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| 1 | Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer显示文摘尽管有最近的进展, oncogenic K 地岬驾驶的胰腺的 ductal 腺癌(PDAC ) 在最致命的人的癌症之中留在现代医学。PDAC 的致病对内在的染色体不稳定性和外来的发炎激活部分可归因。然而,在在胰腺的 tumorigenesis 的这二个事件之间的分子的连接充分还没被建立了。这里,我们证明(HMGB1 ) 细胞内部的高活动性组盒子 1 显著地压制 oncogenic 由禁止染色体的 K-Ras-driven 胰腺的 tumorigenesis 调停不稳定性的支持 inflammatory nucleosome 版本。任何一个单身者的有条件的基因脱离或在胰的 HMGB1 的两等位基因在出生使老鼠变为极其敏感到先锋损害的 oncogenic K-Ras-driven 开始,包括胰腺的 intraepithelial 瘤, intraductal 乳突的 mucinous 瘤,和 mucinous 膀胱的瘤。在胰的 HMGB1 的损失与染色体重新整理和 telomere 畸形描绘的氧化 DNA 损坏和 chromosomal 不稳定性被联系。这些导致煽动性的 nucleosome 版本并且宣传 K-Ras-driven 胰腺的 tumorigenesis。细胞外的 nucleosomes 支持 interleukin 6 (IL-6 ) 由渗入 macrophages/neutrophils 的分泌物并且提高在胰腺的损害表明激活的 oncogenic K 地岬。到 IL-6 或 histone H3 或为先进 glycation 的受体的大美人的抵销的抗体结束产品都限制表明激活的 K 地岬,阻止癌症开发和转移 / 侵略,并且延长在 Pdx1-Cre 的动物幸存; K 地岬 G12D/+;Hmgb1/ 鼠标。由 glycyrrhizin 的 HMGB1 损失的药理学抑制在煽动性的条件下面在老鼠限制 oncogenic K-Ras-driven tumorigenesis。减少在 PDAC 病人的 HMGB1 的原子、全部的细胞的表示与差的全面幸存相关,在 PDAC 与预示、治疗学的关联作为新奇肿瘤 suppressor 支持细胞内部的 HMGB1。 | Rui Kang Yangchun Xie Qiuhong Zhang Wen Hou Qingping Jiang Shan Zhu Jinbao Liu Dexing Zeng Haichao Wang David L Bartlet Timothy R Billiar Herbert J Zeh III Michael T Lotze Daolin Tang | 2017 | Cell Research2017，27，7： | 22 |
| 2 | Effects of preventive acupuncture or moxibustion at the Guanyuan acupoint on expression of interleukin-2 and its receptors in hypothalamus, serum, and uterus of menopausal rats显示文摘BACKGROUND: Previous studies have indicated preventive acupuncture and moxibustion at the Guanyuan point have positive effects on the immune system of menopausal rats. OBJECTIVE: To observe the effects of preventive acupuncture or moxibustion at the Guanyuan point on interleukin-2 (IL-2) and its receptor (IL-2R mRNA) levels in hypothalamus, serum, and uterus of menopausal rats. DESIGN: Randomized control animal experiment. SETTING: School of Acupuncture and Moxibustion, Beijing University of Chinese Medicine. MATERIALS: This study was performed at the Laboratory of Beijing University of Chinese Medicine from November 2004 to July 2005. The vaginal smear method was used to determine the estrus cycle of 9.5-month-old Sprague Dawley (SD) female rats. Three continuous estrus cycles were measured, and 160 rats with estrus cycle disorder, weighing (300 ± 20) g, were included in this study. The rats were randomly divided into four groups: preventive acupuncture group (n =48), preventive moxibustion group (n =48), model groups (n =48), and 10-month-old group (n =16). Sixteen 3.5-month-old healthy SD female rats, weighing (240 ± 20) g, were also assigned to the young group. All rats were clean grade and were purchased from the Laboratory Animal Center, Beijing University of Chinese Medicine. The experiment was in accordance with animal ethics standards. METHODS: Acupuncture was applied to the preventive acupuncture group at 10 months of age. The needle was inserted upward and perpendicularly two fen to a point that was two fen below the Guanyuan point. The rats freely moved around during needle retention (20 minutes). Acupuncture was administered twice a week and continued for eight weeks. A moxa cone (small) moxibustion was applied to the preventive moxibustion group at 10 months of age. The rats were caught gently and kept at the same position as the preventive acupuncture group. The moxa cone was ignited and held to the Guanyuan point directly. Only one moxa cone was used each time. After moxibustion, the local skin turned slightly red. Moxibustion was used twice a week and continued for eight weeks. Nothing except gently catching and lying was administered to the model group and the young group. MAIN OUTCOME MEASURES: Radioimmunoassay, in situ hybridization, and similar methods were employed to detect IL-2 in serum and the uterus, as well as IL-2R mRNA expression in the hypothalamus and uterus arcuate