南方红豆杉不同部位紫杉烷类含量累积规律分析

目的:测定南方红豆杉不同组织器官紫杉烷类物质的含量,优选出最佳采收部位,为其开发利用提供依据。方法:分别采集南方红豆杉植株主干树皮、侧皮、根皮、须根、茎、叶六个组织器官材料,运用HPLC法检测紫杉烷类物质含量,确定其最佳利用组织器官。结果:南方红豆杉四种紫杉烷类在组织中的分布明显地受组织分化的影响,其中10-脱乙酰巴卡亭Ⅲ在叶中最多,7-表-10-去乙酰基紫杉醇在侧皮中最多,紫杉醇、三尖杉宁碱则在根中最多。结论:叶是合成紫杉醇前体物质的主要器官,而皮与根则是合成及积累紫杉醇的主要组织器官。     

Adding Pertuzumab to Trastuzumab and Taxanes in HER2 positive breast cancer

Introduction: The monoclonal antibody trastuzumab has improved the median disease free and overall survival of patients with early stage breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2). Despite this advance, some patients experience cancer relapse and novel approaches are always needed. One such advance is the monoclonal antibody pertuzumab, which prevents dimerisation between members of the HER family of transmembrane glycoprotein receptors.

Areas covered: In this review, the authors analyse recent research which has focused on the development of new HER2 targeting agents for HER2-positive breast cancer, particularly pertuzumab, and its addition to trastuzumab and taxanes.

Expert opinion: Pertuzumab has significantly improved disease control in patients with advanced HER2 positive breast cancer when added to chemotherapy and trastuzumab. Although pertuzumab has also increased response rates in the preoperative setting, this has not yet translated into increased overall survival. The authors believe that future research should focus on improvements in novel biomarkers to select patients for new treatments.     

Role of taxanes in pancreatic cancer

Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.     

紫杉类与蒽环类药物联合治疗三阴性乳腺癌疗效分析

目的：比较紫杉类和蒽环类药物联合与单纯蒽环类药物治疗三阴性乳腺癌的疗效。方法：585例三阴性乳腺癌患者中,术后行紫杉联合蒽环类辅助化疗228例,蒽环类辅助化疗357例,分析其复发、转移和生存情况。结果：紫杉联合蒽环类组与蒽环类组患者复发率、转移率与死亡率分别为7.9%与13.2%、21.9%与35.9%、18.0%与28.6%（P＜0.05）,与蒽环类方案相比,紫杉联合蒽环类方案延长了临床II、III期、非特殊型浸润性癌、淋巴结阳性患者的总生存期,提高了总生存率。结论：紫杉类与蒽环类药物联合辅助化疗,对于具有晚临床分期、非特殊型浸润性癌及淋巴结阳性特征的三阴性乳腺癌有显著的治疗效果。     

The androgen receptor as a surrogate marker for molecular apocrine breast cancer subtyping

The Androgen Receptor (AR) is a potential prognostic marker and therapeutic target in breast cancer. We evaluated AR protein expression in high-risk breast cancer treated in the adjuvant setting. Tumors were subtyped into luminal (ER+/PgR±/AR±), molecular apocrine (MAC, [ER−/PgR−/AR+]) and hormone receptor negative carcinomas (HR-negative, [ER−/PgR−/AR−]). Subtyping was evaluated with respect to prognosis and to taxane therapy. High histologic grade (p < 0.001) and increased proliferation (p = 0.001) more often appeared in MAC and HR-negative than in luminal tumors. Patients with MAC had outcome comparable to the luminal group, while patients with HR-negative disease had increased risk for relapse and death. MAC outcome was favorable upon taxane-containing treatment; this remained significant upon multivariate analysis for overall survival (HR 0.31, 95%CI 0.13–0.74, interaction p = 0.035) and as a trend for time to relapse (p = 0.15). In conclusion, AR-related subtyping of breast cancer may be prognostic and serve for selecting optimal treatment combinations.     

Mechanism of taxane neurotoxicity

The two taxanes (paclitaxel and docetaxel) are widely employed in standard antineoplastic practice. Although these agents are now well established, some toxic side effects have been reported. Toxicity of these agents includes bone marrow suppression (principally neutropenia), hypersensitivity reactions, cutaneous reactions, edema and neurotoxicity. The most prominent neurotoxicity is a sensory neuropathy. Controlling neuropathy is crucial for maintaining the quality of life of patients because it is usually persistent and hard to manage. The precise mechanism for taxane-induced neuropathy is still unknown. The taxanes are known to promote aggregation of intracellular microtubules. Abnormal aggregation of microtubules in the neuronal cells may cause this neuropathy. In addition, the taxanes have been suggested to have intrinsic toxicity and directly injure the cells. A better understanding of the mechanism for this neuropathy may improve the quality of life of patients who undergo taxane antineoplastic therapy.     

