血管生成抑制剂治疗肺癌的研究现状

肿瘤血管生成是一个内皮细胞增殖、迁移以形成新血管来营养肿瘤的过程,抗血管生成治疗的基本原理是基于肿瘤需要血管来生长、转移这个概念。最近血管生成抑制剂已进入临床,并用于治疗肺癌。现综述如下。     

消化道肿瘤抗血管生成治疗的临床研究进展

消化道肿瘤的生长，转移与复发是血管生成依赖的，故以肿瘤血管生成的各个环节及其发生过程中的生化改变为靶点，研制血管生成的抑制剂，可使肿瘤处于休眠状态，有效地抑制肿瘤生长，侵袭，转移和复发，将成为肿瘤防治的一条新途径。本文主要综述消化道肿瘤抗血管生成治疗的临床试验研究进展。     

肿瘤血管生成及其抗血管生成治疗的研究进展

肿瘤的生长和转移依赖于新生血管形成,血管内皮生长因子及其受体是目前发现的最重要的促肿瘤血管生长因子,在肿瘤血管生成过程中发挥关键作用。鉴于肿瘤血管生成在肿瘤生长、浸润和转移中的重要作用,近年来开始了抗血管生成治疗肿瘤的新方法——抗血管生成疗法。本文着重综述了肿瘤血管生成及其抗肿瘤血管生成治疗的研究进展。     

缺血性脑卒中后血管生成研究的进展

缺血性脑卒中是大脑血液和氧气供应不足的结果.最近的研究表明,缺血性脑卒中后新血管形成不仅可以改善脑缺血区域血供,还可以促进神经发生,改善动物模型和患者的神经功能.本文就缺血性脑卒中后血管生成的研究进展做以下综述.     

抗肺癌血管生成治疗的进展

没有血管生成,实体瘤直径不会超过3mm。肿瘤的生长和转移都依赖于新生血管的形成。抗肿瘤血管生成治疗是近年来逐渐兴起的一种新的抗癌方法,肿瘤血管生成的机制也成为近年来肿瘤领域研究的热点。本文就两年来抗肺癌肿瘤血管生成治疗进展作一综述。     

血管生成抑制剂-细胞毒药物联用对胰腺癌生长和转移的实验治疗

目的探讨血管生成抑制剂-细胞毒药物联用疗法[TNP-470/2＇,2＇-二氟脱氧胞苷(Gemcitabine)]对胰腺癌裸鼠原位移植模型(SOI)生长、转移的抑制作用.方法单用疗法24只胰腺癌SOI模型随机分为T30组(TNP-470 30 mg/kg,皮下注射,隔日一次,疗程8周)、G100组(Gemcitabine 100mg/kg,腹腔内给药,术后第0、3、6、9天)和对照组;联用疗法32只SOI模型随机分为T15组、G50组、对照组和联用组(采用T30+G50),术后第10周处死裸鼠.结果G100侧重于抑制胰腺癌生长,T30则侧重抑制胰腺癌转移,两者均无显著的改善预后作用;T15和G50无显著的抗肿瘤生长和转移作用;只有联用组能显著抑制胰腺癌生长、转移和改善预后,T30可使G50的抑瘤率提高2倍,并获得2/8只的肿瘤治愈率;T30组的微血管密度为7.13±2.99/高倍视野,显著低于T15组的10.53±3.22/高倍视野和对照组的14.50±5.93/高倍视野(P＜0.05).结论血管生成抑制剂-细胞毒药物联用疗法(TNP470 30 mg/kg和Gemcitabine 50 mg/kg)能有效抑制肿瘤生长和转移,有助于减少细胞毒药物剂量及不良反应,为安全有效的抗肿瘤策略.     

