Abstract：
:We exploited the differential activation of hypoxia-inducible factor (HIF)-dependent gene expression in tumors versus normal tissue for the design of a targeted oncolytic herpes simplex virus type-1 (HSV-1). A gene that is essential for viral replication, infected cell polypeptide 4 (ICP4), was placed under the regulation of an HIF-responsive promoter and then introduced into the thymidine kinase locus (U(L)23) of HSV d120, which contains partial deletions in the two endogenous ICP4 genes. Recombinant HIF-HSV was isolated and their derivation from d120 was verified by expression of a truncated, non-functional form of ICP4 protein. Disruption of the U(L)23 locus was confirmed by loss of thymidine kinase expression and resistance to acyclovir. Unexpectedly, HIF-HSV expressed ICP4 and induced tumor cell lysis at similar levels under normoxia and hypoxia. The lack of HIF-dependent ICP4 transgene expression by HIF-HSV was due to two factors that have not previously been reported-reversion of the ICP4 gene region to its wild-type configuration and increased HIF-transcriptional activity under normoxia when cells were infected with any strain of HSV-1. The findings that an oncolytic HSV-1 is genetically unstable and can activate a tumor-related promoter in a non-specific manner have important implications for any proposed use of this virus in cancer therapy.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Longo SL,Griffith C,Glass A,Shillitoe EJ,Post DEdoi
10.1038/cgt.2010.62subject
Has Abstractpub_date
2011-02-01 00:00:00pages
123-34issue
2eissn
0929-1903issn
1476-5500pii
cgt201062journal_volume
18pub_type
杂志文章abstract：:In this study, we have applied high-density oligonucleotide microarray technology to characterize biologic changes associated with adenoviral vector-mediated target cell infection. We infected a human melanoma cell line, M21, with the tropism-modified vectors, Ad5lucRGD and Ad5/3luc1. In addition, we infected the M21 ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700776
更新日期：2005-02-01 00:00:00
abstract：:Chimeric Antigen Receptor (CAR) T-cell therapy, as an approved treatment option for patients with B cell malignancies, demonstrates that genetic modification of autologous immune cells is an effective anti-cancer regimen. Erythropoietin-producing Hepatocellular receptor tyrosine kinase class A2 (EphA2) is a tumour ass...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-020-00221-4
更新日期：2020-09-01 00:00:00
abstract：:Mammary carcinomas that develop in C3 (1)/SV40 T- antigen (TAg) transgenic mice have lost the p53-mediated induction of p21, leading to increased cellular proliferation and significant elevations of cyclins and Cdks. To test whether p21 could serve as a target for anticancer therapy for this mammary cancer model, a re...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700275
更新日期：2001-01-01 00:00:00
abstract：:The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancer...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700226
更新日期：2000-09-01 00:00:00
abstract：:Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the γ3...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2017.33
更新日期：2017-09-01 00:00:00
abstract：:Lung cancer is the most frequently occurring cancer in the world and causes more deaths in the United States than does colon, breast, and prostate cancer combined. Despite advances in treatment modalities including radiation, surgery, and chemotherapy, the overall survival in lung cancer remains low. The cytokine tumo...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700394
更新日期：2001-11-01 00:00:00
abstract：:ING4 as a member of inhibitor of growth (ING) tumor suppressor family has potent inhibitory effects on a variety of tumors. Interleukin-24 (IL-24), a cytokine-tumor suppressor, also shows broad-spectrum and tumor-specific antitumor activities. In this report, we constructed an ING4/IL-24 bicistronic adenovirus (Ad-ING...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2011.31
更新日期：2011-09-01 00:00:00
abstract：:The Ki-ras gene is frequently mutated and/or overexpressed in human cancer. Since it is suspected to play a key role in the pathogenesis of many tumors, there is interest to search for strategies aiming at the specific inhibition of this oncogene. In this paper, we investigated the capacity of a 20 mer G-rich oligonuc...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700722
更新日期：2004-07-01 00:00:00
abstract：:Metastasis is the principal cause of cancer death and occurs through multiple, complex processes. Epithelial to mesenchymal transition (EMT) is an important process during embryonic development and has also been hypothesized to exhibit a significant role in cancer cell invasion and metastasis. MicroRNAs (miRNAs) are a...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2017.1
更新日期：2017-02-01 00:00:00
abstract：:The Holliday Junction-Recognition Protein (HJURP) was reported as overexpressed in several cancers and also strongly correlated with poor prognosis of patients, especially in glioblastoma (GBM), the most common and deadly type of primary brain tumor. HJURP is responsible for loading the histone H3 variant-the Centrome...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-019-0103-0
更新日期：2020-05-01 00:00:00
abstract：:Use of a recombinant vaccinia virus expressing human interleukin-2 (IL-2) was evaluated for preparation of tumor vaccines. A/J mice were immunized against neuroblastoma (C1300) cells using a preparation of C1300 cells infected/transfected with the recombinant virus, vCF13, expressing IL-2. A second recombinant vaccini...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected int...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700630
更新日期：2003-10-01 00:00:00
abstract：:Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential r...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-020-00253-w
更新日期：2020-11-30 00:00:00
abstract：:Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-017-0001-2
更新日期：2018-02-01 00:00:00
abstract：:Most cancer vaccines to date have made use of common tumor antigens or allogenic cancer cell lines. The majority of tumor antigens may, however, be unique patient-specific antigens. Dendritic cells (DCs) are the most potent antigen-presenting cells known. The present report is a full-scale preclinical evaluation of au...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700837
更新日期：2005-06-01 00:00:00
abstract：:Lung metastases are a frequent complication of osteosarcoma and a treatment that would reduce the severity of this complication would be of great benefit to patients. We have used a formulation consisting of polyethyleneimine (PEI) and a p53 gene administered in aerosol to treat established lung micrometastases as a m...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700343
更新日期：2001-09-01 00:00:00
abstract：:The ability of viruses to readily infect tumor cells both in vitro and in vivo has resulted in their study as antitumor agents through a variety of strategies. Replicating and conditionally replicating viruses and recombinant viruses encoding genes for toxins and/or prodrugs have been studied for their direct antitumo...
