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  • 1
    Publication Date: 1992-04-22
    Print ISSN: 0020-7136
    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
    Published by Wiley
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 47 (1994), S. 1-16 
    ISSN: 1432-1041
    Keywords: Antitumour agents ; Gallium trinitrate ; Spirogermanium ; Budotitane ; Titanocene dichloride ; metal compounds ; non-platinum-metal complexes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the antitumour activity of the inorganic complex cis-diammine-dichloroplatinum(II) (cisplatin) was discovered. This led to the development of other types of non-organic cytostatic drugs. Cisplatin has developed into one of the most frequently used and most effective cytostatic drugs for the treatment of solid carcinomas. Numerous other metal compounds containing platinum, other platinum metals, and even non-platinum metals were then shown to be effective against tumours in man and experimental tumours in animals. These compounds comprise main-group metallic compounds of gallium, germanium, tin, and bismuth, early-transition metal complexes of titanium, vanadium, niobium, molybdenum, and rhenium, and late-transition metal complexes of ruthenium, rhodium, iridium, platinum, copper, and gold. Several platinum complexes and four non-platinum-metal antitumour agents have so far entered early clinical trials. Gallium trinitrate and spirogermanium have already passed phase II clinical studies and have shown limited cytostatic activity against certain human carcinomas and lymphomas. The two early-transition metal complexes budotitane and titanocene dichloride have just reached the end of phase I clinical trials and have been found to have an unusual pattern of organ toxicity in man. Titanocene dichloride will soon enter phase II clinical studies.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 67 (1980), S. 415-416 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 68 (1981), S. 272-273 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 68 (1981), S. 273-274 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 266 (1991), S. 563-578 
    ISSN: 1432-0878
    Keywords: Xenografted human carcinomas ; Basal lamina ; Development, following heterotransplantation ; Electron microscopy ; Immunofluorescence microscopy ; Man ; Mouse (NMRI, nu/nu)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The development of the basal lamina (BL), the key structure of the basement membrane (BM), was investigated in three xenografted human carcinomas of the sigmoid colon (CA 1), the lung (L 261), and the hypopharynx (H-Stg 1) following heterotransplantation to athymic mice. The study involved the use of electron microscopy and indirect immunofluorescence techniques employing highly specific antibodies against the intrinsic BL components, heparan sulfate proteoglycan, laminin and type-IV collagen. Following transplantation, the extracellular matrix material of the transplanted tumors decomposed and was phagocytozed by invading macrophages within 1 to 2 days. During this stage, no specific binding of the applied antibodies to BL components could be detected within the xenografts. Following the ingrowth of host-derived connective tissue between days 2 to 6, small fluorescence-positive granules appeared within the cytoplasm and around those tumor cells that were located close to the invaded strands of connective tissue. Ultrastructurally, typical secretory granules were detectable in the cytoplasm of many xenografted carcinoma cells. Thereafter, a tannic acid-positive, patchy material appeared in the extracellular space of CA 1 and L 261 and aggregated to form small fragments of a discontinuous BL. In the H-Stg 1 xenografts, this material assembled to form continuous mono-, bi- and multilayered structures. Large amounts of excess BL material remained accumulated in the L 261 and H-Stg 1 xenografts until the end of the observation period (day 24). These findings reveal that discontinuities of the BL occur independent of the active invasion processes of tumor cells, since xenografted human carcinomas neither grow invasively nor metastasize in nude mice. Moreover, they confirm that these discontinuities are not caused by a quantitatively insufficient production of BL material, but rather arise from qualitative imbalances of the composition of the synthesized BL material.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 264 (1991), S. 563-576 
    ISSN: 1432-0878
