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 (HSV-1-tk) marker gene expression. To test proportional coexpression of therapeutic and marker genes, a model fusion gene comprising green fluorescent protein (gfp) and HSV-1-tk genes was generated (tkgfp gene) and assessed for the functional coexpression of the gene product, TKGFP fusion protein, in rat 9L gliosarcoma, RG2 glioma, and W256 carcinoma cells. Analysis of the TKGFP protein demonstrated that it can serve as a therapeutic gene by rendering tkgfp transduced cells sensitive to ganciclovir or as a screening marker useful for identifying transduced cells by fluorescence microscopy or fluorescence-activated cell sorting (FACS). TK and GFP activities in the TKGFP fusion protein were similar to corresponding wild-type proteins and accumulation of the HSV-1-tk-specific radiolabeled substrate, 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodo-uracil (FIAU), in stability transduced clones correlated with gfp-fluorescence intensity over a wide range of expression levels. The tkgfp fusion gene itself may be useful in developing novel cancer gene therapy approaches. Valuable information about the efficiency of gene transfer and expression could be obtained by non-invasive imaging of tkgfp expression with FIAU and clinical imaging devices (gamma camera, positron-emission tomography [PET], single photon emission computed tomography [SPECT]), and/or direct visualization of gfp expression in situ by fluorescence microscopy or endoscopy.
journal_name
Neoplasiajournal_title
Neoplasia (New York, N.Y.)authors
Jacobs A,Dubrovin M,Hewett J,Sena-Esteves M,Tan CW,Slack M,Sadelain M,Breakefield XO,Tjuvajev JGdoi
10.1038/sj.neo.7900007keywords:
subject
Has Abstractpub_date
1999-06-01 00:00:00pages
154-61issue
2eissn
1522-8002issn
1476-5586journal_volume
1pub_type
杂志文章相关文献
NEOPLASIA文献大全abstract::Numerous human tumor types, including ovarian cancer, display a significant expression of the CD44 family of cell surface proteoglycans. To develop tumor-targeted drugs, we have initially evaluated whether the CD44 ligand hyaluronic acid (HA) could serve as a backbone for paclitaxel (TXL) prodrugs. HA-TXL was prepared...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07229
更新日期:2007-06-01 00:00:00
abstract::BUB1 (budding uninhibited by benzimidazoles-1) is required for efficient TGF-β signaling, through its role in stabilizing the TGFBR1 and TGFBR2 complex. Here we demonstrate that TGFBR2 phosphorylates BUB1 at Serine-318, which is conserved in primates. S318 phosphorylation abrogates the interaction of BUB1 with TGFBR1 ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2020.02.001
更新日期:2020-04-01 00:00:00
abstract::It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/s1476-5586(03)80009-x
更新日期:2003-03-01 00:00:00
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
更新日期:2019-11-01 00:00:00
abstract:PURPOSE:Foxhead box M1 (FOXM1) expression has been shown to be linked with human papillomavirus (HPV) 16/18-infected cervical cancer. However, the mechanism underlying the induction of FOXM1 in HPV 16/18-infected cancers remains elusive. EXPERIMENTAL DESIGN:The mechanistic actions of FOXM1 induced by the E6/NKX2-1 axi...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2014.09.010
更新日期:2014-11-20 00:00:00
abstract::Several studies have linked vascular density, identified in histologic sections, to "metastatic risk." Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if hum...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900129
更新日期:2001-03-01 00:00:00
abstract::Ras-transformed intestinal epithelial cells are resistant to the growth inhibitory actions of TGFbeta and have a marked decrease in expression of the TGFbeta type II receptor (TGFbetaRII). Rat intestinal epithelial cells (RIE) were stably transfected with activated Ras, Sos and Raf constructs and tested for expression...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900099
更新日期:2000-07-01 00:00:00
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
更新日期:2001-09-01 00:00:00
abstract::EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vi...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.81578
更新日期:2009-06-01 00:00:00
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
更新日期:2013-11-01 00:00:00
abstract::Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths in America. Nearly two thirds of newly diagnosed CRC cases include lymph node (LN) involvement, and LN metastasis is one of the strongest negative prognostic factors for CRC. It is thought that CRC tumors ...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.11324
更新日期:2011-09-01 00:00:00
abstract::Adenosine monophosphate-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer. Clinical trials using the United States Food and Drug Administration (FDA)-approved, AMPK-activating, antidiabetic drug metformin a...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.131434
更新日期:2013-12-01 00:00:00
abstract::c-Cbl, a RING-type ubiquitin E3 ligase, downregulates various receptor tyrosine kinases (e.g., epidermal growth factor receptor (EGFR)), leading to inhibition of cell proliferation. Moreover, patients with myeloid neoplasm frequently harbor c-Cbl mutations, implicating the role of c-Cbl as a tumor suppressor. Recently...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1016/j.neo.2015.06.003
