Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids
- Autores
- Finocchiaro, L.M.E.; Bumaschny, V.F.; Karara, A.L.; Fiszman, G.L.; Casais, C.C.; Glikin, G.C.
- Año de publicación
- 2004
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- We have developed multicellular spheroids (MCS) established from LM05e and LM3 spontaneous Balb/c-murine mammary adenocarcinoma and B16 C57-murine melanoma derived cell lines as an in vitro model to study the efficacy of the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide system. We demonstrated for the first time that HSVtk-expressing cells assembled as MCS manifested a GCV resistance phenotype compared to the same cells grown as sparse monolayers. HSVtk-expressing LM05e, LM3 and B16 spheroids were 16-, three- and nine-fold less sensitive to GCV than their respective monolayers, even though they could express transgenes 10-, eight- and five-fold more efficiently. Mixed populations of HSVtk- and their respective βgal-expressing cells displayed a cell-type specific bystander effect that was higher in monolayers than in MCS. However, HSVtk-expressing cells in two- or three-dimensional cultures were always significantly more sensitive to GCV than the βgal-expressing counterparts, supporting the feasibility of this suicide approach in vivo. We present evidence showing that HSVtk-expressing tumor cells, when transferred from monolayers to MCS, displayed: (i) lower GCV cytotoxic activity and bystander effect; (ii) higher and efficient expression of genes transferred as lipoplexes; (iii) lower cell proliferation rates; and (iv) changes in intracellular Bax/Bcl-xL rheostat of mitochondria-mediated apoptosis.
Fil:Finocchiaro, L.M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Casais, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Glikin, G.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. - Fuente
- Cancer Gene Ther. 2004;11(5):333-345
- Materia
-
Lipofection
Murine adenocarcinoma
Suicide gene therapy
ganciclovir
suicide substrate
thymidine kinase
animal cell
animal tissue
apoptosis
article
breast adenocarcinoma
bystander effect
cell growth
cell proliferation
cell specificity
cell type
controlled study
drug cytotoxicity
drug efficacy
gene expression regulation
gene transfer
Herpes simplex virus
in vitro study
in vivo study
intracellular transport
melanoma cell
mitochondrion
monolayer culture
mouse
multicellular spheroid
nonhuman
phenotype
population structure
priority journal
protein assembly
sensitivity analysis
statistical significance
transgene
virus resistance
Adenocarcinoma
Animals
Antiviral Agents
bcl-2-Associated X Protein
beta-Galactosidase
Bystander Effect
Cell Division
Cell Line, Tumor
Drug Resistance
Ganciclovir
Gene Therapy
Mammary Neoplasms, Animal
Melanoma
Mice
Mice, Inbred BALB C
Proto-Oncogene Proteins c-bcl-2
Simplexvirus
Spheroids, Cellular
Thymidine Kinase
Transfection
Viral Proteins
Animalia
Murinae
Simplexvirus - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by/2.5/ar
- Repositorio
- Institución
- Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
- OAI Identificador
- paperaa:paper_09291903_v11_n5_p333_Finocchiaro
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Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroidsFinocchiaro, L.M.E.Bumaschny, V.F.Karara, A.L.Fiszman, G.L.Casais, C.C.Glikin, G.C.LipofectionMurine adenocarcinomaSuicide gene therapyganciclovirsuicide substratethymidine kinaseanimal cellanimal tissueapoptosisarticlebreast adenocarcinomabystander effectcell growthcell proliferationcell specificitycell typecontrolled studydrug cytotoxicitydrug efficacygene expression regulationgene transferHerpes simplex virusin vitro studyin vivo studyintracellular transportmelanoma cellmitochondrionmonolayer culturemousemulticellular spheroidnonhumanphenotypepopulation structurepriority journalprotein assemblysensitivity analysisstatistical significancetransgenevirus resistanceAdenocarcinomaAnimalsAntiviral Agentsbcl-2-Associated X Proteinbeta-GalactosidaseBystander EffectCell DivisionCell Line, TumorDrug ResistanceGanciclovirGene TherapyMammary Neoplasms, AnimalMelanomaMiceMice, Inbred BALB CProto-Oncogene Proteins c-bcl-2SimplexvirusSpheroids, CellularThymidine KinaseTransfectionViral ProteinsAnimaliaMurinaeSimplexvirusWe have developed multicellular spheroids (MCS) established from LM05e and LM3 spontaneous Balb/c-murine mammary adenocarcinoma and B16 C57-murine melanoma derived cell lines as an in vitro model to study the efficacy of the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide system. We demonstrated for the first time that HSVtk-expressing cells assembled as MCS manifested a GCV resistance phenotype compared to the same cells grown as sparse monolayers. HSVtk-expressing LM05e, LM3 and B16 spheroids were 16-, three- and nine-fold less sensitive to GCV than their respective monolayers, even though they could