Abstract:
:To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Jang S,Yu XM,Odorico S,Clark M,Jaskula-Sztul R,Schienebeck CM,Kupcho KR,Harrison AD,Winston-McPherson GN,Tang W,Chen Hdoi
10.1038/cgt.2015.37subject
Has Abstractpub_date
2015-08-01 00:00:00pages
410-6issue
8eissn
0929-1903issn
1476-5500pii
cgt201537journal_volume
22pub_type
杂志文章abstract::Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bc...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700673
更新日期:2004-04-01 00:00:00
abstract::Ad-PPE-Fas-c is an adenovector that expresses Fas-c under the control of the modified pre-proendothelin-1 (PPE-1) promoter. Fas-c is a chimeric death receptor containing the extracellular portion of tumour necrosis factor 1 receptor (TNFR1) and the transmembrane and intracellular portion of Fas. We recently demonstrat...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2008.20
更新日期:2008-08-01 00:00:00
abstract::Oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a variety of cancers. We recently developed MOA5, a tumor-specific midkine promoter-regulated oncolytic vector based on human adenovirus serotype 5 (Ad5). We modified the binding tropism of MOA5 by replacing the cell-binding domain of the ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2014.7
更新日期:2014-03-01 00:00:00
abstract::Previous studies have indicated that the cytokine interleukin (IL)-21 may induce both innate and adaptive immune responses against tumors. The goal of this study was to evaluate a new adoptive immunotherapy strategy that combined lymphocytes from mice immunized with a murine myeloma vaccine secreting murine IL-21 (mIL...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.23
更新日期:2010-10-01 00:00:00
abstract::Clear cell renal cell carcinoma (ccRCC) is the highest mortality, invasion, and metastasis subtype of renal cell carcinoma. Bone morphogenetic protein (BMP) family has recently emerged as a group of cancer-related proteins in multiple pathogenesis of cancers. Currently, little is known about the prediction role of BMP...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0107-9
更新日期:2020-05-01 00:00:00
abstract::The zinc-fingers and homeoboxes (ZHX) family is a group of nuclear homodimeric transcriptional repressors that interact with a subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. The members of ZHX family form homodimers or heterodimers with other members o...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2015.16
更新日期:2015-05-01 00:00:00
abstract::Prostate cancer is one of the most commonly diagnosed cancers and the second leading cause of cancer deaths in Americans. The high mortality rate is mainly attributed to the invasiveness and metastasis of advanced prostate cancer. Targeting the molecules involved in metastasis could be an effective mode of treatment f...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.16
更新日期:2010-09-01 00:00:00
abstract::Cationic liposomes are considered to be safe vectors for gene transfer, but they are less efficient at delivering DNA to cells when compared with retroviral vectors. Cationic liposomes complexed with DNA were targeted to specific cells in vitro by means of monoclonal antibodies (mAbs) or ligands associated with the li...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-07-01 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::A nonviral gene delivery vector has been developed in our laboratory based on the cationic polymer, poly(2-(dimethylethylamino)ethyl methacrylate) (p(DMAEMA)). p(DMAEMA)-based polyplexes have been successfully used for the transfection of OVCAR-3 cells in vitro. However, these polyplexes were unable to transfect OVCAR...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700311
更新日期:2001-06-01 00:00:00
abstract::Although early stage cholangiocarcinoma (CC) can be cured by surgical extirpation, the options for treatment of advanced stage CC are very few and suboptimal. Oncolytic virotherapy using replication-competent vaccinia virus (VACV) is a promising new strategy to treat human cancers. The ability of oncolytic VACV GLV-1h...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2015.60
更新日期:2015-12-01 00:00:00
abstract::Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We created a recombinant replicating VSV (rrVSV) that preferentially infected Her2/neu expressing breast cancer cells. We now used this rrVSV to treat macroscopic peritoneal tumor implants of a mouse mammary tumor cell line stably transfected to e...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2008.55
更新日期:2009-01-01 00:00:00
abstract::Arming oncolytic adenoviral vectors with anticancer transgenes that can be expressed in a tumor-selective manner may enable the engineering of vectors with increased potency, while retaining their safety profile. Armed oncolytic adenoviral vectors were constructed in which transgene expression has been linked via modi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7701093
更新日期:2008-01-01 00:00:00
abstract::The DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) is epigenetically silenced in some tumors by MGMT gene promoter methylation. MGMT-hypermethylated solid tumors have enhanced susceptibility to the cytotoxic effects of alkylating chemotherapy such as temozolomide, compared with non-methylated tumors. ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2017.27
更新日期:2017-08-01 00:00:00
abstract::Apatinib, a selective vascular endothelial growth factor receptor 2-tyrosine kinase inhibitor, has demonstrated activity against a wide range of solid tumors, including advanced hepatocellular carcinoma (HCC). Preclinical and preliminary clinical results have confirmed the synergistic antitumor effects of apatinib in ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-0186-7
更新日期:2020-06-12 00:00:00
abstract::Gliomas express a higher amount of Fas than normal brain tissue. It is of interest to know whether expression of the Fas receptor is unfavorable to the antiapoptotic pathways in gliomas. In this study, we introduced the Fas gene via an adenovirus vector (Adeno-Fas) into the A-172, U251, and U-373 MG glioma cell lines,...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700110
更新日期:2000-02-01 00:00:00
abstract::We recently described a novel nonviral/viral vector for gene transfer, the plasmovirus (Noguiez-Hellin P, Robert-le Meur M, Laune S, et al. C R Acad Sci Paris, Sciences de la Vie. 1996;319:45-50; Noguiez-Hellin P, Robert-le Meur M, Salzmann J-L, et al. Proc Natl Acad Sci USA. 1996;93:4175-4180). Plasmoviruses are plas...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral inject...
