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.

Potential Mechanisms of Melatonin in Osteosarcoma and Bone-Related Neoplasms: Updated Review.

Melatonin (N-acetyl-5-methoxytryptamine) is a secretory product of the pineal gland. A great number of studies have been investigating the functions of this indoleamine in various diseases. Excessive proliferation, reduction in apoptosis, increased angiogenesis, invasion, and metastasis are all processes associated with cancerous tissues. In several cancer types, melatonin is reported to significantly impact these processes. Although bone cancer is relatively rare, it is a serious disease that often becomes metastatic, leading to an unsatisfactory prognosis. In recent decades, significant advances have been made in the therapeutic strategies for bone cancer. Nevertheless, few changes have occurred to patients' outcomes or therapeutic methods. Currently used therapeutic strategies including chemotherapy and radiotherapy often show serious side effects. Moreover, therapeutic options are not sufficient in certain cases, such as metastatic forms of the disease. Therefore, there is a need for a more precise definition of the molecular pathways and cellular functions associated with bone cancer to find novel therapeutic approaches. With such advances, the development of new effective therapies for patients with advanced stage or metastatic forms of the disease will be achieved, resulting in an improved prognosis. This review summarizes what is known about the functions of melatonin in osteosarcoma and Ewing's sarcoma. We explain the underlying mechanisms of action by which melatonin serves as an antitumor agent in bone cancer as well as provide an insight into its synergistic effects with other chemotherapeutic drugs.

Resveratrol Effects on Molecular Pathways and MicroRNAs in Gastrointestinal Cancers.

Gastrointestinal (GI) cancers are one of the most prevalent types of neoplasms worldwide. The incidence of GI cancers is increasing rapidly. Despite all advances in the management of GI cancers, treatment options for these disorders are still limited and there are no effective therapeutic approaches. Hence, finding new treatment strategies seems to be necessary to decrease mortality in patients with such cancers. The application of natural products has found a prominent role in the management of some neoplastic disorders. Resveratrol is a phytochemical found in various fruits and plants such as red grapes and tea. Recently, the effects of resveratrol on the microRNAs in the management of some neoplastic disorders have been investigated. This review is aimed to illustrate the molecular pathways related to resveratrol and evaluate the impacts of resveratrol on the different microRNAs in the milieu of the prevention and treatment of GI cancers.

Virus, Exosome, and MicroRNA: New Insights into Autophagy.

Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.

Molecular and cellular mechanisms of melatonin in breast cancer.

Breast cancer is considered as one of the most important health problems due to its poor prognosis and high rate of mortality and new diagnosed cases. Annually, a great number of deaths are reported in men and women; this means that despite all the improvements in cancer diagnosis and treatment, still, an intense need for more effective approaches exists. Melatonin is a multivalent compound which has a hand in several cellular and molecular processes and therefore, is an appropriate candidate for treatment of many diseases like cancer. Currently, considerable properties of this agent have oriented the research towards investigating its effects specifically in breast cancer. In this review, we gathered a bunch of evidence in order to give a new sight for breast cancer treatment utilizing melatonin. We expect that in coming years, melatonin will become one of the most common therapeutic drugs with lesser side-effects than other chemotherapeutic drugs.

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.

Molecular Signaling Pathways as Potential Therapeutic Targets in Osteosarcoma.

Among primary bone malignancies, osteosarcoma (OS) is the most common form causing morbidity and mortality in both adults and children. The interesting point about this malignancy is that nearly 10-20% of its newly diagnosed cases have developed metastasis. This adds up to the fact that the survival rate of both metastatic and non-metastatic patients of osteosarcoma has not changed in the past 30 years; therefore, it has been suggested that we need to revise our therapeutic options for OS. In recent years, diverse signaling pathways have drawn the attention of the scientific community since they can be great candidates for treating complicated diseases, such as cancer. In this review, we have tried to explain the pathophysiology of osteosarcoma with the help of different signaling pathways taking part in its initiation/progression and explore how this pathway can be targeted for providing more efficient methods.

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.

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.

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.

An insight into the roles of piRNAs and PIWI proteins in the diagnosis and pathogenesis of oral, esophageal, and gastric cancer.

P-Element induced wimpy testis (PIWI)-interacting RNA (piRNA) is a member of the non-coding RNAs family. Four PIWI proteins are found to be expressed in humans. The number of studies focusing on the roles of piRNAs and PIWI proteins in the field of cancer is increasing. Oral, esophageal, and gastric cancers are considered as important causes of death. PIWI proteins and piRNAs are suggested to be involved in the pathogenesis of these diseases. Thus, studying these molecules may be beneficial for finding new therapeutics. Since it is shown that currently used biomarkers for these cancers have low sensitivity and specificity, there is a necessity for identifying novel non-invasive biomarkers which are highly sensitive and specific. This paper will provide an insight into current knowledge about the functions of PIWI proteins and piRNAs in the oral, esophageal, and gastric cancer. We discuss how PIWI proteins and piRNAs can be involved in the pathogenesis of these cancers. Moreover, we review the studies concerning with the roles of PIWI proteins and piRNAs as biomarkers which are used for diagnostic and prognostic purposes.

Molecular and Biological Functions of Melatonin in Endometrial Cancer.

Endometrial cancer is the fifth leading cancer among women. This rate is higher in developed countries and its incidence is increasing worldwide. Diabetes mellitus, obesity, hypertension and arteriosclerosis are major risk factors for endometrial cancer. Melatonin is a hormone synthesized in the pineal and extra-pineal organs such as the digestive tract, bone marrow, retina and more. Evidence shows the potential effects of melatonin in endometrial cancer inhibition. Therefore, the focus of this paper is to review this outstanding evidence and to summarize the molecular and biological mechanisms of melatonin for the inhibition of endometrial cancer.