Leiomyosarcoma of the Prostate: Case Report and Review of 54 Previously Published Cases

Prostate leiomyosarcoma is an extremely rare and highly aggressive neoplasm that accounts for less than 0.1% of primary prostate malignancies. We present a patient with primary leiomyosarcoma of the prostate and review 54 cases reported in the literature to discuss the clinical, diagnostic and therapeutic aspects of this uncommon tumor. Median survival was estimated at 17 months (95% C.I. 20.7–43.7 months) and the 1-, 3-, and 5-year actuarial survival rates were 68%, 34%, and 26%, respectively. The only factors predictive of long-term survival were negative surgical margins and absence of metastatic disease at presentation. A multidisciplinary approach is necessary for appropriate management of this dire entity

EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF

Background:: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods:: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN), p-Iκ:B-α (phosphorylated Iκ:B-α), EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results:: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion:: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production

EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF

Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN), p-Iκ:B-α (phosphorylated Iκ:B-α), EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production

Systemic therapy of metastatic bladder cancer in the molecular era: current status and future promise

Importance of the field: Platinum-based chemotherapy is considered the standard-of-care first-line therapy for metastatic bladder cancer. Despite the initial high response rate, the vast majority of patients eventually progress and succumb to their disease, urging the need for development of novel therapies. Areas covered in this review: This article discusses the main signaling pathways implicated in the pathogenesis of bladder carcinomas, reviews recently completed and ongoing clinical trials, and anticipates the future direction of molecularly targeted agents. What the reader will gain: This manuscript presents the current status of conventional chemotherapy in advanced bladder cancer, and provides a comprehensive review of molecular targeted agents currently in clinical development for this disease. Take home message: Improved understanding of the biology of urothelial carcinogenesis has paved the way for the development of novel molecularly targeted therapies, several of which are currently tested in clinical trials. In this regard, VEGF and EGFR pathways are emerging as important therapeutic targets for metastatic bladder cancer, either alone or in combination with conventional chemotherapeutics. Other therapies, including aurora kinase inhibitors, endothelin receptor antagonists, RAS/MAPK pathway inhibitors and novel immunologic strategies, may also prove helpful in the treatment of this disease

Predictive value of telomerase reverse transcriptase expression in patients with high risk superficial bladder cancer treated with adjuvant BCG immunotherapy

We conducted a prospective study to determine whether expression of telomerase reverse transcriptase (hTERT) is associated with recurrence-free-survival (RFS) or development of invasive disease in patients with high risk superficial bladder cancer (SBC) that received adjuvant BCG immunotherapy. Thirty patients with high-grade T1 tumors were evaluated. Pre-BCG TURBT and post-BCG specimens were analyzed for hTERT nucleolar expression by immunohistochemistry. Post-BCG hTERT expression was statistically significantly lower than pre-BCG hTERT expression. Pre-BCG hTERT nucleolar staining in more than 75% of cells was associated with worse RFS (9 months vs. not yet reached, P = 0.05), while post-BCG hTERT nucleolar staining in more than 50% of the cells was associated with worse RFS (6 months vs. not yet reached, P = 0.001) and development of invasive disease. In multivariate analysis, post-BCG hTERT expression was independently associated with RFS and development of invasive disease. Immunohistochemical evaluation of hTERT may help define a subset of high risk SBC patients that will eventually fail BCG and may therefore benefit from early salvage cystectomy

Educational and Social-Ethical Issues in the Pursuit of Molecular Medicine

Molecular medicine is transforming everyday clinical practice from an empirical art to a rational ortho-molecular science. The prevailing concept in this emerging framework of molecular medicine is a personalized approach to disease prevention, diagnosis, prognosis, and treatment. In this mini-review, we discuss the educational and social-ethical issues raised by the advances of biomedical research as related to medical practice; outline the implications of molecular medicine for patients, physicians, and researchers; and underline the responsibilities of academia and the pharmaceutical industry to translate the scientific knowledge to a meaningful improvement of the quality of life across all members of society