Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high incidence (40.6%) of elevated serum pancreatic phospholipase A2 (PLA2) was demonstrated in patients with various malignancies. Serum PLA2 was significantly increased in cancer patients compared with healthy sex- and age-matched blood donors (358.4 +/- 168.0 vs. 241.7 +/- 69.0 ng/dl; p less than 0.01). No correlation was observed between serum PLA2 and carcinoembryonic antigen (CEA) in these patients. Although patients with advanced and distantly metastatic cancer of the liver, gallbladder and pancreas showed higher PLA2 levels in serum than those with early cancer, patients with other cancers showed no correlation between serum PLA2 and clinical stage. A combined assay of PLA2 and CEA increased the sensitivity of detection of cancers to 60.8%.
 ...
PMID:Serum immunoreactive pancreatic phospholipase A2 in patients with various malignant tumors. 170 53

Cultured SK-OS-10 cells (human osteogenic sarcoma metastatic to lung) shed microvesicles (dia. 300-1000 nm) that contained procoagulant and proaggregatory activities inhibitable by hirudin, by anti-tissue factor antibody and by phospholipase A2. These results show that SK-OS-10 cells belong to a group including U87MG human glioblastoma and HL-60 promyelocytic leukemia in which these activities are due to a thrombin-dependent mechanism arising from the presence of tissue factor on the surface of the tumor cells and their shed microvesicles.
Invasion Metastasis 1987
PMID:Tissue factor-dependent activation of platelets by cells and microvesicles of SK-OS-10 human osteogenic sarcoma cell line. 303 40

Platelet-aggregating and thrombin-generating activities of B16 and 3LL cells were inhibited by trypsin, phospholipase A2 and by heating, but not by neuraminidase. It was confirmed that the platelet aggregation effect of these cells is due to thrombin generation. The lung-colonizing ability of treated cells injected intravenously was directly proportional to the ability to generate thrombin and to aggregate platelets. These results suggest that B16 and 3LL cells aggregate platelets through thrombin generation probably via their heat-labile surface lipoprotein, and that emboli composed of platelets, fibrin, and tumor cells may aid further the metastatic process.
Invasion Metastasis 1986
PMID:Platelet-aggregating activities of metastasizing tumor cells. IV. Effects of cell surface modification on thrombin generation, platelet aggregation and subsequent lung colonization. 394 Oct 29

A number of factors have been identified which are chemotactic for tumor cells. Recent studies have shown that, in addition to inducing directional motility in the Boyden chamber assay, these factors also induce a number of other responses. Included among these responses are cell swelling and foreign surface adhesiveness. The adherence response has been studied in detail using the Walker 256 carcinosarcoma cells and several other cell types. In the Walker cells, treatment with the C5a-derived tumor cell chemotactic peptide, the synthetic tripeptide, N-formyl-methionyl-leucyl-phenylalanine or with 12-O-tetradecanoyl phorbol ester induces a rapid, transient adherence response. The response is completely inhibited by several agents known to block the activity of phospholipase A2 or the metabolism of arachidonic acid through the lipoxygenase pathway but is not inhibited by inhibition of the cyclooxygenase pathway. This suggests that lipoxygenase metabolites of arachidonic acid may actually mediate the adherence response. It has been shown that chemotactic factor treatment of animals that are bearing circulating tumor cells induces a localization of these cells at the site of chemotactic factor injection. On the basis of these observations it has been hypothesized that tumor cells respond to chemotactic factors in much the same way that leukocytes do and that tumor cell localization at metastatic sites in vivo may be influenced by chemotactic factors in much the same way that leukocyte localization at inflammatory sites is.
Cancer Metastasis Rev 1982
PMID:Chemotaxis of metastatic tumor cells. 718 18

Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg2+ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity: protein by trypsin; lipid by phospholipase A2 and non-ionic detergents; and sialic acid by neuraminidase. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.
 ...
PMID:Characterization of the platelet-aggregating activity of tumor cells. 735 51

Ovarian cancer is a highly metastatic disease. Lysophosphatidic acid (LPA) levels are elevated in ascites from ovarian cancer patients, but its potential role in ovarian cancer metastasis has just begun to be revealed. In this work, we show that LPA stimulates invasion of primary ovarian cancer cells, but not ovarian epithelial or borderline ovarian tumor cells, although these benign cells indeed respond to LPA in cell migration. We have found that LPA downregulates tissue inhibitor of metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional role in LPA-induced invasion as negative regulators. G(i) protein, phosphatidylinositol-3 kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), cytosolic phospholipase A(2) and urokinase type plasminogen activator (uPA) are required for LPA-induced cells invasion. TIMP3 may affect two independent downstream targets, vascular endothelial growth factor receptor and p38 MAPK. In vivo, LPA stimulates tumor metastasis in an orthotopic ovarian tumor model, which can be inhibited by a PI3K inhibitor, LY294002. In summary, LPA is likely a key component for promoting ovarian metastasis in vivo. LPA downregulates TIMP3, which may have targets other than metalloproteinases. Our in vivo metastasis mouse model is useful for studying the efficacy of therapeutic regimes of ovarian cancer.
 ...
PMID:Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion. 1713 Aug 43

