Biomedical subjects

T Wolloscheck

Publications and source records attributed to T Wolloscheck.

5 recordsLinked to original sources

PubMed2005

The VEGF receptor tyrosine kinase inhibitor, ZD6474, inhibits angiogenesis and affects microvascular architecture within an orthotopically implanted renal cell carcinoma.

The proangiogenic vascular endothelial growth factor-A (VEGF) is essential for the development of new tumor vessels. ZD6474 is a novel inhibitor of VEGF receptor-2 (VEGFR-2) tyrosine kinase activity, which also has additional activity against epidermal growth factor (EGF) receptor tyrosine kinase. The antitumor activity of different schedules of ZD6474 in a clinically relevant, metastasizing, murine renal cell carcinoma (RENCA) model was evaluated in this study. RENCA cells were inoculated into the left kidney of 24 mice (day 0). Daily ZD6474 (50 mg/kg p.o.) treatment was initiated 1 day or 10 days after tumor cell inoculation and continued until day 21. Following treatment, kidney weight and volume were assessed and blood vessel density determined by CD31 staining. Visible metastases in the lungs, spleen, and lymph nodes were quantified using a dissection microscope. In an additional study, animals were treated according to the same regimen and quantitative three-dimensional microvascular corrosion casting was performed to enable detailed assessment of the tumor vascular architecture. Therapy initiated on day 1 or day 10 resulted in a 79% and 59% reduction in primary tumor volume, a 79% and 60% reduction in the number of lung metastases, and a 58% and 59% reduction in vessel density of primary tumors compared with the control group, respectively. Corrosion casting proved a 5.4- and 3.2-fold lower vascular volume compared with untreated tumors, observations that paralleled with significant architectural alterations. In this RENCA model, ZD6474 was a highly active inhibitor of tumor angiogenesis, primary tumor growth and tumor metastasis.

Animals↗

PubMed2005

[Microvessel visualisation: applications and limitations].

Vessel systems and the microvascular unit may be studied by a variety of morphological techniques which enable improved structure-function analyses. Two-dimensional light and electron microscopic sectioning techniques with and without specific markers are complemented by 3D vascularisation and perfusion study techniques. Static ex vivo modalities still prevail, however, the future will be dominated by intravital high-resolution techniques.

Animals↗

PubMed2004

Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia.

This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O(2)) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced the median oxygen partial pressure (pO(2)) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO(2) was significantly improved (median pO(2)=4 mmHg), however not reaching the control level. These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure). In animals under chronic inspiratory hypoxia, the number of perfused vessels increased (compared to acute hypoxia), although the perfusion pattern found in control tumours was not reached. In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed. These results suggest that long-term adaptation of tumours to chronic hypoxia in vivo, while not affecting vascularity, does influence the functional status of the microvessels in favour of a more homogeneous perfusion.

Acute Disease↗

PubMed2004

Inguinal hernia: measurement of the biomechanics of the lower abdominal wall and the inguinal canal.

BACKGROUND: The stability of the lower abdominal wall may play a considerable role in the development of inguinal hernia. Therefore, the strength of the individual wall layers needs to be quantified. Despite numerous advances in hernia repair, comparatively few systematic biomechanic and morphometric analyses have been performed. Our aim was to establish and apply a standardised procedure for testing the abdominal wall layers' stability. METHODS: After dissecting the abdominal walls of 16 cadavers into separate layers, we used a spherical punch and a force transducer to investigate the forces necessary to foraminate the layer. In addition, maximum tensile-strength and suction tests and histologic morphometry were performed. RESULTS: The transversalis fascia was torn up on an average of 10.5 N, the peritoneum including pre- and subperitoneal tissue on 46.6 N, the aponeurosis of obliquus internus abdominis muscle on 51.7 N, and the aponeurosis of obliquus externus abdominis muscle on 92.6 N. Tensile tests of tissue strips obtained from defined areas showed comparable results. In contrast, surgical mesh revealed values between 60 and 150 N in punching tests. Left-right comparisons, as well as comparisons of the individual areas, revealed considerable intra- and inter-individual differences. CONCLUSIONS: Biological hernia repair should focus on a reinforcement of the tissue layers with the highest biomechanic stability. Reinforcement of the transversal fascia must be questioned according to our results of poor mechanical resistance.

Abdominal Wall↗

PubMed2001

[Aortic valve structures as landmarks for determining coronary artery ostia in transthoracic echocardiography].

BACKGROUND: Occasionally, coronary arteries are recorded in transthoracal echocardiography. The question was if this modality could be used as non-invasive screening method of the coronaries. A prerequisite for this is an exact and reproducible measurement of the origin of the coronary arteries. MATERIAL AND METHOD: The topography of the coronary ostia in relation to the aortic valve was examined morphometrically in the aortae of 20 embalmed cadavers and 50 patients of a cardiologist's practice who underwent transthoracal echocardiography. RESULTS: In all cases, the coronary arterial orifices were located eccentrically in the coronary sinus, shifted to the non-coronary aortic sinus. The distance between left coronary orifice to the commissure of the left and the right semilunar valvula was 13.3 mm on average in the anatomical measurements, whereas in the echocardiography this distance was 14.3 mm. The distance between the left ostium and the attachment of the left and the posterior semilunar valvula 9.4 mm, corresponding to 11.6 mm in echocardiography. The distance between right coronary orifice and the attachment of the right and the left semilunar valvula was 18.0 and 17.3 mm respectively, and the distance between right coronary orifice and the commissure of the right and the posterior semilunar valvula accounted for 8.5 and 9.7 mm respectively. On the average, the ostia were located 3.9 mm below the level of the sinotubular junction. Multiple ostia occurred in 65%, 92% of these were in the right coronary aortic sinus, shifted from the main orifice to the attachment of the right and the left semilunar valvula. CONCLUSION: In the cardiologist's routine, the attachments of the aortic leaflets proved to be very useful as landmarks. The coronary arterial orifices have been educible in nearly all cases. These results show that transthoracal echocardiography may be used in the screening for coronary artery disease.

Aged↗