Identification and angiogenic role of the novel tumor endothelial marker CLEC14A.

Tumor endothelial markers (TEMs) that are highly expressed in human tumor vasculature compared with vasculature in normal tissue hold clear therapeutic potential. We report that the C-type lectin CLEC14A is a novel TEM. Immunohistochemical and immunofluorescence staining of tissue arrays has shown that CLEC14A is strongly expressed in tumor vasculature when compared with vessels in normal tissue. CLEC14A overexpression in tumor vessels was seen in a wide range of solid tumor types. Functional studies showed that CLEC14A induces filopodia and facilitates endothelial migration, tube formation and vascular development in zebrafish that is, CLEC14A regulates pro-angiogenic phenotypes. CLEC14A antisera inhibited cell migration and tube formation, suggesting that anti-CLEC14A antibodies may have anti-angiogenic activity. Finally, in endothelial cultures, expression of CLEC14A increased at low shear stress, and we hypothesize that low shear stress due to poor blood flow in the disorganized tumor vasculature induces expression of CLEC14A on tumor vessels and pro-angiogenic phenotypes.

Comparison of pathological diagnostic criteria for Alzheimer disease.

Because the clinical picture of Alzheimer disease (AD) is often difficult to discriminate from other dementing illnesses, the diagnosis of AD requires neuropathological confirmation. However, for the pathological diagnosis of AD, there are no unanimously accepted criteria. The three currently used sets of pathological criteria (Khachaturian: Khachaturian, Arch Neurol 1985;42:1097-105; Tiemy: Tierney et al., Can J Neurol Sci 1986; 13:424-6; CERAD: Mirra et al., Neurology 1991;41:479-86) for the disease differ from each other considerably. We applied these criteria to the first 43 consecutive subjects (37 demented) with no neuropathology other than AD-type pathology from autopsies after longitudinal prospective clinical study in the Oxford Project to Investigate Memory and Ageing (OPTIMA). The results show that the CERAD category of definite AD corresponds closely with the cases that fulfill Tierney A3 inclusion criteria for AD. The combined CERAD categories of possible, probable, and definite AD correspond closely to cases fulfilling Khachaturian criteria forAD. The influence of a clinical diagnosis of dementia when Khachaturian and CERAD criteria were applied was considerable because between 9.3% and 90.7% of patients would have been categorized differently depending on whether clinical dementia was present or absent.

Apoptosis-related protein expression in the hippocampus in Alzheimer's disease.

Recent research indicates that apoptotic mechanisms may be involved in cell death in Alzheimer's disease (AD). We studied the expression of three members of the Bcl-2 protein family, Bcl-2, Bcl-x, and Bax, in a selection of senile and DS-related AD patients as well as in controls. These proteins are all associated with apoptotic mechanisms. In contrast to previous reports, neuronal Bcl-2 labeling was not detected in our cases, although there was some weak and inconsistent glial cell labeling. Neuronal Bcl-x expression was virtually absent in controls and the presence of the protein in AD patients was neither consistent nor specific. Some reactive glial cells were strongly labeled with the Bcl-x antibody. In contrast Bax, a protein that is believed to promote apoptosis, was widely expressed by neurones but was mainly present in areas other than CA1 in the hippocampus. Neuritic elements of some senile plaques were clearly and strongly labeled with this antibody, whereas neurofibrillary tangles and neuropil threads were not. Double labeling studies indicated that AT8-positive cells and neurites were never Bax-positive and vice versa. The possible implications of the different expression patterns are discussed in relation to neurone death in AD.