Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report successful operations for a meningeal hemangiopericytoma using sufficient amounts of Preoperative Autologous Transfusion (PAT) and Hemodilutional Autologous Transfusion (HAT). A 23-year-old woman with amenorrhea and bilateral visual field disturbance was found to have a huge intracranial tumor. MRI showed a well-enhanced cystic mass in the left middle fossa, suprasellar, intrasellar, sphenoidal sinus, and cavernous sinus. Preoperatively, the tumor was thought to be a cystic pituitary tumor or meningioma. Surgical removal was planned in three steps. The first operation was carried out via the transsphenoidal approach. Total blood loss was 1348 ml and 2 MAP infusion were required to control bleeding. Histopathological diagnosis was hemangiopericytoma. After preparation of PAT 400 ml and HAT 800 ml, we carried out the second partial removal operation mainly via the interhemispheric approach. Total blood loss was 1829 ml and required autologous transfusion only. After preparation of PAT 1200 ml and HAT 400 ml, the last total removal operation was carried out mainly via the pterional and subtemporal approach. Total blood loss was 1813 ml and required autologous transfusion only. We needed 2 MAP infusion in the first operation, but were able to perform total removal successfully without homologous blood transfusion because a sufficient amount of PAT and HAT had been prepared preoperatively. Hemangiopericytoma required postoperative radiation therapy to avoid local recurrence. After successful removal of the tumor surgically, postoperative radiation therapy was able to be carried out efficiently.
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PMID:[Successful treatment of a huge meningeal hemangiopericytoma using Preoperative Autologous Transfusion and Hemodilutional Autologous Transfusion: case report]. 1209 90

Modulation of gap junctional intercellular communication (GJIC) is a known cellular event associated with tumor promotion. The present study was undertaken to test the potential preventive effect of mushroom Phellinus linteus extract (PL) on the inhibition of GJIC, induced by hydrogen peroxide (H(2)O(2)), in WB-F344 rat liver epithelial cells (WB cells). Cells were pre-incubated with PL (5 and 25 microg/ml) for 24 h and this was followed by co-treatment with PL and H(2)O(2) (500 microM) for 1 h. PL (at 5 and 25 microg/ml) prevented the inhibition of GJIC and blocked the hyper-phosphorylation of connexin 43 by H(2)O(2). Moreover, H(2)O(2) activated p38 kinase, extracellular signal-regulated protein kinases (ERK)1/2 and c-Jun N-terminal kinase (JNK) in WB cells. The present study indicates that PL is able to inactivate both ERK1/2 and p38 MAP kinases. However, PL did not affect the JNK pathway. For this reason, to elucidate the relation between MAP kinases and GJIC, we treated cells with PD98059 (an MEK inhibitor) and SB202190 (a p38 kinase inhibitor). These inhibitors were also found to prevent the inhibition of GJIC induced by H(2)O(2), which suggests that PL may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinases. In addition, our results indicate that the p38 kinase signaling pathway may be closely related functionally to the gap junction in rat liver epithelial cells.
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PMID:The roles of ERK1/2 and p38 MAP kinases in the preventive mechanisms of mushroom Phellinus linteus against the inhibition of gap junctional intercellular communication by hydrogen peroxide. 1211 74

Drm/Gremlin, a member of the Dan family of BMP antagonists, is known to function in early embryonic development, but is also expressed in a tissue-specific fashion in adults and is significantly downregulated in transformed cells. In this report, we demonstrate that overexpression of Drm in the tumor-derived cell lines Daoy (primitive neuroectodermal) and Saos-2 (osteoblastic), either under ecdysone-inducible or constitutive promoters, significantly inhibits tumorigenesis. Furthermore, Drm overexpression in these cells increases the level of p21(Cip1) protein and reduces the level of phosphorylated p42/44 MAP kinase. Finally, our data indicate that Drm can induce p21(Cip1) transcriptionally via a novel pathway that is independent of p53 and the p38 and p42/44 MAP kinases. These results provide evidence that Drm can function as a novel transformation suppressor and suggest that this may occur through its affect on the levels of p21(Cip1) and phosphorylated p42/44 MAPK.
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PMID:Drm/Gremlin transcriptionally activates p21(Cip1) via a novel mechanism and inhibits neoplastic transformation. 1213 12

