I.V. Administration of L-GNRH-PE66 efficiently inhibits growth of colon adenocarcinoma xenografts in nude mice.
When developing new anti-cancer therapeutic treatments, it is crucial to find the correct route of administration and timetable for treatment. Recently, we constructed the L-GnRH-PE66 chimeric protein, which can target and kill adenocarcinoma cells both in vitro and in vivo. We examined the ability of the L-GnRH-PE66 chimeric protein to inhibit tumor growth in colon carcinoma xenografted nude mice, using different routes of administration and various timetables of treatment. In addition, we examined the ability of the chimeric protein to inhibit tumor growth of large tumors that resemble those encountered in human patients in the clinical setting. We found that an i.v. dose of 12.5 microg given every 48 hr was the most efficacious in inhibiting tumor growth. Tumors treated with this concentration of the chimeric protein were 4.4 times smaller in volume and 3.4 times smaller in weight than those in the control groups. This protocol of L-GnRH-PE66 treatment is an improvement on our previously suggested treatment for adenocarcinoma in humans. An i.v. injection every 48 hr is effective, less toxic and less painful. Our results further support the use of L-GnRH-PE66 as an effective treatment for adenocarcinoma in humans.
Ben-Yehudah
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Department of Cellular Biochemistry and Human Genetics, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
Prus
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Lorberboum-Galski
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D036002:ADP Ribose Transferases; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005098:Exotoxins / Q000008:administration & dosage* / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005098:Exotoxins; C120462:L-GnRH-PE66 protein, chimeric; D011993:Recombinant Fusion Proteins; D007987:Gonadotropin-Releasing Hormone; D036002:ADP Ribose Transferases