肝癌抗血管形成和放射治疗的实验与临床研究
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摘要
目的
实体性肿瘤在其发展过程中都有大量的肿瘤新生血管形成，血管形成是肿瘤细胞生长、侵袭和转移的基础。原发性肝细胞癌是临床常见恶性肿瘤之一，发病隐匿，复发和转移率高，对传统治疗方法反应差，预后不佳；肿瘤血管形成活跃也是其突出的特征。血管形成是在多种生长因子的调控下实现的，其中血管内皮生长因子(VEGF)是血管形成的主要调控因子，它能促进内皮细胞分裂、增殖和血管构建，诱导血管形成；抑制内皮细胞凋亡；增加新生血管通透性；诱导细胞外基质和基底膜分解酶表达升高或活性增强。VEGF在肿瘤血管形成和瘤细胞侵袭、转移过程中具有至关重要的作用。
肝癌的传统治疗方法有手术切除、放射治疗和介入等，手术是最有效的根治性治疗措施，但临床上大部分病人就诊时己失去手术治疗机会。肝癌对化疗不敏感，肝癌细胞对放疗也不敏感，而肝脏却是放射敏感器官。随着放疗设备和技术的进步，肝癌的放疗疗效有了极大的提高，但肝癌的高转移特性制约了作为局部治疗措施的放疗的作用，放疗后复发和转移仍是导致患者死亡的主要原因。因而寻求更有效的治疗方法延长肝癌患者的生存期，是临床迫切的需要。
有大量实验研究表明，抗血管形成治疗能抑制多种肿瘤生长，但其作用是暂时的。放疗与抗血管形成治疗联合对一些肿瘤的协同抑制作用已得到实验证实，但联合治疗肝癌的研究未见报道。我们利用肝癌血管形成丰富的特点，应用外照射放疗与抗VEGF抗体(VEGF mAb)联合治疗肝癌裸鼠移植瘤，观察联合
OBJECTIVE
There is abundant new vessel formation in the development of solid tumors. Neovascularization is an obligatory event connected with the growth, invasion and metastasis of tumors. Primary hepatocellular carcinoma(HCC) is one of the most common malignant hypervascular tumors characterized by neovascularization. Respond poorly to traditional treatments, recurrence and metastasis are common in HCC and associated with poor prognosis. Angiogenesis is triggered by a variety of growth factors and vascular endothelial growth factor(VEGF) is the principal regulator in the complex process of vessel formation. VEGF facilitates endothelial cell fission, proliferation and vessel construction, inducing angiogenesis, inhibiting apoptosis of endothelial cells, improving permeability of new blood vessel, promoting the expression and activity of enzymes in decomposing extracellular matrix and basement membrane. VEGF plays a pivotal role in the course of angiogenesis and tumor growth, invasion and metastasis.
The mainstay of HCC treatments today consists of surgery, radiotherapy, and chemotherapy. Surgical treatment is the most effective method, but the great majority patients with HCC have no chance for surgical treatment when the disease was
实体性肿瘤在其发展过程中都有大量的肿瘤新生血管形成，血管形成是肿瘤细胞生长、侵袭和转移的基础。原发性肝细胞癌是临床常见恶性肿瘤之一，发病隐匿，复发和转移率高，对传统治疗方法反应差，预后不佳；肿瘤血管形成活跃也是其突出的特征。血管形成是在多种生长因子的调控下实现的，其中血管内皮生长因子(VEGF)是血管形成的主要调控因子，它能促进内皮细胞分裂、增殖和血管构建，诱导血管形成；抑制内皮细胞凋亡；增加新生血管通透性；诱导细胞外基质和基底膜分解酶表达升高或活性增强。VEGF在肿瘤血管形成和瘤细胞侵袭、转移过程中具有至关重要的作用。
肝癌的传统治疗方法有手术切除、放射治疗和介入等，手术是最有效的根治性治疗措施，但临床上大部分病人就诊时己失去手术治疗机会。肝癌对化疗不敏感，肝癌细胞对放疗也不敏感，而肝脏却是放射敏感器官。随着放疗设备和技术的进步，肝癌的放疗疗效有了极大的提高，但肝癌的高转移特性制约了作为局部治疗措施的放疗的作用，放疗后复发和转移仍是导致患者死亡的主要原因。因而寻求更有效的治疗方法延长肝癌患者的生存期，是临床迫切的需要。
有大量实验研究表明，抗血管形成治疗能抑制多种肿瘤生长，但其作用是暂时的。放疗与抗血管形成治疗联合对一些肿瘤的协同抑制作用已得到实验证实，但联合治疗肝癌的研究未见报道。我们利用肝癌血管形成丰富的特点，应用外照射放疗与抗VEGF抗体(VEGF mAb)联合治疗肝癌裸鼠移植瘤，观察联合
OBJECTIVE
There is abundant new vessel formation in the development of solid tumors. Neovascularization is an obligatory event connected with the growth, invasion and metastasis of tumors. Primary hepatocellular carcinoma(HCC) is one of the most common malignant hypervascular tumors characterized by neovascularization. Respond poorly to traditional treatments, recurrence and metastasis are common in HCC and associated with poor prognosis. Angiogenesis is triggered by a variety of growth factors and vascular endothelial growth factor(VEGF) is the principal regulator in the complex process of vessel formation. VEGF facilitates endothelial cell fission, proliferation and vessel construction, inducing angiogenesis, inhibiting apoptosis of endothelial cells, improving permeability of new blood vessel, promoting the expression and activity of enzymes in decomposing extracellular matrix and basement membrane. VEGF plays a pivotal role in the course of angiogenesis and tumor growth, invasion and metastasis.
The mainstay of HCC treatments today consists of surgery, radiotherapy, and chemotherapy. Surgical treatment is the most effective method, but the great majority patients with HCC have no chance for surgical treatment when the disease was
引文
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