Abstract:
:Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI-2 in the development of esophageal carcinoma. Western blotting revealed that TFPI-2 was downregulated in 75% of esophageal carcinomas and in most esophageal carcinoma cell lines. Immunohistochemistry revealed that TFPI-2 was significantly downregulated in tumor tissues and in lymph node metastases. Experimental overexpression of TFPI-2 in KYSE450, KYSE510, YES2, and EC9706 cells significantly inhibited their invasive ability. Overexpression of TFPI-2 in EC9706 cells inhibited xenograft tumor growth and invasion into surrounding tissues, as well as reduced lung metastasis. Further studies demonstrated that recombinant TFPI-2 protein significantly inhibited the activity of matrix metalloproteinases and tumor-related angiogenesis. Parenteral treatment with recombinant TFPI-2 protein significantly suppressed xenograft growth and metastasis. Together, these data indicate that TFPI-2 inhibits tumor invasion and angiogenesis both in vitro and in vivo, and suggest a potentially important therapeutic role for recombinant TFPI-2 in the treatment of malignant esophageal carcinomas.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Ran Y,Pan J,Hu H,Zhou Z,Sun L,Peng L,Yu L,Sun L,Liu J,Yang Zdoi
10.1089/hum.2008.129subject
Has Abstractpub_date
2009-01-01 00:00:00pages
41-9issue
1eissn
1043-0342issn
1557-7422journal_volume
20pub_type
杂志文章abstract::Gene therapy for heart diseases requires availability of an efficient vector for gene transfer into myocardium. Recombinant adenovirus expressing the Escherichia coli beta-galactosidase (beta-Gal) gene was shown to infect rat cardiocytes efficiently in vivo. However, a time course of gene expression showed that transg...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.10-1265
更新日期:1995-10-01 00:00:00
abstract::Immunoisolation of allogeneic cells within a membrane-bound device is a unique approach for gene therapy. We employed an immunoisolation device that protects allograft, but not xenograft, cells from destruction, to implant a human fibroblast line (MSU 1.2) in athymic rodents. Cells, transduced with the MFG-human facto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.6-879
更新日期:1998-04-10 00:00:00
abstract::Therapeutic levels of expression of the beta-globin gene have been difficult to achieve with conventional retroviral vectors without the inclusion of DNase I-hypersensitive site (HS2, HS3, and HS4) enhancer elements. We generated recombinant adeno-associated viral (AAV) vectors carrying an antisickling human beta-glob...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.173
更新日期:2008-04-01 00:00:00
abstract::Adenovirus type 5 (Ad5) is a commonly used vector for gene therapy, but its efficacy is limited by high seroprevalence and off-target hepatic and splenic sequestration. In order to circumvent these limitations, the use of vectors derived from rare species adenoviruses is appealing. The opportunity to retarget rare spe...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2014.016
更新日期:2014-04-01 00:00:00
abstract::Deficiencies in different steps of purine metabolism give rise to a number of human inherited disorders. Lesch-Nyhan syndrome is a severe neurological disorder, caused by a deficiency in the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). HPRT-deficient mice have been generated, but have proved to...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.13-1491
更新日期:1996-08-20 00:00:00
abstract::We reported total correction of blood coagulation plasma factor VIII (FVIII) activity, using adeno-associated virus serotype 8 (AAV8) vectors for liver-specific gene transfer in hemophilia A mice. We now show, irrespective of immunosuppression or route of administration, total long-term correction of hemophilia A mice...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.427
更新日期:2006-04-01 00:00:00
abstract::Serum-induced inactivation of retroviruses is the most critical limitation for in vivo gene transfer therapy. To solve this problem, we searched for reagents that protect retroviruses from inactivation. The effects of the protease inhibitors FOY-007 and FOY-305 and of an inhibitor of the complement pathway FUT-175, al...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.13-1575
更新日期:1997-09-01 00:00:00
abstract::Replication-deficient adenoviruses are known to induce acute injury and inflammation of infected tissues, thus limiting their use for human gene therapy. However, molecular mechanisms triggering this response have not been fully defined. To characterize this response, chemokine expression was evaluated in DBA/2 mice f...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018364
更新日期:1999-04-10 00:00:00
abstract::Fabry disease, caused by a deficiency of lysosomal enzyme alpha-galactosidase A (alpha-gal A), is one of the inherited disorders potentially treatable by gene transfer to hematopoietic stem cells. In this study, a high-titer amphotropic retroviral producer cell line, MFG-alpha-gal A, was established. CD34+ cells from ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016302
更新日期:1999-12-10 00:00:00
abstract::Recombinant adeno-associated virus (rAAV) is a prototypical gene therapy vector characterized by excellent safety profiles, wide host range, and the ability to transduce differentiated cells. Numerous rAAV-based vectors providing efficient and sustained expression of transgenes in target tissues have been developed fo...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2005.16.551
更新日期:2005-05-01 00:00:00
abstract::Cell-based gene transfer using a stent platform would provide a significant advantage in terms of site-specific gene expression in the vasculature. The current study presents a novel stent design that allows stable in vivo transgene expression over a 4-week period in the vasculature. A mesh-stent coated with fibronect...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252792567
更新日期:2002-02-10 00:00:00
abstract::Recombinant adeno-associated viral (AAV) vectors of serotypes 6, 8, and 9 were characterized as tools for gene delivery to dopaminergic neurons in the substantia nigra for future gene therapeutic applications in Parkinson's disease. While vectors of all three serotypes transduced nigral dopaminergic neurons with equal...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.174
