Tomohiro Osaki

Chitin, Chitosan, and Its Derivatives for Wound Healing: Old and New Materials

Chitin (β-(1-4)-poly-N-acetyl-d-glucosamine) is widely distributed in nature and is the second most abundant polysaccharide after cellulose. It is often converted to its more deacetylated derivative, chitosan. Previously, many reports have indicated the accelerating effects of chitin, chitosan, and its derivatives on wound healing. More recently, chemically modified or nano-fibrous chitin and chitosan have been developed, and their effects on wound healing have been evaluated. In this review, the studies on the wound-healing effects of chitin, chitosan, and its derivatives are summarized. Moreover, the development of adhesive-based chitin and chitosan are also described. The evidence indicates that chitin, chitosan, and its derivatives are beneficial for the wound healing process. More recently, it is also indicate that some nano-based materials from chitin and chitosan are beneficial than chitin and chitosan for wound healing. Clinical applications of nano-based chitin and chitosan are also expected.

Distinct recurrence pattern and outcome of adenocarcinoma of the gastric cardia in comparison with carcinoma of other regions of the stomach

BackgroundCarcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. The prognosis for adenocarcinoma of the upper stomach is considered to be relatively poorer than carcinomas of the more distal stomach. We have therefore investigated patients with carcinoma of the gastric cardia in order to evaluate the underlying cause of this poor prognosis.Materials and MethodsClinicopathologic features and postoperative prognosis of 101 patients with carcinoma of the cardia were evaluated and compared with findings on 1884 patients with tumors in other regions of the stomach.ResultsTumors of the cardia had a mean size of 6.8 cm, which was significantly larger than the mean size of 5.9 cm for tumors found in the middle- and lower third of the stomach. The incidence of serosal invasion, lymph node metastasis, and lymphatic and blood vessel invasion was higher in association with adenocarcinoma of the cardia than with adenocarcinoma in remaining parts of the stomach. In the analysis of patients who had undergone curative resection, the 5-year survival rates were 61.6, 79.1, and 82.6% in patients with carcinoma of the cardia, upper one-third, and remaining middle- and lower one-third of the stomach, respectively, and the differences were statistically significant. Multivariate analysis indicated that adenocarcinoma of the gastric cardia is an independent prognostic factor. With regard to the site of recurrence, both lymph node and hematogenous recurrence were observed more frequently in the cardia than in the remaining parts of the stomach.ConclusionsOur data indicate that the prognosis of patients with adenocarcinoma of the gastric cardia is extremely poor. To improve their prognosis, new treatments in addition to gastrectomy with extensive lymph node dissection are needed.

Anticancer and Anti-Inflammatory Properties of Chitin and Chitosan Oligosaccharides

Previous reports indicate that N-acetyl-d-glucosamine oligomers (chitin oligosaccharide; NACOS) and d-glucosamine oligomers (chitosan oligosaccharide; COS) have various biological activities, especially against cancer and inflammation. In this review, we have summarized the findings of previous investigations that have focused on anticancer or anti-inflammatory properties of NACOS and COS. Moreover, we have introduced recent evaluation of NACOS and COS as functional foods against cancer and inflammatory disease.

EFFECT OF AGE ON PROGNOSIS IN PATIENTS WITH GASTRIC CANCER

Background:  The incidence of gastric cancer among the elderly has recently been increasing; however, the prognostic value of age in patients with gastric cancer remains elusive.

Decreased NKG2D Expression on CD8+ T Cell Is Involved in Immune Evasion in Patients with Gastric Cancer

Purpose: Some studies suggest that the immunoreceptor NKG2D expression on CD8+ T cells is down-regulated and this reduction may be involved in immune evasion in cancer patients. The present study was designed to investigate NKG2D expression on CD8+ T lymphocytes and its relationship to immune evasion in gastric cancer patients. Experimental Design: NKG2D expression on both circulating and tumor-infiltrating CD8+ T cells was evaluated by multicolor flow cytometry. Soluble MHC class I chain-related gene A (MICA) in the sera was quantitated by ELISA. Transwell experiments were carried out to determine the effect of cancer cells on NKG2D expression. Results: NKG2D expression on circulating CD8+ T cells was down-regulated and significantly correlated with IFN-γ production in gastric cancer patients (r = 0.68; P = 0.007). NKG2D expression was closely related to undifferentiated cancer (P = 0.021) as was the depth of invasion (P = 0.012). There was no difference in soluble MICA between gastric cancer patients and normal controls. NKG2D expression on CD8+ T cells was remarkably reduced in the tissue of gastric cancer compared with peripheral blood (P = 0.046). Complete removal of tumor by surgery restored NKG2D expression on CD8+ T cells (P = 0.0049). Transwell experiments showed that this down-regulation was induced by direct contact between cancer cells and CD8+ T cells and that soluble factors did not affect the NKG2D expression. This phenomenon was blocked by the addition of anti-MICA antibodies. Conclusions: Decreased NKG2D expression may be one of the key mechanisms responsible for immune evasion by tumors in gastric cancer.

