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Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868
Summary The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01 CDDP . Transforming growth factor α (TGF-α)-stimulated growth w...
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| Published in: | British journal of cancer 1999-03, Vol.79 (7), p.1098-1103 |
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| container_end_page | 1103 |
| container_issue | 7 |
| container_start_page | 1098 |
| container_title | British journal of cancer |
| container_volume | 79 |
| creator | Simpson, B J B Bartlett, J M S Macleod, K G Rabiasz, G Miller, E P Rae, A L Gordge, P Leake, R E Miller, W R Smyth, J Langdon, S P |
| description | Summary
The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01
CDDP
. Transforming growth factor α (TGF-α)-stimulated growth was completely inhibited by concentrations ≥ 0.3 μ
M
in the PE01 and PE04 cell lines and by ≥ 0.1 μ
M
in SKOV-3 cells. TGF-α inhibition of PE01
CDDP
growth was reversed by concentrations ≥ 0.1 μ
M
ZM 252868. TGF-α-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations ≥ 0.3 μ
M
, completely inhibited TGF-α-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 μ
M
ZM 252868 in PE01, SKOV-3 and PE01
CDDP
cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor. |
| doi_str_mv | 10.1038/sj.bjc.6690175 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2362251</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69656459</sourcerecordid><originalsourceid>FETCH-LOGICAL-c486t-b78ac2ece02d926d3a0ea8c5b93b22be21a46f399e3dbd002ad69bfef097bc783</originalsourceid><addsrcrecordid>eNqFkbFuFDEQhi0EIkegpUQuEArFXmzvrtduIqEoCZGCaEJDY9ne8Z2XPTvYe0H3GrxJXiTPhI87IBSIyrbmm3_8z4_QS0rmlNTiOA9zM9g555LQrn2EZrStWUUF6x6jGSGkq4hk5AA9y3koT0lE9xQd0HITXcNm6PtlWHrjJx8Djg5PSYfsYlr5sMCLFL9NS-y0nWLC93f46PrivLq_e1utoPd6gv4XAs6BnTL2ReRWJ68DtjpYSNjCOOLRB8jYbLDG0ybFXJ74iw86Q-n4Ob7of_6AWcsEF8_RE6fHDC_25yH6dH52ffq-uvp4cXn67qqyjeBTZTqhLQMLhPWS8b7WBLSwrZG1YcwAo7rhrpYS6t70hDDdc2kcOCI7YztRH6KTne7N2hRDFkJxP6qb5Fc6bVTUXv1dCX6pFvFWsZoz1tIi8GYvkOLXNeRJrXzeGtYB4jorLnnLm1b-F6QdY4KKroDzHWjLlnIC9_s3lKht3ioPquSt9nmXhlcPPTzAdwEX4PUe0Nnq0ZV8rc9_OC4aKbc6xzssl0pYQFJDXKdQ1v-vyT8AlbvIFA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17228187</pqid></control><display><type>article</type><title>Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868</title><source>Open Access: PubMed Central</source><creator>Simpson, B J B ; Bartlett, J M S ; Macleod, K G ; Rabiasz, G ; Miller, E P ; Rae, A L ; Gordge, P ; Leake, R E ; Miller, W R ; Smyth, J ; Langdon, S P</creator><creatorcontrib>Simpson, B J B ; Bartlett, J M S ; Macleod, K G ; Rabiasz, G ; Miller, E P ; Rae, A L ; Gordge, P ; Leake, R E ; Miller, W R ; Smyth, J ; Langdon, S P</creatorcontrib><description>Summary
The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01
CDDP
. Transforming growth factor α (TGF-α)-stimulated growth was completely inhibited by concentrations ≥ 0.3 μ
M
in the PE01 and PE04 cell lines and by ≥ 0.1 μ
M
in SKOV-3 cells. TGF-α inhibition of PE01
CDDP
growth was reversed by concentrations ≥ 0.1 μ
M
ZM 252868. TGF-α-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations ≥ 0.3 μ
M
, completely inhibited TGF-α-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 μ
M
ZM 252868 in PE01, SKOV-3 and PE01
CDDP
cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6690175</identifier><identifier>PMID: 10098742</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Antineoplastic agents ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell Division - drug effects ; Drug Resistance ; Enzyme Inhibitors - pharmacology ; Epidemiology ; Female ; General aspects ; Humans ; Medical sciences ; Molecular Medicine ; Oncology ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Pharmacology. Drug treatments ; Phosphorylation - drug effects ; Proto-Oncogene Proteins - drug effects ; Proto-Oncogene Proteins - metabolism ; Quinazolines - pharmacology ; Receptor, Epidermal Growth Factor - antagonists & inhibitors ; Receptor, Epidermal Growth Factor - drug effects ; Receptor, Epidermal Growth Factor - metabolism ; Receptor, ErbB-2 - drug effects ; Receptor, ErbB-2 - metabolism ; Receptor, ErbB-3 ; Regular ; regular-article ; Signal Transduction ; Transforming Growth Factor alpha - antagonists & inhibitors ; Transforming Growth Factor alpha - pharmacology ; Tumor Cells, Cultured - drug effects</subject><ispartof>British journal of