Antagonism of VEGF by genetically engineered dendritic cells is essential to induce antitumor immunity against malignant ascites.

Abstract:

:Malignant ascitis (MA) is a highly intractable and immunotherapy-resistant state of advanced gastrointestinal and ovarian cancers. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryrosine kinase receptor-1 (sFLT-1), was a major cause of MA resistance to dendritic cell (DC)-based immunotherapy. We found that the ratio of VEGF-A/sFLT-1 was increased not only in murine but also in human MA, and F-gene-deleted recombinant Sendai virus (rSeV/dF)-mediated secretion of human sFLT-1 by DCs augmented not only the activity of DCs themselves, but also dramatically improved the survival of tumor-bearing animals associated with enhanced CTL activity and its infiltration to peritoneal tumors. These findings were not seen in immunodeficient mice, indicating that a VEGF-A/sFLT-1 imbalance is critical for determining the antitumor immune response by DC-vaccination therapy against MA.

journal_name

Mol Cancer Ther

authors

Sugiyama M,Kakeji Y,Tsujitani S,Harada Y,Onimaru M,Yoshida K,Tanaka S,Emi Y,Morita M,Morodomi Y,Hasegawa M,Maehara Y,Yonemitsu Y

doi

10.1158/1535-7163.MCT-10-0479

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

540-9

issue

3

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-10-0479

journal_volume

10

pub_type

杂志文章
  • p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR.

    abstract::High Mycoplasma infection in gastric cancer tissues suggests a possible association between Mycoplasma infection and tumorigenesis. By using human gastric cancer cells AGS and mouse melanoma cells B16F10 stably expressing p37, the major immunogen of Mycoplasma hyorhinis, we found that p37 enhanced cell motility, migra...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-07-2191

    authors: Gong M,Meng L,Jiang B,Zhang J,Yang H,Wu J,Shou C

    更新日期:2008-03-01 00:00:00

  • Synergistic antitumor effect of S-1 and HER2-targeting agents in gastric cancer with HER2 amplification.

    abstract::Amplification of human epidermal growth factor receptor 2 (HER2) has been detected in 20% to 30% of gastric cancers and is associated with a poor outcome. Combination therapies with HER2-targeting agents and cytotoxic agents are considered a potential therapeutic option for gastric cancer with HER2 amplification. We h...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-10-0045

    authors: Tanizaki J,Okamoto I,Takezawa K,Tsukioka S,Uchida J,Kiniwa M,Fukuoka M,Nakagawa K

    更新日期:2010-05-01 00:00:00

  • Insulin-like growth factor-I receptor tyrosine kinase inhibitor cyclolignan picropodophyllin inhibits proliferation and induces apoptosis in multidrug resistant osteosarcoma cell lines.

    abstract::Insulin-like growth factor-I receptor (IGF-IR) is an important mediator of tumor cell survival and shows prognostic significance in sarcoma. To explore potential therapeutic strategies for interrupting signaling through this pathway, we assessed the ability of cyclolignan picropodophyllin (PPP), a member of the cyclol...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-0115

    authors: Duan Z,Choy E,Harmon D,Yang C,Ryu K,Schwab J,Mankin H,Hornicek FJ

    更新日期:2009-08-01 00:00:00

  • HMG-CoA Reductase Inhibition Delays DNA Repair and Promotes Senescence After Tumor Irradiation.

    abstract::Despite significant advances in combinations of radiotherapy and chemotherapy, altered fractionation schedules and image-guided radiotherapy, many cancer patients fail to benefit from radiation. A prevailing hypothesis is that targeting repair of DNA double strand breaks (DSB) can enhance radiation effects in the tumo...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0288

    authors: Efimova EV,Ricco N,Labay E,Mauceri HJ,Flor AC,Ramamurthy A,Sutton HG,Weichselbaum RR,Kron SJ

    更新日期:2018-02-01 00:00:00

  • Nordihydroguaiaretic acid, a cytotoxic insulin-like growth factor-I receptor/HER2 inhibitor in trastuzumab-resistant breast cancer.

    abstract::The majority of patients with HER2-overexpressing metastatic breast cancer who initially respond to the HER2-targeted antibody trastuzumab show disease progression within 1 year. The identification of novel agents that effectively inhibit survival of cancer cells that have progressed on trastuzumab is critical for imp...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0012

    authors: Rowe DL,Ozbay T,Bender LM,Nahta R

    更新日期:2008-07-01 00:00:00

  • Tumor-Associated Macrophages Can Contribute to Antitumor Activity through FcγR-Mediated Processing of Antibody-Drug Conjugates.

    abstract::The primary mechanism of antibody-drug conjugates (ADC) is targeted delivery of a cytotoxic payload to tumor cells via cancer-associated membrane receptors. However, the tumor microenvironment likely plays a role in ADC penetration, distribution, and processing and thus impacts the overall antitumor activity. Here, we...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0019

    authors: Li F,Ulrich M,Jonas M,Stone IJ,Linares G,Zhang X,Westendorf L,Benjamin DR,Law CL

    更新日期:2017-07-01 00:00:00

  • High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer cell and angiogenesis.

    abstract::The present study aimed to investigate the therapeutic efficacy of combining vascular endothelial growth factor (VEGF) receptor blockade using tyrosine kinase inhibitor PTK787 with hypoxia for the treatment of hepatocellular carcinoma (HCC). The in vivo effects of the treatments were determined in a rat orthotopic HCC...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-06-0149

    authors: Yang ZF,Poon RT,Liu Y,Lau CK,Ho DW,Tam KH,Lam CT,Fan ST

    更新日期:2006-09-01 00:00:00

  • Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity.

    abstract::Programmed cell death 4 (Pdcd4), originally identified as an inhibitor of murine cellular transformation, inhibits protein synthesis by directly interacting with eukaryotic initiation factor 4A (eIF4A) of the translation initiation complex. The relevance of Pdcd4 to a broad range of human cancers derived from multiple...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Jansen AP,Camalier CE,Stark C,Colburn NH

    更新日期:2004-02-01 00:00:00

  • Epidermal growth factor-like domain 7 predicts response to first-line chemotherapy and bevacizumab in patients with metastatic colorectal cancer.

    abstract::The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined with bevacizumab, in patients wit...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1158/1535-7163.MCT-14-0131

    authors: Hansen TF,Nielsen BS,Sørensen FB,Johnsson A,Jakobsen A

    更新日期:2014-09-01 00:00:00

  • TTK Inhibitors as a Targeted Therapy for CTNNB1 (β-catenin) Mutant Cancers.

    abstract::The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of chromosome segregation and is the subject of novel targeted therapy approaches by small-molecule inhibitors. Although the first TTK inhibitors have entered phase I dose escalating studies in combination with taxane chemotherapy, a patient stratifi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0342

    authors: Zaman GJR,de Roos JADM,Libouban MAA,Prinsen MBW,de Man J,Buijsman RC,Uitdehaag JCM

    更新日期:2017-11-01 00:00:00

  • Breast cancer-derived bone metastasis can be effectively reduced through specific c-MET inhibitor tivantinib (ARQ 197) and shRNA c-MET knockdown.

    abstract::Breast cancer exhibits a propensity to metastasize to bone, resulting in debilitating skeletal complications associated with significant morbidity and poor prognosis. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. We have shown the involvement...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-11-0277

    authors: Previdi S,Abbadessa G,Dalò F,France DS,Broggini M

    更新日期:2012-01-01 00:00:00

  • Targeting the Akt/mammalian target of rapamycin pathway for radiosensitization of breast cancer.

    abstract::The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to be activated by radiation. The mammalian target of rapamycin (mTOR) is downstream of Akt, and we investigated the effects of radiation on Akt/mTOR signaling in breast cancer cell models. RAD001 (everolimus), a potent derivative of the mTOR inhibitor rapa...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-05-0400

    authors: Albert JM,Kim KW,Cao C,Lu B

    更新日期:2006-05-01 00:00:00

  • Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer.

    abstract::Several studies have shown antitumor activities of the melanoma differentiation-associated gene 7 (mda-7) and the nonsteroidal anti-inflammatory drug sulindac when used as a monotherapies against a wide variety of human cancers. However, the combined effects of mda-7 and sulindac have not previously been tested. There...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Oida Y,Gopalan B,Miyahara R,Inoue S,Branch CD,Mhashilkar AM,Lin E,Bekele BN,Roth JA,Chada S,Ramesh R

    更新日期:2005-02-01 00:00:00

  • Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities.

    abstract::Betulinic acid (BA), a pentacyclic triterpene isolated from birch bark and other plants, selectively inhibits the growth of human cancer cell lines. However, the poor potency of BA hinders its clinical development, despite a lack of toxicity in animal studies even at high concentrations. Here, we describe six BA deriv...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-07-0180

    authors: Liby K,Honda T,Williams CR,Risingsong R,Royce DB,Suh N,Dinkova-Kostova AT,Stephenson KK,Talalay P,Sundararajan C,Gribble GW,Sporn MB

    更新日期:2007-07-01 00:00:00

  • Enhanced Antitumor Efficacy of Oncolytic Adenovirus-loaded Menstrual Blood-derived Mesenchymal Stem Cells in Combination with Peripheral Blood Mononuclear Cells.

