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Biomedical subjects

Z Dong

Publications and source records attributed to Z Dong.

316 records · Page 18Linked to original sources
PubMed1990

[Regulation of tumor necrosis factor-alpha mRNA expression in murine peritoneal macrophages].

The expression of tumor necrosis factor-alpha (TNF-alpha) mRNA in murine inflammatory peritoneal macrophages (M phi) was studied with a sensitive liquid hybridization method. Upon exposure to 10-1000 ng/ml of lipopolysaccharide (LPS), M phi were induced to express TNF-alpha mRNA in a dose-dependent manner. mRNA was detectable within 1 h after stimulation, peaked at about 2 h and then gradually declined. A 10 min treatment with LPS was enough to stimulate the maximal level of TNF-alpha mRNA, as determined in a 2 h period. Although calcium ionophore A23187 and macrophage activating factor (MAF) (both can activate M phi to mediate tumoricidal activity) did not induce TNF-alpha mRNA expression by themselves, they did act synergistically with LPS. Treatment of M phi with retinoic acid strongly inhibited LPS-induced TNF-alpha mRNA expression, whereas trifluoperazine had an opposite effect. Cycloheximide not only synergized with LPS but also induced TNF-alpha mRNA expression by itself. In contrast, actinomycin D completely blocked LPS-induced TNF-alpha gene activation. These findings indicate that LPS-induced TNF-alpha mRNA expression is not solely due to an increase in intracellular free calcium ion and is independent of the protein kinase C pathway of signal transduction. In addition, TNF gene activity may be regulated by short-lived protein repressor(s).

Animals↗
PubMed1990

[Studies on characteristics of macrophage-derived cytotoxic factor].

Macrophage-derived cytotoxic factor (M phi-CF) obtained from murine peritoneal macrophages stimulated with calcium ionophore A 23187 and lipopolysacchride was characterized. It had a relative molecular mass of 52,000 +/- 3400 Daltons as determined by gel filtration on Sephadex G-100 column. It was stable in a pH range of 6-10, and at 56 degrees C for 1 h. It was sensitive to pronase and trypsin, but its cytotoxicity was not destroyed by pepsin or 2-mercaptoethanol. Protease inhibitors (phenylmethylsulfonyl fluoride, 8-hydroxyquinine, and soybean trypsin inhibitor) had no significant effect on its cytotoxicity. Pretreatment of target cells with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) protected them from the cytotoxic effect of M phi-CF. These characteristics of M phi-CF are essentially similar to those of tumor necrosis factor (TNF).

Animals↗
PubMedDate not supplied

Radioimmunoguided surgery in gastric cancer using 131-I labeled monoclonal antibody 3H11.

A clinical trial of radioimmunoguided surgery (RIGS) using 131-I labeled monoclonal antibody (MAb) 3H11 was performed on 25 cases with gastric cancer in this study. The results showed that the route of the administration of radiolabeled MAb is the key point of successful RIGS for gastric cancer. The RIGS in 19 cases in the group of submucosal injection via endoscope was very satisfying. For the detection of metastatic lymph nodes, the sensitivity rate of RIGS was 99.2% (118/119), the specificity, 97.7% (43/44), and the accuracy 98.8% (161/163). The accuracy rate in detecting tumor infiltration of the gastric wall was 95.9% (94/98), the sensitivity 94.6% (35/37), and the specificity 96.7% (59/61). Thus, the use of RIGS may improve the radical resectability rate and possibly the overall survival rate in patients with gastric cancer.

Adult↗
PubMedDate not supplied

PI-3 kinase in signal transduction, cell transformation, and as a target for chemoprevention of cancer.

