Hypoxia-inducible regulation of a prodrug-activating enzyme for tumor-specific gene therapy.

Abstract:

:Previous studies have suggested that tumor hypoxia could be exploited for cancer gene therapy. Using hypoxia-responsive elements derived from the human vascular endothelial growth factor gene, we have generated vectors expressing a bacterial nitroreductase (NTR) gene that can activate the anticancer prodrug CB1954. Stable transfectants of human HT1080 tumor cells with hypoxia-inducible vectors were established with G418 selection. Hypoxic induction of NTR protein correlated with increased sensitivity to in vitro exposure of HT1080 cells to the prodrug. Growth delay assays were performed with established tumor xenografts derived from the same cells to detect the in vivo efficacy of CB1954 conversion to its cytotoxic form. Significant antitumor effects were achieved with intraperitoneal injections of CB1954 both in tumors that express NTR constitutively or with a hypoxia-inducible promoter. In addition, respiration of 10% 02 increased tumor hypoxia in vivo and enhanced the antitumor effects. Taken together, these results demonstrate that hypoxia-inducible vectors may be useful for tumor-selective gene therapy, although the problem of delivery of the vector to the tumors, particularly to the hypoxic cells in the tumors, is not addressed by these studies.

journal_name

Neoplasia

authors

Shibata T,Giaccia AJ,Brown JM

doi

10.1038/sj.neo.7900189

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

40-8

issue

1

eissn

1522-8002

issn

1476-5586

journal_volume

4

pub_type

杂志文章
  • 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

  • Cytokines and chemokines are expressed at different levels in small and large murine colon-26 tumors following intratumoral injections of CpG ODN.

    abstract::Direct tumor injections of (CpG ODN) into murine colon tumor 26 (CT-26) tumors can induce a potent antitumor response. Tumor size at the beginning of treatment determines the final therapeutic outcome, with smaller tumors responding favorably to CpG ODN therapy whereas large tumors do not. CpG ODN injections in small ...

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

    pub_type: 杂志文章

    doi:10.1593/neo.04166

    authors: Sharma S,Karakousis CP,Takita H,Shin K,Brooks SP

    更新日期:2004-09-01 00:00:00

  • JAK kinase inhibition abrogates STAT3 activation and head and neck squamous cell carcinoma tumor growth.

    abstract::Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC). AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in seve...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.01.003

    authors: Sen M,Pollock NI,Black J,DeGrave KA,Wheeler S,Freilino ML,Joyce S,Lui VW,Zeng Y,Chiosea SI,Grandis JR

    更新日期:2015-03-01 00:00:00

  • Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells.

    abstract::Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breas...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900229

    authors: Oh JS,Kucab JE,Bushel PR,Martin K,Bennett L,Collins J,DiAugustine RP,Barrett JC,Afshari CA,Dunn SE

    更新日期:2002-05-01 00:00:00

  • Functional coexpression of HSV-1 thymidine kinase and green fluorescent protein: implications for noninvasive imaging of transgene expression.

    abstract::Current gene therapy technology is limited by the paucity of methodology for determining the location and magnitude of therapeutic transgene expression in vivo. We describe and validate a paradigm for monitoring therapeutic transgene expression by noninvasive imaging of the herpes simplex virus type 1 thymidine kinase...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900007

    authors: Jacobs A,Dubrovin M,Hewett J,Sena-Esteves M,Tan CW,Slack M,Sadelain M,Breakefield XO,Tjuvajev JG

    更新日期:1999-06-01 00:00:00

  • 15-lipoxygenase-1 production is lost in pancreatic cancer and overexpression of the gene inhibits tumor cell growth.

    abstract::Pancreatic cancer patients have an abysmal prognosis because of late diagnosis and lack of therapeutic options. Pancreatic intraepithelial neoplasias (PanINs), the precursor lesions, are a potential target for chemoprevention. Targeting eicosanoid pathways is an obvious choice because 5-lipoxygenase (5-LOX) has been s...

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

    pub_type: 杂志文章

    doi:10.1593/neo.07565

    authors: Hennig R,Kehl T,Noor S,Ding XZ,Rao SM,Bergmann F,Fürstenberger G,Büchler MW,Friess H,Krieg P,Adrian TE

    更新日期:2007-11-01 00:00:00

  • Chronic pancreatitis and systemic inflammatory response syndrome prevent impact of chemotherapy with gemcitabine in a genetically engineered mouse model of pancreatic cancer.

    abstract:BACKGROUND AND AIMS:BACKGROUND AND AIMSGemcitabine is the standard therapy for patients with pancreatic cancer with metastatic disease. Patients with metastatic pancreatic cancer presenting with increased values of C-reactive protein do not respond to gemcitabine. So far, no studies have evaluated the correlation betwe...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.05.010

    authors: Knoop RF,Sparn M,Waldmann J,Plassmeier L,Bartsch DK,Lauth M,Hudemann C,Fendrich V

    更新日期:2014-06-01 00:00:00

  • Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells.

    abstract::BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFV600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactiva...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.02.009

    authors: Mologni L,Costanza M,Sharma GG,Viltadi M,Massimino L,Citterio S,Purgante S,Raman H,Pirola A,Zucchetti M,Piazza R,Gambacorti-Passerini C

    更新日期:2018-05-01 00:00:00

  • N-myc downstream regulated gene 1 (NDRG1) is fused to ERG in prostate cancer.

    abstract::A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation-specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal o...