cancer, 1999-03, Vol.79 (7), p.1098-1103</ispartof><rights>The Author(s) 1999</rights><rights>1999 INIST-CNRS</rights><rights>Copyright © 1999 Cancer Research Campaign 1999 Cancer Research Campaign</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-b78ac2ece02d926d3a0ea8c5b93b22be21a46f399e3dbd002ad69bfef097bc783</citedby><cites>FETCH-LOGICAL-c486t-b78ac2ece02d926d3a0ea8c5b93b22be21a46f399e3dbd002ad69bfef097bc783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362251/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362251/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1684995$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10098742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Simpson, B J B</creatorcontrib><creatorcontrib>Bartlett, J M S</creatorcontrib><creatorcontrib>Macleod, K G</creatorcontrib><creatorcontrib>Rabiasz, G</creatorcontrib><creatorcontrib>Miller, E P</creatorcontrib><creatorcontrib>Rae, A L</creatorcontrib><creatorcontrib>Gordge, P</creatorcontrib><creatorcontrib>Leake, R E</creatorcontrib><creatorcontrib>Miller, W R</creatorcontrib><creatorcontrib>Smyth, J</creatorcontrib><creatorcontrib>Langdon, S P</creatorcontrib><title>Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Summary
The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01
CDDP
. Transforming growth factor α (TGF-α)-stimulated growth was completely inhibited by concentrations ≥ 0.3 μ
M
in the PE01 and PE04 cell lines and by ≥ 0.1 μ
M
in SKOV-3 cells. TGF-α inhibition of PE01
CDDP
growth was reversed by concentrations ≥ 0.1 μ
M
ZM 252868. TGF-α-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations ≥ 0.3 μ
M
, completely inhibited TGF-α-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 μ
M
ZM 252868 in PE01, SKOV-3 and PE01
CDDP
cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell Division - drug effects</subject><subject>Drug Resistance</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Epidemiology</subject><subject>Female</subject><subject>General aspects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphorylation - drug effects</subject><subject>Proto-Oncogene Proteins - drug effects</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Quinazolines - pharmacology</subject><subject>Receptor, Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Receptor, Epidermal Growth Factor - drug effects</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Receptor, ErbB-2 - drug effects</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Receptor, ErbB-3</subject><subject>Regular</subject><subject>regular-article</subject><subject>Signal Transduction</subject><subject>Transforming Growth Factor alpha - antagonists & inhibitors</subject><subject>Transforming Growth Factor alpha - pharmacology</subject><subject>Tumor Cells, Cultured - drug effects</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><recordid>eNqFkbFuFDEQhi0EIkegpUQuEArFXmzvrtduIqEoCZGCaEJDY9ne8Z2XPTvYe0H3GrxJXiTPhI87IBSIyrbmm3_8z4_QS0rmlNTiOA9zM9g555LQrn2EZrStWUUF6x6jGSGkq4hk5AA9y3koT0lE9xQd0HITXcNm6PtlWHrjJx8Djg5PSYfsYlr5sMCLFL9NS-y0nWLC93f46PrivLq_e1utoPd6gv4XAs6BnTL2ReRWJ68DtjpYSNjCOOLRB8jYbLDG0ybFXJ74iw86Q-n4Ob7of_6AWcsEF8_RE6fHDC_25yH6dH52ffq-uvp4cXn67qqyjeBTZTqhLQMLhPWS8b7WBLSwrZG1YcwAo7rhrpYS6t70hDDdc2kcOCI7YztRH6KTne7N2hRDFkJxP6qb5Fc6bVTUXv1dCX6pFvFWsZoz1tIi8GYvkOLXNeRJrXzeGtYB4jorLnnLm1b-F6QdY4KKroDzHWjLlnIC9_s3lKht3ioPquSt9nmXhlcPPTzAdwEX4PUe0Nnq0ZV8rc9_OC4aKbc6xzssl0pYQFJDXKdQ1v-vyT8AlbvIFA</recordid><startdate>19990301</startdate><enddate>19990301</enddate><creator>Simpson, B J B</creator><creator>Bartlett, J M S</creator><creator>Macleod, K G</creator><creator>Rabiasz, G</creator><creator>Miller, E P</creator><creator>Rae, A L</creator><creator>Gordge, P</creator><creator>Leake, R E</creator><creator>Miller, W R</creator><creator>Smyth, J</creator><creator>Langdon, S P</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7TO</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19990301</creationdate><title>Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868</title><author>Simpson, B J B ; Bartlett, J M S ; Macleod, K G ; Rabiasz, G ; Miller, E P ; Rae, A L ; Gordge, P ; Leake, R E ; Miller, W R ; Smyth, J ; Langdon, S P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c486t-b78ac2ece02d926d3a0ea8c5b93b22be21a46f399e3dbd002ad69bfef097bc783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell Division - drug effects</topic><topic>Drug