Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma.

Abstract:

:Wnt/beta-catenin signaling plays an important role in normal development. However, its aberrant activation is associated with several cancers. The aim of this study is to examine the Wnt/beta-catenin pathway in patients with advanced pancreatic adenocarcinoma (n = 31). Paraffin sections from tumors (n = 16) and normal pancreata (n = 3) were used to determine the localization of beta-catenin. An additional 15 frozen tumors, adjacent normal pancreata (n = 5), or normal pancreata (n = 4) were utilized for protein isolation. Tumors were also examined for mutations in exon 3 of the CTNNB1 gene. More than 65% of the tumors showed an increase in total beta-catenin, consistent with its enhanced membranous, cytoplasmic, and nuclear localization, but only two showed mutations in CTNNB1. The majority of the remaining tumors demonstrated concurrent increases in Wnt-1 and frizzled-2 (positive regulators) and a decrease in Ser45/Thr41-phospho-beta-catenin. Electrophoretic mobility shift assay demonstrated beta-catenin-T-cell factor binding in tumors only. Adenomatous polyposis coli and axin, which are both negative regulators, remained unchanged. Unexpectedly, total glycogen synthase kinase-3beta protein was elevated in these tumors. Elevated levels of E-cadherin were also observed, although E-cadherin-beta-catenin association in tumors remained unaffected. Thus, Wnt/beta-catenin activation was observed in 65% of pancreatic adenocarcinomas, independently of beta-catenin gene mutations in most tumors.

journal_name

Neoplasia

authors

Zeng G,Germinaro M,Micsenyi A,Monga NK,Bell A,Sood A,Malhotra V,Sood N,Midda V,Monga DK,Kokkinakis DM,Monga SP

doi

10.1593/neo.05607

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

279-89

issue

4

eissn

1522-8002

issn

1476-5586

journal_volume

8

pub_type

杂志文章
  • Impact of metronomic UFT/cyclophosphamide chemotherapy and antiangiogenic drug assessed in a new preclinical model of locally advanced orthotopic hepatocellular carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce t...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.91872

    authors: Tang TC,Man S,Lee CR,Xu P,Kerbel RS

    更新日期:2010-03-01 00:00:00

  • In vivo confocal fluorescence imaging of the intratumor distribution of the photosensitizer mono-L-aspartylchlorin-e6.

    abstract::We present an in vivo fluorescence microscopic evaluation of intratumor distribution of the photosensitizer mono-L-aspartylchlorin-e6 (NPe6) in an intradermal mouse EMT6 tumor model. Although the identification of favorable photophysical and pharmacological properties has led to the development of new photosensitizers...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.08104

    authors: Mitra S,Foster TH

    更新日期:2008-05-01 00:00:00

  • Progressive genomic instability in the Nup98-HoxD13 model of MDS correlates with loss of the PIG-A gene product.

    abstract::The Nup98-HoxD13 (NHD13) fusion gene was identified in a patient with therapy-related myelodysplastic syndrome (MDS). When transgenically expressed in hematopoietic cells, mice faithfully recapitulate human disease with serial progression from peripheral blood (PB) cytopenias and increased bone marrow (BM) blasts to a...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.07.004

    authors: Byrne M,Bennett RL,Cheng X,May WS

    更新日期:2014-08-01 00:00:00

  • B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma.

    abstract::We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumor regression in rod...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.11024

    authors: Candolfi M,Curtin JF,Yagiz K,Assi H,Wibowo MK,Alzadeh GE,Foulad D,Muhammad AK,Salehi S,Keech N,Puntel M,Liu C,Sanderson NR,Kroeger KM,Dunn R,Martins G,Lowenstein PR,Castro MG

    更新日期:2011-10-01 00:00:00

  • Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a MAFIA-Based Glioma Model.

    abstract::Monocytes/macrophages are an influential component of the glioma microenvironment. However, understanding their diversity and plasticity constitute one of the most challenging areas of research due to the paucity of models to study these cells' inherent complexity. Herein, we analyzed the role of monocytes/macrophages...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.03.003

    authors: Gabrusiewicz K,Hossain MB,Cortes-Santiago N,Fan X,Kaminska B,Marini FC,Fueyo J,Gomez-Manzano C

    更新日期:2015-04-01 00:00:00

  • Radiocurability is associated with interstitial fluid pressure in human tumor xenografts.

