Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo.

Abstract:

:A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at different stages of disease and following therapy. We developed and assessed a novel method for monitoring the T-cell receptor (TCR)-dependent nuclear factor of activated T cells (NFAT)-mediated activation of T cells by optical fluorescence imaging (OFI) and positron emission tomography (PET). The herpes simplex virus type 1 thymidine kinase/green fluorescent protein [HSV1-tk/GFP (TKGFP)] dual reporter gene was used to monitor NFAT-mediated transcriptional activation in human Jurkat cells. A recombinant retrovirus bearing the NFAT-TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting NFAT-specific enhancer. Transduced Jurkat cells were used to establish subcutaneous infiltrates in nude rats. We demonstrated that noninvasive OFI and nuclear imaging of T-cell activation is feasible using the NFAT-TKGFP reporter system. PET imaging with [(124)I]FIAU using the NFAT-TKGFP reporter system is sufficiently sensitive to detect T-cell activation in vivo. PET images were confirmed by independent measurements of T-cell activation (e.g., CD69) and induction of GFP fluorescence. PET imaging of TCR-induced NFAT-dependent transcriptional activity may be useful in the assessment of T cell responses, T-cell-based adoptive therapies, vaccination strategies and immunosuppressive drugs.

journal_name

Neoplasia

authors

Ponomarev V,Doubrovin M,Lyddane C,Beresten T,Balatoni J,Bornman W,Finn R,Akhurst T,Larson S,Blasberg R,Sadelain M,Tjuvajev JG

doi

10.1038/sj.neo.7900204

keywords:

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

480-8

issue

6

eissn

1522-8002

issn

1476-5586

journal_volume

3

pub_type

杂志文章
  • In vivo selection and characterization of metastatic variants from human pancreatic adenocarcinoma by using orthotopic implantation in nude mice.

    abstract::We determined whether the implantation of human pancreatic cancer cells into the pancreas of nude mice can be used to select variants with increasing metastatic potential. COLO 357 line fast-growing cells were injected into the spleen or pancreas of nude mice. Hepatic metastases were harvested, and tumor cells were re...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900005

    authors: Bruns CJ,Harbison MT,Kuniyasu H,Eue I,Fidler IJ

    更新日期:1999-04-01 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

  • 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

  • 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

  • Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma.

    abstract::We characterized the molecular genetic consequences of a balanced chromosome translocation t(8;22)(p21;q12), which occurred as the sole cytogenetic aberration in short-term cultured cells from an intrathoracic mature teratoma in a 15-year-old girl. Fluorescence in situ hybridization and reverse transcription-polymeras...

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

    pub_type: 杂志文章

    doi:10.1593/neo.06139

    authors: Jin Y,Mertens F,Kullendorff CM,Panagopoulos I

    更新日期:2006-05-01 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

  • 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

  • Cellular basis of antiproliferative and antitumor activity of the novel camptothecin derivative, gimatecan, in bladder carcinoma models.

    abstract::To investigate the cellular/molecular basis of the activity of a novel lipophilic camptothecin, gimatecan (ST1481), against slowly proliferating cells, we performed a comparative study of topotecan and gimatecan in human bladder cancer models (HT1376 and MCR). Gimatecan was significantly more effective than topotecan ...

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

    pub_type: 杂志文章

    doi:10.1593/neo.04397

    authors: Ulivi P,Zoli W,Fabbri F,Brigliadori G,Ricotti L,Tesei A,Rosetti M,De Cesare M,Beretta GL,Corna E,Supino R,Zunino F

    更新日期:2005-02-01 00:00:00

  • Tel, a frequent target of leukemic translocations, induces cellular aggregation and influences expression of extracellular matrix components.

    abstract::Tel is an Ets transcription factor that is the target of chromosome translocations in lymphoid and myeloid leukemias and in solid tumors. It contains two functional domains, a pointed oligomerization domain and a DNA-binding domain. Retroviral transduction of a wild-type Tel cDNA into a clonal subline of NIH3T3 fibrob...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900064

    authors: Van Rompaey L,Dou W,Buijs A,Grosveld G

    更新日期:1999-12-01 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

  • Generation and characterization of novel local and metastatic human neuroblastoma variants.

    abstract::Neuroblastoma (NB) is the most commonly occurring solid tumor in children. The disease usually arises in the adrenal medulla, and it is characterized by a remarkable heterogeneity in its progression. Most NB patients with an advanced disease have massive bone marrow infiltration at diagnosis. Lung metastasis represent...