抗血管生成治疗肿瘤研究的进展

肿瘤血管生成是一个多步骤复杂的调控事件。针对肿瘤血管形成分子机制所设计的抗血管生成策略,已经成为目前肿瘤治疗的热点研究领域。本文就肿瘤血管生成特点及其调控、抗肿瘤血管生成治疗研究现状、存在问题和今后研究方向作一综述。     

环氧化酶抑制剂吲哚美辛对胰腺癌新生血管生成的抑制作用

目的 通过观察环氧化酶(COX)抑制剂吲哚美辛对胰腺癌血管内皮生长因子(VEGF)表达及对体内外血管生成的的影响,探讨其对胰腺癌生长抑制的作用机制.方法 用RT-PCR方法检测不同浓度吲哚美辛对BxPC3细胞VEGF mRNA表达的调节作用;应用小管形成实验研究吲哚美辛对ECV304细胞体外血管生成的影响;建立裸鼠胰腺癌BxPC3细胞种植瘤模型,应用吲哚美辛给荷瘤裸鼠灌胃(3 mg·kg-1·d-1体重,共4周),观察其对种植瘤生长曲线、瘤重及种植瘤组织VEGF mRNA表达的影响;采用Ⅷ因子免疫组化染色评估瘤组织中微血管密度(MVD).结果 (1)小管形成实验中,吲哚美辛组ECV304细胞数较少,细胞排列差,偶可见条索状细胞链,中空闭合管状结构缺如.(2)吲哚美辛呈剂量依赖性抑制BxPC3细胞VEGF mRNA表达.(3)应用吲哚美辛给荷瘤裸鼠灌胃4周后,平均瘤重(0.495±0.31)g,显著小于对照组瘤重(1.57±1.06)g,抑瘤率为67%.吲哚美辛显著下调种植瘤VEGF mRNA表达.(4)对照组MVD为5.98±1.27,吲哚美辛组为2.02±0.28,差异有显著性(P＜0.01).结论 COX抑制剂吲哚美辛可下调VEGF mRNA的表达,抑制胰腺癌体内、体外血管的生成,抑制裸鼠种植瘤新生血管的生成,这可能是其抑制胰腺癌裸鼠种植瘤生长的重要原因.     

环氧化酶抑制剂吲哚美辛对胰腺癌新生血管生成的抑制作用

目的通过观察环氧化酶(COX)抑制剂吲哚美辛对胰腺癌血管内皮生长因子(VEGF)表达及对体内外血管生成的的影响,探讨其对胰腺癌生长抑制的作用机制。方法用RT-PCR方法检测不同浓度吲哚美辛对BxPC3细胞VEGFmRNA表达的调节作用;应用小管形成实验研究吲哚美辛对ECV304细胞体外血管生成的影响;建立裸鼠胰腺癌BxPC3细胞种植瘤模型,应用吲哚美辛给荷瘤裸鼠灌胃(3mg.kg-1.d-1体重,共4周),观察其对种植瘤生长曲线、瘤重及种植瘤组织VEGFmRNA表达的影响;采用Ⅷ因子免疫组化染色评估瘤组织中微血管密度(MVD)。结果(1)小管形成实验中,吲哚美辛组ECV304细胞数较少,细胞排列差,偶可见条索状细胞链,中空闭合管状结构缺如。(2)吲哚美辛呈剂量依赖性抑制BxPC3细胞VEGFmRNA表达。(3)应用吲哚美辛给荷瘤裸鼠灌胃4周后,平均瘤重(0.495±0.31)g,显著小于对照组瘤重(1.57±1.06)g,抑瘤率为67%。吲哚美辛显著下调种植瘤VEGFmRNA表达。(4)对照组MVD为5.98±1.27,吲哚美辛组为2.02±0.28,差异有显著性(P<0.01)。结论COX抑制剂吲哚美辛可下调VEGFmRNA的表达,抑制胰腺癌体内、体外血管的生成,抑制裸鼠种植瘤新生血管的生成,这可能是其抑制胰腺癌裸鼠种植瘤生长的重要原因。     

