title: Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model.
abstract: 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 degrees 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan. shigeaki@med.nagoya-u.ac.jp
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Hamaguchi
authors.forename: Iwai
authors.initials: I
authors.lastname: Tohnai
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Kenji
authors.initials: K
authors.lastname: Mitsudo
authors.forename: Toshio
authors.initials: T
authors.lastname: Shigetomi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Minoru
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000556:secondary / Q000628:therapy*; D005260:Female; D006979:Hyperthermia, Induced; D008081:Liposomes; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000517:prevention & control; D008280:Magnetics / Q000627:therapeutic use*; D009333:Neck; D011817:Rabbits; D013696:Temperature; D014062:Tongue Neoplasms / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: D008081:Liposomes