression in fibroblasts.

E-cadherin mediates homophilic adhesion of epithelial cells and is a major determinant of epithelial differentiation during embryonic development and tumor progression. At cell junctions, E-cadherin associates with beta-catenin, which also functions as a transcriptional co-activator of the canonical Wnt signaling pathway by interacting with TCF transcription factors. Here, we have analyzed whether E-cadherin plays a role in the control of gene expression in Wnt-dependent and -independent cellular systems.

Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002--Medical Research Council Adult Leukaemia Working Party.

Purpose: Early mortality in multiple myeloma (MM) is usually attributed to combined effects of active disease and comorbid factors. We have studied early deaths in a series of large multicenter trials to assess direct causes of death, their predictability, and whether current management strategies have reduced their frequency.

Patients And Methods: A total of 3,107 newly diagnosed patients entered onto United Kingdom Medical Research Council MM trials from 1980 to 2002 were studied.

Development of two search strategies for literature in MEDLINE-PubMed: nursing diagnoses in the context of evidence-based nursing.

Purpose: To develop and validate search filters for MEDLINE via PubMed according to two categories of the NLINKS-EBN matrix.

Methods: The search results of the search filters were compared to a gold standard.

Findings: The usage of nursing classification terms for the literature search in evidence-based nursing (EBN) is still limited because taxonomies are neither widely used in nursing literature nor applied for indexing by MEDLINE.

The role of the Wnt signalling pathway in colorectal tumorigenesis.

Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes. Mutations in the tumour suppressor APC (adenomatous polyposis coli) genes occur early in the development of CRC and lead to the stabilization of the Wnt pathway component beta-catenin and to the constitutive activation of Wnt signalling.

Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma.

Background: While the Wnt pathway has been widely implicated in hepatocarcinogenesis, the role of cyclin D1 as a direct downstream target gene of beta-catenin-lymphoid enhancer factor-1 (LEF-1)/T-cell factor (TCF) signaling is controversely discussed.

Methods: By immunohistochemical analyses we studied the subcellular localization of LEF-1/TCF and cyclin D1 in 162 hepatocellular carcinoma (HCC). Single- and double-label imaging by brightfield and confocal laser scanning microscopy was quantitated and correlated with beta-catenin, the Ki67(+) proliferation fraction (PF), tumor size, grade, the Okuda stage and patient survival.