Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune-response induction in transplanted syngeneic rats.
BACKGROUND
The hyperthermic effect of magnetic particles was examined in rat prostate cancer in vivo. Magnetic cationic liposomes (MCLs) have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis losses.


METHODS
Rat prostate cancer cells (PLS 10; androgen independent) were injected subcutaneously into the flank of F344 rats. MCLs were injected into rat prostate cancer nodules that had grown to 5-6 mm in diameter, and were then exposed to an AMF. Tumor growth rates were measured. To examine whether hyperthermia caused immune induction for PLS 10, cytotoxicity assays and immunohistochemical staining for CD3, CD4, CD8, and Heat Shock Protein (HSP) 70 were performed.


RESULTS
The tumor temperature increased to 45 degrees C whereas the body temperature remained at around 38 degrees C. Tumor regression was observed in the hyperthermic group. CD3, CD4, and CD8 immunocytes were present in the tumor tissues of the rats exposed to hyperthermia, but they were not detected in any of the tumor tissue of untreated rats. HSP70 also appeared in the viable area at its boundary with the necrotic area. The cytotoxic activity of tumor-transplanted rats for PLS 10 cells increased in hyperthermic-treatment rats.


CONCLUSIONS
These results suggest that hyperthermia using MCLs is an effective therapy for prostate cancer, since this treatment appears to kill the prostate cancer cells not only directly by heating but also by inducing an immune response. This therapy may cure not only the primary lesion but also metastatic lesions.
Kawai
Noriyasu
N
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. norikawa@med.nagoya-cu.ac.jp
Ito
Akira
A
Nakahara
Yoko
Y
Futakuchi
Mitsuru
M
Shirai
Tomoyuki
T
Honda
Hiroyuki
H
Kobayashi
Takeshi
T
Kohri
Kenjiro
K
D000818:Animals; D002412:Cations; D002455:Cell Division; D052203:Ferrosoferric Oxide; D006979:Hyperthermia, Induced / Q000295:instrumentation / Q000379:methods*; D007501:Iron / Q000494:pharmacology*; D008081:Liposomes / Q000494:pharmacology; D008280:Magnetics / Q000627:therapeutic use*; D008297:Male; D009368:Neoplasm Transplantation; D010087:Oxides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D002412:Cations; D008081:Liposomes; D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide