Advances in chitosan-based drug delivery systems in melanoma: A narrative review.

Melanoma accounts for the minority of skin cancer cases. However, it has the highest mortality rate among the subtypes of skin cancer. At the early stages of the disease, patients show a good prognosis after the surgery, but developing metastases leads to a remarkable drop in patients' 5-year survival rate. Despite the advances made in the therapeutic approaches to this disease, melanoma treatment is still facing several obstacles. Systemic toxicity, water insolubility, instability, lack of proper biodistribution, inadequate cellular penetration, and rapid clearance are some of the challenges that should be addressed in the field of melanoma treatment. While various delivery systems have been developed to circumvent these challenges, chitosan-based delivery platforms have indicated significant success. Chitosan that is produced by the deacetylation of chitin can be formulated into different materials (e.g., nanoparticle, film, and hydrogel) due to its characteristics. Both in vitro and in vivo studies have reported that chitosan-based materials can be used in drug delivery systems while offering a solution for the common problems in this area, such as enhancing biodistribution and skin penetration as well as the sustained release of the drugs. Herein, we reviewed the studies concerning the role of chitosan as a drug delivery system in melanoma and discussed how these drug systems are used for delivering chemotherapeutic drugs (e.g., doxorubicin and paclitaxel), genes (e.g., TRAIL), and RNAs (e.g., miRNA199a and STAT3 siRNA) successfully. Furthermore, we take a look into the role of chitosan-based nanoparticles in neutron capture therapy.

CircRNAs: A Novel Strategy in Diagnosis and Treatment of Thyroid Cancer.

Thyroid cancer is one of the most frequent cancers globally, and its incidence has risen recently. The clinical behavior of thyroid cancer includes a wide range, from benign to invasive malignant tumors. Thus, precious diagnostic activities before therapeutic work are required. Circular RNAs (circRNAs) along with microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are known as non-coding RNAs (ncRNAs). Large amounts of investigations have indicated that circRNAs can participate in multiple cellular processes, especially in tumorigenesis. Furthermore, circRNAs are stable in blood or plasma, as well as they are specific in different tissues. Therefore, they could serve as a potential diagnostic biomarker for cancer cells. Limited studies investigated the role of circRNAs in some processes involved in thyroid cancer. In this review, we summarized the current evidence on the potential clinical involvement of circRNAs in thyroid cancer.

Cervical Cancer and Novel Therapeutic and Diagnostic Approaches using Chitosan as a Carrier: A Review.

In our knowledge, using appropriate carriers in the delivery of chemotherapeutic drugs, would result in better targeting and therefore it would increase the effectiveness and decrease the side effects of drugs. Chitosan, a natural polymer derived from chitin, has attracted the attention of pharmaceutical industries recently. New research works show that chitosan can not only be used in drug delivery but it can also have some usages in the prevention and diagnosis of cancer. This means that using chitosan Nanoformulations can be a promising approach for prevention, diagnosis, and specially treatment of cervical cancer, the fourth common cancer among the women of the world. We aim to investigate the related papers to find a novel method and preventing more women from suffering.

Effects of Berberine on Leukemia with a Focus on Its Molecular Targets.

Leukemia is common among both women and men worldwide. Besides the fact that finding new treatment methods may enhance the life quality of patients, there are several problems that we face today in treating leukemia patients, such as drugs' side effects and acquired resistance to chemotherapeutic drugs. Berberine is a bioactive alkaloid found in herbal plants (e.g., Rhizoma coptidis and Cortex phellodendri) and exerts several beneficial functions, including anti-tumor activities. Furthermore, berberine exerts antiproliferative and anti-inflammatory effects. Up to now, some studies have investigated the roles of berberine in different types of leukemia, including acute myeloid leukemia and chronic lymphocytic leukemia. In this review, a detailed description of the roles of berberine in leukemia is provided. We discuss how berberine involves different molecular targets (e.g., interleukins and cyclins) and signaling pathways (e.g., mTOR and PI3K) to exert its anti-tumor functions and how berberine is effective in leukemia treatment when combined with other therapeutic drugs.

Resveratrol and Cardiac Fibrosis Prevention and Treatment.

