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Biomedical subjects

M A Konerding

Publications and source records attributed to M A Konerding.

At least 19 recordsLinked to original sources

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↗

AdVEGF165 gene transfer increases survival in overdimensioned skin flaps.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. VEGF A also plays an important role in wound healing of the skin by promoting angiogenesis and by stimulating blood vessel growth. Therefore we tested the hypothesis that flap survival could be increased by the preoperative injection of AdVEGF(165). METHODS: We studied the effect of AdVEGF(165) in an overdimensioned ischemic random-pattern-flap model in the rat (n = 50) with a length-to-width ratio of 4 : 1. VEGF cDNA was administered in two concentrations of 5 x 10(8) plaque-forming units (pfU) and 1 x 10(9) pfU using a recombinant adenoviral vector. Recombinant virus was injected subdermally 7, 3 or 0 days prior to flap harvest for the lower concentration and 7 days prior for the higher concentration. Flap survival and necrosis were observed at day 7, the day the animals were sacrificed. RESULTS: Adenoviral gene transfer with VEGF(165) 3 and 7 days before flap harvest showed a significantly increased flap survival of 50% together with a significantly reduced necrosis (p < 0.01). Injection using a titer of 1 x 10(9) pfU 7 days prior to surgery increased flap survival even more, though failing to reach statistical significance compared to the lower concentration. VEGF protein concentration in the injected skin was significantly higher than in controls (p < 0.01). Flap perfusion was increased as well, demonstrated by indocyanine green (ICG) fluoroscopy (p < 0.001). CONCLUSIONS: Our results confirm the important role of VEGF(165) on angiogenesis in ischemic flaps. Indeed by injecting VEGF(165) at 3 to 7 days preoperatively in a concentration of 1 x 10(9) pfU our data show that length-to-width ratio for random-pattern-flaps could be increased from 2 : 1 to 3 : 1 and therefore may allow a wider range of applications of this simple flap technique.

Adenoviridae↗

Protecting the endothelial integrity of internal thoracic arteries.

BACKGROUND: Previous functional studies on human internal thoracic arteries, comparing the effect of the traditional harvesting method (occlusion with a clip) with a method leaving the artery perfused, revealed considerably impaired endothelial function associated with enhanced contractility after clipping. We have now investigated whether these observations could be correlated (1) with plasma markers of endothelial dysfunction, and (2) with structural changes in the endothelial layer. METHODS: 32 patients were randomly distributed into groups of clipped and perfused arteries. Arterial blood samples were obtained from both the artery and extracorporeal circulation to determine sP-selectin, sE-selectin, sL-selectin, and thrombomodulin using enzyme-linked immunosorbent assay. Arteries from three patients were examined by scanning electron microscopy. RESULTS: Concentrations of sP-selectin and thrombomodulin were significantly higher in plasma from clipped arteries compared to perfused arteries, whereas sE-selectin and sL-selectin concentrations were similar within the groups. Scanning electron microscopy revealed significant structural changes and loss of endothelial cells in clipped arteries. CONCLUSION: Biochemical and structural results support our findings that leaving the internal thoracic artery perfused preserves endothelial function in the arterial graft.

Biomarkers↗

[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↗

[Angiogenesis VEGF165 gene therapy with AdVEGF- a new delay procedure for flaps].

A regular tissue functioning requires the adequate supply of oxygen and nutrient via blood vessels. The sequences of formation and maturation of vessels are initiated and maintained by different growth factors. The VEGF growth factor plays an exceptional role in these mechanisms. The creation of sublethal ischemia as an angiogenic stimulus known as "Delay" is a well established procedure in plastic surgery, although the underlying molecular biological mechanisms still remain unknown. The important role of VEGF and its regulation depending on oxygen pressure suggest a strong connection between this growth factor and the delay phenomenon. The VEGF concentration in skin and underlying muscle was measured in overdimensioned random pattern flaps on 32 male Sprague-Dawley rats after either VEGF gene therapy or circumcision without elevation of the flap and compared to controls. Additional random pattern flaps were raised seven days post gene therapy or delay. The effect on the flap perfusion was measured postoperatively using Indocyanine green Laser Fluoroscopy and the size of the surviving and necrotic areas of the flaps were analysed. The skin of the random pattern flaps showed both in the Delay group and in the VEGF gene therapy group a significantly elevated VEGF concentration compared to the controls. The underlying rectus abdominis muscle showed no significant differences in VEGF concentration between the groups. The flap perfusion postoperatively was significantly increased solely in the VEGF gene therapy group. The analysis of the surviving area of the flaps showed a significant increase over the controls in the gene therapy group. The Delay procedure results in a significantly and locally raised concentration of the VEGF growth factor. The gene therapeutical use of this growth factor allows us to raise flap perfusion and to reduce necrosis. Both VEGF gene therapy and Delay seem to promote similar mechanisms whereas the gene therapy produced superior results in this setting.

