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)

Retinoic acid receptor alpha (RARalpha) plays an important role in mediating all-trans retinoic acid (ATRA) signals. In this study, we found that ATRA up-regulated RARalpha mRNA and protein expression in gastric cancer BGC-823 cells. However, in breast cancer MCF-7 cells it down-regulated RARalpha protein expression with no effect on its RARalpha mRNA. Immunoprecipitation/Western blot analysis showed that, although sumoylated and ubiquitinated RARalpha existed simultaneously in both cancer cell lines, ATRA exerted different regulatory effects on sumoylation and ubiquitination of RARalpha. In MCF-7 cells, ATRA treatment enhanced the ubiquitination of RARalpha and the subsequent degradation of RARalpha through the ubiquitin/proteasome pathway. This resulted in a reduction in the DNA binding activity of RARalpha/retinoid X receptor alpha (RXRalpha) heterodimer, the separation of RXRalpha from RARalpha and the translocation of RXRalpha from the nucleus to the cytoplasm. By contrast, in BGC-823 cells, ATRA augmented sumoylation, not ubiquitination, of RARalpha. The stability of sumoylated RARalpha was significantly stronger than in non-sumoylated RARalpha. These results also showed an increase in the DNA binding activity of the RARalpha/RXRalpha heterodimer and the stability of nuclear localization of this heterodimer, which normally facilitates the ATRA signal transduction. In conclusion, our results reveal a novel mechanism for the regulation of RARalpha-dependent signal transduction through the ubiquitin/proteasome pathway in breast cancer cells and the sumoylation pathway in gastric cancer cells.
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PMID:Ubiquitinated or sumoylated retinoic acid receptor alpha determines its characteristic and interacting model with retinoid X receptor alpha in gastric and breast cancer cells. 1517 3

Trefoil factors family 2 (TFF2), also known as spasmolytic polypeptide, is primarily expressed in the mucus neck cells of gastrointestinal tracts. It has been proposed that TFF2 plays an important physiological role in protection, repair, and healing of gastrointestinal mucosa. To investigate the cis-acting regulatory element that control TFF2 tissue-specific expression, we studied the basal TFF2 promoter activity through transient transfection in several human cancer cell lines. Expression of TFF2 was found to be significantly greater in human breast cancer MCF-7 cells compared to other cancer cells. Results from TFF2 promoter luciferase reporter constructs revealed that the basal level of TFF2 promoter activity was overall more than two-fold higher in MCF-7 cells compared to that of other cell lines examined. Using EMSA assays and site-directed mutagenesis, we identified a cell line-specific transcriptional regulation element located in the TFF2 promoter 5'-flank sequence at -32/-27, and which contains a CCAAT/enhance binding proteins (C/EBPs) consensus-binding site. Mutation of this consensus site reduced the basal promoter activity by more than 50% in MCF-7 cells but had no effect in human gastric cancer cells. In conclusion, we have identified a CCAAT sequence as a cell line-specific cis-acting regulatory element that may contribute to the high level expression of TFF2 in MCF-7 cells. These results also suggest the possibility that TFF2 could play a role in mammary gland tumorigenesis.
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PMID:Characterization of a CCAAT-enhancer element of trefoil factor family 2 (TFF2) promoter in MCF-7 cells. 1517 80

Seven new cadinane sesquiterpenes, (-)-(1R,6S,7S,10R)-1-hydroxycadinan-3-en-5-one (1), (+)-(1R,5S,6R,7S, 10R)-cadinan-3-ene-1,5-diol (2), (+)-(1R,5R,6R,7S,10R)-cadinan-3-ene-1,5-diol (3), (+)-(1R,5S,6R,7S,10R)-cadinan-4(11)-ene-1,5-diol (4), (+)-(1R,5R,6R,7R,10R)-cadinan-4(11)-ene-1,5,12-triol (5), (-)-(1R,4R,5S,6R,7S, 10R)-cadinan-1,4,5-triol (6), and (-)-(1R,6R,7S,10R)-11-oxocadinan-4-en-1-ol (7), together with nine known compounds were isolated from the brown alga Dictyopteris divaricata. The structures of the new natural products, as well as their absolute configuration, were established by means of spectroscopic data including IR, HRMS, 1D and 2D NMR, single-crystal X-ray diffraction, and CD. All compounds were inactive against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), breast cancer (MCF-7), hepatoma (Bel7402), and colon cancer (HCT-8) cell lines.
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PMID:Cadinane sesquiterpenes from the brown alga Dictyopteris divaricata. 1549 33