更新日期:2015-06-01 00:00:00
abstract::Tumor necrosis factor (TNF) has been implicated in inflammation-associated tumor progression. Although multiple reports identified a role for TNF signaling in established cancers, few studies have assessed the impact of TNF blockade on early tumor formation promotion. We aimed at exploring the effects of TNF neutraliz...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.111224
更新日期:2011-12-01 00:00:00
abstract::We report that daurinol, a novel arylnaphthalene lignan, is a promising potential anticancer agent with adverse effects that are less severe than those of etoposide, a clinical anticancer agent. Despite its potent antitumor activity, clinical use of etoposide is limited because of its adverse effects, including myelos...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.11972
更新日期:2011-11-01 00:00:00
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
更新日期:2012-02-01 00:00:00
abstract::Cancer, a proliferative disease hallmarked by abnormal cell growth and spread, is largely dependent on tumor neoangiogenesis, with evidence of vascular endothelial dysfunction. Novel ways to assess vascular function in cancer include measuring levels of circulating endothelial cells (CEC). Rare in healthy individuals,...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1593/neo.05592
更新日期:2006-02-01 00:00:00
abstract::Human carcinoembryonic antigen (CEA) and the CEA family member CEACAM6 (formerly nonspecific cross-reacting antigen [NCA]) function in vitro, at least, as homotypic intercellular adhesion molecules and, in model systems, can block the terminal differentiation and anoikis of several different cell types. We have recent...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900201
更新日期:2002-03-01 00:00:00
abstract::To survive and metastasize, tumors interact with surrounding tissues by secreting growth factors and cytokines. In return, surrounding host tissues respond by changing their secretome. Numerous factors theoretically function as therapeutic targets or biomarkers of cancer growth and metastatic risk. However, it is uncl...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.10166
更新日期:2010-05-01 00:00:00
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
更新日期:2012-11-01 00:00:00
abstract::Heparanase-1 (HPR1), an endoglycosidase that specifically degrades heparan sulfate (HS) proteoglycans, is overexpressed in a variety of malignancies. Our present study sought to determine whether oncogene BRAF and RAS mutations lead to increased HPR1 expression. Reverse transcription-polymerase chain reaction analysis...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.10790
更新日期:2010-11-01 00:00:00
abstract::Cancers are complex, adaptive ecosystems. They remain the leading cause of disease-related death among children in North America. As we approach computational oncology and Deep Learning Healthcare, our mathematical models of cancer dynamics must be revised. Recent findings support the perspective that cancer-microenvi...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1016/j.neo.2020.09.008
更新日期:2020-12-01 00:00:00
abstract::Glioblastomas are malignant brain tumors that are rarely curable, even with aggressive therapy (surgery, chemotherapy, and radiation). Glioblastomas frequently display loss of PTEN and/or epidermal growth factor receptor activation, both of which activate the PI3K pathway. This pathway can increase vascular endothelia...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.06535
更新日期:2006-11-01 00:00:00
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
更新日期:2014-03-01 00:00:00
abstract::Increases in the levels and/or activity of nonreceptor tyrosine kinases c-Src and c-Yes are often associated with colorectal carcinogenesis. The physiological consequences of increased c-Yes activity during the early and late stages of tumorigenesis, in addition to the degree of redundancy between c-Yes and c-Src in c...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.07442
更新日期:2007-09-01 00:00:00
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
更新日期:2014-10-23 00:00:00
abstract::Activation of the Wnt-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate, and endometrium. To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by beta-catenin/Tcf complex in a huma...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1038/sj.neo.7900132
更新日期:2001-01-01 00:00:00
abstract::Tumor-associated macrophages (TAMs) invade the tumor stroma in many cancers, yet their role is incompletely understood. To visualize and better understand these critical cells in tumor progression, we screened a portfolio of rationally selected, injectable agents to image endogenous TAMs ubiquitously in three differen...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章
doi:10.1593/neo.09356
更新日期:2009-05-01 00:00:00
abstract::Treatment decisions in oncology are increasingly guided by information on the biologic characteristics of tumors. Currently, patient-specific information on tumor biology is obtained from the analysis of biopsy material. Positron emission tomography (PET) provides quantitative estimates of regional biochemistry and re...
journal_title:Neoplasia (New York, N.Y.)
pub_type: 杂志文章,评审
doi:10.1038/sj.neo.7900075
更新日期:2000-01-01 00:00:00
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
更新日期:2010-12-01 00:00:00