While the developmental role of the SOX transcription factors in fetal chondrocyte differentiation is well documented, much less is known about the expression of SOX family members in normal and ...osteoarthritic adult cartilage. Therefore, the aim of the present study was to present a thorough analysis of SOX gene expression in normal and osteoarthritic human adult cartilage.
RNA from normal and osteoarthritic knee cartilage from human adults was analyzed by gene expression profiling using GeneChip technology (Affymetrix) and quantitative real time PCR.
Most members of the SOX transcription factor family showed no or very low expression levels in normal and osteoarthritic cartilage from adults. In contrast, SOX9 expression was fairly high in normal cartilage, amounting to approximately 20% of GAPDH levels. SOX9 transcript levels were substantially reduced in osteoarthritis. SOX6 levels were reduced, albeit starting from a low basis expression in normal tissue.
The presented data indicate that the role of the SOX transcription factor family in adult human cartilage is most probably restricted to a few members, with SOX9 being the most prominent. Furthermore, the reduction of SOX9 and SOX6 transcript levels in osteoarthritic chondrocytes might be responsible for the loss of phenotypic stability of osteoarthritic chondrocytes.
Background and purpose
This study investigated the prognostic value of androgen receptor (AR) expression of tumor cells in patients treated with surgery and subsequent radio(chemo)therapy for locally ...advanced squamous cell carcinoma of the head and neck (SCCHN).
Material and methods
The impact of AR and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively studied in 163 patients with nonmetastatic stage III/IV SCCHN. Additional factors included age, gender, ECOG performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, HPV status, extent of resection, and concurrent chemotherapy.
Results
On multivariate analysis, improved LRC was significantly associated with pre-RT hemoglobin levels ≥ 12 g/dl (risk ratio RR 2.22; 95 % confidence interval CI 1.19–4.13; p = 0.013), tumor site (RR 1.39; 95 % CI 1.14–1.70; p = 0.001), lower T category (RR 1.67; 95 % CI 1.18–2.44; p = 0.003), and lower N category (RR 4.18; 95 % CI 1.90–10.55; p < 0.001). Improved MFS was associated with AR expression (RR 2.21; 95 % CI 1.01–5.41; p = 0.048), better ECOG performance status (RR 3.19; 95 % CI 1.50–7.14; p = 0.003), lower T category (RR 2.24; 95 % CI 1.47–3.65; p < 0.001), and lower N category (RR 5.33; 95 % CI 2.07–16.63; p < 0.001). OS was positively associated with AR expression (RR 1.99; 95 % CI 1.06–4.00; p = 0.032), better ECOG performance status (RR 2.20; 95 % CI 1.20–4.09; p = 0.010), pre-RT hemoglobin levels ≥ 12 g/dl (RR 2.13; 95 % CI 1.19–3.82; p = 0.012), lower T category (RR 1.81; 95 % CI 1.30–2.62; p < 0.001), and lower N category (RR 3.41; 95 % CI: 1.65–7.80; p < 0.001).
Conclusion
Tumor cell expression of AR was an independent prognostic factor for MFS and OS and should be considered in future prospective trials.
Genetic modification of human bone marrow mesenchymal stem cells (MSC) is highly valuable for their exploitation in basic science and therapeutic applications, for example in cancer. We present here ...a new, fast and easy-to-use method to enrich a functional population of lentiviral (LV)-transduced MSC expressing enhanced green fluorescent protein (eGFP). We replaced the eGFP gene by a fusion gene of puromycin acetyltransferase and eGFP. Upon LV gene transfer and puromycin selection, we quickly obtained a pure transduced MSC population, in which growth, differentiation capacity and migration preferences were not compromised. Furthermore, we are the first to report the migration velocity of MSC among which 30% were moving and velocity of about 15 mum h(-1) was not altered by LV transduction. Manipulated MSC underwent senescence one passage earlier than non-transduced cells, suggesting the use for therapeutic intervention in early passage numbers. Upon tail vein application in nude mice, the majority of LV-transduced MSC could be detected in human orthotopic pancreatic tumor xenografts and to a minor extent in mouse liver, kidney and lung. Together, LV transduction of genes to MSC followed by puromycin selection is a powerful tool for basic research and improves the therapeutic prospects of MSC as vehicles in gene therapy.
Background and purpose
This study investigated the prognostic value of tumor cell expression of vascular endothelial growth factor (VEGF) and its receptor fms-related tyrosine kinase 1 (FLT-1) in ...patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who had been treated with adjuvant radiotherapy or radiochemotherapy.
Material and methods
The impact of tumor cell VEGF and FLT-1 expression plus 11 additional factors on loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) was retrospectively evaluated in 157 patients. The additional factors were age, gender, performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papillomavirus (HPV) status, extent of resection and chemotherapy.
Results
On multivariate analysis, improved LRC was significantly associated with an absence of VEGF expression (risk ratio, RR: 5.02; p = 0.009), lower T-category (RR: 2.00; p < 0.001), lower N-category (RR: 3.75; p < 0.001) and pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.20; p = 0.029). Improved MFS was significantly associated with an absence of VEGF expression (RR: 7.46; p = 0.002), lower T-category (RR: 1.97; p = 0.002), lower N-category (RR: 3.29; p = 0.005) and a favorable tumor location (RR: 1.34; p = 0.033); HPV positivity showed a trend towards improved MFS (RR: 1.43; p = 0.09). Improved OS was significantly associated with an absence of VEFG expression (RR: 3.22; p = 0.041), pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.47; p = 0.009), lower T-category (RR: 1.92; p < 0.001) and lower N-category (RR: 3.39; p < 0.001). FLT-1 expression was significantly associated with LRC and OS in the univariate but not in the multivariate analysis.
