紫杉类药物耐药的相关分子生物学指标

耐药是影响紫杉类药物临床疗效的重要因素。回顾与紫杉类耐药相关的分子生物学指标，并从多药耐药(MDR)机制、微管、凋亡因子、细胞周期蛋白监控、HER—2、BRCA—1、BRCA-2、紫衫醇耐药相关基因—3等方面分别加以阐述。     

紫杉类药物疗效预测分子研究进展

不同个体对紫杉类药物疗效存在差异，药物遗传学和药物基因组学的快速发展，使得分子标签指导下的个体化的化疗成为可能，本文将对紫杉类药物疗效预测相关的分子标记物作一综述。     

紫杉类药物疗效预测分子研究进展

不同个体对紫杉类药物疗效存在差异,药物遗传学和药物基因组学的快速发展,使得分子标签指导下的个体化的化疗成为可能,本文将对紫杉类药物疗效预测相关的分子标记物作一综述.     

含紫杉类药物联合治疗中晚期恶性肿瘤37例

目的　观察含紫杉类药物的联合化疗对晚期恶性肿瘤的临床疗效及安全性。方法　用含紫杉类药物 (紫杉醇Paclitaxel,泰索帝Taxotere)的联合化疗方案治疗 3 7例中晚期恶性肿瘤患者 ,可评价疗效者 3 6例 ,其中非小细胞肺癌 (NSCLC) 11例 ,小细胞肺癌 (SCLC) 3例 ,乳腺癌 15例 ,胃癌 2例 ,大肠癌 5例。结果　CR 3例 ,PR 14例 ,SD 13例 ,PD 6例 ,总有效率 47.2 % ,WBC下降占 91.7% ,脱发占 88.9% ,肌肉关节痛占 69.4% ,指趾麻木占 5 8.3 %。结论　紫杉类药物对NSCLC ,乳腺癌 ,大肠癌及伴有肝转移的恶性肿瘤有较高的疗效 ,且毒性可耐受     

乳腺癌化疗紫杉类药物敏感性相关基因的生物信息学分析

[目的]评价乳腺癌化疗紫杉类药物敏感性相关基因的研究状况,并对未来研究方向进行预测。[方法]选用Embase、Medline/Pubmed、BIOSIS Preview数据库为文献来源,对2001～2010年期间与乳腺癌化疗紫杉类药物敏感性相关基因的文献进行计量学分析。[结果]相关文献93篇,文献中涉及429个基因。生物信息学分析说明所涉及的基因及其产物处于相互联系的复杂网络之中,同时为关键基因和瓶颈基因主要有PLK1、CCND1、ESR1、FEN1、CDKN1A、CCNA2、TP53、SRC、EGFR、PIK3CA、MDM2、CCNB1、VEGFA、TOP2A、BRCA1、Bcl-2、FOXM1、EP300、CTNNB1、BIRC5等。[结论]乳腺癌化疗紫杉类药物敏感性相关基因的研究可能在未来研究中更受关注,我们预测的关键基因可能成为未来研究的热点。     

紫杉类药物治疗晚期恶性肿瘤的临床观察

目的　观察以紫杉类为主的联合化疗方案治疗晚期恶性肿瘤的临床疗效及毒副反应。方法　治疗晚期恶性肿瘤 34例 ,所用紫杉类药物包括国产的紫素、紫杉醇 ,进口的泰素、泰索帝、安素泰等。用药前 6、12小时分别给予地塞米松 10～ 2 0mg ,用药前半小时给予苯海拉明 5 0mg ,西米替丁 30 0mg。化疗方案采用联合化疗方案。结果　全组总有效 8例 ,总有效率 2 3.6 %。毒副反应主要为白细胞减少。肌肉关节痛者 13例 ,腹泻发生者 4例 ,脱发Ⅲ～Ⅳ度者 3例 ,手足麻木者 6例 ,2例出现心电图ST -T改变 ,出现过敏反应者 1例 ,为轻度过敏反应 ,1例出现转氨酶一过性升高。结论　紫杉类药物联合化疗对晚期恶性肿瘤仍有一定应用价值 ,疗效较好 ,毒性反应轻 ,耐受性好。     