    abstract::Interstitial fluid pressure (IFP) has been shown to be an independent prognostic parameter for disease-free survival in cervical carcinoma patients treated with radiation therapy. However, the underlying mechanisms are not fully understood. The main aims of this study were to investigate whether tumor radiocurability ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.91152

    authors: Rofstad EK,Gaustad JV,Brurberg KG,Mathiesen B,Galappathi K,Simonsen TG

    更新日期:2009-11-01 00:00:00

  • Characterization and Targeting of Platelet-Derived Growth Factor Receptor alpha (PDGFRA) in Inflammatory Breast Cancer (IBC).

    abstract:PURPOSE:Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a un...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.03.002

    authors: Joglekar-Javadekar M,Van Laere S,Bourne M,Moalwi M,Finetti P,Vermeulen PB,Birnbaum D,Dirix LY,Ueno N,Carter M,Rains J,Ramachandran A,Bertucci F,van Golen KL

    更新日期:2017-07-01 00:00:00

  • Elevated p21-activated kinase 2 activity results in anchorage-independent growth and resistance to anticancer drug-induced cell death.

    abstract::p21-activated kinase 2 (PAK-2) seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.81446

    authors: Marlin JW,Eaton A,Montano GT,Chang YW,Jakobi R

    更新日期:2009-03-01 00:00:00

  • Targeting antiapoptotic Bcl-2 family members with cell-permeable BH3 peptides induces apoptosis signaling and death in head and neck squamous cell carcinoma cells.

    abstract::Head and neck squamous cell carcinomas (HNSCC) are frequently characterized by chemotherapy and radiation resistance, and by overexpression of Bcl-XL, an antiapoptotic member of the Bcl-2 protein family. In this report we examined whether cell-permeable peptides derived from the BH3 domains of proapoptotic Bax, Bad, o...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07394

    authors: Li R,Boehm AL,Miranda MB,Shangary S,Grandis JR,Johnson DE

    更新日期:2007-10-01 00:00:00

  • CXCR4 regulates the early extravasation of metastatic tumor cells in vivo.

    abstract::Recent studies have demonstrated that the chemokine receptor CXCR4 plays a crucial role in organ-specific metastasis formation. Although a variety of studies showed the expression of chemokine receptors, in particular, CXCR4, by gastrointestinal tumors, the precise mechanisms of chemokine receptor-mediated homing of c...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.09272

    authors: Gassmann P,Haier J,Schlüter K,Domikowsky B,Wendel C,Wiesner U,Kubitza R,Engers R,Schneider SW,Homey B,Müller A

    更新日期:2009-07-01 00:00:00

  • PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment.

    abstract::Pancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attent...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.09.003

    authors: Saito K,Iioka H,Maruyama S,Sumardika IW,Sakaguchi M,Kondo E

    更新日期:2019-12-01 00:00:00

  • High Expression of HLA-G in Ovarian Carcinomatosis: The Role of Interleukin-1β.

    abstract::The present study focuses on the influence of the tumor microenvironment on the expression of HLA-G in ovarian cancer and its impact on immune cells. We used carcinomatosis fluids (n = 16) collected from patients diagnosed with epithelial ovarian cancer, detected by an increase in CA125 levels. Our results indicate th...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.01.001

    authors: Ullah M,Azazzen D,Kaci R,Benabbou N,Pujade Lauraine E,Pocard M,Mirshahi M

    更新日期:2019-03-01 00:00:00

  • p27KIP1 deletions in childhood acute lymphoblastic leukemia.

    abstract::The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has been assigned to chromosome band 12p12, a region often affected by cytogenetically apparent deletions or translocations in childhood acute lymphoblastic leukemia (ALL). As described here, fluorescence in situ hybridization (FISH) analysis o...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900033

    authors: Komuro H,Valentine MB,Rubnitz JE,Saito M,Raimondi SC,Carroll AJ,Yi T,Sherr CJ,Look AT

    更新日期:1999-08-01 00:00:00

  • Hepatitis B virus X protein inhibits tumor suppressor miR-205 through inducing hypermethylation of miR-205 promoter to enhance carcinogenesis.

    abstract::The infection of hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC), in which HBV X protein (HBx) plays crucial roles. MicroRNAs are involved in diverse biologic functions and in carcinogenesis by regulating gene expression. In the present study, we aim to investigate ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.131362

    authors: Zhang T,Zhang J,Cui M,Liu F,You X,Du Y,Gao Y,Zhang S,Lu Z,Ye L,Zhang X

    更新日期:2013-11-01 00:00:00

  • Colorectal cancer "methylator phenotype": fact or artifact?