Conclusion
VEGF expression proved to be an independent negative predictor for LRC, MFS and OS in patients treated for locally advanced SCCHN with adjuvant radiotherapy or radiochemotherapy. FLT-1 expression was not significant in multivariate analyses.
Background and purpose
This study re-evaluated the prognostic value of HPV status for loco-regional control (LRC), metastases-free survival (MFS), and survival (OS) in patients with locally advanced ...squamous cell carcinoma of the head and neck (SCCHN). A modified definition of HPV positivity was used in the current study compared to the authors’ previous study.
Patients and methods
In the previous study of the same 170 patients, a tumor was defined as HPV-positive if it showed a positive in situ hybridization result in ≥ 10 % of tumor cells and/or positive p16 immunostaining. In the current analysis, tumors were considered HPV-positive only if they showed positive results for both in situ hybridization and p16 immunostaining. In addition to HPV status, the same 11 potential prognostic factors were investigated for treatment outcomes as in the preceding study.
Results
In the multivariate analysis of the current study, HPV positivity was significantly associated with improved LRC risk ratio (RR) 9.78; p < 0.001, MFS (RR 7.17; p = 0.008), and OS (RR 6.61; p < 0.001). In the previous study, HPV positivity was associated with LRC (RR 2.34; p = 0.014) and OS (RR 2.19; p = 0.019), but not with MFS (RR 2.04; p = 0.11).
Conclusions
Applying the new definition of HPV positivity, the impact of HPV status on the prognosis of patients irradiated for locally advanced SCCHN was more prominent than in our previous study and associated with all three investigated endpoints.
Background and purpose
Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) ...in patients treated with surgery followed by radiotherapy.
Patients and methods
The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model.
Results
On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity risk ratio (RR): 7.33; 95 %-confidence interval (CI): 2.88–19.05; p < 0.001, lower T-category (RR: 2.42; 95 %-CI: 1.47–4.33; p < 0.001), lower N-category (RR: 12.36; 95 %-CI: 3.48–78.91; p < 0.001), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 4.18; 95 %-CI: 1.73–10.53; p = 0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95 %-CI: 0.97–2.82; p = 0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22–11.80; p < 0.001), lower T-category (RR: 2.17; 95 %-CI: 1.38–3.68; p < 0.001), lower N-category (RR: 3.86; 95 %-CI: 1.60–10.85; p = 0.002), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 3.20; 95 %-CI: 1.46–7.30; p = 0.004). HPV-positivity showed a trend (RR: 2.36; 95 %-CI: n.a.; p = 0.054).
Conclusions
Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials.
Bloodstream candida infections can seed the eye via hematogenous spread and result in chorioretinitis or endophthalmitis. If undetected and untreated, this can result in permanent vision loss. Past ...studies evaluating incidence of ocular candidiasis among hospitalized patients with positive fungal blood cultures have demonstrated variable rates of occurrence, but recent studies have generally shown a lower incidence than was reported several decades ago. Given low rates of occurrence, the utility of screening patients with dilated fundus exams has been called into question. The primary aim of this investigation is to identify the rate of chorioretinitis and endophthalmitis based on dilated fundoscopy for patients with fungemia at a tertiary care hospital.
This study was a retrospective chart review of adult patients admitted to the medical centre of the University of Arkansas for Medical Sciences (UAMS) between May 1, 2014 and December 31, 2017, who had positive fungal blood cultures during their hospitalization.
There were 324 positive fungal cultures in 290 patients. Of this initial group, there were 161 eye exams. Ocular examination identified 7 of 161 patients (4.3%) with chorioretinitis or endophthalmitis.
These outcomes along with previous studies support the current guidelines that screening with dilated fundus examination for these patients is appropriate and necessary.
Objective
To identify resident applicant characteristics that increase the odds of matching to otolaryngology residency.
Study Design
Cross‐sectional analysis.
Methods
Residency applications to our ...institution from 2009 through 2013 were reviewed. The available data represented 81.1% of applicants to otolaryngology programs nationwide. Online public records were searched to determine whether an applicant matched to an otolaryngology residency position. Factors that were significantly associated with the odds of matching were determined using logistic regression.
Results
A total of 1,479 unique applications were analyzed. On univariate analysis, 27 demographic, academic, personal, medical school, prior training, and application‐specific factors were associated with the odds of matching into otolaryngology. On multivariate analysis, indicators of academic achievement, such as Alpha Omega Alpha Honor Medical Society (AOA) status, whether applicant received awards, and publications, were significantly associated with the odds of matching (odds ratio OR 2.03, 1.39, 1.66, respectively). The odds of matching increased with increasing step 1 scores (P < 0.001). Attending a medical school ranked by the U.S. News & World Report and being a U.S. citizen born in the United States significantly increased the odds of matching (OR 1.55 and 2.04, respectively), whereas being a non‐U.S. senior medical student significantly decreased the odds of matching (OR 0.33).
Conclusion
Multiple factors are associated with successfully matching into an otolaryngology residency. Although this information allows medical students to determine the strength of their application, these criteria have not been correlated with resident success. We urge selection committees to begin identifying applicant selection methods that reflect the values we want to cultivate in our future colleagues.
Level of Evidence
N/A. Laryngoscope, 127:1052–1057, 2017
PDF
