Abstract：
:Salmonella typhimurium (hereafter S. typhimurium), as Gram-negative facultative anaerobic bacteria, are good candidates for cancer therapy and delivering therapeutic antitumor agents. However, it is necessary to reduce the virulence of such bacteria and enhance their tumor-targeting ability, and their immunostimulatory ability to induce tumor cell apoptosis. In this study, we constructed a S. typhimurium mutant named S634 harboring aroA mutation and additional mutations involved in modifications of lipid A. Upon intraperitoneal infection in mice, the aroA-deficient strain S634 showed greatly attenuated virulence and preferential accumulation within tumor tissue. We next investigated the ability of S636, the asd mutant derivative of S634, to deliver the anti-angiogenic agent "endostatin" (S636/pES) and to inhibit tumor growth in mouse CT26 colon carcinoma and B16F10 melanoma models. S636/pES-treated tumor-bearing mice showed suppressed tumor growth and prolonged survival, compared to mice treated with either the bacteria carrying empty plasmids or PBS intraperitoneally. Immunohistochemical studies demonstrated that, when tumor-bearing mice were infected with S636/pES, Salmonella colonization and endostatin expression were accompanied by the increase of apoptosis level and suppression of tumor angiogenesis within tumor tissues. Our findings showed that endostatin gene therapy delivered by attenuated S. typhimurium displays therapeutic antitumor effects in murine tumor models.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Liang K,Liu Q,Li P,Han Y,Bian X,Tang Y,Kong Qdoi
10.1038/s41417-018-0021-6subject
Has Abstractpub_date
2018-08-01 00:00:00pages
167-183issue
7-8eissn
0929-1903issn
1476-5500pii
10.1038/s41417-018-0021-6journal_volume
25pub_type
杂志文章abstract：:In this study, we investigated the safety and efficacy in cancer patients of a single intra-tumor injection of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene (AdV/TK) followed by systemic administration of ganciclovir (GCV). In 18 patients with malignant tumors refractory to standard...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2009.19
更新日期：2009-09-01 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 have constructed and tested five recombinant adenoviruses (Ads) that express a variety of immunomodulators, including CD40 ligand (CD40L), a potent costimulator of several components of the immune system. We demonstrate that CD40L expressed from Ad in K1735 mouse melanoma cells leads to a strong reduction in tumori...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700475
更新日期：2002-07-01 00:00:00
abstract：:The original version of this Article contained an error in the spelling of the author Ahmed Abdelanabi, which was incorrectly given as Abdelanabi Ahmed. This has now been corrected in both the PDF and HTML versions of the Article. ...
journal_title：Cancer gene therapy
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41417-019-0096-8
更新日期：2020-04-01 00:00:00
abstract：:Stathmin is the founding member of a family of microtubule-destabilizing proteins that have a critical role in the regulation of mitosis. Stathmin is expressed at high levels in breast cancer and its overexpression is linked to disease progression. Although there is a large body of evidence to support a role for stath...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2013.21
更新日期：2013-05-01 00:00:00
abstract：:The herpes simplex virus thymidine kinase (HSV-TK) gene is being developed in the treatment of many different types of tumors. The HSV-TK gene sensitizes tumor cells to the antiviral drug ganciclovir (GCV) and mediates the bystander effect in which unmodified tumor cells are killed as well. Although this approach has ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700063
更新日期：1999-09-01 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：:Malignant tumors express tumor-related antigens, but effective antitumor immunity does not occur in the primary host. One hypothesis is that there is insufficient stimulation of T-cell responses due to ineffective antigen presentation. An approach to overcome these deficiencies is to modify tumor cells to express majo...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:Delivery of the full-length tumor antigen might be more successful in immunotherapy than single peptides and has the advantage that patients no longer need to be selected for their HLA type. In this study, we tested the in vitro induction of CAMEL/NY-ESO-ORF2-specific T cells by dendritic cells infected with an adenov...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700674
更新日期：2004-03-01 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：:T cells can be reprogrammed to redirect specificity to tumor-associated antigens (TAAs) through the enforced expression of chimeric antigen receptors (CARs). The prototypical CAR is a single-chain molecule that docks with TAA expressed on the cell surface and, in contrast to the T-cell receptor complex, recognizes tar...