Three bisnorsesquiterpenes (1-3) with novel carbon skeletons and a norsesquiterpene (4) have been isolated from the brown alga Dictyopteris divaricata. By means of spectroscopic data including IR, HRMS, 1D and 2D NMR techniques, single-crystal X-ray diffraction, and CD, their structures including absolute configurations were proposed as (+)-(1R,6S,9R)-1-hydroxyl-6-isopropyl-9-methylbicyclo[4.3.0]non-4-en-3-one (1), (-)-(1S,6S,9R)-1-hydroxyl-6-isopropyl-9-methylbicyclo[4.3.0] non-4-en-3-one (2), (+)-(5S,6R,9S)-5-hydroxyl-6-isopropyl-9-methylbicyclo[4.3.0]non-1-en-3-one (3), and (-)-(1R,7S,10R)-1-hydroxy-11-norcadinan-5-en-4-one (4). Biogenetically, the carbon skeleton of 1-3 may be derived from the co-occurring cadinane skeleton by ring contraction and loss of two carbon units, and compound 4 from the oxidation of cadinane derivatives. Compounds 1-4 were inactive (IC50 > 10 microg/mL) against several human cancer cell lines including lung adenocarcinoma (A549), stomach cancer (BGC-823), breast cancer (MCF-7), hepatoma (Bel7402), and colon cancer (HCT-8) cell lines.
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PMID:Norsesquiterpenes from the brown alga Dictyopteris divaricata. 1618 Aug 4

In this report, we describe the expression and function of human Sp5, a member of the Sp family of zinc finger transcription factors. Like other family members, the Sp5 protein contains a Cys2His2 zinc finger DNA binding domain at the C-terminus. Our experiments employing Gal4-Sp5 fusion proteins reveal multiple transcriptional domains, including a N-terminal activity domain, an intrinsic repressive element, and a C-terminal synergistic domain. Elevated expression of Sp5 was noted in several human tumors including hepatocellular carcinoma, gastric cancer, and colon cancer. To study the effects of the Sp5 protein on growth properties of human cancer cells and facilitate the identification of its downstream genes, we combined an inducible gene expression system with microarray analysis to screen for its transcriptional targets. Transfer of Sp5 into MCF-7 cells that expressed no detectable endogenous Sp5 protein elicited significant growth promotion activity. Several of the constitutively deregulated genes have been associated with tumorigenesis (CDC25C, CEACAM6, TMPRSS2, XBP1, MYBL1, ABHD2, and CXCL12) and Wnt/beta-Catenin signaling pathways (BAMBI, SIX1, IGFBP5, AES, and p21WAF1). This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against human cancers.
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PMID:Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers. 1638 80

Olive oil is an integral ingredient of the "Mediterranean diet" and accumulating evidence suggests that it may have a potential role in lowering risk of several cancers. We recently hypothesized that the anti-cancer actions of olive oil may relate to its monounsaturated fatty acid (MUFA) oleic acid (OA; 18:1n-9) content to specifically regulate oncogenes. In this study, transient transfection experiments with human Her-2/neu promoter-driven luciferase gene established the ability of OA to specifically repress the transcriptional activity of Her-2/neu gene. Gene repression was seen in tumour-derived cell lines with Her-2/neu gene amplification and overexpression, including SK-Br3 (56% reduction), SK-OV3 (75% reduction) and NCI-N87 (55% reduction) breast, ovarian and stomach cancer cell lines, respectively. Also marginal decreases in promoter activity were observed in cancer cells expressing physiological levels of Her-2/neu (20% reduction in MCF-7 breast cancer cells). Remarkably, OA treatment in Her-2/neu-overexpressing cancer cells was found to induce up-regulation of the Ets protein polyomavirus enhancer activator 3 (PEA3), a transcriptional repressor of Her-2/neu promoter. Also, an intact PEA3 DNA-binding-site at endogenous Her-2/neu gene promoter was essential for OA-induced repression of this gene. Moreover, OA treatment failed to decrease Her-2/neu protein levels in MCF-7/Her2-18 transfectants, which stably express full-length human Her-2/neu cDNA controlled by a SV40 viral promoter. OA-induced transcriptional repression of Her-2/neu through the action of PEA3 protein at the promoter level may represent a novel mechanism linking "Mediterranean diet" and cancer.
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PMID:A genomic explanation connecting "Mediterranean diet", olive oil and cancer: oleic acid, the main monounsaturated fatty acid of olive oil, induces formation of inhibitory "PEA3 transcription factor-PEA3 DNA binding site" complexes at the Her-2/neu (erbB-2) oncogene promoter in breast, ovarian and stomach cancer cells. 1640 75

