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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study a state of temporary defibrinogenation was induced in rats by Defibrase treatment. It was found that the formation of pulmonary metastases after intravenous tumour cell injection was decreased in defibrinogenated rats. However, defibrinogenation did not influence the effect of trauma and infusion of dextran 1000 on metastasis formation. Both these procedures stimulated the formation of metastases in defibrinogenated rats. These results indicate, that fibrinogen and/or fibrin are of importance for the formation of metastases but that the stimulating effect of trauma and dextran 1000 on metastasis formation is independent of fibrinogen and/or fibrin.
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PMID:Pulmonary metastasis formation after intravenous tumour cell injection in defibrinogenated rats. 12 72

The purpose of the present paper was to study clinical, morphological and immunological aspects of late rejection of renal allotransplants. We have, therefore, analyzed the occurrence and nature of renal transplant disease and graft failure among 125 recipients surviving for 1 to more than 8 years after transplantation. In this population transplant disease as defined by the appearance of heavy proteinuria and/or steadily declining graft function occurred in 22 patients. At the closure date of the study on December 31, 1972 complete graft failure had occurred in 12 of these 22 patients and 4 of these have died. In addition two patients died in the presence of normal graft function, due to chronic hepatitis and metastatic cancer respectively. As based on clinical findings, pathophysiological features and renal lesions the patients with late transplant disease were classified into two groups and described accordingly. Group A, termed glomerular transplant disease, included a majority of 16 patients, constituting a rather homogenous idsease entity in relation to course of disease, clinical findings and renal lesions as studied by light-, immunofluorescence- and electron microscopy. All these patients presented with heavy proteinuria, which was non-selective in all but two, resulting eventually in complete loss of graft function in eight cases. All these patients developed hypoalbuminemia and hypercholesterolemia, and one half manifested a classical nephrotic syndrome. Arterial hypertension occurred in all patients except two. Glomerular structure as studied by light microscopy revealed a number of lesions of a rather polymorphous pattern in all patients in group A. Endomesangial proliferation, hyperplasia and segmental proliferation of epithelial cells and thickening of capillary walls were prominent features, although the degree of severity, extension and type of lesion occurred in such varying proportions that classification into any well characterized category of glomerulonephritis was not possible. All cases in group A revealed immune deposits, most frequently containing IgG, IgM, complement and fibrinogen. IgA, IgD and IgE were also demonstrated in a lesser proportion of cases in this group. The immunofluorescent pattern was a mixed granular and linear, and in no case strictly linear or granular alone. The ultrastructural investigation contains a detailed analysis of the
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PMID:Late failure or human renal transplants. An analysis of transplant disease and graft failure among 125 recipients surviving for one to eight years. 23 63

Trauma produced by amputation of a limb bearing the primary tumor influenced pulmonary metastases of the Carcinosarcoma of Walker 256 of the rat. This enhancement was present in 38% of the animals following the removal of a limb bearing the primary tumor; and in 29% of those in which the controlateral limb without tumor was amputated. A significant prolongation of the clotting time, an elevation of fibrinogen factor II and VII and a rapid consumption of factor VIII present soon after trauma may have been the parameter responsible for the increase of pulmonary metastases seen in this study.
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PMID:Role of operative trauma: explosive metastases of similar size following amputation of the primary leg tumor. 51 75

Effect of urokinase on the tumor growth and metastasis formation of rabbit V2 carcinoma, having low thromboplastic and high fibrinolytic activities, was examined. Weight of the tumor and lymphogenous metastases tended to increase, but the number of metastatic foci in the lungs was unchanged by the administration of urokinase. Diminution of fibrin deposits and connective tissue reaction in association with increase in the pattern of invasive growth was recognized at the advancing border of the tumors in the urokinase-treated group. In the intravenously induced pulmonary metastases, the number of metastatic foci decreased significantly in the urokinase-treated group. Fibrin was demonstrated at the site of tumor cell embolism by the conjugated anti-rabbit fibrinogen antibody. The growth of metastatic foci in the lungs was not affected by the treatment with urokinase. Enhancing effect of urokinase on fibrin resolution might promote the local tumor growth and release of tumor cells into the vessels, but interfere with the lodgement of tumor cells in remote organs.
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PMID:Effect of urokinase on growth and metastases of rabbit V2 carcinoma. 64 Mar 28

