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2017 ; 14
(3
): 3019-3027
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis
via depletion of NK cells in an experimental lung metastasis mouse model of colon
cancer
#MMPMID28928840
Shimaoka H
; Takeno S
; Maki K
; Sasaki T
; Hasegawa S
; Yamashita Y
Oncol Lett
2017[Sep]; 14
(3
): 3019-3027
PMID28928840
show ga
Current therapy for rheumatoid arthritis (RA) relies on global suppression of the
immune response or specific blockade of inflammatory cytokines. However, it is
unclear how immunosuppressants affect patients with cancer. Therefore, in the
present study, the effect of three biological agents, tofacitinib, anti-mouse
IL-6 receptor antibody (MR16-1) and etanercept, which are used for the treatment
of RA diseases, on a tumor-bearing mouse model was investigated. The effect of
the three agents was examined using a mouse lung-metastasis model with the murine
colon 26 cancer cell line. Lymphocyte subsets and natural killer (NK) cells in
peripheral blood and spleen were analyzed using fluorescence-activated cell
sorting, and the number of lung surface nodules was examined. In the continuous
tofacitinib administration (15 mg/kg/day) group, the number of lung surface
nodules was significantly increased compared with that of the vehicle-treated
group (vehicle, 1.20±0.58; tofacitinib, 35.6±10.81; P<0.01). NK cell number in
the blood and spleen of tofacitinib-treated mice was decreased 10-fold, and the
percentage of cluster of differentiation (CD)11(+)CD27(-) NK cells was
significantly reduced. MR16-1 [8 mg/mouse; once a week; intraperitoneal (i.p.)]
or etanercept (1 mg/mouse; 3 times a week; i.p.) treatment did not affect the
number of NK cells or lung metastasis. In the present study, immunosuppressants
that target cytokines, including tofacitinib, were demonstrated to inhibit the
proliferation and differentiation of NK cells, and exhibit the potential to
promote cancer metastasis using a mouse model of lung metastasis.