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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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Anti-tumour activity of 9ACG against CL1-5 human lung adenocarcinoma xenografts. (A) BALB/c nu/nu mice implanted with CL1-5 tumour cells on day 0 were i.v. injected with PBS (solid lines) or 50 mg kg−1 9ACG (dashed lines) on days 10 and 20. Results show the tumour sizes of individual mice. Mean body weights of control or 9ACG-treated mice are shown relative to mean weights on day 5. Bars, s.e. (B) Nude mice implanted with CL1-5 cells on day 0 were i.v. injected with PBS (PBS) or 50 mg kg−1 9ACG (9ACG) on day 10, s.c. injected with 3 mg kg−1 9AC in Lipiodol on day 10 (9AC), or i.v. injected with 10 mg kg−1 irinotecan on days 10, 12 and 14 (CPT-11). The ratio of long-term survivors (>120 days tumour-free) in each group is indicated. (C) Nude mice implanted with CL1-5 cells on day 0 received i.v. injections of PBS (PBS) or 8 mg kg−1 9ACG (9ACG) on days 11, 13, 15, 24, 26 and 28 or 1.8 mg kg−1 topotecan on days 11, 12, 13, 14 and 15 (topotecan). Mean body weights of the PBS, 9ACG or topotecan treated mice are shown relative to mean weights on day 8. Significant differences between the mean weight of mice treated with topotecan or PBS are indicated: *P⩽0.05; **P⩽0.0005. Error bars are not shown for clarity.
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fig4: Anti-tumour activity of 9ACG against CL1-5 human lung adenocarcinoma xenografts. (A) BALB/c nu/nu mice implanted with CL1-5 tumour cells on day 0 were i.v. injected with PBS (solid lines) or 50 mg kg−1 9ACG (dashed lines) on days 10 and 20. Results show the tumour sizes of individual mice. Mean body weights of control or 9ACG-treated mice are shown relative to mean weights on day 5. Bars, s.e. (B) Nude mice implanted with CL1-5 cells on day 0 were i.v. injected with PBS (PBS) or 50 mg kg−1 9ACG (9ACG) on day 10, s.c. injected with 3 mg kg−1 9AC in Lipiodol on day 10 (9AC), or i.v. injected with 10 mg kg−1 irinotecan on days 10, 12 and 14 (CPT-11). The ratio of long-term survivors (>120 days tumour-free) in each group is indicated. (C) Nude mice implanted with CL1-5 cells on day 0 received i.v. injections of PBS (PBS) or 8 mg kg−1 9ACG (9ACG) on days 11, 13, 15, 24, 26 and 28 or 1.8 mg kg−1 topotecan on days 11, 12, 13, 14 and 15 (topotecan). Mean body weights of the PBS, 9ACG or topotecan treated mice are shown relative to mean weights on day 8. Significant differences between the mean weight of mice treated with topotecan or PBS are indicated: *P⩽0.05; **P⩽0.0005. Error bars are not shown for clarity.

Mentions: Intravenous administration of 50 mg kg−1 9ACG on days 10 and 20 resulted in complete regression of six of seven CL1-5 tumours (Figure 4AFigure 4


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)

Anti-tumour activity of 9ACG against CL1-5 human lung adenocarcinoma xenografts. (A) BALB/c nu/nu mice implanted with CL1-5 tumour cells on day 0 were i.v. injected with PBS (solid lines) or 50 mg kg−1 9ACG (dashed lines) on days 10 and 20. Results show the tumour sizes of individual mice. Mean body weights of control or 9ACG-treated mice are shown relative to mean weights on day 5. Bars, s.e. (B) Nude mice implanted with CL1-5 cells on day 0 were i.v. injected with PBS (PBS) or 50 mg kg−1 9ACG (9ACG) on day 10, s.c. injected with 3 mg kg−1 9AC in Lipiodol on day 10 (9AC), or i.v. injected with 10 mg kg−1 irinotecan on days 10, 12 and 14 (CPT-11). The ratio of long-term survivors (>120 days tumour-free) in each group is indicated. (C) Nude mice implanted with CL1-5 cells on day 0 received i.v. injections of PBS (PBS) or 8 mg kg−1 9ACG (9ACG) on days 11, 13, 15, 24, 26 and 28 or 1.8 mg kg−1 topotecan on days 11, 12, 13, 14 and 15 (topotecan). Mean body weights of the PBS, 9ACG or topotecan treated mice are shown relative to mean weights on day 8. Significant differences between the mean weight of mice treated with topotecan or PBS are indicated: *P⩽0.05; **P⩽0.0005. Error bars are not shown for clarity.
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fig4: Anti-tumour activity of 9ACG against CL1-5 human lung adenocarcinoma xenografts. (A) BALB/c nu/nu mice implanted with CL1-5 tumour cells on day 0 were i.v. injected with PBS (solid lines) or 50 mg kg−1 9ACG (dashed lines) on days 10 and 20. Results show the tumour sizes of individual mice. Mean body weights of control or 9ACG-treated mice are shown relative to mean weights on day 5. Bars, s.e. (B) Nude mice implanted with CL1-5 cells on day 0 were i.v. injected with PBS (PBS) or 50 mg kg−1 9ACG (9ACG) on day 10, s.c. injected with 3 mg kg−1 9AC in Lipiodol on day 10 (9AC), or i.v. injected with 10 mg kg−1 irinotecan on days 10, 12 and 14 (CPT-11). The ratio of long-term survivors (>120 days tumour-free) in each group is indicated. (C) Nude mice implanted with CL1-5 cells on day 0 received i.v. injections of PBS (PBS) or 8 mg kg−1 9ACG (9ACG) on days 11, 13, 15, 24, 26 and 28 or 1.8 mg kg−1 topotecan on days 11, 12, 13, 14 and 15 (topotecan). Mean body weights of the PBS, 9ACG or topotecan treated mice are shown relative to mean weights on day 8. Significant differences between the mean weight of mice treated with topotecan or PBS are indicated: *P⩽0.05; **P⩽0.0005. Error bars are not shown for clarity.
Mentions: Intravenous administration of 50 mg kg−1 9ACG on days 10 and 20 resulted in complete regression of six of seven CL1-5 tumours (Figure 4AFigure 4

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