Participation of Hoat Factors on the Effects of Anti-Cancer Drugs:Part 1. Influence of BCG on the Effects of Cyclophosphamide on Tumor Growth and the C e llular Immune Response in Rats
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For the purpose of obtaining some basic knowledge on the immuno-chemotherapy of cancer, studies were made on the effects of BCG on tumor growth and on the cellular immune response in rats, with special reference to its influence on the effects of cyclophosphamide (CPM) administration in Yoshida sarcoma (YS) bearing rats. Th e results obtained were as follows<BR>1) Determination of t he optimum day for BCG administration after subcutaneous (s.c.) YS inoculation combined with CPM treatment on the fifth post-inoculation day: BCG (1mg s.c.) administration on the third day caused early but temporary suppression of tumor growth which was followed by a regrowth, while BCG given on any other day yielded no remarkable influence on tumor growth following CPM administration.<BR>2) Determination of BCG dose: Experiments with various do sages of BCG (O.5 to 4mg) on the 3rd post-inoculation day revealed that a 4mg administration was the most effective by showing remarkable tumoral regression as well as a 100% survival rate.<BR>3) Comparative studies on the effects of immunotherapy (BCG 4mg on the third day), chemotherapy (CPM 40mg/kg on the fifth day), and immuno-chemotherapy (BCG combined with CPM): Immunotherapy alone enabled survival rate of 92.3% and a complete regression rate of 84.6% on the 24th day; the respective immuno-chemotherapy rates were 84.6% and 46.2%, and chemotherapy alone led to tumoral growth of the tumor after an early temporary regression, its rates being 80% and 20% respectively, Tumor implanted rats receiving no treatment, showed progressive tumoral growth, the survival rate being 28.6% without any instance of complete tumoral regression.<BR>So far as this experiment is concerned, the immunotherap y was the most effective, followed by immuno-chemotherapy, the chemotherapy being the least effective.<BR>4) Estimation of in vitro PHA responsiveness of rat spleen cells in various condition (<SUP>3</SUP>HTd Ruptake method); BCG (4mg s.c.) administration in normal rats brought about persistent spleen cell increases, both in count and in reactivity to PHA.<BR>Spleen cells from tumor-bearing rats showed a persistent desce nt in their responsiveness to PHA proportionate to ineffective treatment: In all of the treated animals the responsiveness descended on the 7th to 12th post-implantation day (2th to 7th day after CPM administration), most remarkably in the immuno-chemotherapy group, followed by the chemotherapy group, while the immunotherapy group showed only a slight depression; nevertheless, the responsiveness recovered in concomitance with t umor regression.<BR>These obtained findings, showing the effectiveness of BCG with or without chemotherapy, may prove useful in the practice of immuno- or immuno-chemotherapy against malignant tumors.
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