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 chemotherapeutic/anti-IL-6 combinations. We first studied the correlation of IL-6 expression and find more 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 JNK-IN-8 the RPMI8226 cells. Using RT-PCR, 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 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 DZNeP clinical trial 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.