Novel therapy for the treatment of human carcinoid

B. Mark Evers, Stephen C. Hurlbut, Stephen K. Tyring, Courtney Townsend, Tatsuo Uchida, James C. Thompson

Research output: Contribution to journalArticle

23 Citations (Scopus)

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, α-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 × 106 units, sc, four times a day), IFN + SMS (300 μg/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. It is concluded that combinations of these agents may offer an effective and relatively nontoxic approach for treatment of carcinoid tumors. This unique tumor will provide an excellent model to study effects of various treatment strategies.

Original languageEnglish (US)
Pages (from-to)411-416
Number of pages6
JournalAnnals of Surgery
Volume213
Issue number5
StatePublished - May 1991

Fingerprint

Carcinoid Tumor
Eflornithine
Interferons
Neoplasms
Therapeutics
Growth
Nude Mice
Control Groups
Octreotide
Polyamines
Somatostatin
Tumor Burden
Drinking Water
Theoretical Models
Body Weight
RNA
Cell Line

ASJC Scopus subject areas

  • Surgery

Cite this

Evers, B. M., Hurlbut, S. C., Tyring, S. K., Townsend, C., Uchida, T., & Thompson, J. C. (1991). Novel therapy for the treatment of human carcinoid. Annals of Surgery, 213(5), 411-416.

Novel therapy for the treatment of human carcinoid. / Evers, B. Mark; Hurlbut, Stephen C.; Tyring, Stephen K.; Townsend, Courtney; Uchida, Tatsuo; Thompson, James C.

In: Annals of Surgery, Vol. 213, No. 5, 05.1991, p. 411-416.

Research output: Contribution to journalArticle

Evers, BM, Hurlbut, SC, Tyring, SK, Townsend, C, Uchida, T & Thompson, JC 1991, 'Novel therapy for the treatment of human carcinoid', Annals of Surgery, vol. 213, no. 5, pp. 411-416.
Evers BM, Hurlbut SC, Tyring SK, Townsend C, Uchida T, Thompson JC. Novel therapy for the treatment of human carcinoid. Annals of Surgery. 1991 May;213(5):411-416.
Evers, B. Mark ; Hurlbut, Stephen C. ; Tyring, Stephen K. ; Townsend, Courtney ; Uchida, Tatsuo ; Thompson, James C. / Novel therapy for the treatment of human carcinoid. In: Annals of Surgery. 1991 ; Vol. 213, No. 5. pp. 411-416.
@article{a49f7bccebba4b10805593779bdeb0d5,
title = "Novel therapy for the treatment of human carcinoid",
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, α-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 × 106 units, sc, four times a day), IFN + SMS (300 μg/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. It is concluded that combinations of these agents may offer an effective and relatively nontoxic approach for treatment of carcinoid tumors. This unique tumor will provide an excellent model to study effects of various treatment strategies.",
author = "Evers, {B. Mark} and Hurlbut, {Stephen C.} and Tyring, {Stephen K.} and Courtney Townsend and Tatsuo Uchida and Thompson, {James C.}",
year = "1991",
month = "5",
language = "English (US)",
volume = "213",
pages = "411--416",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Novel therapy for the treatment of human carcinoid

AU - Evers, B. Mark

AU - Hurlbut, Stephen C.

AU - Tyring, Stephen K.

AU - Townsend, Courtney

AU - Uchida, Tatsuo

AU - Thompson, James C.

PY - 1991/5

Y1 - 1991/5

N2 - 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, α-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 × 106 units, sc, four times a day), IFN + SMS (300 μg/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. It is concluded that combinations of these agents may offer an effective and relatively nontoxic approach for treatment of carcinoid tumors. This unique tumor will provide an excellent model to study effects of various treatment strategies.

AB - 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, α-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 × 106 units, sc, four times a day), IFN + SMS (300 μg/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. It is concluded that combinations of these agents may offer an effective and relatively nontoxic approach for treatment of carcinoid tumors. This unique tumor will provide an excellent model to study effects of various treatment strategies.

UR - http://www.scopus.com/inward/record.url?scp=0025775316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025775316&partnerID=8YFLogxK

M3 - Article

C2 - 1708983

AN - SCOPUS:0025775316

VL - 213

SP - 411

EP - 416

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 5

ER -