肝细胞癌血管生成及抗血管生成治疗的研究进展

肝细胞癌（HCC）发生发展与肝癌血管生成存在密切的关系,临床上已逐步开展抗肝癌血管生成治疗.目前的研究表明,肝癌血管生成与血管生成促进因子和抑制因子及其信号转导通路有关,抗肝癌血管生成的药物研发在肝癌血管内皮细胞生成与抑制的理论基础上逐步开展,如贝伐单抗、索拉非尼、沙利度胺、西妥单抗等药物在临床取得一定的疗效,靶向分子药物相互联合治疗、靶向分子药物与TACE.联合治疗等治疗理念已逐步开展研究.本文对近年肝癌血管生成的相关因素,抗肝癌血管生成的机制和治疗方式、效果、进展做一综述.     

膀胱癌血管生成和抗血管生成的研究进展

血管生成是肿瘤特殊生物学行为的重要过程之一。本文就成纤维细胞生长因子，血管内皮生长因子，肝细胞生长因子，胸苷磷酸化酶等若干种参与膀胱癌血管生成的促血管生长因子的最新研究进展作一综述，并探讨抗血管生成在膀胱癌治疗中的现状及应用前景。     

肿瘤抗血管生成靶向治疗

<正>肿瘤血管生成是所有实体肿瘤的共同特征,是实体肿瘤生长和转移必须依赖的病理学基础,与肿瘤的生长、侵袭转移关系极为密切。现已证实,不同实体肿瘤血管内皮细胞所表达的生长因子及其受体均有共性,因此抗血管生成靶向治疗已经成为肿瘤治疗的重要策略。目前,已有数     

乳腺癌抗血管生成治疗的临床研究进展

乳腺癌的生长、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的生化改变为靶点,研制血管生成抑制剂,可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。本文主要综述乳腺癌抗血管生成治疗的临床研究进展。     

血管生成相关因子治疗肝细胞肝癌研究进展

肝细胞肝癌（HCC）是一种富血管性肿瘤，其生长很大程度上依赖于血供的程度。现已证实许多血管生成相关因子与HCC的形成、生长、侵袭、转移、复发及预后关系密切。这些因子包括血管内皮生长因子（vascular endothelial growth factor，VEGF）、Tie-血管生成素、生长抑素、血管他丁、内皮他丁、基质金属蛋白酶、血管生成因子、巨噬细胞游走抑制因子（macrophage migration inhibitory factor，MIF）、Ephrin等，     

乳腺癌抗血管生成治疗的临床研究进展

乳腺癌的生长、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 ,研制血管生成抑制剂 ,可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。本文主要综述乳腺癌抗血管生成治疗的临床研究进展。     

肝细胞癌抗血管生成研究进展

肝细胞肝癌 (hepatocellular carcinoma,HCC)是恶度最高的恶性肿瘤之一 ,预后较差 ,手术切除是其治疗的主要手段 ,而术后复发转移仍是治疗失败的主要原因。 HCC是典型的多血管肿瘤 ,血管生成被认为是其恶性生物学行为基础 ,抗血管生成治疗有望成为改善预后乃至攻克 HCC的一种全     

抗血管内皮生长因子抗体对实验性肝癌的生长抑制作用

目的了解抗血管内皮生长因子(VEGF)抗体对人肝癌的生长抑制作用.方法在已建立的人肝癌裸鼠皮下种植瘤的瘤灶旁,注射抗VEGF抗体,观察肿瘤生长情况,用CD31的免疫组化方法检测肿瘤内部的微血管密度(iMVD),用原位末端转移酶标记技术检测凋亡的肿瘤细胞.结果实验结束后1周,实验组和对照组肿瘤大小(长×宽)是(26.46±19.81) mm2和(105.77±17.40) mm2(P<0.001),2周后是(45.20±23.02) mm2和(150.77±77.41) mm2(P<0.05),而此时肿瘤的iMVD是(2 311±120)个/mm2和(3 900±328)个/mm2 (P<0.001); 肿瘤细胞凋亡指数是15.31% 和 6.83%(P<0.005).结论抗VEGF抗体能通过抑制肿瘤微血管的生长,抑制实验性人肝癌的生长,其实质是增加了肿瘤细胞凋亡.     