紫杉类药物在晚期乳腺癌治疗中的应用

复发或晚期乳腺癌治疗的主要目的是为了延长患者的生存期,控制症状,改善生活质量。该病的治疗以化疗为主,化疗药物包括蒽环类、紫杉类、抗代谢类、烷化剂类等,可以单药、联合或序贯使用。对于晚期乳腺癌患者,近30多年来临床上均以蒽环类药物为基础的方案作为标准化疗方案[1]。虽该方案取得较好的疗效,但由于阿霉素的毒性及累积剂量的限制性,仍需斟酌使用。近年来,紫杉类药物在乳腺癌治疗中已广泛应用,其具有疗效肯定、毒副反应较轻的特点,因而促使越来越多的临床医生在晚期乳腺癌的治疗中倾向于使用紫杉类药物。     

应用紫杉类药物前激素预处理的改进及过敏后再输入的探讨

目的探索简便可靠的紫杉类药物激素预处理方法以及重度过敏反应后再输入的可能性.方法共483例肺癌病例进行1401疗程以紫杉类为主的化疗,其中212例、416疗程采用常规法激素预处理,即在注药前12小时及6小时各口服地塞米松10mg,再在注紫杉类药物前30分钟肌注苯海拉明40mg,静注西米替丁300mg;另外270例、985疗程采用简化法激素预处理,即在静脉点滴紫杉类药物前60分钟,将地塞米松10mg加入10%葡萄糖500ml静滴,再在注药前30分钟将地塞米松10mg、苯海拉明20mg、西米替丁300mg经滴壶先后加入.结果紫杉类药物过敏反应发生率在常规激素预处理组11.3%,在简化预处理组12.5%,两组差异无统计学显著性(P＞0.05).两组发生重度(Ⅲ+Ⅳ度)过敏反应分别为8例(3.8%),12例(4.4%),即共20例重度过敏反应病例经紧急处理又将余下紫杉类药液顺利完成再输入.结论简化激素预处理法对预防减轻紫杉类药物过敏反应具有简便易行、安全可靠的特点.     

表皮生长因子受体-2和雌激素受体对晚期乳腺癌应用紫杉类药物疗效的预测分析

目的 研究表皮生长因子受体-2（HER-2）和雌激素受体（ER）对乳腺癌应用紫杉类药物化疗疗效的预测作用。方法 268例晚期乳腺癌应用紫杉类药物化疗,其中单药紫杉醇71例,单药泰索帝32例,紫杉醇联合组110例,泰索帝联合组55例。应用免疫组化的方法对患者的ER和HER-2生物学指标在蛋白水平进行检测。268例中,行HER-2检测201例,行ER检测242例,行HER-2和ER两项检测者200例。结果 HER-2过表达有效率为56．7％,低表达有效率为33．3％,两组差异有统计学意义（P=0．003）。ER阳性有效率为33．3％,ER阴性患者有效率为48．9％,两组差异有统计学意义（P=0．015）。在HER-2过表达同时ER阴性患者的有效率高达67．6％,其他组各组均在35％左右,HER-2过表达同时ER阴性与其他3组进行两两比较,差异有统计学意义（P〈0．01）;而其他3组之间差异无统计学意义。多因素分析显示HER-2过表达仍有统计学意义（P=0．007）。而ER受体以及KPS评分、葸环类药物、转移部位均不具有统计学意义。结论 HER-2过表达和（或）ER阴性,尤其HER-2过表达对紫杉类药物的疗效可能有预测作用,HER-2过表达可能是乳腺癌紫杉类化疗效果好的分子指标。     

