We are analyzing https://link.springer.com/article/10.1007/s00109-005-0009-1.

Title:
An improved Tet-On regulatable FasL-adenovirus vector system for lung cancer therapy | Journal of Molecular Medicine
Description:
Gene therapy is a new therapeutic approach for the treatment of human cancers. Gene expression systems that can be regulated by drugs have been developed to improve the safety and efficacy of therapeutic transgene delivery. One of the most promising systems is the tetracycline (Tet)-responsive system in the Tet-On configuration. A major problem of the Tet-On system if used in viral vectors is the high basal activity of the Tet response element (TRE) promoter leading to leaky expression of transgenes under uninduced conditions. We therefore evaluated novel TRE promoters for controlling gene expression in an adenovirus vector (AdV) Tet-On system and further investigated them for expression of the pro-apoptotic CD95/Fas ligand (FasL) in human epithelial carcinoma cell line (HeLa) and lung cancer cells. Plasmid-based reporter gene assays showed that modifications within the tetO 7 and minimal immediate early cytomegalovirus promoter (CMV)min sequence of the TRE promoter reduced its leakiness and led to a markedly improved regulatability by doxycycline. Among several TRE promoters tested, a new construct (TRE-Tight1) containing modifications of both the tetO 7 sequence and the CMVmin showed 11-fold reduced leakiness and 1.5-fold increased absolute transgene expression levels after induction, as compared to the original TRE. Under induced conditions, a TRE-Tight1 promoter-dependent AdV expressing the pro-apoptotic CD95L/FasL induced apoptosis and cell lysis in HeLa cells as efficiently as an AdV containing the original TRE promoter. In contrast to the latter, however, the vector with the modified TRE promoter left cells totally unaffected in the absence of the inducer. Stringently regulated induction of apoptosis and cell death by TRE-Tight1-AdV was also demonstrated in three human lung cancer cell lines. These data show that the novel TRE-Tight1 promoter has a high potential for closely controlled and efficient expression of cytotoxic genes in AdV-based anti-cancer approaches.
Website Age:
28 years and 1 months (reg. 1997-05-29).

Matching Content Categories {📚}

Science
Education
Health & Fitness

Content Management System {📝}

What CMS is link.springer.com built with?

Custom-built

No common CMS systems were detected on Link.springer.com, and no known web development framework was identified.

Traffic Estimate {📈}

What is the average monthly size of link.springer.com audience?

🌠 Phenomenal Traffic: 5M - 10M visitors per month

Based on our best estimate, this website will receive around 5,000,019 visitors per month in the current month.
However, some sources were not loaded, we suggest to reload the page to get complete results.

check SE Ranking
check Ahrefs
check Similarweb
check Ubersuggest
check Semrush

How Does Link.springer.com Make Money? {💸}

We're unsure if the website is profiting.

Websites don't always need to be profitable; some serve as platforms for education or personal expression. Websites can serve multiple purposes. And this might be one of them. Link.springer.com could be getting rich in stealth mode, or the way it's monetizing isn't detectable.

Keywords {🔍}

article, gene, pubmed, cas, google, scholar, expression, cancer, ther, cells, system, vector, wang, lung, therapy, poller, fechner, human, promoter, cell, apoptosis, berlin, tre, adenovirus, vectors, ligand, fas, teton, sipo, hurtado, picó, transgene, access, control, mol, bujard, privacy, cookies, content, journal, research, regulated, tetracycline, transcriptional, tight, med, charitéuniversitätsmedizin, data, information, publish,

Topics {✒️}

pro-apoptotic cd95/fas ligand adv-based anti-cancer approaches month download article/chapter tetracycline-dependent transcriptional activators generation tetracycline-regulatable promoter replication-competent adenovirus vector ecdysone-inducible gene switch monoclonal antibody-induced apoptosis adenovirus-mediated fasl expression prostate cancer cells generation tetracycline-responsive promoters adenovirus-mediated gene transfer recombinant adenoviral vectors oncolytic adenovirus replication tet response element m2 tetracycline transactivator high basal activity lung cancer therapy full article pdf cancer gene therapy cd95l/fasl overcomes tetracycline-responsive promoter cd95/fas signaling tre promoter reduced lung cancer cells privacy choices/manage cookies therapeutic transgene delivery single adenovirus vector original tre promoter tre-tight1 promoter gene therapy platform fas ligand expression adenovirus-mediated expression fas-mediated apoptosis tetracycline-responsive promoters skin cancer center tts expression cassettes cardiovascular research center early cytomegalovirus promoter tre-tight1-adv anti-inflammatory cytokines human melanoma cells intrinsic apoptosis resistance almudena hurtado picó human melanoma xenotransplants controlling gene expression check access instant access article sipo tre promoters tested