journal_title：Cancer gene therapy
pub_type： 杂志文章,评审
doi：10.1038/cgt.2014.69
更新日期：2015-03-01 00:00:00
abstract：:Glioma is the most common tumor in the central nervous system that portends a poor prognosis. Key genes negatively related to survival may provide targets for therapy to improve the outcome of glioma. Here, we report a protein-coding gene CLEC5A, which is the top 1 gene by univariate Cox regression analysis of 524 pri...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-019-0140-8
更新日期：2020-09-01 00:00:00
abstract：:Immune responses to tumor-associated antigens are often dampened by a tumor-induced state of immune anergy. Previous work has attempted to overcome tumor-induced T-cell anergy by the direct injection of vectors carrying the genes encoding one of a variety of cytokines. We hypothesised that the polyclonal stimulation o...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700461
更新日期：2002-05-01 00:00:00
abstract：:The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatm...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700331
更新日期：2001-07-01 00:00:00
abstract：:Macrophages plasticity is a key feature in cancer progression. Neoplastic cells can alter their immune functions and orient them into a pro-tumoral phenotype. In this context, we developed a new therapeutic strategy to switch macrophages phenotype and reactivate their anti-tumoral functions. We showed a dual activity ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-020-00286-1
更新日期：2021-01-05 00:00:00
abstract：:At the Eleventh International Conference on Gene Therapy of Cancer (December 12-14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely...
journal_title：Cancer gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.cgt.7700602
更新日期：2003-07-01 00:00:00
abstract：:The majority of human neuroblastomas express low to undetectable levels of major histocompatibility complex (MHC) class I and II antigens (MHC-I and -II). We studied the effects of gamma interferon (gamma-IFN) transduction on expression of these antigens in six human neuroblastoma cell lines with and without genomic a...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:RNA interference (RNAi) is a natural cellular regulatory process that inhibits gene expression by transcriptional, post-transcriptional and translational mechanisms. Synthetic approaches that emulate this process (small interfering RNA (siRNA), short hairpin RNA (shRNA)) have been shown to be similarly effective in th...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2010.35
更新日期：2010-11-01 00:00:00
abstract：:Prostate cancer is the second most common cancer in men globally. Prostate cancer patients at advanced stages are usually treated with androgen deprivation therapy (ADT). However, with disease progression, it often becomes the incurable castration-resistant prostate cancer (CRPC). JC polyomavirus (JCPyV) is a human DN...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-019-0083-0
更新日期：2019-07-01 00:00:00
abstract：:A phase I clinical trial using autologous, IL-7 gene-modified tumor cells in patients with disseminated melanoma has been recently completed. Although no major clinical responses were observed, increased antitumor cytotoxicity was measured in postvaccine peripheral blood lymphocytes in a subset of treated patients. To...
journal_title：Cancer gene therapy
pub_type： 临床试验,杂志文章
doi：10.1038/sj.cgt.7700435
更新日期：2002-03-01 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：:Tumor-endothelial interaction contributes to local prostate tumor growth and distant metastasis. In this communication, we designed a novel approach to target both cancer cells and their "crosstalk" with surrounding microvascular endothelium in an experimental hormone refractory human prostate cancer model. We evaluat...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700790
更新日期：2005-03-01 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：:As an initial assessment of the feasibility of employing the adenovirus serotype 3 (Ad3) fiber knob as a locale for introducing a tropism-modifying motif, we generated an adenoviral vector containing a six-histidine tag genetically fused to the carboxy-terminus of the Ad3 fiber knob. The heterologous tag proved to be ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700543
更新日期：2003-02-01 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：:Melanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-020-00274-5
更新日期：2020-12-14 00:00:00
abstract：:Oncolytic reovirus administration has been well tolerated by cancer patients in clinical trials. However, its anti-cancer efficacy as a monotherapy remains to be augmented. We and others have previously demonstrated the feasibility of producing replication-competent reoviruses expressing a heterologous transgene. Here...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-018-0063-9
更新日期：2019-09-01 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：:Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 f...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700957
更新日期：2006-08-01 00:00:00
abstract：:Intratumoral (i.t.) administration of cytokine genes expressed by viral vectors represents a rational approach that induces cytokine secretion at the site they are needed, and i.t. vaccinia virus (VV) has shown promise in mesothelioma patients. However, we and others have shown that the mesothelioma tumor microenviron...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2009.85
更新日期：2010-06-01 00:00:00
