Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed,and monoclonal antibodies targeting human epidermal

growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC.Hepatocyte growth factor and its receptor,c-MET(MET),play key roles in tumor growth through activated signaling pathways from receptor in GC cells.Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC.This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target GPCR Compound Library半抑制浓度 in patients 获悉更多 with GC.Preclinical studies in animal models have shown that MET antibodies or smallmolecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells.These drugs are now being evaluated in clinical trials as treatments for metastatic

or unresectable GC.
肺癌高居我国恶性肿瘤病死率的首位,严重威胁着人类的健康,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)包括鳞状细胞癌、腺癌等,与小细胞癌比较其癌细胞生长分裂较慢,扩散转移较晚,约占肺癌的80%~90%。大多数患者就诊时已处于晚期,错失了外科手术的最佳时机,因此,内科治疗成为NSCLC晚期患者的主要治疗方法。近些年来,随着NSCLC相关驱动基因的陆续发现,分子靶向治疗方面的研究取得了质的飞跃,为NSCLC晚期患者提供了新的治疗手段。本文就NSCLC的相关驱动基因进行综述,希望对临床上NSCLC晚期患者的个体化治疗有所裨益。
The last two decades have witnessed a paradigm shift from cytotoxic drugs to targeted therapy in medical oncol?ogy and pharmaceutical innovation. Inspired by breakthroughs in molecular and cellular biology, a

number 什么 of novel synthesized chemical compounds and recombinant antibodies have been developed to selectively target oncogenic signaling pathways in a broad array of tumor types. Although targeted therapeutic agents show impressive clinical eicacy and minimized adverse efects compared with traditional treatments, the challenging drug?resistant issue has also emerged to limit their beneits to cancer patients. In this regard, we aim to improve targeted therapy by present?ing a systematic framework regarding the drug resistance mechanisms and alternative approaches to re?sensitize cancer cells/tissues therapeutically.
Crizotinib是由辉瑞公司开发的,主要用于治疗通过FDA批准的检测方法诊断为间变性淋巴瘤激酶(ALK)阳性的局部晚期或转移的非小细胞肺癌(NSCLC),它是目前惟一个治疗该类疾病的药物。Crizotinib于2011年8月
1.大批新药获批:大量用于治疗癌症和孤儿病的新化学/生物实体获得FDA批准。其中,治疗肺癌的crizotinib和治疗转移性/不可切除性黑色素瘤的vemura fenib被认为是个性化治疗领域的突破。2.

05)。3治疗后1、5、14天,两组患者的外周血CA125、VEGF及MMP-9表达均较治疗前有所降低,且实验组治疗后5、14天外周血CA125、VEGF及MMP-9表达均显著低于对照组,差异有统计学意义(P<0.05)。结论:黄芪多糖能够有效降低非小细胞肺癌患者外周血CA125、VEGF及MMP-9表达,提高其临床疗效,改善放疗所致骨髓抑制。
近年来,”液态活检”概念异军突起,不仅可以辅助诊断某些类型实体肿瘤,而且能够监测复发,评估疗效及肺癌分子表达,更是无创肿瘤筛查方法。其来源主要分为循环肿瘤细胞(circulating 或者 tumor cells,CTCs),循环肿瘤DNA(circulating tumor DNA,ct DNA)等。本文讨论了肺癌领域中CTCs、ct DNA及其他肿瘤标志物的生物学特征、检测方法及临床应用,总结了保证特异性前提下的高敏感度、便于临床应用、可重复性好三个重要评判标准的”液态活检”技术,尤其是肺癌I期敏感度可达67%的靶向PCR CTC技术的应用,以期使”液态活检”真正从科研探索走向临床应用。
前不久,中国药学会抗肿瘤药物专业委员会首届主任委员、中国医学科学院肿瘤医院副院长石远凯教授在”中国新药走向世界的征途”创新药高峰论坛上,高屋建瓴地回顾和展望了肿瘤创新药的全球研发趋向和国际应用态势。他首先谈到,在抗肿瘤药物的发展史上,近代肿瘤化疗是一个重要里程碑。1946年,Gilman和Philips用氨介治疗恶性淋巴瘤是近代肿瘤化疗的开端。1957
近年来随着环境污染、生活方式等的变化,非小细胞肺癌(non-small

cell lung cancer,NSCLC)的发病率和死亡率不断上升。传统以手术结合放化疗的治疗方式对NSCLC的治疗效果不甚理想,寻找有效的药物靶点成为肺癌治疗急需解决的问题。随着测序技术、FISH等检测方法的进步,对肺癌患者的癌症驱动基因进行病理诊断及推动个体化治疗变得可行。本文对NSCLC的常见癌基因分型和信号调控网络以及相应的药物靶点进行综述。
目的探讨局部晚期非小细胞肺癌(NSCLC)脑转移的危险因素及患者生存情况。方法根据随访期间是否发生脑转移,将124例ⅡA~Ⅳ期NSCLC患者分为脑转移组51例和非脑转移组73例,回顾性分析其临床资料,筛选发生脑转移的高危因素,并对比2组生存情况。结果

