The antiangiogenic effect of thalidomide on occult liver metastases: an in vivo study in mice.
OBJECTIVE
To investigate the morphological changes of intratumoral microvessels after administration of thalidomide in occult hepatic metastases.


METHODS
Twenty mice with hepatic metastases created by injection of colon-26 tumor cells into the spleen were enrolled. Ten mice were treated with thalidomide (200 mg/kg) by intraperitoneal injection daily from the first day after inoculation of tumor cells, and the other 10 with saline only. Fifteen days after tumor cell inoculation, the intratumoral microvessels of hepatic metastases in both groups were studied by intravital microscopy and immunohistochemistry.


RESULTS
For the control group, although the intratumoral microvessel density (MVD) and CD34 positive microvessel density (MVD-CD34) of larger metastases (> 400 microm in diameter) were more than those of small metastases respectively (P < 0.01), the intratumoral branch density (BD) was similar to that of small metastases (P > 0.05). For the thalidomide treated group, despite the fact that MVD-CD34 of larger metastases was more than that of small metastases (P < 0.01), the MVD and BD were similar to those of small metastases respectively (P > 0.05). The MVD, BD and MVD-CD34 of small metastases of both groups were similar (P > 0.05); however, those of large metastases in the thalidomide treated group were significantly lower than those in the control group (P < 0.01).


CONCLUSIONS
Thalidomide exerts an antiangiogenic effect on occult hepatic metastases with angiogenesis only, and the different vascular components in the tumor vasculature demonstrate various responses to antiangiogenic therapy.
Liu
Yi
Y
Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, China. liuli79@hotmail.com
Li
Hui
H
Matsui
Osamu
O
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013792:Thalidomide / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D013792:Thalidomide