乳腺癌相关生物学指标对紫杉类药物治疗晚期乳腺癌疗效预测作用分析

目的:回顾性研究雌激素受体(ER)、p53、bcl-2和mdr-1对乳腺癌应用紫杉类药物化疗疗效的预测作用。方法:182例晚期乳腺癌患者应用紫杉类化疗,其中单药紫杉醇组37例,单药泰索帝组22例,紫杉醇联合组78例,泰索帝联合组45例。应用免疫组化的方法对所有患者的ER、p53、bcl-2和mdr-1生物学指标在蛋白水平进行检测。结果:KPS评分、解救情况以及既往蒽环类及转移部位多少对紫杉类药物疗效均无预测作用。ER阳性患者有效率为33.01%(34/103),ER阴性患者有效率为50·63%(40/79),两组相比差异有统计学意义,χ2=5·755,P=0·022;而p53、bcl-2、mdr-1等阳性组与阴性组有效率之间相比,差异无统计学意义(p53χ2=0·004,P=0·950;bcl-2χ2=0·651,P=0·451;mdr-1χ2=0·177,P=0·751;)。多因素分析显示,ER阳性差异仍有统计学意义,P=0·027。而KPS评分、既往应用蒽环类药物、转移部位数目、差异均无统计学意义。结论:ER阴性对紫杉类药物的疗效可能有预测作用,而p53、bcl-2和mdr-1对紫杉类药物无预测作用。     

Assessment of molecular markers of clinical sensitivity to single-agent taxane therapy for metastatic breast cancer.

PURPOSE: The taxanes affect tubulin polymerization and interfere with mitotic transition. A checkpoint blockade at the G(1)-S boundary would be expected to promote taxane-induced apoptotic cell death through a mechanism that may involve p27. Other proposed determinants of clinical taxane sensitivity/resistance include p53, members of the epidermal growth factor receptor (EGFR) superfamily (e.g., HER2, EGFR), and estrogen receptors and progesterone receptors. These molecular markers and their correlation with clinical taxane sensitivity are investigated in this retrospective clinicopathologic study. PATIENTS AND METHODS: We performed immunohistochemistry (IHC) for estrogen receptors, progesterone receptors, HER2, EGFR, p53, and p27 on 144 breast tumor specimens from patients treated for metastatic breast cancer on a series of clinical trials of single-agent taxane chemotherapy for correlation with clinical response (complete or partial response). Patient characteristics that could influence response (i.e., performance status, extent of disease, and prior therapy) were also examined. RESULTS: In univariate analysis, Karnofsky performance status > or = 90% and no prior history of anthracycline therapy correlated with a good clinical response to single-agent taxane (P =.003 and P =.041, respectively). None of the IHC variables tested were predictive of clinical response to taxane therapy, although p27 negativity showed a trend toward significance (P =.075). Concordance between the polyclonal antibody with HercepTest (DAKO, Carpinteria, CA) and the monoclonal antibody CB-11 (BioGenex, San Ramon, CA) was noted (kappa = 0.943); however, neither univariate nor multivariate analysis demonstrated an association between HER2 status and response to taxane chemotherapy. CONCLUSION: The IHC biomarkers studied were not predictive of response to single-agent taxane chemotherapy in patients with metastatic breast cancer. Identification of molecular correlates of taxane response remains an important goal.     

In vitro drug response and molecular markers associated with drug resistance in malignant gliomas.