抗血管生成疗法在肿瘤外科中的作用

肿瘤的发生,发展和侵袭与血管生成密切相关,特别是转移病灶更依赖血管新生的作用,进一步阐明肿瘤血管生成和新生的机理以及开发抗血管生成制剂将在肿瘤治疗中开辟一个崭新的途径。     

人类基因治疗的背景与肝癌基因治疗的研究概况

目的 了解人类基因治疗的背景与肝癌基因治疗的研究概况。方法 采用文献复习的方法对人类基因治疗的临床研究历史与发展，以及肝癌基因治疗方面的一些基础研究进展进行综述和分析。结果 基因治疗作为人类某些遗传疾病的替代治疗方法在临床研究中已取得了较好,冲锋枪量在肿瘤的治疗研究中基本上不处于基础研究阶段。在胆癌的基因治疗研究中，所有的病毒载体如逆转录病毒、腺病毒以及腺病毒的相关病毒各有优缺点，逆转录病毒邕有提高滴度，应该更有前景；所有目的基因TK及p53基因等已在体外及动物实验中取得了较好的效果，但在治疗的特异性和安全性方面还存在较大的缺陷。结论 人类基因治疗的前景是乐观的，肝癌的基因治疗研究也取得了一定成果，但距临床应用还有一段距离。     

EpCAM-Targeted Therapy for Human Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies and the identification of new effective therapies for HCC is urgently needed. We have previously identified EpCAM, one of the hepatic stem/progenitor markers, as a prognostic predictor of patients who received curative hepatectomy for HCC. In this preclinical study, the effects of VB4-845, an immunotoxin targeting EpCAM, were evaluated in HCC.

Methods

In vitro effects of VB4-845 on human HCC cells, the cytotoxic activity, sphere-forming ability, and expression of hepatic stem/progenitor markers were analyzed. In vivo effects of VB4-845 were evaluated using subcutaneous and orthotopic liver xenograft models.

Results

In all HCC cell lines expressing EpCAM, VB4-845 showed potent cytotoxicity and was significantly effective in combination with 5-FU (p < 0.05). Although 5-FU did not affect the sphere-forming ability and increased the populations expressing other stem/progenitor markers CD133 and CD13 (p < 0.05), VB4-845 strongly suppressed the sphere-formation and decreased the population expressing CD133 and CD13 (p < 0.0005, <0.01, respectively). In subcutaneous xenograft models, the combination of VB4-845 plus 5-FU showed significant regression of tumors compared with the control (p = 0.016). Moreover, in orthotopic liver xenograft models, the combination therapy dramatically decreased the tumor volume compared with the control (p = 0.0011).

Conclusions

Our preclinical investigation suggests that EpCAM-targeted therapy may offer a promising and novel approach for the treatment of HCC with a poorer prognosis.     

降阶治疗在肝细胞肝癌治疗中的进展

目的 总结肝癌降阶治疗在肝癌治疗中的进展与地位。方法 通过检索MEDLINE 和PubMed数据库相关文献并对其进行分析与综述。结果 晚期肝癌临床预后差,降阶治疗后肝切除或肝移植术能显著改善患者的预后,但是不同的降阶治疗方法,不同的入组标准,使患者的临床疗效参差不齐。结论 根据不同的病情,选用合理的降阶治疗方法,可以提高患者的远期预后。     

分子靶向药物在肝癌治疗中的应用

肝癌是临床上最常见的恶性肿瘤之一,是世界上第5大常见肿瘤,在肿瘤致死原因中仅次于肺癌和胃癌,居第3位。肝癌的全球发病率逐年增长,发病人数超过62.6万人/年,死亡人数接近60万人/年。肝癌在组织病理学上分为3种类型,其中90%是肝细胞型肝癌(HCC),另外10%为肝胆管细胞癌(ICC)和混合型肝癌(MHC)。由于起病隐袭,早期缺乏特异性症状,确诊时大多数患者已达局部晚期或已出现远     

