Disposition characteristics of macromolecules in the perfused tissue-isolated tumor preparation.
Disposition characteristics of macromolecules in the perfused tissue-isolated tumor preparation.
复制标题
灌注组织分离肿瘤制剂中大分子的分布特征。
作者：
H. Imoto;Y. Sakamura;K. Ohkouchi;R. Atsumi;Y. Takakura;H. Sezaki;M. Hashida
采用单通道血管灌注技术，研究了具有不同理化特性的模型大分子和丝裂霉素 C 大分子前药（即丝裂霉素 C-葡聚糖缀合物）在 Walker 256 癌组织分离肿瘤制剂中的分布特征。在持续输注实验中，所有放射性标记的大分子都在肿瘤组织中积累，但分布的程度和模式差异很大，具体取决于它们的电荷。与中性或带负电的大分子相比，带正电的大分子显着积累。此外，它们在活体区域的浓度显着高于坏死区域，而中性和阴性化合物分布在坏死区域而不是活体区域。带正电荷的二乙氨基乙基和中性葡聚糖的组织浓度-时间过程的药代动力学分析表明，它们的运动是通过对流流体流动发生的，并且带正电荷的大分子的高组织积累可以通过静电相互作用产生的强结合来解释。对于与组织的亲和力可忽略不计的中性和阴离子大分子，建议活区和坏死区之间的最终浓度梯度由其组织液含量决定。因此，本研究揭示了肿瘤组织中大分子与其理化性质相关的基本配置特征。
Disposition characteristics of model macromolecules with different physicochemical characteristics and macromolecular prodrugs of mitomycin C, namely mitomycin C-dextran conjugates, were studied in tissue-isolated tumor preparations of Walker 256 carcinoma with the use of a single-pass vascular perfusion technique. In constant infusion experiments, all radiolabeled macromolecules accumulated in the tumor tissue, but the degree and pattern of distribution greatly varied, depending on their electric charges. Positively charged macromolecules were markedly accumulated compared with those that were neutral or negatively charged. In addition, their concentrations were significantly higher in viable than in necrotic regions, while neutral and negative compounds were distributed in necrotic rather than in viable regions. Pharmacokinetic analysis of tissue concentration-time courses of positively charged diethylaminoethyl and neutral dextrans showed that their movement occurred by convective fluid flow, and that high tissue accumulation of positively charged macromolecules could be explained by strong binding due to electrostatic interaction. For neutral and anionic macromolecules with negligible affinity to the tissue, it was suggested that the final concentration gradient between the viable and necrotic regions was decided by their tissue fluid content. Thus, the present study revealed the basic disposition characteristics of macromolecules in tumor tissue relative to their physicochemical properties.
影响因子：
11.2
作者：
Y. Boucher;L. T. Baxter;R. Jain
通讯作者：
Y. Boucher;L. T. Baxter;R. Jain
影响因子：
11.2
作者：
Y. Matsumura;H. Maeda
通讯作者：
Y. Matsumura;H. Maeda