    Keywords: Organoid culture ; High density culture ; Human tumors ; Histiotypic reorganization ; Morphological study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the present study we describe a new method to cultivate human tumors, which allows organoid differentiation under in vitro conditions. Diverse tumors of different origin and various histopathology which had been heterotransplanted to athymic mice were dissociated into single cells and seeded at high cell density onto a membrane filter consisting of cellulose nitrate at the gas-medium interface. Within a few days, the tumor cells reorganized and differentiated into organoid structures which exhibited the typical histological characteristics of the original tissues. Due to the formation of organoid aggregates, which was also previously seen with normal fetal cells, this type of culture has been described as ‘organoid culture’. In the case of adenocarcinomas of the lung and the colon including the rectum, glandular structures with central lumina, adjacent microvilli, and junctional complexes were formed. Numerous specific intercellular contacts such as desmosomes and tight junctions occurred as well as interdigitations of adjacent cell membranes. In a tumor of the rectum, a typical brush border differentiated at the surface of the reorganized tumor-tissue aggregate. Epidermoid carcinomas of the head and neck developed structures resembling the spinous layer of the epidermis, exhibiting numerous desmosomes and intracytoplasmic bundles of tonofilaments radiating into the desmosomes. Most tumors produced a fragmentary monolayered or multilayered basal lamina of similar morphological appearance as under in vivo conditions. These results illustrate the organoid reorganization and differentiation of human tumor cells under the experimentally rather simple conditions of the organoid culture systems and clearly demonstrate that this in vitro system comes close to the in vivo situation as far as certain differentiation phenomena are concerned.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 272 (1993), S. 395-405 
    ISSN: 1432-0878
    Keywords: Xenografted human carcinomas ; Basal lamina ; Type-VII collagen ; Anchoring fibrils, basal lamina ; Immunohistochemical study ; Athymic mice (NMRI nu/nu)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution of type-VII collagen, the main molecular component of the anchoring fibrils (AF) attaching the basal lamina (BL, lamina densa of the basement membrane) to the surrounding connective tissue, was investigated in four xenografted human carcinomas of the hypopharynx (H-Stg 1), the lung (L 261), the sigmoid colon (CA 1), and the rectum (R 85). The studies were performed with a recently prepared, affinity-purified and highly specific antibody to type-VII collagen by using the indirect immunofluorescence and the APAAP (alkaline phosphatase anti-alkaline phosphatase) techniques. For comparison, the localization of the intrinsic BL components laminin and type-IV collagen were additionally analyzed in all four carcinomas. It was shown that type-VII collagen usually colocalized to laminin and type-IV collagen and was deposited at the borderline between carcinoma cell clusters and the surrounding strands of connective tissue in a similar, but more diffuse and less continuous distribution than both intrinsic BL components. In the squamous cell carcinoma H-Stg 1 and the adenocarcinoma L 261, type-VII collagen was additionally accumulated in enlarged extracellular spaces between carcinoma cells, away from the contact zone to the connective tissue and again colocalized to laminin and type-IV collagen. Numerous carcinoma cells of both xenografts showed remarkable intracytoplasmic immunoreactivity for the antibody to type-VII collagen. Even in the case of the gastrointestinal carcinomas CA 1 and R 85, faint immunoreactivity for type-VII collagen was found at the contact zone between the mucosal epithelium and the surrounding connective tissue. These results confirm that epithelial carcinoma cells are obviously involved with the synthesis of the main molecular component of AF usally attaching the BL to the adjacent connective tissue and hint at a possible correlation between the localization of type-VII collagen and the observed pattern of the BL. However, it cannot be decided whether there is a direct causal relation between both phenomena or whether they are both the consequence of an independent but common cause, such as abnormal cellular differentiation of carcinoma cells. In no case, can the discontinuities in the distribution of type-VII collagen be explained by active tumor cell invasion since xenografted human carcinomas neither invade nor metastasize.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 198 (1979), S. 373-380 
    ISSN: 1432-0878
    Keywords: Ventral cochlear nucleus ; Calyceal processes ; Flattened synaptic vesicles ; Ultrastructure ; Morphometric study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In this paper we report the appearance of flat vesicle-containing endings in aldehyde-fixed ventral cochlear nucleus of rats with qualitative and quantitative properties suggesting they should be identified as calyceal processes. Their synaptic vesicles are elongate and significantly smaller than the vesicles in the calyces of Lenn and Reese (1966). Therefore these endings are flat vesicular calyceal processes, possibly of inhibitory function.
    Type of Medium: Electronic Resource
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