Schema {🗺️}

WebPage:
      mainEntity:
         headline:An improved Tet-On regulatable FasL-adenovirus vector system for lung cancer therapy
         description:Gene therapy is a new therapeutic approach for the treatment of human cancers. Gene expression systems that can be regulated by drugs have been developed to improve the safety and efficacy of therapeutic transgene delivery. One of the most promising systems is the tetracycline (Tet)-responsive system in the Tet-On configuration. A major problem of the Tet-On system if used in viral vectors is the high basal activity of the Tet response element (TRE) promoter leading to leaky expression of transgenes under uninduced conditions. We therefore evaluated novel TRE promoters for controlling gene expression in an adenovirus vector (AdV) Tet-On system and further investigated them for expression of the pro-apoptotic CD95/Fas ligand (FasL) in human epithelial carcinoma cell line (HeLa) and lung cancer cells. Plasmid-based reporter gene assays showed that modifications within the tetO 7 and minimal immediate early cytomegalovirus promoter (CMV)min sequence of the TRE promoter reduced its leakiness and led to a markedly improved regulatability by doxycycline. Among several TRE promoters tested, a new construct (TRE-Tight1) containing modifications of both the tetO 7 sequence and the CMVmin showed 11-fold reduced leakiness and 1.5-fold increased absolute transgene expression levels after induction, as compared to the original TRE. Under induced conditions, a TRE-Tight1 promoter-dependent AdV expressing the pro-apoptotic CD95L/FasL induced apoptosis and cell lysis in HeLa cells as efficiently as an AdV containing the original TRE promoter. In contrast to the latter, however, the vector with the modified TRE promoter left cells totally unaffected in the absence of the inducer. Stringently regulated induction of apoptosis and cell death by TRE-Tight1-AdV was also demonstrated in three human lung cancer cell lines. These data show that the novel TRE-Tight1 promoter has a high potential for closely controlled and efficient expression of cytotoxic genes in AdV-based anti-cancer approaches.
         datePublished:2005-12-31T00:00:00Z
         dateModified:2005-12-31T00:00:00Z
         pageStart:215
         pageEnd:225
         sameAs:https://doi.org/10.1007/s00109-005-0009-1
         keywords:
            Cancer gene therapy
            Tet-On system
            CD95/Fas-ligand
            Apoptosis
            Tetracycline response element
            Molecular Medicine
            Human Genetics
            Internal Medicine
         image:
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig1_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig2_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig3_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig4_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig5_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig6_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig7_HTML.gif
            https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig8_HTML.gif
         isPartOf:
            name:Journal of Molecular Medicine
            issn:
               1432-1440
               0946-2716
            volumeNumber:84
            type:
               Periodical
               PublicationVolume
         publisher:
            name:Springer-Verlag
            logo:
               url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
               type:ImageObject
            type:Organization
         author:
               name:Isaac Sipo
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Almudena Hurtado Picó
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Xiaomin Wang
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Jürgen Eberle
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Iver Petersen
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Department of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Stefan Weger
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Institute of Infectious Diseases, Department of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Wolfgang Poller
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               type:Person
               name:Henry Fechner
               affiliation:
                     name:Charité-Universitätsmedizin Berlin
                     address:
                        name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
         isAccessibleForFree:
         hasPart:
            isAccessibleForFree:
            cssSelector:.main-content
            type:WebPageElement
         type:ScholarlyArticle
      context:https://schema.org
ScholarlyArticle:
      headline:An improved Tet-On regulatable FasL-adenovirus vector system for lung cancer therapy
      description:Gene therapy is a new therapeutic approach for the treatment of human cancers. Gene expression systems that can be regulated by drugs have been developed to improve the safety and efficacy of therapeutic transgene delivery. One of the most promising systems is the tetracycline (Tet)-responsive system in the Tet-On configuration. A major problem of the Tet-On system if used in viral vectors is the high basal activity of the Tet response element (TRE) promoter leading to leaky expression of transgenes under uninduced conditions. We therefore evaluated novel TRE promoters for controlling gene expression in an adenovirus vector (AdV) Tet-On system and further investigated them for expression of the pro-apoptotic CD95/Fas ligand (FasL) in human epithelial carcinoma cell line (HeLa) and lung cancer cells. Plasmid-based reporter gene assays