A prospectively randomized, double-blind clinical trial was conducted to evaluate the effect of immunotherapy with transfer factor (TF) as an adjunct to radiotherapy of patients with stage III nasopharyngeal carcinoma (NPC). The TF was derived from normal young adults with a proven history of infectious mononucleosis and from normal blood donors with elevated antiviral capsid antigen antibody activity. TF prepared in this fashion was previously shown to convert the leukocytes of patients with NPC to a reactive state in vitro and when administered to NPC patients in vivo was associated with apparent slowing of tumor growth, marked lymphocytic infiltration of the tumor, and reconstitution of delayed cutaneous hypersensitivity reactions. From 1974 to 1977, 100 patients with NPC were entered in the study; one-half of the patients were treated with radiotherapy alone and one-half received radiotherapy and an 18-month course of TF immunotherapy. The patients were followed for at least 5 years. No significant difference in disease-free survival or survival was noted between the two groups of patients. The use of this particular preparation and dose schedule of TF in patients with NPC with regional disease was devoid of any anti-tumor activity.

Adult↗

PubMedDate not supplied

Cytogenetic analysis of an immunogenic mutant of the L5178Y lymphoma.

A mutant of the uniformly lethal L5178Y lymphoma, called the L5178Y/Manitoba (L5178Y/M), was rejected after subcutaneous challenge in syngeneic DBA/2 mice. Karyotypic analysis revealed that the parent L5178Y lymphoma had four chromosome markers, with the mutant L5178Y/M sharing one of them as well as possessing two distinguishing markers. One diploid and two hypotetraploid clones were isolated from the L5178Y/M; they contained all the marker chromosomes and were also rejected by the syngeneic host. In addition to the shared chromosome markers, the L5178Y/M possessed antigens in common with the parent L5278Y. DBA/2 mice made immune to the mutant by subcutaneous immunization were able to slow the growth of the parent tumor but not the unrelated P-815-X2 mastocytoma.

Animals↗

PubMedDate not supplied

Selective sensitization of adriamycin-resistant P388 murine leukemia cells to antineoplastic agents following transfection with human DNA topoisomerase II alpha.

Previous studies have demonstrated decreased levels of DNA topoisomerase II alpha protein and messenger RNA in the Adriamycin-resistant P388 murine leukemia cell line P388/ADR/7 compared to the sensitive P388/4 cell line. An allelic fusion event involving the topoisomerase II alpha and the retinoic acid receptor a genes has been identified in these cells that probably contributes to the decreased topoisomerase II activity in P388/ADR/7 cells. However, this allelic mutation may be a minor contributor or even incidental to the resistance phenotype, since these cells display other candidate mechanisms of resistance, including increased P-glycoprotein, increased glutathione-S-transferase activity and an increased onset of DNA repair. To establish a role for topoisomerase II alpha in mediating the Adriamycin resistance phenotype, complementation of the mutant allele was attempted by transfecting the murine P388/ADR/7 cells with a human topoisomerase II alpha expression construct under the control of the human metallothionein IIA promoter. The majority of transfected cell lines that were obtained by selection in hygromycin B contained copies of the integrated expression construct that were rearranged. Only two of thirty-two transfected cell lines were found to contain a single, unrearranged copy of the human topoisomerase II alpha cDNA. P388/ADR/7 cell lines carrying an integrated, intact human topoisomerase II alpha expression vector were more sensitive to Adriamycin, daunorubicin, mitoxantrone, and etoposide, but not to actinomycin D and vincristine compared to control cells transfected with vector alone or cell lines with rearranged topoisomerase II alpha expression constructs. These findings suggest that topoisomerase II alpha is a selective and significant contributor to multifactorial resistance.

Animals↗