Abstract: A number of reports suggest that hyperthermia is an effective adjunctive treatment modality in management of neural crest tumors. Recent studies have demonstrated a synergistic effect of induced hyperthermia when coupled with chloroquine in an in vitro model. This study examines the effect of chloroquine and hyperthermia in an in vivo murine neuroblastoma model. Forty-seven Ajax white mice (weighing 20 to 30 g) received a subaxillary tumor burden (C-1300 murine neuoblastoma) per trochar (1.25 × 106 cells). The tumor was then incubated for 9 days. Mice were then divided into four groups: group 1, controls (n = 15); group 2, hyperthermia (n = 12); group 3, chloroquine (n = 10); and group 4, chloroquine with hyperthermia (n = 10). Hyperthermia was induced with 40 to 69 mW/cm2 at 2,450 MHz microwave radiation for 4 minutes to achieve a temperature of 41.5°C for 10 of 14 treatment days. Chloroquine was administered intraperitoneally at a dose of 40 mg/kg body weight for 10 of 14 treatment days. Mice were weighed and tumor size was determined daily. Animals were killed on day 21 and postmortem examination was performed, with tumors graded histologically. Animal weight, tumor weight, and tumor size were similar for all groups (P > .05). Mortality was 6% in group 1, 25% in group 2, 50% in group 3, and 40% in group 4 (P < .05). Rate of tumor metastases was also statistically different from controls: group 1, 0%; group 2, 60%; group 3, 90%; and group 4, 90% (P < .05). Chloroquine acts by altering lysosomal function and as a DNARNA polymerase inhibitor. In vitro this mechanism apparently allows for increased tumor kill when hyperthermia is added. However, in the in vivo model, inhibition of host rapid cell replication (reticuloendothelial system, and white cell production) by chloroquine may explain the increased incidence of metastatic spread and mortality. In addition, microwave-induced hyperthermia alone (previously reported to reduce tumor burden) when administered in a repeated fashion also resulted in an increased metastatic rate. This may be due to increased tumor perfusion and seeding as a result of a chronically induced hyperemic state.

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003001 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003001 | SxmlIndent | more

{{Explor lien
   |wiki=    Sante
   |area=    ChloroquineV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     ISTEX:30B9008C771B81BC01E9C4C21693983AF89B8D19
   |texte=   The effect of chloroquine and hyperthermia on murine neuroblastoma
}}