    abstract::Several studies have evaluated the efficacy of using human oncolytic adenovirus (OAdv)-loaded mesenchymal stem cells (MSC) for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow-mesenchymal stem cells infected with the OAdv ICOVIR-5, for treatment of patients wit...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-18-0431

    authors: Moreno R,Fajardo CA,Farrera-Sal M,Perisé-Barrios AJ,Morales-Molina A,Al-Zaher AA,García-Castro J,Alemany R

    更新日期:2019-01-01 00:00:00

  • Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105.

    abstract::TRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasm...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0916

    authors: Liu Y,Starr MD,Brady JC,Rushing C,Pang H,Adams B,Alvarez D,Theuer CP,Hurwitz HI,Nixon AB

    更新日期:2018-10-01 00:00:00

  • Transduction of green fluorescent protein increased oxidative stress and enhanced sensitivity to cytotoxic drugs in neuroblastoma cell lines.

    abstract::Green fluorescent protein (GFP) is employed as a selection marker for gene transduction and to track tumor cells. Transduction of enhanced GFP (eGFP) into human neuroblastoma cell lines via a lentiviral vector significantly sensitized CHLA-20 (wild-type and functional TP53), and to a lesser extent CHLA-90 cells (multi...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Goto H,Yang B,Petersen D,Pepper KA,Alfaro PA,Kohn DB,Reynolds CP

    更新日期:2003-09-01 00:00:00

  • Ref-1/APE1 as a Transcriptional Regulator and Novel Therapeutic Target in Pediatric T-cell Leukemia.

    abstract::The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets but has yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pa...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0099

    authors: Ding J,Fishel ML,Reed AM,McAdams E,Czader MB,Cardoso AA,Kelley MR

    更新日期:2017-07-01 00:00:00

  • Dual PI3K/mTOR Inhibitors Induce Rapid Overactivation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2.

    abstract::The PI3K/AKT/mTOR pathway, which is aberrantly stimulated in many cancer cells, has emerged as a target for therapy. However, mTORC1/S6K also mediates negative feedback loops that attenuate upstream signaling. Suppression of these feedback loops opposes the growth-suppressive effects of mTOR inhibitors and leads to dr...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-14-0669

    authors: Soares HP,Ming M,Mellon M,Young SH,Han L,Sinnet-Smith J,Rozengurt E

    更新日期:2015-04-01 00:00:00

  • KD5170, a novel mercaptoketone-based histone deacetylase inhibitor, exerts antimyeloma effects by DNA damage and mitochondrial signaling.

    abstract::Histone deacetylase inhibitors have emerged as promising anticancer drugs. Using an unbiased ultrahigh throughput screening system, a novel mercaptoketone-based histone deacetylase inhibitor series was identified that was optimized to the lead compound, KD5170. KD5170 inhibited the proliferation of myeloma cell lines ...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0183

    authors: Feng R,Ma H,Hassig CA,Payne JE,Smith ND,Mapara MY,Hager JH,Lentzsch S

    更新日期:2008-06-01 00:00:00

  • A Spatio-Temporal Model of Macrophage-Mediated Drug Resistance in Glioma Immunotherapy.

    abstract::The emergence of drug resistance is often an inevitable obstacle that limits the long-term effectiveness of clinical cancer chemotherapeutics. Although various forms of cancer cell-intrinsic mechanisms of drug resistance have been experimentally revealed, the role and the underlying mechanism of tumor microenvironment...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0634

    authors: Zheng Y,Bao J,Zhao Q,Zhou T,Sun X

    更新日期:2018-04-01 00:00:00

  • Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer.

    abstract::Our previous studies and those of others have indicated that X-linked inhibitor of apoptosis protein (XIAP) holds promise as a target gene in colon cancer gene therapy. In this study, we constructed an adenoviral vector to deliver small hairpin RNA (shRNA) against XIAP (XIAP-shRNA) into colon cancer cells and tested i...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-0509

    authors: Dai Y,Qiao L,Chan KW,Yang M,Ye J,Zhang R,Ma J,Zou B,Lam CS,Wang J,Pang R,Tan VP,Lan HY,Wong BC

    更新日期:2009-09-01 00:00:00

  • ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo.

    abstract::ABT-263 is a potent, orally bioavailable inhibitor of the antiapoptotic Bcl-2 family members Bcl-2, Bcl-x(L), and Bcl-w, which is currently in phase I clinical trials. Previous work has shown that this compound has low nanomolar cell-killing activity in a variety of lymphoma and leukemia cell lines, many of which over...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-08-0268

    authors: Ackler S,Xiao Y,Mitten MJ,Foster K,Oleksijew A,Refici M,Schlessinger S,Wang B,Chemburkar SR,Bauch J,Tse C,Frost DJ,Fesik SW,Rosenberg SH,Elmore SW,Shoemaker AR

