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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplastic growth and metastatic spread of adenocarcinomas is characterized by a marked increase of urokinase-type plasminogen activator (u-PA) and a decrease of tissue-type plasminogen activator (t-PA). In this study, the authors determined the activity and antigen levels of u-PA and t-PA, and their inhibitors, plasminogen-activator inhibitors types 1 and 2 (PAI-1 and PAI-2), in normal mucosa, adenomatous polyps, and adenocarcinomas of the human colon. The decrease in t-PA activity in the neoplastic tissues, determined enzymatically and zymographically, was significantly correlated with an increase in PAI-1 and PAI-2, in particular in carcinomas. In spite of significantly higher inhibitor levels in the neoplastic tissues, u-PA was found to be increased as well, both in antigen level and in activity. The authors conclude that PAI-1 and PAI-2 are significantly increased in neoplastic tissue of the human colon and contribute considerably to the decrease of t-PA activity in carcinomas. However, the malignancy-associated increase in u-PA seems not to be affected by the plasminogen activator inhibitors. Thus, it appears that there is an imbalance between plasminogen activators and their inhibitors in colonic neoplasia in favor of u-PA, which may contribute to plasmin-mediated growth, invasiveness, and metastasis. This feature was also noticed in adenomatous polyps, supporting the malignant potency of adenomas.
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PMID:Imbalance of plasminogen activators and their inhibitors in human colorectal neoplasia. Implications of urokinase in colorectal carcinogenesis. 195 18

Nude mice given inoculations s.c. of a human squamous carcinoma--HEp3 (1.5 x 10(6) cells/mouse)--developed invasive tumors that produced high levels of urokinase-type plasminogen activator (uPA) and metastasized predictably to the lungs and lymph nodes of the host. To investigate the role of uPA in invasion and metastasis, mice given inoculations of tumor cells were treated daily with s.c. injections of specific, anti-human uPA antibodies (rabbit polyclonal, 150 inhibitory units; mouse monoclonal, 3000 inhibitory units/mouse/day). Control mice received either saline or preimmune rabbit immunoglobulins. A total of approximately 50 mice was studied. The tumors were surgically excised 10 to 17 days postinoculation when weighing 1 to 2 g. Antibody administration was discontinued after tumor excision. Two strategies were used: (a) following the removal of tumors the mice were maintained and observed until respiratory distress, indicative of lung metastasis, was evident; or (b) their lungs were examined for evidence of metastasis on the day of tumor removal. While histological sections of s.c. tumors excised from control mice indicated extensive local invasion, evidence of invasion was absent in most tumors excised from mice in which tumor uPA was inhibited by the antibody (P less than 0.025). The inhibition of local invasion did not, however, lead to a reduced incidence of distant metastasis. Since we found that the presence of HEp3 tumors in mice elicits a pronounced granulocytosis, we propose that this response may facilitate the spread of tumor cells by a mechanism independent of endogenous tumor proteases.
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PMID:Inhibition of urokinase-type plasminogen activator by antibodies: the effect on dissemination of a human tumor in the nude mouse. 198 89

The ability of tumor cells to respond to microenvironmental factors present in the target organ may be necessary for successful metastasis. Many studies suggest that urokinase-type plasminogen activator (u-PA) has a significant role in several steps of the metastatic process. In previous work it had been observed that lung conditioned media stimulated the migration and growth in vitro of cells from a murine mammary adenocarcinoma (M3) with moderate lung metastasizing potential. In the same experiments liver conditioned medium exerted a marked cytostatic effect on M3 cells. The aim of the present work to investigate whether conditioned media from lung, kidney or liver, were able to modulate u-PA in vitro secretion by these murine M3 cells. Secreted u-PA measured by fibrinolytic assay, was significantly increased only when M3 primary cultured cells were treated for 24h with lung conditioned media prepared from normal mice or from mice bearing a small tumor. Exposure to kidney or liver conditioned media did not modify the u-PA secretion pattern already shown by the tumor cells. The activity shown by lung conditioned media seemed to be specific for these syngeneic tumor cells, as no effect was observed on murine embryo cells. These results suggest that soluble factors released by the target organ could specifically induce tumor cells in vivo to enhance the production of degradative enzymes, thus facilitating the last steps of the metastatic cascade.
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PMID:Soluble factors released by the target organ enhance the urokinase-type plasminogen activator activity of metastatic tumor cells. 201 17

