Changes in the microvascular architecture of colorectal liver metastases following the administration of SMANCS/lipiodol.
BACKGROUND
Liver metastases are the major cause of death for patients with colorectal cancer. Surgical resection is at present the only curative option. Styrene maleic acid neocarzinostatin [SMANCS/Lipiodol (S/L)] targets the unique vascular architecture of tumor blood vessels, which are hyperpermeable and lack a well-developed lymphatic system. Here we report changes in the microvascular architecture of liver metastases by scanning electron microscopy (SEM) following the administration of S/L.


METHODS
Liver metastases were induced by the intrasplenic injection of dimethylhydrazine induced colon cancer cells in mice. In this model tumor angiogenesis occurs at day 10, while exponential tumor growth occurs at day 16. Changes in the tumor microvasculature were observed at 3 weeks following treatment with S/L at these time points by SEM of corrosion casts.


RESULTS
Tumors treated with S/L at day 10 appear similar to day 10 controls. Tumor vessels, 50 +/- 18 microm in diameter, are easily identified from hepatic vessels. Within the hepatic sinusoids are avascular spaces, 144 +/- 60 microm in diameter, which correspond to tumor cell aggregates at the initial stages of growth. Similarly, day 16 treated tumors appear comparable to day 16 controls. These vessels are narrower (84 +/- 32 microm vs. 150 +/- 70 microm) than their control counterparts. This is in contrast to vessels (216 +/- 36 microm in diameter) of a complex nature at 3 weeks.


CONCLUSIONS
S/L exerts a marked and immediate effect on the tumor microvessels at both the angiogenic and the exponential phases of tumor growth. This agent is effective at the microvascular level during inhibition of metastatic growth.
Kuruppu
Darshini
D
Monash University Department of Surgery, Alfred Hospital, Prahran, Victoria, 3181, Australia.
Christophi
C
C
Maeda
Hiroshi
H
O'Brien
Paul E
PE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003287:Contrast Media / Q000494:pharmacology; D016319:Corrosion Casting; D007459:Iodized Oil / Q000494:pharmacology; D008102:Liver Circulation / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008299:Maleic Anhydrides / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D008833:Microcirculation / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011137:Polystyrenes / Q000494:pharmacology*; D009353:Zinostatin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000970:Antineoplastic Agents; D003287:Contrast Media; D008299:Maleic Anhydrides; D011137:Polystyrenes; C035755:poly(maleic acid-styrene)neocarzinostatin; D007459:Iodized Oil; D009353:Zinostatin