Preclinical activity of trans-indazolium [tetrachlorobisindazoleruthenate(III)] (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and haematopoietic progenitor cells
Trans-indazolium[tetrachlorobisindazoleruthenate(III)] (KP 1019) is a new heavy metal complex with promising activity against tumour cell lines and in animal models. We studied the antineoplastic effects of KP 1019 (final concentrations: 1, 10, 100 μg/ml) on in vitro proliferation of clonogenic cell...
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| Veröffentlicht in: | European journal of cancer (1990) 1997-12, Vol.33 (14), p.2404-2410 |
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| container_title | European journal of cancer (1990) |
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| creator | Depenbrock, H. Schmelcher, S. Peter, R. Keppler, B.K. Weirich, G. Block, T. Rastetter, J. Hanauske, A.-R. |
| description | Trans-indazolium[tetrachlorobisindazoleruthenate(III)] (KP 1019) is a new heavy metal complex with promising activity against tumour cell lines and in animal models. We studied the antineoplastic effects of KP 1019 (final concentrations: 1, 10, 100
μg/ml) on
in vitro proliferation of clonogenic cells from freshly explanted human tumours in a capillary soft agar cloning system, and compared the activity of KP 1019 with conventional antineoplastic agents. 53 of 75 specimens (71%) showed adequate growth in controls. KP 1019 inhibited tumour colony formation in a concentration-dependent manner in both short- (1
h) and long-term (21
d) exposure experiments. KP 1019 at 100
μg/ml with 1
h exposure was as active as bleomycin, cisplatin, doxorubicin, etoposide, 5-fluorouracil, methotrexate, mitomycin-C and vinblastine, with only paclitaxel more active than KP 1019 (
P
=
0.002). The antitumour activity of KP 1019 was more pronounced after long-term exposure, indicating the potential schedule dependency of KP 1019. Activity was observed against non-small cell lung, breast and renal cancer. We conclude that if appropriate plasma levels can be achieved in patients, KP 1019 may have significant clinical activity against a variety of different tumour types. |
| doi_str_mv | 10.1016/S0959-8049(97)00277-3 |
| format | Article |
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μg/ml) on
in vitro proliferation of clonogenic cells from freshly explanted human tumours in a capillary soft agar cloning system, and compared the activity of KP 1019 with conventional antineoplastic agents. 53 of 75 specimens (71%) showed adequate growth in controls. KP 1019 inhibited tumour colony formation in a concentration-dependent manner in both short- (1
h) and long-term (21
d) exposure experiments. KP 1019 at 100
μg/ml with 1
h exposure was as active as bleomycin, cisplatin, doxorubicin, etoposide, 5-fluorouracil, methotrexate, mitomycin-C and vinblastine, with only paclitaxel more active than KP 1019 (
P
=
0.002). The antitumour activity of KP 1019 was more pronounced after long-term exposure, indicating the potential schedule dependency of KP 1019. Activity was observed against non-small cell lung, breast and renal cancer. We conclude that if appropriate plasma levels can be achieved in patients, KP 1019 may have significant clinical activity against a variety of different tumour types.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/S0959-8049(97)00277-3</identifier><identifier>PMID: 9616290</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Biological and medical sciences ; Cell Division - drug effects ; clonogenic growth ; Dose-Response Relationship, Drug ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - drug effects ; human tumours ; Humans ; Indazoles - pharmacology ; Medical sciences ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - pathology ; Organometallic Compounds - pharmacology ; Other treatments ; ruthenium complexes ; Treatment. General aspects ; Tumor Cells, Cultured ; Tumor Stem Cell Assay ; Tumors</subject><ispartof>European journal of cancer (1990), 1997-12, Vol.33 (14), p.2404-2410</ispartof><rights>1997 Elsevier Science Ltd</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-443e7198837b5d8482a5e00ab02c6087c34e6351062eae49dd42630f71fcb1713</citedby><cites>FETCH-LOGICAL-c389t-443e7198837b5d8482a5e00ab02c6087c34e6351062eae49dd42630f71fcb1713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0959-8049(97)00277-3$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2118883$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9616290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Depenbrock, H.