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

    pub_type: 杂志文章

    doi:10.1593/neo.08402

    authors: Nevo I,Sagi-Assif O,Edry Botzer L,Amar D,Maman S,Kariv N,Leider-Trejo LE,Savelyeva L,Schwab M,Yron I,Witz IP

    更新日期:2008-08-01 00:00:00

  • Accelerated degradation of caspase-8 protein correlates with TRAIL resistance in a DLD1 human colon cancer cell line.

    abstract::The tumor-selective cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) makes TRAIL an attractive candidate as an anticancer agent. However, resistance to TRAIL poses a challenge in anticancer therapy with TRAIL. Therefore, characterizing the mechanisms of resistance and developing stra...

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

    pub_type: 杂志文章

    doi:10.1593/neo.04688

    authors: Zhang L,Zhu H,Teraishi F,Davis JJ,Guo W,Fan Z,Fang B

    更新日期:2005-06-01 00:00:00

  • CD4+ and CD8+ T-cell skewness in classic Kaposi sarcoma.

    abstract::It is widely accepted that a deranged immune system plays a key role in the onset and evolution of classic Kaposi sarcoma (CKS). Nevertheless, the usage of the T-cell receptor (TCR) β-variable (BV) chain repertoire expressed by peripheral blood lymphocytes in patients with CKS is still unknown. With the aim of providi...

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

    pub_type: 杂志文章

    doi:10.1596/neo.11646

    authors: Galleu A,Fozza C,Simula MP,Contini S,Virdis P,Corda G,Pardini S,Cottoni F,Pruneddu S,Angeloni A,Ceccarelli S,Longinotti M

    更新日期:2012-06-01 00:00:00

  • Genome-wide screening of genes showing altered expression in liver metastases of human colorectal cancers by cDNA microarray.

    abstract::In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analy...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900185

    authors: Yanagawa R,Furukawa Y,Tsunoda T,Kitahara O,Kameyama M,Murata K,Ishikawa O,Nakamura Y

    更新日期:2001-09-01 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

  • Targeting Liver Cancer and Associated Pathologies in Mice with a Mitochondrial VDAC1-Based Peptide.

    abstract::Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. Despite progress in identifying risk factors, the incidence of HCC is increasing. Moreover, therapeutic options are limited and survival is poor. Therefore, alternative and innovative therapeutic strategies are urgently required. R-Tf-D-LP4, a c...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.02.012

    authors: Pittala S,Krelin Y,Shoshan-Barmatz V

    更新日期:2018-06-01 00:00:00

  • Identification and characterization of CD44RC, a novel alternatively spliced soluble CD44 isoform that can potentiate the hyaluronan binding activity of cell surface CD44.

    abstract::Soluble CD44 proteins generated by proteolytic cleavage or aberrant intron retention have been shown to antagonize the ligand binding activity of the corresponding cell surface receptor, inducing apoptosis and inhibiting tumor growth. Interestingly, such findings appear to contradict recent studies demonstrating a cor...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900045

    authors: Chiu RK,Carpenito C,Dougherty ST,Hayes GM,Dougherty GJ

    更新日期:1999-11-01 00:00:00

  • A Pre-Clinical Assessment of the Pan-ERBB Inhibitor Dacomitinib in Pediatric and Adult Brain Tumors.

    abstract::Glioblastoma in adults, and medulloblastoma and pineoblastoma that mainly affect children, are aggressive brain tumors. The survival for patients with glioblastoma remains dismal. While the cure rate for medulloblastoma exceeds 70%, this figure has stagnated over the past few decades and survivors still contend with s...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.02.004

    authors: Endersby R,Whitehouse J,Hii H,Greenall SA,Johns TG,Gottardo NG

    更新日期:2018-05-01 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

  • Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes.

    abstract::Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles f...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2020.11.001

    authors: Fernández-Blanco B,Berbegall AP,Martin-Vañó S,Castel V,Navarro S,Noguera R

    更新日期:2021-01-01 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

  • Detection of colorectal adenomas using a bioactivatable probe specific for matrix metalloproteinase activity.

    abstract::A significant proportion of colorectal adenomas, in particular those that lack an elevated growth component, continue to escape detection during endoscopic surveillance. Elevation of the activity of matrix metalloproteinases (MMPs), a large family of zinc endopeptidases, in adenomas serves as a biomarker of early tumo...

