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

The interaction of the potent tumor-promoting agent phorbol myristate acetate (PMA) with purified rat liver plasma membranes suspended in phosphate-buffered saline (PBS), pH 7.4, was studied by fluorescence spectrophotometry. Exposure of membranes to PMA caused up to 21% decrease of the native membrane emission, i.e. the fluorescence of both tryptophan and tyrosine, compared to non-treated membranes. The decrease in the membrane emission varied with both the PMA and the membrane concentration. Treatment of rat liver plasma membranes with biologically less active analogs of PMA, phorbolol myristate acetate (PHMA) and 4a alpha-phorbol didecanoate (4a alpha-PDD), resulted in a 5-10% decrease of the native membrane emission. These studies suggest that PMA causes alterations in membrane structure which are due, at least in part, to conformational changes in the membrane proteins.
 ...
PMID:Fluorescence studies on the interaction of the tumor promoter phorbol myristate acetate and related compounds with rat liver plasma membranes. 18 50

We have examined the effect of the tumor promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA), on the actin-containing elements of the cytoskeleton of chick embryo fibroblasts (CEF). TPA at concentrations as low as 7.3 times 10-10M indices a reversible change in the cytoskeleton as visualized by indirect immunofluorescence using anti-actin antibodies. Cells incubated with TPA lose the ordered actin-containing structures found in normal cells and resemble Rous sarcoma virus-transformed cells in that the immunofluorescent actin pattern is diffuse. The TPA effects are both dose-and time-dependent. Analogs of TPA which are inactive as tumor promoters do not induce cytoskeletal changes at the concentrations tested, while a second tumor promoter, PDD, is also able to cause alterations in actin-containing structures. The action of TPA requires de novo synthesis of both RNA and protein. The direct cytoskeletal changes are neither plasmin-dependent nor subject to inhibition by incubating the cells with high levels of protease inhibitors during the exposure to TPA. However, plasminogen does increase the sensitivity of cells to TPA.
 ...
PMID:Tumor promoters induce changes in the chick embryo fibroblast cytoskeleton. 57 62

cis-Platinum (II)diamminodichloride (PDD), an anti-tumor agent, induced auxotrophic mutations in Escherichia coli, some of which were reverted to prototrophy by exposure to PDD, 2-aminopurine (2-AP), and N-methyl-N'-nitro-N-mitrosoguanidine (NTG), but not ICR derivatives. Similarly, various 2-AT-, NTG-, and ultraviolet light-induced auxotrophs were reverted to prototrophy by PDD. Some PDD-induced auxotrophs carried nonsense mutations and others could be phenotypically suppressed growth with streptomycin. Although these findings suggest that PDD promotes base substitutions, this mutagen may also cause base subtractions because (like NTG) it induced, at reduced frequency, reversion to prototrophy of certain ICR-induced auxotrophs. Isomeric trans-platinum (II)diamminodichloride, which lacks anti-tumor activity, was an ineffective mutagen. Near-optimal conditions for PDD-induced mutagenesis entailed prolonged cultivation with low levels of mutagen where the frequency of forward mutation to auxotrophy was 10-3 and that of a selected trp isolate to prototrophy was 10-2.
 ...
PMID:Mutagenic properties of cis-plantinum(II)diammino-dichloride in Escherichia coli. 109 11

The development of Candida meningitis in a patient following partial resection of a glioblastoma raised suspicion that transforming growth factor (TGF-beta), an immunosuppressive cytokine known to be produced by this tumor, would be elevated in his cerebrospinal fluid (CSF). By using a highly specific bioassay, the concentration of TGF-beta was found to be 609 pg/mL, which was 10-fold greater than the mean CSF TGF-beta value in control subjects with no neurologic disease. Increased CSF TGF-beta levels were also detected in patients with other central nervous system (CNS) diseases: malignancies and AIDS dementia complex. These findings suggest that TGF-beta may play an immunopathogenetic role in the CNS.
 ...
PMID:Glioblastoma, transforming growth factor-beta, and Candida meningitis: a potential link. 131 5

