Combination Chemotherapy of Rauscher Leukemia and Ascites Tumors by Narcissus Alkaloid with Standard Drugs and Effect on Cellular Immunity

Therapeutic Activity of Pretazettine on Rauscher Leukemia: Combination of Antiviral Activity and Cellular Protein Inhibition

“…Although PTZ inhibits the viral reverse transcriptase and the virus replication in vitro [16], it also inhibits cellular protein synthesis [15] which sec ondarily affects the viral process in the cells [1,5], We have confirmed that PTZ at low concentrations could specifically suppress the protein synthesis of leukemic blood cells in vitro and such effective concentrations could be maintained at least 6 h in the splenic blood of mice given the nontoxic dose. Also, the specific activity of PTZ over the indirect effect of cellular protein inhibi tion on suppressing the viral process has been demonstrated in acutely-infected cells but not in chronically-infected cells.…”

“…The 0.1 ,«Ci of each ,4C-precursor was added to 1 ml of whole blood cultures previously diluted 10-fold with Hanks solution and the nucleated white cell num ber was counted. After 1 h incubation at 37 °C, the acid-precipitable fraction was collected, washed on a filter paper (Whatman 3 MM) and counted in a toluene-based scintillation cocktail [5]. PTZ was added just before addition of the precursors for the in vitro experiments; PTZ (1 mg) had previously been injected subcutaneous ly (s.c.) into leukemic mice 3, 6 and 24 h before collecting the blood for the in vivo-in vitro experi ments.…”

“…The effect of PTZ in mice seems due to its potent antiviral ac tivity along with moderate antitumor activ ity without affecting humoral and cellular immunity or general health. This allows a long-term administration [5,16]. The alka loid is inhibitory to the growth of Rauscher virus and cellular protein synthesis in cell cultures in low concentration [6,15] and a viral reverse transcriptase in a cell-free sys tem at higher concentration [7].…”

Therapeutic Activity of Pretazettine, a Narcissus Alkaloid, on Spontaneous AKR Leukemia

“…In addition to its therapeutic activity against Rauscher viral erythrogenous or myelogenous elukemia [6,8], PTZ has been found to be active against spontaneous AKR leukemia, a lymphocytic type of natu ral malignancy occurring without the inocu lation of any artificial inducers [13,17]. About 20°/o of the mice in a lot of AKR/J retired breeders, 5-7 months of age when treatment with PTZ was started, could be diagnosed as leukemic in advanced stage by palpation of spleen and lymph nodes which is reported to be a more reliable indicator than that of white blood cell counts for di agnosis [15].…”

Therapeutic Activity of Pretazettine, Standard Drugs, and the Combinations on Intraperitoneally Implanted Lewis Lung Carcinoma in Mice

“…It is well known that CY has a strong immunosup pressive action [10][11][12], and therefore it is suggested that the relatively low therapeu tic activity of CY is the result of overall in teractions between the tumor cell kill act ivity and the immunosuppressive action which makes the natural defense mechan isms weak. PTZ is not immunosuppressive at therapeutic doses [13]. The therapeutic activity of CY, PTZ.…”