Intraoperative radio frequency interstitial thermal ablation (RITA) may result in a reduction of the functional hepatic reserve. To assess this further, we evaluated perioperative lactate levels as a measure of hepatic dysfunction. Sixteen patients scheduled for open RITA (O-RITA) were enrolled in the study. Arterial lactate levels (mmol/L) were measured prior to tumor needle insertion (T0), after O-RITA completion (T1), after wound closure (T2) and 24 hrs after surgery (T3). Correlation between hemodynamic parameters including MAP, and CVP, at T0, T1, T2, T3 and the perioperative rate of lactate production were also analyzed. Total bilirubin, transaminases and international normalized ratio for prothrombin activity (INR) were measured preoperatively and postoperative at day 1, 2, 3 and 7. Data are expressed as mean +/- SD and analyzed with ANOVA. Additionally, the Duncan post hoc test was used for multiple comparisons of the differences in mean values. A p-value <0.05 was considered significant. Lactate levels did not increase significantly at time points specified above (P = NS). Similarly, hemodynamic parameters analyzed did not show any significant change at the different time points (P = NS). Total bilirubin and INR did not demonstrate statistically significant changes at the aforementioned time points. Serum transaminases peaked during the immediate postoperative period and normalized to preoperative values by one-week post surgery. These results demonstrate that O-RITA does not induce hyperlactatemia and does not reduce the functional residual liver parenchyma.
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PMID:Lactate levels in open interstitial thermal ablation for liver tumors. 1214 73

Proper stimulation of cell cycle progression and DNA synthesis requires cooperating signals from integrin and growth factor receptors. We previously found that the proinflammatory peptide, macrophage migration inhibitory factor (MIF), functions as an autocrine mediator of growth factor-dependent ERK MAP kinase activation and cell cycle progression. We now report that MIF secretion is induced by cell adhesion to fibronectin in quiescent mouse fibroblasts. Adhesion-mediated release of MIF subsequently promotes integrin-dependent activation of MAP kinase, cyclin D1 expression, and DNA synthesis. Secretion of MIF requires protein kinase C activity, and recombinant MIF reconstitutes the activation of MAP kinases in the presence of protein kinase C inhibition. Finally, we show that cells deficient in MIF have significantly higher retinoblastoma tumor suppressor and lower E2F transcriptional activities. These results suggest that MIF is an important autocrine mediator of adhesion-dependent signaling events and may provide mechanistic insight into how MIF regulates proliferative and oncogenic processes.
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PMID:Adhesion-dependent signaling by macrophage migration inhibitory factor (MIF). 1229 13

We have investigated mechanisms of mitochondrial stress-induced phenotypic changes and cell invasion in tumorigenic but poorly invasive human pulmonary carcinoma A549 cells that were partly depleted of mitochondrial DNA (mtDNA). Depletion of mtDNA (genetic stress) caused a markedly lower electron transport-coupled ATP synthesis, loss of mitochondrial membrane potential, elevation of steady state [Ca(2+)](c), and notably induction of both glycolysis and gluconeogenic pathway enzymes. Markers of tumor invasion, cathepsin L and TGFbeta1, were overexpressed; calcium-dependent MAP kinases (ERK1 and ERK2) and calcineurin were activated. The levels of anti-apoptotic proteins Bcl2 and Bcl-X(L) were increased, and the cellular levels of pro-apoptotic proteins Bid and Bax were reduced. Both mtDNA-depleted cells (genetic stress) and control cells treated with carbonyl cyanide m-chlorophenylhydrazone (metabolic stress) exhibited higher invasive behavior than control cells in a Matrigel basement membrane matrix assay system. MtDNA-depleted cells stably expressing anti-sense cathepsin L RNA, TGFbeta1 RNA, or treated with specific inhibitors showed reduced invasion. Reverted cells with 80% of control cell mtDNA exhibited marker protein levels, cell morphology and invasive property closer to control cells. Our results suggest that the mitochondria-to-nucleus signaling pathway operating through increased [Ca(2+)](c) plays an important role in cancer progression and metastasis.
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PMID:Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells. 1242 Feb 21

