Lateral epicondylitis (LE) is difficult to manage and can result in significant patient morbidity. Currently, the clinical use of platelet-rich plasma (PRP) for painful tendons has received attention, but its efficacy remains controversial. This study aimed to investigate the clinical effects of PRP and its biological components. A total of 156 patients with LE were randomly divided into group 1, treated with a single injection of 2-ml autologous PRP, and group 2, treated with a control received only physical therapy without injection. Both groups used a tennis elbow strap and performed stretching and strengthening exercises during 24 weeks' follow-up. Pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and magnetic resonance imaging (MRI). White blood cell count, platelet count, and levels of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, transforming growth factor-β (TGF-β), vascular endothelial growth factor, epithelial growth factor, and interleukin-1 β in PRP were measured and investigated for statistical correlation with the clinical score. At 24 weeks, all pain and functional variables, including VAS score, Mayo Clinic performance scores, and MRI grade, improved significantly in group 1 (p < 0.05). PDGF-AB, PDGF-BB, and TGF-β levels were more significantly increased in PRP than in whole blood. TGF-β level significantly correlated with Mayo Clinic performance score and MRI grade improvement. Thus, TGF-β level in PRP is considered to play a pivotal role in tendon healing. These results may contribute to identifying the best protocol for PRP application in tendinopathies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:913-920, 2018.
Receptor tyrosine kinase MET (c-MET) has received considerable attention as a potential target for gastric cancer (GC) therapy and a number of c-MET inhibitors have been developed. For successful drug development, proper preclinical studies especially using patient derived cancer cell lines are very important. We profiled MET and MET-related characteristics in 49 GC cell lines to utilize them as models in preclinical studies of GC. Forty-nine cell lines were analyzed for genetic, biological, and molecular status to characterize MET and MET-related molecules. Four c-MET inhibitors were tested to elucidate the dependency on MET pathway in the 49 GC cell lines. Six of 49 cell lines were MET amplified with overexpression of c-MET and p-MET. The variants of MET were not associated with c-MET expression or amplification. Hs746T showed an exon 14 deletion in conjunction with MET amplification. The cell lines were divided into 6 MET amplified, 2 c-MET overexpressed, 2 hepatocyte growth factor (HGF) overexpressed, and 39 MET-negative subgroups. Except tivantinib, the c-MET inhibitors showed higher inhibition (%) in MET amplified than in MET nonamplified cell lines that MET amplified cell lines showed MET pathway dependency. However, the c-MET overexpressed and HGF overexpressed cell lines showed moderate dependency on MET pathway. Well-characterized cell lines are very important in studying drug development. Our 49 GC cell lines had various characteristics of MET and MET-related molecules and MET pathway dependency. These provide a promising platform for development of various RTK inhibitors including c-MET inhibitors.
BackgroundSeveral methods using simple anteroposterior (AP) radiographs have been suggested for the measurement of anteversion of the cup component after total hip arthroplasty. Herein, we compared six widely used anteversion measurement methods using two different types of AP radiograph, the conventional pelvis AP and hip-centered AP radiographs, to identify the measurement method and the type of radiograph that would provide the highest accuracy and reliability.MethodsWe developed two custom-made bi-planar anteversion measurement models for the validation test. The models were designed for pelvis AP and hip-centered AP radiographs, respectively. The radiographs were acquired using the inclination angles of both models, changing from 10° to 70° at 10° increments. For each inclination angle, anteversion was changed from 0° to 30° at 5° increments. The measurements were obtained independently by two orthopedic surgeons blinded from each other’s measurements, using the methods of 1) Pradhan et al., 2) Lewinnek et al., 3) Widmer et al., 4) Liaw et al., 5) Hassan et al., and 6) Ackland et al. The measurements were repeated after 2 months. The accuracy, compared with that of the reference angle, and intra-observer and inter-observer reliabilities of each method were calculated.ResultsThe highest accuracy was found when the method of Liaw et al. was used with hip-centered AP radiographs, which showed a difference of 1.37° ± 1.73 from the reference angle. Moreover, regardless of the type of radiograph, the methods by Pradhan et al., Lewinnek et al., and Liaw et al. showed excellent correlations with the reference anteversion. However, substantial differences were found when the methods by Widmer et al., Hassan et al., and Ackland et al. were used, regardless of the type of radiograph used. When anteversion was measured in an inclination between 30° and 50°, the method of Pradhan et al., when used with pelvis AP radiographs, showed the highest accuracy (1.23° ± 0.92°). We also found no significant difference in anteversions between the measurements made on pelvic and hip-centered AP radiographs. Both interobserver and intraobserver reliabilities were high for all the measurements tested.ConclusionsThe methods by Pradhan et al., Liaw et al., and Lewinnek et al. may provide relatively accurate anteversion measurements with high reliability, regardless of the type of radiograph.