Cardiovascular diseases are some of the major causes of morbidity and mortality in developed and developing countries. Cardiac fibrosis is one of the most often pathological changes of heart tissues. It occurs as a result of extracellular matrix proteins accumulation at myocardia. Cardiac fibrosis results in impaired cardiac systolic and diastolic functions and is associated with other effects. Therapies with medicines have not been sufficiently successful in treating chronic diseases such as CVD. Therefore, the interest for therapeutic potential of natural compounds and medicinal plants has increased. Plants such as grapes, berries and peanuts contain a polyphenolic compound called "resveratrol" which has been reported to have various therapeutic properties for a variety of diseases. Studies on laboratory models show that resveratrol has beneficial effects on cardiovascular diseases, including myocardial infarction, high blood pressure cardiomyopathy, thrombosis, cardiac fibrosis, and atherosclerosis. In vitro animal models using resveratrol indicated protective effects on the heart by neutralizing reactive oxygen species, preventing inflammation, increasing neoangiogenesis, dilating blood vessels, suppressing apoptosis and delaying atherosclerosis. In this review, we are presenting experimental and clinical results of studies concerning resveratrol effects on cardiac fibrosis as a CVD outcome in humans.

Beta-glucans is a Potential Inhibitor of Ovarian Cancer: Based on Molecular and Biological Aspects.

Ovarian cancer is a lethal type of cancer which is initiated to the ovaries and affects 1 out of every 75 women. Due to the high number of deaths (almost 152,000) related to this cancer, it seems that novel efficient therapeutic methods are required in this field. Beta-glucans are a type of glucose linear polymers which have been proven to have a lot of advantageous activities. Recently, investigations have declared that these polysaccharides have the potential to be used as anti-cancer drugs. These agents are able to affect several mechanisms such as inflammation and apoptosis, and that is how cancers are prone to be affected by them. In this review, we attempt to investigate the role of beta-glucans on ovarian cancer. We hope that this paper would give some novel insights into the field of ovarian cancer treatment.

The Effects of Sterol-Related Signaling Pathways on Glioma.

Gliomas are considered as one of the important brain tumors in adults due to their impact on life quality and cognitive functions. Current methods that are used for treating glioma are not satisfying enough. Understanding cellular and molecular events underlying its pathogenesis and progression may lead to the discovery of novel therapeutic approaches. Sterols are a subtype of steroids and are essential for the physiologic functions of eukaryotic cells. Sterols can be produced by protozoans and microheterotrophs. Moreover, they are found in some natural sources, such as plants, animals, fungi, microalgae, and yeasts. Besides the roles of sterols in physiologic processes, studies have shown that they are involved in pathologic processes, including tumorigenesis and tumor progression. As investigations have revealed, sterol-related signaling pathways are involved in glioma and targeting them may result in new therapeutic options for patients. Thus, we summarized some of the sterol-related signaling pathways in glioma and how they can be associated with other signaling pathways, including EGFR/PI3K/Akt/mTOR, P53, and retinoblastoma protein.

Chitosan as possible inhibitory agents and delivery systems in leukemia.

Leukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.

Nanocellulose-based Delivery Systems and Cervical Cancer: Review of the Literature.

It has become clear that targeted therapy is one of the best options for decreasing the unpleasant side effects of existing common methods and reducing the number of deaths occurred due to many types of cancer. Biocompatible and non-toxic delivery systems are provided by nanomedicine for aiding targeted therapy in many diseases containing cancer. Cervical cancer (CC) is not only the most common gynecological cancer but also is ranked as the fourth common cancer between both men and women. Chemotherapy, radiotherapy, surgery, and immunotherapy are the approaches, which are being used for treating CC patients. However, more efficacy of these methods can be achieved with the help of nanomedicine and novel delivery systems. Nanocellulose is one of the agents used for designing these systems in order to deliver different drugs to a diversity of cancerous cells. In this review, we aim to investigate the competency of nanocellulose for establishing novel therapeutic methods for cervical cancer. We hope that our results help develop more drug delivery systems for targeted therapy to reduce the side effects and induce the efficacy of anti-cancer drugs.

Molecular and biological functions of gingerol as a natural effective therapeutic drug for cervical cancer.