2组肺内转移情况、组织学分型、表皮生长因子受体(EGFR)基因型、除脑部以外的远处转移情况、淋巴结转移情况、血清乳酸脱氢酶(LDH)水平及癌胚抗原(CEA)水平差异有统计学意义(P<0.05或<0.01),其中组织学分型、EGFR基因型、纵膈淋巴结转移及血清CEA水平为脑转移的独立影响因素(P<0.05或<0.01)。至随访结束,脑转移组中位生存时间19.60个月,非脑转移组中位生存时间33.40个月,差异有统计学意义(P<0.01)。结论组织学分型、EGFR基因型、纵膈淋巴结转移及血清CEA水平是局部晚期NSCLC发生脑转移的独立影响因素,发生脑转移的患者生存预后较差。
药物安全性和有效性评价是药物临床试验和个体化用药的核心,也是药物基因组学研究的主要内容。药物基因组学研究贯穿于药物研发、上市评价和临床应用整个过程,根据药物代谢酶、转运体、受体相关基因多态性对用药者进行分层分析,评价与药物体内的处置过程、安全性、有效性个体差异的相关性。综述药物基因组学在新药临床试验、个体化用药中的应用研究新进展。
Advanced DNA methyltransferase cancer gastric cancer(AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options STI571 for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in

patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after firstline platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase Ⅰ-Ⅱ trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC.

6%, and the frequencies of EGFR, KRAS, PIK3 CA, PTEN, and MEK1 mutations were 35.5%, 9.1%, 3.6%, 0.9%, and 0.9%, respectively. No mutation was found in the HER2, NRAS, or BRAF genes. Three of the 51 mutant samples harbored double mutations: two PIK3 CA mutations coexisted with KRAS or EGFR mutations, and another KRAS mutation coexisted with a PTEN mutation. Among the 110 samples, 47 were surgical specimens, 60 were biopsy specimens, and 3 were cytological specimens; the corresponding Verteporfin mutation frequencies were 51.1%, 41.7%, and 66.7%, respectively(P = 0.532). Compared to Sanger sequencing, Snapshot specificity was 98.4% and sensitivity

was 100%(positive predictive value, 97.9%; negative predictive value, 100%). The Snapshot assay is a sensitive and easily customized assay for multigene mutation testing in clinical practice.
肺癌是病死率最高的恶性肿瘤,许多肺癌患者发现时已是晚期,丧失了手术机会,以化疗为主的内科治疗在肺癌的治疗中扮演着重要角色。近年来,以表皮生长因子受体等为靶点的靶向药物研制取得重大进展,有些药物已经应用于临床并取得了满意的效果。许多潜在靶点和药物也在世界范围内研究和开发中。现综述肺癌靶向治疗的研究进展。
目的:回顾性分析肺炎性肌纤维母细胞瘤的临床病理特点、诊治现状及预后。方法:选取2009-01-01-2012-12-31河北医科大学第四医院7例因患肺炎性肌纤维母细胞瘤而入院治疗患者,对其临床症状、影像学表现、病理特征及随访资料进行分析。结果:共7例肺炎性肌纤维母细胞瘤患者,占同期胸外科手术的0.078%(7/8

968)。男3例,女4例。年龄23~71岁,平均年龄48.1岁。有呼吸道症状者3例,其余患者均为体检发现,病变位于左上叶者4例,左下叶者2例,右下叶者1例。病灶呈周围型3例,中心型3例,浸润生长1例;术前诊断考虑为癌或癌可能性大的5例,考虑为良性病变者1例,术前明确诊断为肺炎性肌纤维母细胞瘤者1例;本组7例均行手术治疗,其中肺楔形切除2例,肺段切除1例,肺叶切除4例,术后病理诊断均未发现肺门淋巴结转移。所有7例均在定期随访中,1例术后9个月发现纵膈、对侧肺及心包的转移,于术后17个月死亡,其余患者未发现复发或转移。结论:肺炎性肌纤维母细胞瘤是肺部少见的肿瘤,具有一定的异质性,术前明确诊断困难,手术完全切除是首选治疗,多数患者预后良好。
肺癌是中国发病率及死亡率最高的恶性肿瘤。肿瘤细胞在驱动基因的作用下持续生长,并对该驱动基因的抑制剂具有高敏感性。近年来,针对驱动基因的检测技术不断发展,相应的驱动基因靶向药物也层出不穷。本文主要从中国肺癌的驱动基因、驱动基因的检测及针对驱动基因的靶向治疗3个方面进行综述,并展望中国肺癌驱动基因的应用前景。
对非小细胞肺癌分子病理学的深入理解,有助于开展个性化临床治疗和预后。基因检测可以指导非小细胞肺癌靶向药物治疗,提升药物疗效,延长患者生存期。本文简要介绍了与非小细胞肺癌相关的EGFR基因和EML4-ALK融合基因检测方法的研究进展。
蛋白酪氨酸激酶是一类具有酪氨酸激酶活性的蛋白质,其异常表达与肿瘤的侵袭、转移以及肿瘤新生血管的生成等密切相关。以蛋白酪氨酸激酶作为靶点的药物研究已取得了突破性进展,目前已有二十余个小分子蛋白酪氨酸激酶抑制剂用于临床肿瘤的治疗,并有大量的抑制剂处于临床前和临床研究阶段。对近年来小分子蛋白酪氨酸激酶抑制剂的研究进展进行了综述。
医学科技日新月异,20世纪70年代随着单克隆抗体技术的发展,在病理学上开展了免疫组织化学(IHC),其把人们从传统病理组织学(形态学)推向蛋白质水平(抗原、抗体的定性和定位),在现代病理诊断中的应用日益广泛,尤其在肿瘤诊断与鉴别中起着非常重要的作用,对于诊断肿瘤、肿瘤分类、判断预后产生了巨大的影响,扩展了对各种疾病及肿瘤形成过程的认识,提高了病理诊断与研究水平。近来肿瘤的分子病理诊断及靶向治疗的意义成为研究热点。
Gastric Bioactive Compound Library high throughput PCI-32765细胞系 cancer represents

