Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hormonal regulation of two plasminogen activators, tissue-type plasminogen activator (t-PA) and urokinase (u-PA), was studied both in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma and in DMBA-induced rat mammary dysplasia. t-PA activity in DMBA-mammary carcinoma was decreased markedly by oophorectomy and recovered upon estradiol administration to reach the maximum level at 12 hr. In contrast to its effect on DMBA-mammary carcinoma, estradiol had no effect on t-PA activity in DMBA-mammary dysplasia. Furthermore, DMBA-mammary carcinoma cells in primary culture displayed similar estrogen-dependency in production of t-PA, while t-PA production in DMBA-mammary dysplasia cells was not under the control of estradiol in vitro. Moreover, estrogen-stimulated production of u-PA activity was not observed in DMBA-mammary carcinoma cells or DMBA-mammary dysplasia cells both in vivo and in vitro. Taken together, these results suggest that estrogen stimulates the production of t-PA but not u-PA and that this estrogen dependency of t-PA is limited to malignant DMBA-mammary tumor cells.
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PMID:Specific stimulation by estradiol of tissue-type plasminogen activator production in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor cells. 147 14

Hormonal regulation of plasminogen activator expression in 7,12-dimethylbenz[a]anthracene (DMBA)--induced rat mammary carcinomas was studied both in vivo and in vitro and was compared to that in DMBA-mammary dysplasia induced in neonatally androgenised rats. The plasminogen activator activity in DMBA-mammary carcinomas, but not in DMBA-mammary dysplasia, was regulated by oestrogen. This suggests that expression of this enzyme is hormonally regulated in carcinoma cells. Furthermore, in two of six DMBA-mammary carcinoma groups classified in terms of hormonal treatment, plasminogen activator activity was not under the control of oestrogen. Thus, the present results suggest that at the time of carcinogenesis, the hormonal milieu determines the hormone sensitivities of the malignant cells.
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PMID:Hormone control of total plasminogen activator activity is specific to malignant DMBA-induced rat mammary tumours. 156 66

Epithelial cell differentiation was evaluated in 15 samples of duct-acinar dysplasia, a putative premalignant lesion of the prostate, through immunohistochemical staining for five differentiation markers. Prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), Leu-7, pepsinogen II (PG II), and tissue plasminogen activator (t-PA) are all constituents of seminal fluid that are produced by prostatic epithelium. Dysplasia foci were classified into three grades of severity and their locations mapped by camera lucida drawings of each slide. The degree of abnormal staining with each antibody was recorded on the map, and its correlation with dysplasia grade was evaluated. PSA, PAP, and Leu-7 staining were reduced in dysplasia and often absent in severe dysplasia, indicating that reduced differentiation is an early change in prostatic carcinogenesis. PG II and t-PA stains were sometimes positive in a region where they are usually absent, suggesting that deregulation of differentiation markers may accompany reduction in differentiation in these preneoplastic lesions.
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PMID:Immunohistochemical evidence for impaired cell differentiation in the premalignant phase of prostate carcinogenesis. 245 43

Colon carcinoma cells are first found as microscopic foci within benign tumors or adenomas. The carcinoma must invade the adenoma which protrudes into the colon lumen before it can infiltrate the bowel wall. A quantitative model for this process has been developed in tissue culture in which human colon carcinoma cells destroy cocultivated adenoma colonies. 43 adenoma colonies were assayed by cocultivation with carcinoma cells. Constitutive secretion of the urokinase form of plasminogen activator by carcinoma cells apparently plays some role in adenoma destruction as inhibition of this protease by the competitive inhibitor benzamidine reversibly inhibited adenoma destruction (p less than 0.01). Elevation of plasminogen activator secretion by addition of the tumor promoter 12-tetradecanoylphorbol-13-acetate significantly enhanced the destruction of colonies cultured from tubular adenomas with only mild dysplasia (p less than 0.025) and from villous, villotubular and tubular adenomas with moderate to severe dysplasia (p less than 0.0005).
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PMID:Tumor-promoter-enhanced destruction of noninvasive human benign colon tumor cells by cocultivated carcinoma cells. 323 26

