Current Medicinal Chemistry - Volume 25, Issue 16, 2018

Background: Scientific evidence has been accumulated about the effects of polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3 PUFAs might improve the efficiency of anticancer drugs has recently been considered. The role of n-6 PUFAs, in contrast, needs to be better assessed. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. This review aims to report the most updated evidence on the role of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing on the potential mechanisms by which PUFAs exert their effects. Methods: We undertook a structured search in PubMed on February 17th 2017 for peer-reviewed research articles published from 2013. The search syntax used was: PUFA or PUFAs and cancer. Results: Contradictory results were found, most likely due to the genetic background, the different dietary sources used, the interaction among different nutrients, and the tumor subtypes. However, the more recent findings strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the other hand, n-6 PUFAs are often associated with an increased risk of cancer, even if recently their beneficial effects have also been highlighted. Conclusion: N-3 PUFAs may represent a potential therapeutic agent contributing to treat at least some type of human cancers. However, studies with larger sample sizes and longer follow-up times are still needed. To increase the knowledge about how food and nutrition can improve human health it is advisable to deliver an open access nutritional database.

Conventional drugs used for cancer chemotherapy have severe toxic side effects and show individually varied therapeutic responses. The convergence of nanotechnology, biology, material science and pharmacy offers a perspective strategy for cancer chemotherapy. Nanoparticles loaded with anti-cancer drug have been designed to overcome the limitations associated with conventional drugs, several nanomedicines have been approved by FDA and shown good performances in clinical practice. However, the therapeutic efficacies cannot be enhanced. Taking this into account, stimuli responsive nanoparticles present the ability to enhance therapeutic efficacy and reduce side effects. In this review, we systematically summarized the recent progresses of controlled anti-cancer drug release systems based on nanoparticles with different stimuli response including pH, temperature, light, redox and others. If the achievements of the past can be extrapolated into the future, it is highly likely that responsive nanoparticles with a wide array of desirable properties can be eventually developed for safe and efficient cancer therapy.

Background: Developed as an antiviral drug in the 1960s and 1970s, the thymidine analogue 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) was translated to clinical application for treatment of herpes simplex virus infection. In phase I clinical trial of FMAU; however, patients experienced neurotoxicity at the pharmacological dose, and FMAU was withdrawn from the trial. More recently, FMAU has been developed as a tracer for positron emission tomography (PET) imaging in early detection of cancer through its binding to human thymidine kinase, which is upregulated in cancer cells. FMAU radiolabeled with 11C or 18F has been examined for PET imaging of tumor cell proliferation and DNA synthesis. Although many reports have been partially published on FMAU, systematic reviews outlining the historic development and imaging probe are lacking. This review is focused on the identification of kinases, the chemistry of FAMU and its application in cancer diagnosis and therapy assessment. Objective: The aim of this study was to review the historic development of FMAU, from its synthetic development and antiviral activity studies to its radiolabeling and evaluate it as a PET imaging probe for the early detection of cancer and assessment of treatment response, including published reports on the clinical utility of 18F-FMAU. Conclusion: While FMAU was not successful as an antiviral agent, 18F-FMAU is a suitable radiotracer for early detection of cancer and assessment of response to therapy by PET. The process of clinical grade 18F-FMAU production requires further improvement. 18F-FMAU has high potential for clinical application, but further extensive studies are needed to establish this tracer in the diagnosis of various cancers and assessment of their response to therapy.

Background: Guanylate cyclase C (GC-C) receptor is a transmembrane receptor, predominantly expressed in intestinal epithelial cells, which is considered to play a main role in homeostasis and function of the digestive tract. The endogenous ligands for this receptor are the paracrine hormones uroguanylin and guanylin. Upon ligand binding, GC-C receptors increase cyclic guanosine monophosphate (cGMP) levels, regulating a variety of key cell-type specific processes such as chloride and bicarbonate secretion, epithelial cell growth, regulation of intestinal barrier integrity and visceral sensitivity. It has been suggested that GC-C acts as an intestinal tumor suppressor with the potential to prevent the initiation and progression of colorectal cancer. In fact, loss of ligand expression is a universal step in sporadic colorectal carcinogenesis. Interestingly, the role of GC-C is not limited to the digestive tract but it has been extended to several other systems such as the cardiovascular system, kidney, and the central nervous system, where it has been involved in a gut-hypothalamus endocrine axis regulating appetite. Objetive: In this review we summarize the physiology of the GC-C receptor and its ligands, focusing on newly developed drugs like linaclotide, and their suggested role to reverse/prevent the diseases in which the receptor is involved. Conclusion: Available data points toward a relationship between uroguanylin and guanylin and their receptor and pathological processes like gastrointestinal and renal disorders, colorectal cancer, obesity, metabolic syndrome and mental disorders among others. Recent pharmacological developments in the regulation of GC-receptor may involve further improvements in the treatment of relevant diseases.

Background: Asthma represents a worldwide health problem with a strong morbidity and a major impact on the health care system. Multiple efforts have been made towards the development of new strategies for the prevention and treatment of this disorder. In the light of this the present review of the literature aimed at summarizing the latest advances in prevention and treatment of pediatric asthma with a focus on the most effective options of interventions during the first stages of life. Methods: References were identified by searches of PubMed. Search terms used in the search were “pediatric asthma”, “treatment” and “prevention”. We included only meta-analysis, randomized controlled trials, reviews and systematic review articles pertaining to humans and subjects aged 0-18 years. All the interventions have been classified as “non-pharmacological” and “pharmacological”. Results: Non-pharmacological interventions have been focused in identifying the genetic and environmental factors underlying the pathogenesis of this disease, including the individual genetic susceptibility, the early allergic sensitization, the role of the environmental microbiome and the exposure to infections and to pollutants. Moreover, the optimization of the existing pharmacological strategies and the development of new treatment options have improved markedly the management of this disease, thereby reducing the health care costs and ameliorating the quality of life of patients. Conclusion: Childhood asthma prevention and treatment still represents a worldwide challenge. Future efforts should be aimed at identifying high risk target populations, minimizing the costs of each policy of intervention and increasing adherence to treatment strategies.

The conjugation of gold nanoparticles (AuNPs) with biomolecules could create many outstanding biofunctions for the surface-functionalized nanoparticles and extend their biomedical applications. In this review, we summarize the recent advances in the surface bioengineering of AuNPs with biomolecules, such as DNA, proteins, peptides, and biopolymers, in which the details on the structure, functions, and properties of surface- bioengineered AuNPs are discussed. In addition, the surface-biofunctionalization of AuNPs for biomedical applications like biosensing, bioimaging, drug delivery, and tissue engineering are introduced. It is expected that this work will be very helpful for readers to understand the surface functionalization and engineering techniques for various metallic nanoparticles and design novel biomaterials for biomedical applications.