更新日期:2013-06-01 00:00:00
abstract::Mucopolysaccharidosis type IIIA (MPSIIIA) is a rare lysosomal storage disorder caused by mutations in the sulfamidase gene. Accumulation of glycosaminoglycan (GAG) inside the lysosomes is associated with severe neurodegeneration as well as peripheral organ pathological changes leading to death of affected individuals ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.029
更新日期:2012-12-01 00:00:00
abstract::Recombinant vectors based on adeno-associated virus serotype 8 (AAV8) have been successfully used in the clinic and hold great promise for liver-directed gene therapy. Preexisting immunity against AAV8 or the development of antibodies against the therapeutic transgene product might negatively affect the outcomes of ge...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2014.109
更新日期:2015-03-01 00:00:00
abstract::To develop a potential gene therapy strategy for the treatment of hemophilia A, we constructed several retroviral vectors expressing a B-domain-deleted factor VIII (FVIII) cDNA. We confirmed previous reports that when the FVIII cDNA is inserted into a retroviral vector, the vector mRNA is decreased resulting in signif...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.11-1363
更新日期:1995-11-01 00:00:00
abstract::The therapeutic use of neurotrophic factors for neurodegenerative diseases is promising, however, optimal methods for continuous delivery of these substances to the human central nervous system (CNS) remains problematic. One approach would be to graft genetically engineered human cells that continuously secrete high l...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.3-331
更新日期:1997-02-10 00:00:00
abstract::Malignant pleural mesothelioma (MPM) is a fatal disease with a median survival of less than 14 months. For the first time, a genetically engineered vaccinia virus is shown to produce efficient infection, replication, and oncolytic effect against MPM. GLV-1h68 is a replication-competent engineered vaccinia virus carryi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.036
更新日期:2008-08-01 00:00:00
abstract::Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete m...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018823
更新日期:1999-02-10 00:00:00
abstract::Human papillomavirus type 16 (HPV16) is associated with the development of anogenital cancers and their precursor lesions, intraepithelial neoplasia. Treatment strategies against HPV-induced intraepithelial neoplasia are not HPV specific and mostly consist of physical removal or ablation of lesions. We had previously ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.115
更新日期:2010-07-01 00:00:00
abstract::With the aim of developing new gene transfer tools for treating CF with gene therapy, we have synthesized a novel family of molecules named cationic phosphonolipids. The most efficient among them were selected by in vitro screening to compare their activities in vivo in mouse lungs. We used a reporter gene whose activ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.16-2309
更新日期:1998-11-01 00:00:00
abstract::Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across the permeabilized membrane. To in...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hgt.2008.060
更新日期:2008-11-01 00:00:00
abstract::La Crosse virus (LACV)-mediated encephalitis is the most frequently reported arboviral disease in the United States, but to date no vaccine against this virus is available. We have established a new animal model, genetically targeted mice lacking a functional interferon type I receptor (IFNAR-1). These mice show an ag...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017653
更新日期:1999-07-01 00:00:00
abstract::Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limit...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2014.001
更新日期:2014-04-01 00:00:00
abstract::Baculovirus vectors recently have been shown to be capable of efficient transduction of human hepatoma cells and primary hepatocytes in culture. This paper describes the generation of a novel recombinant baculovirus (VGZ3) in which the vesicular stomatitis virus glycoprotein G (VSV G) is present in the viral envelope....
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.17-2011
更新日期:1997-11-20 00:00:00
abstract::The central nervous system (CNS) is a predominant site of involvement in several lysosomal storage diseases (LSDs); and for many patients, these diseases are diagnosed only after the onset of symptoms related to the progressive accumulation of macromolecules within lysosomes. The mucopolysaccharidosis type VII (MPS VI...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015707
更新日期:2000-03-01 00:00:00
abstract::Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.166
更新日期:2017-05-01 00:00:00
abstract::Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem cell-derived retina now offers the ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.027
更新日期:2018-10-01 00:00:00
abstract::Human serum is known to inactivate many retroviruses, including murine leukemia viruses (MLV). Exposure of vectors based on MLV to human serum components would presumably decrease the efficiency of gene transfer in vivo. Human serum also lyses xenogeneic cells, which would affect the survival of retroviral vector pack...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.5-635
更新日期:1995-05-01 00:00:00
abstract::Genome engineering has gone mainstream because of breakthroughs in defining and harnessing naturally occurring, customizable DNA recognition cursors (protein or RNA-guided). At present, most gene editing relies on these cursors to direct custom DNA endonucleases to a specific genomic sequence to induce a double-strand...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.071
更新日期:2016-06-01 00:00:00
abstract::The transfer of a drug resistance gene into hematopoietic cells is an approach being investigated to overcome the problem of myelosuppression produced by anticancer drugs. Chemotherapeutic agents are often given in combination in order to increase their effectiveness. Consequently, there is an advantage in designing v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.17-2537
更新日期:1998-11-20 00:00:00