Animals↗

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↗

Fungal polysaccharopeptide inhibits tumor angiogenesis and tumor growth in mice.

Angiogenesis is crucial to tumor growth and metastasis, and interruption of this process is a prime avenue for therapeutic intervention of tumor proliferation. The present study has made use of the S180 tumor-bearing mouse model to investigate the polysaccharopeptide, PSP, isolated from the edible mushroom Coriolus versicolor, a herbal medicine known for its anti-angiogenesis properties. Quantitative analysis of microcorrosion casting of the tumor tissue showed more angiogenic features such as dense sinusoids and hot spots, in control (untreated) than in PSP-treated animals. Immunostaining of tumor tissues with antibody against the endothelial cell marker (Factor VIII) demonstrated a positive correlation in that both the vascular density and tumor weight were lower in mice treated with PSP. Morphometric analysis of corrosion casts revealed that, even though the total amount of new vessel production was reduced, the basic tumor type-specific vascular architecture was retained. However, the expression of vascular endothelial cell growth factor (VEGF) in these tumors was suppressed. In conclusion, anti-angiogenesis should be one of the pathways through which PSP mediated its anti-tumor activity.

Administration, Oral↗

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↗

[Endovascular aneurysm treatment: Radiological and macropathological findings of the endoluminal surface of modular stent grafts].

PURPOSE: Characterization of the endoluminal surface of a modular stent graft and correlation of macropathological findings with results of radiological methods. METHODS: Aneurysms of the infrarenal aorta were created in 36 mongrel FBI dogs using autologous material. Endovascular treatment was performed with modular stent grafts using two polyester-covered nitinol stents connected with overlap within the aneurysm. Follow-up was 1 and 6 weeks, and 6 months for 12 animals, respectively. Results were documented using sonography, intravascular ultrasound (IVUS), spiral CT, MRI, and digital subtraction angiography (DSA). After fixation, the aorta was prepared and incised lengthwise. Before histopathological work-up, the different segments were macropathologically characterized and correlated with the respective findings of the radiological methods. RESULTS: 4 cases showed high grade stenosis within the stent grafts and graft occlusion occurred in two cases. The connection sites of these modular stent grafts showed steps and partial separation of the graft components was causative in 5 of these cases. Migration of graft components occurred in three cases, one of them with complete disconnection of the modular device. Irregulartities and deposits on the endoluminal surface were systematically underestimated with all radiological techniques used. IVUS showed moderate concordance concerning deployment and unfolding of the stent graft, however, irregularities of the endoluminal surface were systematically underestimated. Concordance of MRI, sonography, and CT was worse. Contrast-enhanced T1-w MRI detected endoluminal deposits with moderate concordance. However, the thickness of deposits was underestimated. DSA, IVUS, and CT showed only poor concordance with macropathological findings. CONCLUSIONS: The connection site of modular stent grafts predisposes to stenosis, occlusion, and disconnection of the modular device. Stent deployment and unfolding of the membrane might be examined with IVUS. MRI is useful for detecting endoluminal deposits and stenosis. However, radiological methods will underrate irregularities and deposits of the endoluminal surface.

Animals↗

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↗

[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↗

[Diagnosis of acute lung embolism with spiral CT and 3D reconstruction. Development of an animal model and technical probe in an ex-vivo experiment].

