Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radioactive proline-labeled procollagen, accumulated during a 3-hr incubation of normal and transformed BALB 3T3 cultures, was treated with pepsin and the resulting collagen components were analyzed by carboxymethyl-cellulose chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis in the presence or absence of reducing agent. Collagen in the medium of three subclones of BALB 3T3 A-31 that exhibited contact-inhibition of growth at confluence, as well as in the medium of one that did not, consisted of alpha(1) and alpha(2) subunits in the ratio of 3:1, suggesting that 3T3 cells synthesize type I collagen, [alpha(1)(I)](2)alpha(2), and another type, which we have designated X, composed of alpha(1) chains, which may or may not be identical to alpha(1)(I). Culture medium from 3T3 transformed by Kirsten or Moloney sarcoma virus contained type I collagen and another type differing from I and X and designated as type Y. The latter appeared to be similar to type III collagen [alpha(1)(III)](3), since it contained intrahelical disulfide bonds. Analysis of intracellular collagen also demonstrated the presence of type III in Ki-3T3 and its absence from 3T3 cells. Collagen components from the medium of a simian virus 40 transformant were identical to those of the contact-inhibited clones, while the collagen from a 4-nitroquinoline-1-oxide-induced transformant was composed mainly of two components differing from alpha(1)(I), alpha(2), or alpha(1)(III). These results suggest that the type of collagen accumulated in transformed cell cultures may be specifically related to the transforming agent.
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PMID:Specific changes in the collagen phenotype of BALB 3T3 cells as a result of transformation by sarcoma viruses or a chemical carcinogen. 19 25

The structure of canine transmissible venereal sarcoma (CTVS) has been examined from 14 to 71 days after implantation. During early growth, the tumour appears to be composed primarily of loosely arranged, round cells and a few fibroblast-like cells. As the tumour mass increases, the round cells become tightly packed with highly interdigitating plasma membranes. The number of irregularly shaped round cells and fibroblast-like cells increases with increasing tumour mass. Collagen and reticular fibres can be found in early tumours, frequently in association with the round cells, and in regions devoid of fibroblast-like cells. During tumour regression, cellular degradation is evident in fibroblast-like and irregularly shaped cells as well as round cells. The data suggest that transformation may occur in the course of tumour growth, causing morphological change from round to fibroblast-like cells, and that CTVS is an undifferentiated round-cell sarcoma capable of differentiation in a fibroblastic direction. Also present, primarily in tumour cells from newborn dogs, are cytoplasmic lamellar arrays and crystalline virus-like structures, both previously described in other forms of tumor cells.
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PMID:Canine transmissible venereal sarcoma: electron microscopic changes with time after transplantation. 57 57

Of 49 cases of synovial sarcoma, which represent 5.8% of all soft tissue sarcomas with confirmed diagnosis in the files of the Kiel Pediatric Tumor Registry (Kiel, Germany), 35 occurred in patients up to the age of 18 years. The lower extremities were the most common. The 35 cases included 21 biphasic and 14 monophasic fibrous synovial sarcomas. The different cell types constituting synovial sarcoma could be demonstrated by conventional light microscopic study, but more readily so by immunohistochemical study, particularly when antibodies against cytoskeletal components were applied. Aberrant antigen expression was noticed for the neural markers, protein S-100, and neuron-specific enolase. Moreover, four tumors were positive for Ki M7. Collagen type IV was found in all tumors tested. For the 20 patients enrolled in the Cooperative Soft Tissue Sarcoma Study of the German Society of Pediatric Oncology (GPO) the survival rate at 7 years is 63%. When five patients with initial recurrence are excluded, the survival rate is 72%. It is concluded that immunohistochemical study is useful in the diagnosis and differential diagnosis of synovial sarcomas despite certain limitations. Multimodality treatment approach has improved the overall prognosis. There is no relationship between histologic subtype and prognosis according to the classification scheme employed in this study.
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PMID:Synovial sarcoma in children and adolescents. A report from the Kiel Pediatric Tumor Registry. 170 63

Collagen IV dimers of two collagen IV molecules connected by their C-terminal globular NC1 domains were isolated by limited digestion with bacterial collagenase from mouse Engelbreth-Holm-Swarm (EHS) sarcoma tissue. The collagenous domains were only 300 nm long as compared to 400 nm of intact collagen IV but the disulfide bonds in the N-terminal region of the major triple helix were retained. Unfolding of the collagenous domains as monitored by circular dichroism occurred in a temperature range of 30 to 44 degrees C with a midpoint at 37 degrees C. The transition is significantly broader than that of the continuous triple helices in collagens I, II and III, a feature which can be explained by the frequent non-collagenous interruptions in the triple-helical domain of collagen IV. Refolding at 25 degrees C following complete unfolding at 50 degrees C was monitored by circular dichroism, selective proteolytic digestion of non-refolded segments and by a newly developed method in which the recovered triple-helical segments were visualized by electron microscopy. Triple-helix formation was found to proceed in a zipper-like fashion from the C-terminal NC1 domains towards the N-terminus, indicating that this domain is essential for nucleations. For collagen IV dimers with intact NC1 domains the rate of triple-helix growth was of comparable magnitude to that of collagen III, demonstrating that the non-collagenous interruptions do not slow down the refolding process where the rate-limiting step is the cis-trans isomerization of proline peptide bonds. Refolding was near to 100% and the refolding products were similar to the starting material as judged by thermal stability and electron microscopic appearance. Removal of the NC1 domains by pepsin or dissociation of their hexametric structures by acetic acid led to a loss of the refolding ability. Instead products with randomly dispersed short triple-helical segments were formed in a slow reaction. In no case, even when the disulfide bonds in the N-terminal region of the triple-helical domain were intact, was refolding from the N- towards the C-terminus observed. Taken together with results in other collagens, this suggests that C to N directionality might be an intrinsic property of triple-helix folding.
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PMID:Folding of collagen IV. 285 Jan 75