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

    pub_type: 杂志文章

    doi:10.1593/neo.09572

    authors: Pflueger D,Rickman DS,Sboner A,Perner S,LaFargue CJ,Svensson MA,Moss BJ,Kitabayashi N,Pan Y,de la Taille A,Kuefer R,Tewari AK,Demichelis F,Chee MS,Gerstein MB,Rubin MA

    更新日期:2009-08-01 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

  • 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

  • PI3K/Akt pathway activation attenuates the cytotoxic effect of methyl jasmonate toward sarcoma cells.

    abstract::Methyl jasmonate (MJ) acts both in vitro and in vivo against various cancer cell lines. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway results in decreased susceptibility to cytotoxic agents in many types of cancer cells. We found a strong inverse correlation between the basal level of phospho-Akt ...

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

    pub_type: 杂志文章

    doi:10.1593/neo.08636

    authors: Elia U,Flescher E

    更新日期:2008-11-01 00:00:00

  • Strain background determines lymphoma incidence in Atm knockout mice.

    abstract::About 10% to 30% of patients with ataxia-telangiectasia (A-T) develop leukemias or lymphomas. There is considerable interpatient variation in the age of onset and leukemia/lymphoma type. The incomplete penetrance and variable age of onset may be attributable to several factors. These include competing mortality from o...

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

    pub_type: 杂志文章

    doi:10.1593/neo.131980

    authors: Genik PC,Bielefeldt-Ohmann H,Liu X,Story MD,Ding L,Bush JM,Fallgren CM,Weil MM

    更新日期:2014-02-01 00:00:00

  • Fibrin Deposit on the Peritoneal Surface Serves as a Niche for Cancer Expansion in Carcinomatosis Patients.

    abstract::Peritoneal metastasis (PM) is a very serious complication of gastrointestinal and gynecological malignancies which is poorly documented. Modified mesothelial cell layer and their microenvironments can favor fibrin deposition for cancer cell adhesion. Scanning and transmission electron microscopy of peritoneal surface ...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.08.006

    authors: Shahid S,Iman A,Matti U,Rachid K,Assaf A,Eveno C,Marc P,Massoud M

    更新日期:2019-11-01 00:00:00

  • Surface expression of precursor N-cadherin promotes tumor cell invasion.

    abstract::The expression of N-cadherin (NCAD) has been shown to correlate with increased tumor cell motility and metastasis. However, NCAD-mediated adhesion is a robust phenomenon and therefore seems to be inconsistent with the "release" from intercellular adhesion required for invasion. We show that in the most invasive melano...

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

    pub_type: 杂志文章

    doi:10.1593/neo.10954

    authors: Maret D,Gruzglin E,Sadr MS,Siu V,Shan W,Koch AW,Seidah NG,Del Maestro RF,Colman DR

    更新日期:2010-12-01 00:00:00

  • Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma.

    abstract::Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and ...

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

    pub_type: 杂志文章

    doi:10.1593/neo.91122

    authors: Nakahara Y,Northcott PA,Li M,Kongkham PN,Smith C,Yan H,Croul S,Ra YS,Eberhart C,Huang A,Bigner D,Grajkowska W,Van Meter T,Rutka JT,Taylor MD

    更新日期:2010-01-01 00:00:00

  • Interdependence of gemcitabine treatment, transporter expression, and resistance in human pancreatic carcinoma cells.

    abstract::Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU) alters the cellular transporter expression profile and that modulation of the exp...

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

    pub_type: 杂志文章

    doi:10.1593/neo.10576

    authors: Hagmann W,Jesnowski R,Löhr JM

    更新日期:2010-09-01 00:00:00

  • DNA repair gene polymorphisms may be associated with prognosis of upper urinary tract transitional cell carcinoma.

    abstract::Upper urinary tract transitional cell carcinoma (UUT-TCC) is quite an uncommon disease, and its prognosis differs among individuals irrespective of tumor stage. DNA repair gene polymorphisms are reported to result in the modulation of the repair capacity and might influence the prognosis of UUT-TCC. We examined the as...

