Specific values for baseline and adhere to-up TTB measurements are shown in Desk two.Important anti-angiogenic results of regorafenib had been noticed in the investigated colon carcinoma xenografts with a AM-2282 drastically (p<0.05) lower tumor microvascular density, quantified by CD-31 stainings, in the regorafenib-treated therapy than in control group (7.0 2.4 vs. 16.1 5.9). Significant anti-proliferative effects of regorafenib were noted, with a significantly (p<0.03) lower number of proliferating cells in therapy than in control group (Ki-67, 434.0 62.9 vs. 663.0 98.3). Representative tumor sections with stainings for CD-31 and Ki-67 are displayed in Fig. 5. 752187-80-7 individual values of immunohistochemical stainings are displayed in Table 3.Fig 3. Line diagrams of the development of individual values of perfusion MRI parameters of tumor microcirculation in the therapy and the control group. a. Note the significant (p<0.01) unidirectional decline of tumor plasma flow (mL/100mL/min) in all tumors under regorafenib therapy and a significant unidirectional increase of tumor perfusion (p<0.03) in untreated control group between baseline (day0) and follow-up (day 7). b. Note the significant (p<0.01) unidirectional decrease of tumor plasma volume (%) in all tumors of the regorafenib-treated therapy group between day 0 and day 7 as well as non-uniform, non-significant (p>.05) modifications in management team. c. Note the important (p<0.01) unidirectional decline of tumor endothelial permeability in all tumors under regorafenib treatment between baseline and follow-up as well as a non-uniform development of individual values with non-significant (p>.05) adjustments of suggest PS in the handle team. doi:ten.1371/journal.pone.0115543.g003 Fig 4. Improvement of personal values of tumor glucose metabolism, assessed by PET as tumor-tobackground ratio (TTB), in the treatment and in the manage team among baseline and comply with-up. Notice the almost unidirectional decrease of individual TTB values with a slight enhance of TTB in only a single tumor of the regorafenib-taken care of therapy team as effectively as a drastically (p<0.01) decreased mean TTB between day 0 and day 7. In the control group a uniform increase of individual TTB values can be observed with a significant (p<0.03) rise of mean TTB in the untreated colon carcinoma xenografts. doi:10.1371/journal.pone.0115543.g004 Note the significant (p<0.01) decrease of tumor TTB between day 0 and day 7 in the therapy group, as well as the significantly (p<0.01) increased glucose metabolism in the control group on day7. significant difference (p<0.01) between baseline and follow-up significant difference (p<0.03) between baseline and follow-up significant difference (p<0.01) between therapy and control group doi:10.1371/journal.pone.0115543.t002 Fig 5. Representative tumor sections of human colon carcinoma xenografts with immunohistochemical stainings for tumor cell proliferation (Ki-67) and tumor microvascular density (CD-31) for the regorafenibtreated therapy (left column) and the control group (right column) ex vivo. Note the significantly (p<0.03) lower number of Ki-67-positive, proliferating cells (stained in brown) in the therapy group, consistent with antiproliferative effects of regorafenib, as well as the significantly (p<0.03) higher number of CD-31-positive endothelial cells (stained in brown) in the untreated control group, consistent with anti-angiogenic effects of regorafenib. Good to moderate, significant correlations were observed between tumor plasma flow PF and PET tumor-to-background ratio TTB (r = 0.78 p<0.01) (Fig. 6), between PV and TTB (r = 0.67 p<0.01) and between PS and TTB (r = 0.75 p<0.01) (Table 4).PF showed moderate, but significant correlations with CD-31, as a marker of tumor microvascular density (r = 0.51 p<0.05) and with Ki-67, as a marker of tumor cell proliferation (r = 0.57 p<0.03).
