The delicate balance of macrophages in colorectal cancer; their role in tumour development and therapeutic potential.

Most tumours are heavily infiltrated by immune cells. This has been correlated with either a good or a bad patient prognosis, depending on the (sub) type of immune cells. Macrophages represent one of the most prominent leukocyte populations in the majority of tumours. Functions of macrophages range from cytotoxicity, to stimulation of tumour growth by secretion of cytokines, growth and angiogenic factors, or suppressing immune responses. In most tumours macrophages are described as cells with immune suppressing, and wound healing properties, which aids tumour development. Yet, increasing evidence shows that macrophages are potent inhibitors of tumour growth in colorectal cancer. Macrophages in this respect show high plasticity. The presence of high macrophage numbers in the tumour may therefore become advantageous, if cells can be reprogrammed from tumour promoting macrophages into potent effector cells. Enhancing cytotoxic properties of macrophages by microbial products, pro-inflammatory cytokines or monoclonal antibody therapy are promising possibilities, and are currently tested in clinical trials.

Evaluation of peri-tumoral vessels surrounding colorectal liver metastases after intravenous injection of extruded magnetoliposomes in rats: correlation with 3T MRI and histopathology.

BACKGROUND: Magnetoliposomes have pronounced signal-enhancing effect on T1-weighted (T1w) images of the liver using qualitative analysis which may be benefical for demonstrating peritumoral vasculature. PURPOSE: To correlate peri-tumoral vasculature (ring-enhancement) surrounding colorectal liver metastases after injection of magnetoliposomes using T1-weighted (T1w) imaging with histopathology in a rat model. MATERIAL AND METHODS: All experiments were approved by the responsible Animal Care Committee. Three rats injected with CC531 coloncarcinoma cells in the portal vein were imaged at 3T using a small diameter four channel coil. The presence of liver metastases, signal intensity changes within intrahepatic vessels, peri-tumoral vasculature (ring-enhancement) surrounding liver metastases on T1w imaging and histopathology, and the histopathological distribution of iron particles were evaluated. SS SE-EPI and T1w GE sequences were used. Images were evaluated qualitatively and MRI findings were correlated with histopathology. RESULTS: Fifteen liver metastases were present which were all detected at MRI (mean diameter 2.4 mm (SD 0.8 mm, range 1.5-4.7 mm)). Ring-enhancement surrounding liver metastases at contrast-enhanced T1w GE sequences was present in all liver metastases. Correlation with histopathology showed the corresponding presence of dilated sinusoids filled with iron particles surrounding the liver metastases. CONCLUSION: Blood-pooling of iron oxide particles within magnetoliposomes was demonstrated with increased and hyperintensity of vessels after injection of magnetoliposomes. Qualitatively, ring-enhancement surrounding the liver metastases was seen on T1w imaging and corresponded histopathologically with the presence of iron particles (magnetoliposomes) within the dilated sinusoids surrounding the liver metastases.

Insufficient ability of omental milky spots to prevent peritoneal tumor outgrowth supports omentectomy in minimal residual disease.

BACKGROUND: The greater omentum is frequently involved in the course of gastrointestinal and ovarian tumors. Therefore, common practice in surgical treatment for especially gastric and ovarian cancer includes removal of the greater omentum. Paradoxically, many immune cells, such as macrophages that accumulate in so-called milky spots, reside within the omentum and are cytotoxic against tumor cells ex vivo. Consequently, omental macrophages might play an important role in killing tumor cells, and may hereby prevent development into local peritoneal recurrences. In the present study, we therefore evaluated the role of the omentum and the clinical relevance of omentectomy in minimal residual disease (MRD). METHODS: Tumor cell dissemination patterns on the omentum in a rat model were examined using DiI-labelled CC531s tumor cells. Additionally, intra peritoneal (i.p.) tumor load was investigated in rats that underwent omentectomy or sham laparotomy followed by i.p. injection of CC531s cells on day 21, which represented MRD. RESULTS: At 4 h post injection, tumor cells predominantly adhered on milky spots. Number of cells thereafter declined rapidly suggesting initial tumor killing functions in these specific immune aggregates. Despite initial reduction observed in milky spots, numbers of tumor cells however increased at fatty tissue stripes that border the omentum. This indicated proliferation at these locations, which corresponded to macroscopic observations of the omenta on day 21 after tumor cell injection. Omentectomy resulted in reduced intra-abdominal tumor load, which was completely attributable to the absence of the omentum, as tumor development did not differ on other sites. Even in the MRD group microscopic clusters of tumor cells located in the omentum eventually developed into macroscopic nodules. CONCLUSION: Since the ability of omental milky spots is, even in MRD, insufficient to prevent intra abdominal tumor outgrowth, omentectomy, which reduces tumor load, is recommended in surgical treatment of intra abdominal tumors that are prone to disseminate intraperitoneally.

Decreased smooth muscle cell/extracellular matrix ratio of media of femoral artery in patients with atherosclerosis and hyperhomocysteinemia.

The aim of this study was to determine whether the morphology of the muscular femoral artery in patients with atherosclerosis and hyperhomocysteinemia differs from that of atherosclerotic vessels from patients with normal homocysteine levels. Whole-vessel biopsies of the superficial femoral artery were taken from patients with symptomatic atherosclerotic disease with and without hyperhomocysteinemia and from patients without atherosclerosis from traumatic amputations. The morphology of these specimens was studied qualitatively by light and electron microscopy and quantitatively by light microscopy in combination with a video overlay system. Atherosclerotic lesions in patients with hyperhomocysteinemia were morphologically similar to those in patients with normal homocysteine levels, except for a significantly decreased smooth muscle cell/extracellular matrix ratio of the media in hyperhomocysteinemic patients (P=0.02 versus normohomocysteinemic atherosclerotic group and P=0.001 versus group without a history of cardiovascular disease). Hyperhomocysteinemia is associated with a significant decrease of the smooth muscle cell/extracellular matrix ratio of the media of muscular femoral arteries without significant changes in medial thickness. Further investigations should concentrate on the cause of this newly discovered phenomenon and its impact on vascular compliance.