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

    pub_type: 杂志文章

    doi:10.1593/neo.07982

    authors: Sasaki M,Sakano S,Okayama N,Akao J,Hara T,Kawai Y,Ohmi C,Hinoda Y,Naito K

    更新日期:2008-03-01 00:00:00

  • Diffusion-weighted magnetic resonance imaging allows noninvasive in vivo monitoring of the effects of combretastatin a-4 phosphate after repeated administration.

    abstract::The noninvasive assessment of anticancer treatment efficacy is very important for the improvement of therapeutic window. The purpose of the present study was to evaluate the antitumoral effects of the vascular targeting agent, combretastatin A-4 phosphate (CA-4-P), at selected time points after repeated intraperitonea...

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

    pub_type: 杂志文章

    doi:10.1593/neo.04748

    authors: Thoeny HC,De Keyzer F,Chen F,Vandecaveye V,Verbeken EK,Ahmed B,Sun X,Ni Y,Bosmans H,Hermans R,van Oosterom A,Marchal G,Landuyt W

    更新日期:2005-08-01 00:00:00

  • Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia.

    abstract::Anoikis, a cell death mechanism triggered upon cell-matrix detachment, is regarded as a physiological suppressor of metastasis that can be regulated by a diverse array of signals. The protein encoded by GDF2 is BMP9 and is a member of the bone morphogenetic protein family and the transforming growth factor (TGF) β sup...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.11.003

    authors: Varadaraj A,Patel P,Serrao A,Bandyopadhay T,Lee NY,Jazaeri AA,Huang Z,Murphy SK,Mythreye K

    更新日期:2015-11-01 00:00:00

  • Mutational analysis of DBD*--a unique antileukemic gene sequence.

    abstract::DBD* is a novel gene encoding an 89 amino acid peptide that is constitutively lethal to leukemic cells. DBD* was derived from the DNA binding domain of the human glucocorticoid receptor by a frameshift that replaces the final 21 C-terminal amino acids of the domain. Previous studies suggested that DBD* no longer acted...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900253

    authors: Ji YS,Johnson BH,Webb MS,Thompson EB

    更新日期:2002-09-01 00:00:00

  • Telomere length on chromosome 17q shortens more than global telomere length in the development of breast cancer.

    abstract::It is known that total telomere length is shorter in invasive breast cancer than in normal breast tissue but the status of individual telomere lengths has not been studied. Part of the difficulty is that usually telomere length in interphase cells is measured on all chromosomes together. In this study we compared norm...

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

    pub_type: 杂志文章

    doi:10.1593/neo.07106

    authors: Rashid-Kolvear F,Pintilie M,Done SJ

    更新日期:2007-04-01 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

  • Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation.

    abstract::Inhibitors of histone deacetylases have been shown to enhance the sensitivity of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand TRAIL-mediated cytotoxicity. Valproic acid (VA), a commonly used antiepileptic agent whose pharmacokinetics and toxicity profiles are well described, is a histone dea...

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

    pub_type: 杂志文章

    doi:10.1593/neo.05823

    authors: Ziauddin MF,Yeow WS,Maxhimer JB,Baras A,Chua A,Reddy RM,Tsai W,Cole GW Jr,Schrump DS,Nguyen DM

    更新日期:2006-06-01 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

  • 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

  • BJ-TSA-9, a novel human tumor-specific gene, has potential as a biomarker of lung cancer.

    abstract::Using bioinformatics, we have identified a novel tumor-specific gene BJ-TSA-9, which has been validated by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). BJ-TSA-9 mRNA was expressed in 52.5% (21 of 40) of human lung cancer tissues and was especially higher in lung adenocarcinoma (...

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

    pub_type: 杂志文章

    doi:10.1593/neo.05406

    authors: Li Y,Dong X,Yin Y,Su Y,Xu Q,Zhang Y,Pang X,Zhang Y,Chen W

    更新日期:2005-12-01 00:00:00

  • Targeting AGTR1/NF-κB/CXCR4 axis by miR-155 attenuates oncogenesis in glioblastoma.

    abstract::Glioblastoma (GBM) represents the most aggressive malignancy of the central nervous system. Increased expression of Angiotensin II Receptor Type 1 (AGTR1) has been associated with proliferative and infiltrative properties of glioma cells. However, the underlying mechanism of AGTR1 upregulation in GBM is still unexplor...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.08.002

    authors: Singh A,Srivastava N,Yadav A,Ateeq B

    更新日期:2020-10-01 00:00:00

  • Tracking the migration of dendritic cells by in vivo optical imaging.

    abstract::We report herein a method to track the migration of dendritic cells (DCs) using optical imaging. With the assistance of the delivery module, fluorescein isothiocyanate (FITC) could internalize inside DCs within 15 minutes of incubation. The fluorescent signal was mostly cytoplasmic and could be detected using in vivo ...

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

    pub_type: 杂志文章

    doi:10.1593/neo.07586

    authors: Pham W,Xie J,Gore JC

    更新日期:2007-12-01 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