Abstract：
:The aggressive biology of human pancreatic adenocarcinoma has been linked with overexpression of vascular endothelial growth factor (VEGF). Constitutive activation of the transcription factor Sp1 plays a critical role in VEGF overexpression. Recent studies indicated that celecoxib, a selective cyclooxygenase-2 inhibitor, exhibits potent antitumor activity. However, the underlying molecular mechanisms of this activity remain unclear. In the present study, we used a pancreatic cancer model to determine the role of Sp1 in the antitumor activity of celecoxib. Treatment of various pancreatic cancer cells with celecoxib suppressed VEGF expression at both the mRNA and protein level in a dose-dependent manner. VEGF promoter deletion and point mutation analyses indicated that a region between nucleotide -109 and -61 and its intact Sp1-binding sites were required for the inhibition of VEGF promoter activity by celecoxib. Also, celecoxib treatment reduced both Sp1 DNA binding activity and transactivating activity. This decreased activity correlated with reduced Sp1 protein and its phosphorylation as determined using Western blot analysis. Furthermore, in an orthotopic pancreatic cancer animal model, celecoxib treatment inhibited tumor growth and metastasis. The antitumor activity was consistent with inhibition of angiogenesis as determined by evaluating tumor microvessel formation, which correlated with decreased Sp1 activity and VEGF expression. Collectively, our data provide a novel molecular mechanism for the antitumor activity of celecoxib and may help further improve its effectiveness in controlling pancreatic cancer growth and metastasis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Wei D,Wang L,He Y,Xiong HQ,Abbruzzese JL,Xie Kdoi
10.1158/0008-5472.can-03-1945subject
Has Abstractpub_date
2004-03-15 00:00:00pages
2030-8issue
6eissn
0008-5472issn
1538-7445journal_volume
64pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Inhibiting angiogenesis has become a major therapeutic strategy for cancer treatment. To identify common intracellular mediators, we previously analyzed gene expression profiles of endothelial cells after treatment with angiogenesis inhibitors. Filamin A interacting protein 1-like (FILIP1L; previously known as down-re...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-1087
更新日期：2008-09-15 00:00:00
abstract：:Endocannabinoids have been implicated in cancer. Increasing endogenous 2-arachidonoylglycerol (2-AG) by blocking its metabolism inhibits invasion of androgen-independent prostate cancer (PC-3 and DU-145) cells. Noladin ether (a stable 2-AG analog) and exogenous CB1 receptor agonists possess similar effects. Conversely...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-3136
更新日期：2004-12-15 00:00:00
abstract：:As with many types of cancer, cell motility is an important factor in the progression and metastasis of hepatocellular carcinomas (HCC). HCC is associated with significant fibrosis in the liver. The fibrotic microenvironment in the liver is characterized by an altered composition of the extracellular matrix (ECM) and ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-12-01 00:00:00
abstract：:Tumor development is angiogenesis dependent, and vascular endothelial growth factor (VEGF) is a key growth factor in this process. We demonstrate that high expression of VEGF mRNA in 55 superficial bladder cancers was associated with earlier recurrence (P = 0.001; hazard ratio, 3.09) and progression to a more invasive...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:It has been suggested that oxygen-carrying blood substitutes, perfluorochemical (PFC) emulsions, can increase blood flow and oxygen delivery to poorly perfused tumor regions. Local cerebral blood flow was measured in male Wistar rats bearing intracranial Walker 256 tumor with and without blood-PFC exchange using [14C]...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-06-15 00:00:00
abstract：:Phenotypic variability of the human neuroblastoma cell line SK-N-SH was studied with the use of three subclones that interconvert at a slower rate than the parent cell line, i.e., a neuroblast-type subclone (SH-SY5Y), a nonneuronal, strongly substrate adherent subclone (SH-EP), and an intermediate type subclone (SH-IN...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:Levels of epidermal growth factor receptor (EGF-R) and insulin-like growth factor receptor (IGF-R) in breast cancer tissue were evaluated. The binding of growth factors was compared to the content of estrogen receptors (ER) and progesterone receptors (PgR). EGF-R correlated negatively to the ER and PgR (Kendall correl...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput metho...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-03-0932
更新日期：2004-08-01 00:00:00
abstract：:Genomic imprinting is an epigenetic modification of the gamete or zygote leading to parental origin-specific gene expression in somatic cells of the offspring. We have previously identified a cluster of imprinted genes on human chromosome 11p15.5, a region involved in Beckwith-Wiedemann syndrome, Wilms' tumor, and ova...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:The aim of this current study was to examine the significance of CD44 expression in mediating cancer cell adhesion to human bone marrow endothelial cell(s) (hBMEC). Differential CD44 expression on two metastatic prostate cancer cell lines, PC3 (CD44 +ve) and DU145 (CD44 -ve) and four breast cancer cell lines was confi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-0389
更新日期：2004-08-15 00:00:00
abstract：:We have analyzed the mechanism of activation of two human ras oncogenes. We have also identified a rasN gene from a human gastric adenocarcinoma which efficiently induced both morphological transformation and tumorigenicity of NIH3T3 cells in a transfection assay. The rasN gene in tumor tissue DNA did not appear to be...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:In a European joint project carried out in 6 laboratories a disease-oriented program was set up consisting of a panel of 7 tumor types, each represented by 4 to 8 different human tumor lines, for secondary screening of promising anticancer drugs. Human tumor lines were selected on the basis of differences in histology...
