In: Chemotherapy17 Nov 2014
Xenografts and In vitro Drug Sensitivity Testing
Over 150,000 cases of lung cancer occur in the USA annually, nearly 90% of whom will die of their disease with a median life expectancy of less than 1 year. Obviously, we need both new drugs as well as new therapeutic concepts. While the latter ideas are discussed by other contributors to this issue, this report will focus on the use of animal and cell culture models for the selection of individualized chemotherapy as well as for the identification of new therapeutic agents. cialis professional
Animal models have been utilized extensively for screening new agents, as well as for attempts at selecting individualized therapies. While earlier models focused on the use of electively immunosuppressed rodents or xenografting into immunologically privileged sites such as hamster cheek pouch, recent efforts have widely utilized athymic nude mice. A large number and variety of human lung cancers have been xenografted, with reported success rates usually in the range of 30-40%. Of interest, the take rate of small cell lung cancer (SCLC) is higher in male nude mice than in females, perhaps reflecting the worse prognosis of this disease in men. Many of these xenografts retain the morphologic and biological characteristics of the original tumors. The usual site of transplantation is subcutaneous, and approximately 10-107 cells are required for a successful take. However, subcutaneous human xenografts seldom invade surrounding tissues or metastasize to distant locations. This is not due to loss of tumorigenidty, blit reflects retention of some host defenses by the athymic mouse, including natural killer cell activity. Thus, longevity of the host animal cannot be utilized as an end-point of drug efficacy. These findings have led to a search for other potential transplantation sites having specialized applications. We and others have utilized intracranial and intra-peritoneal inoculations.
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