MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies showed altered expression levels of several microRNAs in glioblastomas. In this study, we examined the expression levels of selected microRNAs in 22 primary glioblastomas and six specimens of adult brain tissue by real-time PCR method. In addition, we examined methylation status of MGMT promoter by methylation-specific real-time PCR, as this has been shown to be a predictive marker in glioblastomas. MGMT methylation status was not correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiR-221 (p=0,016), miR-222 (p=0,038), miR-181b (p=0,036), miR-181c (p=0,043) and miR-128a (p=0,001) were significantly down-regulated in glioblastomas. The most significant change was observed for up-regulation in miR-21 expression in glioblastomas (p<0,001). MiR-181b and miR-181c were significantly down-regulated in patients who responded to RT/TMZ (p=0,016; p=0,047, respectively) in comparison to patients with progredient disease. Our data indicate for the first time that expression levels of miR-181b and miR-181c could serve as a predictive marker of response to RT/TMZ therapy in glioblastoma patients.

Currently, there are no effective biomarkers for ovarian cancer prognosis or prediction of therapeutic response. The objective of this study was to examine a panel of 10 serum biochemical parameters for their ability to predict response to chemotherapy, progression and survival of ovarian cancer patients. Sera from ovarian cancer patients were collected prior and during chemotherapy and were analysed by enzyme-linked immunosorbent assay for CA125, kallikreins 5, 6, 7, 8, 10 and 11, B7-H4, regenerating protein IV and Spondin-2. The odds ratio and hazard ratio and their 95% confidence interval (95% CI) were calculated. Time-dependent receiver-operating characteristic (ROC) curves were utilised to evaluate the prognostic performance of the biomarkers. The levels of several markers at baseline (c0), or after the first chemotherapy cycle (rc1), predicted chemotherapy response and overall or progression-free survival in univariate analysis. A multiparametric model (c0 of CA125, KLK5, KLK7 and rc1 of CA125) provided predictive accuracy with area under the ROC curve (AUC) of 0.82 (0.62 after correction for overfitting). Another marker combination (c0 of KLK7, KLK10, B7-H4, Spondin-2) was useful in predicting short-term (1-year) survival with an AUC of 0.89 (0.74 after correction for overfitting). All markers examined, except KLK7 and regenerating protein IV, were powerful predictors of time to progression (TTP) among chemotherapy responders. Individual and panels of biomarkers from the kallikrein family (and other families) can predict response to chemotherapy, overall survival, short-term (1-year) survival, progression-free survival and TTP of ovarian cancer patients treated with chemotherapy.

The known challenge of underutilization of data and biological material from biorepositories as potential resources for medical research has been the focus of discussion for over a decade. Recently developed guidelines for improved data availability and reusability—entitled FAIR Principles (Findability, Accessibility, Interoperability, and Reusability)—are likely to address only parts of the problem. In this article, we argue that biological material and data should be viewed as a unified resource. This approach would facilitate access to complete provenance information, which is a prerequisite for reproducibility and meaningful integration of the data. A unified view also allows for optimization of long-term storage strategies, as demonstrated in the case of biobanks. We propose an extension of the FAIR Principles to include the following additional components: (1) quality aspects related to research reproducibility and meaningful reuse of the data, (2) incentives to stimulate effective enrichment of data sets and biological material collections and its reuse on all levels, and (3) privacy-respecting approaches for working with the human material and data. These FAIR-Health principles should then be applied to both the biological material and data. We also propose the development of common guidelines for cloud architectures, due to the unprecedented growth of volume and breadth of medical data generation, as well as the associated need to process the data efficiently.

To outline an outpatient-based treatment for children with relapsed solid tumors, who already have been extensively pretreated, we defined a 4-drug protocol named COMBAT (combined oral maintenance biodifferentiating and antiangiogenic therapy). Using this protocol, we performed a pilot study to determine its feasibility in children with relapsed and/or high-risk pediatric solid tumors. Patients and Methods: 22 children received the COMBAT protocol. Treatment consisted of daily celecoxib administration along with daily 13-cisretinoic acid (2 weeks on / 2 weeks off) and cycles of metronomic temozolomide (90 mg/m2 for 42 days) and low-dose etoposide (21 days). The treatment was scheduled for a period of 1 year. Results: 9 of the 14 patients assessable for response demonstrated evidence of treatment benefit manifested as prolonged disease stabilization or response. The protocol medication was well tolerated with very good compliance. Only minimal side effects where observed which responded to dose modification or local therapy. Conclusions: The COMBAT regimen is well tolerated by patients with intensive prior therapy including myeloablative regimens. Favorable responses observed in this cohort of patients support the further exploration of this and/or similar strategies in the treatment of pediatric solid tumors.

Background: The outcome of children with refractory/relapsed malignancies remains poor and novel therapies are urgently required. One of the promising approaches is metronomic chemotherapy. We present the clinical results of 74 children with advanced solid tumors treated according to treatment recommendation with data registry in three European pediatric centers. Methods: COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) included low-dose daily temozolomide, etoposide, celecoxib, vitamin D, fenofibrate and retinoic acid. From 2004 to 2010, 74 children were enrolled. Results: The 2-year overall survival (OS) was 43.1% (median 15.4, range 1.3–69.9 months). Of the 74 patients, 50 patients (68%) died and 24 are alive: 6 (8%) with progressive disease, 7 (9%) with stable disease/partial response and 11 (15%) in complete response. Median time to response was 6 months. Of 62 patients with initially measurable disease, 25 (40%) had radiological response or stable disease. Fourteen of 25 showing clinical benefit responded within the first 6 months. The treatment was well tolerated on an outpatient basis. Regarding non-hematological toxicity of grade ≥2, hepatotoxicity of grade 3 occurred in 8 children and grade 3 cheilitis in 16 children. Conclusion: COMBAT is a feasible and effective treatment option for patients with relapsing/refractory malignancies. The treatment is well tolerated with a low acute toxicity profile.