Potentiation of the anti‐tumor effect of actinomycin D by tumor necrosis factor α in mice: Correlation between in vitro and in vivo results
The anti‐tumor effects of actinomycin D (Act D) and recombinant human tumor necrosis factor (TNF)‐α have been studied on 4 established murine tumor cell lines: MmB16 melanoma, Lewis lung (LL/2) carcinoma, L1 sarcoma and L1210 leukemia. During short‐term incubation (24 hr) Act D produced dose‐depende...
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Veröffentlicht in: | International journal of cancer 1996-05, Vol.66 (3), p.374-379 |
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creator | Lasek, Witold Giermasz, Adam Kuc, Katarzyna Wańkowicz, Anna Feleszko, Wojciech Golab, Jakub Zagożdżon, Radoslaw Stoklosa, Tomasz Jakóbisiak, Marek |
description | The anti‐tumor effects of actinomycin D (Act D) and recombinant human tumor necrosis factor (TNF)‐α have been studied on 4 established murine tumor cell lines: MmB16 melanoma, Lewis lung (LL/2) carcinoma, L1 sarcoma and L1210 leukemia. During short‐term incubation (24 hr) Act D produced dose‐dependent cytostatic/cytotoxic effects against MmB16, LL/2 and L1 tumor cells but did not reduce the viability of these cells even at high concentration (10 μg/ml), below a threshold of 30–60%. However, L1210 leukemic cells were highly susceptible to Act D, and no viable cells were detected in cultures incubated with 1 μg/ml of Act D. TNF‐α alone, when used under the same culture conditions, had only a negligible effect on all cell lines tested. However, the combination of this cytokine with Act D produced synergistic cytotoxic effects against MmB16, LL/2 and L1 cells but not against L1210 leukemia cells. In an in vivo model of regional therapy in which tumor‐bearing mice were treated with Act D and TNF‐α, a correlation with in vitro results was observed. In mice bearing MmB16 melanoma, LL/2 carcinoma and L1 sarcoma, the most potent anti‐tumor effects were observed in mice treated with Act D and TNF‐α together. This treatment led to a delay of tumor growth and induced complete tumor regression in some cases. On the contrary, TNF‐α did not enhance the effect of Act D in mice injected with L1210 leukemia cells. Our results show that TNF‐α can potentiate the anti‐tumor effects of Act D against tumors weakly susceptible to Act D and may be a useful adjuvant to chemotherapy in the local treatment of neoplasia. © 1996 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/(SICI)1097-0215(19960503)66:3<374::AID-IJC18>3.0.CO;2-B |
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During short‐term incubation (24 hr) Act D produced dose‐dependent cytostatic/cytotoxic effects against MmB16, LL/2 and L1 tumor cells but did not reduce the viability of these cells even at high concentration (10 μg/ml), below a threshold of 30–60%. However, L1210 leukemic cells were highly susceptible to Act D, and no viable cells were detected in cultures incubated with 1 μg/ml of Act D. TNF‐α alone, when used under the same culture conditions, had only a negligible effect on all cell lines tested. However, the combination of this cytokine with Act D produced synergistic cytotoxic effects against MmB16, LL/2 and L1 cells but not against L1210 leukemia cells. In an in vivo model of regional therapy in which tumor‐bearing mice were treated with Act D and TNF‐α, a correlation with in vitro results was observed. In mice bearing MmB16 melanoma, LL/2 carcinoma and L1 sarcoma, the most potent anti‐tumor effects were observed in mice treated with Act D and TNF‐α together. This treatment led to a delay of tumor growth and induced complete tumor regression in some cases. On the contrary, TNF‐α did not enhance the effect of Act D in mice injected with L1210 leukemia cells. Our results show that TNF‐α can potentiate the anti‐tumor effects of Act D against tumors weakly susceptible to Act D and may be a useful adjuvant to chemotherapy in the local treatment of neoplasia. © 1996 Wiley‐Liss, Inc.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/(SICI)1097-0215(19960503)66:3<374::AID-IJC18>3.0.CO;2-B</identifier><identifier>PMID: 8621260</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Antibiotics, Antineoplastic - therapeutic use ; Antibiotics, Antineoplastic - toxicity ; Antineoplastic agents ; Biological and medical sciences ; Cell Line ; Dactinomycin - therapeutic use ; Dactinomycin - toxicity ; Drug Synergism ; General aspects ; Leukemia L1210 - drug therapy ; Lung Neoplasms - drug therapy ; Medical sciences ; Melanoma, Experimental - drug therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - pathology ; Pharmacology. Drug treatments ; Sarcoma, Experimental - drug therapy ; Time Factors ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha - therapeutic use ; Tumor Necrosis Factor-alpha - toxicity</subject><ispartof>International journal of cancer, 1996-05, Vol.66 (3), p.374-379</ispartof><rights>Copyright © 1996 Wiley‐Liss, Inc.