Effects of several caspase inhibitors (Z-VAD-FMK, a broad caspase inhibitor; Ac-LEHD-CHO, a caspase-8 inhibitor; Ac-IETD-CHO, a caspase-9 inhibitor; Ac-DMQD-CHO, a caspase-3 inhibitor) on etodolac treatment (48 h) (n = 5).

<p>Each of these caspase inhibitors inhibited etodolac-induced apoptosis of FMS-1 cells incompletely but significantly. On the other hand, in FPS-1 cells, only Z-VAD-FMK and Ac-LEHD-CHO significantly inhibited etodolac-induced apoptosis. P-values of each analysis were calculated based on Student’s t-test (**, P<0.01; NS, not significant).</p

Effect of etodolac treatment on FPS-1 and FMS-1 cells (n = 5).

<p>Etodolac significantly reduced cell viability of FMS-1 cells in a dose-dependent manner. P-values compared with the control were calculated based on Student’s t-test (*, P<0.05; **, P<0.01).</p

Univariate and multivariate analysis of overall survival (Cox proportional hazards model).

<p>*including the cases in which only a biopsy was performed; CI, confidence interval.</p

Activities of caspase-8, -9, and -3 with etodolac treatment (24 and 48 h) (n = 3).

<p>Both in FPS-1 and FMS-1 cells, etodolac significantly activated caspase-8, -9, and -3 at both 24 and 48 h compared with the control group. However, the differences of caspase-activities were much smaller in FPS-1 cells than those in FMS-1 cells. P-values were calculated based on Student’s t-test (*, P<0.05; **, P<0.01).</p

Diffuse, strong, and cytoplasmic-positive immunoreactivity for COX-2 in MPNST (immunohistochemical score, 4+) (immune-peroxidase stain, ×400).

<p>Diffuse, strong, and cytoplasmic-positive immunoreactivity for COX-2 in MPNST (immunohistochemical score, 4+) (immune-peroxidase stain, ×400).</p

Morphology of FPS-1 (A) and FMS-1 (D) cells after etodolac treatment for 72 h.

<p>Nuclear fragmentations were observed only in FMS-1 cells (D, arrow). Both in FPS-1 (B) and FMS-1 (E) without etodolac treatment, cells were viable and no apoptotic cells were observed (May-Giemsa staining, ×400). Evaluation of apoptosis using agarose gel electrophoresis (C, FPS-1; F, FMS-1). Only DNA samples from the FMS-1 cells (F) after etodolac treatment for 72 h revealed the DNA ladder, indicating apoptosis. M, marker, 100-bp DNA ladder; E, etodolac treatment; C, control (without etodolac treatment).</p

Kaplan-Meier curve of overall survival evaluated for COX-2 overexpression.

<p>Overexpression of COX-2 was significantly associated with a decreased probability of overall survival (P = 0.0495).</p

Statistical relationship between immunohistochemical result of COX-2 and other variables.

<p>*Percentage of positive cases; NA, not available.</p