Tumor-related angiogenesis.

In recent years, tumor-related angiogenesis has become an important field of research in oncology. It could be stated that growth of solid tumors is completely dependent on neovascularization to provide the tumor with all required nutrients. Special compounds (tumor angiogenesis factor[s]) are released by tumor cells into the environment to stimulate different types of normal cells to become active for the tumor. In particular, endothelial cells of neighboring capillaries are induced to react. They disintegrate their own basal lamina, detach from their neighbors, enter the extracellular matrix, and migrate toward the tumor mass. Cell divisions occur within such sprouts, thereby increasing the number of migrating endothelial cells. Strands of such cells are formed, and inter- and intracellular lumina develop. Loops of these hollow strands anastomose to form a network of new vessels which become connected with the blood circulation. The tumor mass thus becomes vascularized and can continue to grow. The prevention of neoangiogenesis has an enormous impact on cancer treatment by inhibiting the growth of the tumor. In this review, all important aspects of tumor-related angiogenesis are presented.

Fractionation of synaptophysin-containing vesicles from rat brain and cultured PC12 pheochromocytoma cells.

Synaptophysin is a transmembrane glycoprotein of neuroendocrine vesicles. Its content and distribution in subcellular fractions from cultured PC12 cells, rat brain and bovine adrenal medulla were determined by a sensitive dot immunoassay. Synaptophysin-containing fractions appeared as monodispersed populations similar to synaptic vesicles in density and size distribution. Membranes from synaptic vesicles contained approximately 100-times more synaptophysin than chromaffin granules. In conclusion, synaptophysin is located almost exclusively in vesicles of brain and PC12 cells which are distinct from dense core granules.

Ultrastructural studies on the lung colonization by nonmetastatic rat tumor cells.

The events during the settlement of BSp73AS (AS) tumor cells in the syngeneic rat lung are described. Although AS cells show highly invasive behavior in vitro, subcutaneous primary tumors grow solidly without detectable metastatic spreading. However, AS cells when applied to the syngeneic rats via the tail vein give rise to lung colonies which grow rapidly at the site of the cells' primary arrest in the capillaries. The colonization comprises formation of microemboli, penetration of the endothelium including the basal lamina, and invasion of the lung tissue. Within two weeks, large colonies develop, thereby compressing, invading, and destroying their surroundings without detectable preference in direction. This establishment of AS tumors in the lung reflects the high invasive potential of AS cells and displays many of the morphological features observed during the formation of colonies of metastatic cell lines. Thus, we conclude that a nonmetastatic tumor cell line, such as AS, may possess almost the whole set of properties necessary for successful metastasis.

Tumor-related reconstitutive vascularization. An ultrastructural study.

The nonmetastatic derivative of the pancreatic adenocarcinoma BSp73 of the BDX rat, BSp73 AS (AS), was used to generate solid lung colonies by the intravenous route. Vascularization could be seen within the tumor nodules and in the surrounding, highly disorganized lung tissue. We concentrate here on the formation of capillaries in the surroundings of pulmonary AS foci. The formation of capillary lumina can be described as follows: first, a lumen is formed between an endothelial cell (EC) and its basal lamina (BL) by partial detachment of the EC. The denuded BL is then re-coated by EC protrusions until the lumen is newly lined. A similar process is observed at the abluminal surface of ECs of vessels just beneath the surface of alveolar lumina. In this case, ECs detach from their BL and generate stilts, thus bulging adluminally. The naked BL is then recoated by EC protrusions. Finally, small closed lumina are formed by the ECs. These events occurring during vascularization are interpreted as morphogenetic reactions of normal cells to tumor-derived stimuli. Vascularization of this kind takes place within peritumoral, disturbed alveolar tissue and appears to be aimed at reconstituting a normal alveolar histology in order to overcome the destruction caused by the tumor. In this study we show the highly complex reactions between normal and neoplastic tissue.

Ultrastructural analysis of experimentally induced invasion in the rat lung by tumor cells metastasizing lymphatically.

The colonization of the lung by the rat tumor cells BSp73 ASML which have the ability to metastasize via the lymphatic system was studied at the ultrastructural level. Tumor cells arriving in the lung after i.v. injection become transiently embolized; within hours, however, they begin to extravasate from the blood capillaries. Swelling cellular protrusions open a limited area between endothelium and basal lamina through which tumor cells erupt. Tumor cells then form metastases in the interstitial tissue and, in an apparently lymphotropic action, intravasate the lymphatic vessels in a similar manner to a reverse diapedesis-like process. Within the lympatic system they settle, spread, and build up extensive tumor foci particularly in the subpleural region.

Electrotransfer of proteins after isoelectric focusing (with or without urea) on fabric-reinforced, immobilized pH gradient gels.

In the present article a procedure is described which combines the horizontal isoelectric focusing (IEF) of proteins on fabric-reinforced polyacrylamide gels with the subsequent electrophoretic transfer of the proteins to nitrocellulose or Immobilon. The application of a carrier material that is permeable for current and molecules and that serves as a physical support of the IEF gel is one of the central prerequisites for the method to work. Moreover, it is important to fix the pH gradient topographically by the use of Immobilines mainly in order to avoid distortion of the protein pattern during the electrotransfer (Western blot). The Western blot can be performed either in the submerse or in the so-called "semi-dry" blotting system. Our procedure is compatible with IEF protocols employing buffer systems with or without urea. The efficacy of our method is demonstrated by the IEF and Western blotting of several known marker proteins.

[Hypothyroidism and endocrine orbitopathy]. / Hypothyreose und endokrine Orbitopathie.

The 34-year old woman, by profession a farmer, presented herself with the symptoms of hypothyroidism, which were confirmed by laboratory investigations. Chronic autoimmune thyroiditis was assumed due to the constellation of primary hypothyroidism in association with elevated thyroid autoantibodies. Substitution with levothyroxine induced a full clinical recovery, but persistent hyperthyroidism occurred even after discontinuation of levothyroxine treatment. Mild ophthalmopathy developed and Graves disease was diagnosed. The primary manifestation of Graves' disease with hypothyroidism was caused by blocking TSH receptor antibodies. Chronic autoimmune thyroiditis, Graves' disease and the importance of thyroid autoantibodies are discussed.