ERCC2 rs1799793多态性与三阴性乳腺癌铂类化疗疗效的关系

背景与目的:DNA修复基因的多态性可以影响DNA损伤修复能力,从而影响患者的化疗疗效。切除修复交叉互补基因2(excision repair cross-complementing group 2,ERCC2)参与核苷酸切除修复和基因转录,在DNA损伤修复中起重要作用。本研究旨在初步探讨ERCC2单核苷酸多态性与三阴性乳腺癌铂类药物化疗疗效的关系。方法:全组患者中位年龄46岁,中位化疗周期数为4个周期。60例接受铂类药物化疗的晚期或局部晚期三阴性乳腺癌患者,收集其临床病理资料和随访信息,采用高通量MassARRAY时间飞行质谱生物芯片系统分析入组患者ERCC2基因候选位点的单核苷酸多态性,观察比较不同基因型与化疗疗效之间的关系。结果:接受含铂方案治疗的总体有效率为66.7%。60例中53例获得ERCC2 rs1799793位点检测结果,ERCC2rs1799793位点等位基因型有GG、GA 2种,频率分别为81.1%、18.9%。GG基因型患者化疗有效30例,无效13例;GA基因型患者化疗有效3例,无效7例。两组的化疗有效率分别为69.8%和30.0%,疗效差异有统计学意义(P=0.030),携带GG基因型的患者化疗敏感性高于携带GA基因型患者。结论:ERCC2基因rs1799793多态性与三阴性乳腺癌患者接受铂类药物化疗的临床疗效有关。     

瑞宁得治疗绝经后妇女晚期乳腺癌临床研究

目的 研究瑞宁得（ａｎａｓｔｒｏｚｏｌｅ）治疗绝经后妇女晚期乳腺癌的临床疗效和不良反应。方法 采用多中心开放非随机自身对照方法,６１例绝经妇女晚期乳腺癌患者口服瑞宁得每日１次,每次１ｍｇ连服４－６周,疗前２周内及治疗４周后的３天内检测血中雌二醇（Ｅ２）水平,同时评价疗效和不良反应。结果 ６０例可评价疗效和不良反应,部分缓解（ＰＲ）１３例,好转（ＭＲ）２例,缓解率２１．７％,有效率２５．０％,绝经时     

New strategies in achieving antiangiogenic effect: Multiplex inhibitors suppressing compensatory activations of RTKs

Pathological angiogenesis plays a crucial role in malignant neoplasia. Vascular normalization has been confirmed as a promising strategy to promote chemotherapy efficacy. However, compensatory activation of alternative angiogenic receptor tyrosine kinases (RTKs) reduces vascular normalization and induces resistance. Moreover, complexity and heterogeneity of angiogenesis make it difficult to treat with single‐target agents. Accordingly, it has been proposed that multiplex inhibition of RTKs could enhance treatment efficacy and overcome resistance on the basis of the vascular normalization concept. Meanwhile, it is feasible to develop multiplex inhibitors against VEGFR‐2/Tie‐2/EphB4 because of their highly conserved ATP‐binding pockets. These inhibitors possess the properties of not only stabilizing the vascular normalization “time window” but also preventing the occurrence of resistance. This novel strategy has yielded promising results in the discovery of antiangiogenic agents. This review highlights the recent progress on the development of such angiogenesis inhibitors.     

Making smart drugs smarter: The importance of linker chemistry in targeted drug delivery

Smart drugs, such as antibody-drug conjugates, for targeted therapy rely on the ability to deliver a warhead to the desired location and to achieve activation at the same site. Thus, designing a smart drug often requires proper linker chemistry for tethering the warhead with a vehicle in such a way that either allows the active drug to retain its potency while being tethered or ensures release and thus activation at the desired location. Recent years have seen much progress in the design of new linker activation strategies. Herein, we review the recent development of chemical strategies used to link the warhead with a delivery vehicle for preferential cleavage at the desired sites.     

