Architectural heterogeneity in tumors caused by differentiation alters intratumoral drug distribution and affects therapeutic synergy of antiangiogenic organoselenium compound.
Architectural heterogeneity in tumors caused by differentiation alters intratumoral drug distribution and affects therapeutic synergy of antiangiogenic organoselenium compound.
复制标题
DOI：
10.1155/2010/396286
复制
发表时间：
2010
影响因子：
--
通讯作者：
Bhattacharya A
中科院分区：
文献类型：
--
作者：
Rustum YM;Tóth K;Seshadri M;Sen A;Durrani FA;Stott E;Morrison CD;Cao S;Bhattacharya A
肿瘤分化增强了形态学和微血管异质性，促进了缺氧，这阻碍了肿瘤内药物递送、分布并损害了治疗效果。在这项研究中，肿瘤生物异质性的细胞毒性化疗和硒之间的相互作用的影响进行了检查，使用面板的人肿瘤异种移植物代表癌症的头部和颈部和肺部沿着与组织微阵列分析的人手术样本。肿瘤分化状态、微血管密度、间质液压力、血管表型和药物递送与硒增强化疗疗效的程度相关。在H69肿瘤中观察到抗肿瘤活性的显著增强，该肿瘤表现出良好的血管化、低分化表型。相比之下，抗血管生成硒对化疗疗效的调节在具有多个无血管缺氧分化区域的分化良好的肿瘤中通常较低或不存在。肿瘤组织形态学异质性在研究的临床样本中普遍存在，代表了化疗的主要和关键生理障碍。
Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.