Dengue vaccine: opportunities and challenges

Despite many successes in the field of vaccinology over the past century, several important scourges for which effective vaccines remain elusive continue to be threats to public health. The mosquito-borne dengue virus causes millions of infections in tropical and subtropical regions throughout the world, and is responsible for an annual mortality that measures in the thousands. The ubiquitous presence of dengue virus, and its potentially lethal complications, have made the development of an effective vaccine against the virus a priority. However, before such a vaccine can be created, the basic immunology surrounding dengue infection must be clarified. Such research is underway, including efforts focusing on the response of T-cells and the potentially central role of this response in dengue pathophysiology. 'Shaping' the T-cell response may be the key to successful dengue vaccine design.     

Rotavirus vaccines: opportunities and challenges

Each year rotavirus gastroenteritis episodes in young children cause more than 500,000 deaths and 2.4 million hospital admissions worldwide. Vaccine development became a priority when improved personal hygiene and living standards failed to significantly reduce this disease burden. Rotavirus vaccines were developed mimicking natural immunity by protecting against severe gastroenteritis in young children, which would otherwise lead to health-care attendance, hospitalization or even death. Licensed rotavirus vaccines appear safe and are well-tolerated. In high and middle-income countries they provide 80-100% protection against severe disease and 70-80% protection against rotavirus gastroenteritis of any severity, depending upon the population studied. However, rotavirus vaccines remain to be fully evaluated in low-income countries where reduced immunogenicity of oral vaccines, greater strain diversity and difficulties reaching target populations might decrease immunization program performance. Nevertheless, if these challenges are met, rotavirus vaccines should help reduce the 5% of all childhood deaths attributable to rotavirus gastroenteritis.     

Management of retinoblastoma: opportunities and challenges

Nano-delivery systems have significantly evolved over the last decade for the treatment of cancer by enabling site-specific delivery and improved bioavailability. The widely investigated nanoparticle systems are biodegradable polyesters, dendrimers, liposomes, mesoporous silica and gold nanoparticles. These particles when conjugated with different targeting motifs enhance the therapeutic efficiency of the drug molecules and biocompatibility. However, the application of such systems towards the treatment of retinoblastoma (RB), a rapidly spreading childhood eye cancer, still remains in its infancy. Nanoparticle-based systems that have been investigated for RB therapy have displayed improved drug delivery to the most restricted posterior segment of the eyes and have increased intra-vitreal half-life of the chemotherapy agents highlighting its potential in treatment of this form of cancer. This review focuses on the challenges involved in the treatment of RB and highlights the attempts made to develop nano-dimensional systems for the treatment of RB.     

口服前药研究：机遇与挑战

前药研究是提高生物药剂学分类系统中第III和IV类药物口服吸收的有效途径之一。本文综述了近年来口服前药研究的进展，主要包括经典前药设计和靶向前药设计。经典前药设计重在改善母体药物的油水分配系数或减少药物的代谢。靶向前药设计重在主动利用胃肠道的生理特性靶向组织、酶及肠内流转运器，其中靶向小肠内流转运器-肽类转运器的口服前药成为目前研究的热点。前药研究还面临选题，设计和体内研究等方面的挑战。     

Gold nanoparticles: opportunities and challenges in nanomedicine

Importance of the field: Site-specific drug delivery is an important area of research that is anticipated to increase the efficacy of the drug and reduce potential side effects. Owing to this, substantial work has been done developing non-invasive and targeted tumor treatment with nanoscale metallic particles.

Areas covered in this review: This review focuses on the work done in the last few years developing gold nanoparticles as cancer therapeutics and diagnostic agents. However, there are challenges in using gold nanoparticles as drug delivery systems, such as biodistribution, pharmacokinetics and possible toxicity. Approaches to limit these issues are proposed.

What the reader will gain: Different approaches from several different disciplines are discussed. Potential clinical applications of these engineered nanoparticles are also presented.