In view of the possible role of platelets and coagulation mechanisms in the growth and dissemination of solid tumors, a number of hematological parameters were followed during development of an experimental syngeneic tumor in mice, Lewis lung carcinoma. This tumor, when transplanted i.m. in C57BL/6 mice, grows locally and spontaneously metastasizes to the lungs. The transplanted animals survive for about 4 weeks. Metastases are visible from the third week. A slight but constant increase in plasma fibrinogen level and marked thrombocytopenia were first observed during the second week after tumor implantation. No other significant changes in coagulation and fibrinolysis parameters were detected. Moreover, the animals developed marked hemolytic anemia, possibly microangiopathic in origin. 125I-labelled fibrinogen survival was decreased by about 20% during the second week after tumor implantation and was not further reduced later. Fibrinogen turnover was progressively accelerated, being more than doubled by the end of the third week. Labeled fibrinogen accumulated in the primary tumor and in the lungs (its rate of disappearance from the tumor was much slower than that from lungs or blood). 51Cr-labeled platelet survival did not change throughout the observation period, whereas platelet turnover was markedly reduced from the end of the second week, suggesting defective platelet production. 51Cr-labeled RBC survival was drastically reduced to about 30% of the controls starting from the second week. The occurence of low-grade, localized intravascular coagulation could be suggested on the basis of these data. Moreover, when Lewis lung carcinoma cells were abruptly injected i.v. through the tall vein, more impressive signs of intravascular coagulation could be seen. Indeed, there was a rapid decrease in the number of platelets, a reduction in fibrinogen, and an increase in fibrin-fibrinogen degradation products. The effects of i.v. injection of Lewis lung carcinoma cells indicate a relevant interference of cancer cells with the hematostatic system. In contrast, the tenuous evidence fo coagulation disorders in animals receiving injections of tumor cells i.m. seems to indicate a limited effect on hemostasis of the same cells during i.m. tumor growth.
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PMID:Blood coagulation changes in mice bearing Lewis lung carcinoma, a metastasizing tumor. 83 Apr 14

The intravenous injection of high molecular dextran (HMD), increased pulmonary metastases of the carcinosarcoma of Walker 256, from 35 per-cent of the control animals to 64 per-cent of the animals treated with HMD. A significant prolongation of the clotting time and prothrombin; and a decrease in fibrinogen levels platelets, hematocrit and factors II, V, VII and VIII were observed following the infusion of HMD. There was no obvious untoward side effect of HMD in any of the animals studies.
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PMID:The effect of high molecular dextran on coagulation and metastes. 101 21

During the process of tumor cell invasion and metastasis, tumor cells are known to interact with extracellular matrix proteins, endothelial cells, platelets and other organ-specific structures. Integrins are cell surface molecules which mediate cell-matrix and cell-cell interactions and are likely to be important for tumor cell survival and dissemination. The purpose of this study was to characterize the integrin and proteolytic enzyme repertoire from low (A375P), medium (A375M) and high metastatic (A375SM) human melanoma cell lines. These cell lines are also invasive through human amniotic membranes in vitro and their invasiveness parallels the reported metastatic phenotype. The types and levels of expression of the various integrin receptors were analysed by quantitative immunoprecipitation using a panel of monoclonal antibodies directed to known integrin subunits. In addition, cDNA probes to the integrin subunits were used in quantitative northern blot analysis. These data show that the integrin alpha v beta 3 increases 50- to 100-fold as these cells progress to a more metastatic phenotype. alpha 4 beta 1 levels also appeared to increase several fold, while other beta 1 integrins did not differ in their expression levels. The increased alpha v beta 3 expression in the more metastatic cells resulted in an increased adhesion to vitronectin and fibrinogen substrates in cell attachment assays. However, alpha v- and beta 3-specific antibodies did not inhibit A375 cell invasion through the amnion. Each cell line was found to release similar quantities of a 72-kDa gelatinase/type IV collagenase and tissue type plasminogen activator. These results suggest that during the progression of these tumor cells from a low to high metastatic phenotype, marked changes in integrin expression occurred which may facilitate interactions with platelets, endothelial cells and specific extracellular matrix proteins to promote metastasis.
Clin Exp Metastasis 1992 Mar
PMID:Integrin expression in human melanoma cells with differing invasive and metastatic properties. 131 Dec 25

