Integrin-associated CD151 is a suppressor of prostate cancer progression.

Owing to the complexity of interacting molecular networks on the cell surface, integrin-associated tetraspanin CD151 remains controversial regarding its clinical importance and functional impact in prostate cancer. The current study evaluated dynamics and clinical importance of CD151 expression and its function in prostate cancer by IHC analysis of two independent patient cohorts (n=80, 181), bioinformatic interrogation of the TCGA database, and evaluation of gene knockdown effect at the cellular level. Our data showed that aside from high mRNA expression, CD151 was primarily localized to intercellular junctions at the plasma membrane in normal prostate glands or benign tissues, regardless of nature of antibodies used. By contrast, in primary tumors from patients with metastatic disease, CD151 was largely localized in the cytosol. Furthermore, the level of the cell-cell junction-linked CD151 was inversely associated with Gleason grade and tumor stage (P<0.001 for both). The portion of primary tumors expressing junctional CD151 was also three-fold less in the metastatic patient population than its counterpart (P<0.001). In line with these observations, CD151 and its associated α3ß1 or α6ß4 integrin inversely correlated with androgen receptor (AR) at the mRNA level (Spearman coefficient: -0.44, -0.48 and -0.42) in the TCGA cohort. Expression of these adhesion molecules also correlated with DNA methylation in their promoters (Spearman coefficient: -0.37, -0.71 and -0.82). Combined, these data suggest that CD151 and associated integrins are linked to tumor metastasis through AR and the epigenetic program. Meanwhile, CD151 knockdown in E-cadherin-positive tumor cells led to increased cell proliferation and induction of the epithelial-mesenchymal transition (EMT)-like phenotype. Given the strong RGD-binding integrin dependence of EMT-featured tumor cells, we examined focal adhesion kinase (FAK), their key signaling effector, in the above patient cohorts. In contrast to CD151, FAK exhibited positive correlation with tumor grade and stage as well as AR and p53 inactivation at either mRNA, protein or genomic level. Taken together, our results suggest that CD151 represses prostate cancer by antagonizing cell proliferation, EMT and the signaling of RGD-binding integrins. Since this anti-tumorigenic role is prone to the AR-mediated transcriptional and epigenetic regulation, CD151 and possibly α3ß1 and α6ß4 integrins are of potential biomarkers for metastatic prostate cancer.

Recurrent Bladder Cancer in a Teenage Male.

Urothelial cell carcinoma of the bladder is exceedingly rare in pediatric patients. Based on current literature, bladder cancer in this population is thought to be low-grade, noninvasive, and unlikely to recur, suggesting significant biologic differences when compared to the adult population. This is a 15-year-old male diagnosed with low-grade urothelial cell carcinoma with subsequent multifocal recurrence on surveillance cystoscopy managed by induction and maintenance intravesical Bacillus Calmette-Guerin. This case highlights the challenges of management and surveillance of this rare disease.

Predictive value of epithelial-mesenchymal-transition (EMT) signature and PARP-1 in prostate cancer radioresistance.

INTRODUCTION: Epithelial-mesenchymal-transition (EMT) has been previously identified as a contributor to prostate cancer progression to metastasis and therapeutic resistance to antiandrogens and radiotherapy. In this study we conducted a retrospective analysis to investigate the significance of radiation-induced EMT and consequential changes to the tumor microenvironment in biochemical recurrence and response to radiotherapy in prostate cancer patients. METHODS: Expression profiling and localization for EMT effectors, E-Cadherin, N-Cadherin, ß-catenin and Vimentin was assessed in human prostate tumor specimens pre- and post-radiotherapy and correlated with biochemical recurrence. In addition, immunoreactivity of the DNA repair enzyme, polymerase (PARP-1) and the cytoskeletal-remodeling regulator, cofilin was evaluated in prostate tumor specimens pre- and post-radiotherapy and correlated with pre-treatment prostate-specific antigen levels (PSA). RESULTS: Our findings identified that characteristic changes associated with the EMT phenotype and its reversal to mesenchymal-epithelial-transition (MET) within the tumor microenvironment correlate with biochemical recurrence and resistance to radiotherapy among prostate cancer patients. Moreover, elevated PARP-1 expression among the tumor cells undergoing EMT implicates that DNA repair mechanisms may potentially reverse the cytotoxic effects of radiotherapy-induced DNA breaks. CONCLUSIONS: Our results suggest that EMT programming effectors, integrated with the actin cytoskeleton regulator cofilin and mesenchymal PARP-1 expression profile provide a signature of potential predictive significance of therapeutic response to radiotherapy in a subset of prostate cancer patients.

