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Extensive research in the area of active-specific immunotherapy has led to the approval of the first therapeutic cancer vaccine sipuleucel-T (Provenge⠪) in 2010. Even though a major milestone for the field of cancer immunotherapy, many obstacles towards successful integration of vaccination strategies into the oncologists' armamentarium remain. This chapter discusses possible future perspectives for cancer vaccines as a treatment modality in oncology with special focus on biomarkers (response prediction and patient selection), requirements for clinical trial design, and combination therapies (standard of care and new molecular entities). Extensive research in the area of active-specific immunotherapy has led to the approval of the first therapeutic cancer vaccine sipuleucel-T (Provenge⠪) in 2010. Even though a major milestone for the field of cancer immunotherapy, many obstacles towards successful integration of vaccination strategies into the oncologists' armamentarium remain. This chapter discusses possible future perspectives for cancer vaccines as a treatment modality in oncology with special focus on biomarkers (response prediction and patient selection), requirements for clinical trial design, and combination therapies (standard of care and new molecular entities). [ABSTRACT FROM AUTHOR]

A novel method for amplifying the activity of major histocompatibility complex (MHC) class II helper epitopes entails linking a 4-amino-acid moiety (LRMK) from the invariant chain (Ii) of MHC (referred to as Ii-Key) to the N-terminal end of the epitope peptide either directly or using a simple polymethylene spacer (-ava-). Ii-Key catalyzes binding of the linked epitope to the MHC class II molecule, thereby enhancing the overall potency of presentation. HER-2(776–790) (or AE36), which is derived from the intracellular domain of HER-2/neu, has been intensively used as an Ii-key/HER-2(776–790) (or AE37) fusion (hybrid) vaccine in clinical trials. This chapter describes procedures for the synthesis, reconstitution, sterility testing, and storage of both AE36 and AE37 for their use in clinical trials. Also provided is a detailed information about their in vivo administration and analysis of in-depth protocols for monitoring of immune activation upon vaccination with AE37. [ABSTRACT FROM AUTHOR]

It has been almost two decades since the first genetically engineered oncolytic virus was reported in 1991. Since then, many novel strategies have been developed to further improve oncolytic virus tumor selectivity and antitumoral potency, which are the two most important factors that would eventually determine the clinical safety and efficacy of any cancer therapeutics. Importantly, some oncolytic viruses have been recently shown to specifically target cancer stem cells that are resistant to radiation and chemotherapy and are presumably responsible for tumor metastases and relapse. The host immune response is a double-edged sword for virotherapy. How to finely balance host antitumoral and antiviral immune responses will be a key to the success of virotherapy. Numerous clinical trials with many oncolytic virus constructs from seven different species indicate that oncolytic viruses are generally safe and evidence of antitumoral activity has also been demonstrated in many clinical trials. With the first approval of oncolytic adenovirus H101 in China for human use, more sophisticated oncolytic viruses will soon become available either as monotherapies or in combination with existing treatments for human malignancies. [ABSTRACT FROM AUTHOR]

Recent preclinical work investigating the role of progenitor cell therapies for central nervous system injuries has shown potential neuroprotection in the setting of traumatic brain injury, spinal cord injury, and ischemic stroke. Although the exact mechanism of action remains controversial, the growing amount of preclinical data demonstrating the potential benefit associated with progenitor cell therapy for neurological injury warrants the development of well-controlled clinical trials to investigate therapeutic safety and efficacy. In this chapter, we review the currently active or recently completed clinical trials investigating the safety and potential efficacy of bone marrow-derived progenitor cell therapies for the treatment of traumatic brain injury, spinal cord injury, and ischemic stroke. Our review of the literature shows that although the preliminary clinical trials reviewed in this chapter offer novel data supporting the potential efficacy of stem/progenitor cell therapies for central nervous system injury, a great deal of additional work is needed to ensure the safety, efficacy, and mechanisms of progenitor cell therapy prior to widespread clinical trials. [ABSTRACT FROM AUTHOR]

Traumatic brain injury is increasing in frequency, and approximately one third of patients with severe injuries suffer an unfavorable outcome (death, vegetative state, or severe disability). There are no reparative therapies for traumatic brain injury. The neuroinflammatory components of traumatic brain injury with the associated enhanced permeability of the blood–brain barrier are potential pathophysiological targets for progenitor cell-based therapy. Initial proposed mechanisms of action based on transdifferentiation/replacement of destroyed tissue using non-embryonic cells have been largely discounted. The issues of engraftment of cells in the central nervous system and the potential paracrine mechanism of action are still debated. Progenitor cell modulation of the global immune response has been proposed as a principal putative mechanism of action to minimize secondary brain injury. Early clinical studies suggest that there may be a tissue volume-preserving effect based on paired follow-up imaging/volumetric mapping. The logistical, regulatory, and practical barriers to implanting progenitor cell therapies for traumatic brain injury are significant. [ABSTRACT FROM AUTHOR]

