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

Patient-Reported Outcome Measurement Compared with Professional Judgment of Cosmetic Results after Breast-Conserving Therapy

Background: In the present study, we set out to compare patient-reported outcomes with professional judgment about cosmesis after breast-conserving therapy (bct) and to evaluate which items (position of the nipple, color, scar, size, shape, and firmness) correlate best with subjective outcome. Methods: Dutch patients treated with bct between 2008 and 2009 were analyzed. Exclusion criteria were prior amputation or bct of the contralateral breast, metastatic disease, local recurrence, or any prior cosmetic breast surgery. Structured questionnaires and standardized six-view photographs were obtained with a minimum of 3 years’ follow-up. Cosmetic outcome was judged by the patients and, based on photographs, by 5 different medical professionals using 3 different scoring systems: the Harvard scale, the Sneeuw questionnaire, and a numeric rating scale. Agreement was scored using the intraclass correlation coefficient (icc). The association between items of the Sneeuw questionnaire and a fair–poor Harvard score was estimated using logistic regression analysis. Results: The study included 108 female patients (age: 40–91 years). Based on the Harvard scale, agreement on cosmetic outcome between the professionals was good (icc: 0.78). In contrast, agreement between professionals as a group compared with the patients was found to be fair to moderate (icc range: 0.38–0.50). The items “size” and “shape” were identified as the strongest determinants of cosmetic outcome. Conclusions: Cosmetic outcome was scored differently by patients and professionals. Agreement was greater between the professionals than between the patients and the professionals as a group. In general, size and shape were the most prominent items on which cosmetic outcome was judged by patients and professionals alike

Adenovirus-Derived Vectors for Prostate Cancer Gene Therapy

Prostate cancer is a leading cause of death among men in Western countries. Whereas the survival rate approaches 100% for patients with localized cancer, the results of treatment in patients with metastasized prostate cancer at diagnosis are much less successful. The patients are usually presented with a variety of treatment options, but therapeutic interventions in prostate cancer are associated with frequent adverse side effects. Gene therapy and oncolytic virus therapy may constitute new strategies. Already a wide variety of preclinical studies has demonstrated the therapeutic potential of such approaches, with oncolytic prostate-specific adenoviruses as the most prominent vector. The state of the art and future prospects of gene therapy in prostate cancer are reviewed, with a focus on adenoviral vectors. We summarize advances in adenovirus technology for prostate cancer treatment and highlight areas where further developments are necessary.Gene regulation and cell differentiatio

Adenovirus-derived vectors for prostate cancer gene therapy

Prostate cancer is a leading cause of death among men in Western countries. Whereas the survival rate approaches 100% for patients with localized cancer, the results of treatment in patients with metastasized prostate cancer at diagnosis are much less successful. The patients are usually presented with a variety of treatment options, but therapeutic interventions in prostate cancer are associated with frequent adverse side effects. Gene therapy and oncolytic virus therapy may constitute new strategies. Already a wide variety of preclinical studies has demonstrated the therapeutic potential of such approaches, with oncolytic prostate-specific adenoviruses as the most prominent vector. The state of the art and future prospects of gene therapy in prostate cancer are reviewed, with a focus on adenoviral vectors. We summarize advances in adenovirus technology for prostate cancer treatment and highlight areas where further developments are necessary.Gene regulation and cell differentiatio