The vascular system plays a role of key importance during tumour growth and metastasis formation. In addition, the effectiveness of almost all therapeutic modalities, including drug therapy and radiotherapy, is influenced by the micro-architecture and the gradients of essential nutrients around each vessel. This underlines the importance of the vascular architecture, its origin and effectiveness as a nutrient delivery system. The knowledge that tumour vasculature is abnormal has led to concepts such as angiogenic attack and vascular targeting (Folkman, 1976;Denekamp, 1984;Bicknell, 1994;Folkman and D'Amore, 1996). This, in turn, has led to many more studies of tumour vasculature and primary as well as secondary angiogenesis. However, even though our knowledge of the mechanisms underlying angiogenesis has increased dramatically in the past 25 years, few quantitative data are available on the vascular network architecture and pattern formation in tumours.The fact that the tumour vascularity differs in many aspects from the vasculature of normal organs and tissues was already recognized in the last century (Virchow, 1863; Thiersch, 1865). Thomlinson and Gray (1955) indicated the importance of intervessel spacing because of the threefold increase in radioresistance that accompanies reduction of pO 2 concentrations below critical level. The important question as to whether the vascular architecture of an individual tumour is tumour type-specific has been controversial (Warren, 1979;Vaupel and Gabbert, 1986.) This is due, at least in part, to the methodologies used. Most reports confine themselves to qualitative observations and comparisons of gross vascular patterns in host and tumour, or to blood vessel density, length and diameter measurements, which in turn vary with the staining and counting techniques (Davidson et al, 1994;Endrich and Vaupel, 1998). Recently, morphometric analyses have been introduced in which the features of tumour cells (proliferation rate, oxygenation, angiogenic growth factor production) have been mapped by sequential staining of the same section, allowing the influence of the vascular assay on clinically relevant aspects of cell populations to be mapped. Vascular and metabolic profiles (VAMP) have illustrated marked differences between different types of tumour of the same general histology, for brain tumours and those from the head and neck region. Less et al (1991) introduced the first suitable approach for determining branching patterns and vessel dimensions in corrosion casts of mammary carcinomas. They established a quantitative classification scheme which takes account of the unique features of tumour microvascular network topology. However, it should be recognized that measurements were made on planar twodimensional (2D) projected images of three-dimensional (3D) specimens. All attempts to determine distances in corrosion casts geometrically after 2D projection inevitably include a considerable error. Measurements of vascular parameters such as intercapillary distance and vessel se...
Sirius Red staining is presented as a method for collagen determination, enabling quantitative morphometric measurements to be performed in locally defined tissue areas. The advantage of this method is especially shown for alveolar lung tissue. By excluding the bronchial areas in the tissue sections, the differences in the degree of fibrosis proved to be more discrete after different loads of quartz dust than by any other method. The difference of 12 micrograms collagen measured colorimetrically represented a 1.2-fold increase. The collagen measured in the alveolar tissue by the morphometric method rose from 9.8 to 28.6%. This is a 2.9-fold increase, underlining the vast improvement in sensitivity. Thus, this method is specifically suitable for the evaluation of very small fibrotic lesions. The quartz doses given are particularly low compared to most other investigations. Histologic lung and lymph node sections from female Wistar rats injected intratracheally with differing quantities of quartz dust (0.03, 0.1, 0.5, 1.75 mg) were stained with Sirius Red, and the collagen fibers measured with a quantitative image analysis. The results for lymph nodes using different methods (wet weight determination, quantitative measurement of quartz typical areas, colorimetric and morphometric collagen determination) showed a high correlation at the different doses. This showed that the morphometric method is suitable for the quantitative measurement of collagen. Corresponding results were also found in the comparative lung tissue measurements (colorimetric and morphometric collagen determination). However, the morphometric method has the decisive advantage that measurements can be restricted to defined tissue areas and do not destroy the section.
Silicon carbide (SiC) dust and other dusts for comparison were injected intratracheally at a high dose (50 mg) into rats and the response of the lungs and the lymph nodes was studied after an appropriate experimental period. The indices studied were: histological changes in the lung and lymph nodes, organ weights, the formation of coliagenous fibres, and the appearance of quartz typical areas.
The question of lung damage as a result of exposure to silicon carbide (SiC) was investigated by inhalation experiments to obtain information on the qualitative response of lung tissue to the test substance (SiC) Old occupational studies showed that employees involved with synthetic abrasives had an up to twofold increase in the incidence of tuberculosis. This was considered to be the result of a silicogenic effect. On the other hand, it was also shown that such workers developed significantly less fibroses than those working with sandstone.IIn a more recent epidemiological study based on medical examinations and lung radiographs, no increase in lung disease was found in workers that used synthetic abrasives in conjunction with premanufactured silicon carbide (SiC) abrasive wheels. There was, however, a limited pneumoconiosis hazard in those concerned with SiC production.2Only few reports are available on the causes. Open lung biopsies from two employees working for a fireproof brick manufacturing plant found substantial amounts of SiC and other dusts but not quartz.3 An interstitial fibrosis in lung tissue was diagnosed in a further case after only a one year exposure to various non-quartz abrasive dusts. As the patient was a heavy smoker and also subjected to other inhalative noxious compounds in his earlier working life, this could not be unequivocally related to the abrasive dusts.Significant increases in pulmonary diseases have also been reported by SiC manufacturing plants. In the most comprehensive study to date, 171 men from SiC industrial manufacturing branches were examined radiologically and by means of lung function tests; 35% of workers showed shadows on the radiographs with average profusion greater than 0/1 and 14% had average profusion readings of greater than 1/1. In this report the highest quartz concentration amounted to 0-1 mg/m3 whereas that of SiC was 057 mg/m3.4 Exposures to quartz and other crystalline SiO2 compounds in the manufacturing plants must be taken into account as competing causes; according to our findings these can be present in significantly greater concentrations than the mentioned values for SiC and quartz.5 6 Moreover, manufacture related exposures to SiO2 also exist.7 The recent study by Durand et al 8 concerning alterations in chest radiographs was based on a cohort of 128 workers exposed to SiC in a manufacturing plant. The authors reported that the workers were exposed to crystalline SiO2 during various manufacturing stages. Also, SiC fibres were present in the respired air. Both must be considered to be confounders during exposure to SiC dust.The results from animal experiments are contradictory: older studies with ill defined experimental
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