Resistance</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Epidemiology</topic><topic>Female</topic><topic>General aspects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphorylation - drug effects</topic><topic>Proto-Oncogene Proteins - drug effects</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Quinazolines - pharmacology</topic><topic>Receptor, Epidermal Growth Factor - antagonists & inhibitors</topic><topic>Receptor, Epidermal Growth Factor - drug effects</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Receptor, ErbB-2 - drug effects</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Receptor, ErbB-3</topic><topic>Regular</topic><topic>regular-article</topic><topic>Signal Transduction</topic><topic>Transforming Growth Factor alpha - antagonists & inhibitors</topic><topic>Transforming Growth Factor alpha - pharmacology</topic><topic>Tumor Cells, Cultured - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Simpson, B J B</creatorcontrib><creatorcontrib>Bartlett, J M S</creatorcontrib><creatorcontrib>Macleod, K G</creatorcontrib><creatorcontrib>Rabiasz, G</creatorcontrib><creatorcontrib>Miller, E P</creatorcontrib><creatorcontrib>Rae, A L</creatorcontrib><creatorcontrib>Gordge, P</creatorcontrib><creatorcontrib>Leake, R E</creatorcontrib><creatorcontrib>Miller, W R</creatorcontrib><creatorcontrib>Smyth, J</creatorcontrib><creatorcontrib>Langdon, S P</creatorcontrib><collection>SpringerOpen</collection><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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Simpson, B J B</au><au>Bartlett, J M S</au><au>Macleod, K G</au><au>Rabiasz, G</au><au>Miller, E P</au><au>Rae, A L</au><au>Gordge, P</au><au>Leake, R E</au><au>Miller, W R</au><au>Smyth, J</au><au>Langdon, S P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>1999-03-01</date><risdate>1999</risdate><volume>79</volume><issue>7</issue><spage>1098</spage><epage>1103</epage><pages>1098-1103</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Summary
The modulating effects of the epidermal growth factor (EGF) receptor-specific tyrosine kinase inhibitor ZM 252868 on cell growth and signalling have been evaluated in four ovarian carcinoma cell lines PE01, PE04, SKOV-3 and PE01
CDDP
. Transforming growth factor α (TGF-α)-stimulated growth was completely inhibited by concentrations ≥ 0.3 μ
M
in the PE01 and PE04 cell lines and by ≥ 0.1 μ
M
in SKOV-3 cells. TGF-α inhibition of PE01
CDDP
growth was reversed by concentrations ≥ 0.1 μ
M
ZM 252868. TGF-α-stimulated tyrosine phosphorylation of both the EGF receptor and c-erbB2 receptor in all four cell lines. The inhibitor ZM 252868, at concentrations ≥ 0.3 μ
M
, completely inhibited TGF-α-stimulated tyrosine phosphorylation of the EGF receptor and reduced phosphorylation of the c-erbB2 protein. EGF-activated EGF receptor tyrosine kinase activity was completely inhibited by 3 μ
M
ZM 252868 in PE01, SKOV-3 and PE01
CDDP
cells. These data indicate that the EGF receptor-targeted TK inhibitor ZM 252868 can inhibit growth of ovarian carcinoma cells in vitro consistent with inhibition of tyrosine phosphorylation at the EGF receptor.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>10098742</pmid><doi>10.1038/sj.bjc.6690175</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 1999-03, Vol.79 (7), p.1098-1103 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2362251 |
| source | Open Access: PubMed Central |
| subjects | Antineoplastic agents Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cell Division - drug effects Drug Resistance Enzyme Inhibitors - pharmacology Epidemiology Female General aspects Humans Medical sciences Molecular Medicine Oncology Ovarian Neoplasms - drug therapy Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Pharmacology. Drug treatments Phosphorylation - drug effects Proto-Oncogene Proteins - drug effects Proto-Oncogene Proteins - metabolism Quinazolines - pharmacology Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - drug effects Receptor, Epidermal Growth Factor - metabolism Receptor, ErbB-2 - drug effects Receptor, ErbB-2 - metabolism Receptor, ErbB-3 Regular regular-article Signal Transduction Transforming Growth Factor alpha - antagonists & inhibitors Transforming Growth Factor alpha - pharmacology Tumor Cells, Cultured - drug effects |
| title | Inhibition of transforming growth factor α (TGF-α)-mediated growth effects in ovarian cancer cell lines by a tyrosine kinase inhibitor ZM 252868 |
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