乳腺癌复发相关因素研究进展

乳腺癌是女性最常见的恶性肿瘤之一,发病率呈逐年上升趋势。乳腺癌患者治疗后的复发状况是决定预后的关键,因此对影响乳腺癌复发相关因素的研究显得尤为重要。随着新的检测方法不断更新,我们对乳腺癌的临床病程及生物学行为的研究更加深入,发现了许多影响乳腺癌复发的分子生物学指标,本文就对乳腺癌复发相关因素研究的进展作一综述。     

乳腺癌内分泌药物治疗研究近况

乳腺癌是女性最常见的恶性肿瘤之一,其发生率已跃居女性恶性肿瘤首位。随着医学分子生物学研究的深入,乳腺癌的内分泌机制已越来越清楚,乳腺癌综合治疗的理念已日趋成熟,以内分泌药物为主的综合治疗使得乳腺癌患者的存活得到了明显的延长。乳腺癌内分泌治疗和研究也越来越受到重视,并成为乳腺癌重要治疗手段之一。因此,正确把握乳腺癌内分泌治疗药物的选择和时机将有助于提高乳腺癌内分泌治疗的效果。     

乳腺癌治疗新进展

乳腺癌在全球范围内是中年女性最常见的恶性肿瘤,在我国某些地区乳腺癌发病率已上升为女性恶性肿瘤的第一位,严重影响妇女的身心健康。近年来随着乳腺癌基础与临床研究的不断深入,乳腺癌的治疗取得了很大的成就,对其治疗研究已成为恶性肿瘤的研究热点之一。本文就近年来乳腺癌治疗方面的研究进展进行综述。     

代谢组学在乳腺癌生物标志物中的应用进展

乳腺癌是发生在乳腺上皮细胞处的恶性肿瘤,随着发病率的升高,乳腺癌已成为女性最常见的恶性肿瘤。乳腺癌患者的代谢发生显著改变,所以对乳腺癌代谢进行研究是寻找乳腺癌治疗靶点的途径之一。代谢组学作为新兴发展的学科,能够利用质谱和核磁共振技术对乳腺癌的代谢谱进行全方面的分析,提供肿瘤发生发展的关键信息。本文综述了近年来代谢组学在乳腺癌中的研究进展,以期为乳腺癌的临床治疗和研究提供新的思路。     

管腔型乳腺癌研究进展

利用免疫组化技术对乳腺癌从基因水平上加以分型,不仅能够判断肿瘤的预后,还能够预测肿瘤对治疗的反应,为肿瘤的个体化治疗提供依据。本文以管腔型乳腺癌为研究方向,从六个方面论述了管腔型乳腺癌的认识过程;管腔型乳腺癌的形态特征;管腔型乳腺癌的免疫表型;管腔型乳腺癌的基因表达;管腔型乳腺癌的分子遗传学;管腔型乳腺癌的临床特点及预后,为管腔型乳腺癌的进一步研究提供综述。     

年轻乳腺癌诊断延迟影响因素及现状

目前年轻乳腺癌发生率呈逐年上升趋势.年轻乳腺癌恶性程度高,延迟诊断会导致确诊时多为晚期.为改善年轻乳腺癌患者预后,提高年轻乳腺癌早期诊断率,该文对近年来有关年轻女性乳腺癌诊断延迟影响因素的研究进行了综述.     

全血硒水平与乳腺癌关系探讨

动物实验显示硒有益于预防病毒或化学物质引起的乳腺癌;流行病学研究也显示在谷物和其它粮食含硒高的国家和地区,妇女乳腺癌死亡率较低,但有关血硒水平与人类乳腺癌发病的关系研究较少。我们对105例乳腺癌病人及相同数量的对照进行了全血硒水平与乳腺癌发病关系的病例对照研究。     

乳腺癌研究新进展

乳腺癌是女性最常见的恶性肿瘤之一,发病率仅次于子宫颈癌,并有超过的趋势,近年来,关于乳腺癌的研究很多,也取得了很多实质性的成果,本文在影响因素、诊断、治疗及预防四个方面对乳腺癌的研究新成果进行了综述.     

Hedgehog信号通路在乳腺癌化学致癌进展中的作用

逐渐增多的研究表明,人们生活中经常接触到的一些化学物质是导致乳腺癌发生的危险因素;同时一些研究证实,Hedgehog(Hh)信号通路在乳腺癌患者组织中存在异常激活,参与乳腺癌的发生、调节乳腺癌干细胞生物学特性、促进肿瘤组织血管新生和乳腺癌细胞侵袭转移等生物学过程。本文通过对化学物质与Hh信号通路在乳腺癌发生、发展研究的最新进展进行综述,为进一步阐述乳腺癌发病机制和乳腺癌的预防及控制提供科学线索。     

SIRT1 c-Myc在乳腺癌中的表达及其对预后的影响

乳腺癌是目前严重威胁女性健康的第一位恶性肿瘤,全球每年新增病例约有130万例,我国正以每年3%～4%的增长率急剧上升。研究发现SIRT1[1-3]、c-Myc[7-9]参与了乳腺癌的发生、发展,但是SIRT1与c-Myc是否共同参与了乳腺癌发生、发展及其二者与乳腺癌预后关系的研究未见报道,本实验探讨了SIRT1及c-Myc在乳腺癌中的表达及其与预后的     

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Aim： Prenatal nicotine exposure （PNE） alters the hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods： Maternal Wistar rats were injected with nicotine （1.0 mg/kg, sc） twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results： UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical ＂catch-up＂ growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration （caused further increases in the serum ACTH and corticosterone levels）, but also significantly changed the glucose and lipid metabolism after UCS （caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids）. The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion： PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.     

