Interleukin-6 (IL-6), which plays a significant role in the pathogenesis of MM, also regulates DNA methylation. However, attempts to bring IL-6 blockade to the clinic have had limited success. We hypothesize that IL-6 regulation of hypermethylation may be an important pathway leading to rational LXH254 MAPK inhibitor chemotherapeutic/anti-IL-6 combinations. We first studied the correlation of IL-6 expression and dependence in MM cell lines: U266B1, RPMI8226, and KAS6/1. We confirmed that KAS6/1 is IL-6-dependent whereas U266B1 and
RPMI8226 cells are IL-6-independent and that blocking IL-6 inhibited the growth of U266B1 (36% inhibition; p<0.05) and KAS6/1 (68% inhibition; p<0.01), but not the RPMI8226 cells. Using RT-PCR, selleck chemical we showed that U266B1 cells express IL-6, but RPMI8226 and KAS6/1 cells do not. This IL-6 expression pattern correlates with the anti-IL-6 inhibition findings. To correlate IL-6 sensitivity with hypermethylation of TSG, we investigated promoter methylation of CDH1 and DcR1. We found that the promoter of DcR1 and CDH1 is methylated in U266B1 cells and un-methylated in RPMI8226 cells. Furthermore, the DcR1 promoter was un-methylated in KAS6/1 cells. These data support our hypothesis that an IL-6-dependent pathway may regulate hypermethylation of TSG in MM. Newer chemotherapeutic agents that affect
methylation are being studied in combination with IL-6 blockade.”
“Ni(0.6)Cu(0.2)Zn(0.2)Fe(2)O(4) powder was synthesized by the solid-state reaction method. The crystal structure was found to be a cubic spinel with the lattice constant alpha(0) of 8.373 angstrom and internal structure parameter (x) of the find more oxygen was 0.254. Ni and Cu ions in NiCuZn ferrite prefer octahedral sites B and Zn ions prefer tetrahedral sites A. Based on the distribution probability, we have analyzed Mossbauer spectra measured at 4.2 K as 5 sets with six-lines. Hyperfine fields of A and B sites at 4.2 K in zero magnetic field were H(hf)(B(0)) = 547 kOe, H(hf)(B(1)) = 532 kOe, H(hf)(B(2)) = 519 kOe, H(hf)(B(3))
= 491 kOe, and H(hf)(A) = 507 kOe. Applied-field Mossbauer spectra of the Ni(0.6)Cu(0.2)Zn(0.2)Fe(2)O(4) were measured with external field under 50 kOe, parallel to the incident gamma-ray at 4.2 K. The hyperfine field H(hf)(A) of A sites under 50 kOe was 521 kOe, larger than that under no applied-field. At B site the average value of hyperfine field < H(hf()B)> was 447 kOe, smaller than < H(hf)(B)> = 522 kOe under no applied-field. Also, we noticed that the second and fifth absorption lines of Mossbauer spectra completely disappeared above 10 kOe, indicating that the spins of Fe ions at A and B sites were collinear to the applied-field. The Fe valence state was determined to be ferric from the isomer shift values. (C) 2011 American Institute of Physics. [doi: 10.1063/1.