Role of TGFB1 polymorphism in the development of metastatic brain tumors in non-small cell lung cancer patients.

We conducted a case-control study to investigate the role of 3 single-nucleotide polymorphisms of the gene encoding transforming growth factor-b1 (TGFB1) in the development of metastatic brain tumors in non-small cell lung cancer patients. The polymorphisms in TGFB1 rs4803455, rs1800469, and rs1800470 were evaluated by polymerase chain reaction-restriction fragment length polymorphism. Odds ratios and their corresponding 95% confidence intervals were used to assess the influence of TGFB1 rs4803455, rs1800469, and rs1800470 on metastatic brain tumors. We found that cases were more likely to have a later disease stage when compared with control subjects, without brain metastasis. Individuals carrying the TGFB1 rs1800469 TT and CT+TT genotypes had an increased risk of developing brain metastasis compared with the rs1800469 CC genotype. Moreover, a significant interaction was observed between the rs1800469 polymorphism and disease stage. However, no significant association between polymorphisms rs4803455 and rs1800470 and the risk of developing brain metastasis were observed. We found that the TGFB1 rs1800469 polymorphism may be predictive biomarker for the risk of developing brain metastasis in non-small cell lung cancer patients.

Gray matter anomalies in anterior cingulate cortex as a correlate of depressive symptoms in drug-naïve idiopathic restless legs syndrome.

BACKGROUND: Depressive symptoms are frequent in idiopathic restless legs syndrome (RLS). However, little is known, so far, about the neurological basis. The present study aimed to explore the neuroanatomical anomalies in depressed drug-naïve RLS patients using voxel-based morphometry (VBM) analysis. METHODS: We recruited 16 drug-naïve idiopathic RLS patients with depressive symptoms (RLS-D), 18 drug-naïve idiopathic RLS patients without depressive symptoms (RLS-ND), and 18 normal controls. All participants underwent structural MRI scans on a 3-T MR system. The differences in regional gray matter (GM) density were determined across groups by VBM8. Additional regression analysis was used to identify any associations between regional GM density and clinical symptoms. RESULTS: GM density of the bilateral anterior cingulate cortex (ACC) was significantly reduced in RLS-D patients when compared to RLS-ND patients or to the healthy controls. However, there were no significant differences of GM density either when the whole RLS group or the RLS-ND group was compared to healthy controls, respectively. Particularly, we found GM density of right ACC was negatively correlated with the severity and duration of depressive symptoms in RLS-D patients. CONCLUSIONS: Depressive symptoms are associated with GM anomalies in ACC in patients with RLS. We propose that ACC is perhaps an important neuroimaging marker for facilitating treatment strategies in patients with RLS when assessing depressive symptoms.

Effect of traffic rule breaking behavior on pedestrian counterflow in a channel with a partition line.

In this paper a partition line is used in the counterflow system to present the default (conventional) traffic rule: pedestrians prefer to walk on a certain side on the road during movement, e.g., the right-hand side in China or the left-hand side in Japan. Based on the counterflow model of Takimoto (model A), we introduced two modified models, i.e., model B and C, to study the effects of a partition line in the consideration of people who do not obey the default traffic rule. Model B represents that factor in time scale, while model C in space scale. In model B, there are pedestrians who cross the partition line but choose not to obey the default traffic rule with a probability p(nor), while in model C, if a pedestrian crosses the partition line and goes away from it further than a certain nonobeying-rule threshold distance d(t), he will not obey the traffic rule. It is found that the behavior of traffic rule breaking influences much the counterflow when it is at the choking flow state rather than at the free moving or stopped state. Furthermore, it is shown that the default traffic rule is not always positive to the counterflow in all situations. It depends on the game result of these two opposite sides: to use the channel width as much as possible and to avoid the interference from the other group as far as possible.

Cellular automaton simulation of pedestrian counter flow considering the surrounding environment.

This paper presents a cellular automaton model without step back to simulate the pedestrian counter flow in a channel. The consideration of the surrounding environment when people make judgments on moving directions is added to a random walker model also without step back. Two types of walkers: the right walkers going to the right and the left walkers going to the left are taken into account. The characteristics of counterflow are clarified. Influences of the different interaction radius values and system sizes on movement are studied. Phase transition from free moving to jamming is observed with the increase of entrance density. It is found that the critical entrance density pc at the transition point does not depend on the system size when the interaction radius value is large. Simulation results are represented as a comparison with the random walker model.

Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB.

BACKGROUND: Treatment of neuropathic pain remains a challenge. The current study investigated the therapeutic effect of intrathecal administration of NF-kappaB antisense oligodeoxynucleotides (ODNs) on mechanical allodynia and thermal hyperalgesia in a chronic constriction injury (CCI) model of rats. METHODS: Lumbar intrathecal catheters were implanted in male Sprague-Dawley rats and a CCI model was established. Thermal and mechanical nociceptive thresholds were assessed with paw withdrawal latency (PWL) to radiant heat and von Frey filaments. The phosphorothioate-modified antisense ODNs to p65 subunit of NF-kappaB were administered intrathecally on each of five consecutive days post-CCI. Nuclear NF-kappaB p65 expression was assessed by western blot. RESULTS: CCI induced mechanical allodynia and thermal hyperalgesia and significantly increased NF-kappaB p65 protein expression. Intrathecal injection of antisense ODN markedly suppressed the expression of NF-kappaB p65 protein and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia. CONCLUSION: The activation of NF-kappaB pathway may contribute to neuropathic pain in CCI rats. Suppression of NF-kappaB could be a potential new strategy for the treatment of neuropathic pain.

Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity.

To increase the antitumor effects of cytosine deaminase (AdCD) gene therapy and induce more potent antitumor immunity, Th1 cytokine interleukin-18 encoded adenovirus (AdIL18) was combined with adenovirus encoding CD (AdCD) for the therapy of established murine B16 melanoma. Combination therapy of the tumor-bearing mice with AdIL 18 and AdCD/5FC inhibited the growth of the subcutaneous B16 tumors more significantly, compared with AdIL 18 or AdCD/5FC alone. In vivo depletion analysis with anti-CD4, anti-CD8 or anti-NK 1.1 McAb illustrated that both CD8+ T cells and CD4+ T cells played key roles in the augmented antitumor response of the combined therapy. Peptide/MHC tetramer represents a powerful and general tool for rapid, highly sensitive, and direct analysis of antigen-specific T cells. In this study, we prepared H-2Kb/TRP-2180-188 tetramer, which was demonstrated to bind H-2Kb-restricted, B16 melanoma-specific CD8+ T cells. B16 specific H-2Kb/TRP2180-188 tetramer was used to stain the tumor-specific CD8+ T cells and the results showed that CD8+ tetramer+ T cells were about 3-5% of the splenic CD8+ T cells derived from tumor-bearing mice after combined therapy. The CTL cytotoxicity was markedly induced in mice after combined therapy, suggesting efficient induction of tumor-specific CD8+ T cells after combined gene therapy with AdCD/5FC/AdIL18. IL-18 gene transfer could significantly augment the cytotoxicity of NK cells and macrophages, and increase the production of interleukin-2 and interferon-gamma, as compared with treatments with AdCD/5FC, AdlacZ/5FC or PBS. These data suggested that in vivo IL-18 gene transfer could augment the antitumor effects of CD suicide gene therapy through efficient induction of antitumor immunity.