血管生成抑制剂TNP-47O与细胞毒药物Gemcitabine的抗胰腺癌生长和转移作用的比较研究

目的　探讨血管生成抑制剂 (TNP- 4 70 )和细胞毒药物 (Gemcitabine)对胰腺癌裸鼠原位移植模型 (SOI)生长、转移的抑制作用及其作用机制。方法　把胰腺癌细胞株 SW1990皮下种植生长的癌组织移植于裸鼠胰腺尾部 ,制备胰腺癌 SOI模型 ;2 4只 SOI模型随机分为 TNP组 (TNP- 4 70 30 m g/ kg,皮下注射 ,隔日一次 ,疗程 8周 )、GEM组 (Gemcitabine 10 0 mg/ kg,腹腔内注射 ,术后第 0、3、6、9天给药 )和对照组 ,术后第 10周处死裸鼠。结果　 Gemcitabine侧重于抗胰腺癌生长 ,TNP- 4 70则侧重抑制胰腺癌转移 ,两者均无显著的预后改善作用 ;TNP组的微血管密度 (MVD)显著低于 GEM组和对照组 ,GEM组的肿瘤增殖指数 (PI)显著低于 TNP组和对照组 (均 P<0 .0 5 )。结论　血管生成抑制剂和细胞毒药物在抗肿瘤生长和转移的侧重点和作用机制方面均存在显著差异。     

选择性COX-2抑制剂联合顺铂对肺癌新生血管的影响及机制研究

目的研究选择性环氧化酶2(COX-2)抑制剂尼美舒利(NIM)单独应用以及联合顺铂(DDP)对肺癌A549细胞裸鼠移植瘤血管生成的影响及其机制,为肺癌的治疗提供新思路。方法培养肺癌A549细胞,构建肺癌A549裸鼠移植瘤模型。依据随机数字表法将研究对象分为4组进行药物干预:对照组、NIM组、DDP组、NIM+DDP组,每组8只,观察一般状态。给药后第22天处死裸鼠,获取肿瘤组织,测量称取瘤重、瘤径,计算并比较各组体积抑瘤率。用CD31标记微血管,采用微血管计数法检测各组微血管密度。采用免疫组织化学检测肺癌A549裸鼠移植瘤内血管内皮生长因子的表达。结果本研究成功构建肺癌A549裸鼠移植瘤模型。NIM+DDP组第9、13、17、21天的移植瘤体积增长较其他3组慢(P值均<0.001)。NIM+DDP组体积抑瘤率最大。NIM+DDP组较其他3组移植瘤微血管密度低(F=27.861,P<0.001)。结论选择性COX-2抑制剂单独使用有抑制新生血管生成的作用,推测选择性COX-2抑制剂具有抗肿瘤能力,可能成为肺癌靶向治疗因子。选择性COX-2抑制剂联合DDP对新生血管因子表达的抑制效果更显著,对肺癌A549细胞裸鼠移植瘤的生长的抑制更显著。     

Progress in the therapy of small cell lung cancer

Small cell lung cancer (SCLC) accounts for approximately 14% of all cases of lung cancer. Combination chemotherapy is the most effective treatment modality for SCLC and recently, several new active drugs have emerged. Combinations of platinum agents with CPT-11 or gemcitabine have been successfully compared in phase III trials against the cisplatin/etoposide standard. Modest improvements in the outcome of patients with SCLC have been noted over the last two decades. Thoracic irradiation given concurrently with chemotherapy improves survival compared with sequential chemotherapy and radiation, but this approach is associated with more toxicity. Moreover, the optimal doses and fractionation of thoracic irradiation remain to be determined. Three-dimensional treatment planning is under investigation. Prophylactic cranial irradiation (PCI) has established a role in the management of patients who have achieved a complete response to the initial therapy. Novel molecular targeted therapies are among the strategies currently being investigated in SCLC.     

Epidermal growth factor receptor inhibitors in lung cancer therapy

Over the past decade our evolving knowledge and understanding of cancer biology has allowed rapid progression in the development of targeted cancer therapy. Improving lung cancer mortality has remained a difficult task; however, therapeutic agents directed against the epidermal growth factor receptor (EGFR) have provided physicians with a valuable new tool to integrate into multimodality therapy. EGFR inhibitors have been shown to elicit meaningful antitumor effects and quality-of-life benefits with acceptable toxicity. The rationale, utility, toxicity profile, and therapeutic strategy of EGFR-targeted therapy will be reviewed.     

