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The mitotoxin, basic fibroblast growth factor-saporin, effectively targets human prostatic carcinoma in an animal
1Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02908, USA.
Purpose:
The antitumor activity of the mitotoxin basic fibroblast growth factor-saporin (bFGF-SAP) against human prostatic carcinoma DU 145 was examined in athymic nude mice. Therapeutic efficacy was evaluated on the basis of dose, route of administration and treatment schedule.
Materials And Methods:
Chemical conjugate or recombinant bFGF-SAP (0.02 to 50 micrograms/kg.) was administered by intravenous tail injection, intraperitoneal injection, or local or distal subcutaneous injection beginning 5 days (or 60 to 121 days for large tumor studies) after subcutaneous implantation of DU 145 cells. Tumor growth was monitored as long as 140 days by external caliper measurements.
Results:
Recombinant bFGF-SAP, though less cytotoxic than its chemical conjugate form, effectively targeted DU 145 tumors growing as xenografts in nude mice in a dose-dependent manner. Antitumor response to treatment by intravenous, intraperitoneal, or distal subcutaneous injection suggested similar bioavailability of the mitotoxin administered by each route; local subcutaneous injection to the tumor site resulted in statistically better antitumor response. Schedules that included at least 1 bFGF-SAP treatment beyond day 23 increased long-term antitumor efficacy independent of total dose. Moreover, recombinant bFGF-SAP induced dramatic reduction of large, established tumors.
Conclusions:
These studies suggest a therapeutic potential for bFGF receptor-directed toxins in targeting prostate cancer; further, these data suggest that treatment of established tumors (> 3 weeks) results in qualitatively and quantitatively improved tumor responses.
Insights
Basic fibroblast growth factor-saporin (bFGF-SAP) shows therapeutic potential against prostate cancer. Local subcutaneous administration and extended treatment schedules improved antitumor efficacy in mice, even for established tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate cancer remains a significant health concern with a need for novel therapeutic strategies.
- Targeting specific receptors on cancer cells offers a promising approach for selective toxicity.
- Basic fibroblast growth factor receptor (bFGF-R) is expressed on various cancer cells, including prostate carcinoma.
Purpose of the Study:
- To evaluate the antitumor activity of basic fibroblast growth factor-saporin (bFGF-SAP), a mitotoxin, against human prostate carcinoma DU 145 xenografts in athymic nude mice.
- To assess the therapeutic efficacy based on dose, route of administration, and treatment schedule.
Main Methods:
- DU 145 cells were implanted subcutaneously in nude mice.
- Recombinant or chemically conjugated bFGF-SAP was administered via intravenous, intraperitoneal, or subcutaneous injections at varying doses and schedules.
- Tumor growth was monitored using external caliper measurements for up to 140 days.
Main Results:
- Recombinant bFGF-SAP demonstrated dose-dependent targeting of DU 145 xenografts.
- Local subcutaneous injection yielded superior antitumor response compared to other routes.
- Treatment schedules including bFGF-SAP beyond 23 days enhanced long-term efficacy, and established tumors showed significant reduction.
Conclusions:
- bFGF receptor-directed toxins show therapeutic potential for prostate cancer treatment.
- Treating established tumors (over 3 weeks) with bFGF-SAP leads to improved tumor responses, both qualitatively and quantitatively.