BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.
Cell Movement , Cell Proliferation , Neovascularization, Pathologic , Prostatic Neoplasms , Male , Animals , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Humans , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Cell Line, Tumor , Mice, Knockout , Glycoproteins/metabolism , Neoplasm Invasiveness , Mice , Gene Expression Regulation, Neoplastic , Angiogenesis , Zn-Alpha-2-Glycoprotein
Osteonecrosis of the humeral head is an uncommon condition, and treatment options are controversial. The shoulder is the second most common location for osteonecrosis, typically presenting between the second and fifth decades of life. Early diagnosis and treatment are essential because osteonecrosis may progress and lead to significant pain and loss of function. Nonoperative options are limited and are based on addressing the cause of the osteonecrosis. Multiple surgical treatments have been described, and these techniques continue to evolve. Open core decompression of the humeral head has been found to be an effective surgical option to restore blood supply and stimulate new bone formation. The evolution of arthroscopic techniques combined with biological adjuncts allows a minimally invasive approach with potential to accelerate revascularization and bone growth. We describe our technique for arthroscopic-assisted intraosseous bioplasty of the humeral head for the treatment of osteonecrosis.
Current clinical brain tumour therapy practices are based on tumour resection and post-operative chemotherapy or X-ray radiation. Resection requires technically challenging open-skull surgeries that can lead to major neurological deficits and, in some cases, death. Treatments with X-ray and chemotherapy, on the other hand, cause major side-effects such as damage to surrounding normal brain tissues and other organs. Here we report the development of an integrated nanomedicine-bioelectronics brain-machine interface that enables continuous and on-demand treatment of brain tumours, without open-skull surgery and toxicological side-effects on other organs. Near-infrared surface plasmon characteristics of our gold nanostars enabled the precise treatment of deep brain tumours in freely behaving mice. Moreover, the nanostars' surface coating enabled their selective diffusion in tumour tissues after intratumoral administration, leading to the exclusive heating of tumours for treatment. This versatile remotely controlled and wireless method allows the adjustment of nanoparticles' photothermal strength, as well as power and wavelength of the therapeutic light, to target tumours in different anatomical locations within the brain.
Brain Neoplasms , Nanoparticles , Photochemotherapy , Animals , Brain Neoplasms/drug therapy , Cell Line, Tumor , Gold/therapeutic use , Mice , Theranostic Nanomedicine
Cartilage defects of the humeral head in young, active patients provide a challenge to treating surgeons. The causes of humeral head osteochondral lesions are variable, but these lesions most commonly result from trauma and recurrent glenohumeral instability. Palliative and reparative techniques such as arthroscopic debridement and microfracture have traditionally been used as surgical treatment but have high failure rates. Similarly to surgical trends in the knee, cartilage restoration in the shoulder is becoming more prevalent in younger patients. Osteochondral allograft transplantation (OAT) has been used as a joint-preserving surgical option to restore hyaline cartilage in multiple joints for decades. Although OAT is more commonly used to re-establish the subchondral bony architecture in the treatment of recurrent shoulder instability, the procedure may also be indicated in young, active patients with focal humeral head chondral defects. OAT has been shown in early studies to provide improvement in functional outcome scores and good long-term graft survival with relatively low rates of complications. This report describes our straightforward, reproducible technique for the treatment of large, oblong chondral defects of the humeral head using OAT.
Superior capsular reconstruction is a powerful tool for the treatment of massive irreparable rotator cuff tears. Several authors have described this evolving technique. Issues of graft sizing, graft passage, graft tensioning, and suture management make this a challenging procedure even in the hands of experienced shoulder surgeons. We describe our arthroscopic technique for superior capsular reconstruction using nonirradiated human acellular dermis. We introduce several techniques for graft passage and tensioning that may help to simplify this challenging procedure and make it more reproducible.
BACKGROUND: Ulnar collateral ligament (UCL) injuries represent one of the most common impairments to the throwing arm of professional pitchers. Return to play and postoperative performance metrics have been studied extensively, but pitch selection before and after surgery has not been evaluated. PURPOSE/HYPOTHESIS: This study aimed to characterize the effects of UCL reconstruction on pitch selection in Major League Baseball (MLB) pitchers. We hypothesized that pitchers will throw fewer fastballs and a greater percentage of off-speed pitches after undergoing UCL reconstruction. STUDY DESIGN: Retrospective cohort study; Level of evidence, 3. METHODS: Using publicly available data, we evaluated MLB pitchers who underwent UCL reconstruction between 2003 and 2014. Pitching data were collected for the 2 seasons before UCL reconstruction as well as the first 2 seasons after reconstruction; the data consisted of the total number of pitches thrown and the percentage of fastballs, curveballs, changeups, and sliders. Repeated-measures analysis of variance was used with post hoc least significant difference pairwise t tests to evaluate for statistical significance at P < .05. RESULTS: Overall, 87 pitchers (mean age, 28.2 ± 3.5 years) met all inclusion and exclusion criteria. There was a statistically significant difference in the total number of pitches thrown before and after surgery (P < .01) as well as in the percentage of fastballs thrown before and after surgery (P = .02). There was also a statistically significant increase in the use of curveballs between 1 and 2 years postoperatively (7.5% and 8.8%, respectively; P = .01). No other findings were statistically significant. CONCLUSION: Pitchers who underwent UCL reconstruction were shown to have a statistically significant decline in the percentage of fastballs thrown postoperatively as compared with before injury, with a compensatory trend toward an increased use of curveballs and sliders.
