Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We immunohistochemically examined 186 lung adenocarcinomas for the presence of prognostic indicators of local growth of tumor, invasiveness and metastasis. Of the examined tumors, 67% showed a high expression of transforming growth factor alpha (TGF alpha); 50% for epidermal growth factor (EGF), 45% for EGF receptor (EGFR), and 30% for urokinase type plasminogen activator (uPA). In the EGFR-high cases, the 5-year survival rates of patients with high TGF alpha and low TGF alpha were 36% and 85%, respectively. In the EGFR-low cases, there was no statistical difference between the two groups. These findings suggested the presence of autocrine growth mechanisms. On the other hand, the high expression of uPA was modulated by TGF alpha and/or EGF. The 5-year survival rates of patients with high uPA and low uPA were 20% and 51%, respectively. The tumors with high expression of uPA showed degradation of the matrix components, including laminin and fibronectin. These findings suggested that uPA played a role to break through the surrounding basement membrane of blood and lymphatic vessels, and connective tissue for their growth and metastasis. We wish to emphasize the usefulness of the immunohistochemical evidences, such as autocrine growth mechanism and breakdown of extracellular matrix, as a possible parameters of tumor development, invasiveness and metastasis.
 ...
PMID:[Immunohistochemical evidences of prognostic parameters associated with tumor development of pulmonary adenocarcinoma]. 194 64

We measured antigen levels of two kinds of plasminogen activators, tissue type plasminogen activator (t-PA) and urokinase type plasminogen activator (UK), as well as their primary inhibitor, type-1 plasminogen activator inhibitor (PAI-1) in the tissue extracts of benign and malignant breast tumors. Tumor tissues of 36 fibroadenomas and 39 breast cancers were examined. t-PA levels were not different in both groups. Malignant tumors contained the significantly higher levels of UK than benign tumors (p less than 0.001). Furthermore in breast cancer tissues, UK antigen levels of tumors with axillary lymph node involvements were significantly higher than those of tumors without lymph node involvements (p less than 0.05). PAI-1 antigen levels of breast cancer tissues were dramatically higher than those of fibroadenoma (p less than 0.001). PAI-1 levels of node positive carcinomas showed also values significantly higher than node negative ones (p less than 0.01). When we divided cancer tissues into three groups as node negative tumors, tumors with positive axillary nodes fewer than four and tumors with four or more positive nodes, PAI-1 levels increased corresponding to the progression of lymph node involvements (p less than 0.05). Immunohistochemical studies, using mouse monoclonal antibodies to human UK and PAI-1, showed that those immunoreactivities were diffusely distributed in the cytoplasm of human breast cancer cells. Their staining patterns were very similar to each other.
 ...
PMID:Increase in levels of plasminogen activator and type-1 plasminogen activator inhibitor in human breast cancer: possible roles in tumor progression and metastasis. 194 23

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.
 ...
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.
 ...
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.
 ...
PMID:Soluble factors released by the target organ enhance the urokinase-type plasminogen activator activity of metastatic tumor cells. 201 17

Malignant tumors are generally characterized by extensive local tissue invasion and destruction of ECM which may be due to increased constitutive expression and activity of secreted proteases. Moreover, a large number of diverse protease activities may be constitutively over-expressed in a simultaneous or co-ordinated fashion, thereby significantly increasing cellular invasive potential of the cells. To explore this relationship, we have measured steady-state levels of mRNA coding for urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), transin and tissue-specific inhibitor of metalloproteinases (TIMP); as well as gelatinolytic, caseinolytic and plasminogen activator activities secreted by SPI, a non-metastatic mouse mammary carcinoma cell line and 4 metastatic sublines derived from it. mRNA encoding metalloproteinase transin was increased 15- to 20-fold, while TIMP transcripts were decreased 3-fold in the metastatic sublines compared to parental SPI tumor cells. Metastatic sublines secreted higher levels of gelatinase (i.e., 92 kDa and 64 kDa) as well as proteases with caseinolytic activity (i.e., 115 kDa and 57 kDa) when compared with SPI cells. Moreover, these enzymes were identified as neutral metalloproteinases. Although the amount of uPA mRNA appeared to be the same in SPI and the metastatic sublines, the latter secreted 1.5-3 times more uPA activity into the culture supernatants. Metastatic competence in the SPI tumor model is therefore associated with increased secretion of several metalloproteinase activities and uPA, as well as decreased TIMP expression, consistent with a more invasive phenotype.
 ...
PMID:Constitutive expression and secretion of proteases in non-metastatic SP1 mammary carcinoma cells and its metastatic sublines. 204

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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Protein and messenger RNA levels of plasminogen activators and inhibitors analyzed in 22 human tumor cell lines. 210 39


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