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

    pub_type: 杂志文章

    doi:10.1593/neo.11400

    authors: Clapper ML,Hensley HH,Chang WC,Devarajan K,Nguyen MT,Cooper HS

    更新日期:2011-08-01 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

  • Bcl-2-enhanced efficacy of microtubule-targeting chemotherapy through Bim overexpression: implications for cancer treatment.

    abstract::Bcl-2 is commonly overexpressed in tumors, where it is often associated with unfavorable outcome. However, it has also been linked to a favorable sensitivity to microtubule-targeting agents (MTAs). We show that Bcl-2-overexpressing lung and breast cancer cells were more sensitive to both paclitaxel and vinorelbine. Bc...

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

    pub_type: 杂志文章

    doi:10.1593/neo.121074

    authors: Savry A,Carre M,Berges R,Rovini A,Pobel I,Chacon C,Braguer D,Bourgarel-Rey V

    更新日期:2013-01-01 00:00:00

  • Heightened expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-delta in human endometrial adenocarcinoma.

    abstract::Epidemiological studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduce the risk and mortality from colorectal cancer, in part by inhibiting prostaglandin (PG) synthesis. Cyclooxygenase (COX), the rate-limiting enzyme in PG biosynthesis, exists in two isoforms, COX-1 and COX-2. Genetic...

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

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900119

    authors: Tong BJ,Tan J,Tajeda L,Das SK,Chapman JA,DuBois RN,Dey SK

    更新日期:2000-11-01 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

  • GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche.

    abstract::Our recent studies have shown that annexin II, expressed on the cell surface of osteoblasts, plays an important role in the adhesion of hematopoietic stem cells (HSCs) to the endosteal niche. Similarly, prostate cancer (PCa) cells express the annexin II receptor and seem to use the stem cell niche for homing to the bo...

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

    pub_type: 杂志文章

    doi:10.1593/neo.91384

    authors: Shiozawa Y,Pedersen EA,Patel LR,Ziegler AM,Havens AM,Jung Y,Wang J,Zalucha S,Loberg RD,Pienta KJ,Taichman RS

    更新日期:2010-02-01 00:00:00

  • A Novel Method for Quantifying Total Thoracic Tumor Burden in Mice.

    abstract::Mouse models are powerful tools to study lung cancer initiation and progression in vivo and have contributed significantly to recent advances in therapy. Using micro-computed tomography to monitor and study parenchymal and extra-parenchymal metastases in existing murine models of lung cancer is challenging owing to a ...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.08.003

    authors: Viswanath P,Peng S,Singh R,Kingsley C,Balter PA,Johnson FM

    更新日期:2018-10-01 00:00:00

  • Improved clearance during treatment of HPV-positive head and neck cancer through mTOR inhibition.

    abstract::Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) incidence is increasing at a near epidemic rate. We investigated whether the mammalian (or mechanistic) target of rapamycin (mTOR) inhibitor, rapamycin, can be used as a concurrent agent to standard-of-care cisplatin/radiation therapy (CR...

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

    pub_type: 杂志文章

    doi:10.1593/neo.13432

    authors: Coppock JD,Wieking BG,Molinolo AA,Gutkind JS,Miskimins WK,Lee JH

    更新日期:2013-06-01 00:00:00

  • CTHRC1 acts as a prognostic factor and promotes invasiveness of gastrointestinal stromal tumors by activating Wnt/PCP-Rho signaling.

    abstract::Gastrointestinal stromal tumors (GISTs) are the major gastrointestinal mesenchymal tumors with a variable malignancy ranging from a curable disorder to highly malignant sarcomas. Metastasis and recurrence are the main causes of death in GIST patients. To further explore the mechanism of metastasis and to more accurate...

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

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.03.001

    authors: Ma MZ,Zhuang C,Yang XM,Zhang ZZ,Ma H,Zhang WM,You H,Qin W,Gu J,Yang S,Cao H,Zhang ZG

    更新日期:2014-03-01 00:00:00