Vitamin K2 in multiple sclerosis patients.

BACKGROUND: Vitamin K2 (VK2) belongs to the vitamin K family and comprises a number of subtypes differing in length of side chains consisting of isoprenoid groups (menaquinone-n, MK-n). It is essential for a number of physiological functions although the full spectrum of activity has not yet been elucidated. Due to its role in protection of mitochondrial damage, VK2 could be relevant in preventing disease progress in multiple sclerosis (MS). METHODS: We measured VK2 serum levels by the double antibody sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique in MS patients and age and sex matched controls, both under vitamin D supplementation, and related it to disease characteristics and treatment. RESULTS: Overall, 45 MS patients (31 females and 39 of the relapsing-remitting type) and 29 healthy controls (19 females) were included in the analysis. The MS patients had vastly lower VK2 blood levels than controls (235 ± 100 ng/ml vs. 812 ± 154 ng/ml, respectively). Female patients had significantly lower VK2 levels than males and a decrease with age by approximately 10% per decade was found. The VK2 levels were lower with increasing numbers of attacks per year and were higher in patients with optic nerve lesions. No consistent relationship with medications was detected. CONCLUSION: The substantially lower levels of VK2 in MS patients could be due to depletion, lower production in the gut, diminished absorption or, less likely, reduced intake of precursor vitamin K1. The role of VK2 in MS development and progress deserves further study.

Clinical neuropathology practice guide 3-2013: levels of evidence and clinical utility of prognostic and predictive candidate brain tumor biomarkers.

A large number of potential tissue biomarkers has been proposed for brain tumors. However, hardly any have been adopted for routine clinical use, so far. For most candidate biomarkers substantial controversy exists with regard to their usefulness in clinical practice. The multidisciplinary neurooncology taskforce of the Vienna Comprehensive Cancer Center Central Nervous System Unit (CCC-CNS) addressed this issue and elaborated a four-tiered levels-of-evidence system for assessing analytical performance (reliability of test result) and clinical performance (prognostic or predictive) based on consensually defined criteria. The taskforce also consensually agreed that only biomarker candidates should be considered as ready for clinical use, which meet defined quality standards for both, analytical and clinical performance. Applying this levels-of-evidence system to MGMT, IDH1, 1p19q, Ki67, MYCC, MYCN and ß-catenin, only immunohistochemical IDH1 mutation testing in patients with diffuse gliomas is supported by sufficient evidence in order to be unequivocally qualified for clinical use. For the other candidate biomarkers lack of published evidence of sufficiently high analytical test performance and, in some cases, also of clinical performance limits evidence-based confirmation of their clinical utility. For most of the markers, no common standard of laboratory testing exists. We conclude that, at present, there is a strong need for studies that specifically address the analytical performance of candidate brain tumor biomarkers. In addition, standardization of laboratory testing is needed. We aim to regularly challenge and update the present classification in order to systematically clarify the current translational status of candidate brain tumor biomarkers and to identify specific research needs for accelerating the translational pace.

Value of 1H-magnetic resonance spectroscopy chemical shift imaging for detection of anaplastic foci in diffusely infiltrating gliomas with non-significant contrast-enhancement.

OBJECTIVE: In diffusely infiltrating gliomas (DIG), positron emission tomography (PET) imaging is a powerful method for detection of anaplastic foci. Recently, (1)H-magnetic resonance spectroscopy chemical shift imaging (CSI) using choline/creatine (Cho/Cr) or choline/N-acetylaspartate (Cho/NAA) ratios has emerged as a new non-invasive, widely available alternative. The authors therefore correlated CSI with (11)C-methionine (MET)-PET data in a series of DIG with non-significant contrast-enhancement (CE). METHODS: Thirty-two patients with DIG were examined with single-slice CSI on a T MRI and MET-PET. Maximum pathological intratumoural ratios of CSI (=CSI(max)) and maximum tumour-to-normal-brain PET ratios (=PET(max); T/N ratio) were determined. Coregistration of MRI with CSI and PET was performed, and the topographic overlap of CSI(max) and PET(max) was analysed. Histological criteria of anaplasia as well as cell proliferation rate were assessed in tumour samples inside and outside CSI(max). RESULTS: CSI showed a pathological ratio in all patients, whereas PET demonstrated a pathological T/N ratio in 21/32 patients. Topographical correlation of CSI(max) and PET(max) revealed a ≥ 50% overlap in 18/21 and <50% overlap in 3/21 patients, respectively. Cho/Cr(max) and Cho/NAA(max) showed a ≥ 50% overlap in 24/32 and a <50% overlap in 8/32 patients. Cell proliferation rate was significantly higher inside than outside the CSI(max) (13.6% vs 6.9%, p<0.001). CONCLUSION: The results indicate that CSI is a promising method for detection of anaplastic foci within DIG with non-significant CE. Intraoperative use of CSI by multimodal neuronavigation may increase the reliability of detection of malignant areas in glioma surgery and therefore optimise allocation of patients to adjuvant treatments.

Prognostic relevance of p53 protein expression in glioblastoma.

TP53 plays a key role in cellular response to DNA-damaging agents, and mutation of this gene, which is associated with immunohistochemically detectable p53 protein accumulation, may influence response to chemo- and radiotherapy. We investigated immunohistochemically the influence of p53 protein accumulation in 114 consecutive cases of primary glioblastoma treated by surgery and adjuvant radio- and chemotherapy. In addition, we determined cellular proliferation index using the antibody MIB-1 and apoptotic index of tumor cells using the TUNEL-assay. Twenty-nine patients (25.4%) were considered as positive with regard to p53 protein expression (>50% p53 immunostained tumor cells). Patients with p53 positive glioblastomas were significantly younger (mean age 54.4+/-2 years) than those with p53 negative tumors (mean age 61.4+/-1.1 years) (p=0.002, Mann-Whitney test). While no significant difference in apoptotic index was found, we observed a significantly higher MIB-1 labeling index (LI) in patients with p53 positive tumors (median LI: 36.4%) compared to p53 negative ones (median LI: 23.8%) (p=0.005, Mann-Whitney test). p53 protein expression was associated with significantly longer survival in univariate analysis (p=0.0399, log-rank test). In multivariate analysis of overall survival (Cox regression) only postoperative Karnofsky performance status remained as independent prognostic factor. We conclude that glioblastoma patients with immunohistochemically detectable p53 protein expression, who received adjuvant radio- and chemotherapy, have a significantly better overall survival, possibly due to increased sensitivity to this adjuvant treatment.