Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effect of medroxyprogesterone acetate (MPA) on secondary spreading of endometrial cancer. There was no significant difference in the adhering capacity of dispersed Ishikawa cells (derived from well-differentiated endometrial cancer) to a cell basement membrane matrix, fibronectin or laminin between cells treated with MPA, with cortisol, and without treatment. The adhering capacity of cells treated with cortisol to collagen type IV was higher than that without treatment. However, the adhering capacity was little affected by treatment with MPA. These results indicate that although cortisol may induce the initial process of metastasis by inducing the attachment of tumor cells to the basement membrane of vascular endothelium, MPA has no influence on the attachment, although it has a glucocorticoid action similar to that of cortisol. There was no significant difference in tumor angiogenesis factor (TAF) or fibroblast growth factor (FGF) activity of the tumor extract from Ishikawa cell colonies between cortisol-treated and control group. TAF or FGF activity of the MPA-treated group was lower than that of the control group. MPA may reduce the neovascularization in the terminal process of metastasis via the reduction of TAF and FGF produced by tumor cells, in spite of its glucocorticoid action.
Invasion Metastasis 1989
PMID:Effect of medroxyprogesterone acetate on secondary spreading of endometrial cancer. 252 39

Hematogenous metastasis requires the arrest and extravasation of blood-borne tumor cells, possibly involving direct adhesive interactions with vascular endothelium. Cytokine activation of cultured human endothelium increases adhesion of melanoma and carcinoma cell lines. An inducible 110-kD endothelial cell surface glycoprotein, designated INCAM-110, appears to mediate adhesion of melanoma cells. In addition, an inducible endothelial receptor for neutrophils, ELAM-1, supports the adhesion of a human colon carcinoma cell line. Thus, activation of vascular endothelium in vivo that results in increased expression of INCAM-110 and ELAM-1 may promote tumor cell adhesion and affect the incidence and distribution of metastases.
 ...
PMID:An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. 258 7

Angiosarcoma is a rare tumour of vascular endothelium seen most commonly on the skin. particularly the scalp. Only 4% occur in the pharynx, oral cavity or paranasal sinuses, either as primary or metastatic disease. As a mode of presentation, oral bleeding is also very rare, but is a grave sign and usually indicates widespread disease. A rapidly fatal case is presented, including post-mortem material, which illustrates many of the features of this rare oral tumour.
 ...
PMID:Oral presentation of disseminated angiosarcoma. 294 82

Amongst 15,000 autopsies performed between 1969 and 1984 in the Department of Pathology of the University Hospital of Innsbruck (Austria) 237 cases (1.6%) with brain metastases were found. The mean age of patients was 61.2 years and 148 patients out of 230 cases with satisfactory records were male (64.3%). Multiple lesions were found in 58%. In absolute figures carcinoma of the lung, followed by malignant melanoma and breast carcinoma were, as in other series, the most frequent primary site for brain metastases. The relative frequency of brain metastases in various anatomical regions of the brain showed that malignant melanoma tends to metastasize to the frontal and temporal lobes, breast carcinoma to the cerebellum and the basal ganglia, large cell carcinoma of the lung to the occipital lobe and squamous cell carcinoma of the lung to the cerebellum. Metastases of small cell carcinoma of the lung were found equally distributed in all regions of the brain. Our study supports the results of several experimental investigations, suggesting the possibility that specific cell surface properties of metastasizing tumour cells and particular properties of the vascular endothelium of the target organs of metastasis are responsible for the location of metastases. The results of this study suggest that there are substantial differences in regard to these properties even within one target organ.
 ...
PMID:Site preference of metastatic tumours of the brain. 312 19

An important step in the metastatic process is the interaction of blood-borne malignant cells with the vascular endothelium. Among the agents that may interfere with this process are pyrimido-pyrimidines, such as RX-RA 85, developed originally as an antiplatelet agent. Using an endothelial cell momolayer attachment assay we have investigated the effects of RX-RA 85 on tumor cell and endothelial cell properties. Exposure of bovine aortic endothelial cells for 3 h to greater than 4 micrograms/ml RX-RA 85 produced toxic effects, resulting in vacuole formation, retraction and finally rounding up of the cells. Endothelial cells derived from different sources behaved dissimilarly; human brain, human meninges, mouse brain, mouse lung and rat lung endothelial cells were less sensitive to drug treatment than bovine aortic endothelial cells. RX-RA 85 treatment of bovine aortic endothelial cells increased B16-F1 melanoma cell adhesion. When B16-F1 cells were exposed to 4-8 micrograms/ml RX-RA 85, increased adhesion to the subendothelial matrix occurred, whereas exposure to higher drug concentrations (8-16 micrograms/ml RX-RA 85) decreased adhesion. Indirect immunofluorescence staining of cytoskeletal structures in B16-F1 cells adhering to and spreading on matrix revealed that the differential effects of RX-RA 85 on the organization of microtubules and microfilaments might explain the dose-dependent differences in adhesion kinetics.
Clin Exp Metastasis 1987 Sep
PMID:Effects of the pyrimido-pyrimidine derivative RX-RA 85 on metastatic tumor cell-vascular endothelial cell interactions. 365 52