Thrombospondin (TSP) is a 450 kDa adhesive glycoprotein. It is present in high concentrations in the platelet alpha-granule and can readily be secreted following platelet activation where local concentrations can be increased by 3-4 orders of magnitude. TSP is also synthesized by a variety of other cells and is incorporated into their extracellular matrix. TSP is a homotrimer with a number of functional domains, at least four of which might serve as receptor recognizing regions. The amino-terminal heparin binding domain interacts with heparin, other glycosaminoglycans and glycolipids and likely recognizes specific cell surface proteoglycans. The central disulfide cross-linked region, 210 kDa non-reduced and 70 kDa reduced, contains a peptide motif CSVTCG which is apparently responsible for binding to glycoprotein IV (CD36) with high affinity. Immediately adjacent to the calcium binding region of TSP, which undergoes considerable molecular relaxation in the absence of calcium, is an RGDA sequence. TSP has been demonstrated to bind to integrins of the alpha v beta 3 and alpha IIb beta 3 class. The carboxy-terminal region of TSP also contains at least one binding epitope for a cell receptor. There are 2 well characterized genes for TSP and truncated forms of TSP have been detected which have inhibitory effects on angiogenesis. Finally, TSP can interact with fibrinogen and fibronectin, perhaps on cellular surfaces, which might serve as secondary receptor-like mechanisms for TSP binding and subsequent mediation of cell adhesion.
Cancer Metastasis Rev 1992 Nov
PMID:Thrombospondin as a mediator of cancer cell adhesion in metastasis. 138 98

A volume of data that has accumulated for over a century has suggested that fibrin may facilitate the persistence and progression of malignancy. Techniques that have been developed recently have shown that fibrin is indeed a component of the connective tissue stroma in human malignancy but in only a few tumor types. However, therapeutic intervention studies with drugs that limit thrombin activity or enhance fibrinolysis have shown favorable clinical effects in at least one such tumor type. These favorable findings affirm the concept that cause-and-effect relationships do, in fact, exist between thrombin generation with fibrin formation and tumor progression, and suggest that a rational basis exists for the design of future drug intervention trials that target reactions relevant to specific tumor types. These findings also provide a basis for the design of experiments capable of defining further the role of fibrin in the integrity of these tumor types. Because fibrinogen is found much more commonly than fibrin in the connective tissue of a variety of human malignancies, attention might reassumably be directed to determining the possible contribution of this molecule as well as of fibrin to tumor progression.
Cancer Metastasis Rev 1992 Nov
PMID:The role of fibrin in tumor metastasis. 142 19

Clinical trials of drugs that influence coagulation and fibrinolysis pathways have been undertaken in patients with malignancy because these pathways are capable of influencing malignant progression. The validity of this concept was originally confirmed in experimental animal models of malignancy. Earlier pilot studies in human disease have been succeeded by definitive prospective randomized clinical trials that have revealed heterogeneity of responsiveness to anticoagulant and fibrinolytic agents that may be attributable to differences in mechanisms of interaction of the tumor cells of various types of malignancy with these pathways in vivo. In certain tumor types studied thus far, increased tumor response rates and prolongation of survival have been observed that suggest the possibility that substantial benefit may be realized from this treatment approach in patients with malignancy. In addition, the availability of newer and potentially more effective therapeutic agents holds promise for even greater gains in previously tested tumor types. The ability to design treatment regimens that correspond to defined mechanisms that pertain to specific tumor types should permit future studies to be designed rationally. Current data suggest that anticoagulant and fibrinolytic agents might reasonably be tested in tumor types characterized by the existence of a tumor cell-associated coagulation pathway with thrombin generation and conversion of fibrinogen to fibrin (such as small cell carcinoma of the lung). By contrast, protease inhibitors might reasonably be tested in tumor types characterized by expression of tumor cell plasminogen activators. Expansion of current views on the possible role of antithrombic drugs in cancer therapy is justified. For example, antithrombotic drugs classified as non-steroidal anti-inflammatory agents may inhibit carcinogenesis while polyanionic drugs with anticoagulant properties, such as suramin and heparin, may inhibit growth factor interactions with cells. Intriguing new opportunities clearly exist for interactions between clinical and basic investigators that may provide both novel biologic insights and improved patient care.
Cancer Metastasis Rev 1992 Nov
PMID:Clinical trials with anticoagulant and antiplatelet therapies. 142 26


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