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Novel therapy for the treatment of human carcinoid
B M Evers1, S C Hurlbut, S K Tyring
1Department of Surgery, University of Texas Medical Branch, Galveston, TX 77550.
Abstract:
Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study introduces a novel human pancreatic carcinoid tumor cell line (BON) for preclinical research. Combination therapy with alpha-interferon and alpha-difluoromethylornithine effectively suppressed tumor growth in mice.
Area of Science:
- Oncology
- Medical Research
Background:
- Carcinoid tumor treatment is limited by the lack of effective experimental models.
- A long-term cell line of a functioning human pancreatic carcinoid tumor (BON) was established.
- This BON cell line produces tumors in nude mice, serving as a preclinical model.
Purpose of the Study:
- To evaluate the efficacy of alpha-interferon (IFN), a somatostatin analog (SMS 201-995), and alpha-difluoromethylornithine (DFMO) in inhibiting BON tumor growth.
- To assess the impact of treatment initiation timing on therapeutic outcomes.
Main Methods:
- BON tumor fragments were implanted subcutaneously into male BALB/c nude mice.
- Two studies were conducted: one with treatment initiated at tumor implantation, and another after established tumor growth.
- Mice received treatments including IFN, SMS, DFMO, and combinations thereof.
- Tumor growth, body weight, and tumor characteristics were monitored.
Main Results:
- In the initial study, IFN alone or in combination with SMS or DFMO suppressed tumor growth when treatment began at implantation.
- In the second study, when treatment commenced after tumor establishment, only combinations of IFN with DFMO were effective in suppressing tumor growth.
- The combination of IFN, DFMO, and SMS also showed efficacy in established tumors.
Conclusions:
- The developed BON cell line is a valuable model for studying carcinoid tumors.
- Combination therapy, particularly with alpha-interferon and alpha-difluoromethylornithine, shows promise for treating functioning pancreatic carcinoid tumors.
- Timing of treatment initiation is critical for therapeutic success in this model.