Hasina R, Lingen M W
Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Medical Center Maywood, IL 60153, USA.
J Dent Educ. 2001 Nov;65(11):1282-90.
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that develops after years of chronic exposure to alcohol and tobacco products. Exposure to these agents results in alterations of genes that are important in the regulation of various cellular functions. This loss of regulation allows the tumor cells to survive and grow in an unchecked manner by allowing the cells to perform functions that contribute to the growth of the tumor. Some of these important changes include the acquisition of immortality and the ability to invade tissue and/or metastasize to other sights, as well as acquiring the ability to induce angiogenesis. Angiogenesis, the growth of new blood vessels from pre-existing ones, is a complex phenomenon that is absolutely required for the continued growth and survival of solid neoplasms. Without new blood vessels to provide nutrients and remove waste, tumors would be unable to grow larger than 2-3 mm in diameter. Therefore, one could envision its potential role in both the treatment and prevention of malignancies such as HNSCC. The concept of chemoprevention is extremely important in HNSCC since patients often develop multiple independent lesions throughout the mucosa of the upper aerodigestive tract. Therefore, the comprehensive treatment of this disease must address not only the initial primary neoplasm, but also prevent the progression of the premalignant lesions lurking throughout the rest of the mucosal surfaces. This review will outline the basic changes that occur in tumor cells that result in the switch to angiogenic phenotype. In addition, it will discuss the present status of using antiangiogenic agents in the treatment of cancer. Finally, this paper will present a rationale for the use of multiple antiangiogenic agents as a means of developing new chemotherapeutic and chemopreventive protocols that may result in reduced patient toxicity while maintaining similar clinical efficacies.
头颈部鳞状细胞癌（HNSCC）是一种侵袭性恶性肿瘤，在长期慢性接触酒精和烟草制品后发生。接触这些物质会导致对各种细胞功能调节至关重要的基因发生改变。这种调节的丧失使肿瘤细胞能够不受控制地存活和生长，因为细胞能够执行有助于肿瘤生长的功能。其中一些重要变化包括获得永生、侵袭组织和/或转移到其他部位的能力，以及获得诱导血管生成的能力。血管生成，即从已有的血管生长出新的血管，是一种复杂的现象，对于实体肿瘤的持续生长和存活绝对必要。没有新的血管来提供营养和清除废物，肿瘤直径将无法超过2 - 3毫米。因此，可以设想其在治疗和预防HNSCC等恶性肿瘤中的潜在作用。化学预防的概念在HNSCC中极其重要，因为患者通常会在上呼吸道消化道黏膜各处出现多个独立病变。因此，这种疾病的综合治疗不仅必须针对最初的原发性肿瘤，还必须预防潜伏在其余黏膜表面的癌前病变的进展。本综述将概述肿瘤细胞中导致向血管生成表型转变的基本变化。此外，还将讨论使用抗血管生成药物治疗癌症的现状。最后，本文将阐述使用多种抗血管生成药物作为开发新的化疗和化学预防方案的一种手段的基本原理，这些方案可能在保持相似临床疗效的同时降低患者毒性。
