Loading…
Ganciclovir Uptake in Human Mammary Carcinoma Cells Expressing Herpes Simplex Virus Thymidine Kinase
Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma ce...
Saved in:
Published in: | Nuclear medicine and biology 1998-05, Vol.25 (4), p.367-373 |
---|---|
Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c515t-bd987e8bd775480f5139cea18384ed7cb4a75e69bcb20ac05193010225de7c4a3 |
---|---|
cites | cdi_FETCH-LOGICAL-c515t-bd987e8bd775480f5139cea18384ed7cb4a75e69bcb20ac05193010225de7c4a3 |
container_end_page | 373 |
container_issue | 4 |
container_start_page | 367 |
container_title | Nuclear medicine and biology |
container_volume | 25 |
creator | Haberkorn, Uwe Khazaie, Khashayarsha Morr, Iris Altmann, Annette Müller, Markus van Kaick, Gerhard |
description | Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (
r = 0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk. |
doi_str_mv | 10.1016/S0969-8051(97)00210-2 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_79951308</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0969805197002102</els_id><sourcerecordid>79951308</sourcerecordid><originalsourceid>FETCH-LOGICAL-c515t-bd987e8bd775480f5139cea18384ed7cb4a75e69bcb20ac05193010225de7c4a3</originalsourceid><addsrcrecordid>eNqFkUtv1DAUhS1EVYbSn1DJC4RgkWI7cWyvEBqVDqKIRR9by7HvgCFxUt9J1f57PJ3RbLu6i_ud-ziHkDPOzjnj7edrZlpTaSb5R6M-MSY4q8QrsuBaicq0vHlNFgfkDXmL-JcVXcPZMTk2bW2E0QsSLl3y0ffjQ8z0dtq4f0Bjoqt5cIn-dMPg8hNduuxjGgdHl9D3SC8epwyIMf2mK8gTIL2Ow9TDI72LeUZ68-dpiCEmoD9icgjvyNHa9Qin-3pCbr9d3CxX1dWvy-_Lr1eVl1xuqi4YrUB3QSnZaLaWvDYeHNe1biAo3zVOSWhN5zvBnC9vmZpxJoQMoHzj6hPyYTd3yuP9DLixQ0RfTnYJxhmtMqbMZPpFsNgkmTKygHIH-jwiZljbKcetJ5Yzu43BPsdgtx5bo-xzDFYU3dl-wdwNEA6qve-l_37fd-hdv87bFPCACdHUkjcF-7LDoLj2ECFb9BGShxAz-I0NY3zhkP8aV6Qd</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16450795</pqid></control><display><type>article</type><title>Ganciclovir Uptake in Human Mammary Carcinoma Cells Expressing Herpes Simplex Virus Thymidine Kinase</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Haberkorn, Uwe ; Khazaie, Khashayarsha ; Morr, Iris ; Altmann, Annette ; Müller, Markus ; van Kaick, Gerhard</creator><creatorcontrib>Haberkorn, Uwe ; Khazaie, Khashayarsha ; Morr, Iris ; Altmann, Annette ; Müller, Markus ; van Kaick, Gerhard</creatorcontrib><description>Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (
r = 0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk.</description><identifier>ISSN: 0969-8051</identifier><identifier>EISSN: 1872-9614</identifier><identifier>DOI: 10.1016/S0969-8051(97)00210-2</identifier><identifier>PMID: 9639298</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Antiviral Agents - metabolism ; Antiviral Agents - pharmacokinetics ; Biological and medical sciences ; Breast Neoplasms - enzymology ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Ganciclovir ; Ganciclovir - metabolism ; Ganciclovir - pharmacokinetics ; Gene therapy ; Genetic Therapy ; Genetic Vectors ; Gynecology. Andrology. Obstetrics ; HSV thymidine kinase ; Humans ; Mammary carcinoma ; Mammary gland diseases ; Medical sciences ; Neoplasms - therapy ; Phosphorylation ; Simplexvirus - enzymology ; Simplexvirus - genetics ; Thymidine Kinase - genetics ; Tomography, Emission-Computed ; Transfection ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Nuclear medicine and biology, 1998-05, Vol.25 (4), p.367-373</ispartof><rights>1998 Elsevier Science Inc.