Drug development is needed to improve chemotherapy of patients with locally advanced or metastatic colon carcinoma, who otherwise have an unfavorable prognosis. DNA topoisomerase I, a nuclear enzyme important for solving topological problems arising during DNA replication and for other cellular functions, has been identified as a principal target of a plant alkaloid 20(S)-camptothecin. Significantly increased concentrations of this enzyme, compared to that in normal colonic mucosa, were found in advanced stages of human colon adenocarcinoma and in xenografts of colon cancer carried by immunodeficient mice. Several synthetic analogs of camptothecin, selected by tests with the purified enzyme and tissue-culture screens, were evaluated in the xenograft model. Unlike other anticancer drugs tested, 20(RS)-9-amino-camptothecin (9-AC) induced disease-free remissions. The overall drug toxicity was low and allowed for repeated courses of treatment.

An in vitro line was derived from an American Burkitt lymphoma, designated Ra #1, which produced malignant tumors when inoculated into thymus-deficient nude mice. The cells have B-lymphocyte characteristics, with surface-associated mu and kappa chains and Epstein-Barr virus (EBV) receptors, and can be readily infected with EBV in vitro. B95–8 virus induced EBV-determined nuclear antigen (EBNA) but not early antigen (EA) in Ra #1 cells, whereas P3HR-1 virus induced both EBNA and EA, but the EA level was much lower than in the prototype Raji strain. EBNA and EA levels were comparable in Ra #1 and in the previously established, EBV-infection-sensitive BJA-B lymphoma. The two lines differed, however, because BJA-B could be converted into a permanent EBV-carrying line by the B95–8 but not by the P3HR-1 virus strain, whereas Ra #1 could be converted by the P3HR-1 virus. This demonstrates that different B-lymphocyte-derived lymphoma lines can vary with regard to the restrictive control they can exert on the same virus strain. Furthermore, virus strains vary in their sensitivity to the restrictions of the same host cell. Permanent EBV conversion of the Ra #1 cell did not appear to change the cellular controls, as judged by the unchanged sensitivity of the cell to viral antigen (EA, viral capsid antigen) induction by P3HR-1 virus superinfection.

A well-differentiated squamous cell carcitionoa and three poorly differentiated carcinomas of the nasopharynx were analyzed for the presence of Epstein- After correction for mouse cell admixture, the latter tumors were found to contain about 80, 55, and 160 Epstein-Barr virus genome equivalents per human cell. The virus-determined nuclear antigen was localized in the large carcinoma cell clusters in all three mnouse-passaged tumors positive for the viral 1)NA, but other virus-determined antigens were not detected, indicating the absence of virus induction. In contrast to the original tumor biopsies, the nude-mousepassaged tumors showed virtually no lvmphocytic infiltration. It is concluded that the Epstein-Barr virus DNA found in biopsies of human nasophiaryngeal carcinomas is localized in the neoplastic cells.