An expression vector was constructed in which TGF-beta 1 was placed under the control of the metallothionein promoter. Cys223 and Cys225 in the TGF-beta 1 propeptide were converted to serines, mutations which result in dissociation of the pro-peptide and secretion of bioactive TGF-beta 1 [Brunner, A.M., Marquardt, H., Malacko, A.R., Lioubin, M.N. and Purchio, A.F. (1989) J. Biol. Chem., 264, 13660-13664]. A fibrosarcoma was transfected with this plasmid and a clone (17.18) was selected in which TGF-beta 1 mRNA was able to be induced six-fold following zinc sulphate treatment. These cells increased the secretion of bioactive TGF-beta 1 14-fold and exhibited a coincidental increase in jun-B mRNA expression, suggesting that secreted TGF-beta 1 was acting to induce this early response gene by autocrine activation. Following zinc sulphate induction, the tumor cells became progressively more motile and able to invade collagen gels. In contrast to parental tumor not bearing the TGF-beta 1 expression vector, zinc sulphate stimulation of clone 17.18 enhanced collagenase IV and procathepsin L mRNA levels and enhanced the secretion of many collagenolytic proteases into the medium. Since the action of TGF-beta generally decreases proteolysis by suppression of protease transcription, we compared the response of normal parental fibroblasts to ras-transformed fibrosarcomas and confirmed that TGF-beta could greatly enhance collagenase IV and procathepsin L mRNA levels while having little effect on non-transformed fibroblasts. These experiments indicate that induction of TGF-beta secretion can enhance motility and protease production through autocrine activation, thus increasing the invasion potential of fibrosarcomas.
 ...
PMID:Autocrine induction of tumor protease production and invasion by a metallothionein-regulated TGF-beta 1 (Ser223, 225). 131 70

Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor for many cell types, including tumor cells. We recently have reported the establishment and characterization of two human gastric scirrhous carcinoma cell lines, HSC-39 and HSC-43. Here we examined the effect of TGF-beta 1 on the growth of these lines as compared to five other human gastric adenocarcinoma cell lines. Proliferation of HSC-39 and HSC-43 cells was strongly inhibited by TGF-beta 1, whereas the other gastric adenocarcinoma cell lines were unresponsive to TGF-beta 1. Both HSC-39 and HSC-43 cells gradually lost viability following exposure to TGF-beta 1. This response was dose dependent up to 4 ng/ml. When TGF-beta 1 was removed, the cells failed to exhibit regrowth, indicating an irreversible growth-inhibitory effect of this agent, leading to cell death. DNA fragments were observed consisting of multimers of approximately 180 base pairs 24 h after TGF-beta 1 treatment. The chromatin condensation of each cell line was confirmed by Hoechst 33258 fluorochrome staining. Ultrastructurally, condensed and fragmented nuclei were observed in TGF-beta 1-treated cells. These features are generally associated with apoptotic processes. Both cell death and DNA fragmentation were partially inhibited by cycloheximide, suggesting the requirement for new protein synthesis. Our results suggest that TGF-beta 1 induces cell death in human gastric scirrhous carcinoma cells in vitro which is mediated by activation of a signal transduction pathway for apoptosis.
 ...
PMID:Transforming growth factor beta 1 induces apoptotic cell death in cultured human gastric carcinoma cells. 131 36

Cytokines can have both negative and positive effects on cells undergoing carcinogenesis. The promotion and progression phases of carcinogenesis may be affected by autocrine loops involving cytokines with growth factor activities such as IL-1, IL-2, low molecular weight B cell growth factor, TNF, IL-3, GM-CSF, M-CSF and IL-9. Aberrations in cytokine receptors such as the truncated EGF receptor present in v-erB promotes the growth of neoplastic cells. Aberrant signaling mechanisms, as found with spleen focus-forming virus, which mimics the ligand that activates the erythropoietin receptor, can also contribute to proliferation of preneoplastic and neoplastic cells. In contrast, cytokines such as interferons, LIF, TGF-beta, TNF and leukoregulin, with antiproliferative or differentiating activities, are sometimes capable of inhibiting carcinogenesis. Transfection of tumor cells with cytokine genes, such as IL-2, IL-4 and TNF, can cause suppression of in vivo tumor cell growth by mobilizing host immune and inflammatory cell responses. Thus cytokines and their receptors may play a direct role in early stages of tumor cell development and growth.
 ...
PMID:Cytokines as positive and negative regulators of tumor promotion and progression. 132 42