PurposeThe aim of the current study is to report the advantage and disadvantage of total hip arthroplasty performed in direct anterior approach (DAA) by comparing it to the posterolateral approach (PLA).Materials and MethodsTwenty-five hip arthroplasty done in DAA (12 total hip arthroplasty [THA] and 13 bipolar hemiarthroplasty [BHA]) were compared with the same number done in PLA (13 THA and 12 BHA). Intraoperative assessments including operation time, anesthetic time, bleeding amount were recorded with intraoperative complications. Immediate postoperatively, position of the prosthesis and leg length discrepancy were measured and were compared between the two approaches.ResultsThe operation time was 22 minutes and 19 minutes longer in DAA for THA and BHA respectively while the anesthetic time difference was 26 and 10 respectively. However, these parameters showed no statistical difference. No significance was found when bleeding amount was compared. For DAA, cup alignment was within safe zone in 100% both for inclination and for anteversion while this was 83.3% and 75.0% respectively in PLA. Leg length difference was 3 mm in DAA and 5 mm in PLA but had no significant difference. Tensor fascia lata tear was the most common complication occurring in 9 patients.ConclusionAlthough significant was not reached there was trend toward more operation time and anesthetic time when DAA was used. However, the trend also showed that cup and stem were likely to be in more accurate position and in adequate size which is likely due to the accurate use of fluoroscopy.
Background/Aim: Casein kinase 2 (CK2) is involved in multiple cellular processes. Furthermore, its overexpression in several human cancers has been associated with tumor progression. In this study, we evaluated the efficacy of the CK2 inhibitor, CX-4945, in gastric cancer cell lines and explored the potential predictive biomarkers for CX-4945 sensitivity. Materials and Methods: The sensitivity to CX-4945 was screened in 49 gastric cancer cell lines by the MTT assay. The mRNA and protein expression of CK2 subunits (α and α') were determined using qRT-PCR and western blot. Furthermore, the activity of CK2α was measured by ELISA. Gene expression and mutations were analyzed via whole-exome and RNA sequencing. Results: The sensitivity to CX-4945 was determined by the inhibition rate (%) at the effective dose (10 μM) which ranged from-1% to 89% in 49 gastric cancer cell lines. CK2α', but not CK2α, mRNA expression was correlated with CX-4945 sensitivity. Conclusion: In this study, CX-4945 showed modest antitumor efficacy in gastric cancer cell lines. CK2 might represent a potential therapeutic target for gastric cancer. Gastric cancer is the most commonly diagnosed cancer in Korea and increased annual screenings indicated that the proportion of early gastric cancer increased to 73.6% of all cancer cases (1). Based on a Korea National Cancer Incidence Database (KNCI DB), gastric cancer is the second (15.2%) and third (9.5%) highest in males and females, respectively. Also, gastric cancer recorded as the forth (9.2%) and sixth (7.9%) highest cause of death in males and females, respectively (2). In America and Europe gastric cancer burden remains high (3). Several agents have been developed to treat metastatic gastric cancer including those targeting the epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor receptor (HGFR/C-Met). However, except for trastuzumab and ramucirumab, most of them have failed to show efficacy in gastric cancer (4-6). A comprehensive understanding of gastric cancer biology is needed for new drug development (7, 8). Casein kinase 2 (CK2) is a serine/threonine kinase that is a tetramer of two catalytic subunits α and α', and a regulatory subunit β. CK2 plays a critical role in multiple cellular processes such as DNA repair, maintenance of cell viability, protection of cells from apoptosis, and cell-cycle regulation (9, 10). Dysregulation of CK2 plays an important role in cancer progression via regulation of signal transduction pathways, including PI3K/AKT and the MAPK pathway (11, 12). CK2α phosphorylates p53/p21 and increases C-myc, which regulates tumor progression. Furthermore, CK2α overexpression is associated with epithelial-mesenchymal transition (EMT) (13). CK2 overexpression is also correlated with poor prognosis in various cancer types (14, 15). In gastric 6171
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