An experimental transplantable canine brain tumor model with the advantages of rapid tumor growth within 10 days and relative safety for the investigator is presently available. The tumor is produced by intracerebral inoculation of cultured cells derived from a canine brain tumor induced by the Schmidt-Ruppin strain of the Rous-Sarcoma virus (SR-RSV). It has potential use as a model in experiments designed to evaluate the effectiveness of chemotherapy and radiotherapy with serial computerized tomography scans. However, characterization of the induced tumor is essential. Ideally, it should have features attributable to glioma and/or neuroectodermal tumors. Utilizing the technique of intracerebral inoculation of cells cultured from the original dog brain tumor induced by SR-RSV, Salcman et al identified the tumor they induced in brains of mongrel puppies as a glioma by light microscopic criteria (Reference). The purpose of our study was to further characterize this experimental tumor by electron microscopic and immunohistochemical techniques. Tumor was induced in 6 mongrel puppies. Stains of the tumor for immunohistochemical reactivity to glial fibrillary acid protein, S-100 protein and 210K neurofilament protein were all negative. With the electron microscope, the intracerebral tumor cells were mostly undifferentiated. They had a few cell processes, occasional punctate adhesions and some microvilli-like structure. The tumor cell nucleus was usually oval shaped and sometimes had nuclear indentations. The cytoplasm contained abundant free ribosomes, some rough endoplasmic reticulum and mitochondria. Collagen fibers and basal lamina were not observed in the intercellular spaces. The capillaries within the tumor were characterized by proliferation of immature endothelial cells which were non-fenestrated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Brain tumor induced in dogs by intracerebral inoculation of SR-RSV induced cultured tumor cells--electron microscopic study]. 299 91

An efficient and reliable procedure for the isolation and culture of endothelium from large vessels of small animals (e.g., rat) is described, which takes advantage of endothelial cell-extracellular matrix interactions to promote the outgrowth of cells from tissue explants. The procedure may also permit the isolation by nonenzymatic means, of endothelial cells from other vessels and tissues. Rings and opened segments of aortic tissue were placed on a variety of substrates including: untreated tissue culture plastic; films of fibronectin, laminin, type I collagen, and gelatin; gels of type I collagen (Vitrogen, Collagen Corporation, Palo Alto, California), of basement membrane components derived from the EHS sarcoma (Matrigel, Collaborative Research Inc., Lexington, Massachusetts), and of agar and agarose. The medium used was OPTI-MEM or RPMI 1640 (Gibco Laboratories, Grand Island, New York) with 3% or 20% fetal calf serum, and 50 micrograms/ml endothelial cell growth supplement. Only explants on Vitrogen and on Matrigel produced a significant and consistent outgrowth of cells and this occurred shortly after the initiation of explants. Virtually no outgrowth occurred from explants on the other substrata, even after 10 days in culture. On Vitrogen gels, the cells emerged from the explants as single stellate and bipolar cells, whereas those on Matrigel grew as chains and sheets from the edges of the explant. Cells were passaged from both types of gels onto plastic or glass surfaces. The passaged cells isolated from both gel matrices exhibited specific endothelial cell characteristics including a "cobbled" morphology at confluence, positive staining for von Willebrand factor, and uptake of Di-I-Ac-low density lipoprotein. Because rat and other small animal aortic endothelial cells are resistant to isolation by enzymatic treatment, this technique provides a simple means to obtain large numbers of this cell type. Further, the method permits study of endothelial cell functions in vitro, and the roles which the extracellular matrix may play in these processes.
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PMID:Isolation of rat aortic endothelial cells by primary explant techniques and their phenotypic modulation by defined substrata. 329 52