Cervical cancer is one of the most common and important gynecological cancers, which has a global concern with an increasing number of patients and mortality rates. Today, most women in the world who suffer from cervical cancer are developing advanced stages of the disease. Smoking and even exposure to secondhand smoke, infections caused by the human papillomavirus, immune system dysfunction and high-risk individual-social behaviors are among the most important predisposing factors for this type of cancer. In addition, papilloma virus infection plays a more prominent role in cervical cancer. Surgery, chemotherapy or radical hysterectomy, and radiotherapy are effective treatments for this condition, the side effects of these methods endanger a person's quality of life and cause other problems in other parts of the body. Studies show that herbal medicines, including taxol, camptothecin and combretastatins, have been shown to be effective in treating cervical cancer. Ginger (Zingiber officinale, Zingiberaceae) is one of the plants with valuable compounds such as gingerols, paradols and shogoals, which is a rich source of antioxidants, anti-cancer and anti-inflammatory agents. Numerous studies have reported the therapeutic effects of this plant through various pathways in cervical cancer. In this article, we look at the signaling mechanisms and pathways in which ginger is used to treat cervical cancer.

The role of DNA damage response in chemo- and radio-resistance of cancer cells: Can DDR inhibitors sole the problem?

Up to now, many improvements have been made in providing more therapeutic strategies for cancer patients. The lack of susceptibility to common therapies like chemo- and radio-therapy is one of the reasons why we need more methods in the field of cancer therapy. DNA damage response (DDR) is a set of mechanisms which identifies DNA lesions and triggers the repair process for restoring DNA after causing an arrest in the cell cycle. The ability of DDR in maintaining the genome stability and integrity can be favorable to cancerous cells which are exposed to radiation therapy or are treated with chemotherapeutic agents. When DDR mechanisms are error-free in cancer cells, they can escape the expected cellular death and display resistance to treatment. In this regard, targeting different components of DDR can help to increase the susceptibility of advanced tumors to chemo- and radio-therapy.

Chitosan and Wnt/ß-catenin Signaling Pathways in Different Cancers.

It has been a while since the disease of cancer was discovered in 16th and 17th century but still, this disease is one of the most lethal diseases in the world, which is taking a great number of lives every year. Cancer statistics suggest that there are still a lot of improvements that we have to make in the field of cancer treatment in order to overcome this deadly disease. Currently, nanotechnology has provided some more effective methods in this field, which has gained a lot of attention. Novel drug delivery systems that work using nanoparticles might be the answer to many unsolved questions in treating cancer. Chitosan is a natural glucose polymer which has the potential to be utilized as a proper drug carrier due to its advantageous features. Chitosan-based delivery systems are able to affect cancerous cells in many pathways. Wnt signaling pathways, which are one of the most essential ingredients of cancer pathogenesis, can be the target of chitosan nanoformulations. In this paper, we discussed the specific impacts of chitosan and its nanoformulations on each component of the Wnt/catenin pathway. Our conclusions might give novel insights for designing more efficient therapeutic approaches for several kinds of cancer.

The effects of chitosan-based materials on glioma: Recent advances in its applications for diagnosis and treatment.

Glioma is known as the most common primary brain tumor occurring in adolescents and is considered as a lethal disease worldwide. Despite the advancements in presently available therapeutic approaches (i.e. radiation therapy and chemotherapy), the rate of amelioration in glioma patients is still low. In this regard, it seems that there is a need for reconsidering and enhancing current therapies and/or discovering novel therapeutic platforms. Chitosan is a natural polysaccharide with several beneficial characteristics, including biocompatibility, biodegradability, and low toxicity. Without causing toxic effects on healthy cells, chitosan nanoparticles are attractive targets in cancer therapy which lead to the sustained release and enhanced internalization of chemotherapeutic drugs as well as higher cytotoxicity for cancer cells. Hence, these properties turn it into a suitable candidate for the treatment of various cancers, including glioma. In the viewpoint of glioma, cancer inhibition is possible through targeting glioma-associated signaling pathways and molecules such as MMP-9, VEGF, TRAIL and nuclear factor-κB by chitosan and its derivatives. Moreover, it has been acknowledged that chitosan and its derivatives can be applied as a delivery system for carrying a diverse range of therapeutic agents to the tumor site. Besides the anti-glioma effects of chitosan and its derivatives, these molecules can be utilized for culturing glioma cancer cells; providing a better understanding of glioma pathogenesis. Furthermore, it is documented that 3D chitosan scaffolds are potential targets that offer advantageous drug screening platforms. Herein, we summarized the anti-glioma effects of chitosan and also its utilization as drug delivery systems in the treatment of glioma.

Chitosan applications in studying and managing osteosarcoma.