a serious health problem on a global scale. It is the second leading cause of cancer-related death worldwide. Novel therapeutic targets are desperately needed because the meager improvement in the cure rate of about 10% realized by adjunctive treatments to surgery is unacceptable as > 50% patients with localized gastric cancer succumb to their disease. Either postoperative chemoradiotherapy(United States),pre-and post-operative chemotherapy(Europe),and adjuvant chemotherapy after a D2 resection(Asia) can all be regarded as standards of care in the localized gastric cancer management. In metastatic disease the addition of trastuzumab to chemotherapy is standard of care in Her2 positive disease. In the HER2 negative population,the treatments remain limited.

Unfortunately, some of these new approaches have met with mixed results. Furthermore, no clear metrics are available to determine whether these designs are more successful than previous

strategies. This review examines the evolution of phase I trials and draws upon several examples of strategies that have been successful as well as those that have not, and outlines a pragmatic approach to phase I trials as our understanding of the molecular biology of individual malignancies emerges.
利用局部和全身两种不同的治疗途径,科学家宣称他们在肺癌和黑色素瘤的治疗上取得了积极的进展。治疗上的一大进步针对进展期肺癌某些异常的基因,通过靶向治疗,大部分患者肿瘤明显缩小。尽管临床试验在82例患者的小范围内进行,而且也无对照组,但试验结果却有显著的临床价值。相关报告近期在
2010年ASCO会议上,关于非小细胞肺癌的研究精彩纷呈,将影响今后NSCLC的临床实践及研究方向,全文就晚期NSCLC的有关治疗进展作一综述。
传统的化疗治疗晚期非小细胞肺癌已经到了一个平台期,靶向药物为突破这一”瓶颈”提供了行之有效的解决方案。文中系统回顾了近年来的大型随机临床研究,提供目前靶向药物在晚期非小细胞肺癌中的应用规范,并提出靶向治疗中存在的问题及可能解决的方法。
1文献来源研究一:Takeuchi

Selleck CP673451 K,Choi YL,Soda M,et al.Multiplex MK8776 reverse transcription-PCR screening for EML4-ALK fusion transcripts[J].Clin Cancer Res,2008,14(20):6618-6624.
非小细胞肺癌切除后辅助化疗问题一直存在争议。已证明Ⅱ-Ⅲa期可从辅助化疗中获益,Ⅰb期可口服辅助化疗获益。尽管新药物的出现有力地提高了辅助化疗的疗效,但患者依从程度的提高有待于给药方案的改进。肿瘤分子标志物和酪氨酸激酶抑制药是今后提高术后辅助化疗疗效的研究方向。

上海抗肿瘤药专利创收四亿元我国自主知识产权生物医药专利向世界证明了自身价值。2010年8月26日,中科院上海生科院知识产权与技术转移中心宣布,将一项蛋白抗肿瘤药物专利授权给跨国制药集团赛诺菲-安万特公司,合同金额超过4亿元,并外加日后销售额提成。业内认为,此项专利作价之高,在国内科研领域堪称罕见。上海生科院生化与细胞所的这一成果,被国际肿瘤生物学权威杂志《癌细胞》以11页篇幅报道,并随刊配发了由两位美国科学家撰写的2页评论,称中国科学家所做工作乃”肿瘤新生血管形成研究‘必读’”。
MTH1酶属于Nudix水解酶,具有清理细胞核苷酸池内氧化嘌呤核苷酸,防止核酸氧化损伤的功能。多项研究表明MTH1酶在神经退行性疾病、抗衰老等,尤其是抗肿瘤方面发挥关键作用,有望成为抗肿瘤药物的新靶标。近年国内外有关MTH1酶抑制剂的研究也逐渐增多,该文概述了MTH1酶的转录和翻译、结构特点、催化机制、应用等各方面信息,特别是对其各类抑制剂的研究现状进行了较为全面的综述。
Pancreatic

cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility G007 LK of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available.