Continuing professional development: is the future Pathology Interactive?
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
P Van Diest
Publications and source records attributed to P Van Diest.
Prognostic factors following enucleation of 111 uveal melanomas.
Follow up information was retrieved on 111 patients who underwent enucleation for uveal melanoma between 1964 and 1987, allowing a minimum postoperative period of 5 years. Univariate survival analysis was carried out using Kaplan-Meier curves and the differences between the curves were analysed with the Mantel-Cox test. Multivariate analysis used the Cox proportional hazards model. Univariate analysis isolated each of the following as significant prognosticators: largest tumour diameter (LTD) (p < 0.002), presence of epithelioid cells (p < 0.03), and glaucoma (p < 0.001). A combination of cell type, glaucoma, and LTD (p < 0.0001) had strong and independent prognostic significance in multivariate analysis. The results of this series are compared with previous studies and the value of cell type information and new quantitative parameters is discussed.
Adolescent↗
An ultrastructural study of the endonasal microcirculation in the Wistar rat during fetal and early postnatal life.
Fenestrated capillaries were observed prenatally in the lateral nasal wall and in glandular capillaries of the nasal mucosa of the rat. The number of fenestrations increased towards full term and during postnatal life. Specific ultrastructural features in the vascular bed were found to be primarily determined in utero.
Animals↗
Preponderance of lysosomal bodies in cultured fibroblasts from patients with recessive epidermolysis bullosa dystrophica. An electron microscopic study.
Fibroblasts of skin explants from three normal men and six patients with recessive epidermolysis bullosa dystrophica (EBD-R) were cultured in Dulbecco's medium, grown to confluence, sectioned and studied with the electron microscope. The normal control fibroblasts from the 6th to 13th passage (secretory phase) showed irregular or lobed nuclei with centrally scattered chromatin. They also had prominent RER, Golgi complexes, variously shaped mitochondria and cytoskeletal microfibrils. Their peripheral cytoplasm exhibited many vacuoles and a small number of these were autophagic lysosomes. In addition to the ultrastructural features described in the control fibroblasts, the EBD-R cells from the 6th passage contained remarkable numbers of strongly electron dense lysosomal bodies through their entire cytoplasm with very few empty vacuoles. It is speculated that the accumulation of these lysosomes may be connected with a primary metabolic cellular defect in the dermal fibroblasts of patients with EBD-R akin to that described in mucopolysaccharide storage diseases.
Adult↗
Epidermal growth factor receptor targeting enhances adenoviral vector based suicide gene therapy of osteosarcoma.
BACKGROUND: Despite improvements in the treatment of osteosarcoma (OS) there are still too many patients who cannot benefit from current treatment modalities. Therefore, new therapeutic approaches are warranted. Here we explore the efficacy of targeted adenoviral based suicide gene therapy. METHODS AND RESULTS: Immunohistochemistry and FACS analysis detected low or absent expression levels of the primary adenovirus receptor CAR on human primary OS and human OS cell lines. These results predict a low infection efficiency and thus a reduced therapeutic effect. Targeting the adenoviruses to another receptor highly expressed on OS could overcome this limitation. We found epidermal growth factor receptor (EGFR) to be widely expressed on primary OS. Immunohistochemistry on primary tumor samples and FACS analysis on primary short-term cultures and four OS cell lines showed that EGFR was consistently expressed. The recombinant bispecific single-chain antibody 425-s11 redirects adenoviral vectors towards the EGFR. Adenovirus transduction experiments in the presence or absence of 425-s11 showed significantly enhanced gene transfer with the targeted adenoviral vector compared with the native vector (OS cell lines 2.5 to 7.2 times enhanced gene transfer and OS primary short term cultures 1.7 to 10 times enhanced gene transfer). On this basis, targeted suicide gene therapy experiments with AdCMVHSV-TK in combination with ganciclovir were performed. These experiments demonstrated up to 3.5-fold enhanced kill of OS cell lines and primary short-term cultures by the EGFR targeted vector. CONCLUSIONS: Suicide gene therapy with adenovirus targeted towards EGFR may have favorable therapeutic characteristics for future gene therapy applications in OS.
Adenoviridae↗