    更新日期:2008-10-01 00:00:00

  • Therapeutic Targeting of miR-29b/HDAC4 Epigenetic Loop in Multiple Myeloma.

    abstract::Epigenetic abnormalities are common in hematologic malignancies, including multiple myeloma, and their effects can be efficiently counteracted by a class of tumor suppressor miRNAs, named epi-miRNAs. Given the oncogenic role of histone deacetylases (HDAC) in multiple myeloma, we investigated whether their activity cou...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-15-0985

    authors: Amodio N,Stamato MA,Gullà AM,Morelli E,Romeo E,Raimondi L,Pitari MR,Ferrandino I,Misso G,Caraglia M,Perrotta I,Neri A,Fulciniti M,Rolfo C,Anderson KC,Munshi NC,Tagliaferri P,Tassone P

    更新日期:2016-06-01 00:00:00

  • TWIST1 Polymorphisms Predict Survival in Patients with Metastatic Colorectal Cancer Receiving First-Line Bevacizumab plus Oxaliplatin-Based Chemotherapy.

    abstract::The epithelial-mesenchymal transition (EMT) is an important mechanism of resistance to angiogenesis inhibition. The ability of EMT pathway genetic variants to predict the efficacy of antiangiogenic therapy is unknown. We analyzed associations between functional SNPs in EMT-related genes and outcomes in metastatic colo...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-15-0751

    authors: Matsusaka S,Zhang W,Cao S,Hanna DL,Sunakawa Y,Sebio A,Ueno M,Yang D,Ning Y,Parekh A,Okazaki S,Berger MD,Ichikawa W,Mizunuma N,Lenz HJ

    更新日期:2016-06-01 00:00:00

  • Interstitial gene delivery in human xenograft prostate tumors using titanium metal seeds.

    abstract::Gene therapy is a promising approach for the treatment of cancers. Strategies for gene vector delivery include systemic and local-regional approaches. Intratumoral delivery of vectors has generally employed direct injections into single or multiple locations throughout the tumor volume. However, this approach leads to...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:

    authors: Jung M,Zhang Y,Dimtchev A,Subramanian MR,Suthanthiran K,Dritschilo A

    更新日期:2004-06-01 00:00:00

  • CCR5-Dependent Homing of T Regulatory Cells to the Tumor Microenvironment Contributes to Skin Squamous Cell Carcinoma Development.

    abstract::Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selec...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-17-0341

    authors: de Oliveira CE,Gasparoto TH,Pinheiro CR,Amôr NG,Nogueira MRS,Kaneno R,Garlet GP,Lara VS,Silva JS,Cavassani KA,Campanelli AP

    更新日期:2017-12-01 00:00:00

  • Cell-penetrating TAT-FOXO3 fusion proteins induce apoptotic cell death in leukemic cells.

    abstract::FOXO proteins are Akt-regulated transcription factors involved in the control of cell cycle, DNA repair, stress defense, apoptosis, and tumor suppression. We reported that plasmid-based overexpression of constitutively active FOXO3 in cells from chronic lymphocytic leukemia (CLL) reduced their survival, suggesting tha...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-10-0482

    authors: Essafi M,Baudot AD,Mouska X,Cassuto JP,Ticchioni M,Deckert M

    更新日期:2011-01-01 00:00:00

  • Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines.

    abstract::The effect of vascular endothelial growth factor (VEGF) ligands and cediranib on tumor cell proliferation, migration, and invasion was determined. It has recently been suggested that autocrine signaling through the VEGF receptor (VEGFR) pathway may play a role in tumor cell survival, invasion, and migration. The purpo...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-0380

    authors: Morelli MP,Brown AM,Pitts TM,Tentler JJ,Ciardiello F,Ryan A,Jürgensmeier JM,Eckhardt SG

    更新日期:2009-09-01 00:00:00

  • Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin.

    abstract::Luteolin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of preventive and/or therapeutic agent for cancers. E-cadherin, a marker of epithelial cells, mediates cell-cell adhesion. Decreased expression of E-cadherin results in a loss of c...

    journal_title:Molecular cancer therapeutics

    pub_type: 杂志文章

    doi:10.1158/1535-7163.MCT-09-0191

    authors: Zhou Q,Yan B,Hu X,Li XB,Zhang J,Fang J

    更新日期:2009-06-01 00:00:00