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Biomedical subjects

E Fait

Publications and source records attributed to E Fait.

6 recordsLinked to original sources

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon.

Despite the significance of tumour neoangiogenesis and the extensive knowledge on the molecular basis of blood vessel formation currently no quantitative data exist on the 3D microvascular architecture in human primary tumours and their precursor lesions. This prompted us to examine the 3D vascular network of normal colon mucosa, adenomas and invasive carcinomas by means of quantitative microvascular corrosion casting. Fresh hemicolectomy specimens from 20 patients undergoing cancer or polyposis coli surgery were used for corrosion casting, factor VIII and VEGF immunostaining. In addition, immunostaining was done on colorectal tissue from 33 patients with metastatic and non-metastatic carcinomas, polyposis coli and adenomas. This first quantitative analysis of intervessel and interbranching distances, branching angles and vessel diameters in human cancer specimens revealed distinct patterns of the microvascular unit in the tumour centre and periphery. Irrespective of the tumour localization and grading all individual tumours displayed qualitatively and quantitatively the same vascular architecture. This gives further evidence for the existence of a tumour type-specific vascular architecture as recently demonstrated for experimental tumours. Metastatic tumours displayed different vascular architectures only within hot spots, in terms of smaller intervascular distances than in non-metastatic tumours. Pre-cancerous lesions have in part virtually the same vascular architecture like invasive carcinomas. Comparison of VEGF immunostaining also suggests that angiogenesis sets in long before the progress towards invasive phenotypes and that the so-called angiogenic switch is more likely a sequence of events.

Adenoma↗

Evidence for characteristic vascular patterns in solid tumours: quantitative studies using corrosion casts.

The vascular architecture of four different tumour cell lines (CaX, CaNT, SaS, HEC-1B) transplanted subcutaneously in mice was examined by means of microvascular corrosion casting in order to determine whether there is a characteristic vascular pattern for different tumour types and whether it differs significantly from two normal tissues, muscle and gut. Three-dimensional reconstructed scanning electron microscope images were used for quantitative measurements. Vessel diameters, intervessel and interbranch distances showed large differences between tumour types, whereas the branching angles were similar. In all tumours, the variability of the vessel diameters was significantly higher than in normal tissue. The quantitative data provide strong evidence for a characteristic vascular network determined by the tumour cells themselves.

Adenocarcinoma↗

The vascular architecture of the chick chorioallantoic membrane: sequential quantitative evaluation using corrosion casting.

Microvascular corrosion casting was used for evaluating qualitatively and quantitatively angiogenesis in the chick chorioallantoic membrane (CAM). Series of CAMs from day 8 to 18 were examined. The density of plexus capillaries increases rapidly until day 10 and then remains constant. The vessels connected to the plexus (first order vessels) increase in number and length between days 10 and 12. The vessels initiating from first-order vessels (second order) also increase in number but remain nearly the same in lengths and diameters. Compared to previous studies using stereomicroscopy, significant differences in vessel numbers and lengths exist, which can be explained by the low resolution and magnification resulting in too low vascular densities of the pre- and post-capillaries. The third-order vessels increase in number until day 12 when they reach a plateau, whereas higher-order vessels increase in number. These results give an insight into the vascular development of this organ, and provide the basis for assessing the targets and effects of angiogenic or antiagiogenic agents.

Journal Article↗

Impact of fibroblast growth factor-2 on tumor microvascular architecture. A tridimensional morphometric study.