New Approaches to the Treatment of Hepatic Malignancies Angiogenesis and Antiangiogenic Therapy of Colon Cancer Liver Metastasis

The fact that tumor growth and metastatic spread relies on angiogenesis has been widely proven and accepted. The understanding of cancer biology and metastasis formation has led to the development of new therapeutic approaches that target tumor biology. The survival and establishment of metastatic lesions depend on a shift in the normal balance of proangiogenic and antiangiogenic factors that favor angiogenesis. Colorectal cancer is one of the leading cancer deaths worldwide. Angiogenesis has been associated with colon cancer progression and metastatic spread, thereby significantly affecting patient survival. New experimental approaches that inhibit angiogenic processes have demonstrated promising antineoplastic effects on metastatic colorectal cancer and are partially being investigated in clinical trials. This review focuses on angiogenesis in colorectal cancer metastasis formation as a target for antiangiogenic therapy, describing the experience from experimental studies and current clinical trials.     

Early Hepatocellular Carcinoma: Pathology, Imaging, and Therapy

Background In 1987, Japanese researchers proposed to define the pathological concept of early hepatocellular carcinoma (HCC). However, there are some conceptual differences between the East and the West in the diagnosis and treatment of early HCC. Methods To provide up-to-date data for making a worldwide consensus, this article has collected six papers focused on the management of early HCC, which were presented in the Fifth International Meeting of “Hepatocellular Carcinoma: Eastern and Western Experiences” in Houston in January 2007. Results In the pathological perspective, the common criteria to discriminate early HCC from dysplastic nodule included hepatocytic invasion of portal triads and septa (stromal invasion). The current imaging modalities such as contrast-enhanced ultrasound (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI) with the use of intravenous contrast material with multiphasic imaging could enhance their ability to accurately characterize early HCC. From the treatment perspective, a single early HCC had a high chance for cure by resection, ablation, or transplantation, which proved to be the earliest clinical entity (Stage 0 HCC). Conclusions Early HCC is characterized by its incipient malignant nature and by an extremely favorable clinical outcome, thereby justifying its definition. Proceedings of the Fifth International Meeting Hepatocellular Carcinoma: Eastern and Western Experiences held in Houston, TX, January 11–13, 2007.     

Treatment Options and Surveillance Strategies After Therapy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer death worldwide. Recurrence rates after curative intent treatment for HCC are high; 5-year disease-free survival ranges from only 19 to 81 %. There is no direct evidence to guide the optimal frequency and method of surveillance for recurrent HCC after curative intent treatment. In contrast, there is strong evidence supporting both primary screening for HCC in patients with chronic liver disease. After resection, HCC tends to recur locally, whereas the pattern after transplantation is more at extrahepatic sites. In theory, if an HCC recurrence is discovered early, more therapeutic options are available for treatment of the recurrent HCC. As such, close surveillance after curative intent therapy may have the potential to prolong survival. We herein review the available literature derived from primary surveillance of patients with cirrhosis, as well as data on postoperative surveillance of HCC patients. In aggregate, although data remain scarce, close surveillance with α-fetoprotein and cross-sectional imaging every 3–4 months for 3 years after curative intent therapy, followed by surveillance every 6–12 months thereafter, seems the most prudent approach to follow-up of patients with HCC in the postsurgical setting.     

Systemic Therapy for Hepatocellular Carcinoma: Cytotoxic Chemotherapy,Targeted Therapy and Immunotherapy

Conventional cytotoxic chemotherapy has not provided clinical benefit or prolonged survival for patients with advanced HCC. This review summarizes the results of prospective clinical trials of several categories of systemic therapy, with emphasis on the more promising results from recent trials of biologically targeted therapeutic agents in HCC. Proceedings of the 5th International Meeting Hepatocellular Carcinoma: Eastern and Western Experiences held in Houston, TX, January 11–13, 2007.