Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells
We have selected a panel of human tumor xenografts for in vitro and in vivo studies that allows an indication of selectivity of action of novel chemotherapeutic agents. We report here the antitumor activity of the flavone flavopiridol (previously designated L86-8275), which has been selected for fur...
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| Veröffentlicht in: | Clinical cancer research 1997-02, Vol.3 (2), p.273-279 |
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| creator | DREES, M DENGLER, W. A ROTH, T LABONTE, H MAYO, J MALSPEIS, L GREVER, M SAUSVILLE, E. A FIEBIG, H. H |
| description | We have selected a panel of human tumor xenografts for in vitro and in vivo studies that allows an indication of selectivity
of action of novel chemotherapeutic agents. We report here the antitumor activity of the flavone flavopiridol (previously
designated L86-8275), which has been selected for further studies based in part on its behavior in the anticancer drug screening
system of the United States National Cancer Institute. Eighteen human tumor and five cell line-derived xenografts established
by serial passage in nude mice in our laboratory were used as tumor models for in vitro investigations using a modified double-layer
soft agar assay. In vivo investigations were completed in nude mice bearing advanced-stage s.c. growing prostate cancer xenografts.
Antitumor activity in vitro (test/control |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_pasca</sourceid><recordid>TN_cdi_pubmed_primary_9815683</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>9815683</sourcerecordid><originalsourceid>FETCH-LOGICAL-h266t-8209fe19460df8364b024b9306a300ef6d6a695a2fe492c50d7730836f3c67ab3</originalsourceid><addsrcrecordid>eNpdj8FLwzAYxYsoc07_BCEHET0U0qRJGm8yNhUGXvRcvqaJjbRNSbLJ_nszNjx4eo_3fnx87yybF4yJnBLOzpPHospxSclldhXCN8ZFWeByls1kVTBe0Xk2rXvYucl627oePWwqnldEsMcnFHSvVbQ7jWCMNm4H5xEcAhv3yI4oqXepa_-lO4dMQifvQoSokQKv7OgGQEr3fbjOLgz0Qd-cdJF9rlcfy9d88_7ytnze5B3hPKYnsDS6kCXHrakoLxtMykZSzIFirA1vOXDJgBhdSqIYboWgOIGGKi6goYvs9nh32jaDbuvJ2wH8vj4tT_3dqYegoDceRmXDH0ZEVXB5wO6PWGe_uh_rda0SqL3XQadhXU1rkmBKfwGkU2_j</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>DREES, M ; DENGLER, W. A ; ROTH, T ; LABONTE, H ; MAYO, J ; MALSPEIS, L ; GREVER, M ; SAUSVILLE, E. A ; FIEBIG, H. H</creator><creatorcontrib>DREES, M ; DENGLER, W. A ; ROTH, T ; LABONTE, H ; MAYO, J ; MALSPEIS, L ; GREVER, M ; SAUSVILLE, E. A ; FIEBIG, H. H</creatorcontrib><description>We have selected a panel of human tumor xenografts for in vitro and in vivo studies that allows an indication of selectivity
of action of novel chemotherapeutic agents. We report here the antitumor activity of the flavone flavopiridol (previously
designated L86-8275), which has been selected for further studies based in part on its behavior in the anticancer drug screening
system of the United States National Cancer Institute. Eighteen human tumor and five cell line-derived xenografts established
by serial passage in nude mice in our laboratory were used as tumor models for in vitro investigations using a modified double-layer
soft agar assay. In vivo investigations were completed in nude mice bearing advanced-stage s.c. growing prostate cancer xenografts.