NF—κB抑制剂与紫杉烷对未分化甲状腺癌细胞凋亡的诱导作用

目的探讨联合核因子κB（NF-κB）抑制剂和紫杉烷对未分化甲状腺癌（ATC）凋亡的诱导效果。方法应用Western blot鉴定单独或联合用药后ATC细胞内凋亡关键因子（PARP、Caspase3、XIAP和survivin）的变化。采用Annexin V—FITC／PI双标记染色流式细胞仪鉴定用药后癌细胞的凋亡变化。结果联合紫杉烷和NF—κB抑制剂后PARP失活裂解产物和Capsase 3活化水解产物的增多较单用紫杉烷更加显著（P〈0．01）,单用紫杉烷会使凋亡抑制因子XIAP和survivin增加,而联合NF-κB抑制剂则可使二者的表达受到明显抑制（P〈0．01）。流式细胞仪鉴定亦证明联合用药可产生协同诱导凋亡的效果（P〈0．01）。结论NF-κB制剂可提高化疗敏感性和化疗疗效。     

TPF或PF方案诱导化疗治疗局部晚期头颈鳞癌的Meta分析

目的通过Meta分析,比较紫杉类＋顺铂＋氟尿嘧啶与N$13＋氟尿嘧啶诱导化疗治疗局部晚期头颈鳞癌的疗效和安全性。方法通过MEDLINE、EMBASE、Cochrane图书馆、CBM等数据库检索国内外已发表和未发表的相关文献。选择治疗组为紫杉类＋Nell＋氟尿嘧啶诱导化疗,对照组为顺铂＋氟尿嘧啶诱导化疗的局部晚期头颈鳞癌的随机对照研究。由2位评价者分别按上述检索策略收集资料,按纳入、排除标准人选,对总生存期、无进展生存期、完全缓解率、客观缓解率及毒性反应等进行Meta分析。结果共纳入4个随机对照研究。紫杉类＋顺铂＋氟尿嘧啶诱导化疗与NSA＋氟尿嘧啶诱导化疗相比,前者的总生存期（风险比0．76,P=0．0001）、无进展生存期（风险比0．73,P〈0．00001）、完全缓解率（危险比1．5,P=0．03）、客观缓解率（危险比1．2,P〈0．00001）均显著优于后者;在毒性反应方面,除3／4度中性粒细胞减少的发生率前者高于后者外,其余3／4度血液学毒性和3／4度消化道毒性的发生率两者相当或是前者低于后者。结论目前证据表明．紫杉类＋顺铂＋氟尿嘧啶诱导化疗与顺铂＋氟尿嘧啶诱导化疗相比,显示了更优的疗效及安全性,可作为局部晚期头颈鳞癌诱导化疗的一线选择。     

晚期食管癌不同化疗方案疗效对比

目的：分析氟尿嘧啶类、紫杉类、铂类药物不同组合方案在晚期食管癌治疗中的效果及毒副作用,探讨晚期食管癌最佳药物治疗方案。方法回顾分析2009年9月-2012年5月扬州市第一人民医院治疗的97例晚期或复发转移食管癌患者的临床资料。按其化疗方案进行分组,将采用氟尿嘧啶联合铂类、氟尿嘧啶类联合紫杉类、紫杉类联合铂类以及三药联合方案治疗的患者分为A（22例）、B（21例）、C（39例）、D（15例）四组,分析各组疗效及毒副作用。结果四组患者客观有效率分别为45.5%、42.9%、48.7%、53.3%,差异无统计学意义（P〉0.05）。远期疗效分析,四组进展生存期、总生存期比较,差异均无统计学意义（P〉0.05）,尽管三药联合方案在一定程度上提高了中位无进展生存期,但差异无统计学意义（P〉0.05）。对一线治疗患者进行分层分析,各组间差异均无统计学意义（P〉0.05）。各组化疗相关毒副作用均主要为骨髓抑制、恶心呕吐及便秘,D组腹泻和手足综合征发生例数较C组明显增加（P〈0.05）。结论氟尿嘧啶、紫杉类、铂类药物不同组合方案在晚期食管癌治疗中效果并无明显差异,化疗相关不良反应表现不同,三药联合方案毒副作用发生率较高,对体力状况评分较好患者可谨慎使用。