Carcinoid tumors are endocrine neoplasms derived from neuroectodermal cells (enterochromaffin cells) of the neural crest.!.? These tumors, primarily found in the gastrointestinal tract, are uncommon but not rare, with a reported incidence in various autopsy series ranging from 0.1 to 1.4 percent. l Originally called “Karzinoide” by Oberndorfer “to describe their relatively benign appearance, carcinoid tumors produce numerous vasoactive substances, including serotonin [5-hydroxytryptamine;(5-HT)], and a host of biogenic amines and hormones as identified by immunohistochemical and radioimmunoassay The release of these amines and peptides can cause the devastating sequelae known as the carcinoid syndrome, with characteristic symptoms of flushing, diarrhea, bronchoconstriction, and cardiac valvular disease. l,?

The treatment of patients with carcinoid tumors has been directed mainly toward the symptomatic management of the carcinoid syndrome. A multitude of blocking agentsL7 (for example, methysergide, cyproheptadine, and ketanserin) or the inhibitory hormone, somatostatin,” 16 have all been used to relieve the myriad symptoms caused by the release of the various products of carcinoid tumors. Antiproliferative agents commonly used to slow carcinoid tumor growth have included combinations of streptozotocin, 5-fluorouracil, doxrubicin, and cyclopho-~ phamide.~.’~-l” These chemotherapeutic agents have been evaluated in a limited number of nonrandomized clinical trials and, for the most part, have been found to be ineffective in slowing the growth of carcinoid tumor^.^^.^^.^^ In addition, treatment with these toxic agents often causes harmful side effects. The development of effective treatment regimens for patients with carcinoid tumors has been hampered, in part, by the lack of effective models of carcinoid tumor that would allow evaluation of the possible efficacy of chemotherapeutic agents, the characterization of genetic alterations that may contribute to the pathogenesis, and the assessment of clinical behavior of these tumors. Previous carcinoid tumor models have included analysis of gastric carcinoids spontaneously originating in African rodents (Mastomys natalensis) 20 and human carcinoid tumors transplanted into the anterior chamber of the eye of immunosuppressed rats. 21.22 Although valuable in studying production and release of various amines, these models contribute little in clarifying aspects of in vivo growth and behavior of human carcinoids. Our laboratory has successfully established a functioning human carcinoid tumor, BON, derived from a lymph node metastasis of a pancreatic~ arcinoid.~~.~~ We