Spatial and temporal characteristics of elevated temperatures in municipal solid waste landfills.

Elevated temperatures in waste containment facilities can pose health, environmental, and safety risks because they generate toxic gases, pressures, leachate, and heat. In particular, MSW landfills undergo changes in behavior that typically follow a progression of indicators, e.g., elevated temperatures, changes in gas composition, elevated gas pressures, increased leachate migration, slope movement, and unusual and rapid surface settlement. This paper presents two MSW landfill case studies that show the spatial and time-lapse movements of these indicators and identify four zones that illustrate the transition of normal MSW decomposition to the region of elevated temperatures. The spatial zones are gas front, temperature front, and smoldering front. The gas wellhead temperature and the ratio of CH4 to CO2 are used to delineate the boundaries between normal MSW decomposition, gas front, and temperature front. The ratio of CH4 to CO2 and carbon monoxide concentrations along with settlement strain rates and subsurface temperatures are used to delineate the smoldering front. In addition, downhole temperatures can be used to estimate the rate of movement of elevated temperatures, which is important for isolating and containing the elevated temperature in a timely manner.

Management of Vesicoureteral Reflux by Endoscopic Injection of Dextranomer/Hyaluronic Acid in Adults.

A 74-year-old man presented for evaluation after discovery of a left bladder-wall tumor. He underwent transurethral resection of bladder tumor (TURBT) operation for treatment of low-grade, Ta urothelial cancer of the bladder. The patient developed recurrent disease and returned to the operating room for repeat TURBT, circumcision, and administration of intravesical mitomycin C. The patient developed balanitis xerotica obliterans 4 years post-circumcision, requiring self-dilation with a catheter. He subsequently developed 3 consecutive episodes of left-sided pyelonephritis. Further investigation with voiding cystourethrogram (VCUG) revealed Grade 3, left-sided vesicoureteral reflux (VUR). Due to existing comorbidities, the patient elected treatment with endoscopic dextranomer/hyaluronic acid injection. A post-operative VCUG demonstrated complete resolution of left-sided VUR. This patient has remained symptom free for 8 months post-injection, with no episodes of pyelonephritis.

Inflammation in prostate cancer progression and therapeutic targeting.

Chronic inflammation contributes to the onset and progression of human cancer, via modifications in the tumor microenvironment by remodeling the extracellular matrix (ECM) and initiating epithelial mesenchymal transition (EMT). At the biological level, chronically inflamed cells release cytokines that are functionally dictating a constitutively active stroma, promoting tumor growth and metastasis. In prostate cancer, inflammation correlates with increased development of "risk factor" lesions or proliferative inflammatory atrophy (PIA). Chronic inflammation in benign prostate biopsy specimens can be associated with high-grade prostate tumors in adjacent areas. In this article, we discuss the current understanding of the incidence of inflammation in prostate cancer progression and the significance of the process in therapeutic targeting of specific inflammatory signaling pathways and critical effectors during tumor progression. Further understanding of the process of chronic inflammation in prostate tumor progression to metastasis will enable development and optimization of novel therapeutic modalities for the treatment of high-risk patients with advanced disease.

Hand-held dynamometry correlation with the gold standard isokinetic dynamometry: a systematic review.

OBJECTIVE: To examine the current evidence regarding the reliability and validity of hand-held dynamometry for assessment of muscle strength in the clinical setting. DATA SOURCES: A search was conducted of the following databases: Cochrane, MEDLINE, PubMed, PEDro, OTseeker, Index to Chiropractic Literature (ICL), and MANTIS, from inception until January 29, 2010. STUDY SELECTION: The MeSH subject heading "muscle strength dynamometer" was searched, in isolation and in combination with the text word phrases "hand-held dynamometer" and "isokinetic." Four hundred fifty-four different studies met this search and were reviewed for possible inclusion. DATA EXTRACTION: Two independent reviewers assessed the quality of the included manuscripts. The PEDro data collection system was used in conjunction with the Cochrane Diagnostic Test Accuracy Description. A third reviewer was used when there was disagreement between the primary reviewers. DATA SYNTHESIS: Seventeen manuscripts met the inclusion criteria for this review, with a total of 19 studies (2 of the manuscripts involved 2 separate studies) that compared hand-held dynamometry with an identified reference standard (isokinetic muscle strength testing). The results demonstrated minimal differences between hand-held dynamometry and isokinetic testing. CONCLUSIONS: Considering hand-held dynamometry's ease of use, portability, cost, and compact size, compared with isokinetic devices this instrument can be regarded as a reliable and valid instrument for muscle strength assessment in a clinical setting.

