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[肿瘤转移的诊断与治疗]

[Diagnosis and treatment of tumor metastases].

作者信息

Petruzelka L

机构信息

Onkologická klinika 1. lékarské fakulty UK a VFN, Praha.

出版信息

Vnitr Lek. 2001 Aug;47(8):555-60.

Abstract

More than half the patients with malignat tumours have at the time of diagnosis already remote metastases or they develop remote dissemination after different intervals following termination of local treatment. Organ complications in case of metastatic dissemination are for the majority of patients the most life threatening condition. In therapeutic decisions the approach to some solid tumours is the same as in systemic diseases. The possibility to achieve a long-term therapeutic effect during conventional systemic therapy are limited in metastatizing solid tumours of adult age. Assessment of the extent of the disease incl. detection of metastatic dissemination is of decisive importance for the selection of therapeutic strategy. Imaging methods such as computed tomography, ultrasonography and nuclear magnetic resonance provide basic structural anatomic information. The limitating factor is obtaining functional information on tumor tissues and the possibility to differentiate the residual disease from non-viable or necrotic tumor masses. These data can be provided by radiopharmacological imaging methods such as positron emission tomography. Introduction of new imaging methods is becoming increasingly important when new therapeutic methods are used where the effect of the therapeutic result does not mean necessarily reduction of the tumour volume. Research of the metastatic process involved revolutionary changese lucidating individual stages linked in a cascade pattern. The metastatic potential of human tumours correlates with the expression of a number of genes regulating tumour growth (EGF - epidermal growth factor, IGF - insulin like growth factor) motility of tumour cells (AMF - autocrine motility factor) the process of angiogenesis (VEGF vascular endothelial growth factor, bFGF - basal fibroblastic growth factor, interleukin-8) and the invasiveness (genes for the matrix of metalloproteinase MMP-2/MMP-9). Expression of the surface glycoporotein E-cadherin which influences the cohesiveness of cells is in an inverse relationship with the invasiveness and metastatic potential. Identification of the appropriate genes in a heterogeneous tumour population calls for multiparametric, multivariation analysis of gene expression. Understanding of this complex problem opened new possibilities of therapeutic action and improved curability of neoplastic diseases in all stages of the disease. Gradual more detailed understanding of individual stages of a multigrade process of metastatizing helped to reveal new potential target structures for treatment. In the process of angiogenesis these are metalloproteinases, angiogenic growth factors, endothelial cells and vascular structures of tumours. Practical use for therapeutic purposes will develop on the basis of results of clinical studies which are underway.

摘要

超过半数的恶性肿瘤患者在确诊时已出现远处转移,或者在局部治疗结束后的不同时间段内发生远处播散。对于大多数患者而言,转移性播散导致的器官并发症是最危及生命的情况。在治疗决策中,针对某些实体瘤的治疗方法与治疗全身性疾病相同。在常规全身治疗期间,实现长期治疗效果的可能性在成年转移性实体瘤中有限。评估疾病范围,包括检测转移性播散,对于选择治疗策略至关重要。诸如计算机断层扫描、超声检查和核磁共振等成像方法可提供基本的结构解剖信息。限制因素在于获取肿瘤组织的功能信息以及区分残留病灶与无活力或坏死肿瘤块的可能性。这些数据可由正电子发射断层扫描等放射性药物成像方法提供。当使用新的治疗方法时,引入新的成像方法变得越来越重要,因为治疗结果的效果不一定意味着肿瘤体积的缩小。对转移过程的研究涉及揭示以级联模式相连的各个阶段的革命性变化。人类肿瘤的转移潜能与许多调节肿瘤生长的基因(如表皮生长因子EGF、胰岛素样生长因子IGF)、肿瘤细胞的运动性(自分泌运动因子AMF)、血管生成过程(血管内皮生长因子VEGF、碱性成纤维细胞生长因子bFGF、白细胞介素-8)以及侵袭性(基质金属蛋白酶MMP-2/MMP-9的基因)的表达相关。影响细胞黏附性的表面糖蛋白E-钙黏蛋白的表达与侵袭性和转移潜能呈负相关。在异质性肿瘤群体中识别合适的基因需要对基因表达进行多参数、多变量分析。对这一复杂问题的理解为治疗行动开辟了新的可能性,并提高了肿瘤疾病在各个阶段的治愈率。对转移性多级过程各个阶段的逐步更详细理解有助于揭示新的潜在治疗靶点结构。在血管生成过程中,这些靶点包括金属蛋白酶、血管生成生长因子、内皮细胞和肿瘤的血管结构。基于正在进行的临床研究结果,将开发其治疗用途。

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