nuclei, of the preventive acupuncture group, preventive moxibustion group, model groups (at 12, 14, and 16 months), 10 month old group (at 10 months), and the young group (at 4 months). RESULTS: All 176 rats were included in the final analysis. ① IL-2R mRNA: IL-2R mRNA expression decreased significantly in the uterus of 12-, 14-, and 16-month-old model groups and in the hypothalamus of 14- and 16-month-old model groups (P < 0.05-0.01). Compared to the same month-aged model groups, the expression of IL-2R mRNA increased significantly in the hypothalamus and uterus of 16-month-old preventive acupuncture or moxibustion groups (P < 0.05-0.01).② IL-2: IL-2 in serum of 12- and 14-month-old model groups and in the uterus of 12-, 14-, and 16-month-old model groups decreased significantly compared to the young group (P < 0.05-0.01). IL-2 serum levels increased significantly in the 16-month-old group with preventive moxibustion; in addition, IL-2 expression levels increased significantly in the uterus of the 12-month-old group with preventive moxibustion, as well as the 12- and 16-month-old groups with preventive acupuncture (P < 0.05-0.01). CONCLUSION: As a rat ages and becomes menopausal, IL-2R mRNA expression in the hypothalamus anduterus, as well as IL-2 levels in the serum and uterus, decrease. However, preventive acupuncture and preventive moxibustion can repress the decrease to some extent. This effect is even greater in the late stages of menopause (16-month-old rats). | Xiaohong Li Yuwei He Jieping Xie Lufen Zhang Dengfang Zhou Jinghui Zhai Rui Zhan Jun Zhou Limin Qu Yangchun Tian | 2008 | Neural Regeneration Research2008，3，1： | 5 |
| 3 | Synthesis and evaluation of ^(64)Cu-radiolabeled NOTA-cetuximab(^(64)Cu-NOTA-C225) for immuno-PET imaging of EGFR expression显示文摘Objective: Epidermal growth factor receptor(EGFR) is overexpressed in a wide variety of solid tumors, serving as a well-characterized target for cancer imaging or therapy. In this study, we aimed to design and synthesize a radiotracer, ^(64) Cu-NOTA-C225, targeting EGFR for tumor positron emission tomography(PET) imaging.Methods: Cetuximab(C225) was conjugated to a bifunctional chelator, p-isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA), and further radiolabeled with copper-^(64) for PET imaging. ^(64) CuNOTA-IgG and Cy5.5-C225 were also synthesized as control probes. A431 and A549 mouse models were established for micro-PET and/or near-infrared fluorescence(NIRF) imaging.Results: ^(64) Cu-NOTA-C225 exhibited stability in vivo and in vitro up to 24 h and 50 h post-injection,respectively. A431 tumors with average standard uptake values(SUVs) of 5.61±0.69, 6.68±1.14, 7.80±1.51 at 6, 18 and 36 h post-injection, respectively, which were significantly higher than that of moderate EGFR expressing tumors(A549), with SUVs of 0.89±0.16, 4.70±0.81, 2.01±0.50 at 6, 18 and 36 h post-injection, respectively. The expression levels of A431 and A549 were confirmed by western blotting. Additionally, the tracer uptake in A431 tumors can be blocked by unlabeled cetuximab, suggesting that tracer uptake by tumors was receptor-mediated.Furthermore, NIRF imaging using Cy5.5-C225 showed that the fluorescence intensity in tumors increased with time, with a maximal intensity of 8.17 E+10(p/s/cm^2/sr)/(μW/cm^2) at 48 h post-injection, which is consistent with the paradigm from micro-PET imaging in A431 tumor-bearing mice.Conclusions: The ^(64) Cu-NOTA-C225 PET imaging may be able to specifically and sensitively differentiate tumor models with different EGFR expression levels. It offers potentials as a PET radiotracer for imaging of tracer EGFR-positive tumors. | Xiaoxia Xu Teli Liu Fei Liu Xiaoyi Guo Lei Xia Qing Xie Nan Li Haifeng Huang Xianteng Yang Yangchun Xin Hua Zhu Zhi Yang | 2019 | Chinese Journal of Cancer Research2019，31，2： | 1 |
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