Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog
Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a dai...
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
1990 |
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| Umfang: |
9 |
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| Reproduktion: |
Springer Online Journal Archives 1860-2002 |
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| Übergeordnetes Werk: |
in: Investigational new drugs - 1983, 8(1990) vom: Jan., Seite 33-41 |
| Übergeordnetes Werk: |
volume:8 ; year:1990 ; month:01 ; pages:33-41 ; extent:9 |
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NLEJ197076394 |
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| 245 | 1 | 0 | |a Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog |
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| 520 | |a Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. | ||
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| 700 | 1 | |a Siddik, Zahid H. |4 oth | |
| 700 | 1 | |a Travis, Elizabeth L. |4 oth | |
| 700 | 1 | |a Followill, David |4 oth | |
| 700 | 1 | |a Ayele, Workenesh |4 oth | |
| 700 | 1 | |a Burditt, Tim |4 oth | |
| 700 | 1 | |a Krakoff, Irwin H. |4 oth | |
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(DE-627)NLEJ197076394 DE-627 ger DE-627 rakwb eng Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog 1990 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. Springer Online Journal Archives 1860-2002 Newman, Robert A. oth Siddik, Zahid H. oth Travis, Elizabeth L. oth Followill, David oth Ayele, Workenesh oth Burditt, Tim oth Krakoff, Irwin H. oth in Investigational new drugs 1983 8(1990) vom: Jan., Seite 33-41 (DE-627)NLEJ188985484 (DE-600)2009846-7 1573-0646 nnns volume:8 year:1990 month:01 pages:33-41 extent:9 http://dx.doi.org/10.1007/BF00216922 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 8 1990 1 33-41 9 |
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(DE-627)NLEJ197076394 DE-627 ger DE-627 rakwb eng Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog 1990 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. Springer Online Journal Archives 1860-2002 Newman, Robert A. oth Siddik, Zahid H. oth Travis, Elizabeth L. oth Followill, David oth Ayele, Workenesh oth Burditt, Tim oth Krakoff, Irwin H. oth in Investigational new drugs 1983 8(1990) vom: Jan., Seite 33-41 (DE-627)NLEJ188985484 (DE-600)2009846-7 1573-0646 nnns volume:8 year:1990 month:01 pages:33-41 extent:9 http://dx.doi.org/10.1007/BF00216922 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 8 1990 1 33-41 9 |
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(DE-627)NLEJ197076394 DE-627 ger DE-627 rakwb eng Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog 1990 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. Springer Online Journal Archives 1860-2002 Newman, Robert A. oth Siddik, Zahid H. oth Travis, Elizabeth L. oth Followill, David oth Ayele, Workenesh oth Burditt, Tim oth Krakoff, Irwin H. oth in Investigational new drugs 1983 8(1990) vom: Jan., Seite 33-41 (DE-627)NLEJ188985484 (DE-600)2009846-7 1573-0646 nnns volume:8 year:1990 month:01 pages:33-41 extent:9 http://dx.doi.org/10.1007/BF00216922 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 8 1990 1 33-41 9 |
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(DE-627)NLEJ197076394 DE-627 ger DE-627 rakwb eng Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog 1990 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. Springer Online Journal Archives 1860-2002 Newman, Robert A. oth Siddik, Zahid H. oth Travis, Elizabeth L. oth Followill, David oth Ayele, Workenesh oth Burditt, Tim oth Krakoff, Irwin H. oth in Investigational new drugs 1983 8(1990) vom: Jan., Seite 33-41 (DE-627)NLEJ188985484 (DE-600)2009846-7 1573-0646 nnns volume:8 year:1990 month:01 pages:33-41 extent:9 http://dx.doi.org/10.1007/BF00216922 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 8 1990 1 33-41 9 |
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(DE-627)NLEJ197076394 DE-627 ger DE-627 rakwb eng Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog 1990 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. Springer Online Journal Archives 1860-2002 Newman, Robert A. oth Siddik, Zahid H. oth Travis, Elizabeth L. oth Followill, David oth Ayele, Workenesh oth Burditt, Tim oth Krakoff, Irwin H. oth in Investigational new drugs 1983 8(1990) vom: Jan., Seite 33-41 (DE-627)NLEJ188985484 (DE-600)2009846-7 1573-0646 nnns volume:8 year:1990 month:01 pages:33-41 extent:9 http://dx.doi.org/10.1007/BF00216922 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 8 1990 1 33-41 9 |
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assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog |
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Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog |
| abstract |
Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. |
| abstractGer |
Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. |
| abstract_unstemmed |
Summary The antitumor efficacy as well as hematologic and pulmonary toxicity of Liblomycin, a new lipophilic analog of bleomycin, was evaluated in BDF1 mice. In comparison to bleomycin which was without any antitumor efficacy against P388 leukemia, a dose of 10 mg/kg Liblomycin administered on a daily schedule for 10 consecutive days resulted in a significant increase in animal survival (% T/C of 190). This therapeutic dose and schedule of drug administration did not produce any evidence of pulmonary histopathologic injury; at a similar dose and schedule bleomycin resulted in greater than 40% consolidation of alveolar lung space. Mouse lung collagen synthesis measured as rate of [3H]hydroxyproline formation was increased almost 4-fold by bleomycin 7 days following a single maximally tolerated i.v. injection (133 mg/kg); in contrast, Liblomycin (60 mg/kg) did not significantly alter the rate of lung collagen synthesis compared to saline injected control animals. Lung function was assessed by whole body plethysmography. Bleomycin produced an increase in breathing rates above control values by day 15 following administration of drug at 10 mg/kg (d1–10). Mice treated with Liblomycin did not exhibit an increased rate of breathing. Liblomycin, in contrast to bleomycin, produced mild and transient leukopenia and thrombocytopenia suggesting that this toxicity will be a limiting one in future clinical trials. The only other toxicity noted in this study was the appearance after repeated intraperitoneal administration of Liblomycin of a hepatic collagenous fibrous capsule. The capsule formation resulted in an abnormal and grossly lobulated liver which was believed to have affected animal survival. Intravenous administration of Liblomycin, however, was not associated with any detectable hepatic injury. |
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Assessment of pulmonary and hematologic toxicities of liblomycin, a novel bleomycin analog |
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Newman, Robert A. Siddik, Zahid H. Travis, Elizabeth L. Followill, David Ayele, Workenesh Burditt, Tim Krakoff, Irwin H. |
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