journal_title:Cancer gene therapy
pub_type: 临床试验,杂志文章
doi:10.1038/sj.cgt.7700019
更新日期:1999-07-01 00:00:00
abstract::MicroRNAs (miRNAs) were discovered more than a decade ago as noncoding, single-stranded small RNAs (approximately 22 nucleotides) that control the timed gene expression pattern in Caenorhabditis elegans life cycle. A number of these evolutionarily conserved, endogenous miRNAs have been shown to regulate mammalian cell...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2008.8
更新日期:2008-06-01 00:00:00
abstract::Survivin is expressed in most cancers but is undetectable in differentiated adult cells, and plays an important role both in the suppression of apoptosis and mitotic spindle checkpoint; thus it has attracted great interest as a potential drug target. In this study, we investigated the antigene and antiproliferative ef...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700581
更新日期:2003-05-01 00:00:00
abstract::Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of seru...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00216-1
更新日期:2020-12-09 00:00:00
abstract::Typically, gene transfer strategies utilize a promoter/transgene arrangement that treat these elements independently and do not offer any interplay between them. Our goal was to establish a promoter/transgene combination that would result in improvement in both expression and therapeutic effect by utilizing the transc...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700846
更新日期:2005-12-01 00:00:00
abstract::We previously developed the "immunogene" approach toward cancer gene therapy using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we describe an improved immunogene system, in which the antigen-binding (Fab) fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were conjugated with...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract::The antitumor activity of a recombinant canarypox virus expressing wild type murine p53 (ALVAC-p53) was investigated in two murine syngeneic tumors harboring an endogenous p53 mutation (CMS4 and TS/A). Direct intratumor injections of ALVAC-p53 in CMS4 pre-established subcutaneous tumors induced total tumor regression ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700279
更新日期:2001-02-01 00:00:00
abstract::Over the past several years we have obtained considerable evidence indicating that adenoviruses-expressing interferon α (Ad-IFNα) can overcome resistance to the IFNα protein itself. Since cancer cells infected with Ad-IFNα also show high perinuclear cytoplasmic IFNα expression, we were interested in whether endoplasmi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.26
更新日期:2011-09-01 00:00:00
abstract::Selection of suitable delivery system is one of the crucial aspects in gene therapy that determines the efficiency of gene therapy. The past two decades have witnessed extensive efforts for finding safe and efficient vectors to overcome the limitations of viral vectors. The utilization of DNA transposon-based vectors ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2015.68
更新日期:2016-02-01 00:00:00
abstract::To investigate a novel suicide gene for nasopharyngeal carcinoma (NPC) therapy, the yCDglyTK gene was constructed by fusing yeast cytosine deaminase (CD) and herpes simplex type 1 thymidine kinase. The expression of the yCDglyTK gene was detected by RT-PCR and Western blotting, and its bioactivity was demonstrated by ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700728
更新日期:2004-12-01 00:00:00
abstract::Drug metabolizing transgene products, which activate bioreductive cytotoxins, can be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6 transgenes ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700933
更新日期:2006-06-01 00:00:00
abstract::Retroviral replicating vectors (RRVs) have achieved efficient tumor transduction and enhanced therapeutic benefit in a wide variety of cancer models. Here, we evaluated two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), which utilize different cellular recept...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-018-0037-y
更新日期:2019-02-01 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