Peri-operative immune modulation by polyadenylic-polyuridylic acid in patients with breast cancer undergoing surgery : and establishment of optimum dose in vitro
PAPU has a wide range of effects on various immunological cells and functions. It has been shown to enhance cellular and humoral immunity, in particular anti-cancer host defences, in both animals and man. In a small number of clinical trials (breast and stomach cancers) it appears to have a beneficial adjuvant effect, in terms of prolongation of disease free and overall survival. However, the most beneficial therapeutic regimen has yet to be established. Previously, PAPU has been used in low doses (60 mg and 100 mg) in the post-operative period. This thesis was designed to evaluate the effects of a much higher dose of PAPU, given in the peri-operative period on both cellular and humoral immune responses in patients with breast cancer undergoing surgery. We have shown that PAPU stimulates the natural killer (NK) cell and lymphokine activated killer (LAK) cell activity. These cells are believed to play an important role in the host resistance against metastatic dissemination in patients with malignant disease and have also been reported to have substantial anti-tumour activity against a wide range of different types of tumour cells. In addition, PAPU also enhanced the release of C-reactive protein (CRP) and associated cytokines [interleukin 1b (IL1b), interelukin 6 (IL6) and tumour necrosis factor a (TNFa)], as well as stimulated T lymphocytes in the peri-operative period. CRP is believed to play a pivotal role in the host defences. In addition, an optimum immunomodulatory dose of PAPU has been defined by an in vitro analysis of natural cytotoxicity and mitogen response assays of peripheral blood mononuclear (PBM) cells in healthy volunteers. PAPU was used in a concentration of 1ul/ml, 10ul/ml, 100ul/ml, 250ul/ml and 500 ul/ml. 100ul/ml was noticed to produce maximum stimulation of NK and LAK cell cytotoxicity.