All malignant tumors shed cells into the circulation. The number of circulating tumor cells bears no relation to the extent of secondary growth. This is determined by the number of tumor cells that cross the vessel wall and implant in extravascular sites. The rate of cellular emigration is regulated by the permeability of vessels harbouring tumor emboli, permeability in turn being dependent on the amount of alpha, 2, macro-globulin (AMG) lining vascular endothelium. Agents which inactivate or digest AMG, e.g. proteases, have been shown to promote the dissemination of tumor. Some tumors secrete large amounts of proteases. These enzymes are believed to lyse the AMG layer and so to facilitate the emigration of tumor cells. On this hypothesis, inhibitors of such proteases would have anti-metastatic properties. Present experiments lend support to this view. The proteinase inhibitor Trasylol, when allowed to act on tumor cells, has been shown to impair their capacity of setting up haematogenous metastases. It does not affect their viability or transplantability. It is suggested therefore, that blood-borne tumor dissemination might be inhibited by perfusing the (primary) tumor bed with proteinase inhibitor, possibly in association with AMG.
 ...
PMID:On the prevention of haematogenous tumor metastases rats. The role of the proteinase inhibitor "Trasylol". 616 35

Metastasis, a multistep process by which cancer disseminates through the body, mainly by intravascular routes, constitutes a major problem in cancer. When cancer cells are injected directly into the veins of animals, they are apparently arrested in the vascular bed of the first organ encountered and gradually released over the next 24 h. These interactions with the microvasculature are often associated in some manner with the death of many cancer cells, and are thought to contribute to the inefficiency of the metastatic process. We have made a theoretical analysis of cancer cells deformed into capillaries with respect to their intravascular velocity, adhesion to the vascular endothelium and intravascular destruction, in terms of the dynamics of the thin liquid film separating the surfaces of the blood vessels and cancer cells. Our calculations, which are based on previously reported experimental observations, indicate that the transit of cancer cells through the microvasculature is discontinuous, being interrupted by adhesions between the two. In addition, in some cases cell membrane rupture (and cell death) will occur when the critical membrane tension of the cancer cells is exceeded by the sum of their initial equilibrium membrane tension and the increased tension in the cancer cell membranes caused by friction generated as they move over the intraluminal surfaces of the capillaries. Our calculations on membrane rupture are consistent with previously unexplained observations by Sato and Suzuki relating cancer cell deformability to death on transpulmonary passage, and constitute a novel mechanism for "metastatic inefficiency" in terms of intravascular cancer cell death.
 ...
PMID:A fluid mechanical analysis of the velocity, adhesion, and destruction of cancer cells in capillaries during metastasis. 620 63

