Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model

Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model
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DOI:
10.1111/j.1349-7006.2003.tb01527.x
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发表时间:
2003-09-01
期刊:
影响因子:
5.7
通讯作者:
Ueda, M
Ueda, M
中科院分区:
医学2区
文献类型:
--
作者:
Hamaguchi, S;Tohnai, I;Ueda, M

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本文观察了热疗对雌性日本白色兔VX 7舌癌颈淋巴结转移的影响。磁性脂质体(ML)与中性表面电荷和94.1 nm的大小被用作加热介质。在肿瘤移植后20天将ML注射到舌中,我们检查它们是否到达转移性颈深淋巴结。ML注射后24小时,在淋巴结中检测到最高的磁铁矿浓度,其次是舌、脾、血液和肝脏。将家兔分为三组:I组作为对照; II组仅注射ML; III组注射ML并在ML注射后24 h进行热疗,通过向颈部区域施加交变磁场(118 kHz,384 Oe)产生。根据坏死与转移性肿瘤的比例百分比和凋亡指数(AI)(定义为TUNEL阳性细胞的比例)评价热效应。Ⅲ组淋巴结温度达44 ℃以上。Ⅲ组的平均坏死面积为58.0%,显著高于Ⅰ组(19.6%)和Ⅱ组(20.4%)。Ⅲ组AI为22.9%,显著高于Ⅰ组(1.67%)和Ⅱ组(1.42%)。组I和组II之间的差异无统计学显著性。第三组肿瘤部位周围的ML显示坏死或凋亡阳性细胞诱导的高温。这些结果表明,注射到舌中的ML可以靶向颈部淋巴结转移,并以足以产生治疗有效温度的浓度在那里积累。
The effect of hyperthermia on cervical lymph node metastasis of VX7 tongue cancer in female Japanese white rabbits was investigated. Magnetoliposomes (MLs) with a neutral surface charge and a size of 94.1 nm were used as heating mediators. MLs were injected into the tongue 20 days after tumor transplantation, and we examined whether they reached the metastatic deep cervical lymph node. The highest magnetite concentration 24 h after ML injection was detected in the lymph node, followed by tongue, spleen, blood, and liver. Rabbits were separated into three groups: group I as the control; group II with ML injection alone; and group III with ML injection and hyperthermia 24 h after ML injection, generated by applying an alternating magnetic field (118 kHz, 384 Oe) to the neck region. The hyperthermic effect was evaluated in terms of the percentage of necrosis in proportion to the metastatic tumor and the apoptotic index (AI), defined as the ratio of TUNEL-positive cells. The temperature of lymph nodes in group III reached over 44 C. The mean area of necrosis in group III was 58.0%, which was significantly higher than that in group I (19.6%) or group II (20.4%). The AI in group III was 22.9%, significantly higher than in group I (1.67%) or II (1.42%). The difference between group I and II was not statistically significant. Group III tumor sites around MLs showed necrosis or apoptosis-positive cells induced by hyperthermia. These results indicate that MLs injected into the tongue can target cervical lymph node metastases and accumulate there at concentrations sufficient to generate therapeutically effective temperatures.