    abstract::It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP)," characterized by preferential proximal location in the colon, but otherwise poorly defined. The...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04502

    authors: Anacleto C,Leopoldino AM,Rossi B,Soares FA,Lopes A,Rocha JC,Caballero O,Camargo AA,Simpson AJ,Pena SD

    更新日期:2005-04-01 00:00:00

  • CCN6 knockdown disrupts acinar organization of breast cells in three-dimensional cultures through up-regulation of type III TGF-β receptor.

    abstract::While normal cells in the human breast are organized into acinar structures, disruption of the acinar architecture is a hallmark of cancer. In a three-dimensional model of morphogenesis, we show that down-regulation of the matrix-associated tumor suppressor protein CCN6 (WNT1-inducible-signaling pathway protein 3) dis...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.121322

    authors: Pal A,Huang W,Toy KA,Kleer CG

    更新日期:2012-11-01 00:00:00

  • Valproic acid upregulates NKG2D ligand expression through an ERK-dependent mechanism and potentially enhances NK cell-mediated lysis of myeloma.

    abstract::Modulation of the antitumor immune response through the engagement of NKG2D receptors with their ligands (L) on targets represents a promising therapeutic approach against cancer. In this study, we tested the effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on the expression of NKG2D ligands in m...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.121236

    authors: Wu X,Tao Y,Hou J,Meng X,Shi J

    更新日期:2012-12-01 00:00:00

  • Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells.

    abstract::Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whet...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.09.003

    authors: Mukherjee A,Ma Y,Yuan F,Gong Y,Fang Z,Mohamed EM,Berrios E,Shao H,Fang X

    更新日期:2015-09-01 00:00:00

  • Tumor angiogenesis phenotyping by nanoparticle-facilitated magnetic resonance and near-infrared fluorescence molecular imaging.

    abstract::One of the challenges of tailored antiangiogenic therapy is the ability to adequately monitor the angiogenic activity of a malignancy in response to treatment. The α(v)β(3) integrin, highly overexpressed on newly formed tumor vessels, has been successfully used as a target for Arg-Gly-Asp (RGD)-functionalized nanopart...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.121148

    authors: Jarzyna PA,Deddens LH,Kann BH,Ramachandran S,Calcagno C,Chen W,Gianella A,Dijkhuizen RM,Griffioen AW,Fayad ZA,Mulder WJ

    更新日期:2012-10-01 00:00:00

  • Loss of p12CDK2-AP1 expression in human oral squamous cell carcinoma with disrupted transforming growth factor-beta-Smad signaling pathway.

    abstract::We examined correlations between TGF-beta1, TbetaR-I and TbetaR-II, p12(CDK2-AP1), p21(WAF1), p27(KIP1), Smad2, and p-Smad2 in 125 cases of human oral squamous cell carcinoma (OSCC) to test the hypothesis that resistance to TGF-beta1-induced growth suppression is due to the disruption of its signaling pathway as a con...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.06580

    authors: Peng H,Shintani S,Kim Y,Wong DT

    更新日期:2006-12-01 00:00:00

  • Targeting histone deacetylase SIRT1 selectively eradicates EGFR TKI-resistant cancer stem cells via regulation of mitochondrial oxidative phosphorylation in lung adenocarcinoma.

    abstract::Lung adenocarcinoma (LAD) is a human malignancy successfully treated with the tyrosine kinase inhibitor (TKI) gefitinib; however, the enrichment of therapy resistant cancer stem cells (CSCs) in such patients is assumed to be a source of treatment failure. Evaluation of LAD cell populations treated with the TKI inhibit...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.10.006

    authors: Sun J,Li G,Liu Y,Ma M,Song K,Li H,Zhu D,Tang X,Kong J,Yuan X

    更新日期:2020-01-01 00:00:00

  • Vascular endothelial-targeted therapy combined with cytotoxic chemotherapy induces inflammatory intratumoral infiltrates and inhibits tumor relapses after surgery.

    abstract::Surgery is the most effective therapy for cancer in the United States, but disease still recurs in more than 40% of patients within 5 years after resection. Chemotherapy is given postoperatively to prevent relapses; however, this approach has had marginal success. After surgery, recurrent tumors depend on rapid neovas...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.12208

    authors: Judy BF,Aliperti LA,Predina JD,Levine D,Kapoor V,Thorpe PE,Albelda SM,Singhal S