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c515t-bd987e8bd775480f5139cea18384ed7cb4a75e69bcb20ac05193010225de7c4a3</citedby><cites>FETCH-LOGICAL-c515t-bd987e8bd775480f5139cea18384ed7cb4a75e69bcb20ac05193010225de7c4a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2243514$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9639298$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haberkorn, Uwe</creatorcontrib><creatorcontrib>Khazaie, Khashayarsha</creatorcontrib><creatorcontrib>Morr, Iris</creatorcontrib><creatorcontrib>Altmann, Annette</creatorcontrib><creatorcontrib>Müller, Markus</creatorcontrib><creatorcontrib>van Kaick, Gerhard</creatorcontrib><title>Ganciclovir Uptake in Human Mammary Carcinoma Cells Expressing Herpes Simplex Virus Thymidine Kinase</title><title>Nuclear medicine and biology</title><addtitle>Nucl Med Biol</addtitle><description>Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (
r = 0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk.</description><subject>Antiviral Agents - metabolism</subject><subject>Antiviral Agents - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - enzymology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Ganciclovir</subject><subject>Ganciclovir - metabolism</subject><subject>Ganciclovir - pharmacokinetics</subject><subject>Gene therapy</subject><subject>Genetic Therapy</subject><subject>Genetic Vectors</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>HSV thymidine kinase</subject><subject>Humans</subject><subject>Mammary carcinoma</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Neoplasms - therapy</subject><subject>Phosphorylation</subject><subject>Simplexvirus - enzymology</subject><subject>Simplexvirus - genetics</subject><subject>Thymidine Kinase - genetics</subject><subject>Tomography, Emission-Computed</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0969-8051</issn><issn>1872-9614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><recordid>eNqFkUtv1DAUhS1EVYbSn1DJC4RgkWI7cWyvEBqVDqKIRR9by7HvgCFxUt9J1f57PJ3RbLu6i_ud-ziHkDPOzjnj7edrZlpTaSb5R6M-MSY4q8QrsuBaicq0vHlNFgfkDXmL-JcVXcPZMTk2bW2E0QsSLl3y0ffjQ8z0dtq4f0Bjoqt5cIn-dMPg8hNduuxjGgdHl9D3SC8epwyIMf2mK8gTIL2Ow9TDI72LeUZ68-dpiCEmoD9icgjvyNHa9Qin-3pCbr9d3CxX1dWvy-_Lr1eVl1xuqi4YrUB3QSnZaLaWvDYeHNe1biAo3zVOSWhN5zvBnC9vmZpxJoQMoHzj6hPyYTd3yuP9DLixQ0RfTnYJxhmtMqbMZPpFsNgkmTKygHIH-jwiZljbKcetJ5Yzu43BPsdgtx5bo-xzDFYU3dl-wdwNEA6qve-l_37fd-hdv87bFPCACdHUkjcF-7LDoLj2ECFb9BGShxAz-I0NY3zhkP8aV6Qd</recordid><startdate>19980501</startdate><enddate>19980501</enddate><creator>Haberkorn, Uwe</creator><creator>Khazaie, Khashayarsha</creator><creator>Morr, Iris</creator><creator>Altmann, Annette</creator><creator>Müller, Markus</creator><creator>van Kaick, Gerhard</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19980501</creationdate><title>Ganciclovir Uptake in Human Mammary Carcinoma Cells Expressing Herpes Simplex Virus Thymidine Kinase</title><author>Haberkorn, Uwe ; Khazaie, Khashayarsha ; Morr, Iris ; Altmann, Annette ; Müller, Markus ; van Kaick, Gerhard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c515t-bd987e8bd775480f5139cea18384ed7cb4a75e69bcb20ac05193010225de7c4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Antiviral Agents - metabolism</topic><topic>Antiviral Agents - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - enzymology</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Ganciclovir</topic><topic>Ganciclovir - metabolism</topic><topic>Ganciclovir - pharmacokinetics</topic><topic>Gene therapy</topic><topic>Genetic Therapy</topic><topic>Genetic Vectors</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>HSV thymidine kinase</topic><topic>Humans</topic><topic>Mammary carcinoma</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Neoplasms - therapy</topic><topic>Phosphorylation</topic><topic>Simplexvirus - enzymology</topic><topic>Simplexvirus - genetics</topic><topic>Thymidine Kinase - genetics</topic><topic>Tomography, Emission-Computed</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haberkorn, Uwe</creatorcontrib><creatorcontrib>Khazaie, Khashayarsha</creatorcontrib><creatorcontrib>Morr, Iris</creatorcontrib><creatorcontrib>Altmann, Annette</creatorcontrib><creatorcontrib>Müller, Markus</creatorcontrib><creatorcontrib>van Kaick, Gerhard</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nuclear medicine and biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haberkorn, Uwe</au><au>Khazaie, Khashayarsha</au><au>Morr, Iris</au><au>Altmann, Annette</au><au>Müller, Markus</au><au>van Kaick, Gerhard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ganciclovir Uptake in Human Mammary Carcinoma Cells Expressing Herpes Simplex Virus Thymidine Kinase</atitle><jtitle>Nuclear medicine and biology</jtitle><addtitle>Nucl Med Biol</addtitle><date>1998-05-01</date><risdate>1998</risdate><volume>25</volume><issue>4</issue><spage>367</spage><epage>373</epage><pages>367-373</pages><issn>0969-8051</issn><eissn>1872-9614</eissn><abstract>Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (
r = 0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>9639298</pmid><doi>10.1016/S0969-8051(97)00210-2</doi><tpages>7</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0969-8051 |
ispartof | Nuclear medicine and biology, 1998-05, Vol.25 (4), p.367-373 |
issn | 0969-8051 1872-9614 |
language | eng |
recordid | cdi_proquest_miscellaneous_79951308 |
source | ScienceDirect Freedom Collection 2022-2024 |
subjects | Antiviral Agents - metabolism Antiviral Agents - pharmacokinetics Biological and medical sciences Breast Neoplasms - enzymology Breast Neoplasms - genetics Breast Neoplasms - metabolism Ganciclovir Ganciclovir - metabolism Ganciclovir - pharmacokinetics Gene therapy Genetic Therapy Genetic Vectors Gynecology. Andrology. Obstetrics HSV thymidine kinase Humans Mammary carcinoma Mammary gland diseases Medical sciences Neoplasms - therapy Phosphorylation Simplexvirus - enzymology Simplexvirus - genetics Thymidine Kinase - genetics Tomography, Emission-Computed Transfection Tumor Cells, Cultured Tumors |
title | Ganciclovir Uptake in Human Mammary Carcinoma Cells Expressing Herpes Simplex Virus Thymidine Kinase |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T07%3A27%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ganciclovir%20Uptake%20in%20Human%20Mammary%20Carcinoma%20Cells%20Expressing%20Herpes%20Simplex%20Virus%20Thymidine%20Kinase&rft.jtitle=Nuclear%20medicine%20and%20biology&rft.au=Haberkorn,%20Uwe&rft.date=1998-05-01&rft.volume=25&rft.issue=4&rft.spage=367&rft.epage=373&rft.pages=367-373&rft.issn=0969-8051&rft.eissn=1872-9614&rft_id=info:doi/10.1016/S0969-8051(97)00210-2&rft_dat=%3Cproquest_cross%3E79951308%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c515t-bd987e8bd775480f5139cea18384ed7cb4a75e69bcb20ac05193010225de7c4a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=16450795&rft_id=info:pmid/9639298&rfr_iscdi=true |