The Wnt-dependent signaling pathways as target in oncology drug discovery

Our current understanding of the Wnt-dependent signaling pathways is mainly based on studies performed in a number of model organisms including, Xenopus, Drosophila melanogaster, Caenorhabditis elegans and mammals. These studies clearly indicate that the Wnt-dependent signaling pathways are conserved through evolution and control many events during embryonic development. Wnt pathways have been shown to regulate cell proliferation, morphology, motility as well as cell fate. The increasing interest of the scientific community, over the last decade, in the Wnt-dependent signaling pathways is supported by the documented importance of these pathways in a broad range of physiological conditions and disease states. For instance, it has been shown that inappropriate regulation and activation of these pathways is associated with several pathological disorders including cancer, retinopathy, tetra-amelia and bone and cartilage disease such as arthritis. In addition, several components of the Wnt-dependent signaling pathways appear to play important roles in diseases such as Alzheimer’s disease, schizophrenia, bipolar disorder and in the emerging field of stem cell research. In this review, we wish to present a focused overview of the function of the Wnt-dependent signaling pathways and their role in oncogenesis and cancer development. We also want to provide information on a selection of potential drug targets within these pathways for oncology drug discovery, and summarize current data on approaches, including the development of small-molecule inhibitors, that have shown relevant effects on the Wnt-dependent signaling pathways

Intramural leiomyomas of the bladder in asymptomatic men

Bladder leiomyomas are rare benign mesenchymal tumors, which account for less than 0.43% of all bladder tumors with approximately 200 cases described in the literature. These tumors may be classified into 3 different locations: endovesical, intramural and extravesical. Endovesical is the most common form, accounting for 63-86% of the cases, while intramural occurs in 3-7% and extravesical in 11-30%. The intramural form, especially small tumors, may not produce symptoms hardening detection. We report two cases of intramural bladder leiomyomas in asymptomatic men observed incidentally by transabdominal ultrasonography during the follow-up of benign prostatic hyperplasia. We discuss the diagnosis and management of these lesions

Urinary incontinence following surgery for BPH: the role of aging on the incidence of bladder dysfunction

PURPOSE: The reported incidence of urinary incontinence (UI) due to bladder dysfunction following surgery of BPH is variable. We described the causes of incontinence in a large group of men that developed this unsual complication and analyzed the influence of age on the prevalence of bladder dysfunction. MATERIALS AND METHODS: We wvaluated a total of 125 patients with urinary incontinence following surgical treatment for BPH : Transurethral resection of the prostate (81men) and open prostatectomy (44 men). A third group of 21 patients with incontinence following radical prostatectomy was used for comparison. All patients underwent urodynamic analysis. Urethral Sphincter Insufficiency (USI)was defined as involuntary loss of urine induced by Valsalva maneuver in the absence of a detrusor contraction. Bladder dysfunction was defined as detrusor overactivity and/or decreased compliance. RESULTS: Urethral sphincter insufficiency was the most common etiology of urinary incontinence in the three groups of patients. However, bladder dysfunction was observed in 59.3%, 56.8% and 57.1% of patients who underwent transurethral resection, open prostatectomy and radical prostatectomy, respectively. Median patient age was 69 and 75 years for patients with and without bladder dysfunction, respectively. A logistic regression model for the presence of bladder dysfunction showed that age was a statistically significant predictor. CONCLUSIONS: Urethral Sphincter insufficiency is the main cause of incontinence following surgery for BPH. Bladder dysfunction may be the isolated cause of incontinence in approximately 25% of patients. The chances of bladder dysfunction rises 5.3% for each year added to patient age. Patients older than 70 years have twice the probablility of post procedural incontinence