PURPOSE: Drug resistance in malignant gliomas contributes to poor clinical outcomes. We determined the in vitro drug response profiles for 478 biopsy specimens from patients with the following malignant glial histologies: astrocytoma (n = 71), anaplastic astrocytoma (n = 39), glioblastoma multiforme (n = 259), oligodendroglioma (n = 40), and glioma (n = 69). EXPERIMENTAL DESIGN: Samples were tested for drug resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin, dacarbazine, paclitaxel, vincristine, and irinotecan. Biomarkers associated with drug resistance were detected by immunohistochemistry, including multidrug resistance gene-1, glutathione S-transferase pi (GSTP1), O(6)-methylguanine-DNA methyltransferase (MGMT), and mutant p53. RESULTS: In vitro drug resistance in malignant gliomas was independent of prior therapy. High-grade glioblastomas showed a lower level of extreme drug resistance than low-grade astrocytomas to cisplatin (11% versus 27%), temozolomide (14% versus 27%), irinotecan (33% versus 53%), and BCNU (29% versus 38%). A substantial percentage of brain tumors overexpressed biomarkers associated with drug resistance, including MGMT (67%), GSTP1 (49%), and mutant p53 (41%). MGMT and GSTP1 overexpression was independently associated with in vitro resistance to BCNU, whereas coexpression of these two markers was associated with the greatest degree of BCNU resistance. CONCLUSIONS: Assessment of in vitro drug response and profiles of relevant tumor-associated biomarkers may assist the clinician in stratifying patient treatment regimens.     

The clinical significance of molecular markers to bladder cancer

Stage and grade of transitional cell carcinoma are currently the most useful tools for taking therapeutic decisions and evaluating the prognosis of bladder cancer patients. However, as there are remarkable differences in biological behavior and "biological potential" of tumors classified in the same stage, it is very difficult to predict which superficial tumors will recur and which tumors will give distant metastases. During the last two decades, the better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression has provided a large number of molecular markers of bladder cancer, with a potential diagnostic and prognostic value. This article reviews comprehensively the molecular role and evaluates the clinical significance and the perspectives of these molecular markers. We concluded that, although at the moment there is not a single marker able to predict with accuracy the biological potential of bladder cancer, the most promising markers, at this point, are deletions of chromosome 9, and the tumor suppressor gene p53. Clinical studies are in progress for the assessment of other biological molecules with prognostic potential, such as the E-cadherin, the protein p120, and the telomerase.     

甲状腺乳头状癌相关分子标志物的研究进展

甲状腺乳头状癌是头颈部最常见的恶性肿瘤,近年来的发病率呈现增长趋势。虽然大多数甲状腺乳头状癌的预后较好,但也有一部分患者因为复发或者发生转移而导致预后差。分子标志物检测在甲状腺乳头状癌的诊断、治疗及预后方面有很重要的作用,文章就甲状腺乳头状癌相关的主要分子标志物进行综述。     

Emerging molecular markers of cancer

Alterations in gene sequences, expression levels and protein structure or function have been associated with every type of cancer. These 'molecular markers' can be useful in detecting cancer, determining prognosis and monitoring disease progression or therapeutic response. But what is the best way to identify molecular markers and can they be easily incorporated into the clinical setting?     

Breast cancer and molecular markers

Molecular markers have long been studied and used in part as a marker for prediction of prognosis and deciding the treatment for patients with breast cancer. Now development of novel decision-making biomarkers for adjuvant chemotherapy is desired for many patients with hormone receptor-positive early breast cancer. Thanks to recent advances in molecular marker studies on breast cancer, the update committee has systematically reviewed the literature and updated recommendations for the use of tumor markers in breast cancer, one of the ASCO clinical practice guidelines, in 2007. In the revised guideline, gene expression profiling assays are topics in six newly added categories. In this review, the key guideline recommendations and two innovative gene expression profiling assays have been summarized.     

乳腺癌相关分子病理学标志物研究进展

乳腺癌是女性发病率最高的恶性肿瘤，占女性恶性肿瘤的15％。乳腺癌分子病理学能够在基因和蛋白水平上检测瘤细胞的激素受体、生长因子、特异性蛋白、抑癌基因及癌基因等变化，并通过以上检查结果反映肿瘤细胞的分化、生长速度和转移侵袭性，为临床医师制定手术、放疗和化疗方案提供依据，提供有价值的预后信息和靶点治疗新思路。通过对这些生物标志物的阐述，可以更深入的认识乳腺癌的生物学行为。