Ice hockey players using a weighted implement when training on the ice: a randomized control trial.

The purpose of this study was to investigate the potential for improving hockey players'performance using a weighted implement on the ice. Forty-eight players were tested using a grip strength dynamometer They also were assessed on their abilities to stick-handle. The participants were randomly placed into a control or research group. The conditioning drills were performed for 10-15 min 3 days/week for 6 weeks. Use of the weighted implement resulted in a significantly enhanced grip strength endurance and stick-handling ability (p < .05). Using weighted implements prior to a regular ice hockey training session may be of benefit to young hockey players to enhance their grip strength endurance and stick-handling abilities.

Severe aberrant glenohumeral motor patterns in a young female rower: a case report.

BACKGROUND: This case features an 18-year-old female with glenohumeral dysrhythmia and subluxation-relocation patterns. This unusual case highlights the need for careful examination and consideration to the anatomical structures involved.Conventional approaches to shoulder examination include range of motion, orthopaedic tests and manual resistance tests. We also assessed the patient's cognitive ability to coordinate muscle function. With this type of assessment we found that co-contraction of local muscle groups seemed to initially improve the patients abnormal shoulder motion. With this information a rehabilitation method was instituted with a goal to maintain the improvement. CASE PRESENTATION: An 18-year-old female with no history of trauma, presented with painless kinesiopathology of the left shoulder (in abduction) consisting of dysrhythmia of the glenohumeral joint and early lateral rotation of the scapula. Examination also showed associated muscle atrophy of the lower trapezius and surrounding general muscle weakness. We used an untested functional assessment method in addition to more conventional methods.Exercise rehabilitation interventions were subsequently prescribed and graduated in accordance with what is known as the General Physical Rehabilitation Pyramid. CONCLUSION: This paper presents an unusual case of aberrant shoulder movement. It highlights the need for careful examination and thought regarding the anatomical structures and normal motor patterns associated with the manoeuvre being tested. It also emphasised the use of co-contraction during examination in an attempt to immediately improve a regional dysrythmia if there is suspicion of a regional aberrant motor pattern. Further research may be warranted to test this approach.

Introduction of a pyramid guiding process for general musculoskeletal physical rehabilitation.

Successful instruction of a complicated subject as Physical Rehabilitation demands organization. To understand principles and processes of such a field demands a hierarchy of steps to achieve the intended outcome. This paper is intended to be an introduction to a proposed pyramid scheme of general physical rehabilitation principles. The purpose of the pyramid scheme is to allow for a greater understanding for the student and patient. As the respected Food Guide Pyramid accomplishes, the student will further appreciate and apply supported physical rehabilitation principles and the patient will understand that there is a progressive method to their functional healing process.

Detecting lung injury in patients with pulmonary edema.

OBJECTIVE: Current entry rules for clinical trials of acute lung injury (ALI) depend on clinical criteria and arterial blood gas measurements. The objective of this study was to determine whether estimates of pulmonary vascular permeability could be used to more accurately identify patients with ALI for this purpose. DESIGN AND SETTING: Cross-sectional study in a university hosptial in a large metropolitan city. PATIENTS AND PARTICIPANTS: 21 patients with noncardiogenic pulmonary edema, 7 patients with hydrostatic forms of pulmonary edema, and 10 healthy volunteers. INTERVENTIONS: Positron emission tomographic (PET) imaging with (68)Ga-labeled transferrin, or gamma-camera scintigraphy (gamma-S) with (99m)Tc-labeled albumin. All patients were studied within 24 h of onset, and all were selected exclusively on the basis of radiographic, not clinical, criteria. PET estimates of PTCER were used as a "gold standard." MEASUREMENTS AND RESULTS: Radioactivity data were analyzed to compute the pulmonary transcapillary escape rate (PTCER) and the normalized slope index. PTCER by gamma-S was more strongly correlated to PTCER(PET) than normalized slope index by gamma-S. Although PTCER(gamma) was significantly correlated with PaO2/FIO2, it did not distinguish patients with noncardiogenic pulmonary edema from those with hydrostatic pulmonary edema. CONCLUSIONS: These data cast doubt on whether the gamma-S method can be used as a screening tool in clinical trials of ALI.