Tine Rosenberg

Novel approaches for quantifying protein biomarkers in gliomas: benefits and pitfalls

The therapeutic paradigm of gliomas is changing from a general approach towards an individualized and targeted approach. Accordingly, the search for prognostic and predictive biomarkers, as well as the demand for quantitative, feasible and robust methods for biomarker analysis increases. We find that software classifiers can identify and quantify the expression of a given biomarker within different subcellular compartments and that such classifiers can exclude frequently occurring nontumor cells, thereby avoiding potential bias. The use of a quantitative approach provides a continuous measurement of the expression, allowing establishment of new cut-points and identification of patients with specific prognoses. However, some pitfalls must be noted. This article focuses on benefits and pitfalls of novel approaches for quantifying protein biomarkers in gliomas.

Acute hypoxia induces upregulation of microRNA-210 expression in glioblastoma spheroids.

AIM Tumor hypoxia and presence of tumor stem cells are related to therapeutic resistance and tumorigenicity in glioblastomas. The aim of the present study was therefore to identify microRNAs deregulated in acute hypoxia and to identify possible associated changes in stem cell markers. MATERIALS & METHODS Glioblastoma spheroid cultures were grown in either 2 or 21% oxygen. Subsequently, miRNA profiling was performed and expression of ten stem cell markers was examined. RESULTS MiRNA-210 was significantly upregulated in hypoxia in patient-derived spheroids. The stem cell markers displayed a complex regulatory pattern. CONCLUSION MiRNA-210 appears to be upregulated in hypoxia in immature glioblastoma cells. This miRNA may represent a therapeutic target although it is not clear from the results whether this miRNA may be related to specific cancer stem cell functions.

Intermittent, low dose carbon monoxide exposure enhances survival and dopaminergic differentiation of human neural stem cells

Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson’s disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson’s disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species. The present study investigated the effect of CO produced by a novel CO-releasing molecule on dopaminergic differentiation of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4 significantly increased the relative content of β-tubulin III-immunoreactive immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons, as assessed 6 days after differentiation. Also the number of microtubule associated protein 2-positive mature neurons had increased significantly. Moreover, the content of apoptotic cells (Caspase3) was reduced, whereas the expression of a cell proliferation marker (Ki67) was left unchanged. Increased expression of hypoxia inducible factor-1α and production of reactive oxygen species (ROS) in cultures exposed to CO may suggest a mechanism involving mitochondrial alterations and generation of ROS. In conclusion, the present procedure using controlled, short-term CO exposure allows efficient dopaminergic differentiation of human neural stem cells at low cost and may as such be useful for derivation of cells for experimental studies and future development of donor cells for transplantation in Parkinson’s disease.

Can the Ni classification of vessels predict neoplasia? A systematic review and meta-analysis

The Ni classification of vascular change from 2011 is well documented for evaluating pharyngeal and laryngeal lesions, primarily focusing on cancer. In the planning of surgery it may be more relevant to differentiate neoplasia from non‐neoplasia. We aimed to evaluate the ability of the Ni classification to predict laryngeal or hypopharyngeal neoplasia and to investigate if a changed cutoff value would support the recent European Laryngological Society (ELS) proposal of perpendicular vascular changes as indicative of neoplasia.

Reproducibility of Automated Voice Range Profiles, a Systematic Literature Review

OBJECTIVE Reliable voice range profiles are of great importance when measuring effects and side effects from surgery affecting voice capacity. Automated recording systems are increasingly used, but the reproducibility of results is uncertain. Our objective was to identify and review the existing literature on test-retest accuracy of the automated voice range profile assessment. STUDY DESIGN Systematic review. DATA SOURCES PubMed, Scopus, Cochrane Library, ComDisDome, Embase, and CINAHL (EBSCO). METHODS We conducted a systematic literature search of six databases from 1983 to 2016. The following keywords were used: phonetogram, voice range profile, and acoustic voice analysis. Inclusion criteria were automated recording procedure, healthy voices, and no intervention between test and retest. Test-retest values concerning fundamental frequency and voice intensity were reviewed. RESULTS Of 483 abstracts, 231 full-text articles were read, resulting in six articles included in the final results. The studies found high reliability, but data are few and heterogeneous. CONCLUSION The reviewed articles generally reported high reliability of the voice range profile, and thus clinical usefulness, but uncertainty remains because of low sample sizes and different procedures for selecting, collecting, and analyzing data. More data are needed, and clinical conclusions must be drawn with caution.

Therapeutic use of the HPV vaccine on recurrent respiratory papillomatosis: a systematic review and meta-analysis

BACKGROUND Recurrent respiratory papillomatosis is a benign condition caused by human papillomavirus (HPV). Surgery is the mainstay of treatment, but numerous adjuvant therapies have been applied to improve surgical outcome. Recently, HPV vaccination has been introduced, but only smaller studies of its effect have been published. The present meta-analysis is intended as a possible substitute for a proposed but not yet realized multicenter randomized controlled trial. METHODS A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. PubMed, Embase, and Cochrane were systematically searched. All retrieved studies (n = 593) were reviewed and qualitatively assessed. In addition, 2 previously unpublished data sets were included. The systematic review included 11 studies, comprising 133 patients, of whom 63 patients from 5 studies were eligible for meta-analysis. A random-effects meta-analysis was conducted for the mean difference in number of surgical procedures per month before and after vaccination. RESULTS The number of surgical procedures per month was significantly reduced after HPV vaccination compared with before vaccination (estimated mean, 0.06 vs 0.35). The mean intersurgical interval increased from 7.02 months (range, 0.30-45 months) before to 34.45 months (2.71-82 months) after HPV vaccination. CONCLUSION The present study supports the continued use of the HPV vaccine as an adjuvant treatment for recurrent respiratory papillomatosis.

Heterogenic expression of stem cell markers in patient-derived glioblastoma spheroid cultures exposed to long-term hypoxia

Aim: To investigate the time profile of hypoxia and stem cell markers in glioblastoma spheroids of known molecular subtype. Materials & methods: Patient-derived glioblastoma spheroids were cultured up to 7 days in either 2% or 21% oxygen. Levels of proliferation (Ki-67), hypoxia (HIF-1α, CA9 and VEGF) and stem cell markers (CD133, nestin and musashi-1) were investigated by immunohistochemistry. Results: Hypoxia markers as well as CD133 and partially nestin increased in long-term hypoxia. The proliferation rate and spheroid size were highest in normoxia. Conclusion: We found differences in hypoxia and stem cell marker profiles between the patient-derived glioblastoma cultures. This heterogeneity should be taken into consideration in development of future therapeutic strategies.

Can videostroboscopy predict early glottic cancer? A systematic review and meta-analysis

Correct assessment of patients with a glottic lesion is crucial for ensuring proper treatment in cases of cancer or premalignancy and for avoiding unnecessary surgery. For years, videostroboscopy (VS) has been the gold standard for assessing such lesions, but diagnostic difficulties have been described. We aim to estimate the diagnostic accuracy of VS in differentiating early glottic cancer from noninvasive lesions by conducting a systematic review and meta‐analysis of published studies.

Can videostroboscopy predict early glottic cancer

Correct assessment of patients with a glottic lesion is crucial for ensuring proper treatment in cases of cancer or premalignancy and for avoiding unnecessary surgery. For years, videostroboscopy (VS) has been the gold standard for assessing such lesions, but diagnostic difficulties have been described. We aim to estimate the diagnostic accuracy of VS in differentiating early glottic cancer from noninvasive lesions by conducting a systematic review and meta‐analysis of published studies.