Antitumor activity in vitro (test/control </= 30%) of flavopiridol was observed at the very low concentration of 0.1 ng/ml
in three of four prostatic xenografts and in one melanoma xenograft. Overall, in 14 of 23 (61%) tumor xenografts, drug treatment
resulted in a IC70 of <10 ng/ml, demonstrating the high antiproliferative potential of flavopiridol. Toxicity to in vitro
bone marrow cultures was evident only at 100 ng/ml, indicating potential high selectivity for susceptible tumor cells. Comparison
of tumor cells with bone marrow samples tested showed clear prostate carcinoma and moderate melanoma selectivity. In vivo
studies of flavopiridol confirmed antitumor activity in both prostate cancer xenografts investigated. At the maximal tolerated
dose of 10 mg/kg/day administered p.o. on days 1-4 and 7-11, flavopiridol effected tumor regression in PRXF1337 and tumor
stasis lasting for 4 weeks in PRXF1369. We conclude that flavopiridol shows strong prostate-and moderate melanoma-specific
antitumor activity in vitro. The prostate antitumor activity is also reflected by the two in vivo models studied. Initial
clinical efforts with flavopiridol might consider early evaluation in patients with prostate carcinoma.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 9815683</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Chemotherapy ; Colony-Forming Units Assay ; Drug Screening Assays, Antitumor ; Flavonoids - pharmacology ; Flavonoids - therapeutic use ; Humans ; Male ; Medical sciences ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Pharmacology. Drug treatments ; Piperidines - pharmacology ; Piperidines - therapeutic use ; Prostatic Neoplasms - drug therapy ; Tumor Cells, Cultured</subject><ispartof>Clinical cancer research, 1997-02, Vol.3 (2), p.273-279</ispartof><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2781693$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9815683$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DREES, M</creatorcontrib><creatorcontrib>DENGLER, W. A</creatorcontrib><creatorcontrib>ROTH, T</creatorcontrib><creatorcontrib>LABONTE, H</creatorcontrib><creatorcontrib>MAYO, J</creatorcontrib><creatorcontrib>MALSPEIS, L</creatorcontrib><creatorcontrib>GREVER, M</creatorcontrib><creatorcontrib>SAUSVILLE, E. A</creatorcontrib><creatorcontrib>FIEBIG, H. H</creatorcontrib><title>Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>We have selected a panel of human tumor xenografts for in vitro and in vivo studies that allows an indication of selectivity
of action of novel chemotherapeutic agents. We report here the antitumor activity of the flavone flavopiridol (previously
designated L86-8275), which has been selected for further studies based in part on its behavior in the anticancer drug screening
system of the United States National Cancer Institute. Eighteen human tumor and five cell line-derived xenografts established
by serial passage in nude mice in our laboratory were used as tumor models for in vitro investigations using a modified double-layer
soft agar assay. In vivo investigations were completed in nude mice bearing advanced-stage s.c. growing prostate cancer xenografts.
Antitumor activity in vitro (test/control </= 30%) of flavopiridol was observed at the very low concentration of 0.1 ng/ml
in three of four prostatic xenografts and in one melanoma xenograft. Overall, in 14 of 23 (61%) tumor xenografts, drug treatment
resulted in a IC70 of <10 ng/ml, demonstrating the high antiproliferative potential of flavopiridol. Toxicity to in vitro
bone marrow cultures was evident only at 100 ng/ml, indicating potential high selectivity for susceptible tumor cells. Comparison
of tumor cells with bone marrow samples tested showed clear prostate carcinoma and moderate melanoma selectivity. In vivo
studies of flavopiridol confirmed antitumor activity in both prostate cancer xenografts investigated. At the maximal tolerated
dose of 10 mg/kg/day administered p.o. on days 1-4 and 7-11, flavopiridol effected tumor regression in PRXF1337 and tumor
stasis lasting for 4 weeks in PRXF1369. We conclude that flavopiridol shows strong prostate-and moderate melanoma-specific
antitumor activity in vitro. The prostate antitumor activity is also reflected by the two in vivo models studied. Initial
clinical efforts with flavopiridol might consider early evaluation in patients with prostate carcinoma.