It is estimated that oral cancers will present with more than 400,000 new cases worldwide, establishing this malignancy as the sixth most common cancer globally. In association with the ˵field″ effects of these epithelial neoplasias, oral cancers are marked by high frequencies of local invasion and recurrence, and 5-year survival times of less than 60% depending upon the stage of the initial lesion. Epidemiological studies support the hypothesis that a decreased oral cancer incidence is associated with lifestyle changes, including diminished exposure to alcohol and tobacco and increased dietary incorporation of fruits and vegetables. Food-based approaches to cancer prevention, including dietary exposure to black raspberries, emphasize the potential for complex mixtures of bioactive food components to inhibit several processes and mechanistic states within a multistep oral carcinogenesis archetype. Both pre-clinical and clinical models of black raspberry administration have demonstrated a striking capacity of black raspberries and their derivatives to specifically modulate gene transcriptional profiles in a manner that favors oral cancer prevention strategies. [ABSTRACT FROM AUTHOR]

It is considered that the first properly controlled trial in history was performed by James Lind. This Scottish surgeon and ship΄s doctor was the first who conducted a trial with an appropriately controlled design from a modern point of view. In 1747 when scurvy was a common disease among sailors James Lind administered different acidic substances to 12 sailors affected with scurvy to test who benefits most. Five pairs of the seamen were given vinegar, mustard and garlic purges, and elixir of vitriol. The sixth pair was given two oranges and one lemon per day and recovered within 6 days. Objective and reliable evaluation of appropriate treatments against diseases has become a great need in medical research especially in the last century. Today healthcare professionals are required to base their decisions on the highest level of evidence. Evidence based medicine aims to rationalize this decision process in medical treatment and legitimates a certain treatment - or rejects it. In the process of finding the best treatment available it became obvious that different kinds of clinical trials might not provide the same level of evidence and differences between study designs are more than trivial. Today clinical trials are currently seen to have the highest level of evidence and to be the ˵Gold Standard″ in clinical research. [ABSTRACT FROM AUTHOR]

A clinical trial of a new scintillation dosimeter confirms its usefulness for in vivo dosimetry during prostate HDR brachytherapy treatment. The dosimeter consists of a plastic scintillator coupled to an optical fibre with a radio-opaque platinum marker placed at the tip. The combination of tissue equivalence, real time readout and small size makes this dosimeter uniquely suited for in vivo verification of patient treatments. The angular dependence of the dosimeter is important and was determined both theoretically using Monte Carlo simulation and experimentally using a phantom with an HDR 192Ir source. We found that the radio-opaque marker did not compromise the angular response of the dosimeter. A realistic test of the effects of the radio-opaque marker for brachytherapy was obtained from simulation and experiment with the source travelling along a line at a fixed distance from the scintillator axis and parallel to it. Fifteen prostate HDR brachytherapy patients were recruited to the clinical trial. The treatment volume and the position of the dosimeter could be accurately determined in the patient frame of reference by viewing the images of gold prostate markers and the platinum marker in the radiograph. For all but one patient the dose received by the urethra was within 1.5 Gy of the dose calculated by the planning system. [ABSTRACT FROM AUTHOR]

Prostate cancer is an attractive and appropriate target for primary prevention because of its incidence, prevalence, and disease-related mortality. Despite PSA-induced stage migration, a high cure rate for localized disease, and improved understanding of prostate cancer biology, most men who develop metastatic disease are still destined to die of prostate cancer. It seems self-evident that an effective prevention strategy would spare many men from this burden of diagnosis and cure. The molecular pathogenesis of prostate cancer also lends itself to a primary prevention strategy. Clinically evident prostate cancer is rare in men ]> 50 years old, while the precancerous lesion PIN (prostatic intraepithelial neoplasia) is apparent at autopsy in men ]> 30. Furthermore, the prevalence of PIN is similar in populations at much different risks of developing clinically evident cancer, suggesting that external environmental influences are important and potentially modifiable. This chapter will review the scientific and epidemiologic evidence supporting the role of selenium and vitamin E in the prevention of prostate cancer and the design of the Selenium and Vitamin E Cancer Prevention Trial. [ABSTRACT FROM AUTHOR]

Providing an evidence base for the rational delivery of medicines and treatments is the cornerstone of modern health care delivery. Much of this evidence base is gained through conducting clinical trials. Superficially, designing a clinical trial seems straightforward. However, in practice many unforeseen difficulties arise with long setting up times, poor recruitment rates and patients or interventions not behaving in the way expected. Unfortunately, clinical trials examining the efficacy of pre-, pro- and synbiotics have developed a reputation for being published in low impact journals and reaching unconvincing conclusions. As a generalization, the reason for this poor reputation is that the trials have tended to be too small and have not used meaningful clinical endpoints. [ABSTRACT FROM AUTHOR]