单核苷酸多态与乳腺癌治疗反应相关研究进展

单核苷酸多态(SNP)指基因组DNA序列中频率大于1%的单核苷酸变异。这种变异有时导致其编码不同的蛋白从而引起生物学特征的变化,在乳腺癌的治疗上表现为不同患者出现不同的治疗反应和毒性。研究不同基因的SNP与乳腺癌治疗反应的相关性可以为实现乳腺癌个体化治疗提供坚实的理论基础。     

去甲长春花碱为主方案治疗蒽环类药物耐药性晚期乳腺癌的疗效

目的：观察抗肿瘤新药去甲长春花碱（Navelbine,NVB）为主的联合方案化疗治疗蒽环类耐药的晚期乳腺癌的疗效。方法：1995年9月－1999年2月，以此法治疗晚期腺癌21例，其中，NVB＋ADM治疗9例，NVB＋DDP治疗8例，NVB＋MTI4例。全组化疗共54周期，中位数3周期（2－4周期）。结果：CR2例，PR8例，SD8例，PD3例，总有效率（CR＋PR）47．6％。全组中位缓解期5个月（2－17个月）。主要剂量限制毒性为骨髓抑制，以白细胞减少为主，Ⅱ－Ⅲ度白细胞减少发生率为90．5％。静脉炎发生率为14．3％（3／21）。结论：以NVB为主的联化化疗对蒽环类药物耐药的转移性乳腺癌有较好的疗效，且毒性可以耐受，可以考虑作为后续化疗方案。     

疏肝补肾方药对疲劳大鼠海马CA1区中蛋白激酶C表达的影响

目的:研究疏肝补肾方药对于疲劳大鼠海马CA1区中蛋白激酶C(PKC)水平的变化.方法:成年雄性Spargue-Dawley大鼠36只,随机分为模型组(MG)、对照组(CG)和疏肝补肾组(LK).应用大鼠游泳运动结合睡眠剥夺建立疲劳大鼠复合模型,以Y迷宫实验评定其学习记忆能力.取大鼠海马CA1区以Western Blot定量检测,并以Real-time PCR技术分析海马CA1区PKC的mRNA表达.结果:Y迷宫实验显示,用药后大鼠的学习和记忆能力优于模型组,疏肝补肾组大鼠在正确反应率和达标所需训练次数皆与模型组有差异(P＜0.01或0.05).Western Blot结果显示,模型组PKC的蛋白表达明显低于对照组(P＜0.05),疏肝补肾组高于模型组(P＜0.01).Real-time PCR结果显示,在mRNA水平上模型组及疏肝补肾组与对照组比较都有明显差异(P＜0.01),疏肝补肾组PKC mRNA表达高于模型组(P＜0.01).结论:疲劳引起大鼠海马CA1区的PKC水平下调,而使用疏肝补肾方药可改善之,提示可能籍由疏肝补肾法对抗疲劳引起的学习记忆损伤.     

异位性皮炎的记忆性T细胞浸润及ICAM－1表达

为了解粘连分子在异位性皮炎（ＡＤ）炎症及免疫反应过程中的作用，对ＡＤ皮损部位细胞间粘连分子－１（ＩＣＡＭ－１）的表达作了研究。结果虽然正常皮肤表皮不表达ＩＣＡＭ－１，但ＡＤ皮损处角朊细胞则局灶性表达ＩＣＡＭ－１，尤其在有严重单个核细胞浸润及表皮内淋巴细胞移入的部位。免疫表型研究表明，ＡＤ真皮浸润中ＣＤ４＋／ＣＤｗ２９＋／ＣＤ４５ＲＡ－记忆性Ｔ细胞占主导，推测它们可能通过分泌某些细胞因子而诱导角朊细胞表达ＩＣＡＭ－１。ＩＣＡＭ－１与淋巴细胞表面的淋巴细胞功能相关抗原－１（ＬＦＡ－１）之间相互作用可能对淋巴细胞在皮肤内的运行起调控作用。     

Cardia and Non-Cardia Gastric Cancer Have Similar Stage-for-Stage Prognoses After R0 Resection: a Large-Scale,Multicenter Study in China

Although the clinicopathological features of cardia gastric cancer (GC) differ from those of non-cardia GC, it is unclear whether the former has poorer prognosis than the latter. The aim of this study was to compare clinicopathological characteristics and prognosis between cardia and non-cardia GC. From December 2009 to December 2011, 1633 patients who had undergone R0 resection of GC at four Chinese centers were enrolled in this study. Their clinicopathological features and survival outcomes were evaluated. Compared with non-cardia GC, cardia GC was associated with a significantly higher proportion of male patients, older age, more advanced pathological stage, and less-favorable clinicopathological features at diagnosis. The 5-year survival rate was significantly lower in the cardia GC group than in the non-cardia GC group. However, no significant difference in overall survival (OS) was observed between the two groups at any pathological TNM stage. Pathological stage was confirmed as an independent prognostic factor of OS. More advanced disease represents most of the cases in this Chinese population. Compared with patients with non-cardia GC, patients with cardia GC were diagnosed at a more advanced stage and had worse prognosis after undergoing R0 resection. However, cardia and non-cardia GCs have similar stage-for-stage prognoses.