Abiraterone Acetate in Patients with Advanced Castrate Resistant Prostate Cancer: Initial Real Life Experience in 2 Cancer Units
Pages 42-46
Jamal Zekri, Ayman Ramadan, Muthu Kumar and Rasha Haggag

DOI: http://dx.doi.org/10.6000/1927-7229.2016.05.01.6
Published: 05 April 2016

Abstract: Introduction: Abiraterone Acetate (AA) improves outcome of patients with castrate resistant prostate cancer (CRPC) and is currently recommended for chemo-naïve patients and after progression on chemotherapy. We reviewed our initial experience with the use of AA in these patients.

Patients and Methods: Forty six consecutive CRPC patients were treated with AA 1000 mg/day and prednisolone 5 mg twice daily in 2 cancer centres in England and Saudi Arabia. Treatment was continued until disease progression or unacceptable toxicity. Patients achieving prostate specific antigen decline (PSA) ≥ 50% were considered as marker responders.

Results: Median age was 76 (52-91) years. 28 and 18 patients received AA in pre-chemotherapy and post-chemotherapy setting respectively. PSA marker response was achieved in 56.1% (23/41) assessable patients. Objective radiological response rate was seen in 31.6% (6/19) and stable disease in 15.8% (3/19) assessable patients. After a median follow up of 20 months, median time to PSA progression was 12 months (95% CI: 9.5-14.5) and median overall survival was not reached (mean = 21 months, 95% CI: 18-24.5). Toxicity was assessed in 18 patients. All grades adverse events of special interest were hypokalaemia (22%) and hypertension (11%).

Conclusion: In daily clinical practice, AA is an effective treatment for patients with CRPC. It produces meaningful marker and objective responses, marker progression free survival and OS that are comparable to those reported in clinical trials. Monitoring of blood pressure and serum potassium is recommended.

Current Concepts and New Insights from Mouse Models of Mammary Tumors on Epithelial Mesenchymal Transition and its Synergy with Mutant p53
Pages 191-206
A. Piersigilli, A. D. Borowsky, Q. Chen, N.E. Hubbard and R.D. Cardiff
DOI: http://dx.doi.org/10.6000/1927-7229.2015.04.04.8
Published: 18 December 2015

Abstract: Epithelial Mesenchymal Transition (EMT) is the transdifferentiation of epithelial cells into a mesenchymal phenotype. This process occurs during embryogenesis but also in wound healing and in tumors. The neoplastic EMT is characterized by variably complete shedding of epithelial architectural features and acquisition of mesenchymal traits. In immunohistochemistry a variable coexpression of cytokeratins, vimentin or alpha-smooth muscle actin with loss of E-cadherin and other interepithelial adhesion molecules is characteristic. Such transition is associated with mutations both at the genetic (somatic) and epigenetic levels and is believed to confer a more advantageous phenotype for local and distant spread of cancer cells. Mammary carcinoma can exhibit EMT features in humans and mice and it tends to occur more frequently in women with tumors bearing a worse prognosis such as the claudin low subtype within the triple negative cancer. Missense mutation of TP53 is one of the most common mutations in cancer and it is frequently found in EMT tumor types, often with a more aggressive behavior. The current literature and survey of our mouse EMT cases in the Genomic Pathology Center image archives demonstrate a synergy between p53 and EMT that is independent of the initiating oncogene. However, p53 mutation is not sufficient or causal for EMT. Moreover, despite the local malignant behavior, processes such as spontaneous metastases and Mesenchymal Epithelial Transition (MET) appear not to be as frequent and obvious as previously hypothesized.