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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the medium of endometrial carcinoma cultures, anti-urokinase-reacting plasminogen activator was released in contrast to cultures of normal or hyperplastic endometrium.
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PMID:Release of plasminogen activator from normal and neoplastic endometrium. 46 4

Invasion and metastasis of malignant cells require the disruption of the extracellular matrix, degradation of basement membranes, and intrusion into connective tissue and vascular and lymphatic spaces. Several studies have indicated a role for urokinase (u-PA) in proteolysis of the extracellular matrix and hence in stromal invasion and metastasis. Many malignant cells are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an inhibitor of u-PA and is present in several neoplastic cell lines and malignant ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and malignant endometrium from 21 postmenopausal patients. Enzyme-linked immunoassays which measure the bound and unbound, single-and two-chain form of the activator and bound and unbound form of the inhibitor were used. Urokinase was present in four of seven normal (range, 0.15-0.5; median, 0.15 ng/mg protein) and in significantly higher concentrations in all malignant endometrial homogenates (range, 0.41-9.2; median, 3.4 ng/mg protein), P < 0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at low concentrations (range, 1.1-3.1; median, 1.1 ng/mg protein) and in all malignant tissue homogenates at significantly higher levels (range, 1.6-27.3; median, 4.9 ng/mg protein), P < 0.01. Levels of endometrial PAI-2 were higher in stages IC or greater compared to those in stages IA and 1B cancers (P < 0.05). PAI-2 may be useful as a prognostic marker in endometrial cancer.
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PMID:The plasminogen activator urokinase and its inhibitor PAI-2 in endometrial cancer. 142 3

Plasma samples from 17 patients with endometrial cancer and from 52 patients with cervical carcinoma were determined with respect to their levels of components of the fibrinolytic system (tissue-type plasminogen activator antigen, urokinase-type plasminogen activator antigen, plasminogen activator inhibitor activity) and related to the observed alterations of three acute-phase reactants (C-reactive protein, coeruloplasmin, alpha-1-antitrypsin). As shown previously, uterine malignancies, especially at later stages, exhibited significant increases in plasma levels of urokinase-type plasminogen activator antigen as compared to an age-matched control group. In contrast, tissue-type plasminogen activator antigen and plasminogen activator inhibitor activity remained unchanged. Determination of the acute-phase reactants revealed significant changes in the case of C-reactive protein and coeruloplasmin in later tumour stages. However, the increase in urokinase-type plasminogen activator antigen did not correlate with the increase of either C-reactive protein or coeruloplasmin plasma level. These data indicate that the increase in plasma urokinase-type plasminogen activator antigen in patients with uterine malignancies does not follow the pattern of common acute-phase reactants, like C-reactive protein or coeruloplasmin.
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PMID:Relationship between plasma levels of components of the fibrinolytic system and acute-phase reactants in patients with uterine malignancies. 169 Jun 55

Plasma concentrations of urokinase-type plasminogen activator (competitive radioimmunoassay), tissue-type plasminogen activator (sandwich enzyme-linked immunosorbent assay), and plasminogen activator inhibitor (functional assay) were measured in 17 women with endometrial cancer and 52 women with cervical carcinoma. Significantly increased plasma urokinase-type plasminogen activator antigen levels were found (11.3 +/- 4.7 ng/mL) in cervical cancer patients when compared with an age-matched control group (7.4 +/- 0.6 ng/mL). Women with endometrial cancer (9.9 +/- 2.0 ng/mL) showed a similar pattern of plasma urokinase-type plasminogen activator antigen levels. Patients with advanced cervical cancer (International Federation of Gynecology and Obstetrics stages III and IV) revealed higher plasma urokinase-type plasminogen activator antigen levels than those with stages I and II disease. Compared with an age-matched control group, neither carcinoma group showed elevated plasma concentrations of tissue-type plasminogen activator and plasminogen activator inhibitor.
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PMID:Increased plasma levels of urokinase-type plasminogen activator with endometrial and cervical cancer. 313 31

