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At least 955 records · Page 53Linked to original sources
PubMed2003

[u-Plasminogen activator (urinary plasminogen activator, urokinase) (uPA) and its PA-1 type 1 inhibitor are not only prognostically but also predictively significant and support clinical decisions on therapy in primary carcinoma of the breast].

uPA and PAI-1 are the first novel tumor biological prognostic factors in breast cancer for which the prognostic impact has been validated at the highest level of evidence and hence all evaluation criteria for transfer into clinical practice have been fullfilled. Breast cancer patients with high uPA and/or PAI-1 levels in their primary tumor tissue have a significantly lower chance for cure than patients with low levels of both uPA and PAI-1. Our research that was honored with the Schmidt-Matthiesen-Award 2002 shows for the first time that uPA and PAI-1 are not only prognostic factors but also have a predictive impact with regard to response to adjuvant chemotherapy. Patients with high uPA/PAI-1 derive a significantly greater benefit from adjuvant chemotherapy than patients with low uPA/PAI-1. Benefit from adjuvant endocrine therapy is independent of uPA/PAI-1 status. The resulting question about the optimal chemotherapy for patients with high uPA/PAI-1 is currently being addressed in Germany by the NNBC-3 trial in node-negative breast cancer (AGO, EORTC-RBG) as well as the ADEBAR trial in patients with 4 or more involved axillary lymph nodes. Moreover, our results suggest the use of novel therapeutic agents interfering with the uPA system together with conventional chemotherapy in patients with high uPA/PAI-1 already in early stage disease.

Biomarkers, Tumor↗
PubMed1998

Regulation of tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) gene expression in rat hepatocytes in primary culture.

We have performed a comparative study on tPA and PAI-1 mRNA expression in primary cultures of rat hepatocytes and elucidated the possible regulation of these factors by certain hormonal stimulation. The tPA mRNA increased 2- to 4-fold in the presence of cholera toxin (CT), dibutyryl cyclic AMP (dbcAMP), or 3-isobutyl-1-methyl xanthine (IBMX), but slightly decreased in the presence of dexamethasone. The tPA activity was also changed by these agents in a similar fashion. On the contrary, PAI-1 mRNA decreased with CT, dbcAMP, or IBMX, but increased transiently with dexamethasone. From results obtained with cycloheximide, ongoing protein synthesis was judged to be required for both PAI-1 induction with dexamethasone and PAI-1 suppression with IBMX, but not for the tPA induction with IBMX. Dexamethasone exerted opposite regulatory effects on the tPA mRNA expression depending on its concentration: at 10(-8) to 10(-6) M, it suppressed the expression; whereas at 10(-10) M, it elevated the expression.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Recurrent pregnancy loss and its relation to FV Leiden, FII G20210A and polymorphisms of plasminogen activator and plasminogen activator inhibitor.

Thrombophilic disorders and hypofibrinolysis were demonstrated to be risk factors in a majority of women with recurrent pregnancy loss (RPL) and infertility. We investigated the association of FV G1691A mutation, F II G20210A gene polymorphism (PM), 4G/5G PAI-1 and Alu I/D tPA PM in 32 women with infertility and 49 women with at least 2 unexplained early abortions. FV Leiden mutation was significantly more common in women with RPL (10%, p = 0.02) and infertility (19%, p = 0.0005) compared with controls (2%). PAI-1 4G PM and t-PA Alu I PM, alone or in combination, were not associated with RPL or infertility. 9/49 women with RPL showed coagulation disorders with heterozygous FV Leiden mutation (5), FXII (1), protein C (1) or protein S (2) deficiency. However, due to the small number of patients studied, no definite conclusion can be drawn.

Abortion, Habitual↗
PubMed1995

Complex intracellular signal transduction regulates tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) synthesis in cultured human umbilical vein endothelium.

Endothelial cells are central in fibrinolysis because of their high production of both activators (t-PA, uPA) and inhibitors (PAI-1). The t-PA and PAI-1 synthesis could be regulated by signals transduction at several cellular levels. The purpose of this in vitro study, on cultured endothelial cells, was to explore the receptor/second messenger regulation of the t-PA and PAI-1 synthesis. Quiescent confluent human umbilical vein endothelial cells, cultured in passage 1, were exposed to different test substances. Samples from the conditioned medium were collected after 16 and 24 h and analysed for t-PA and PAI-1 antigen. All data presented were related to the data from control dishes (= 100%), in the same experiment. The results from the present study (mean +/- 95% confidence interval) demonstrated the following. (1) Forskolin, with a documented direct cAMP-inducing effect, decreased the basal PAI-1 production to 61 +/- 15%, and Na-nitroprusside, with a documented cGMP-inducing effect, increased the basal PAI-1 production to 141 +/- 38% without affecting the basal t-PA production. The surface receptor agonists isoprenalin or ephedrine, which indirectly affect adenylate cyclase, had no effect on t-PA or PAI-1 production. (2) Phorbolester (PMA), which directly activates proteinkinase C (PKC), increased the basal t-PA and PAI-1 production to 350 +/- 71%, and 163 +/- 35% respectively. (3) Thrombin, but not endothelin-1 (ET-1), increased the basal t-PA and PAI-1 production to 195 +/- 34% and 136 +/- 18%, respectively, indicating an PKC-mediated thrombin effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMedDate not supplied

[Changes of the plasma levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in cerebral infarction induced by the venous occlusion].

