Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as versatile biomaterials because of their non-toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the recent research, trends and prospects in chitosan. Some special pharmaceutical and biomedical applications are also highlighted.

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Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications.

Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries. However, the majority of advanced stage melanoma patients do not respond or will relapse, and the hunt for the "magic bullet" to treat the disease continues. This review examines the mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies which are the two types of checkpoint inhibitors currently available to patients and further explores the future avenues of their use in melanoma and other cancers.

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Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations.

Background Food processing produces large quantities of by-products. Disposal of waste can lead to environmental and human health problems, yet often they can be turned into high value, useful products. For example, crustacean shell wastes from shrimp, crab, lobster, and krill contain large amounts of chitin, a polysaccharide that may be extracted after deproteinisation and demineralization of the exoskeletons. Scope and approach This review summarizes the current state of knowledge of these crustacean shellfish wastes and the various ways to use chitin. This biopolymer and its derivatives, such as chitosan, have many biological activities (e.g., anti-cancer, antioxidant, and immune-enhancing) and can be used in various applications (e.g., medical, cosmetic, food, and textile). Key findings and conclusions Due to the huge waste produced each year by the shellfish processing industry and the absence of waste management which represent an environmental hazard, the extraction of chitin from crustaceans’ shells may be a solution to minimize the waste and to produce valuable compound which possess biological properties with application in many fields. As a food waste, it is important to also be aware of the non-food uses of these wastes.

Industrial applications of crustacean by-products (chitin, chitosan, and chitooligosaccharides): A review

Chitosan as a bioactive polymer: Processing, properties and applications.

T-cell exhaustion was originally identified during chronic infection in mice, and was subsequently observed in humans with cancer. The exhausted T cells in the tumor microenvironment show overexpressed inhibitory receptors, decreased effector cytokine production and cytolytic activity, leading to the failure of cancer elimination. Restoring exhausted T cells represents an inspiring strategy for cancer treatment, which has yielded promising results and become a significant breakthrough in the cancer immunotherapy. In this review, we overview the updated understanding on the exhausted T cells in cancer and their potential regulatory mechanisms and discuss current therapeutic interventions targeting exhausted T cells in clinical trials.

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T-cell exhaustion in the tumor microenvironment

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.

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

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.

https://www.mdpi.com/2079-4983/6/1/33/pdf

Anticancer and Anti-Inflammatory Properties of Chitin and Chitosan Oligosaccharides

Chitin (β-(1-4)-poly-N-acetyl-D-glucosamine) is widely distributed in nature and is the second most abundant polysaccharide after cellulose. Chitin occurs in nature as ordered macrofibrils. It is the major structural component in the exoskeleton of crab and shrimp shells and the cell wall of fungi and yeast. As chitin is not readily dissolved in common solvents, it is often converted to its more deacetylated derivative, chitosan. Chitin, chitosan, and its derivatives are widely used in tissue engineering, wound healing, and as functional foods. Recently, easy methods for the preparation of chitin and chitosan nanofibers have been developed, and studies on biomedical applications of chitin and chitosan nanofibers are ongoing. Chitin and chitosan nanofibers are considered to have great potential for various biomedical applications, because they have several useful properties such as high specific surface area and high porosity. This review summarizes methods for the preparation of chitin and chitosan nanofibers. Further, biomedical applications of chitin and chitosan nanofibers in (i) tissue engineering, (ii) wound dressing, (iii) cosmetic and skin health, (iv) stem cell technology, (v) anti-cancer treatments and drug delivery, (vi) anti-inflammatory treatments, and (vii) obesity treatment are summarized. Many studies indicate that chitin and chitosan nanofibers are suitable materials for various biomedical applications.

Preparation and biomedical applications of chitin and chitosan nanofibers.

Biological adhesive based on carboxymethyl chitin derivatives and chitin nanofibers.

Carcinoma 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. Clinicopathologic 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. Tumors 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. Our 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.

Tomohiro Osaki

Papers

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

Anticancer and Anti-Inflammatory Properties of Chitin and Chitosan Oligosaccharides

Preparation and biomedical applications of chitin and chitosan nanofibers.

Biological adhesive based on carboxymethyl chitin derivatives and chitin nanofibers.

Distinct Recurrence Pattern and Outcome of Adenocarcinoma of the Gastric Cardia in Comparison with Carcinoma of Other Regions of the Stomach