Metallothionein 1 h tumour suppressor activity in prostate cancer is mediated by euchromatin methyltransferase 1

Metallothioneins (MTs) are a group of metal binding proteins thought to play a role in the detoxification of heavy metals. Here we showed by microarray and validation analyses that MT1h, a member of MT, is down‐regulated in many human malignancies. Low expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer. We found that the promoter region of MT1h was hypermethylated in cancer and that demethylation of the MT1h promoter reversed the suppression of MT1h expression. Forced expression of MT1h induced cell growth arrest, suppressed colony formation, retarded migration, and reduced invasion. SCID mice with tumour xenografts with inducible MT1h expression had lower tumour volumes as well as fewer metastases and deaths than uninduced controls. MT1h was found to interact with euchromatin histone methyltransferase 1 (EHMT1) and enhanced its methyltransferase activity on histone 3. Knocking down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 abrogated MT1h tumour suppressor activity. This demonstrates tumour suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Tubeimoside-1 inhibits the proliferation and activation of mouse T lymphocytes through signal transduction pathways

Abstract

Tubeimoside-1 (TBMS1) is one of the important components in Bolbostemma paniculatum (Maxim.) Franque. In the study, its immunosuppressive effects on murine T lymphocyte responses were evaluated in vitro and in vivo. The data showed that TBMS1 inhibited ConA-induced T lymphocyte proliferation, decreased the ratio of CD4⁺/CD8⁺, suppressed IL-2, IFN-γ, IL-4 and IL-6 production and mRNA expression, down-regulate activation of NF-κB, NFAT2 and AP-1 signal transduction pathways in vitro. In addition, administration of TBMS1 significantly inhibited T cell-mediated DTH response in vivo. These findings indicated that TBMS1 inhibits the proliferation and activation of T lymphocytes in mice.     

Suppression,subversion and escape: the role of regulatory T cells in cancer progression

Regulatory T cells (T_regs) are crucial in mediating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. However, in the context of cancer their role is more complex, and they are thought to contribute to the progress of many tumours. As cancer cells express both self‐ and tumour‐associated antigens, T_regs are key to dampening effector cell responses, and therefore represent one of the main obstacles to effective anti‐tumour responses. Suppression mechanisms employed by T_regs are thought to contribute significantly to the failure of current therapies that rely on induction or potentiation of anti‐tumour responses. This review will focus on the current evidence supporting the central role of T_regs in establishing tumour‐specific tolerance and promoting cancer escape. We outline the mechanisms underlying their suppressive function and discuss the potential routes of T_regs accumulation within the tumour, including enhanced recruitment, in‐situ or local proliferation, and de‐novo differentiation. In addition, we review some of the cancer treatment strategies that act, at least in part, to eliminate or interfere with the function of T_regs. The role of T_regs is being recognized increasingly in cancer, and controlling the function of these suppressive cells in the tumour microenvironment without compromising peripheral tolerance represents a significant challenge for cancer therapies.     

Robustness of a Combined Modified Dixon and PROPELLER Sequence with Two Interleaved Echoes in Clinical Head and Neck MRI

Purpose:The combination of modified Dixon (mDixon) and periodically rotated overlapping parallel lines with enhanced reconstruction sequence with two interleaved echoes, which promotes uniform fat-suppression and motion insensitivity, has recently become available for commercial magnetic resonance imaging (MRI) scanners. To compare the robustness of this combination sequence with that of standard Cartesian mDixon sequence for fat-suppressed T₂-weighted imaging in clinical head and neck MRI.Methods:Fifty patients with head and neck tumors were involved this study. All patients underwent MRI using both the combination and standard sequences. Two radiologists independently scored motion artifacts and water–fat separation error using a 4-point scale (1, unacceptable; 4, excellent). Furthermore, comprehensive comparative evaluation was performed using a 5-point scale (1, substantially inferior; 5, substantially superior). Data were statistically analyzed using the Wilcoxon signed-rank test.Results:In the motion artifact assessment, ratings of 3 or 4 points were assigned to 45% (observer-1, 58.0%; observer-2, 32.0%) and 97% (100%; 94.0%) of images for the standard and combination sequences, respectively (P < 0.001). For the water–fat separation error assessment, ratings of 3 or 4 points were assigned to 100% (100%; 100%) and 85% (84.0%; 86.0%) of images, respectively (P < 0.001). In the comprehensive evaluation, of the 100 cases (observer-1, 50; observer-2, 50), 96 were rated at four or five points. In cases with slight or no motion artifacts and water–fat separation errors, the combination sequence was superior to the standard sequence in term of noise and sharpness, and equal in terms of contrast.Conclusion:Although water–fat separation errors increased significantly in the combination sequence, most of these were acceptable. The significantly decreased motion artifacts in the combination sequence significantly improved image quality overall.     

