Intravesical Treatments of Bladder Cancer: Review

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy

Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens

The international outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in 2002–2003 highlighted the need to develop pretested human vaccine vectors that can be used in a rapid response against newly emerging pathogens. We evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is highly attenuated in primates, as a topical respiratory vaccine vector with SARS-CoV as a test pathogen. Complete recombinant NDV was engineered to express the SARS-CoV spike S glycoprotein, the viral neutralization and major protective antigen, from an added transcriptional unit. African green monkeys immunized through the respiratory tract with two doses of the vaccine developed a titer of SARS-CoV-neutralizing antibodies comparable with the robust secondary response observed in animals that have been immunized with a different experimental SARS-CoV vaccine and challenged with SARS-CoV. When animals immunized with NDV expressing S were challenged with a high dose of SARS-CoV, direct viral assay of lung tissues taken by necropsy at the peak of viral replication demonstrated a 236- or 1,102-fold (depending on the NDV vector construct) mean reduction in pulmonary SARS-CoV titer compared with control animals. NDV has the potential for further development as a pretested, highly attenuated, intranasal vector to be available for expedited vaccine development for humans, who generally lack preexisting immunity against NDV

Administrative and Judicial Collective Enforcement of Consumer Law in the US and the European Community

In the consumer society, as it stands today in Western-type democracies, consumers have a far larger choice of products and services originating from all over the world than they did decades ago. Risks associated with products and services have also increased, as have mass problems and mass damages, often in a transborder dimension. The US and the European Community, though battling against common problems, maintain different standard setting and enforcement regimes. This paper focuses on enforcement regimes, thereby distinguishing between administrative enforcement via agencies and judicial collective enforcement via European collective actions and US class actions. The existing theoretical framework depicting administrative and judicial enforcement as alternative strategies is contrasted against modern developments in the US and the EC. In the field of consumer protection administrative control and judicial collective enforcement are being understood more as functional complements than alternatives. Enforcement covers negotiation, settlement, adjudication and arbitration. The analysis of the institutional variables determining the choice between administrative and judicial control – ex ante vs. ex post control, injunctive relief versus damages, personal injuries and economic losses, sector specificity vs. general instruments to protect consumers, public agencies vs. private organisations – provide the ground for preliminary thoughts on a revised theoretical approach