express transgenes 10-, eight- and five-fold more efficiently. Mixed populations of HSVtk- and their respective βgal-expressing cells displayed a cell-type specific bystander effect that was higher in monolayers than in MCS. However, HSVtk-expressing cells in two- or three-dimensional cultures were always significantly more sensitive to GCV than the βgal-expressing counterparts, supporting the feasibility of this suicide approach in vivo. We present evidence showing that HSVtk-expressing tumor cells, when transferred from monolayers to MCS, displayed: (i) lower GCV cytotoxic activity and bystander effect; (ii) higher and efficient expression of genes transferred as lipoplexes; (iii) lower cell proliferation rates; and (iv) changes in intracellular Bax/Bcl-xL rheostat of mitochondria-mediated apoptosis.Fil:Finocchiaro, L.M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Casais, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Glikin, G.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.2004info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12110/paper_09291903_v11_n5_p333_FinocchiaroCancer Gene Ther. 2004;11(5):333-345reponame:Biblioteca Digital (UBA-FCEN)instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesinstacron:UBA-FCENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/ar2025-10-16T09:29:59Zpaperaa:paper_09291903_v11_n5_p333_FinocchiaroInstitucionalhttps://digital.bl.fcen.uba.ar/Universidad públicaNo correspondehttps://digital.bl.fcen.uba.ar/cgi-bin/oaiserver.cgiana@bl.fcen.uba.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:18962025-10-16 09:30:00.032Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesfalse |
dc.title.none.fl_str_mv |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids |
title |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids |
spellingShingle |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids Finocchiaro, L.M.E. Lipofection Murine adenocarcinoma Suicide gene therapy ganciclovir suicide substrate thymidine kinase animal cell animal tissue apoptosis article breast adenocarcinoma bystander effect cell growth cell proliferation cell specificity cell type controlled study drug cytotoxicity drug efficacy gene expression regulation gene transfer Herpes simplex virus in vitro study in vivo study intracellular transport melanoma cell mitochondrion monolayer culture mouse multicellular spheroid nonhuman phenotype population structure priority journal protein assembly sensitivity analysis statistical significance transgene virus resistance Adenocarcinoma Animals Antiviral Agents bcl-2-Associated X Protein beta-Galactosidase Bystander Effect Cell Division Cell Line, Tumor Drug Resistance Ganciclovir Gene Therapy Mammary Neoplasms, Animal Melanoma Mice Mice, Inbred BALB C Proto-Oncogene Proteins c-bcl-2 Simplexvirus Spheroids, Cellular Thymidine Kinase Transfection Viral Proteins Animalia Murinae Simplexvirus |
title_short |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids |
title_full |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids |
title_fullStr |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids |
title_full_unstemmed |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids |
title_sort |
Herpes simplex virus thymidine kinase/ganciclovir system in multicellular tumor spheroids |
dc.creator.none.fl_str_mv |
Finocchiaro, L.M.E. Bumaschny, V.F. Karara, A.L. Fiszman, G.L. Casais, C.C. Glikin, G.C. |
author |
Finocchiaro, L.M.E. |
author_facet |
Finocchiaro, L.M.E. Bumaschny, V.F. Karara, A.L. Fiszman, G.L. Casais, C.C. Glikin, G.C. |
author_role |
author |
author2 |
Bumaschny, V.F. Karara, A.L. Fiszman, G.L. Casais, C.C. Glikin, G.C. |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
Lipofection Murine adenocarcinoma Suicide gene therapy ganciclovir suicide substrate thymidine kinase animal cell animal tissue apoptosis article breast adenocarcinoma bystander effect cell growth cell proliferation cell specificity cell type controlled study drug cytotoxicity drug efficacy gene expression regulation gene transfer Herpes simplex virus in vitro study in vivo study intracellular transport melanoma cell mitochondrion monolayer culture mouse multicellular spheroid nonhuman phenotype population structure priority journal protein assembly sensitivity analysis statistical significance transgene virus resistance Adenocarcinoma Animals Antiviral Agents bcl-2-Associated X Protein beta-Galactosidase Bystander Effect Cell Division Cell Line, Tumor Drug Resistance Ganciclovir Gene Therapy Mammary Neoplasms, Animal Melanoma Mice Mice, Inbred BALB C Proto-Oncogene Proteins c-bcl-2 Simplexvirus Spheroids, Cellular Thymidine Kinase Transfection Viral Proteins Animalia Murinae Simplexvirus |
topic |