Osteosarcoma has a high prevalence among children and adolescents. Common treatments of this disease are not promising enough. Molecular processes involved in the pathogenesis of osteosarcoma are not fully understood. Besides, the remnants of tumor cells after surgery can cause bone destruction and recurrence of the disease. Thus, there is a need to develop novel drugs or enhancing the currently-used drugs as well as identifying bone-repairing methods. Chitosan is a natural compound produced by the deacetylation of chitin. Research has shown that chitosan can be used in various fields due to its beneficial effects, such as biodegradability and biocompatibility. Regarding cancer, chitosan exerts several anti-tumor activities. Moreover, it can be used in diagnostic techniques, drug delivery systems, and cell culture methods. Herein, we aim to discuss the potential roles of chitosan in studying and treating osteosarcoma. We review the literature on chitosan's applications as a drug delivery system and how it can be combined with other substances to improve its ability of local drug delivery. We take a look into the studies concerning the possible benefits of chitosan in the field of bone tissue engineering and 3D culturing. Furthermore, anti-cancer activities of different compounds of chitosan are reviewed.

Effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to analyze the effects of flaxseed oil supplementation on biomarkers of inflammation and oxidative stress in patients with metabolic syndrome (MetS) and related disorders. METHODS: Databases including PubMed, Scopus, EMBASE, Web of Science, and Cochrane Central library were searched until January 31th, 2019. RESULTS: 14 effect sizes from 12 studies were identified eligible to be included in current meta-analysis. Flaxseed supplementation resulted in a significant reduction in interleukin 6 (IL-6) (WMD: -0.22; 95% CI: -0.43, -0.01) and malondialdehyde (MDA) (WMD: -0.17; 95% CI: -0.31, -0.03) and a significant increase in total antioxidant capacity (TAC) levels (WMD: 137.25; 95% CI: 68.04, 206.47). Flaxseed oil supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSIONS: Overall, this meta-analysis demonstrated flaxseed oil supplementation decreased IL-6 and MDA levels, and increased TAC, but did not affect other biomarkers of inflammation and oxidative stress among patients with MetS and related disorders. This suggests that flaxseed oil supplementation may have played an indirect role in improved clinical symptoms in diseases with metabolic disorders.

Melatonin as a potential inhibitor of kidney cancer: A survey of the molecular processes.

Studies have shown that despite the decreasing mortality rates of kidney cancer patients, its incidence is increasing. Therefore, a comprehensive re-evaluation of treatment options is necessary to provide appropriate treatments for the increasing number of patients. Moreover, the side effects caused by surgery, which is the main treatment of this disease, may lead to higher morbidity rates. Consequently, new safer approaches must be examined and considered. Major advancements have been made in the field of targeted agents as well as treatments based on immunotherapy since renal cell carcinoma (RCC) does not respond well to chemotherapy. While the therapeutic options for this cancer are increasing, the resulting complexity of selecting the best strategy for treating the patients is daunting. Moreover, each therapeutic option must be evaluated concerning toxicity, cost, and clinical advantages. Several characteristics, which are beneficial for cancer therapies have been attributed to melatonin. For decades, investigations have explored the application of melatonin in the treatment of cancer; insufficient attention has been paid to this molecule at the clinical level. Melatonin plays a role in cancer therapy due to its anti-tumor effects as well as by enhancing the efficacy of other drugs as an adjuvant. In this review, we discuss different roles of melatonin in the treatment of kidney cancer. The studies concerned with the applications of melatonin as an adjuvant in the immunotherapy of patients with kidney cancer are summarized. Also, we highlight the apoptotic and anti-angiogenic effects of melatonin on renal cancer cells which are mediated by different molecules (e.g., HIF-1 and VEGF, ADAMTS1, and MMP-9) and signaling pathways (e.g., P56, P52, and JNK). Furthermore, we take a look into available data on melatonin's ability to reduce the toxicities caused by kidney carcinogens, including ochratoxin A, potassium bromate, and Fe-NTA.

Circular RNAs as diagnostic biomarker in pancreatic cancer.