Cancer cell detachment in three distinct and critical parts of the metastatic cascade is discussed. The detachment of cancer cells from their parent tumors is an initial early event in metastasis. The site of detachment with respect to proximity to blood vessels may determine the initial dissemination route. Many factors affect cell detachment; we specifically consider the effects of growth-rate, necrosis, enzyme activity, and stress on cell release in terms of metastasis-promoting mechanisms. Detachment is also discussed in relation to active cancer cell locomotion, where localized detachment from the substratum is a prerequisite for translatory movement. The importance of active cell movement in tissue invasion has only recently been assessed, and, in the case of at least some human malignant melanomas, a zone of actively moving cancer cells is believed to precede the growing body of the tumor. The secondary release of cancer cells from temporary arrest sites at the vascular endothelium consequent upon intravascular dissemination is also a major area of investigation. Circulating cancer cells arrest at vascular endothelium or are impacted in small vessels, however, most are released into the circulation and subsequently perish. The blood stream is a hostile environment, and it is probable that cancer cells are sufficiently damaged in translocation by hemodynamic trauma and humoral factors such that they easily detach or are 'sheared-off' the vascular endothelium by blood flow. Another possibility is that in some cases they are processed by 'first organ encounters' and perish before or shortly after arriving in a second organ. Animal studies have shown that, following intravenous injection, 60-100% of the injected dose of viable cancer cells are initially arrested in the lungs, but very few remain after 24 hr. As it is only those retained cells which produce tumors, the mechanisms involved in this secondary release, which occurs in all organs so far examined, are critical to any understanding of the metastatic cascade and metastatic inefficiency. The arrest of cancer cells at the vascular endothelium and their subsequent release have been associated with the presence of platelets, and the deposition of fibrin and manipulation of platelet-aggregating mechanisms and fibrinolysis are discussed in terms of their antimetastatic effects. The role of the reticuloendothelial system, natural killer cells, and polymorphs is discussed in relation to cancer cell clearance from blood vessels and also to inherent cancer cell properties which may act to inhibit their metastasis. Although detachment of cancer cells from a primary tumor may be regarded as metastasis promoting, secondary release of cancer cells may be associated with inhibition of metastasis.
Cancer Metastasis Rev 1983
PMID:Cell detachment and metastasis. 635 10

Our clinical study to prevent relapse and metastases in several sarcomas and malignant lymphomas of the head and neck region with a long-term treatment with mopidamole was initiated in 1972 because the pyrimido-pyrimidine derivative was shown to inhibit platelet aggregation in vivo and to increase significantly the circulation time of intravenously injected, 32P-labelled Ehrlich ascites tumour cells in mouse blood. The aggregation of platelets to circulating tumour cells and their subsequent adhesion to vascular endothelium in turn appeared to be part of the early stages of the metastatic process. It seems, however, that other related mechanisms are also involved in the clinical results obtained. Mopidamole, as other related derivatives, probably inhibits platelet aggregation by inhibition of PDE-induced decomposition of cAMP and may stimulate the synthesis and/or release of prostacyclin from the vessel wall which in turn activates adenylate cyclase involved in cAMP synthesis. The latter mechanism was definitely shown only for the related pyrimido-pyrimidine derivative dipyridamole, the methyl-xanthine derivative pentoxifylline and the methyl-pyrazoline derivative nafazatrom. The increase of cAMP levels by mopidamole results in an inhibition of 3H-thymidine incorporation into human neoplastic cells and a direct inhibition of its mitotic rate. The adding of mopidamole to a culture of a human promyelocytic leukemic cell line promotes a reverse transformation of the malignant cells to normal which appears to be a permanent phenotypic change. Furthermore, mopidamole was shown to diminish significantly spontaneous lung metastases in syngenic Wilms' tumor (nephroblastoma) of the rat, the C1300-neuroblastoma of the mouse and the HM-Kim mammary carcinoma of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Modification of metastasis formation by inhibition of platelet aggregation. Experimental and clinical results]. 636 51

The past decade has witnessed substantial progress in our understanding of the molecular mechanisms of tumor cell interactions with vascular endothelium and extracellular matrix, important events in the metastatic process. This progress has been made possible by the identification and functional characterization of a large number of adhesion molecules involved in tumor cell-vasculature interactions. Essentially, most of the adhesion receptor families so far reported, including integrins, cadherins, selectins, immunoglobulins, and proteoglycans, have been implicated in various stages of tumor progression and metastasis. Disseminating cancer cells often employ ectopic expression of certain adhesion molecules to facilitate their interaction with the vessel wall and matrix, typical examples being the expression of integrins alpha IIb beta 3 and alpha L beta 2 and immunoglobulin family members PECAM-1, ICAM-1, and N-CAM in solid tumor cells. The expression of adhesion molecules in cancer cells and vascular endothelial cells is spatiotemporally regulated, in a dynamic fashion, by a wide diversity of bioactive molecules such as eicosanoid 12(S)-HETE. Recent data indicate that most adhesion molecules, integrins in particular, participate in various signaling functions such as the induction of calcium fluctuation and protein tyrosine phosphorylation. The importance of adhesion molecules in tumor metastasis is also evidenced by their involvement in other important parameters of metastasis such as angiogenesis. Collectively, the accumulated literature suggests that interference with adhesion and signaling represent a future direction for the development of anticancer and antimetastasis therapeutic protocols.
Invasion Metastasis
PMID:Adhesion molecules and tumor metastasis: an update. 765 6


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>