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Colony-Forming Units Assay</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Flavonoids - pharmacology</subject><subject>Flavonoids - therapeutic use</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neoplasm Transplantation</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - pharmacology</subject><subject>Piperidines - therapeutic use</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Tumor Cells, Cultured</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdj8FLwzAYxYsoc07_BCEHET0U0qRJGm8yNhUGXvRcvqaJjbRNSbLJ_nszNjx4eo_3fnx87yybF4yJnBLOzpPHospxSclldhXCN8ZFWeByls1kVTBe0Xk2rXvYucl627oePWwqnldEsMcnFHSvVbQ7jWCMNm4H5xEcAhv3yI4oqXepa_-lO4dMQifvQoSokQKv7OgGQEr3fbjOLgz0Qd-cdJF9rlcfy9d88_7ytnze5B3hPKYnsDS6kCXHrakoLxtMykZSzIFirA1vOXDJgBhdSqIYboWgOIGGKi6goYvs9nh32jaDbuvJ2wH8vj4tT_3dqYegoDceRmXDH0ZEVXB5wO6PWGe_uh_rda0SqL3XQadhXU1rkmBKfwGkU2_j</recordid><startdate>19970201</startdate><enddate>19970201</enddate><creator>DREES, M</creator><creator>DENGLER, W. A</creator><creator>ROTH, T</creator><creator>LABONTE, H</creator><creator>MAYO, J</creator><creator>MALSPEIS, L</creator><creator>GREVER, M</creator><creator>SAUSVILLE, E. A</creator><creator>FIEBIG, H. H</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19970201</creationdate><title>Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells</title><author>DREES, M ; DENGLER, W. A ; ROTH, T ; LABONTE, H ; MAYO, J ; MALSPEIS, L ; GREVER, M ; SAUSVILLE, E. A ; FIEBIG, H. H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h266t-8209fe19460df8364b024b9306a300ef6d6a695a2fe492c50d7730836f3c67ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy</topic><topic>Colony-Forming Units Assay</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Flavonoids - pharmacology</topic><topic>Flavonoids - therapeutic use</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neoplasm Transplantation</topic><topic>Pharmacology. Drug treatments</topic><topic>Piperidines - pharmacology</topic><topic>Piperidines - therapeutic use</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DREES, M</creatorcontrib><creatorcontrib>DENGLER, W. A</creatorcontrib><creatorcontrib>ROTH, T</creatorcontrib><creatorcontrib>LABONTE, H</creatorcontrib><creatorcontrib>MAYO, J</creatorcontrib><creatorcontrib>MALSPEIS, L</creatorcontrib><creatorcontrib>GREVER, M</creatorcontrib><creatorcontrib>SAUSVILLE, E. A</creatorcontrib><creatorcontrib>FIEBIG, H. H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DREES, M</au><au>DENGLER, W. A</au><au>ROTH, T</au><au>LABONTE, H</au><au>MAYO, J</au><au>MALSPEIS, L</au><au>GREVER, M</au><au>SAUSVILLE, E. A</au><au>FIEBIG, H. H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>1997-02-01</date><risdate>1997</risdate><volume>3</volume><issue>2</issue><spage>273</spage><epage>279</epage><pages>273-279</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>We have selected a panel of human tumor xenografts for in vitro and in vivo studies that allows an indication of selectivity
of action of novel chemotherapeutic agents. We report here the antitumor activity of the flavone flavopiridol (previously
designated L86-8275), which has been selected for further studies based in part on its behavior in the anticancer drug screening
system of the United States National Cancer Institute. Eighteen human tumor and five cell line-derived xenografts established
by serial passage in nude mice in our laboratory were used as tumor models for in vitro investigations using a modified double-layer
soft agar assay. In vivo investigations were completed in nude mice bearing advanced-stage s.c. growing prostate cancer xenografts.
Antitumor activity in vitro (test/control </= 30%) of flavopiridol was observed at the very low concentration of 0.1 ng/ml
in three of four prostatic xenografts and in one melanoma xenograft. Overall, in 14 of 23 (61%) tumor xenografts, drug treatment
resulted in a IC70 of <10 ng/ml, demonstrating the high antiproliferative potential of flavopiridol. Toxicity to in vitro
bone marrow cultures was evident only at 100 ng/ml, indicating potential high selectivity for susceptible tumor cells. Comparison
of tumor cells with bone marrow samples tested showed clear prostate carcinoma and moderate melanoma selectivity. In vivo
studies of flavopiridol confirmed antitumor activity in both prostate cancer xenografts investigated. At the maximal tolerated
dose of 10 mg/kg/day administered p.o. on days 1-4 and 7-11, flavopiridol effected tumor regression in PRXF1337 and tumor
stasis lasting for 4 weeks in PRXF1369. We conclude that flavopiridol shows strong prostate-and moderate melanoma-specific
antitumor activity in vitro. The prostate antitumor activity is also reflected by the two in vivo models studied. Initial
clinical efforts with flavopiridol might consider early evaluation in patients with prostate carcinoma.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>9815683</pmid><tpages>7</tpages></addata></record> |
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| ispartof | Clinical cancer research, 1997-02, Vol.3 (2), p.273-279 |
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| language | eng |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Antineoplastic agents Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biological and medical sciences Chemotherapy Colony-Forming Units Assay Drug Screening Assays, Antitumor Flavonoids - pharmacology Flavonoids - therapeutic use Humans Male Medical sciences Mice Mice, Nude Neoplasm Transplantation Pharmacology. Drug treatments Piperidines - pharmacology Piperidines - therapeutic use Prostatic Neoplasms - drug therapy Tumor Cells, Cultured |
| title | Flavopiridol (L86-8275): selective antitumor activity in vitro and activity in vivo for prostate carcinoma cells |
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