Pancreatic cancer is one of the causes of death in the world. Unfortunately, common imaging technologies did not succeed in identifying this disease, and because of the absence of sensitive and specific biomarkers, it is not possible to screen and diagnose the disease. Therefore, this disease is usually diagnosed when patient is at an advanced stage of cancer and has lost the chance of surgery, and routine treatments such as radiotherapy and chemotherapy are not very effective. For this reason, the discovery of new biomarkers to overcome the diagnostic and therapeutic problems of pancreatic cancer is essential. Recently, circular RNAs (circRNAs) have been introduced as a group of noncoding RNAs that can play the role of critical regulators in various human diseases including cancer. A lot of studies revealed that circRNAs can have diverse roles in various cancers, including breast, colorectal, lung, renal, gastric, and hepatocellular carcinoma. The results of these researches have demonstrated that change in circRNAs expression levels in the tumor cells affects carcinogenesis, the stages of progression and metastasis of cancer through various mechanisms. Given that several studies have tested the role of circRNAs in pancreatic cancer, we decided to review the mechanisms proposed in these studies to conclude and summarize the work done in this regard.

Effects of chitosan and oligochitosans on the phosphatidylinositol 3-kinase-AKT pathway in cancer therapy.

Phosphatidylinositol 3-kinase (PI3K)-AKT pathway is one of the most important kinase signaling networks in the context of cancer development and treatment. Aberrant activation of AKT, the central mediator of this pathway, has been implicated in numerous malignancies including endometrial, hepatocellular, breast, colorectal, prostate, and, cervical cancer. Thus regulation and blockage of this kinase and its key target nodes is an attractive approach in cancer therapy and diverse efforts have been done to achieve this aim. Chitosan is a carbohydrate with multiple interesting applications in cancer diagnosis and treatment strategies. This bioactive polymer and its derivative oligomers commonly used in drug/DNA delivery methods due to their functional properties which improve efficiency of delivery systems. Further, these compounds exert anti-tumor roles through the stimulation of apoptosis, immune enhancing potency, anti-oxidative features and anti-angiogenic roles. Due to the importance of PI3K-AKT signaling in cancer targeting and treatment resistance, this review discusses the involvement of chitosan, oligochitosaccharides and carriers based on these chemicals in the regulation of this pathway in different tumors.

Chitosan: A compound for drug delivery system in gastric cancer-a review.

Gastric cancer is known as the fourth most common cancer and the second main cause of cancer-related deaths. Gastric cancer has some characteristics including high incidence rates of metastasis and mortality as well as low rates of early diagnosis, radical resection and 5-year survival. Radical surgery and following chemotherapy has been done for patients with early gastric cancer leading to 90 % survival rate in 5-year after operation. Besides, in advanced stage some cases don't have the chance of surgery as well as the risk of metastasis is high in these patients overally leading to poor prognosis. In recent years, finding a suitable drug delivery system for chemotherapeutic drugs in gastric cancer is an considerable subject for researchers. Chitosan is known as an appropriate compound for chemo-drug delivery in cancer treatment due to its high biodegradability and biocompatibility. Moreover, trans-mucosal drug delivery is facilitated by chitosan via its mucoadhesive and cationic features enhancing interaction with mucous membrane. In addition, a large amount of experimental evidence has reported the efficacy of chitosan for drug delivery in gastric cancer. Thus, the aim of this article was to review this evidence as well as new chitosan-based drug delivery systems investigated in gastric cancer.

Anti-tumor activities of probiotics in cervical cancer.

Cervical cancer is considered as an important malignancy among women worldwide. Currently-used treatments of cervical cancer are reported to be cytotoxic for patients. Moreover, these therapies have shown some side effects which can negatively affect the lives of women suffering from this cancer. Therefore, there is need for anti-tumor agents that are less toxic than common therapeutic drugs. Besides, applying agents for preventing or reducing the side effects of cervical cancer therapies can be effective in improving the life quality of cervical cancer patients. Studies have shown that probiotics have several effects on biological processes. One of the most prominent aspects in which probiotics play a role is in the field of cancer. There are multiple studies which have focused on the functions of probiotics in diagnosis, prevention, or treatment of cancer. Besides their direct anti-tumor activities, probiotics can be used as an additional agent for enhancing or modulating other diagnostic and therapeutic methods. Herein, the effects of probiotics on cervical cancer cells are discussed, which may be useful in the prevention and treatment of this cancer. We review the studies concerned with the roles of probiotics in modulating and reducing the gastrointestinal adverse effects caused by cervical cancer therapies. Furthermore, we cover the investigations focusing on the combination of probiotics with other drugs for diagnosis or treatment of cervical cancer.