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Title   Polyadenylic . Polyuridylic Acid 가 위암환자의 항종양주효세포 활성에 미치는 영향 ( Effect of Polyadenylic . Polyuridylic Acid on the Activity of Antitumor Effector Cells from Patients with Adenocarcinoma of Stomach )
Publicationinfo   1992 Jan; 024(01): 19-35.
Key_word   Poly(A). poly(U), Human NK & LAK cells, Cytotoxicity, Surface phenotype
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Abstract   Polyadenylic.polyuridylic acid[poly(A).poly(U)], a synthetic double-stranded complex of polyribonucleotides, is capable of stimulating the immune system and its potent antitumor activities were evidenced in various animal tumor models and recently in human cancers. However, the mechanisms implicating in such antitumor effect of the agent are not fully elucidated. The purpose of this study is to determine whether poly(A).poly(U) could influence the activities of nonspecific antitumor effector cells, particularly of natural killer(NK) and lymphokine-activated killer(LAK) cells, both being considered to play an important role in host immune surveillance against cancers. A total of 53 patients with adenocarcinoma of stomach were divided into 2 groups: 25 patients in poly(A).poly(U)-treated group and 28 patients in placebo-treated group. After curative surgery, they were injected intravenously with 100 mg of poly(A).poly(U) or placebo. Peripheral blood samples were taken from each patients twice: just before surgery and 1 to 2 days after the injections. Peripheral blood mononuclear cells(PBMNC) were prepared and submitted to in vitro cytotoxic assays by a 4h-51Cr release technique using NK-sensi- tive K562 and NK-resistant Raji target cells and also to surface phenotype determinations by an immunofluoresence technique using monoclonal antibodies. A part of PBMNC were put in culture with medium containing-300 units/m1 of recombinant human interleukin-2 (rIL-2) for 5 days and the same tests as above were performed with cultured cells. The main results were as follows: 1) Fresh PBMNC from patients treated with placebo after surgery showed a cytotoxicity significantly lower against K562 cells than those from the same patients before surgery. However, the PBMNC from poly(A).poly(U)-treated patients showed no such difference in their cytotoxicities between blood samples taken from patients before and after surgery. Cytotoxicities of these PBMNC to Raji target cella were very low and almost null in both groups regardless of surgery. 2) In contrast, cultured PBMNC from patients of both groups showed highly increased cytotoxic activities not only against K562 but also to Raji targets and these activities were more pronounced in cells from poly(A).poly(U)-treated patients. 3) Proliferations of PBMNC under the same culture condition, measured by the tech- nique of H-thymidine incorporation, were more accelerated in cells from poly(A).poly(U)- treated patients as compared to those from placebo-treated patients#. 4) The number of CD16' and CD56' cells were significantly increased on fresh PBMNC from poly(A).poly(U)-treated patients. However, cultured PBMNC from both groups showed a non-homogeneous mixed cell population expressing various levels of CD3, CD4, CDS, CD25, CD16, and CD56 positivities. It can be concluded that poly(A).poly(U) has increased significantly cytotoxic activities of both fresh and cultured PBMNC from operated stomach cancer patients which reflect respectively enhanced NK and LAK cell activities and these could be partly the mechanism governing antitumor effect of the agent.
저 자   박호규(Ho Kyu Park),박선경(Sun Kyung Park),이미리나(Millina Lee),신전수(Seon Soo Chin),민진식(Jin Sik Min),윤정구(Jung Koo Youn)