癌症生物学与医学（英文版）杂志

乳腺癌前病变和乳腺癌中α、γ-tubulin蛋白表达的免疫荧光定量分析及其意义

目的:研究乳腺导管上皮不典型增生(ADH)、导管内癌(DCIS)及浸润性导管癌(IDC)中α-tubulin和г-tubulin表达的变化及其意义,进一步探讨中心体异常与乳腺癌发生发展的相关性.方法:研究样本被分为导管上皮不典型增生、导管内癌和浸润性导管癌3组,每组30例.采用流式细胞免疫荧光定量分析技术和免疫组织化学方法,检测上述各组中心体微管蛋白α-tubulin和г-tubulin表达水平,与30例正常乳腺组的检测结果比较,并进行统计学分析.结果: 在全部样本组中гα-tubulin及г-tubulin FITC标记的阳性细胞数均数不同,差异有显著性(P=0.000),浸润性导管癌组的过表达高,正常组织组低.α-tubulin、г-tubulin表达水平随着细胞增殖级别的增加和分化程度的变差呈增高趋势.除不典型增生组和导管内癌组两组间比较以外,其余各组间差异均有显著性(P=0.001).在每组中α-tubulin和г-tubulin的表达程度无统计学差异(P＜0.05),显示免疫荧光定量分析和免疫组织化学检测结果趋于一致.结论:乳腺癌发生的早期阶段即存在着中心体蛋白的过度表达,推测这种异常表达在促进细胞恶性转化、形成乳腺癌过程中可能扮演了重要角色.对于中心体蛋白过表达的检测,免疫荧光定量和免疫组化两种技术可相互补充.

作者：牛昀；张彤文；王颍；韦丽；魏锡胤；牛瑞芳 刊期： 2008年第01期

Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor (EGFR) regulate cellular homeostatic processes. EGFR activates downstream signaling cascades that promote tumor cell survival, proliferation and migration. Dysregulation of EGFR signaling as a consequence of overexpression, amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant phenotypes. Consequently, concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit EGFR. However, limited therapeutic beneifts to cancer patients have been derived from EGFR-targeted therapies. A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell masses. Here, we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs (miRs) as downstream effector molecules utilized by EGFR to promote tumor initiation, progression and that play a role in resistance to EGFR inhibitors. We also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.

作者： 刊期： 2013年第04期

hTere are notable differences in the incidence and mortality rates for prostate cancer between Asia and Western countries. It is also recognized that there are differences in thinking with regard to treatment options. Recently it is also the case that opinions have been reported concerning the differences between Asian and Western patients with regard to their reaction to androgen depletion therapy (ADT). Given that ADT is a method of treatment that focuses on the elimination of testosterone, an inevitable symptom of its administration is testosterone losing syndrome. It is for this reason that in Western countries ADT has only been recommended in cases of advanced or metastatic cancer. On the other hand, in Asia, ADT is used in relatively many cases, including non-metastatic localized cancer and invasive localized cancer. To date, however, there has been little substantive discussion concerning this difference in utilization of ADT. ADT-related drugs for prostate cancer and the development of new drugs for castration resistant prostate cancer (CRPC) have been actively tested in recent years. It could be the case that analyzing the differences in concepts about ADT between Asia and the West could contribute to the effective use of ADT-related drugs and also help to build new treatment strategies for prostate cancer.

作者： 刊期： 2013年第04期

31例原发性中枢神经系统恶性淋巴瘤临床分析

目的:分析免疫正常的原发性中枢神经系统恶性淋巴瘤患者的临床表现、影像学特点和病理表现并探讨其诊断、治疗方法.方法:回顾分析1995年7月至2006年6月经过病理证实的31例原发中枢神经系统恶性淋巴瘤病例的临床、实验室检查、影像学、病理结果及治疗效果.18例采用手术+放疗+化疗方法,5例单纯手术治疗.其中化疗CHOP方案11例,替尼泊苷(VM26)+司莫司汀(me-CCNU)7例.结果:原发性中枢神经系统恶性淋巴瘤临床表现复杂,无特异性,主要为颅内压增高和神经功能缺损为主,误诊率高.脑脊液检查无阳性结果.31例均为B细胞淋巴瘤.31例中获随访24例,随访时间6～98个月,其中手术+放疗+化疗组中位生存期20个月,单纯手术组中位生存期10个月.应采取综合治疗.结论:原发性中枢系统恶性淋巴瘤缺乏特异性临床表现,术前难以确诊,预后不良.病理检查是确诊的唯一方法.手术的主要目的是解除肿瘤引起的颅内高压,单纯手术后,短时间内复发,应该采取手术、放疗、化疗综合治疗,这是延长生存期和改善生存质量的关键.

