Development of tumor volume with and without anti-YKL-40 treatment.

<p>T2 and T2* weighted MRI of two Balb/c scid mice with LOX tumors treated with isotype (<b>A</b>) or anti-YKL-40 monoclonal antibody (<b>B</b>) before injection of antibody (d0), five days (d5) and seven days (d7) after start of treatment. Observed hemorrhage is indicated by arrow.</p

Vessels and single S1P1 positive cells in the xenograft tumors: Immunohistochemical staining of anti-YKL-40 treated and control tumors for murine S1P1 (as in Figure 6B, right panel).

<p>Asterisks: vessels; arrows: Single S1P1 positive cells (<b>A</b>). Intratumoral bleeding leaves tumor tissue mostly intact: Histochemical Masson-Goldner staining of anti-YKL-40 treated and control tumors. nuclei: brown/black; connective tissue: green; erythrocytes: red (<b>B</b>).</p

Tumor growth as observed by MRI after injection of 10⁶ LOX melanoma cells during treatment with anti-YKL-40 monoclonal antibody or isotype control.

<p>For each animal, tumor volume calculated on basis of MRI data at each time point was divided by the tumor volume at day 0. <b>Black curve:</b> treatment with anti-YKL-40 antibody; <b>grey curve:</b> treatment with isotype control; **: P = 0.0011, two way ANOVA (<b>A</b>). T2* weighted MRI of two Balb/c scid mice with LOX tumors treated with isotype or anti-YKL-40 monoclonal antibody seven days after start of treatment. Observed hemorrhage is indicated by arrows (<b>B</b>).</p

Rapid effect of anti-YKL-40 treatment: T1 and T2 weighted MRI of two Balb/c scid mice with LOX tumors treated with anti-YKL-40 monoclonal antibody or isotype control before injection of antibody (d0), six hours (6 h) and 24 hours (24 h) after antibody injection.

<p>Bleeding can be seen as dark shades in the tumor (<b>A</b>). Two dissected tumors (each cut in half) 24 hours after i.v. treatment with anti-YKL-40 antibody or isotype treatment (<b>B</b>).</p

LOX melanoma cells express YKL-40 <i>in vitro</i>: FACS anaylsis of <i>in vitro</i> expression of YKL-40 by LOX and U87 cells.

<p>There is a subpopulation of 21.1% with strong YKL-40 expression (M1) in the U87 cells (<b>A</b>). Anti-YKL-40 significantly reduces tube formation: Tube formation of HUVECs in U87 conditioned medium after 12 h. Medium was additionally supplemented with: Nothing (U87), 5 µg/ml anti-YKL-40 mononclonal antibody (5 µg/ml moAb) or 10 µg/ml anti-YKL-40 (10 µg/ml moAb). Representative photographs of wells with tube formation (upper panel) and column bar graph (means with SD, lower panel). The differences were significantly different (** : P = 0.0086, 1 way ANOVA) (<b>B</b>).</p

No significant difference in proliferation was observed between anti-YKL-40 treated and control tumors (N = 5, each).

<p>Given is the number of human Ki-67 positive cells per field of vision as determined by immunohistochemistry. Representative tumor stainings to the right (<b>A</b>). Significant difference in vessel formation between anti-YKL-40 treated and control tumors (N = 5, each). Given is the percentage of murine S1P1 positive area per field of vision as determined by immunohistochemistry. Representative tumor stainings to the right (<b>B</b>). No significant difference in leukocyte infiltration was observed between anti-YKL-40 treated and control tumors (N = 5, each). Given is the number of murine CD45 positive cells per field of vision as determined by immunohistochemistry. Representative tumor stainings to the right (<b>C</b>).</p

Allele distribution of the CGEN-40003 amplicon according to EULAR response.

<p>The Y-axis indicates percentage of patients. The X-axis indicates EULAR response (good, moderate, none). The colored boxes indicate the size (base pair) of the longest allele.</p

Association between genotype and EULAR good response versus EULAR moderate response/no response.

*<p>Odds ratio for EULAR good response being 512 positive,</p>***<p>after correction for dependency.</p

Association between genotype and EULAR good response versus EULAR no response.

*<p>Odds ratio for EULAR good response being 512 positive; #adjusted p-value;</p>**<p>Odds ratio for EULAR good response when both alleles are ≤280;</p>***<p>after correction for dependency.</p

Demographic and clinical characteristics at baseline.

<p>Values are given as median (range) or number (percentage of total).</p>#<p>3 patients had missing smoking status.</p>##<p>115 patients had missing anti-CCP values.</p