Inactivation of the tumor suppressor gene PTEN and overexpression of VEGF are two of the most common events observed in high-grade malignant gliomas. The purpose of this study was to determine whether PTEN controls VEGF expression in gliomas under normoxic conditions. Transfer of PTEN to human glioma cells resulted in the transduction of a functional PTEN protein as evidenced by the upregulation of p27 and modification of the phosphorylation status of Akt. Under normoxic conditions, enzyme-linked immunosorbent assay and Northern blot analyses showed downregulation of VEGF in PTEN-treated cells. Moreover, conditioned media from PTEN-treated glioma cells significantly diminished the ability of endothelial cells to grow and migrate. Western blot assays demonstrated that, in a normoxic environment, PTEN downregulates HIF-1 alpha. Finally, promoter activity assays showed that the VEGF promoter region containing the HIF-1alpha binding site is necessary and sufficient for PTEN-mediated downregulation of VEGF. Experiments with PI3-K inhibitors and kinase assays suggested that PI3-K is mediating the effect of PTEN on VEGF, and not the p42/p48 or p38 MAP kinases. These results indicate that restoration of PTEN function in gliomas may induce therapeutic effect by downregulating VEGF. Furthermore, this close functional relationship between PTEN and VEGF suggests that a better understanding of the transduction signal regulated by PTEN might enhance the knowledge of the cause and physiology of vascular and inflammatory diseases.
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PMID:Mechanisms underlying PTEN regulation of vascular endothelial growth factor and angiogenesis. 1250 54

Many drugs vary in potency and/or toxicity according to the time of day when they are administered. In this study, we investigated whether antitumor efficacy of angiogenesis inhibitor, TNP-470 [O-(chloroacetyl-carbamoyl) fumagillol], could be improved by optimizing the dosing schedule. Tumor-bearing mice were housed under standardized light/dark cycle conditions (lights on at 7:00 AM, off at 7:00 PM) with food and water ad libitum. The antitumor effect of TNP-470 (30 mg/kg s.c.) was more potent in mice injected with the drug at the early light phase than it was when administered at the early dark phase. The diurnal change in the antitumor effect of TNP-470 was parallel to that in its antiangiogenic activity. The variation in the effects of TNP-470 was closely related to the diurnal variations in its inhibitory action on methionine aminopeptidase activity in tumor masses. There was a significant dosing time-dependent change in the concentration of TNP-470 in plasma. The higher concentration of TNP-470 in plasma was observed when its antitumor and antiangiogenic activities were increased. These results suggest that therapeutic efficacy of TNP-470 can be enhanced by choosing the most appropriate time of day to administer the drug.
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PMID:Optimizing the dosing schedule of TNP-470 [O-(chloroacetyl-carbamoyl) fumagillol] enhances its antitumor and antiangiogenic efficacies. 1253 20

Genetic aberrations are the primary events leading to carcinogenesis in various tissues and are characteristic for certain tumor types. Amplification of N-myc and deletion of 1p significantly correlate with poor prognosis of neuroblastoma patients. Very little informations is available on the regulation of N-myc expression by external factors. Insulin-like growth factor-II (IGF-II) has been identified as an autocrine growth factor in neuroblastoma. Four neuroblastoma cell lines were examined for their expression of IGF-II and IGF-receptor. Stimulation of neuroblastoma cells with IGF-II leads to an increased activity of the MAP-kinase Erk1, an induction of N-myc expression and an enhanced proliferation rate. In order to disrupt the signal transduction of the IGF-receptor, we inactivated the Ras-proteins in neuroblastoma cells by inhibition of the farnesyl-protein transferase by FTI-277. This inactivation prevented activation of MAP-kinase Erk1 and induction of N-myc expression by IGF-II. Inactivation of Ras by farnesyltransferase inhibitors might become a promising new approach in future treatments of neuroblastoma tumors.
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PMID:Induction of N-myc in neuroblastoma by autocrine IGF-II depends on farnesylated Ras. Application of farnesyltransferase inhibitors. 1255 57

Resveratrol is a plant polyphenol found in grapes and red wine. It has been found to have beneficial effects on the cardiovascular system. Resveratrol also inhibits the growth of various tumor cell lines in vitro and inhibits carcinogenesis in vivo. In this study we examined the effect of resveratrol on growth of two human melanoma cell lines. We found that this plant polyphenol inhibited growth and induced apoptosis in both cell lines, with the amelanotic cell line A375 being more sensitive. The potential involvement of different MAP kinases in the action of resveratrol was also examined. Although resveratrol did not alter the phosphorylation of p38 or JNK MAP kinases in either cell line, it induced phosphorylation of ERK1/2 in A375, but not in SK-mel28 cells. These results suggest that in vivo studies of the effect of resveratrol on melanoma are warranted and that this plant polyphenol might have effectiveness as either a therapeutic or chemopreventive agent against melanoma.
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PMID:Resveratrol is a potent inducer of apoptosis in human melanoma cells. 1256 70


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