Marie Karlikova

Pre-graduate and post-graduate education in personalized medicine in the Czech Republic: statistics, analysis and recommendations.

The main goal of personalized medicine is the individualized approach to the patient’s treatment. It could be achieved only by the integration of the complexity of novel findings in diverse “omics” disciplines, new methods of medical imaging, as well as implementation of reliable biomarkers into the medical care. The implementation of personalized medicine into clinical practice is dependent on the adaptation of pre-graduate and post-graduate medical education to these principles. The situation in the education of personalized medicine in the Czech Republic is analyzed together with novel educational tools that are currently established in our country. The EPMA representatives in the Czech Republic in cooperation with the working group of professionals at the Faculty of Medicine in Pilsen, Charles University in Prague have implemented the survey of personalized medicine awareness among students of Faculty of Medicine in Pilsen—the “Personalized Medicine Questionnaire”. The results showed lacking knowledge of personalized medicine principles and students’ will of education in this domain. Therefore, several educational activities addressed particularly to medical students and young physicians were realized at our facility with very positive evaluation. These educational activities (conferences, workshops, seminars, e-learning and special courses in personalized medicine (PM)) will be a part of pre-graduate and post-graduate medical education, will be extended to other medical faculties in our country. The “Summer School of Personalized Medicine in Plzen 2015” will be organized at the Faculty of Medicine and Faculty Hospital in Pilsen as the first event on this topic in the Czech Republic.

PIVKA-II as a Potential New Biomarker for Hepatocellular Carcinoma – A Pilot Study

Aim: The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence (PIVKA-II) for hepatocellular carcinoma (HCC) diagnostics and compare it with alpha-foetoprotein (AFP), a routinely used tumour marker. Materials and Methods: A total of 332 participants were enrolled in this study: 64 with HCC, 48 with liver metastases of colorectal cancer origin, 42 with liver cirrhosis and 178 healthy individuals. Serum levels of PIVKA-II were measured using the chemiluminescent assay of the Architect 1000i System (Abbott, USA) and AFP levels using the chemiluminescent assay by DxI 800 (Beckman Coulter, USA). Results: PIVKA-II achieved better clinical sensitivity than AFP and the difference in this sensitivity was statistically significant. PIVKA-II achieved the best sensitivity (96.9%) in distinguishing between the HCC and control groups with the proposed cut-off value of 60 mAU/ml. Conclusion: Our recommendation is for addition of PIVKA-II to the routine panel of HCC tumour markers.

Relationship between follicular volume and oocyte competence, blastocyst development and live-birth rate: optimal follicle size for oocyte retrieval

To analyze oocyte competence in gonadotropin‐releasing hormone agonist (GnRHa) stimulation cycles with regard to maturity, fertilization and blastocyst rate, as well as clinical outcome (pregnancy and live‐birth rate), in relation to follicular volume, measured by three‐dimensional transvaginal sonography (3D‐TVS), and follicular fluid composition.

Stability of total prostate-specific antigen and free prostate-specific antigen after 10 years’ storage

Introduction: PSA is a serine protease composed of 240 amino acids in a single polypeptide chain and is a routine parameter in prostate cancer diagnostics. The aim of our study was to test the long-term stability of tPSA and fPSA after 10 years’ storage at −80°C. Materials and methods: We analyzed two aliquots from 55 serum samples. The first was assayed in routine testing at the time of establishing the diagnosis. The second was thawed for further testing after approximately 10 years’ storage at −80°C. The mean of storage time was 10.41 years (min–max: 9.35–11.40 years). We compared the results of tPSA and fPSA. We calculated the fPSA/tPSA ratio and compared the results of clinical evaluation. Serum tPSA and fPSA levels were assayed using chemiluminescent kits Access Hybritech PSA and free PSA. All measurements were performed using the instrument UniCel® DxI 800. Results: tPSA decreased 3.59% on average with a correlation r=0.9213, and fPSA increased at an average of 2.41% with a correlation r=0.9338. The fPSA/tPSA ratio increased 0.80% on average with a correlation r=0.9174. On clinical evaluation, five samples had fallen to a less malignant category and three samples had risen to a higher malignant category compared with the original results. Conclusion: The stability of tPSA and fPSA levels in serum is sufficient after 10 years’ storage at −80°C. Calculation of the fPSA/tPSA ratio is not recommended due to the change in the category of malignancy of 15% of the samples.

Optimal Use of Biomarkers in Oncology.

