We showed that good responders of cisplatin in NSCLC could be identified by the promoter methylation of TGM2 and that TGase 2 inhibition appears to be an effective cisplatin-sensitizing modality in NSCLC.

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Cell therapy using MSCs (mesenchymal stem cells) might be effective treatment for refractory GVHD (graft-versus-host disease). However, the fate and distribution of MSCs after transplantation remains unclear. In this study, an animal model was developed to monitor the dynamic distribution of MSCs in mice with GVHD. A GVHD mouse model was established by transplanting C57BL/6 donor bone marrow cells and C57BL/6 EGFP (enhanced green fluorescent protein) splenocytes into lethally irradiated BALB/c nude recipient mice. Donor MSCs were obtained from MHC-identical C57BL/6 RFP (red fluorescent protein) mice and infused into the recipient mice on the same transplantation day. In vivo movement of the donor splenocytes (EGFP) and MSCs (RFP) were evaluated by measuring the biofluorescence (IVIS-Xenogen system). Donor splenocytes and MSCs reached the lungs first, and then the gastrointestinal tract, lymph nodes and skin, in that order; the transit time and localization site of these cells were very similar. In the recipient mouse with GVHD, the number of detectable cells declined with time, as assessed by biofluorescence imaging and confirmed by RT (real-time)-PCR. This bioimaging system might be useful for preclinical testing and the design of therapeutic strategies for monitoring the dynamic distribution of MSCs with GVHD.

Immunohistochemical staining with CKAP2 monoclonal antibody can be considered to be a new, effective approach to the assessment of proliferation activity in cancer tissues.

Cordyceps (CS) is a traditional Chinese herb with various biological effects that include immune modulation. CBG-CS-2 is a strain, Paecilomyces hepiali, of the Cordyceps spp. The anti-inflammatory effects of CBG-CS-2 were investigated. The water-soluble fraction of CBG-CS-2 has high anti-inflammatory activity in LPS-induced Raw264.7 macrophages. We tested the role of CBG-CS-2 on the anti-inflammation cascade in LPS-stimulated Raw264.7 cells. CBG-CS-2 significantly decreased NO production, iNOS expression, and pro-inflammatory cytokine secretion in a dose-dependent manner. To investigate the mechanism by which CBG-CS-2 inhibits NO, iNOS, and pro-inflammatory cytokines, we examined the activities of NF-κB and AP-1 in LPS-activated macrophages. The results demonstrate that CBG-CS-2 suppresses the production and expression of NO, iNOS, and pro-inflammatory cytokines in LPS-activated macrophages via inhibition of NF-κB and AP-1, which may play an important role in inflammation. These findings suggest that CBG-CS-2 has modulatory effects on the inflammatory system in macrophages, and that it can serve as a useful anti-inflammatory dietary supplement or drug.

Acute Graft-versus-Host Disease (GVHD) remains a major complication after allogeneic hematopoietic cell transplantation (HCT). Several publications show a potential benefit of human MSCs for the treatment of refractory GVHD; however, their cellular fate and distribution remain unclear. We set out to develop an animal model that can be used to study the effect of MSCs on GVHD. GVHD was induced by transplantating C3H/he or C57BL/6 donor bone marrow cells (5 × 106) and CD3+ spleen cells (1 × 106) into lethally irradiated BALB/c recipient mice. C3H/10T1/2 cell lines were transfected with a pcDNA3.1-luciferase construct (luc-MSCs). Bioluminescence of these cells was measured (IVIS-Xenogen system) after treatment with luciferin, showing a linear increase of photon emission with rising cell numbers. To track these cells in vivo, groups of mice were injected with various dose luc-MSCs per animal and imaged with bioluminescence imaging at various time points. After transplantation, mice were monitored daily for weight and survival. Differences in symptom severity were compared using a clinical GVHD scoring system. We conclude that this mouse model can be used to study the effects of MSCs on acute GVHD and the described bioluminescence technology provides a sensitive and safe tool for the repeated in vivo tracking of infused luc-MSCs in GVHD target organs.

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