作者：张磊；张学新；刘英姿；邢鹏辉；李建峰；刘海英 刊期： 2008年第01期

Surgery following neoadjuvant chemoradiotherapy (NCRT) is a common multidisciplinary treatment for resectable esophageal cancer (EC). Atfer analyzing 12 randomized controlled trials (RCTs), we discuss the key issues of surgery in the management of resectable EC. Along with chemoradiotherapy, NCRT is recommended for patients with squamous cell carcinoma (SCC) and adenocarcinoma (AC), and most chemotherapy regimens are based on cisplatin, lfuorouracil (FU), or both (CF). However, taxane-based schedules or additional studies, together with newer chemotherapies, are warranted. In nine clinical trials, post-operative complications were similar without significant differences between two treatment groups. In-hospital mortality was signiifcantly different in only 1 out of 10 trials. Half of the randomized trials that compare NCRT with surgery in EC demonstrate an increase in overall survival or disease-free survival. NCRT offers a great opportunity for margin negative resection, decreased disease stage, and improved loco-regional control. However, NCRT does not affect the quality of life when combined with esophagectomy. Future trials should focus on the identiifcation of optimum regimens and selection of patients who are most likely to beneift from speciifc treatment options.

作者： 刊期： 2014年第03期

Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. Atfer one month, bone marrow biopsy and aspiration conifrmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. hTe patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia.

作者： 刊期： 2013年第04期

Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to inlfuence response to targeted therapies. hTe principle goal of precision medicine is to deifne those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few “mountains” [representing the most commonly mutated genes like KARS, epidermal growth factor (EGFR), and anaplastic lymphoma kinase (ALK)] and a vast number of “hills” (representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected.

作者： 刊期： 2014年第03期

脂质体介导入钠/碘同向转运体基因转染肺癌A549细胞及其蛋白表达

目的:研究人钠/碘同向转运体(NIS)基因转染肺癌细胞及其蛋白表达.方法:将体外培养的肺癌A549细胞分为实验组和对照两组:以脂质体Lipofectamine2000为载体,分别介导转染重组质粒pcDNA3-hNIS和空质粒pcDNA3.NIS基因重组质粒pcDNA3-hNIS进行扩增、纯化,并经酶切鉴定和DNA测序.采用Western Blot法和免疫组化法分别检测转染肺癌细胞中NIS蛋白表达.结果:酶切鉴定年:UDNA测序结果表明重组质粒pcDNA3-hNIS中插入的hNIS基因片段大小、方向正确.Western Blot法和免疫组化染色结果显示实验组有NIS蛋白表达,其阳性率达70.6%且主要分布于细胞膜而对照组无表达.两组比较有显著性差异(P=0.000).结论:脂质体Lipofectamine 2000介导转染人钠/碘同向转运体基因pcDAN3-hNIS肺癌细胞能够成功地表达MS蛋白.

作者：严煜；张宏飞；张裕东；王晓谭 刊期： 2008年第01期

三氧化二砷诱导人肝癌细胞株HepG2凋亡的机制研究

目的:探讨三氧化二砷(As2O3)诱导人肝癌细胞株HepG2凋亡的作用及机制.方法:采用MTT法观察不同浓度的As2O3对人类肝癌细胞株HepG2细胞生长的抑制作用:以流式细胞术观察细胞的凋亡率;以Western blot法检测JNK、p-JNK、caspase-3及PARP蛋白在As2O3作用下及SP600125阻断JNK信号转导通路情况下的表达.结果:As2O3均对体外生长的肝癌细胞HepG2具有明显抑制作用,并可诱导细胞凋亡.Western Bloting结果显示,As2O3诱导肝癌细胞HepG2凋亡伴随着Caspase-3和PARP的活化;As2O3作用于HepG2细胞10min后p-JNK蛋白表达开始增加,20分钟达到高峰,30分钟开始减少,总JNK蛋白的含量无明显改变,JNK的激活早于细胞凋亡:用SP600125预处理HepG2细胞株后,可以明显减少Caspase-3和PARP的活化.结论:As2O3可以体外通过诱导细胞凋亡抑制肝癌细胞株HepG2的增殖,细胞凋亡通过Caspase-3途径实现.JNK信号转导通路参与了As2O3诱导的HepG2凋亡反应,并位于Caspase-3的上游.

作者：李航宇；鞠培新；钟鑫平；Xinping Zhong；Jingang Liu 刊期： 2008年第01期

Since the approval of rituximab in 1997, monoclonal antibodies (mAbs) have become an increasingly important component of therapeutic regimens in oncology. hTe success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target speciifcity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding (Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. hTe extremely high affnity of mAbs for their targets, which is desirable with respect to pharmacodynamics (i.e., contributing to the high therapeutic selectivity of mAb), otfen leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and effcacy.

作者： 刊期： 2014年第01期