journal_title：Cancer gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.cgt.7700538
更新日期：2002-12-01 00:00:00
abstract：:The "bystander effect," produced by ganciclovir-mediated killing of cells transduced with a herpes simplex virus thymidine kinase (HSVtk) gene, defines the cooperative killing of non-HSVtk-transduced cells. In vitro, a major contributor to this phenomenon is metabolic cooperation involving transfer of cytotoxic small ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1997-07-01 00:00:00
abstract：:The prognosis of glioblastoma remains poor despite intensive research efforts. Glioblastoma stem cells (GSCs) contribute to tumorigenesis, invasive capacity, and therapy resistance. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a stem cell marker, is involved in the maintenance of GSCs, although ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-020-00282-5
更新日期：2021-01-07 00:00:00
abstract：:Thymidylate synthase (TS) catalyzes de novo production of thymidylate for DNA synthesis and cell proliferation. As such, TS has been a target of antitumor chemotherapy for many years. Our laboratory has identified several antisense oligodeoxynucleotides (ODNs) that downregulate TS mRNA and protein, inhibit cell prolif...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700566
更新日期：2003-04-01 00:00:00
abstract：:Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker for the colorectal cancer (CRC). It plays critical roles in the oncogenesis, progression, and metastasis of CRC. DCLK1 can be an intriguing therapeutic target for CRC treatment. However, the molecular mechanism of how DCLK1 functions is unclear currently....
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-019-0144-4
更新日期：2020-09-01 00:00:00
abstract：:We have described three potential adenovirus type 5 (Ad5)-based replication-competent cancer gene therapy vectors named KD1, KD3, and VRX-007. All three vectors overexpress an Ad5 protein named Adenovirus Death Protein (ADP, also named E3-11.6 K protein). ADP is required for efficient lysis of Ad5-infected cells and s...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700555
更新日期：2003-03-01 00:00:00
abstract：:Targeting tumor vasculature represents an interesting approach for the treatment of solid tumors. The alpha v beta 3 integrins have been found to be specifically associated with angiogenesis in tumors. By using bacteriophage display technology, Ruoslahti et al found that a group of peptides containing the RGD (Arg-Gly...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700707
更新日期：2004-05-01 00:00:00
abstract：:Mesenchymal stem cells (MSCs) have affinity to tumor sites where they home, affecting their biology and growth. Previously, we have isolated mesenchymal cells from the decidua of the human placenta named as decidua-derived MSCs (DMSCs). The aims of the present study were to investigate the migration capacity of DMSCs ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2012.71
更新日期：2013-01-01 00:00:00
abstract：:Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinom...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2011.68
更新日期：2012-01-01 00:00:00
abstract：:To improve the expression levels of transgenes in malignant hematopoietic cells, we developed a novel adenoviral-alphavirus hybrid vector Ad5/F11p-SFV-GFP that contains a Semliki Forest Virus (SFV) replicon and chimeric fibers of Ad5 and Ad11p. Ad5/F11p-SFV-GFP infected >95% of K562, U937 or Jurkat cells and 23.65% of...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2013.37
更新日期：2013-08-01 00:00:00
abstract：:Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It is still unclear if and how miRNAs-221/222 are implicated in breast cancer and the resistance to estrogen receptor modulator tamoxifen. We investigated the roles and mechanisms of miR-221/222 in breast cancer cells, particularly in modula...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2014.29
更新日期：2014-07-01 00:00:00
abstract：:Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700237
更新日期：2000-10-01 00:00:00
abstract：:Angiogenesis is among the most important mechanisms that helps cancer cells to survive, grow and undergo metastasis. Therefore, inhibiting angiogenesis will suppress tumor growth. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are believed to be important players of angiogenesis. The goal of this s...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2016.76
更新日期：2017-01-01 00:00:00
abstract：:The gene transfer of tumor-specific chimeric immunoglobulin T-cell receptors (cIgTCRs) combining antibody-like specificity with the effector cell function could be an attractive tool in immunotherapy. In this study, we directed the human natural killer (NK) cell line YT to tumor cells by gene transfer of a cIgTCR with...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700453
更新日期：2002-04-01 00:00:00