</creatorcontrib><creatorcontrib>Schmelcher, S.</creatorcontrib><creatorcontrib>Peter, R.</creatorcontrib><creatorcontrib>Keppler, B.K.</creatorcontrib><creatorcontrib>Weirich, G.</creatorcontrib><creatorcontrib>Block, T.</creatorcontrib><creatorcontrib>Rastetter, J.</creatorcontrib><creatorcontrib>Hanauske, A.-R.</creatorcontrib><title>Preclinical activity of trans-indazolium [tetrachlorobisindazoleruthenate(III)] (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and haematopoietic progenitor cells</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Trans-indazolium[tetrachlorobisindazoleruthenate(III)] (KP 1019) is a new heavy metal complex with promising activity against tumour cell lines and in animal models. We studied the antineoplastic effects of KP 1019 (final concentrations: 1, 10, 100
μg/ml) on
in vitro proliferation of clonogenic cells from freshly explanted human tumours in a capillary soft agar cloning system, and compared the activity of KP 1019 with conventional antineoplastic agents. 53 of 75 specimens (71%) showed adequate growth in controls. KP 1019 inhibited tumour colony formation in a concentration-dependent manner in both short- (1
h) and long-term (21
d) exposure experiments. KP 1019 at 100
μg/ml with 1
h exposure was as active as bleomycin, cisplatin, doxorubicin, etoposide, 5-fluorouracil, methotrexate, mitomycin-C and vinblastine, with only paclitaxel more active than KP 1019 (
P
=
0.002). The antitumour activity of KP 1019 was more pronounced after long-term exposure, indicating the potential schedule dependency of KP 1019. Activity was observed against non-small cell lung, breast and renal cancer. We conclude that if appropriate plasma levels can be achieved in patients, KP 1019 may have significant clinical activity against a variety of different tumour types.</description><subject>Biological and medical sciences</subject><subject>Cell Division - drug effects</subject><subject>clonogenic growth</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>human tumours</subject><subject>Humans</subject><subject>Indazoles - pharmacology</subject><subject>Medical sciences</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Organometallic Compounds - pharmacology</subject><subject>Other treatments</subject><subject>ruthenium complexes</subject><subject>Treatment. General aspects</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Stem Cell Assay</subject><subject>Tumors</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV9rFDEUxYModa1-hEIeRHYfRpP5l4Q-FFmsDhYtVp9EQiZzZzcyk6xJprB-rn5As91hX30K5JyTnHt_CF1Q8pYSWr-7I6ISGSelWAq2IiRnLCueoAXlTGSEV_lTtDhZnqMXIfwmhDBekjN0Jmpa54Is0MOtBz0Ya7QasNLR3Ju4x67H0SsbMmM79dcNZhrxzwjpTm8H511rwqyAn-IWrIqwbJpm9Qsvv9ytcV3XtOKXuLHd-tsl_nyLU2WxwmqjjA0Rx2l0k8faDc7us9750dgNnqyJASvb4a2CUUW3cwai0Xjn3QaS6FIEhiG8RM96NQR4NZ_n6Mf1h-_rT9nN14_N-v1NpgsuYlaWBTAqOC9YW3W85LmqgBDVklzXhDNdlFAXFSV1DgpK0XVlXhekZ7TXLWW0OEdvju-mAn8mCFGOJhwaKAtuCpKl9QqWk2SsjkbtXQgeernzZlR-LymRB1rykZY8oJCCyUdaski5i_mDqR2hO6VmPEl_PesqJEB9YqJNONlySnmaLtmujjZIy7g34GXQBqyGziS6UXbO_KfIP1mrsnc</recordid><startdate>19971201</startdate><enddate>19971201</enddate><creator>Depenbrock, H.</creator><creator>Schmelcher, S.</creator><creator>Peter, R.</creator><creator>Keppler, B.K.</creator><creator>Weirich, G.</creator><creator>Block, T.</creator><creator>Rastetter, J.</creator><creator>Hanauske, A.-R.</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>19971201</creationdate><title>Preclinical activity of trans-indazolium [tetrachlorobisindazoleruthenate(III)] (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and haematopoietic progenitor cells</title><author>Depenbrock, H. ; Schmelcher, S. ; Peter, R. ; Keppler, B.K. ; Weirich, G. ; Block, T. ; Rastetter, J. ; Hanauske, A.