Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three cases of multicentric reticulohistiocytosis showing typical clinical, histologic, and ultrastructural findings are reported. In one, gastric cancer occurred; in the other two cases, severe polyarthritis was the only detectable internal involvement. The serine proteinases, urokinase and tissue-type plasminogen activator, were evaluated both with the autohistographic technique and spectrophotometric assay in lesional skin and synovia. Urokinase levels appeared grossly increased in the lesional synovia and moderately increased in the lesional skin. We suggest that urokinase, presumably released by the activated proliferating histiocytes, may play a major role in the extracellular matrix degradation leading to erosion of cartilage and adjacent bone in multicentric reticulohistiocytosis.
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PMID:Multicentric reticulohistiocytosis. Report of three cases with the evaluation of tissue proteinase activity. 314 26

The effect of fibrinolytic agents, Tissue Culture Urokinase (TCUK) and Urinary Urokinase (UUK), was investigated in a total of 146 patients with gastric cancer, pulmonary cancer or breast cancer who received various anti-cancer agents, mainly MMC, in combination with the fibrinolytic agents. Assessments were made according to the Koyama-Saito criteria. In order to maintain impartiality of this comparative trial, the drugs were randomly administered to the patients by a card system. The patients who died during the study were excluded from the analysis and the patients with colorectal cancer were also excluded because this disease was not included in the study protocol. As a result, 51 patients given TCUK and 50 patients given UUK (101 in total) were subjected to analyse. The response rate (CR + PR/No. of admitted patients) was 15.6% (8/51) for the TCUK group and 10.0% (5/50) for the UUK group respectively. The patients with measurable lesions in the TCUK group showed a response rate of 25.9% (7/27) and those in the UUK group, 14.3% (4/28). Side effects were observed in 52.1% of patients in the TCUK group and 47.9% in the UUK group. However, these symptoms were related to the anti-cancer agents. Neither a tendency to hemorrhage nor allergic symptoms occurred in association with the two fibrinolytic agents, TCUK and UUK. to UUK in terms of an activity to enhance the chemotherapeutic effect of anti-cancer agents and that combination use of TCUK and anti-cancer agents seems to be useful.
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PMID:[Clinical evaluation of various antineoplastic agents combined with urokinase--a comparison between urokinase from tissue culture (TCUK) and urine-derived urokinase (UUK)]. 682 Sep 18

We aim to elucidate the correlation between clinicopathological parameters and uPA and ECD expression in gastric cancer. Some 125 patients with primary gastric cancer, who were treated at the Second Department of Surgery, Kanazawa University, between 1988 and 1993, were enrolled in this study. The expression of uPA and ECD was evaluated by immunohistochemical staining using a anti-uPA and an anti-ECD monoclonal antibody. The nuclear DNA contents were measured by flow cytometry. Among 125 tumors, 42 (34%) were found to have preserved ECD expression (ECD (+)), and 83 (66%) reduced ECD expression (ECD (-)). uPA immunoreactivity was observed in 82 (65%) of 125 tumors. According to the expression of uPA and ECD status, groups of 22 uPA (-)/ECD (+), 21 uPA (+)/ECD (+), 17 uPA (-)/ECD (-) and 65 uPA (+)/ECD (-) were identified. There was a significant correlation between uPA (+)/ECD (-) status and depth of invasion, liver metastasis, peritoneal dissemination, lymph node metastasis, and venous invasion. Patients with uPA (+)/ECD (-) tumors showed the poorest prognosis and the highest rate of recurrence, as compared with the other groups of patients. No significant correlations were found between uPA (+)/ECD (-) status and DNA ploidy patterns, and histological type. Immunohistochemical analysis of the combination of uPA and ECD expression could be a useful method for the evaluation of metastasis and prognosis in gastric cancer patients. Our results indicate that uPA may have an important role in cancer infiltration and ECD in cancer infiltration and metastasis.
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PMID:[Correlation between the expression of urokinase-type plasminogen activator, E-cadherin and malignancy in gastric cancer]. 761 74