Three cell clones originated by transfection of human endometrial adenocarcinoma HEC-1-B cells with fibroblast growth factor-2 (FGF-2) cDNA and characterized by a different capacity to produce and secrete the growth factor were transplanted subcutaneously in nude mice. Corrosion casting of the tumor microvasculature of xenografts produced by injection of 2 x 10(6) or 10 x 10(6) FGF-2-B9 cells (which produce and secrete significant amounts of FGF-2), 10 x 10(6) FGF-2-A8 cells (which produce comparable amounts of FGF-2 but do not secrete it), or 10 x 10(6) control FGF-2-B8 cells (which produce only trace amounts of FGF-2) was performed after 14 days of growth. Interbranching distances, intervascular distances, branching angles, and vessel diameters were then determined using tridimensional stereo pairs of the casted tumor vascularity. When transplanted at the same concentration, FGF-2-B9 cells grew faster in nude mice compared with FGF-2-A8 and FGF-2-B8 clones. The total amount of new vessel formation was far higher in FGF-2-B9 tumors than in FGF-2-B8 or FGF-2-A8 tumors. Also, vessel courses were more irregular and blind-ending vessels and evasates were more frequent in FGF-2-B9 tumors. Moreover, FGF-2-B9 tumor microvasculature was characterized by a wider average vascular diameter and by an extreme variability of the diameter of each individual vessel along its course between two ramifications. No statistical differences were observed when the distribution curves of the values of intervascular distances, interbranching distances, and branching angles of the microvessel network were compared among the different experimental groups. The distinctive features of the microvasculature of FGF-2-B9 tumors were retained, at least in part, in the smaller lesions produced by injection of a limited number of cells. The data indicate that FGF-2 production and release confer to FGF-2-B9 cells the ability to stimulate the formation of new blood vessels with distinctive architectural features. Neovascularization of FGF-2-B9 lesions parallels the faster rate of growth of the neoplastic parenchyma. This does not affect the overall architecture of the microvessel network that appears to be primed by characteristics of the HEC-1-B tumor cell line and/or by the microenvironment of the host. To our knowledge, this work represents the first attempt to define the influence of a single, defined growth factor on the tridimensional tumor vascular pattern.

Adenocarcinoma↗

Acetylcholine modulates ganglion cell activity in the trout pineal organ.

In the teleost pineal organ light activates functional photoreceptors, which transmit electrical activity to the brain via axons of intermediate ganglion cells. To investigate whether acetylcholine plays a role in the transduction of pineal photoreceptor signals, extracellular recordings were performed from ganglion cells of intact superfused pineal organs of the rainbow trout. Bath-applied acetylcholine increased the spike discharge rate of 96% of achromatic ganglion cells in a dose-dependent manner. The light response curve of ganglion cells, which was obtained by plotting spike rate vs light intensity, was significantly shifted by acetylcholine to higher frequencies. Acetylcholine was also active if applied during synaptic blockade with low Ca2+/high Mg(2+)-medium, demonstrating the presence of cholinergic receptors at the ganglion cell level. These data represent the first demonstration of acetylcholine constituting a postsynaptic modulation of photoreceptor signals in the trout pineal organ.

Acetylcholine↗

Signal transmission in the photosensitive pineal organ of the rainbow trout: modulation of ganglion cell activity by intrinsic dopamine.

The photosensitive pineal organ of the rainbow trout (Oncorhynchus mykiss) transduces photic information into nycthemeral neuronal signals. To investigate origin, cellular localization, and functional significance of pineal catecholamines, we performed HPLC-analysis of catecholamines and tyrosine hydroxylase (TH) activity, as well as immunocytochemical and electrophysiological studies. In biochemical and immunocytochemical investigations, pineal cells were found to contain endogenous TH. Using HPLC-analysis, the presence of a catecholamine precursor (L-dopa), catecholamines (dopamine, norepinephrine, epinephrine), and a metabolite (DOPAC) was demonstrated. The release of L-dopa, dopamine and DOPAC from isolated pineal organs was shown by superfusion experiments. Extracellular recordings were used to monitor the action of dopaminergic drugs on electrical activity of ganglion cells. Dopamine increased the discharge activity of action potentials, whereas dopamine receptor antagonists resulted in a reduction of ganglion cell activity. Our data provide evidence for establishing dopamine as an intrinsic neurotransmitter or neuromodulator in the photosensitive pineal organ of the rainbow trout.

Action Potentials↗