Abstract: Although thyroid carcinoma usually has an excellent prognosis, the lack of therapeutic options is an issue for patients that develop metastases and are resistant to radioiodine therapy. The development of novel molecular targeted therapies and the characterization of several proteins that have a crucial role in the carcinogenesis process of differentiated thyroid cancer have created an opportunity to design new clinical trials for this setting. Moreover, the encouraging initial results of first clinical trials have accelerated the development of placebo-controlled phase III studies that will assess the role of these new agents in the management of differentiated thyroid cancer. ... Read more

Abstract: The dynamic and multiple functions of p53, together with its involvement in the most common non-infectious diseases, underscore the need to elucidate the complexity of the p53 regulatory networks. Pathological conditions such as cancer, neurodegeneration, ischemia, cholestasis, and atherosclerosis are all strongly associated with deregulated levels of apoptosis in which p53 dysfunction has a prominent role. We will highlight recent developments of p53-induced apoptosis in human diseases, with a focus on modulation of liver cell apoptosis. In addition, we will discuss controversies arising from widespread p53 activation as a therapeutic approach to cancer. Recent studies have provided relevant and unprecedented information about mechanistic antiapoptotic functions of the endogenous bile acid, ursodeoxycholic acid (UDCA), suggesting that the finely tuned, complex control of p53 by Mdm-2 (mouse double minute-2, an oncoprotein) is a key step in UDCA modulation of p53-triggered apoptosis. We will also review recent therapeutic strategies and clinical applications of targeted agents, their safety, and efficacy, with particular emphasis on potential benefits of UDCA. ... Read more

Abstract: Anti-epileptic drugs (AEDs) have a variety of mechanisms of action which are reflected through different anticonvulsant activities and behavioral effects. Two categories of AEDs are considered based on psychotropic profile. The first group is characterized by potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission, and comprises of agents such as vigabatrin, tiagabine, and gabapentin. These agents are noted to have sedating effects ranging from cognitive slowing to anti-manic effects. On the other hand, the second group is typified by attenuation of glutamate excitatory neurotransmission and has activating effects including anxiogenic and antidepressant actions. Lamotrigine and felbamate feature in this latter group. Mechanisms of action, chief clinical indications, as well as behavioral profile including comment on chief cognitive effects of the newer AEDs are reviewed in accordance with this dual categorization. In clinical practice, assessment of an individual patient alongside consideration of AED behavioral profile primes for appropriate prescription according to patient mood profile, also permitting exposure of AED-induced behavioral disturbance. ... Read more

Abstract: Mainstays of therapy for type 2 diabetes involve drugs that are insulin-centric, i.e., they are designed to increase insulin secretion and decrease insulin resistance. The usual clinical course for people so treated is to have initially improved glycemic control but over time a need for intensification of drug-based treatment of hyperglycemia. The mechanism for this unrelenting deterioration of β-cell function is related to chronic oxidative stress. This suggests that drug discovery should not exclusively focus on insulin-centric targets, but also include glucose-centric strategies, such as antioxidant protection of the β-cell. This may facilitate repair of β-cells undergoing damage by oxidative stress secondary to chronic hyperglycemia. ... Read more

Abstract: Glioblastoma is the most common and most lethal primary brain tumor. While small progress has been made in treating this cancer in recent years, glioblastoma remains largely resistant to all existing therapies. It has been hoped that dissection of the genetics of this cancer would lead to more targeted and effective treatments, and new advances may finally be bringing this closer to fruition. Within the last few years, high-throughput efforts such as The Cancer Genome Atlas and a massive sequencing project have yielded novel insights and classifications of this dreaded cancer. The likely impact on care delivery in the clinic may only be a few years away. The rapid and exciting pace of advances in glioblastoma genetics has prompted this up-to-date review. ... Read more

Abstract: Standard anti-cancer therapeutic modalities like chemotherapy and radiotherapy evoke host's reactions that include involvement of the immune system. Elucidation of these mechanisms offers the double advantage of enabling a more rational choice of cytotoxic therapy and exploring the combination with immunotherapy. Radiotherapy, a well established local anti-cancer approach, is a particularly interesting partner for immunotherapy, since it can be harnessed to specifically modify the immunogenicity of the primary tumor and its microenvironment, in the attempt to generate an in situ immunization against a patient's own cancer. ... Read more

Abstract: According to the World Health Organization, approximately 220 million people worldwide have type 2 diabetes mellitus. Patients with type 2 diabetes not only have a chronic disease to cope with, they are also at increased risk for coronary heart disease, peripheral vascular disease, retinopathy, nephropathy, and neuropathy. The exact causes of type 2 diabetes are still not clear. Since the 17^th century, it has been suggested that emotional stress plays a role in the etiology of type 2 diabetes mellitus. So far, review studies have mainly focused on depression as a risk factor for the development of type 2 diabetes mellitus. Yet, chronic emotional stress is an established risk factor for the development of depression. The present review provides an overview of mainly prospective epidemiological studies that have investigated the associations between different forms of emotional stress and the development of type 2 diabetes mellitus. Results of longitudinal studies suggest that not only depression but also general emotional stress and anxiety, sleeping problems, anger, and hostility are associated with an increased risk for the development of type 2 diabetes. Conflicting results were found regarding childhood neglect, life events, and work stress. It is important to emphasize that publication-bias may have occurred, resulting from "fishing-expeditions," where authors search their data for significant associations. Publication bias may also be caused by the tendency of reviewers and Editors to reject manuscripts with negative results for publication. It is therefore essential that research groups, who aim to conduct a new epidemiological cohort study, prospectively describe and publish the design of their study. Future research should focus on identifying mechanisms linking different forms of stress and incident type 2 diabetes. ... Read more

Abstract: Human gene therapy has made substantial progress since the initiation of the first clinical trials 20 years ago. Here, we summarized important applications of gene transfer protocols in the treatment of various human diseases using different viral vectors. Recent successful trials on the treatment of ocular diseases and inherited immune deficiencies are particularly encouraging and have raised hopes that human gene therapy as a standard treatment option will finally become a reality. While immune responses and insertional mutagenesis pose obstacles for this novel form of molecular medicine, continuous progress suggests that a wider range of diseases can be treated with gene therapy in the future. ... Read more

Abstract: Coronary artery calcification (CAC) has long been known to occur as a part of the atherosclerotic process; recently it has been shown to be an active process resembling bone formation within the vessel wall. There is good evidence that the extent of CAC reflects the total coronary atherosclerotic burden and this has generated interest in using CAC as a marker of risk. The current consensus is that large amounts of CAC identify a patient highly vulnerable to future events. The advent of CT angiography added the ability to non-invasively detect critical luminal stenoses that are associated with a more immediate risk of events, and to visualize the non-calcified component of the atherosclerotic plaque. ... Read more

Abstract: Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following human papilloma virus vaccine. ... Read more