There is still an urgent need for improved treatments for metastatic cancer. Although the phospholipase A(2) (PLA(2)) crotoxin, an antitumor protein that appears to act by interaction with epidermal growth factor receptors (EGFR), has recently shown activity in breast cancer in phase I clinical trials, it also displayed nonspecific neurotoxicity. Therefore, the aim of this study was to apply a novel concept called polymer-masked-unmasked-protein therapy (PUMPT) to give a bioresponsive dextrin-PLA(2) conjugate that would reduce PLA(2) systemic toxicity but retain antitumor activity following alpha-amylase triggered degradation of dextrin in the tumor interstitium. Dextrin (M(w) approximately 60000 g/mol; approximately 22 mol % succinoylation) and PLA(2) (from honey bee venom) were chosen as models for these initial studies, and the conjugates synthesized contained 6.1 wt % PLA(2), with <1% free enzyme. The conjugate showed decreased ( approximately 36%) enzyme activity compared to native PLA(2), but activity was restored to approximately 100% following incubation with alpha-amylase. Whereas dextrin conjugation caused a marked reduction in PLA(2)'s hemolytic activity, the conjugate was cytotoxic toward MCF-7, HT29, and B16F10 cells at a level that was comparable to, or greater than, that seen for free PLA(2). In these cell lines, cytotoxicity showed partial correlation with the level of EGFR expression. The reduced toxicity and alpha-amylase triggered activity of the dextrin-PLA(2) conjugate confirmed the potential of this approach for further development as a novel anticancer treatment.
 ...
PMID:Dextrin-phospholipase A2: synthesis and evaluation as a bioresponsive anticancer conjugate. 1935 76

Bee venom (BV) (api-toxin) has been widely used in the treatment of some immune-related diseases, as well as in recent times in treatment of tumors. Several cancer cells, including renal, lung, liver, prostate, bladder, and mammary cancer cells as well as leukemia cells, can be targets of bee venom peptides such as melittin and phospholipase A2. The cell cytotoxic effects through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of BV. The induction of apoptotic cell death through several cancer cell death mechanisms, including the activation of caspase and matrix metalloproteinases, is important for the melittin-induced anti-cancer effects. The conjugation of cell lytic peptide (melittin) with hormone receptors and gene therapy carrying melittin can be useful as a novel targeted therapy for some types of cancer, such as prostate and breast cancer. This review summarizes the current knowledge regarding potential of bee venom and its compounds such as melittin to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. The recent applications of melittin in various cancers and a molecular explanation for the antiproliferative properties of bee venom are discussed.
Cancer Metastasis Rev 2012 Jun
PMID:Bee venom in cancer therapy. 2210 81

Thrombospondin type 1 domain-containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A2 receptor 1 (PLA2R1). The prevalence of THSD7A-Ab-positive patients is unknown, and it is unclear whether the clinical presentation differs between patients positive for PLA2R1-Ab or THSD7A-Ab. We screened serum samples of 1276 patients with MN from three different cohorts for the presence of THSD7A-Ab by Western blot analysis and a newly developed indirect immunofluorescence test (IFT). Compared with Western blot analysis, the IFT had a 92% sensitivity and a 100% specificity. The prevalence of THSD7A-associated MN in a prospective cohort of 345 patients with MN was 2.6%, and most were women. In this cohort, the percentage of patients with THSD7A-associated MN and malignant disease significantly exceeded that of patients with PLA2R1-associated MN and malignant disease. In all cohorts, we identified 40 patients with THSD7A-associated MN, eight of whom developed a malignancy within a median time of 3 months from diagnosis of MN. In one patient with THSD7A-associated MN and metastases of an endometrial carcinoma, immunohistochemistry showed THSD7A expression on the metastatic cells and within follicular dendritic cells of the metastasis-infiltrated lymph node. We conclude that the IFT allows sensitive and specific measurement of circulating THSD7A-Ab in patients with MN. Patients with THSD7A-associated MN differ in their clinical characteristics from patients with PLA2R1-associated MN, and more intensive screening for the presence of malignancies may be warranted in those with THSD7A-associated MN.
 ...
PMID:An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy. 2743 55

The objective of this study was to analyze the expression and clinical role of phospholipase D (PLD) in high-grade serous carcinoma (HGSC). PLD1 and PLD2 isoform expression was studied in 125 HGSC specimens (73 effusions, 28 ovarian tumors, 24 solid metastases) using quantitative real-time reverse-transcription polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters, including chemoresponse, and survival. PLD1 and PLD2 isoforms were found in most specimens at all anatomic sites, and their levels were strongly positively related (P<.001 for effusions and solid lesions). PLD2 messenger RNA (mRNA) expression was significantly higher in effusions compared with both carcinomas in the ovary and solid metastases (P<.001). Higher levels of both isoforms were associated with higher CA 125 levels at diagnosis (P<.001), and higher PLD2 mRNA levels in effusions were associated with unfavorable response to chemotherapy (P=.021). Expression levels of the studied isoforms were unrelated to the levels of previously studied mRNAs that form part of the phospholipase A2 pathway or to survival. The present study provides the first evidence of PLD expression in HGSC and suggests a role in mediating progression to effusions and chemoresistance in this cancer.
 ...
PMID:Phospholipase D messenger RNA expression and clinical role in high-grade serous carcinoma. 2808 76


1 2 Next >>