Cancer‐generated lactic acid: a regulatory,immunosuppressive metabolite?

The common preference of cancers for lactic acid‐generating metabolic energy pathways has led to proposals that their reprogrammed metabolism confers growth advantages such as decreased susceptibility to hypoxic stress. Recent observations, however, suggest that it generates a novel way for cancer survival. There is increasing evidence that cancers can escape immune destruction by suppressing the anti‐cancer immune response through maintaining a relatively low pH in their micro‐environment. Tumours achieve this by regulating lactic acid secretion via modification of glucose/glutamine metabolisms. We propose that the maintenance by cancers of a relatively low pH in their micro‐environment, via regulation of their lactic acid secretion through selective modification of their energy metabolism, is another major mechanism by which cancers can suppress the anti‐cancer immune response. Cancer‐generated lactic acid could thus be viewed as a critical, immunosuppressive metabolite in the tumour micro-environment rather than a ‘waste product’. This paradigm shift can have major impact on therapeutic strategy development. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

A 14-mer Peptide from HSP70 Protein is the Critical Epitope Which Enhances NK Activity Against Tumor Cells in vivo

Heat shock protein 70 (Hsp70) has been found to play key roles in tumor immunity due its chaperone function of binding antigenic peptides. Here we report it can also stimulate NK cells in vivo, which is another role in Hsp70s' anti-tumor response. Injecting Hsp70 into mice increased splenic NK cell populations, which may be reason for anti-tumor effect of Hsp70. The Hsp70 14-mer peptide (aa450–463, TRD) was identified as the critical epitope for this stimulatory activity. It was the murine Hsp70 14-mer peptide TRD instead of the corresponding human Hsp70 14-mer peptide TKD that functioned in the mouse experimental model.     

Processing of facial expressions of same-race and other-race faces: distinct and shared neural underpinnings

People understand others’ emotions quickly from their facial expressions. However, facial expressions of ingroup and outgroup members may signal different social information and thus be mediated by distinct neural activities. We investigated whether there are distinct neuronal responses to fearful and happy expressions of same-race (SR) and other-race (OR) faces. We recorded electroencephalogram from Chinese adults when viewing an adaptor face (with fearful/neutral expressions in Experiment 1 but happy/neutral expressions in Experiment 2) and a target face (with fearful expressions in Experiment 1 but happy expressions in Experiment 2) presented in rapid succession. We found that both fearful and happy (vs neutral) adaptor faces increased the amplitude of a frontocentral positivity (P2). However, a fearful but not happy (vs neutral) adaptor face decreased the P2 amplitudes to target faces, and this repetition suppression (RS) effect occurred when adaptor and target faces were of the same race but not when of different races. RS was observed on two late parietal/central positive activities to fearful/happy target faces, which, however, occurred regardless of whether adaptor and target faces were of the same or different races. Our findings suggest that early affective processing of fearful expressions may engage distinct neural activities for SR and OR faces.     

自拟扶正生血汤治疗化疗后骨髓抑制疗效探讨

目的:观察自拟扶正生血汤治疗化疗后骨髓抑制临床疗效。方法:将40例初次化疗患者随机分为2组,其中对照组20例给予重组人粒细胞刺激因子治疗,观察组20例在此基础上加用自拟扶正生血汤辅助治疗,14d为1个周期,观察4周期化疗,统计2组近期疗效和骨髓抑制发生情况,观察治疗前后中性粒细胞、血红蛋白、血小板、白细胞、T淋巴细胞亚群及中医症状评分。结果:观察组客观缓解率显著高于对照组;观察组骨髓抑制发生率显著低于对照组;观察组治疗后中性粒细胞、血红蛋白、血小板及白细胞水平均显著优于对照组;观察组治疗后T淋巴细胞亚群水平和中医症状评分均显著优于对照组、治疗前,差异均有统计学意义。结论:自拟扶正生血汤用于化疗后患者可有效延缓病情进展,降低骨髓抑制发生风险,改善外周血象,并有助于调节细胞免疫功能。