The urokinase-type plasminogen activator (u-PA) was used to study 96 cases of lung adenocarcinoma and 49 cases of lymph node metastatic adenocarcinoma. We made use of the immunohistochemistry of paraffinized samples. u-PA was detected in the cytoplasm of tumor cells, and the number of positive cells was higher in patients with T2 or T3 than in those with T1 disease (P less than 0.01). These u-PA-positive tumor cells were more frequent in patients with N2 than in those with N1 disease (P less than 0.01). Such cells were also detected in patients with N1 rather than N0 disease (P less than 0.01). When we compared the frequency of u-PA-positive tumor cells in metastatic lesions with that in primary ones, the former tended to be higher. On the other hand, the frequency of u-PA-positive cells in primary tumors of patients with a recurrence was higher than in those with no recurrence. Thus, u-PA is an important prognostic indicator associated with tumor growth and lymph node spread. If u-PA is detected in a tumor, a recurrence can be expected.
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PMID:Immunohistochemical evidence of urokinase-type plasminogen activator in primary and metastatic tumors of pulmonary adenocarcinoma. 205 90

Plasma and tumor cells from 103 patients with leukemia or lymphoma at initial presentation were investigated for the presence of plasminogen activator inhibitor-2 (PAI-2) antigen, a potent inhibitor of urokinase. PAI-2 was detected in plasma and leukemic cells of the 21 patients with leukemia having a monocytic component [acute myelomonocytic (M4), acute monoblastic (M5), and chronic myelomonocytic leukemias], and in the three patients with acute undifferentiated myeloblastic leukemia (M0). In contrast, this serine protease inhibitor was undetectable in 79 patients with other subtypes of acute myeloid leukemia or other hematological malignancies. Serial serum PAI-2 determinations in 16 patients with acute leukemia at presentation, during therapy, remission, and relapse revealed that in the five patients with M4-M5, elevated PAI-2 levels rapidly normalized under therapy and during remission, but increased again in the patients with a relapse associated with an M4-M5 phenotype. Thus, PAI-2 seems to be a marker highly specific for the active stages of monocytic leukemia, i.e. presentation and relapse. The presence of PAI-2 in the plasma and cells of patients with M0 may give a clue to a monocytic origin of these cells.
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PMID:Plasminogen activator inhibitor-2 in patients with monocytic leukemia. 205 72

Implantation is a crucial step in human reproduction. Disturbances of this process are responsible for pregnancy failure after both in vivo and in vitro fertilization. The endometrium provides the implanting embryo with a unique substratum where the embryo communicates with biochemical signals, attaches itself, penetrates and grows without blood circulation. The highly proliferative phase of the cytotrophoblast, during early human embryogenesis, may be due to endogenous production of growth factors that may establish autocrine/short range paracrine stimulator loops which explain the tumor-like properties of these tissues. Endometrial BM penetration and stroma invasion may be due to the proteolytic capability of the human embryo. It is suggested that collagenase and the urokinase-like plasminogen activator are responsible for this activity. To clarify the molecular mechanisms involved in human embryo implantation several models are suggested: culture of blastocysts, culture of endometrial cells, and endometrial explant co-culture. Human blastocysts cultured with whole perfused human uteri make it possible to recognize some aspects of the entire implantation process and give us the possibility of improving the benefits provided by new technologies in reproductive medicine and reducing embryonic loss at an early stage.
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PMID:Factors regulating interaction between trophoblast and human endometrium. 206 79