The distribution and nature of extracellular matrix proteins in neurofibroma tissue was studied by indirect immunofluorescence, immunoelectron microscopy, immunoblotting, and rotary shadowing. The most striking feature was an extensive network of basement membranes localized mainly around Schwann cells and small blood vessels. The major components, collagen IV, laminin, and nidogen, were mainly deposited in the lamina densa. Some laminin and nidogen could be extracted with 0.5 M NaCl and were shown by electrophoresis to have the characteristic chain and fragment patterns described previously for these proteins isolated from the mouse Engelbreth-Holm-Swarm (EHS) sarcoma. Fragments of collagen IV and collagen VI were solubilized by limited proteolytic digestion and identified after rotary shadowing. The more remote interstitial regions of the tumor contained cross-striated collagen fibrils which were composed of collagen III (diameter, 20-30 nm) or collagen I (diameter, 40-50 nm). Collagen fibrils thicker than 80 nm were not found. The interstitial regions also contained collagen VI as a fine filamentous network near cells and between collagen fibrils. Deposits of fibronectin were rather small and showed a scattered distribution. The data indicate that Schwann cells contribute considerably to matrix production in neurofibroma which may therefore be a suitable model for studying basement membranes of neuroectodermal origin.
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PMID:Basement membrane proteins, interstitial collagens, and fibronectin in neurofibroma. 392 26

Major components of basement membranes, including collagen IV, laminin, heparan sulphate proteoglycan and nidogen, were isolated from the matrix of the EHS sarcoma. The purified components were analysed for their domain structure and for the participation of distinct domains in molecular interactions and cell binding. Collagen IV consists of four domains which have triple helical or non-collagenous structures. Self-assembly of the protein into a network-like organization occurs by specific interactions between N-terminal triple helical segments and between the C-terminal globules. Cell binding requires a central triple helical segment. Laminin has the shape of an asymmetrical cross; different globular domains within this structure mediate binding to proteoglycan and to cells. The proteoglycan consists of four heparan sulphate chains attached to a small protein core. These chains have the potential to bind laminin, fibronectin and collagen IV. Nidogen was isolated in several molecular forms which showed either self-aggregation or binding to laminin.
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PMID:Laminin, proteoglycan, nidogen and collagen IV: structural models and molecular interactions. 644 Jul 57

The biosynthesis of collagen and fibronectin molecules by cultivated glomerular epithelial or mesangial cells was studied at confluency using radioactive proline or lysine as precursors. Collagen represented 0.5% of the total protein synthesized by the glomerular epithelial cells. About 60% of this collagenous protein were associated to the cell layer, whereas about 40% were secreted into the culture medium. Two major collagenous polypeptides were observed with apparent molecular weights of 185K and 170K, and were identified as two gene products of type IV procollagen. They exhibited ratios of 3- to 4-hydroxyproline, of total hydroxyproline to proline, and of hydroxylysine to lysine characteristic of type IV procollagen. They were degraded by bacterial collagenase. The patterns of peptides obtained after digestion of the 185K and 170K chains of this type IV procollagen with pepsin and V8 protease were identical to those obtained after digestion of type IV procollagen chains purified from a murine tumor (EHS sarcoma). Finally. a purified antibody to type IV collagen specifically immunoprecipitated the collagenous protein produced by the glomerular epithelial cells. By contrast, the mesangial cells synthesized about 5% of collagenous protein. 90% of this collagen were secreted into the cultured medium, whereas about 10% remained associated to the cell layer. Type I, III and IV procollagens were synthesized by the mesangial cells. Fibronectin was found in the medium and cell layer of both epithelial and mesangial cells. Fibronectin molecules were identified by their resistance to bacterial collagenase, their susceptibility to pepsin digestion, and their specific adherence to collagen. It was composed of disulfide-linked peptides of 220K daltons. The data therefore demonstrate that: (a) the glomerular epithelial and mesangial cells synthesize fibronectin molecules and type IV procollagen in vitro; (b) the cultivated mesangial cells also synthesize type I and III collagens. The implications of these findings in certain pathological circumstances, such as diabetes mellitus, are now being investigated.
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PMID:Synthesis of collagen and fibronectin by glomerular cells in culture. 732 12

We describe our experience with intravenous immunoglobulin (IVIg) treatment in fibrotic conditions and our results and experience with the effect of IVIg therapy to prevent metastases in malignancy. We have delineated the mechanisms by which IVIg can affect atherosclerosis (i.e., effect on MMP-9, antiidiotypes to anti-OxLDL), which led to reduced atherosclerosis in animal models. The effect of IVIg on skin fibrosis was assessed in a murine model of scleroderma-like disease. Collagen expression was decreased in the skin of mice treated with mouse IVIg, associated with decreased type I collagen gene expression, and accompanied by inhibition of transforming growth factor (TGF)beta and interleukin (IL)-4 secretion by splenocytes. We also described a favorable response to IVIg treatment in patients with either systemic sclerosis or myelofibrosis. The administration of IVIg to mice inoculated with melanoma or sarcoma cells induced a statistically significant inhibition of metastatic lung foci and prolongation of survival time. IVIg was found to stimulate the production of IL-12, an anti-tumor and anti-angiogenic cytokine. Positive staining of the cytoplasm, cell membrane, and nuclear membrane of several types of malignant tumors by IVIg was immunohistochemically demonstrated.
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PMID:Intravenous immunoglobulin treatment for fibrosis, atherosclerosis, and malignant conditions. 1558 34


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