To examine the fibrinolytic system and platelet factors (PF4 and beta-TG), we conducted a venous occlusion test (V.O. test) on two groups of elderly patients suffering from cerebral infarction, one group being able to walk (A group), the other being bed-ridden for during a long period (B group). Their levels of t-PA, PAI-1 antigen and platelet factors were compared between A or B, A + B and healthy elderly groups. The t-PA antigen level of both group A and B after the V.O. test tended to increase. The t-PA values of A + B groups after the V.O. test were also similar to that of the healthy elderly. The PAI-1 antigen level of both group A and B before the V.O. test was higher than that of the healthy elderly. However, the PAI-1 antigen level of both group A and B tended to decrease after the V.O. test. No remarkable changes were noted in PF4 and beta-TG, which have been thought to reflect platelet function. The above findings suggest that the fibrinolytic activity in A or B groups can recover through stimulation by exercise training and some medical treatment.

Blood Coagulation Tests↗
PubMed2001

Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol.

OBJECTIVE: To investigate the mechanism of prolonged uterine hemorrhage after terminating early pregnancy by mifepristone plus misoprostol. METHODS: Forty-five decidua specimens were obtained from 45 pregnant women with amenorrhea of 6-7 week duration. Fifteen women were treated with mifepristone and 15 were treated with mifepristone plus misoprostol. The remaining 15 served as controls. The tPA and PAI-1 mRNA levels were estimated by reverse transcription-polymerase chain reaction. Chromogenic assay and enzyme-linked immunosorbent assay were used to detect tPA activity and PAI-1 protein level in decidua. RESULTS: The activities of tPA in the mifepristone plus misoprostol group and in the mifepristone group were 46.91 +/- 20.74 IU/mg.protein and 64.25 +/- 35.81 IU/mg.protein respectively, lower than those in the normal decidua group (99.76 +/- 58.61 IU/mg.protein, P < 0.05). tPA mRNA levels in the mifepristone plus misoprostol group were the highest (1.43 +/- 0.39) among the groups. In the mifepristone group, tPA mRNA level (0.90 +/- 0.16) was not significantly different from that in the normal decidua group (0.94 +/- 0.17). The protein and mRNA expression levels of PAI-1 were not significantly different among the three groups (P > 0.05). CONCLUSIONS: Mifepristone plus misoprostol decreased tPA activity in human early decidua by post-transcription pathways, which may influence decidua shedding, endometrial angiogenesis, endometrial remodeling, and cause prolonged uterine hemorrhage after drug abortion.

Abortifacient Agents, Nonsteroidal↗
PubMed1992

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-I (PAI-I) levels in plasma and peritoneal effluent in patients on CAPD.

The formation of fibrin on peritoneal surface has been related to the appearance of adhesions both, in surgical and CAPD patients. It is known that mesothelial cells have fibrinolytic activity related with t-PA production. We studied plasma and overnight peritoneal effluent (OPE) from 20 CAPD stable patients. Antigenic PAI and t-PA were determined. These values and its correspondent peritoneal saturation indexes were compared to urea and creatinine MTCs, peritonitis incidence, UF capacity, protein losses, Pi, Ca, Na, CO2t, urea and creatinine OPE levels. Plasma t-PA 6.64 +/- 4.68 (2.4-20); Plasma PAI-I 24.8 +/- 17.1 (p < 0.001 in respect to controls) (4-62); OPEt-PA 1.46 +/- 0.95 (0.4-4.6); OPE PAI-I 7.3 +/- 5.6 (0-20.4). Peritoneal saturation ratios were for t-PA 29.6 +/- 21% (6-65) and for PAI-I 34 +/- 32% (7-132). In conclusion our data do not support strong relationship between peritoneal t-PA/PAI system and the functional characteristics of the peritoneal membrane although plasma PAI-I, after an increase in patients at early stages on CAPD, shows a tendency to decrease over time and frequent peritonitis. The values of peritoneal saturation ratios for t-PA/PAI are higher than expected for their molecular weight, which suggests local production. An elevated plasma t-PA levels has been found in older patients.

Adult↗