Small colonic adenocarcinomas can be found in focal areas within benign tumors (adenomas), strongly suggesting an adenoma-to-carcinoma sequence. The induction of plasminogen activator (PA) secretion by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) has been used to order histologically distinct classes of human colonic adenomas in primary culture into a sequence from the most benign to the most advanced premalignant state. This ordering is based on the observation that each of five carcinomas examined in an earlier study by E. A. Friedman (Cancer Res., 41: 4588-4599, 1981) and each of seven carcinomas tested in this study released PA in response to TPA, inducing easily scored morphological alterations. Benign tumors either resembled carcinomas in their response to TPA or exhibited no morphological changes. The most benign adenomas by histopathology criteria were the small pure tubular adenomas without dysplasia. Six of seven of these adenomas did not secrete PA in response to TPA. We concluded that malignant cells had acquired the ability to respond to TPA by PA secretion, while tubular adenoma cells were not an advanced enough preneoplastic stage to so respond. TPA treatment of two cultured villous adenomas, one with infiltrating carcinoma and one with focus of moderately dysplastic cells, in the presence of low serum to decrease the plasmin concentration, demonstrated that only a subpopulation of cells secreted PA. Local areas of the monolayer were morphologically altered by the protease, forming clusters of cells loosely attached to the dish. The presence of such subpopulations within cultured adenomas was demonstrated by screening an additional five villous adenomas, 15 villotubular adenomas, and 11 tubular adenomas. The presence of dysplastic cells in 23 of 24 cases correlated with PA secretion. A subpopulation of villous cells, in the absence of dysplastic cells in each of three cases, also secreted PA. We conclude that, during tumor evolution, this villous subpopulation is the first preneoplastic cell type to acquire responsiveness to TPA by PA secretion. This property is maintained as the cells further evolve through premalignant dysplastic stages to carcinoma.
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PMID:A model for human colon carcinoma evolution based on the differential response of cultured preneoplastic, premalignant, and malignant cells to 12-O-tetradecanoylphorbol-13-acetate. 642 77

Matrix proteases and the transcription factor c-Ets-1, which regulates in vitro stromelysin 1, collagenase 1, and urokinase type plasminogen activator gene promoters, are frequently expressed in invasive carcinomas. Using in situ hybridization and immunohistochemistry, we analyzed collagenase 1, stromelysins 1 and 3, matrilysin, urokinase type plasminogen activator, and c-Ets-1 gene expression on serial frozen sections of 39 intraepithelial bronchial lesions, including areas of hyperplasia, metaplasia, dysplasia, carcinoma in situ, and corresponding lung carcinomas in 13 patients. In intraepithelial lesions, expression of all matrix proteases was detected in epithelial cells. Conversely, in microinvasive or invasive lesions, a fibroblastic expression was observed. Collagenase 1 and matrilysin were expressed seldomly in intraepithelial lesions and frequently in carcinomas (p = 0.0016 and p < 0.0001, respectively). Stromelysin 1 was expressed inconsistently in 31% of intraepithelial lesions of all grades and in 50% of carcinomas. Stromelysin 3 and urokinase type plasminogen activator were expressed only, but frequently, in preinvasive lesions (dysplasia, carcinoma in situ) and in carcinomas. The expression of stromelysin 3 in fibroblasts started with dysplasia and carcinoma in situ, but was more frequent in invasive than preinvasive lesions (p = 0.0012). c-Ets-1 was more often expressed in carcinomas than in intraepithelial lesions (p < 0.0001) and was always expressed in fibroblasts. Comparing preinvasive lesions adjacent to or at a distance from squamous lung carcinoma, stromelysin 3 epithelial expression was more frequent in preinvasive lesions adjacent to invasive foci than in others (p = 0.036). We conclude that (a) both epithelial expression of matrix proteases in intraepithelial bronchial lesions and their stromal expression in microinvasive and invasive lesions suggest their role in lung tumor development; (b) c-Ets-1 does not act as a transcriptional activator for matrix proteases genes in preinvasion, although it might regulate collagenase 1 gene during lung tumor progression; and (c) matrix proteases might offer new therapeutic targets for chemoprevention of lung cancer.
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PMID:Changes in the expression of matrix proteases and of the transcription factor c-Ets-1 during progression of precancerous bronchial lesions. 868 34