journal_title：Cancer research
pub_type： 临床试验,杂志文章,多中心研究
doi：
更新日期：1992-11-01 00:00:00
abstract：:Species evolve by mutations and epigenetic changes acting on individuals in a population; tumors evolve by similar mechanisms at a cellular level in a tissue. This article reviews growing evidence about tumor dormancy and suggests that (i) cellular malignancy is a natural byproduct of evolutionary mechanisms, such as ...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-17-0068
更新日期：2017-05-15 00:00:00
abstract：:MTW9, a transplantable mammary tumor in Wistar Furth rats, shows little growth unless host serum prolactin is increased. This study compares the response to ovariectomy of MTW9-MtT, a tumor developed in rats bearing the mammosomatotropic tumor MtTW10 (serum prolactin 500 to 7000 ng/ml) with MTW9-P developed in rats gi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
abstract：:Possible mechanisms whereby alcohol abuse and alcohol-related diseases may promote the development of cancer are analyzed. The mechanisms discussed include: (a) contact-related local effects on the upper gastrointestinal tract; (b) the presence of low levels of carcinogens in alcoholic beverages; (c) induction of micr...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：
更新日期：1979-07-01 00:00:00
abstract：:Oxygen derived free radicals and peroxides result from many antitumor treatments, including radiation and anthracyclines. Doxorubicin cardiotoxicity is thought to result from free radical induced lipid peroxidation. The heart has less active detoxification enzymes than does the liver and depends on selenium dependent ...
journal_title：Cancer research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1985-11-01 00:00:00
abstract：:Recombinant human stem cell factor (SCF) binds to the c-kit receptor on human bone marrow progenitor cells and enhances their survival following irradiation. Since the c-kit receptor has also been detected on malignant cells, experiments were performed to study the effect of SCF on the proliferation and radiation surv...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:Antibodies were produced against 220,000-molecular-weight proteins of Syrian hamster embryo cells. The antiserum containing these antibodies is capable of immunologically staining the surfaces and a fibrillar network around untransformed Syrian hamster embryo cells. The staining is removed by adsorption of the antiser...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-09-01 00:00:00
abstract：:The effect of a number of steroids, growth factors, and peptides on aromatase activity in two estrogen receptor positive breast cancer cell lines (MCF7 and T47D) was investigated. The cells were incubated in Dulbecco's minimum essential medium containing phenol red and 10% fetal calf serum. Pronounced differences in b...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-03-15 00:00:00
abstract：:Overexpression of colony-stimulating factor-1 (CSF-1) and its receptor in breast cancer is correlated with poor prognosis. Based on the hypothesis that blockade of CSF-1 would be beneficial in breast cancer treatment, we developed a murinized, polyethylene glycol-linked antigen-binding fragment (Fab) against mouse (ho...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3523
更新日期：2006-04-15 00:00:00
abstract：:Gene-targeted mice that contain a His6-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in the activation of Myc in the great majority of mouse plasmacytomas. Mice carryin...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1222
更新日期：2005-09-01 00:00:00
abstract：:Estrogen receptor-related receptors (ERR) are orphan nuclear receptors, which are constitutively activated without estrogen binding. Recent evidence indicates that the ligand-independent ERRs may be involved in similar ER-mediated regulatory pathways and modulate estrogen responsiveness in certain target cells. We rec...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-3855
更新日期：2007-05-15 00:00:00
abstract：:We have investigated the behavior of dissociated cells of a moderately differentiated Longnecker transplantable pancreatic acinar carcinoma (Longnecker et al., Cancer Lett., 7: 197-202, 1979) maintained in vitro on acellular seminiferous tubular basement membranes of rat testis. The tumor cells, which grow as solid ma...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:Chemokines play the key role in initiating immune responses by regulating the attraction and homing of immune cells to the lymphoid and nonlymphoid tissues. CXCL14 is a chemokine that in tumors may act as chemoattractant for monocytes and dendritic cells (DC), which may modulate antitumor immune responses in certain c...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0427
更新日期：2010-06-01 00:00:00
abstract：:STAT1 exists in phosphorylated (pSTAT1) and unphosphorylated (uSTAT1) forms each regulated by IFN-γ. Although STAT1 is a key mediator of the IFN-γ signaling pathway, an essential component of the host cancer immunosurveillance system, STAT1 is also overexpressed in certain human cancers where the functions of pSTAT1 a...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-1347
更新日期：2012-09-15 00:00:00
abstract：:The cells of many solid tumors have been found to contain supernumerary centrosomes, a condition known as centrosome amplification. Centrosome amplification, accompanied by the overexpression of an associated kinase, Aurora A (AurA), has been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy,...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-07-15 00:00:00
abstract：:Hereditary nonpolyposis colorectal cancer is associated with inherited defects in DNA mismatch repair. Clinical variation even in cases with identical predisposing mutations suggests the existence of other factors contributing to the phenotype. We addressed the modifying role of the common A/G polymorphism in exon 4 a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-08-15 00:00:00
abstract：:Inflammation plays a role in the progression to cancer and it is linked to the presence of senescent cells. Ulcerative colitis (UC) is a chronic inflammatory disease that predisposes to colorectal cancer. Tumorigenesis in this setting is associated with telomere shortening that can be observed in the nondysplastic epi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1966
更新日期：2011-03-01 00:00:00
abstract：:The class of folate antimetabolites typified by (6R)-dideazatetrahydrofolate (lometrexol, DDATHF) are specific inhibitors of de novo purine synthesis because of potent inhibition of glycinamide ribonucleotide formyltransferase (GART) but do not induce detectable levels of DNA strand breaks. As such, they are a test ca...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-09-15 00:00:00
abstract：:The environmental contaminant 6-nitrochrysene (6-NC) has been shown to induce adenomas and adenocarcinomas in the colons of rats. The present study aimed at providing a better understanding of mechanisms that are responsible for this effect. Three female CD rats were injected i.p. with [3,4,9,10-3H]6-NC [9 mumol/rat (...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