非小细胞肺癌免疫检查点抑制剂治疗进展

<正>肺癌是当前全球男性、发达国家女性死亡率最高的恶性肿瘤疾病,是我国恶性肿瘤第一位死因。在所有的肺癌亚型中,非小细胞肺癌(non-small-cell lung cancer,NSCLC)占肺癌总数的85%[1]。尽管肺癌的治疗方法在不断进展,但肺癌的预后仍不乐观,据报道NSCLC患者的5年生存率不足20%[2]。癌症免疫治疗是一种通过动员自身免疫系统识别和破坏癌细胞的治疗方式,尽管T细胞受体(T cell receptors,TCRs)具有识别和根除肿瘤细胞的能力,但癌细胞能够表达     

肺癌基因治疗的动态

肿瘤是目前危及人类健康的最主要疾病之一,而肺癌的病死率又居恶性肿瘤的首位。尽管放射治疗(放疗)、化学治疗(化疗)及手术治疗等传统治疗癌症的方法已有不断改进和发展,肺癌患者的总体生存率并无明显改善,5年生存率不足15 % [1] 。近年来,肺癌的基因治疗取得了长足的进步,有的研究已进入临床实验阶段。现就其近年的一些进展情况及热点问题简单综述如下。一、基因转移载体成功地将目的基因转入靶器官并获得有效的表达是基因治疗的基础。目前用于基因转移的载体种类较多,用于肺癌基因治疗的主要载体可分为病毒载体和非病毒载体两类(表1) ,各…     

Afatinib（阿法替尼）治疗非小细胞肺癌的研究进展

肺癌是当今世界最常见的恶性肿瘤之一,也是肿瘤导致死亡的首要原因。分子靶向是治疗肺癌的重要手段之一。表皮生长因子受体（epidermalgrowthfactorreceptor,EGFR）酪氨酸激酶（tyrosinekinase,TK）是受体酪氨酸激酶家族中的一员,在上皮源性的多种肿瘤上皮细胞内EGFR都有较高的表达。既往多种研究结果显示,     

Hemostatic complications of angiogenesis inhibitors in cancer patients

Tumor vasculature and tumor-associated neo-angiogenesis have recently become major targets for rational drug design of antineoplastic agents. Five such agents with angiogenesis inhibiting activity (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib) have already obtained US Food and Drug Administration approval for clinical use and many others have entered clinical trials. Vascular complications, including venous or arterial thromboembolism and hemorrhage, have emerged as relevant toxicities in several clinical trials with angiogenesis inhibitors. Given the well-known interplay between the blood clotting system, angiogenesis, and tumor growth, a better understanding of the impact of these new drugs on overall hemostatic balance is required. In this brief overview, we discuss the incidence of hemostatic complications, the likely pathogenetic mechanisms involved, and the critical need to establish in randomized clinical trials the usefulness of thrombosis prophylaxis to prevent these complications. Careful documentation of hemostatic complications during treatment with each of the new antiangiogenic drugs is warranted. Further studies are urgently required to better define the causal association of these new agents with hemostatic complications and to establish the best prophylactic strategy.     

Proteasome inhibitors in lung cancer

Proteasome inhibition is a novel therapeutic approach that is being investigated in non-small cell and small cell lung cancer (NSCLC and SCLC). Proteasome inhibition affects a range of intracellular signals and disrupts the levels of numerous proteins, causing apoptosis via multiple pathways. Importantly, malignant cells are more sensitive to proteasome inhibition than normal cells. A number of proteasome inhibitors have demonstrated activity in preclinical studies, both as single agents and in combination with conventional and novel antineoplastic agents. However, only bortezomib, a dipeptide boronic acid analog, has been investigated in lung cancer clinical trials, in which it has shown activity as a single agent and in combination regimens. Numerous preclinical and clinical studies are ongoing in both NSCLC and SCLC. Proteasome inhibition could potentially play a significant role in the future management of these conditions.     

Home oxygen therapy for terminal lung cancer cases]

Home oxygen therapy (HOT) was introduced as part of the terminal care of 52 lung cancer patients attending our hospital from 1997 to 2000, all of whom subsequently died from their illnesses. We administered a questionnaire about HOT to their bereaved family members. The results confirmed that many of those interviewed thought that HOT improved their quality of life, but probably made the patients more aware of the progression of their disease. As the incidence of lung cancer has been increasing, lung cancer patients have begun to form an increasing proportion of patients receiving HOT in recent years. In addition, the number of patients with a PaO2 of > or = 60 torr at rest at the start of HOT has been increasing. It may be necessary when dealing with terminal lung cancer patients, in whom PaO2 can decrease rapidly over a relatively short period of time, to explore indication criteria for HOT different from those conventionally employed.