Treatment schedulesThe weights of the mice were recorded weekly from the day a tumour was first detected. The mean weight at the start of treatment was 29.5 ± 0.7 (s.em.) g, range 24-34 g. Weekly prophylactic tail-vein injections of 6 mg kg-' DOX-SL were started when the progr growth of a tumour was verified, at an average size of 0.2 cm3. Tumours were excised when they rhed a volume of 0.8-1.0 cm3, at which time the treatments were stopped. Following tumour excision, a mouse was seected for euthanasia by carbon dioxide asphyxiation when it appeared to be in poor health, or no later than 6 weeks after surgery. All mice were necropsied, and the visceral organs removed. The lungs were examined for metastases by taing four stepwise, 5 pm sections of each of the five lobes. The quantity of metastases per mouse was graded on a scale of 0-5 shown in Table I. ResdksThe results presented in Table H show that weekly injections of 6mg kg-' DOX-SL effectively inhibited the development of metastases from mammary carcinomas (X = 7.9, P< 0.005) and prolonged mean survival from 59 days in the placebo group to 88.7 days in the treated group (t = 3.53, P<0.001). The tumours in untreated mice grew progressively, and were surgically removed, 17 ± 0.6 days after detection, at an average size of 0.9 ± 0.08 cm3. In the treated mice
Background. The objective of this study was to determine the ability of doxorubicin, encapsulated in sterically stabilized liposomes (Doxil [Liposome Technology, Inc., Menlo Park, CA]), to inhibit the spontaneous development of mammary carcinomas in mice. Methods. Monthly prophylactic intravenous injections of 6 mg/kg doses of Doxil were started when retired breeding C3H/He mice were 26 weeks old. Mice that developed a mammary carcinoma were then given weekly intravenous injections of 6 mg/kg doses to determine whether the tumors were susceptible or resistant to Doxil therapy. Results. The monthly injections reduced the incidence of first mammary carcinomas in up to 88‐week‐old retired breeding C3H/He mice from 65 of 66 (98%) in untreated mice to 22 of 47 (47%) in treated mice. The first 15 mice that developed a mammary tumor while on the prophylactic protocol were then placed on a weekly therapeutic protocol. The therapeutic use of Doxil cured 3 of 15 mice and inhibited the growth of 12 tumors. Drug resistance as a result of treatments was not observed. The mean survival of tumor‐bearing mice was extended from 24 days in untreated mice to 87 days in treated mice. Toxic side effects were limited to transient weight loss during the weekly Doxil treatments and to epidermal necrosis and dermal fibrosis due to drug extravasation at the sites of intravenous injections. Conclusions. The authors concluded that doxorubicin in sterically stabilized liposomes deserves to be explored further in comparative studies with free doxorubicin for the prophylaxis and therapy of mammary cancer.
The blood of normal C3H mice contains molecular factors that can rapidly lyse mammary carcinoma cells that enter the circulation. The cytotoxic effect of blood on tumor cells during incubation was most clearly demonstrated if fibrin formation was prevented. The conversion of the mammary carcinoma cells to ascites growth increased both the resistance to lysis in plasma and the ability to form lung colonies after intravenous injection. Mice that were surgically cured of numerous 9 mm tumors and survived for an average 10 months had a lower incidence (36%) of spontaneous metastases than mice that experienced one 30 mm tumor and survived for an average 8 weeks (65%). This is interpreted to mean that mice that retained their vitality by early surgical cures, could suppress the development of metastases by the action of normal serum factors that can destroy neoplastic cells that enter the circulation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.