Plasminogen activators (PA) and inhibitors of urokinase were determined by a solid phase 125I-fibrin assay in endometrial tissue homogenates from 87 patients. PA was also determined by a histochemical method. Patients were divided according to histopathological diagnosis into three groups; normal, hyperplastic and cancerous. The mean values and S.D. of PA in control endometria, in hyperplastic endometria and in endometrial cancer were 0.68 +/- 0.55 units per mg protein, 1.9 +/- 1.6 units per mg protein and 3.21 +/- 1.03 units per mg protein, respectively. The results of the histochemical assay of PA correlated with the results of 125I-fibrin assay (R = 0.818, p less than or equal to 0.001). The relative PA activity of urokinase-type was the lowest in normal endometrium; it increased in hyperplastic and it was the highest in carcinomatous endometrium. The urokinase inhibitor activity was similar in control and carcinomatous groups; it was slightly but significantly higher in hyperplasia. The results support the contention that PA reflects malignant transformation of endometrial cells. We suggest that determination of PA may facilitate diagnosis and proper treatment of precancerous and cancerous states of endometrium.
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PMID:Plasminogen activators and their inhibitors in normal, hyperplastic and carcinomatous human endometrium. 372 2

Urokinase (u-PA) induced proteolysis of the extracellular matrix appears to be involved in stromal invasion by tumor cells and metastasis. Many malignant cells are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an inhibitor of u-PA and is present in several neoplastic cell lines and malignant ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and malignant endometrium from 21 postmenopausal patients. Enzyme linked immunoassays which measure the bound and unbound, single and two chain form of the activators and bound and unbound form of the inhibitor were used. Urokinase was present in four of seven normal (range 0.15-0.5, median 0.15 ng/mg protein) and in all malignant endometrial homogenates (range 0.41-9.2, median 3.4 ng/mg protein), p < 0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at low concentrations (range 1.1-3.1, median 1.1 ng/mg protein) and in all malignant tissue homogenates at higher levels (range 1.6-27.3, median 4.9 ng/mg protein), p < 0.01. Levels of PAI-2 were higher in Stage II/III compared to Stage I malignancy (p < 0.01) and in cancers that had invaded 50% or more of the uterine wall compared to less invasive cancers, p < 0.01. PAI-2 may be useful as a prognostic marker in endometrial cancer.
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PMID:Uterine fibrinolytic enzymes in endometrial cancer. 825 95

We inoculated the KLE human endometrial cancer, MCF-7 and ZR-75 human breast cancer, and PC-3 human prostate cancer cells into three-dimensional type I collagen gel system that contained uniformy dispersed MG-63 osteoblast-like cells. Then, we analyzed the morphological evidence of osteoblasts reaction, local invasion around the inoculated cancer cells and expression of the cathepsin D and urokinase-type plasminogen activator (uPA) around the sites of inoculation using immunocytochemistry. The prostate cancer cells produced morphological evidence of blastic reaction presented as an increased number of MG-63 osteoblasts and increase density of type I collagen around the sites of inoculation with PC-3 cells. The inoculated MCF-7 and ZR-75 cells decreased the density of type I collagen and number of osteoblasts and invaded the collagen gel around the sites of inoculation. The KLE endometrial cancer cells and cell-free media produced no reaction at the inoculation sites suggestive of cancer cell-specific interactions with osteoblasts in this system. The expression of uPA was remarkably higher at the inoculation sites of PC-3 cells as compared with those of the other cancer cells. Cathepsin D expression was higher at the sites of inoculation with KLE, MCF-7 and PC-3 cancer cells. MG-63 osteoblasts contained relatively low expression of uPA and cathepsin D. We conclude that this collagen gel system is a useful model for studying the morphological evidence of local invasion and osteoblasts reaction produced in response to local growth of metastatic cancer cell in vitro.
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PMID:Three-dimensional type I collagen gel system containing MG-63 osteoblasts-like cells as a model for studying local bone reaction caused by metastatic cancer cells. 891 85