Phosphatidylinositol-3 kinase (PI-3 K) plays a central role in a broad range of biological effects. However, little is known about its role in phorbol ester- or epidermal growth factor (EGF)-induced signal transduction to the transcriptional machinery of the nucleus and in tumor promoter-induced cell transformation. We have used JB6 cells to study the role of PI-3 K in 12-O-tetradecanoylphorbol-13-acetate (TPA)- or EGF-induced AP-1 activation and neoplastic cell transformation. We demonstrated that TPA, EGF and insulin induce PI-3 K activity in JB6 cells. The induced PI-3 K activity was blocked by a dominant negative mutant of PI-3 K, and by wortmannin or LY294002. Blocking of PI-3 K activity by these inhibitors also blocked TPA- or EGF-induced AP-1 activity and cell transformation. Furthermore, we have investigated the role of PKC and its isozymes in the synergistic induction of PI-3 K by TPA and insulin and found that bisindolylmaleimide, a PKC inhibitor, inhibits TPA-induced PI-3 K. Overexpression of a dominant negative PKC epsilon, but not dominant negative PKC alpha, blocks the TPA- or TPA plus insulin-induced PI-3 K activity. Inositol hexaphosphate (InsP6) is one of the most promising chemopreventive agents as demonstrated by Shamsuddin et al. and others. InsP6 profoundly inhibits EGF- or TPA-induced cell transformation and the signal transduction cascade to Erks and AP-1 activation. InsP6 also inhibits TPA- or EGF-induced PI-3 K activity in vivo and in vitro. These results suggest that the anticarcinogenesis action of InsP6 may be through inhibition of PI-3 K and inhibition of the AP-1 pathway. Because InsP6 is a naturally occurring compound with virtually no toxicity, and may be an effective anticarcinogenesis agent in humans, PI-3 K and AP-1 activities may be useful biomarkers for the effectiveness of InsP6 in clinical studies.

Animals↗
PubMedDate not supplied

Downregulation of mitogen-activated protein kinases in human colon cancers.

BACKGROUND: Activation of the mitogen-activated protein kinases (MAPKs) appears to play an important role in both proliferation and transformation of various cells; the role of MAPK activation in colorectal cancers has not been clearly defined. The purpose of our study was to determine whether MAPK activity and protein levels were increased in colorectal cancers. METHODS: Colorectal cancers and adjacent normal mucosa from 21 patients were extracted for protein. Expression levels and activity of the MAPKs (ERK1/2, JNK1, p38 and ERK3) were assessed by immunoblot analysis and in vitro kinase assays, respectively. In addition, changes in myelin basic protein (MBP) kinase activity and autophosphorylation were determined by in-gel kinase assays. RESULTS: The activities of ERK1/2, JNK1 and p38 were downregulated in the majority of cancers; ERK3 kinase activity was increased in 10 of 21 cancers. The presence of proteins displaying increased MBP phosphorylation and autophosphorylation was identified specifically in the cancers by in-gel kinase assays. CONCLUSIONS: Our findings demonstrate that the constitutive activation of ERK1/2, JNK1 and p38 is not a feature of colorectal cancers. Moreover, our in-gel kinase results suggest that protein kinases, other than the MAPKs assessed, may play a more crucial role in colon carcinogenesis.

Adenocarcinoma↗
PubMedDate not supplied

Transactivation of AP-1 in AP-1-luciferase reporter transgenic mice by arsenite and arsenate.

Arsenic is a recognized carcinogen, which acts as a tumor promoter rather than as an initiator. Signal transduction pathways leading to activation of AP-1 and mitogen-activated protein kinases are proposed to be responsible for the tumor promotion activity by arsenic. Induction of AP-1 DNA binding activity and c-jun and c-fos expression was reported to be only observed in cells responding to arsenite, but not to arsenate. However, in this study, we found that both arsenite and arsenate could induce transactivation of AP-1 in mouse epidermal JB6 AP-1-luciferase reporter stable transfectants, P+1-1. This induction of AP-1 activity by arsenic appears to be through activation of mitogen-activated protein kinases and protein kinase C because increased AP-1 activity by arsenite could be blocked by either treatment of cells with PD98059 or overexpression of dominant negative protein kinase Ca. Furthermore, both arsenite and arsenate could induce transactivation of AP-1 in AP-1-luciferase reporter transgenic mice.

Animals↗
PubMedDate not supplied

Inhibition of arsenite-induced apoptosis by aspirin.

Arsenite exposure and subsequent arsenite-induced toxicity and carcinogenesis are common in many countries. Thus the study of chemopreventive compounds that inhibit arsenite-induced toxicity and carcinogenesis is very valuable. In the present work, we investigated the effect of aspirin on arsenite-induced apoptosis and signal transduction by means of luciferase activity, apoptosis analysis and Western blotting. Arsenite induced AP-1 transcriptional activity at the same concentration (20 microM) as was effective for inducing apoptosis. Arsenite-induced apoptosis and AP-1 transactivation in JB6 cells were blocked by aspirin and salicylate (SA). Both aspirin and SA inhibited arsenite-induced phosphorylation of Erks, but had no effect on phosphorylation of JNKs. SA inhibited arsenite-induced phosphorylation of p38 kinase, but aspirin did not. These results indicate that aspirin and SA inhibit arsenite-induced apoptosis through the inhibition of the Erks/AP-1 pathway.

Animals↗