The use of biomarkers in oncology has been much more extensive than in any other diseases for more than 30 years. Their use has evolved beyond the research laboratory to more routine clinical use as in diagnosis, monitoring of disease status, and treatment efficacy. With the advances in molecular biology, other biomarkers than the “classical” serum markers are being developed for clinical use: gene mutations, microRNA, circulating tumor cells, circulating DNA, and others currently in research. Biomarkers such as these are currently being used for prediction: potential “at risk” for disease as well as response to therapy (predictive biomarkers), and for disease prognosis (prognostic biomarkers). In oncological routine, the correlation of biomarker levels with the clinical status and medical imaging methods is of great significance. The purpose of the correlation is twofold: providing sequential and/or more specific diagnostics and keeping these procedures within affordable economical limits. This special issue includes a number of reviews and research papers dealing with the above mentioned topics. Reviews on Novel Biomarkers. The advances in molecular research and various “–omics” techniques have enabled us to study a number of potential novel cancer biomarkers. Studying gene expressions and molecular pathways may lead to the discovery of new prognostic biomarkers, markers of early diagnostics, or molecular targets for therapy. E. Lastraioli et al. present a review on the expression of hERG1 potassium channels in different types of solid cancer (including breast, esophageal, gastric, colorectal, pancreatic, and other cancers). The authors, on the basis of publication review as well as their own findings, argue that hERG1 could be a novel biomarker and point out the overexpression of hERG1 in solid cancers, a feasible determination by immunohistochemistry and the potential of using them as therapy targets as the monoclonal antibody to block them is already available. M. Rihacek et al. review B-cell activating factor (BAFF), a transmembrane protein, as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. The authors report its proinflammatory properties and its contribution to cancer cachexia. Moreover, BAFF/BAFF-R signaling may be a promising target of future therapy in B-cell derived leukemias and lymphomas. Cytoglobin, a protein of the globin family, is reviewed by T. Bholah et al. Thanks to the advances in molecular research, a possible role of this protein in cancer has been suggested. In their paper, the authors overview different functions of cytoglobin and provide a perspective on potential research areas that may elucidate its role as cancer biomarker. The gene for gamma-glutamylcyclotransferase, an enzyme involved in glutathione metabolism, has recently been investigated and reported as an upregulated protein in various cancers. S. Kageyama et al. report an overview of the activities of GGCT in cancer cells. Imaging Methods and Oncology. Imaging methods provide a useful tool in cancer diagnostics and management. Their applications develop in reflection to new technologies and advances in molecular research. M. Tolia et al. report the value of preirradiated in vivo magnetic resonance spectroscopy parameters in predicting recurrence free survival for patients with high grade gliomas, who undergone postoperative radiotherapy. R. Fusco et al. present the evaluation of the diagnostic value of an imaging protocol that combines dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in patients with suspicious breast lesions. In addition, further research sought to determine if additional information provided by DWI could improve the diagnostic value of breast MRI. Predictive Biomarkers and Risk Factors. J. H. Kim and S. K. Hong report a review, based on meta-analysis of PubMed publications, on potential novel biomarkers in active surveillance of low-risk prostate cancer. These include %[-2] proPSA and Prostate Health Index (PHI), PCA3, TMPRSS2:ERG, the genomic prostate score (GPS), a panel of four kallikrein markers, and the expression levels of different cell cycle progression (CCP) genes. Y. Cao et al. review a meta-analysis of 25 independent epidemiological studies on the association between hormonal and reproductive factors and thyroid cancer risk. As the title of their paper suggests, reproductive factors but not hormonal factors are associated with thyroid cancer risk. R. V. Liubota et al. report risk factors of the invasive breast cancer locoregional recurrence. The authors discovered that the scope of the surgical intervention (breast-conserving surgery (BCS) or radical mastectomy (RME)) does not essentially affect the recurrence appearance frequency or the recurrence-free period duration. However, in the BCS group, risk factors such as the presence of metastases in the regional lymph nodes or the hyperexpression Her/2neu presence increased the frequency of the locoregional breast cancer recurrence appearance. Prognostic Biomarkers. M. Tolia et al. describe a study which aimed to identify whether or not the expression of serum baseline C-reactive protein (CRP) and albumin are related to overall survival in non-small-cell lung cancer (NSCLC). The study results suggested that, in fact, high pretreatment CRP and low albumin serum levels were promising independent prognostic factors of overall survival in NSCLC. Biomarkers in Treatment Monitoring. Several indicators, including tumor markers, are used to monitor whether or not a particular cancer treatment is efficient with tolerable toxicity for patients. However, if a tumor marker has low sensitivity and/or specificity, adding another biomarker to the regimen could potentially enhance the treatment evaluation. S. Kristiansen et al. present a study that focused on the association between hypermethylated DNA and the tumor markers CA 15-3, CEA, and TPA in serum during monitoring of patients with advanced breast cancer. Disease Monitoring and Management. A combination of biomarkers or a set of tests provide a higher sensitivity and/or specificity than a unique biomarker or test. A. Pouliakis et al. report the evaluation of classification and regression trees for the triage of women at risk for cervical intraepithelial neoplasia. The computer-assisted algorithm was based on cytological HPV DNA typing, HPV mRNA detection, p16 immunocytochemical expression, and age and parous status. The authors proposed a methodology which could dramatically reduce the number of women that would require a colposcopy. This special issue aims to prove the importance of biomarkers for the individualisation of the approach to an oncological patient and the improvement of his quality of life. Biomarkers in oncology are an important tool for diagnostics, prognosis, and therapy monitoring on condition that there is a clear goal for the biomarkers determination; biomarkers are monitored systematically and are interpreted in collaboration of the laboratory and the clinician. Single shot biomarker determination is useless and can lead to incorrect assumptions. Marie Karlikova Ondrej Topolcan Olive T. J. Wolfe Vivian Barak Tomas Zima

Education in personalized medicine in Czech Republic

Personalized medicine is a new philosophy in the health care. It consists in the application of innovative diagnostic methods and biotechnologies to the prediction of human pathologies and in the development of prevention and individual therapy-planning. The principal tool of personalized medicine is the application of new methods, mainly those of molecular biology (abbreviated as – omics methods) into all areas of medicine in order to comply with two principal goals: 1/ optimization of early diagnostics, prediction and prognosis, and 2/ rigorous individualization of therapy-planning as well as an individual approach to the patient. Final effect should be a completely new way to the prevention assurance. Actual knowledge of the principles of personalized medicine among clinicians and therefore their application are still low. Technological approaches Our first approach was to find out the level of knowledge among different population groups by means of a surway. The results confirmed the above mentioned statement. We have initiated the education of personalized medicine which is targeted at students of bachelor and master programs as well as at post graduate students, clinicians, academicians and researchers. The education is provided by the means of in-room teaching as well as e-learning and internet resources. Our goal is to provide the teaching in cooperation with national and international medical associations.