To know the effects of sex steroids on the potentials of growth, invasion, and metastasis with neovascularization of endometrial cancer, the expression of plasminogen activator inhibitor (PAI)-1 [an inhibitor of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA)] and its mRNA in well-differentiated uterine endometrial cancer cell line Ishikawa was determined by an enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction-Southern blotting (RT-PCR-SB), respectively, under the influence of sex steroids. In Ishikawa cells, either estradiol or progestins (progesterone, medroxyprogesterone acetate, or 17 alpha-hydroxyprogesterone alone) induced the expression of PAI-1 and its mRNA, and those expressions were increased approximately two-fold by both estradiol and progestin administered together. Therefore, sex steroidal induction of PAI-1 might contribute to the inhibition of invasion and metastasis, concomitantly with the inhibition of neovascularization associated with tPA and uPA activities, in well differentiated endometrial cancer.
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PMID:Sex steroids regulate the expression of plasminogen activator inhibitor-1 (PAI-1) and its mRNA in uterine endometrial cancer cell line Ishikawa. 900 32

To elucidate potential mechanisms involved in the increased incidence of endometrial carcinomas in tamoxifen-treated patients, we examined the in-vitro effects of tamoxifen on endometrial cancer cells. The effects of tamoxifen, alone and in combination with oestradiol, on cell proliferation, plasminogen activator (PA) activity, glycogen synthase and phosphorylase activities, p53 protein concentration, and collagenase expression were assessed in two human adenocarcinoma cell lines. These lines were the oestrogen receptor-positive (Ishikawa) cells, representing a well-differentiated endometrial adenocarcinoma, and oestrogen receptor-negative (HEC-1A) cells, derived from a poorly differentiated endometrial adenocarcinoma. Tamoxifen or oestradiol alone and their combination significantly enhanced cellular proliferation of Ishikawa but not of HEC-1A cells. Both lines produced appreciable PA activity, most of which was of the urokinase type. Tamoxifen and oestradiol stimulated this activity in Ishikawa cells but not in HEC-1A cells. The effect of oestradiol was dose-dependent in a linear fashion, while tamoxifen produced a stimulation peaking at 10(-8) M and declining at higher concentrations. Tamoxifen in combination with oestradiol exhibited a synergistic effect on proliferation and on PA activity. The response of PA extended beyond the increase in proliferation, leading to higher specific activity of PA in the tamoxifen-treated cultures. In Ishikawa cells, oestradiol also increased glycogen synthase and glycogen phosphorylase activities, while tamoxifen markedly suppressed these enzymes. Oestradiol, tamoxifen, and their combination had no apparent effect on the expression of protein p53 in Ishikawa cells, or on gelatinase activity in either Ishikawa or HEC-1A cells. The present findings imply that tamoxifen produces oestrogen-agonistic effects on cell proliferation and PA activity, and oestrogen antagonistic effects on glycogen synthase and glycogen phosphorylase activities, but fails to regulate p53 and gelatinase expression. The tamoxifen-responsive systems were only observed in oestrogen-responsive adenocarcinoma cells. Thus, only certain potential oncogenic effects of tamoxifen can be simulated in vitro, and when present, these effects are enhanced in the presence of oestradiol.
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PMID:Tamoxifen exerts oestrogen-agonistic effects on proliferation and plasminogen activation, but not on gelatinase activity, glycogen metabolism and p53 protein expression, in cultures of oestrogen-responsive human endometrial adenocarcinoma cells. 946 46

We report on a 64-year-old patient with a recurrent endometrial carcinoma which was associated with disseminated intravascular coagulation (DIC) and excessive hyperfibrinolysis. The patient presented with severe bleeding due to hypofibrinogenemia. Fibrin degradation products were excessively elevated and there were also increased levels of activation markers of coagulation. Free plasmin was demonstrated in the circulation and alpha 2-antiplasmin was almost completely depleted. No increase in t-PA or u-PA level was demonstrated. Antifibrinolytic treatment led to a decrease of fibrin degradation products, but to an increase of activation markers of coagulation and was not associated with an increase of fibrinogen. Combination chemotherapy led to a rapid decrease of activation markers of coagulation and a sustained increase of fibrinogen. The beneficial effects on DIC/hyperfibrinolysis occurred despite the absence of any measurable effect of chemotherapy on the tumour. The patient finally died due to progression of the tumour, but without recurrence of the DIC/hyperfibrinolysis.
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PMID:[Disseminated intravascular coagulation (DIG) with massive hyperfibrinolysis in metastatic uterine cancer. Observations on the effects on the coagulopathy of various treatments (a case report)]. 953 80


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