</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F%28SICI%291097-0215%2819960503%2966%3A3%3C374%3A%3AAID-IJC18%3E3.0.CO%3B2-B$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F%28SICI%291097-0215%2819960503%2966%3A3%3C374%3A%3AAID-IJC18%3E3.0.CO%3B2-B$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3068827$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8621260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lasek, Witold</creatorcontrib><creatorcontrib>Giermasz, Adam</creatorcontrib><creatorcontrib>Kuc, Katarzyna</creatorcontrib><creatorcontrib>Wańkowicz, Anna</creatorcontrib><creatorcontrib>Feleszko, Wojciech</creatorcontrib><creatorcontrib>Golab, Jakub</creatorcontrib><creatorcontrib>Zagożdżon, Radoslaw</creatorcontrib><creatorcontrib>Stoklosa, Tomasz</creatorcontrib><creatorcontrib>Jakóbisiak, Marek</creatorcontrib><title>Potentiation of the anti‐tumor effect of actinomycin D by tumor necrosis factor α in mice: Correlation between in vitro and in vivo results</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>The anti‐tumor effects of actinomycin D (Act D) and recombinant human tumor necrosis factor (TNF)‐α have been studied on 4 established murine tumor cell lines: MmB16 melanoma, Lewis lung (LL/2) carcinoma, L1 sarcoma and L1210 leukemia. During short‐term incubation (24 hr) Act D produced dose‐dependent cytostatic/cytotoxic effects against MmB16, LL/2 and L1 tumor cells but did not reduce the viability of these cells even at high concentration (10 μg/ml), below a threshold of 30–60%. However, L1210 leukemic cells were highly susceptible to Act D, and no viable cells were detected in cultures incubated with 1 μg/ml of Act D. TNF‐α alone, when used under the same culture conditions, had only a negligible effect on all cell lines tested. However, the combination of this cytokine with Act D produced synergistic cytotoxic effects against MmB16, LL/2 and L1 cells but not against L1210 leukemia cells. In an in vivo model of regional therapy in which tumor‐bearing mice were treated with Act D and TNF‐α, a correlation with in vitro results was observed. In mice bearing MmB16 melanoma, LL/2 carcinoma and L1 sarcoma, the most potent anti‐tumor effects were observed in mice treated with Act D and TNF‐α together. This treatment led to a delay of tumor growth and induced complete tumor regression in some cases. On the contrary, TNF‐α did not enhance the effect of Act D in mice injected with L1210 leukemia cells. Our results show that TNF‐α can potentiate the anti‐tumor effects of Act D against tumors weakly susceptible to Act D and may be a useful adjuvant to chemotherapy in the local treatment of neoplasia. © 1996 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Dactinomycin - therapeutic use</subject><subject>Dactinomycin - toxicity</subject><subject>Drug Synergism</subject><subject>General aspects</subject><subject>Leukemia L1210 - drug therapy</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Medical sciences</subject><subject>Melanoma, Experimental - drug therapy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Sarcoma, Experimental - drug therapy</subject><subject>Time Factors</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Necrosis Factor-alpha - therapeutic use</subject><subject>Tumor Necrosis Factor-alpha - toxicity</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kU9u1DAUhy0EKkPhCEhesGgXGZ6djOMMFahN-RNUaZAAiZ3lOLYwSuKR7Wk1O06AuAoX4RCcBIcMs7Le-31-T_aH0CsCSwJAn599bOrmnEBVZkDJ6oxUFYMV5OeMrfOLvCzW68vmOmve14S_zJewrDcvaHZ1Dy2Od-6jRZoEWUly9hA9CuEbACErKE7QCWeUUAYL9OODi3qMVkbrRuwMjl81lqnx5_vPuBucx9oYreIUSRXt6Ia9siO-xu0ez8ColXfBBmwSkOrfv3ACBqv0GtfOe93Pw1sd77Qep_DWRu_Smm4ubh32Ouz6GB6jB0b2QT85nKfo85vXn-p32c3mbVNf3mRbWnCedZ2CAjjwQreVWbXpnbQlqVmWZUXbgna8YLyoiKFSAVTcGEi4bgkw4Eblp-jpPHe7awfdia23g_R7cfiXlD875DIo2RsvR2XDEcuBcU7LhH2ZsTvb6_0xJiAmiWJyKCYfYvIh_jsUjIlcJIciKRT_FKYaRL0RVFzNjfwvUNKW8g</recordid><startdate>19960503</startdate><enddate>19960503</enddate><creator>Lasek, Witold</creator><creator>Giermasz, Adam</creator><creator>Kuc, Katarzyna</creator><creator>Wańkowicz, Anna</creator><creator>Feleszko, Wojciech</creator><creator>Golab, Jakub</creator><creator>Zagożdżon, Radoslaw</creator><creator>Stoklosa, Tomasz</creator><creator>Jakóbisiak, Marek</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</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>19960503</creationdate><title>Potentiation of the anti‐tumor effect of actinomycin D by tumor necrosis factor α in mice: Correlation between in vitro and in vivo results</title><author>Lasek, Witold ; Giermasz, Adam ; Kuc, Katarzyna ; Wańkowicz, Anna ; Feleszko, Wojciech ; Golab, Jakub ; Zagożdżon, Radoslaw ; Stoklosa, Tomasz ; Jakóbisiak, Marek</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p2488-ddc0408084eb9f5b0022b1dc077792b42d8468491f2ac0098ff0080eb10608fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - therapeutic use</topic><topic>Antibiotics, Antineoplastic - toxicity</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Dactinomycin - therapeutic use</topic><topic>Dactinomycin - toxicity</topic><topic>Drug Synergism</topic><topic>General aspects</topic><topic>Leukemia L1210 - drug therapy</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Medical sciences</topic><topic>Melanoma, Experimental - drug therapy</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred DBA</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>Sarcoma, Experimental - drug therapy</topic><topic>Time Factors</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Necrosis Factor-alpha - therapeutic use</topic><topic>Tumor Necrosis Factor-alpha - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lasek, Witold</creatorcontrib><creatorcontrib>Giermasz, Adam</creatorcontrib><creatorcontrib>Kuc, Katarzyna</creatorcontrib><creatorcontrib>Wańkowicz, Anna</creatorcontrib><creatorcontrib>Feleszko, Wojciech</creatorcontrib><creatorcontrib>Golab, Jakub</creatorcontrib><creatorcontrib>Zagożdżon, Radoslaw</creatorcontrib><creatorcontrib>Stoklosa, Tomasz</creatorcontrib><creatorcontrib>Jakóbisiak, Marek</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>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lasek, Witold</au><au>Giermasz, Adam</au><au>Kuc, Katarzyna</au><au>Wańkowicz, Anna</au><au>Feleszko, Wojciech</au><au>Golab, Jakub</au><au>Zagożdżon, Radoslaw</au><au>Stoklosa, Tomasz</au><au>Jakóbisiak, Marek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potentiation of the anti‐tumor effect of actinomycin D by tumor necrosis factor α in mice: Correlation between in vitro and in vivo results</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>1996-05-03</date><risdate>1996</risdate><volume>66</volume><issue>3</issue><spage>374</spage><epage>379</epage><pages>374-379</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>The anti‐tumor effects of actinomycin D (Act D) and recombinant human tumor necrosis factor (TNF)‐α have been studied on 4 established murine tumor cell lines: MmB16 melanoma, Lewis lung (LL/2) carcinoma, L1 sarcoma and L1210 leukemia. During short‐term incubation (24 hr) Act D produced dose‐dependent cytostatic/cytotoxic effects against MmB16, LL/2 and L1 tumor cells but did not reduce the viability of these cells even at high concentration (10 μg/ml), below a threshold of 30–60%. However, L1210 leukemic cells were highly susceptible to Act D, and no viable cells were detected in cultures incubated with 1 μg/ml of Act D. TNF‐α alone, when used under the same culture conditions, had only a negligible effect on all cell lines tested. However, the combination of this cytokine with Act D produced synergistic cytotoxic effects against MmB16, LL/2 and L1 cells but not against L1210 leukemia cells. In an in vivo model of regional therapy in which tumor‐bearing mice were treated with Act D and TNF‐α, a correlation with in vitro results was observed. In mice bearing MmB16 melanoma, LL/2 carcinoma and L1 sarcoma, the most potent anti‐tumor effects were observed in mice treated with Act D and TNF‐α together. This treatment led to a delay of tumor growth and induced complete tumor regression in some cases. On the contrary, TNF‐α did not enhance the effect of Act D in mice injected with L1210 leukemia cells. Our results show that TNF‐α can potentiate the anti‐tumor effects of Act D against tumors weakly susceptible to Act D and may be a useful adjuvant to chemotherapy in the local treatment of neoplasia. © 1996 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>8621260</pmid><doi>10.1002/(SICI)1097-0215(19960503)66:3<374::AID-IJC18>3.0.CO;2-B</doi><tpages>6</tpages></addata></record> |
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subjects | Animals Antibiotics, Antineoplastic - therapeutic use Antibiotics, Antineoplastic - toxicity Antineoplastic agents Biological and medical sciences Cell Line Dactinomycin - therapeutic use Dactinomycin - toxicity Drug Synergism General aspects Leukemia L1210 - drug therapy Lung Neoplasms - drug therapy Medical sciences Melanoma, Experimental - drug therapy Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Neoplasms, Experimental - drug therapy Neoplasms, Experimental - pathology Pharmacology. Drug treatments Sarcoma, Experimental - drug therapy Time Factors Tumor Cells, Cultured Tumor Necrosis Factor-alpha - therapeutic use Tumor Necrosis Factor-alpha - toxicity |
title | Potentiation of the anti‐tumor effect of actinomycin D by tumor necrosis factor α in mice: Correlation between in vitro and in vivo results |
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