Increased PD‐1 expression on CD4+ and CD8+ T cells is involved in immune evasion in gastric cancer

Co‐signaling molecules play an important role in T cells. Programmed death‐1 (PD‐1) is an immunoinhibitory receptor and its overexpression on T cells appears to be involved in immune evasion in cancer patients. The present study was designed to investigate PD‐1 expression on T cells and its relationship with immune evasion in gastric cancer patients.

Expression of phosphorylated Akt (pAkt) in gastric carcinoma predicts prognosis and efficacy of chemotherapy

BackgroundThe Akt signaling pathway controls the survival and growth of human cancers. We investigated the expression of phosphorylated Akt (pAkt) in patients with gastric cancer.MethodsThe expression of pAkt was immunohistochemically examined in 140 gastric cancer patients who underwent a gastrectomy. The expression of pAkt was evaluated based on staining intensity, and staining was classified as negative or positive. We examined the expression of pAkt and its association with the clinicopathological findings, prognosis, depth of invasion, the expression of p53, and efficacy of oral fluorouracil chemotherapy after surgery.ResultsExpression of pAkt was positive in 81 (58%) patients and negative in 59 (42%) patients. There were no significant correlations between pAkt expression and the clinicopathological findings. The prognosis of patients with pAkt-negative tumors was superior to that of patients with pAkt-positive tumors, and the difference was significant for T3/T4 gastric cancer (P < 0.05). Among the patients with T3/T4 gastric cancer, postoperative oral fluorouracil treatment was effective in those who were pAkt-positive. Multivariate analysis revealed that pAkt expression and lymph node metastasis were independent prognostic factors. In 88 patients with T3 gastric carcinoma who had undergone curative surgery, in whom we studied the prognostic impact of a combined analysis of pAkt and p53 expression, patients with both pAkt- and p53-positive tumors showed a significantly poorer prognosis than patients with either or both pAkt- and p53-negative tumors (P < 0.05).ConclusionOur results indicate that pAkt expression may be useful for predicting the prognosis and efficacy of fluorouracil treatment in patients with gastric cancer.

Effects of oral administration of fucoidan extracted from Cladosiphon okamuranus on tumor growth and survival time in a tumor-bearing mouse model

We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa), intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa) and high-molecular-weight fucoidan (HMWF: 300–330 kDa). The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet). The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.

α-Chitin nanofibrils improve inflammatory and fibrosis responses in inflammatory bowel disease mice model

We evaluated the anti-inflammatory and anti-fibrosis effects of α-chitin nanofibrils in a mouse model of dextran sulfate sodium (DSS)-induced acute ulcerative colitis (UC). α-Chitin nanofibrils decreased positive areas of nuclear factor-κB staining in the colon tissue (7.2±0.5%/fields in the α-chitin nanofibrils group vs. 10.7±0.9%/fields in the control group; p<0.05). α-Chitin nanofibrils also decreased serum monocyte chemotactic protein-1 concentration in DSS-induced acute UC (24.1±7.8 pg/ml in the α-chitin nanofibrils group vs. 53.5±3.1 pg/ml in the control group; p<0.05). Moreover, α-chitin nanofibrils suppressed the increased positive areas of Massons trichrome staining in colon tissue (6.8±0.6%/fields in the α-chitin nanofibrils group vs. 10.1±0.7%/fields in the control group; p<0.05). On the other hand, α-chitin powder suspension did not show these effects in DSS-induced acute UC mice model. Our results indicated that α-chitin nanofibrils have the anti-inflammatory effect via suppressing NF-κB activation and the anti-fibrosis effects in DSS-induced acute UC mice model.

Evaluation of the effects of chitin nanofibrils on skin function using skin models.

Chitins are highly crystalline structures that are predominantly found in crustacean shells. Alpha-chitin is composed of microfibers, which are made up of nanofibrils that are 2-5 nm in diameter and 30 nm in length and embedded in a protein matrix. Crystalline nanofibrils can also be prepared by acid treatment. We verified the effect of chitin nanofibrils (NF) and nanocrystals (NC) on skin using a three-dimensional skin culture model and Franz cells. The application of NF and NC to skin improved the epithelial granular layer and increased granular density. Furthermore, NF and NC application to the skin resulted in a lower production of TGF-β compared to that of the control group. NF and NC might have protective effects to skin. Therefore, their potential use as components of skin-protective formulations merits consideration.