The bovine 17 alpha-hydroxylase cytochrome P450 gene (CYP17) contains at least two cAMP-responsive sequences (CRS) within its 5'-flanking region. In this study it is demonstrated that one of the sequences, CRS1, is also a target for protein kinase C (PKC)-mediated regulation. Forskolin-induced, CRS1-dependent transcription of a heterologous minimal promoter/structural gene which had been transfected into the mouse adrenocortical tumor cell line Y1 was suppressed by activation of PKC by phorbol esters such as 12-O-tetradecanoyl phorbol-14-acetate and phorbol 12,13-didecanoate-beta (PDD beta). Use of the active and inactive forms of PDD (PDD alpha and PDD beta) as well as down-regulation of PKC by prolonged treatment of the cells with 12-O-tetradecanoyl phorbol-14-acetate demonstrated that the effect of phorbol esters on transcription conferred by CRS1 was mediated through the PKC pathway and not a consequence of general toxicity to the cells. Analysis of the different steps in the signal transduction pathway between the adenylate cyclase and the CRS1 element suggests that phrobol esters do not exert their effect by altering the forskolin-induced cAMP production, activation of PKA, or the binding of nuclear proteins to CRS1. These results establish the CRS1 element as a target not only for PKA, but also for the PKC-mediated signal transduction pathway. They further suggest that PKC interferes with the transcriptional activation competence of factors bound to CRS1 and the minimal promoter.
 ...
PMID:A novel 3',5'-cyclic adenosine monophosphate-responsive sequence in the bovine CYP17 gene is a target of negative regulation by protein kinase C. 132 75

The effects of EGF and TGF-beta 1 on the proliferation of 2 ovarian carcinoma cell lines (IGROV1 and OVCCR1) were evaluated. The cell lines were adapted to grow in a restricted serum (0.5%) medium. EGF was required for proliferation of both ovarian cell lines. Low doses of TGF-beta 1 inhibited clonogenic capacity and attenuated the EGF-mediated stimulation of DNA synthesis in OVCCR1 cells. TGF-beta 1 inhibited OVCCR1 cell proliferation by blocking the cell cycle at the G1/S transition. TGF-beta 1 did not affect either clonal or monolayer growth of IGROV1 cells. Both cell lines express type-I and type-III TGF-beta receptors, suggesting that the unresponsiveness of IGROV1 cells to TGF-beta 1 occurs at a post-receptor level. TGF-beta 1 mRNA was detected in OVCCR1 cells and in 8 out of 11 of the ovarian tumor specimens examined.
 ...
PMID:Transforming growth factor beta 1 (TGF-beta 1) inhibits growth of a human ovarian carcinoma cell line (OVCCR1) and is expressed in human ovarian tumors. 133 Sep 35

We have studied the excessive deposition of extracellular matrix in a patient with fibrolamellar carcinoma of the liver. The collagen matrix was predominantly composed of collagens I, III, and V. Since specific mRNAs for collagens I and III were detected by in situ hybridization, we also provide evidence that the fibroblastoid stromal cells were the major source of this collagen. Occasionally, also tumor cells could be shown to express collagen III-mRNA. Furthermore, some tumor cells showed positive signals for TGF-beta 1, while isolated stromal cells expressed interleukin-6. This cytokine expression may probably be related to the altered control of collagen gene expression.
 ...
PMID:Excessive collagen formation in fibrolamellar carcinoma of the liver: a morphological and biochemical study. 841 1


1 2 3 4 5 6 7 8 9 10 Next >>