Proteases are important for neoplastic invasion but a specific role for the plasminogen activator system in the progression of colorectal epithelial dysplasia to adenomatous lesions remains unclear. Consecutive tissue cryosections of 51 adenomas, 49 distant mucosa samples and five mucosa samples from control subjects were histopathologically analysed for dysplasia grade and tissue type, urokinase plasminogen activator levels and plasminogen activator inhibitor type 1 (PAI-1) using immunosorbent methods. Plasminogen activation and urokinase-mediated proteolytic activity levels were assessed using in situ zymography. Plasminogen activation and tissue-type activator levels were lower in adenomas than in mucosae (P < 0.001). PAI-1 concentration and urokinase levels were higher in adenomas than in mucosae (P < 0.001 and P < 0.001 respectively). In adenomas, urokinase concentration increased in parallel with PAI-1, but only the urokinase levels correlated with the dysplasia grade (P < 0.01). Thus, the alterations in plasminogen activation correlated with epithelial cell dysplasia grading. In the mucosa to adenoma transition, a marked decrease in tissue-type plasminogen activator occurred. In adenomas, this decrease was accompanied by a concomitant increase in urokinase and PAI-1. The urokinase level only continued to rise in parallel with the dysplasia grade. Resulting protease-antiprotease imbalance in high-grade dysplasia may represent the phenotypic change associated with malignant transformation and invasive behaviour.
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PMID:Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas. 946 Oct 1

Mast cells (MC) are multipotent hemopoietic effector cells producing diverse mediators like histamine, heparin, or tissue type plasminogen activator. We report a 75-year-old male patient with myelodysplastic syndrome (MDS) of recent onset (3 months' history) associated with a massive leukemic spread of immature tryptase+ MC (tentative term: myelomastocytic leukemia). The patient presented with pancytopenia, bleeding, hypofibrinogenemia, and an increased cellular tryptase level. Moreover, an excessive elevation of plasmin-antiplasmin complexes (9,200 ng/ml; normal range: 10-150), an elevated D-dimer, and an increase in thrombin-antithrombin III complexes were found. The identity of the circulating MC was confirmed by immunophenotyping (CD117/c-kit+, CD123/IL-3R alpha-, CD11b/C3biR-), biochemical analysis (cellular ratio [ng:ng] of tryptase to histamine >1), and electron microscopy. Bone marrow (bm) examination showed trilineage dysplasia (17% blasts), 30% diffusely scattered MC, and a complex karyotype. No dense, compact MC infiltrates (mastocytosis) were detectable in bm sections. Despite hyperfibrinolysis and mediator syndrome (flushing, headache), the patient received remission induction polychemotherapy (DAV) followed by two cycles of consolidation with intermediate dose ARA-C (2 x 1 g/m2/day on days 1, 3, and 5). He entered complete remission after the first chemotherapy cycle without evidence of recurring MDS. Moreover, in response to chemotherapy, the hyperfibrinolysis and mediator syndrome resolved, and the circulating c-kit+ MC disappeared. We suggest consideration of polychemotherapy as a therapeutic option in patients with high-risk MDS of recent onset, even in the case of MC lineage involvement.
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PMID:Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells. 1033 14

Fibromuscular dysplasia, predominantly found in adult women, is a rare disease of small and middle-sized arteries of the kidney and brain. We present a case of a 12-year-old girl with acute ischemic stroke, due to fibromuscular dysplasia of the distal internal carotid artery and the proximal middle cerebral artery, which was successfully treated with t-PA.
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PMID:Thrombolytic stroke treatment of a 12-year-old girl with intracranial fibromuscular dysplasia. 2208

Synchronous gastric cancer and adenomatous colorectal polyp in patients with Klebsiella pneumoniae-induced pyogenic liver abscess (KP-PLA) and bacteremia is a rare presentation. A 58-year-old man with a 6-month history of diabetes mellitus (DM) presented with febrile sensation and dull abdominal pain in the right upper quadrant of the abdomen. Subsequent to laboratory test results and abdominal computed tomography findings, KP-PLA with bacteremia was diagnosed. After intravenous antibiotic administration, his symptoms improved, and upper endoscopy and colonoscopy were performed to evaluate the cause of KP-PLA. Biopsy specimens of the prepyloric anterior wall revealed a moderately differentiated adenocarcinoma. Endoscopic mucosal resection of the colon revealed high-grade dysplasia. Early gastric cancer (EGC) and adenomatous colorectal polyps with high-grade dysplasia concomitant with KP-PLA and bacteremia were diagnosed in our patient who had DM. Intravenous antibiotic treatment for KP-PLA, subtotal gastrectomy for EGC, and colonoscopic mucosal resection for the colon polyp were performed. After 25 days of hospitalization, subtotal gastrectomy with adjacent lymph node dissection was performed. Follow-up ultrasound imaging showed resolution of the abscess 5 weeks post-antibiotic treatment, as well as no tumor metastasis. Upper gastrointestinal endoscopy and colonoscopy should be performed to evaluate gastric cancer in patients with PLA or bacteremia, accompanied with DM or an immunocompromised condition.
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PMID:Gastric cancer and adenomatous colorectal polyp concomitant with pyogenic liver abscess and bacteremia. 3227 10


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