PURPOSE: To develop a model for simulation the CT morphologic situation of acute pulmonary embolism, to evaluate the accuracy of spiral CT and 3D reconstruction in the detection of artificial emboli and to investigate the influence of the orientation of emboli depending on z-axis orientation. MATERIALS AND METHODS: Standardized artificial emboli made of wax and of defined size and shape were positioned into the pulmonary arteries of porcine lungs. Castings of the embolized pulmonary arterial trees were made by injection of a special opaque resin. After performance of spiral CT the data sets of the emboli and the pulmonary arteries were post-processed. The 3D segmentations were compared with the anatomic preparation to evaluate the accuracy of spiral CT/3D reconstruction-technique. Technical specimens simulating CT-morphology of acute embolized vessels underwent spiral CT in six different positions with respect to the z-axis. The CT data were reconstructed using a standardized and a contrastadapted method with interactive correction. The 3D emboli were analysed under qualitative aspects, and measurements of their extent were done. RESULTS: In nearly 91%, there was complete agreement between CT and the corresponding findings at the anatomical preparation. Measurements of the 3D reconstructed technical specimens showed discrepancies of shape and size in dependence of the size of the original preparation, orientation and reconstruction technique. Overestimation up to 4 mm and underestimation to 2.2 mm were observed. Measurements of preparations with heights from 14 to 26 mm showed variances of +/- 1.5 mm (approximately 6-11%). CONCLUSION: The presented models are suitable to simulate CT morphology of acute pulmonary embolism under ex-vivo conditions. Accuracy in the detection of artificial emboli using spiral CT/3D reconstruction is affected by localization, size and orientation of the emboli and the reconstruction technique.

Acute Disease↗

Focal topographic changes in inflammatory microcirculation associated with lymphocyte slowing and transmigration.

Microcirculation is the primary mechanism for delivering lymphocytes to inflammatory tissues. Blood flow within microvessels ensures a supply of lymphocytes at the blood-endothelial interface. Whether the structure of the inflammatory microcirculation facilitates lymphocyte transmigration is less clear. To illuminate the microcirculatory changes associated with lymphocyte transmigration, we used intravital videomicroscopy to examine the dermal microcirculation after application of the epicutaneous antigen oxazolone. Intravascular injection of fluorescein-labeled dextran demonstrated focal topographic changes in the microcirculation. These focal changes had the appearance of loops or hairpin turns in the oxazolone-stimulated skin. Changes were maximal at 96 h and coincided with peak lymphocyte recruitment. To determine whether these changes were associated with lymphocyte transmigration, lymphocytes obtained from efferent lymph of draining lymph nodes at 96 h were fluorescently labeled and reinjected into inflammatory microcirculation. Epifuorescence intravital video microscopy demonstrated focal areas were associated with lymphocyte slowing and occasional transmigration. In contrast, focal loops and lymphocyte slowing were rarely observed in the contralateral control microcirculation. Results suggest that structural adaptations in inflammatory microcirculation represented by focal topographic changes may contribute to regulation of tissue entry by recirculating lymphocytes.

Adjuvants, Immunologic↗

Effects of thrombin and of the phospholipase C inhibitor, D609, on the vascularity of the chick chorioallantoic membrane.

Microvascular corrosion casting was used to assess the effects of thrombin and D609, a phospholipase C inhibitor, on the vascularity of the chick embryo chorioallantoic membrane (CAM). Discs containing vehicle, thrombin or D609 were placed on the CAM of fertilized white Leghorn eggs on Day 9 of gestation and vascularity was assessed on Day 11. Thrombin caused significant increases in the numbers (43%), diameters (5%) and lengths (17%), of both pre- and postcapillaries (first-order vessels by centripetal ordering). Conversely, D609 caused a decrease in the numbers (27%), lengths (12%) and diameters (8%) of first-order vessels. D609 decreased the total vascular volume of first- to third-order vessels by 32%, whereas thrombin increased vascular volume by 27%. Additionally, thrombin increased capillary plexus density by 6%, whereas D609 decreased capillary plexus density by 3%. These findings provide a quantitative assessment of changing vascularity in the chick CAM--a model assay system in the development of pro- and antiangiogenic agents.