Hsp90 inhibitor BILBO21 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53- MDM2 balance

Aim： To investigate the effects of BILBO21, an inhibitor of heat shock protein 90 （Hsp90） alone or in combination with triptolide （TPL） on T-cell acute lymphoblastic leukemia （T-ALL） and the mechanisms of action. Methods： Human T-ALL cells line Molt-4 was examined. The cell viability was measured using M]-I- assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. Results： Treatment of Molt-4 cells with BILBO21 （50-800 nmol/L） inhibited the cell growth in a dose-dependent manner （the IC~ovalue was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h）. BILBO21 dose-dependently induced Go/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BILBO21 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BILBO21 （50-400 nmol/L） dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL （5-40 nmol/L） dose- dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BILBO21 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. Conclusion： The combination of BILBO21 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.     

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats,dogs and humans in vitro

Aim： （＋）Doxazosin is a long-lasting inhibitor of a1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. Methods： Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. Results： Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [（-）doxazosin： 89.4%-94.3%; （＋）doxazosin： 90.9%-95.4%]. （＋）Doxazosin exhibited significantly higher protein binding capacities than （-）doxazosin in all the three species, and the difference in the bound concentration （Cb） between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog〉human〉rat. Conclusion： （-）Doxazosin and （＋）doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.     

美国与欧洲上市后药品安全风险管理进展概述

近10年来,美国食品药品管理局（FDA）、欧洲药品管理局（EMA）及其他相关单位,对上市后药品安全性监测日益重视,在这一领域取得了显著进展,并且制定了一系列新规定。     

人参北芪片的质量控制研究

目的建立人参北芪片的质量标准,控制制剂的质量。方法采用薄层色谱法对制剂中组成药味人参进行鉴别,采用HPLC-蒸发光散射检测法测定制剂中的黄芪甲苷,并进行方法学考察。结果人参的薄层鉴别中,斑点清晰,阴性无干扰。黄芪甲苷在0.9976～14.9640μg与峰面积呈良好的线性关系,平均回收率为98.06%,RSD为1.60%。结论建立的薄层色谱和高效液相色谱定性、定量方法可以用来控制人参北芪片的质量,方法简便可行。     

Molecular modeling,quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT~ and ETA receptor antagonists

Aim： Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists. Methods： Molecular modeling approach combining quantum-polarized ligand docking （QPLD）, MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists. Results： 3D-QSAR models of the imidazole compounds were developed from the conformer generated by QPLD, and the resulting models showed a good correlation between the predicted and experimental activity. The visualization of the 3D-QSAR model in the context of the compounds under study revealed the details of the structure-activity relationship： substitution of methoxymethyl and cyclooctanone might increase the activity against AT~ receptor, while substitution of cyclohexone and trimethylpyrrolidinone was important for the activity against ETA receptor; addition of a trimethylpyrrolidinone to compound 9 significantly reduced its activity against AT~ receptor but significantly increased its activity against ETA receptor, which was likely due to the larger size and higher intensities of the H-bond donor and acceptor regions in the active site of ETA receptor. Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD and MM/GBSA calculation identified 5 potential lead compounds that might act as dual AT1 and ETA receptor antagonists. Conclusion： This study may provide some insights into the development of novel potent dual ETA and AT1 receptor antagonists. As a result, five compounds are found to be the best dual antagonists against AT1R and ETA receptors.     

树突状细胞的肿瘤个体化治疗

肿瘤免疫治疗这一概念是基于机体的免疫系统在对抗肿瘤时的调节与反应。有效的免疫治疗的最主要的优点在于相对较少的副作用,针对肿瘤细胞的靶向特异性,并且能产生对抗肿瘤特异性抗原的长期记忆[1]。     

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

Aim： To investigate the protective effects of hydrogen sulfide （H2S） against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods： Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35-40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NariS （28 pmol/kg, ip） was injected before the resuscitation. Results： Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-a, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H202 and OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin I expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NariS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion： NariS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway.     

新生儿缺氧缺血性脑病并发热个案报道

1 病案介绍 患儿,男,新生儿(30 min),因颜面及全身皮肤青紫30 min于2011年1月11日转入儿科.患儿系第一胎,第一产,足月,因"胎儿宫内窘迫,脐绕颈2圈,羊水Ⅱ度污染"于入院前30 min在我院妇产科剖宫产分娩,胎头取出顺利,胎盘完整,无羊水呛入,生后无自主呼吸及心跳,颜面及全身皮肤青紫,肌张力差,插鼻管尚有反应,经心肺复苏,约3 min后心跳恢复,10 min后建立自主呼吸,但呼吸不规则,继续气囊加压给氧辅助呼吸至30 min,自主呼吸明显好转,皮肤青紫有所缓解,拔除气管插管后,患儿未出现呼吸暂停,急转入儿科治疗.其母孕期健康,无特殊服药史,父亲体健,非近亲婚配,无传染病史,无家族性遗传及代谢病史.