In recent years, it was revealed that the tumor inhibitory effect of COS is probably related to their induction of lymphocyte cytokines through increasing T-cell proliferation (Figure 1). Basically, the antitumor mechanism of COS is enhanced by acquired immunity via accelerating T-cell differentiation to increase cytotoxicity and maintain T-cell activity [70]. Maeda and Kimura examined the antitumor effects of various low-molecular weight chitosans, such as water-soluble 21- or 46-kDa molecules with low viscosity, produced by enzymatic hydrolysis of over 650-kDa chitosan, which displayed decreased tumor growth and final tumor weight in sarcoma 180-bearing mice due to increase of natural killer cell activity [71,72]. The results indicate the low-molecular-weight water-soluble chitosans and oligochitosans might be useful in preventing tumor growth, partly through enhancing cytotoxic activity against tumors as an immunomodulator [73]. In transdermal delivery of baicalin for an useful drug for the treatment of skin disease, low-molecular-weight chitosans can improve its permeation through mouse skin [74]. In addition, they seem to activate macrophages via the production of cytokines such as interferon (IFN)-γ, interleukin (IL)-12 or -18 from the intraepithelial lymphocytes. In examination of the anticancer activity of chitosan derivatives, there was no clear information describing the relationship between charge properties and their observed activities. In recent years, in several cell lines, one research group observed that cancer-cell viability was significantly reduced regardless of the positive or negative charge of differently charged COS derivatives [75]. Moreover, COS significantly inhibited human hepatocellular (HepG2) carcinoma cell proliferation and down-regulated cell cycle-related gene expressions with decreased DNA content and up-regulation of p21 in vitro. In in vivo observations, COS inhibited tumor growth of HepG2 and Lewis lung carcinoma xenografts and lung tumor nodules as well as lung metastasis [76]. Quan et al. suggest that COS act as inhibitors of heparanase, which is a β-endoglucuronidase, and assist tumor invasion, metastasis and angiogenesis [77].