Giuseppe Chiarioni, Division of Gastrointestinal Rehabilitation, Azienda Ospedaliera di Verona, Ospedale di Valeggio s/M, 37067 Valeggio, Italy S- Editor Gou SX L- Editor Rutherford A E- Editor Zhang DN
Liver metastasis is the main cause of colorectal cancer-related mortality. those Death due to colorectal cancer is often a result of liver metastases. Despite extensive research into the biology of cancer progression, the molecular mechanisms involved in colorectal cancer metastasis are not well characterized.1 Several studies have demonstrated that CXCR4 and its ligand stromal cell-derived factor 1a (SDF-1) are highly expressed in tissues of metastatic growth, such as the lung, liver, and lymph nodes. CXCR4 is necessary for the outgrowth of colon cancer micrometastasis and significantly correlates with survival and liver metastasis.

2�C6 Alkaline phosphatase (ALP) has isoenzymes mainly derived from the leukocytes, bones, colon, placenta, kidneys, and liver.7,8 Elevated serum ALP levels are frequently associated with a variety of diseases, such as in patients with metastatic colorectal cancer.9 Kohne et al10 suggested that to stratify metastatic colorectal cancer patients in clinical trials, it is necessary to measure ALP, white blood cells, hemoglobin, and platelets. However, the significance of ALP in terms of detecting hepatic metastasis or prognosis is not well established. RNA interference was first identified as a defense mechanism against the invasion of foreign genes in the nematode Caenorhabditis elegans and has subsequently been discovered in diverse eukaryotes such as fungi, insects, plants, and vertebrates.

Researchers demonstrated that synthetic siRNAs are able to induce RNAi in mammalian cells.11 There are two types of small RNA molecules, microRNA or miRNA and small interfering RNA, sometimes known as siRNA or silencing RNA, which are central to RNA interference.12 Researchers demonstrated that inhibition of CXCR4 and its ligand CXCL12 signaling by siRNA knockdown has been found to reduce metastasis breast cancer.13 Delivery of therapeutic siRNA to specific tissues is a major challenge for systemic siRNA delivery. One reason is that the backbone of RNA contains ribose, which has a hydroxyl (OH) group in the 2�� position of the pentose ring instead of a hydrogen (H) atom. This extra hydroxyl group makes the RNA backbone more sensitive to hydrolysis.

14 Encapsulation generally provides much better protection Brefeldin_A of siRNAs against serum degradation than chemical modification.15,16 Azzam et al17,18 Hosseinkhani et al19 Eliyahu et al20 and Hosseinkhani et al21 showed that dextran engrafted spermine capable of complexing and transfecting various genes to different cell lines in vitro and in vivo. Dextran is a water-soluble polysaccharide with multiple hydroxyl groups applicable to chemical modification.