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Anti-tumour activity and toxicity of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in mice.

Prijovich ZM, Chen BM, Leu YL, Chern JW, Roffler SR - Br. J. Cancer (2002)

Bottom Line: Cancer chemotherapy is limited by the modest therapeutic index of most antineoplastic drugs.Beta-glucuronidase activated 9-aminocamptothecin glucuronide to produce similar cell killing as 9-aminocamptothecin or topotecan.The in vivo toxicity of 9-aminocamptothecin glucuronide in BALB/c mice was dose-, route-, sex- and age-dependent. 9-aminocamptothecin glucuronide was significantly less toxic to female than to male mice but the difference decreased with age. 9-aminocamptothecin glucuronide and 9-aminocamptothecin produced similar inhibition (approximately 80%) of LS174T human colorectal carcinoma tumours. 9-aminocamptothecin glucuronide cured a high percentage of CL1-5 human lung cancer xenografts with efficacy that was similar to or greater than 9-aminocamptothecin, irinotecan and topotecan.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, and ICTM, Center for Chemistry, Belgrade, Yugoslavia.

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Toxicity of 9ACG. A single i.v. injection of 50 mg kg-1 9ACG was given to male and female 7–8 weeks old BALB/c mice. Control male and female mice were untreated. Mean weights of three mice relative to initial body weights are shown. Significant differences between prodrug and control groups at weight nadirs are indicated: *P⩽0.05. Bars, s.e.
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fig1: Toxicity of 9ACG. A single i.v. injection of 50 mg kg-1 9ACG was given to male and female 7–8 weeks old BALB/c mice. Control male and female mice were untreated. Mean weights of three mice relative to initial body weights are shown. Significant differences between prodrug and control groups at weight nadirs are indicated: *P⩽0.05. Bars, s.e.

Mentions: A single s.c. injection of 2.5 mg kg−1 9AC suspended in lipiodol caused minimal toxicity with 10% weight loss whereas a dose of 5 mg kg−1 produced about 20% weight loss (results not shown). Mice that were i.p. injected with 50 mg kg−1 9ACG experienced progressive weight loss and died within 6 days (results not shown). In contrast, all mice that were i.v. injected with 25 or 50 mg kg−1 9ACG experienced dose-dependent weight loss until day 6 followed by rapid and complete recovery within a week. A more detailed study of toxicity performed in 7–8 week old male and female mice with 50 mg kg−1 9ACG (Figure 1Figure 1


Anti-tumour activity and toxicity of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in mice.

Prijovich ZM, Chen BM, Leu YL, Chern JW, Roffler SR - Br. J. Cancer (2002)

Toxicity of 9ACG. A single i.v. injection of 50 mg kg-1 9ACG was given to male and female 7–8 weeks old BALB/c mice. Control male and female mice were untreated. Mean weights of three mice relative to initial body weights are shown. Significant differences between prodrug and control groups at weight nadirs are indicated: *P⩽0.05. Bars, s.e.
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Related In: Results  -  Collection

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fig1: Toxicity of 9ACG. A single i.v. injection of 50 mg kg-1 9ACG was given to male and female 7–8 weeks old BALB/c mice. Control male and female mice were untreated. Mean weights of three mice relative to initial body weights are shown. Significant differences between prodrug and control groups at weight nadirs are indicated: *P⩽0.05. Bars, s.e.
Mentions: A single s.c. injection of 2.5 mg kg−1 9AC suspended in lipiodol caused minimal toxicity with 10% weight loss whereas a dose of 5 mg kg−1 produced about 20% weight loss (results not shown). Mice that were i.p. injected with 50 mg kg−1 9ACG experienced progressive weight loss and died within 6 days (results not shown). In contrast, all mice that were i.v. injected with 25 or 50 mg kg−1 9ACG experienced dose-dependent weight loss until day 6 followed by rapid and complete recovery within a week. A more detailed study of toxicity performed in 7–8 week old male and female mice with 50 mg kg−1 9ACG (Figure 1Figure 1

Bottom Line: Cancer chemotherapy is limited by the modest therapeutic index of most antineoplastic drugs.Beta-glucuronidase activated 9-aminocamptothecin glucuronide to produce similar cell killing as 9-aminocamptothecin or topotecan.The in vivo toxicity of 9-aminocamptothecin glucuronide in BALB/c mice was dose-, route-, sex- and age-dependent. 9-aminocamptothecin glucuronide was significantly less toxic to female than to male mice but the difference decreased with age. 9-aminocamptothecin glucuronide and 9-aminocamptothecin produced similar inhibition (approximately 80%) of LS174T human colorectal carcinoma tumours. 9-aminocamptothecin glucuronide cured a high percentage of CL1-5 human lung cancer xenografts with efficacy that was similar to or greater than 9-aminocamptothecin, irinotecan and topotecan.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, and ICTM, Center for Chemistry, Belgrade, Yugoslavia.

Show MeSH
Related in: MedlinePlus