Lipofection Murine adenocarcinoma Suicide gene therapy ganciclovir suicide substrate thymidine kinase animal cell animal tissue apoptosis article breast adenocarcinoma bystander effect cell growth cell proliferation cell specificity cell type controlled study drug cytotoxicity drug efficacy gene expression regulation gene transfer Herpes simplex virus in vitro study in vivo study intracellular transport melanoma cell mitochondrion monolayer culture mouse multicellular spheroid nonhuman phenotype population structure priority journal protein assembly sensitivity analysis statistical significance transgene virus resistance Adenocarcinoma Animals Antiviral Agents bcl-2-Associated X Protein beta-Galactosidase Bystander Effect Cell Division Cell Line, Tumor Drug Resistance Ganciclovir Gene Therapy Mammary Neoplasms, Animal Melanoma Mice Mice, Inbred BALB C Proto-Oncogene Proteins c-bcl-2 Simplexvirus Spheroids, Cellular Thymidine Kinase Transfection Viral Proteins Animalia Murinae Simplexvirus |
dc.description.none.fl_txt_mv |
We have developed multicellular spheroids (MCS) established from LM05e and LM3 spontaneous Balb/c-murine mammary adenocarcinoma and B16 C57-murine melanoma derived cell lines as an in vitro model to study the efficacy of the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide system. We demonstrated for the first time that HSVtk-expressing cells assembled as MCS manifested a GCV resistance phenotype compared to the same cells grown as sparse monolayers. HSVtk-expressing LM05e, LM3 and B16 spheroids were 16-, three- and nine-fold less sensitive to GCV than their respective monolayers, even though they could express transgenes 10-, eight- and five-fold more efficiently. Mixed populations of HSVtk- and their respective βgal-expressing cells displayed a cell-type specific bystander effect that was higher in monolayers than in MCS. However, HSVtk-expressing cells in two- or three-dimensional cultures were always significantly more sensitive to GCV than the βgal-expressing counterparts, supporting the feasibility of this suicide approach in vivo. We present evidence showing that HSVtk-expressing tumor cells, when transferred from monolayers to MCS, displayed: (i) lower GCV cytotoxic activity and bystander effect; (ii) higher and efficient expression of genes transferred as lipoplexes; (iii) lower cell proliferation rates; and (iv) changes in intracellular Bax/Bcl-xL rheostat of mitochondria-mediated apoptosis. Fil:Finocchiaro, L.M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Casais, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Glikin, G.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. |
description |
We have developed multicellular spheroids (MCS) established from LM05e and LM3 spontaneous Balb/c-murine mammary adenocarcinoma and B16 C57-murine melanoma derived cell lines as an in vitro model to study the efficacy of the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide system. We demonstrated for the first time that HSVtk-expressing cells assembled as MCS manifested a GCV resistance phenotype compared to the same cells grown as sparse monolayers. HSVtk-expressing LM05e, LM3 and B16 spheroids were 16-, three- and nine-fold less sensitive to GCV than their respective monolayers, even though they could express transgenes 10-, eight- and five-fold more efficiently. Mixed populations of HSVtk- and their respective βgal-expressing cells displayed a cell-type specific bystander effect that was higher in monolayers than in MCS. However, HSVtk-expressing cells in two- or three-dimensional cultures were always significantly more sensitive to GCV than the βgal-expressing counterparts, supporting the feasibility of this suicide approach in vivo. We present evidence showing that HSVtk-expressing tumor cells, when transferred from monolayers to MCS, displayed: (i) lower GCV cytotoxic activity and bystander effect; (ii) higher and efficient expression of genes transferred as lipoplexes; (iii) lower cell proliferation rates; and (iv) changes in intracellular Bax/Bcl-xL rheostat of mitochondria-mediated apoptosis. |
publishDate |
2004 |
dc.date.none.fl_str_mv |
2004 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12110/paper_09291903_v11_n5_p333_Finocchiaro |
url |
http://hdl.handle.net/20.500.12110/paper_09291903_v11_n5_p333_Finocchiaro |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by/2.5/ar |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Cancer Gene Ther. 2004;11(5):333-345 reponame:Biblioteca Digital (UBA-FCEN) instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales instacron:UBA-FCEN |
reponame_str |
Biblioteca Digital (UBA-FCEN) |
collection |
Biblioteca Digital (UBA-FCEN) |
instname_str |
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
instacron_str |
UBA-FCEN |
institution |
UBA-FCEN |
repository.name.fl_str_mv |
Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales |
repository.mail.fl_str_mv |
ana@bl.fcen.uba.ar |
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1846142842845528064 |
score |
12.712165 |