    更新日期:2012-04-01 00:00:00

  • Neoplastic transformation induced by the gep oncogenes involves the scaffold protein JNK-interacting leucine zipper protein.

    abstract::The activated mutants of the α-subunits of G proteins G(12) and G(13) have been designated as the gep oncogenes owing to their ability to stimulate diverse oncogenic signaling pathways that lead to neoplastic transformation of fibroblast cell lines and tumorigenesis in nude mice models. Studies from our laboratory as ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.101622

    authors: Kashef K,Radhakrishnan R,Lee CM,Reddy EP,Dhanasekaran DN

    更新日期:2011-04-01 00:00:00

  • ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.

    abstract::The ZNF198- FGFR1 fusion gene arises as a result of the t(8;13)(p11;q12) in the 8p11 myeloproliferative syndrome. To determine the transforming properties of this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL)-3 dependent cell line Ba/F3. Growth factor independent subclones were obtained in whi...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900035

    authors: Smedley D,Demiroglu A,Abdul-Rauf M,Heath C,Cooper C,Shipley J,Cross NC

    更新日期:1999-10-01 00:00:00

  • A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma.

    abstract::Melanomas are highly radioresistant tumors, mainly due to efficient DNA double-strand break (DSB) repair. Dbait (which stands for DNA strand break bait) molecules mimic DSBs and trap DNA repair proteins, thereby inhibiting repair of DNA damage induced by radiation therapy (RT). First, the cytotoxic efficacy of Dbait i...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.08.008

    authors: Biau J,Devun F,Jdey W,Kotula E,Quanz M,Chautard E,Sayarath M,Sun JS,Verrelle P,Dutreix M

    更新日期:2014-10-23 00:00:00

  • Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway.

    abstract::Chromobox 4 (CBX4) is a core component of polycomb-repressive complex 1 with important roles in cancer biology and tissue homeostasis. Aberrant expression of CBX4 has been implicated in several human malignancies. However, its role and underlying mechanisms in the tumorigenesis of lung adenocarcinoma (LUAD) have not b...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.12.005

    authors: Wang Z,Fang Z,Chen G,Liu B,Xu J,Li F,Li F,Liu H,Zhang H,Sun Y,Tian G,Chen H,Xu G,Zhang L,Hu L,Ji H

    更新日期:2021-02-01 00:00:00

  • Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of a novel histone deacetylase inhibitor, LAQ824, in human colon carcinoma cells and xenografts.

    abstract::The aim of this work was to use phosphorus magnetic resonance spectroscopy ((31)P MRS) to investigate the pharmacodynamic effects of LAQ824, a histone deacetylase (HDAC) inhibitor. Human HT29 colon carcinoma cells were examined by (31)P MRS after treatment with LAQ824 and another HDAC inhibitor, suberoylanilide hydrox...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07834

    authors: Chung YL,Troy H,Kristeleit R,Aherne W,Jackson LE,Atadja P,Griffiths JR,Judson IR,Workman P,Leach MO,Beloueche-Babari M

    更新日期:2008-04-01 00:00:00

  • In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatment with trastuzumab/erlotinib or lapatinib alone: implication of receptors' down-regulation and dimers' disruption.

    abstract::We previously demonstrated the synergistic therapeutic effect of the cetuximab (anti-epidermal growth factor receptor [EGFR] monoclonal antibody, mAb)-trastuzumab (anti-HER2 mAb) combination (2mAbs therapy) in HER2(low) human pancreatic carcinoma xenografts. Here, we compared the 2mAbs therapy, the erlotinib (EGFR tyr...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.111602

    authors: Larbouret C,Gaborit N,Chardès T,Coelho M,Campigna E,Bascoul-Mollevi C,Mach JP,Azria D,Robert B,Pèlegrin A

    更新日期:2012-02-01 00:00:00

  • Noninvasive Bioluminescence Imaging of AKT Kinase Activity in Subcutaneous and Orthotopic NSCLC Xenografts: Correlation of AKT Activity with Tumor Growth Kinetics.

    abstract::Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung can...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.02.005

    authors: Suchowski K,Pöschinger T,Rehemtulla A,Stürzl M,Scheuer W

    更新日期:2017-04-01 00:00:00

  • Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients.

    abstract::The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR ta...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.02.011

    authors: Xiao Z,Gaertner S,Morresi-Hauf A,Genzel R,Duell T,Ullrich A,Knyazev PG

    更新日期:2017-05-01 00:00:00