Table 1.
Microscopical assessment criteria for histological score determination.
Fig 1.
Progress of radiation-induced oral mucositis in mice.
A, Ulcerations primarily occurred around the intermolar eminence (*, bracketed area). B, Measurements of ulcerated areas. C, Photomicrographs of the tongues (H&E stain). Arrow heads point to colonized microbes. ep, epithelium, lp, lamina propria.
Fig 2.
Altered gene expression in radiation-damaged lesions.
Multiplex gene expression analyses of PRRs (A) and cytokines (B, log scale) in the tongue tissues (day 8 post-irradiation). Bars represent the mean values and the error bars are SEM (n = 6 for 15 Gy/PBS; n = 9 for 20 Gy/PBS).
Fig 3.
GM-1111 inhibits TLR2-induced pro-inflammatory cytokine signaling and NLRP3 inflammasome mediated pyroptosis.
A, Human TLR2 was activated with TLR2-specific agonist Pam3CSK4 (3 ng/mL) in the presence of variable concentrations of GM-1111. B, NLRP3 inflammasome mediated pyroptosis was tested in human THP1 cells. Symbols represent the mean values and the error bars are SEM (n = 5 in A; n = 8 in B per concentration).
Fig 4.
GM-1111 reduces single X-ray irradiation-induced oral mucositis.
A, Photographs (left panel) and photomicrographs (right panel) of representative tongues for each treatment group. Measurements of ulcerative lesions (B) and histological severity scores (C). Symbols represent individual values and bars are the mean values for each group. PRR (D) and cytokine (E) gene expression levels in the lesions (n = 9 per group). ** p < 0.01, *** p < 0.001, and NS (not significant, p > 0.05).
Fig 5.
GM-1111 reduces oral mucositis induced by fractionated irradiation.
A, Top row: tongue samples showing the ulcerative lesions (highlighted in red, stained with Toluidine blue). Middle row: photomicrographs (H&E stained) illustrating the ulcerative lesions. Higher magnification photomicrographs (bottom row) showing the lesions in the intermolar eminence. ep, epithelial layer; lp, lamina propria. Arrows indicate colonized microbes. Measurements of ulcerated areas (B) and histological severity scores (C). *p < 0.05, **p < 0.01, ***p < 0.001, and NS (not significant, p > 0.05).
Fig 6.
Treatment with GM-1111 does not interfere with radiation therapy.
A, In vivo bioluminescence imaging of SCC-25-Luc cell tumors (day 38). B, Changes in tumor volume over time. Symbols are the mean values and error bars are SEM (upward direction). Area under the curve (AUC) values are calculated for Group 2 (day 17–38). **p < 0.01, ***p < 0.001, and NS (not significant, p > 0.05). C, Photomicrographs of tongues samples. Tumors are marked with dotted lines. Arrows indicate necrotic foci. Sagittal section (H&E stain, original magnification 2x).