Phenotyping of cytokeratin (CK)18-positive cells in bone marrow is gaining increasing importance for future prognostic screening of carcinoma patients. Urokinase-type plasminogen activator receptor (uPA-R) is one example of a potential aggressive marker for those cells. However, a valid and reliable double staining method is needed. Using monoclonal antibodies against uPA-R and CK18, we modified an immunogold/alkaline phosphatase double staining protocol. UPA-R/CK18-positive tumor cell controls exhibited black uPA-R staining in 15-80% of cases and red CK18 staining in almost 100% of tumor cells. Isotype- and cross-matched controls were completely negative. Bone marrow from healthy donors was always CK18-negative. Reproducibility of CK18-positive cell detection was estimated in a series of specimens from 61 gastric cancer patients comparatively stained with the single alkaline phosphatase-anti-alkaline phosphatase (APAAP) and our double staining method (10(6) bone marrow cells/patient). In four cases, double staining could not reproduce CK18-positive cells. In 34 cases it revealed fewer or equal numbers, and in 23 cases more CK18-positive cells than the APAAP method. Overall quantitative analysis of detected cell numbers (838 in APAAP, range 1-280 in 10(6); double staining 808, range 0-253) demonstrated relative reproducibility of APAAP results by double staining of 97%. Correlation of results between both methods was significant (p < 0.001, linear regression). Sensitivity of double staining tested in logarithmic tumor cell dilutions was one CK18-positive cell in 300,000. Specific uPA-R staining was seen on CK18-positive cells in bone marrow from 29 of 61 patients, and also on single surrounding bone marrow cells. To test the specificity of this staining, bone marrow cytospins from 10 patients without tumor disease were stained for uPA-R with the APAAP method. uPA-R expression was confirmed in all 10 cases, with a mean of 6.5% uPA-R-positive cells in 1000 bone marrow cells (SEM 1.2%). These results suggest that our double staining protocol is a sensitive, reproducible, and specific method for routine uPA-R phenotyping of disseminated CK18-positive cells in bone marrow of carcinoma patients.
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PMID:Immunocytochemical phenotyping of disseminated tumor cells in bone marrow by uPA receptor and CK18: investigation of sensitivity and specificity of an immunogold/alkaline phosphatase double staining protocol. 901 10

For tumor progression, a cascade of linked sequential biological events is essential. We tried to test whether biological therapy can modulate specific biological phenotypes and increase the anti-tumor effect when combined with chemotherapy. Five human gastric cancer cell lines (YCC-1, YCC-2, YCC-3, YCC-7, AGS) were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor inhibitor, Tranexamic acid as a plasmin inhibitor, Lovastatin as an adhesion inhibitor and Adriamycin as a chemotherapeutic agent were selected. The effects of each drug on colony formation and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively to test direct anti-tumor effect. The expression of uPA, PAI-1 was determined by ELISA, while MMPs activity was evaluated by zymography. PPS suppressed the colony-forming activity as much as Adriamycin did, but it showed only cytostatic effects in cell proliferation assay. Migration capacity using Boyden chamber assay was more closely correlated with adhesive capacity than uPA or MMP-2 expression. The motility inhibitory effect of Tranexamic acid was observed in the YCC-7 cell line, which expressed all the required biological phenotypes for migration. In AGS, with high cell motility and adhesiveness, the adhesion was inhibited by Lovastatin and most of the inhibitory effect was recovered by Mevalonate. When PPS was combined with Adriamycin on the Adriamycin-resistant, midkine (MK) gene expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that for a single treatment of PPS or Adriamycin was 40% and 22%, respectively (p=0.001). When we combined Tranexamic acid and Adriamycin, we observed the synergistic effect in YCC-3 and YCC-7, while no combined effect was found in YCC-1. The combination of Lovastatin and Adriamycin did not show any combined effects in any of the cell lines. In conclusion, a synergistic anti-proliferative effect (chemo-sensitization) with combined chemo-biotherapy was found in cancer cells with specific biological target, MK. The anti-motility effect was the greatest when the gastric cancer cells expressed all the specific biological phenotypes.
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PMID:Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer. 1040 90

Two types of gastric adenocarcinoma can be distinguished histopathologically: the diffuse and the intestinal type. Molecular pathology supports this theory by showing differences in the genetic pathways of both tumor types. In addition to known pathomorphological factors of prognosis, e.g., depth of tumor infiltration, number of lymph node metastases and resection margins, a few genes have been suggested to have prognostic impact in gastric carcinoma. Clinically relevant molecules whose expression or structure is altered include the plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1), the cell cycle regulator cyclin E, epidermal growth factor (EGF), the apoptosis inhibitor bcl-2, the cell adhesion molecule E-cadherin, and the multifunctional protein beta-catenin. Gene amplification and protein overexpression of the growth factor receptors c-erbB-2 and K-sam may be prognostic factors for intestinal-type and diffuse-type gastric cancer, respectively. In addition, genetic instability is commonly seen. There has long been evidence for a genetic predisposition to gastric cancer by epidemiological studies and case reports. Very recently, germ line mutations of E-cadherin have been identified that are responsible for a dominantly inherited form of diffuse-type gastric cancer and could be used to identify individuals that are at high risk.
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PMID:Gastric adenocarcinoma: pathomorphology and molecular pathology. 1131 54