-R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-443e7198837b5d8482a5e00ab02c6087c34e6351062eae49dd42630f71fcb1713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Biological and medical sciences</topic><topic>Cell Division - drug effects</topic><topic>clonogenic growth</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>human tumours</topic><topic>Humans</topic><topic>Indazoles - pharmacology</topic><topic>Medical sciences</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Organometallic Compounds - pharmacology</topic><topic>Other treatments</topic><topic>ruthenium complexes</topic><topic>Treatment. General aspects</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Stem Cell Assay</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Depenbrock, H.</creatorcontrib><creatorcontrib>Schmelcher, S.</creatorcontrib><creatorcontrib>Peter, R.</creatorcontrib><creatorcontrib>Keppler, B.K.</creatorcontrib><creatorcontrib>Weirich, G.</creatorcontrib><creatorcontrib>Block, T.</creatorcontrib><creatorcontrib>Rastetter, J.</creatorcontrib><creatorcontrib>Hanauske, A.-R.</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>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Depenbrock, H.</au><au>Schmelcher, S.</au><au>Peter, R.</au><au>Keppler, B.K.</au><au>Weirich, G.</au><au>Block, T.</au><au>Rastetter, J.</au><au>Hanauske, A.-R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preclinical activity of trans-indazolium [tetrachlorobisindazoleruthenate(III)] (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and haematopoietic progenitor cells</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>1997-12-01</date><risdate>1997</risdate><volume>33</volume><issue>14</issue><spage>2404</spage><epage>2410</epage><pages>2404-2410</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Trans-indazolium[tetrachlorobisindazoleruthenate(III)] (KP 1019) is a new heavy metal complex with promising activity against tumour cell lines and in animal models. We studied the antineoplastic effects of KP 1019 (final concentrations: 1, 10, 100
μg/ml) on
in vitro proliferation of clonogenic cells from freshly explanted human tumours in a capillary soft agar cloning system, and compared the activity of KP 1019 with conventional antineoplastic agents. 53 of 75 specimens (71%) showed adequate growth in controls. KP 1019 inhibited tumour colony formation in a concentration-dependent manner in both short- (1
h) and long-term (21
d) exposure experiments. KP 1019 at 100
μg/ml with 1
h exposure was as active as bleomycin, cisplatin, doxorubicin, etoposide, 5-fluorouracil, methotrexate, mitomycin-C and vinblastine, with only paclitaxel more active than KP 1019 (
P
=
0.002). The antitumour activity of KP 1019 was more pronounced after long-term exposure, indicating the potential schedule dependency of KP 1019. Activity was observed against non-small cell lung, breast and renal cancer. We conclude that if appropriate plasma levels can be achieved in patients, KP 1019 may have significant clinical activity against a variety of different tumour types.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>9616290</pmid><doi>10.1016/S0959-8049(97)00277-3</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0959-8049 |
| ispartof | European journal of cancer (1990), 1997-12, Vol.33 (14), p.2404-2410 |
| issn | 0959-8049 1879-0852 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_79599720 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Biological and medical sciences Cell Division - drug effects clonogenic growth Dose-Response Relationship, Drug Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - drug effects human tumours Humans Indazoles - pharmacology Medical sciences Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - pathology Organometallic Compounds - pharmacology Other treatments ruthenium complexes Treatment. General aspects Tumor Cells, Cultured Tumor Stem Cell Assay Tumors |
| title | Preclinical activity of trans-indazolium [tetrachlorobisindazoleruthenate(III)] (NSC 666158; IndCR; KP 1019) against tumour colony-forming units and haematopoietic progenitor cells |
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