Polyadenlic Polyuridylic Acid가 위암환자의 항종양주효세포 활성에 미치는 영향
Effects of Polyadenylic Polyuridylic Acid on the Activity of the Antiumor Effector Cells from Patients with Adenocarcinoma of Stomach
소속 상세정보
박호규
박선경/이미리나/신전수/민진식/윤정구
KMID : 0360319920240010019
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 implication 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 100mg 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-sensitive 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/ml of recombinant human interleukin-2(rIL-2) for 5 days and the same tests as above were performed with cultured cells.
@ES The main results were as follows:
@EN 1) Fresh PBMNC form 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 cells 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 technique of 쿓-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, CD8
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.
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