Urokinase plasminogen activating system (PA system) and vascular endothelial growth factor (VEGF) were recently suggested to contribute synergistically to tumor progression. To evaluate the roles of the PA system and VEGF in gastric cancer, the effects of the PA system and VEGF on tumor angiogenesis and the survival of patients with gastric cancer were investigated. Cancer tissues from 101 gastric cancer patients were assayed immunohistochemically for expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), PA inhibitor-1 (PAI-1) and VEGF protein. The positive rates of uPA, uPAR, PAI-1, VEGF expression were 22.8%, 32.7%, 36.6% and 26.7%, respectively. Positive staining was observed in tumor cells (uPA, uPAR, VEGF), or in both tumor cells and stromal cells (PAI-1). The expressions of uPA, uPAR, PAI-1 and VEGF were significantly correlated with the clinicopathological factors: uPA, depth of tumor invasion, differentiation, lymphatic and vascular invasion; uPAR, tumor size, depth, lymph node involvement, differentiation, vascular invasion; PAI-1, tumor size, depth, lymph node involvement, differentiation, vascular invasion; VEGF, differentiation, vascular invasion. The microvessel density (MVD) assessed immunohistochemically was significantly higher in the patients with expression of uPA, uPAR or VEGF, and stepwise analysis identified uPA as an independent correlated factor with MVD. Furthermore, multivariate analysis demonstrated that depth of tumor invasion, lymph node involvement and uPA expression were independent prognostic factors. uPA is a key factor in the PA system, being associated with a poor outcome of gastric cancer, and contributing not only to invasive activity, but also to angiogenesis.
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PMID:Urokinase-type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer. 1270 73

The levels of urokinase (uPA) and tissue type (tPA) plasminogen activators and their type 1 inhibitor (PAI-1) were determined by immunoassay in tumor cytosols and samples of histologically unaltered adjacent mucosa in gastric cancer patients. Gastric tumor revealed enhanced uPA and PAI-1 matched by decreased tPA in intact mucosa. The expression of uPA and PAI-1 was particularly was high at the later stages of the disease. The concentrations of uPA in tumor tissue increased with age. No significant correlation was established between levels of plasminogen activation system components, on the one hand, and histopathological grading of tumor, on the other.
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PMID:[Urokinase and tissue type plasminogen activators and their type-1 inhibitor (PAI-1) in gastric cancer]. 1278 98

The catalog of gene alterations in human cancer grows rapidly. Gastric cancer is no exception and displays gene changes in multiple oncogenes, suppressor genes, and DNA repair genes. Clinically relevant molecules whose expression or structure is altered include the plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1), the cell-cycle regulator cyclin E, epidermal growth factor (EGF), the apoptosis inhibitor bcl-2, the cell adhesion molecule E-cadherin, and the multifunctional protein beta-catenin. In addition, genetic instability is commonly seen. Gene amplification and protein overexpression of the growth factor receptors c-erbB2 and K-sam may be prognostic factors for intestinal-type and diffuse-type gastric cancer, respectively. The clinical implications of some of the recent findings for diagnosis and therapy are discussed.
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PMID:Molecular mechanisms of carcinogenesis in gastric cancer. 1279 Mar 21

The interaction between the urokinase receptor (uPAR) and its ligand urokinase (uPA) mediates phenomena such as tissue remodelling, chemotaxis, tumour invasion, dissemination, proliferation, and angiogenesis. The broad-spectrum of biological processes that the uPA/uPAR interaction plays a role in has led researchers to speculate that this interaction may be a useful molecular target for therapeutic intervention in several pathological conditions, particularly in the prevention and inhibition of the dissemination of cancer cells. In syngeneic and xenograft murine tumour models, in which metastasis is driven by the uPA/uPAR interaction, inhibition of primary tumour growth, metastasis and angiogenesis has been shown with several proteins acting as uPAR antagonists. Immunohistochemistry, in conjunction with prognostic studies, has implicated the uPA/uPAR interaction in the dissemination of tumours, such as malignant melanoma, colon cancer, non-small cell lung cancer (NSCLC) and stomach cancer, as well as breast and ovarian carcinomas. A potential inhibitor of the uPA/uPAR interaction should result in a significant increase in the disease-free interval and survival time following resection of the primary tumour in a clinical Minimal Residual Disease (MRD) setting. Low molecular weight uPAR antagonists should be orally active, and have few side-effects, excellent bioavailability, favourable pharmacokinetic properties and a long half-life. Furthermore, these compounds should be able to inhibit the dissemination of cancer cells without the need for targeted drug and vector delivery.
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PMID:Urokinase receptor antagonists: novel agents for the treatment of cancer. 1599 80


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