The aim of this study was to determine the benefits of chemotherapy for oesophago-gastric cancer (OGC) in patients 70 years and above (> or =70) in comparison to younger patients. 1080 patients were enrolled into three randomised controlled trials assessing fluorouracil-based combination chemotherapy. Patients received either a platinum-containing regimen (ECF, MCF), PVI 5-FU (protracted venous infusion of 5-fluorouracil)+/-mitomycin C (MMC), or FAMTX. Of the 1080 patients randomised, 257 (23.8%) were aged > or =70 years. There were no significant differences in the incidence of grades 3/4 toxicity between the two cohorts. Objective and symptomatic response rates, failure-free and overall survival were not significantly different. In a multivariate analysis, independent prognostic factors for survival were performance status and locally advanced disease, not age. Patients > or =70 years with OGC obtained similar benefits from palliative chemotherapy with respect to symptomatic response, tumour regression and survival, without increased toxicities.
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PMID:Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: A pooled analysis of three clinical trials. 1646 13

The tripeptide tyroservatide (tyrosyl-seryl-valine, pTyr-Ser-Val-NH2) has been shown to have antitumor effects on experimental hepatocarcinoma. This study aimed to observe the effects of tyroservatide on other five human carcinomas: A549 (nonsmall cell lung carcinoma), BGC-823 (gastric cancer), MCF-7 (breast cancer), K562 (leukemia), A375 (melanoma) and two murine cancers: Lewis lung cancer and B16 (melanoma) in vivo. In vivo nude mice bearing xenografts of five different human tumors or C57BL/6 mice bearing xenografts of two different murine tumors were given daily intraperitoneal injections of tyroservatide or saline as controls, after tumor implantation. The inhibition of xenografts was determined by calculating the tumor volume and measuring tumor weight. Tyroservatide could significantly inhibit the growth of human lung carcinoma A549, human leukemia K562 and human melanoma A375 in nude mice (P<0.05). In addition, tyroservatide significantly inhibited the subcutaneous tumor growth of Lewis lung carcinoma and B16 melanoma (P<0.05). Tyroservatide, however, could not significantly suppress xenografts of BGC-823 and MCF-7 in nude mice (P>0.05). The results obtained indicate that tyroservatide exhibits different effects on different tumors, which will provide clinical applications guidance of tyroservatide as an anticancer drug.
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PMID:Inhibition of five xenografted human cancers and two murine cancers by the tripeptide tyroservatide. 1735 99

In an effort to prepare unsymmetrical cephalostatin analogues with multi-functionality, we tried the route of selective opening of the spiroketal joining rings E and F. In this study, we have tested several borane complexes (like borane-9-BBN, borane-(N-tosyl)-D-valine, and borane-catechol) with some bis-steroidal pyrazine derivatives like 3, 4, and 16 aiming at opening ring-F at only one spiro-system of the dimer. Upon testing these borane reagents, satisfying results were obtained in the case of the keto-methylene 4 using the catechol-borane complex. The structures of the resulting mono-opened and also some double-opened spiro dimers have been completely confirmed. Some of the prepared compounds were tested against three cancer cell lines: HM02 (stomach cancer), HEP G2 (hepatocellular cancer), and MCF 7 (breast cancer).
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PMID:Chemo-, regio-, and stereoselectivity of F-ring opening reactions in the cephalostatin series. 1798 69

Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. In this study, ATF-Fc, an antibody-like molecule comprising the amino-terminal fragment of human uPA (ATF) linked to the Fc fragment of human IgG1 via a flexible linker was developed. Its antitumor activities were evaluated in vitro and in vivo. The results showed that ATF-Fc had obvious cytotoxic effect on several types of tumor cells, which is dependent on cellular expression of uPAR and its Fc fragment. Treatment with ATF-Fc caused a significant suppression on tumor growth and metastasis of xenograft human tumors (MCF-7 breast cancer and BGC-823 gastric cancer) in athymic nude mice. Furthermore, we demonstrated that ATF-Fc had an anti-angiogenesis activity both in vitro and in vivo. In conclusion, we provided a novel therapeutic antibody-like molecule in the management of a variety of solid tumors by disrupting the uPA/uPAR interaction.
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PMID:Inhibition of tumor growth and metastasis by ATF-Fc, an engineered antibody targeting urokinase receptor. 1875 23


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