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.

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.

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.

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.