showed that modifications within the tetO 7 and minimal immediate early cytomegalovirus promoter (CMV)min sequence of the TRE promoter reduced its leakiness and led to a markedly improved regulatability by doxycycline. Among several TRE promoters tested, a new construct (TRE-Tight1) containing modifications of both the tetO 7 sequence and the CMVmin showed 11-fold reduced leakiness and 1.5-fold increased absolute transgene expression levels after induction, as compared to the original TRE. Under induced conditions, a TRE-Tight1 promoter-dependent AdV expressing the pro-apoptotic CD95L/FasL induced apoptosis and cell lysis in HeLa cells as efficiently as an AdV containing the original TRE promoter. In contrast to the latter, however, the vector with the modified TRE promoter left cells totally unaffected in the absence of the inducer. Stringently regulated induction of apoptosis and cell death by TRE-Tight1-AdV was also demonstrated in three human lung cancer cell lines. These data show that the novel TRE-Tight1 promoter has a high potential for closely controlled and efficient expression of cytotoxic genes in AdV-based anti-cancer approaches.
      datePublished:2005-12-31T00:00:00Z
      dateModified:2005-12-31T00:00:00Z
      pageStart:215
      pageEnd:225
      sameAs:https://doi.org/10.1007/s00109-005-0009-1
      keywords:
         Cancer gene therapy
         Tet-On system
         CD95/Fas-ligand
         Apoptosis
         Tetracycline response element
         Molecular Medicine
         Human Genetics
         Internal Medicine
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig1_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig2_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig3_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig4_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig5_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig6_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig7_HTML.gif
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00109-005-0009-1/MediaObjects/109_2005_9_Fig8_HTML.gif
      isPartOf:
         name:Journal of Molecular Medicine
         issn:
            1432-1440
            0946-2716
         volumeNumber:84
         type:
            Periodical
            PublicationVolume
      publisher:
         name:Springer-Verlag
         logo:
            url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
            type:ImageObject
         type:Organization
      author:
            name:Isaac Sipo
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Almudena Hurtado Picó
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Xiaomin Wang
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jürgen Eberle
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Iver Petersen
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Department of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Stefan Weger
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Institute of Infectious Diseases, Department of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Wolfgang Poller
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Henry Fechner
            affiliation:
                  name:Charité-Universitätsmedizin Berlin
                  address:
                     name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:
      hasPart:
         isAccessibleForFree:
         cssSelector:.main-content
         type:WebPageElement
["Periodical","PublicationVolume"]:
      name:Journal of Molecular Medicine
      issn:
         1432-1440
         0946-2716
      volumeNumber:84
Organization:
      name:Springer-Verlag
      logo:
         url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
         type:ImageObject
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Department of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Institute of Infectious Diseases, Department of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
      name:Charité-Universitätsmedizin Berlin
      address:
         name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Isaac Sipo
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Almudena Hurtado Picó
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Xiaomin Wang
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Jürgen Eberle
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Iver Petersen
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Department of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Stefan Weger
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Institute of Infectious Diseases, Department of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Wolfgang Poller
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Henry Fechner
      affiliation:
            name:Charité-Universitätsmedizin Berlin
            address:
               name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
      name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
      name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
      name:Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
      name:Department of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany
      name:Institute of Infectious Diseases, Department of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany
      name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
      name:Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Berlin, Germany
WebPageElement:
      isAccessibleForFree:
      cssSelector:.main-content

External Links {🔗}(139)

Analytics and Tracking {📊}

Google Tag Manager

Libraries {📚}

Clipboard.js
Prism.js

CDN Services {📦}

Crossref

4.48s.

LINK . SPRINGER . COM {}