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

Successful up-scaled population interventions to reduce risk factors for non-communicable disease in adults: Results from the International Community Interventions for Health (CIH) project in China, India and Mexico

Background: Non-communicable disease (NCD) is increasing rapidly in low and middle-income countries (LMIC), and is associated with tobacco use, unhealthy diet and physical inactivity. There is little evidence for up-scaled interventions at the population level to reduce risk in LMIC. Methods: The Community Interventions for Health (CIH) program was a population-scale community intervention study with comparator population group undertaken in communities in China, India, and Mexico, each with populations between 150,000-250,000. Culturally appropriate interventions were delivered over 18-24 months. Two independent cross-sectional surveys of a stratified sample of adults aged 18-64 years were conducted at baseline and follow-up. Results: A total of 6,194 adults completed surveys at baseline, and 6,022 at follow-up. The proportion meeting physical activity recommendations decreased significantly in the control group (C) (44.1 to 30.2%), but not in the intervention group (I) (38.0 to 36.1%), p<0.001. Those eating ≥5 portions of fruit and vegetables daily decreased significantly in C (19.2 to 17.2%), but did not change in I (20.0 to 19.6%,), p=0.013. The proportion adding salt to food was unchanged in C (24.9 to 25.3%) and decreased in I (25.9 to 19.6%), p<0.001. Prevalence of obesity increased in C (8.3 to 11.2%), with no change in I (8.6 to 9.7%,) p=0.092. Concerning tobacco, for men the difference-in-difference analysis showed that the reduction in use was significantly greater in I compared to C (p=0.014) Conclusions: Up-scaling known health promoting interventions designed to reduce the incidence of NCD in whole communities in LMIC is feasible, and has measurable beneficial outcomes on risk factors for NCD, namely tobacco use, diet, and physical inactivity

Expression of COX-2, NF-κB-p65, NF-κB-p50 and IKKα in malignant and adjacent normal human colorectal tissue

Peer reviewedPublisher PD

NF-kappa B/PPAR gamma and/or AP-1/PPAR gamma `on/off&apos; switches and induction of CBP in colon adenocarcinomas: correlation with COX-2 expression

Background and aims: Several studies indicate that peroxisome proliferator-activated receptor gamma (PPAR gamma) represses activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B) transcriptional activity and this negative cross-talk occupies an important role in carcinogenesis. The present study evaluated the differential expression profile of AP-1 constituents (c-FOS and phosphorylated-active pc-JUN), p-I kappa B-alpha (phosphorylated I kappa B-alpha, a signaling intermediate of NF-kappa B pathway), PPAR gamma, cyclic AMP-response element binding-binding protein (CBP, a known AP-1, NF-kappa B, and PPAR gamma transcriptional coactivator), epidermal growth factor receptor (EGF-R), p53, and COX-2 in normal colonic epithelial cells and colon adenocarcinoma cells. Materials and methods: Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from 60 patients with colon adenocarcinomas. A molecular profile was created for each patient and the induction or down-regulation of each pathway from normal to cancer cells was documented. Relationships between transcription factors and downstream molecular targets were evaluated by Spearman’s rho correlation coefficient and validated by nonparametric Kruskal-Wallis test. Results: P-I kappa B-alpha (P &lt; 0.001), CBP (P &lt; 0.001), c-FOS (P=0.047), pc-JUN (P=0.047), and EGF-R (P &lt; 0.001) were up-regulated in colon adenocarcinomas while PPAR gamma (P &lt; 0.001) was concomitantly down-regulated. p-I kappa B-alpha, CBP, pc-JUN, EGF-R, and p53 expression all correlated positively with COX-2 while PPAR gamma expression correlated inversely with COX-2. Interpretation/conclusion: NF-kappa B/PPAR gamma and/or AP-1/PPAR gamma expressional ‘on/off’ switches are common molecular events during colorectal carcinogenesis. Down-regulation of PPAR gamma and induction of the CBP transcriptional coactivator can augment NF-kappa B and AP-1 transcriptional activities leading to up-regulation of COX-2 expression in colon adenocarcinoma cells. p-I kappa B-alpha, pc-JUN, and CBP could potentially provide the basis for future molecular-targeted anticancer therapies

Primary small cell bladder carcinoma: A case report and review of the current literature

Primary small cell bladder carcinoma is an extremely rare and highly aggressive tumor. Unfortunately, the optimal therapeutic strategy for the tumor is still unknown. Recently, a two-stage system for limited and extensive small cell bladder carcinoma has been suggested in analogy to the practiced staging and treatment of small cell lung carcinoma. We present a new case of small cell bladder carcinoma and discuss relevant current literature

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

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

Tumor size and T stage correlate independently with recurrence and progression in high-risk non-muscle-invasive bladder cancer patients treated with adjuvant BCG

We conducted a retrospective study to determine the prognostic significance of age, gender, associated carcinoma in situ, stage, number of tumors, and tumor size for patients with high-risk non-muscle-invasive bladder tumors treated with bacillus Calmette-Gu,rin (BCG). Data were evaluated on 144 high-risk patients with non-muscle-invasive bladder cancer treated with BCG immunotherapy after the initial treatment with transurethral resection. According to their response to BCG, patients were divided into groups, and the differences in factors, associated with recurrence and progression, were evaluated. Patients were categorized into two groups: group A, complete responders without recurrence and without progression, and group B, patients with recurrence and with progression. Furthermore, group B was divided into two subgroups: group B1, patients with recurrence, and group B2, patients with progression. Univariate analysis of group B showed that only tumor size of > 3 cm diameter (hazard ratio (HR) 11.99; 95 % confidence interval (CI) range 5.69-25.3; p < 0.001) is associated with recurrence. After multivariate analysis, the same factor appeared to be prognostic for recurrence as well. In addition, group B2 was statistically correlated with group B1. Univariate analysis proved that tumor stage (Ta or T1) is the unique factor associated with progression (HR 6.4; 95 % CI 1.29-31.9; p = 0.02). Tumor stage seems to be associated with disease's progression after the multivariate analysis too. Tumor size and stage may serve as prognostic factors, because of its independent correlation with recurrence and progression for patients with high-risk non-muscle-invasive bladder tumors treated with BCG