Take home message: As a result of their unique size-dependent physicochemical and optical properties, adaptability, subcellular size and biocompatibility, these nanosized carriers offer a suitable means of transporting small molecules as well as biomacromolecules to diseased cells/tissues.     

Multiple sclerosis therapeutic pipeline: opportunities and challenges

The year 2010 marked the beginning of the era of oral medications for the treatment of multiple sclerosis, with the approval of dalfampridine to improve walking and fingolimod as the first oral disease-modifying agent. This review provides an overview of these and other emerging therapies, with an emphasis on the opportunities for new treatment paradigms they have the potential to offer, followed by a discussion of the challenges they will pose in the new era of multiple sclerosis management. Therapeutics in late-stage development for MS include non-selective immunosupressants, targeted immune-modulators, and monoclonal antibodies. Oral agents including cladribine, teriflunomide, laquinimod, and dimethyl fumarate, as well as monoclonal antibodies alemtuzumab, daclizumab, and rituximab are considered. Potential side effects and adverse event monitoring, including opportunistic infections, emergent malignancies, and other systemic consequences of immunosuppression are discussed in a unified section. Challenges of optimally staging, sequencing, and combining treatments in the expanding multiple sclerosis armamentarium are discussed. This review emphasizes the multifactorial decision making that these new therapeutics will warrant in terms of patient selection and personalization/individualization of therapy, and the increasingly interdisciplinary approach that will be necessitated by the new generation of agents.     

Treatment of postpartum psychosis: challenges and opportunities

Postpartum psychosis is a rare but serious psychiatric illness that follows delivery. Although controversy continues to surround its diagnostic status, it is generally considered an episode of bipolar disorder with accompanying psychotic features. The consequences of untreated postpartum psychosis can be serious due to the associated risk of suicide and infanticide; however, its close temporal association with childbirth should provide an opportunity to undertake prophylactic measures in women at risk for developing postpartum psychosis. This article reviews the literature concerning acute and prophylactic pharmacological treatment and suggests a comprehensive approach for management of postpartum psychosis.     

Osteoporosis: challenges and new opportunities for therapy

Osteoporosis is a chronic disease that affects a large number of both men and women and is characterized by a decrease in bone mass, as well as weakened bones. It causes a significant amount of morbidity and mortality in patients and is often only diagnosed after a fracture occurs. This review will highlight recent advances in the development of novel anabolic approaches for treatment of osteoporosis, such as parathyroid hormone (PTH), calcium sensing receptor modulators, statins and prostanoid receptor agonists. Selected antiresorptive targets (cathepsin K inhibitors and vitronectin receptor antagonists) will also be surveyed.     

Antioxidants for prostate cancer chemoprevention: challenges and opportunities

Extensive research has led to the firm conclusion that antioxidants protect cells from damage caused by oxidative stress and its associated pathological conditions including inflammation. It has also been established that inflammation is a precursor in neoplastic transformation of the prostate. Although, a vast body of experimental and clinical evidence shows efficacy of antioxidants as preventive strategies for prostate cancer, there is a lack of consistent agreement in outcomes especially from recent large-scale randomized clinical trials. Despite these concerns, our understanding of the preventive mechanisms as well as clinical efficacy and safety data indicate that novel antioxidant therapeutics still hold great promise for prostate cancer chemoprevention. We propose that for effective use of antioxidants for prostate cancer prevention, further high impact translational research is needed with special attention on selecting those patients who will benefit from such intervention. Therefore, it is important to validate predictive biomarkers from successful trials and combine this with knowledge of preclinical characterization of antioxidants (and combinations) that will eventually facilitate the development of 'personalized prostate cancer chemoprevention'. In this review, we briefly describe some common and emerging antioxidants that have shown benefits in preclinical and clinical settings. Above all, we focus on summarizing the progress we made thus far in prostate cancer chemoprevention using antioxidants, the heightened interest and challenges in the future.