Allantois↗

Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells.

Proteolysis mediated by the ubiquitin-proteasome system has been implicated in the regulation of programmed cell death. Here we investigated the differential effects of proteasomal inhibitors on the viability of proliferating and quiescent primary endothelial cells in vitro and in vivo. Subconfluent, proliferating cells underwent carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI) -induced apoptosis at low concentrations (EC(50)=24 nM), whereas at least 340-fold higher concentrations of PSI were necessary to obtain the same effect in confluent, contact-inhibited cells. PSI-mediated cell death could be blocked by a caspase-3 inhibitor (Ac-DEVD-H), but not by a caspase-1 inhibitor (Ac-YVAD-H), suggesting that a caspase-3-like enzyme is activated during PSI-induced apoptosis. When applied to the embryonic chick chorioallantoic membrane, a rapidly expanding tissue, PSI induced massive apoptosis also in vivo. PSI treatment of the CAM led to the formation of areas devoid of blood flow due to the induction of apoptosis in endothelial and other cells and to the collapse of capillaries and first order vessels. Our results demonstrate that proteasomal inhibitors such as PSI may prove effective as novel anti-angiogenic and anti-neoplastic substances.

Animals↗

Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice.

BACKGROUND: Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in the progression of atherosclerosis is unknown. In this report, we first demonstrate that intimal vessels occur in advanced lesions of apolipoprotein E-deficient (apoE -/-) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE -/- mice. METHODS AND RESULTS: ApoE -/- mice were fed a 0.15% cholesterol diet. At age 20 weeks, mice were divided into 3 groups and treated for 16 weeks as follows: group 1, recombinant mouse endostatin, 20 mg. kg-1. d-1; group 2, fumagillin analogue TNP-470, 30 mg/kg every other day; and group 3, control animals that received a similar volume of buffer. Average cholesterol levels were similar in all groups. Plaque areas were quantified at the aortic origin. Median plaque area before treatment was 0.250 mm2 (range, 0.170 to 0.348; n=10). Median plaque areas were 0.321 (0.238 to 0.412; n=10), 0.402 (0.248 to 0.533; n=15), and 0.751 mm2 (0.503 to 0.838; n=12) for the endostatin, TNP-470, and control groups, respectively (P</=0.0001). Therefore, endostatin and TNP-470 inhibited plaque growth during the treatment period by 85% and 70%. Intimal smooth muscle cell contents of plaques from control and treated mice were similar. CONCLUSIONS: Prolonged treatment with either angiogenesis inhibitor reduced plaque growth and intimal neovascularization in apoE -/- mice. Although the mechanism of plaque inhibition induced by these agents is not established, these results suggest that intimal neovascularization may promote plaque development.

Animals↗

Correlation of endoanal sonography with cross-sectional anatomy of the anal sphincter.

BACKGROUND: Anal endosonography has become an important imaging method in the diagnosis of anorectal disorders. However, little information exists as to whether anal endosonography reliably defines pelvic floor structures. The aim of this study was to correlate endoanal sonography with cross-sectional anatomy and histology. METHODS: Endosonographic tomograms were obtained from 9 human cadavers before fixation and cross-sectioning at identical levels. Muscular layers were defined by visual inspection, histology, immunohistology, and morphometry using three-dimensional sphincter reconstructions. RESULTS: Endosonography visualized only two muscular layers, whereas anatomic sections always revealed three. Comparisons revealed identical findings with regard to internal sphincter volumes and asymmetries. However, due to its failure to identify the longitudinal muscle, endosonography largely overestimated external sphincter volumes. In contrast to current beliefs, anatomic studies failed to detect striated muscle fibers within the longitudinal muscle and did not show an intersphincteric space. However, anatomic cross sections demonstrated "anterior bands" as newly described anchoring mechanisms for the anal sphincters. CONCLUSIONS: Anal endosonography supplies accurate information with regard to internal anal sphincter dimensions, but does not reliably outline deeper muscular layers. However, despite these drawbacks, comparisons of modern imaging techniques with cross-sectional anatomy may enhance our understanding of pelvic floor anatomy.

Aged↗

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↗