In 22 human tumor cell lines the regulation of production of plasminogen activators urokinase (u-PA) and tissue-type (t-PA) and their inhibitors PAI-1 and PAI-2 was studied. These four components may determine the net plasminogen activator activity, which is often associated with tumor development and metastatic processes. The amount of specific mRNA and protein produced by the cells was measured for all four components. The frequent finding of t-PA (alone or in combination with u-PA) suggests that t-PA can also be a tumor-associated plasminogen activator. In 11 of the 22 cells PAI-1 mRNA and in 6 of the 22 cells PAI-2 mRNA was found, pointing to a possible role of plasminogen activator inhibitors in the tumor-related plasminogen activator activity. This study demonstrates that there are at least two important regulatory steps in the regulation of production of plasminogen activators and their inhibitors: (a) the regulation at the mRNA level, since a high protein amount is always correlated with a high mRNA amount found in the tumor cells; (b) there must be a significant regulatory step at the (post)translational level as can be concluded from differences in mRNA usage.
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PMID:Protein and messenger RNA levels of plasminogen activators and inhibitors analyzed in 22 human tumor cell lines. 210 39

Colon tumor cells are more responsive to certain growth modulators in their local environment in vivo than are normal colonocytes. Examples of this class of compounds are the fecal diglycerides (DGs)(E. Friedman et al., Cancer Res., 49: 544-548, 1989), which may act as endogenous tumor promoters. At the concentration found in vivo, fecal DGs composed of oleic, myristic, and palmitic fatty acids induced mitogenesis of all classes of benign tumor cells and of half of the resected carcinomas tested in primary culture, but induced no detectable mitogenesis of normal colonocytes. Colon tumor cells also exhibit selective responses to these endogenous modulators as measured by another biological parameter, secretion of urokinase from carcinomas than from normal colonocytes. Fecal DGs also induced a 13-fold increase in urokinase mRNA synthesis in colon carcinoma cells and induced secretion of active urokinase from each of five resected carcinomas. Colon carcinomas, at both the primary site and metastatic to the liver, secreted the Mr 55,000 form of urokinase constitutively and secreted the same form upon treatment with fecal DGs. An increase in the steady-state level of urokinase secretion by saturated-chain DGs exhibited a strong dependency on the chain length of the fatty acid residues, those of 14 and 16 carbons having the greatest activity. Thus, fecal DGs composed of oleic, myristic, and palmitic acid residues induce two biological activities selectively in colon tumor cells, each of which would enhance tumor development. Selective mitogenesis would increase adenoma and carcinoma cell number relative to normal colonocyte number, and induction of the proteolytic enzyme urokinase would aid local invasion of the carcinoma within the bowel wall.
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PMID:Urokinase secretion from human colon carcinomas induced by endogenous diglycerides. 210 72

Plasminogen activator inhibitor-type 1 (PAI-1) was identified in extracts of Lewis lung carcinoma, and its immunohistochemical localization was studied together with that of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators. All primary tumors (n = 11) contained heterogeneously distributed immunoreactivity against each of the three components. Most often, areas that contained u-PA immunoreactivity also contained PAI-1 immunoreactivity. However, several areas showed a strong u-PA immunoreactivity, but no or low PAI-1 immunoreactivity. The latter staining pattern was only found in peripheral areas, and usually in areas with histological signs of tissue destruction. Lung metastases always contained u-PA immunoreactivity, while PAI-1 immunoreactivity was found in most, but not all, metastases. t-PA immunoreactivity was found in a few scattered tumor cells, in primary carcinomas as well as metastases. Controls that included absorption with highly purified antigen preparations and immunoblotting, indicated that all the immunoreactivity represented genuine PAI-1, u-PA and t-PA, respectively. The results are consistent with an assumption that the plasminogen activation system, and particularly u-PA and PAI-1, plays a role in regulation of breakdown of extracellular matrix proteins during invasive growth in this carcinoma.
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PMID:Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma. 210 45

Urokinase type plasminogen activator (u-PA) was purified from three different chest fluids obtained from patients with liver cirrhosis and pleuritis, aplastic anemia and pneumonia, and lung tumor, and the relationship between molecular weight and plasminogen activator (PA) activity was examined by zymography. The molecular weights of u-PAs from the chest fluids were 200 Kd, 150-180 Kd, 95 Kd, 55 Kd, 44 Kd, 33 Kd and 14 Kd, and PA activity was observed at molecular weights of 95 Kd, 55 Kd and 33 Kd. Fibrin binding of u-PA was observed at molecular weights of 55 Kd and 33 Kd.
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PMID:Properties of urokinase type-plasminogen activator found in chest fluid. 210 19


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