|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1990 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1989 : ¥1,200,000 (Direct Cost : ¥1,200,000)
==INTRODUCTION== An enthusiasm, shown during the '80s, towards antitumor host responses observed at plasma perfusion over immobilized protein A seems to have subsided. It so happened possibly because of the toxicity problems, of unestablished working mechanism and of rather limited clinical benefits. The present study was undertaken to conquer the difficulties by developing a non-bacterial methodology, and to carry out clinical trials for improved benefits.
==RESULTS== A : Using rabbits and Vx2 carcinoma ; 1. Ex-vivo modulation of serum or plasma with high molar NaCl (1.5 M) or KCl (0.5 M), as well as protein A, have achieved significant prolongations of the survival time. 2. Normal sera (autologous), as well as the supernatant fraction of 3.5% PEG precipitation, did achieve the host response. 3. The response was abrogated when ; a) serum was treated at 56 C for 30 min prior to modulation with 1.5 M NaCl or b) 1.5 M NaCl-treated serum was given at 24th hr of tumor inoculation. 4. Electr
on microscopy detected increase in cytoplasmic materials in the intercellular space as early as 3 hr after infusion of 25 ml protein A-treated plasma. B : Clinical studies ; 1. An infusion of NaCl or KCl treated serum or plasma attained an acute response in the tumor but without any serious generalized complication. 2. Normal plasma (treated with 0.5 M KCl) was also attained the response in patients with breast adenocarcinoma by gross observation (3/3) and by studies with LM (3/3) and EM (1/1). 3. Combine use of chemotherapy and plasma-therapy attained benefits more than the assumed algebraic sum of each modality alone. 4. In vitro cytotoxicity by protein A- treated serum was not observed unless the tumor cells were suspended in the autologous (tumor bearing) serum. 4. Serum treated with 0.5 M KCl or 1.5 M NaCl for 30 min at room temperature showed elevations of levels of C4a, C3a and C5a.
==Conclusions and suggestions== These findings suggest that the response induced by ex-vivo modulated sarum or plasma is beneficial, that infusion of activated C components, especially those of C3, might be the key for the response, though the infused materials themselves are not cytotoxic and the response in the host is antigen dependent. Less