[Lactate Dehydrogenase - Old Tumour Marker in the Light of Current Knowledge and Preanalytic Conditions]. / Laktátdehydrogenáza - starý nádorový marker ve svetle soucasných poznatku a v preanalytických souvislostech.

With the development and subsequent clinical applications of anticancer immuno-and angiomodulatory therapies and expanded knowledge on significance of tumor microenvironment for disease prognosis and treatment outcome, a classical blood analyte, lactate dehydrogenase (LDH), gains in importance as a tumor marker reflecting to some extent immunosupressive and angiogenic tumour milieu. Physical extravascular hemolysis due to complicated or inaccurate blood sampling interferes strongly with quantification of LDH in serum/plasma samples. Upon correlating circulating hemoglobin level with LDH catalytic activities in 99,937 plasma samples we quantified hemolysis interference with LDH plasma levels. An increment of LDH (µkat/l) caused by hemolysis is equal to 0.002 times circulating hemoglobin level (mg/l). Thus, hemolysis interference can be mathematically subtracted from measured LDH using a formula: [LDH (measured) (µkat/l) - 0.002 × circulating hemoglobin (mg/l) ]. In other words, each increment of hemolysis equal to 100mg/l of circulating hemoglobin will result to LDH increase equal to 0.2 µkat/l. As one of the emerging predictors of treatment outcome, a cancer prognostic biomarker and dynamic tumor marker, serum/plasma LDH concentration needs to be interpreted with respect to reported hemolysis level. Also, for these purposes, quantitative determination of serum/plasma levels of free circulating hemoglobin has to be routinely performed.Key words: lactate dehydrogenase - hemolysis - preanalytical error This work was supported by MEYS via NPS I for RECAMO2020 (LO1413). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 3. 2017Accepted: 26. 3. 2017.

Time-course pattern of blood 25-hydroxycholecalciferol is a significant predictor of survival outcome in metastatic colorectal cancer: a clinical practice-based study.

Vitamin D deficiency has been implicated in the epidemiology of common malignancies including colorectal cancer. We studied consecutive blood levels of 25-hydroxycholecalciferol (25-OHD) in relation to other clinical and laboratory variables in metastatic colorectal cancer patients to ascertain whether their variations may be prognostic or predictive parameters of survival outcomes. Eighty four patients treated with first-line oxaliplatin-based chemotherapy with or without bevacizumab were included. The patients were enrolled on the intent-to-treat basis considering their performance status, comorbidities and laboratory parameters to be medically apt for intensive chemotherapy. Overall survival and progression-free survival were selected as the primary outcomes. Progression free survival and overall survival medians were 15.4 months and 41.2 months, respectively. The cut-off levels of 40 nmol/l for 25-OHD and 11 µg/l for first CEA were identified to be clinical decision levels stratifying patients to the respective prognostic groups. We found that the most consistent outcome predictors were i) any patient surgery, ii) CEA and, independently, iii) time-related blood levels of 25-OHD. We confirmed fundamental and consistent vitamin D deficiency in metastatic colorectal cancer. We demonstrated that all patients with at least one blood level above 40 nmol/l versus all below this cut-off showed profound differences in their disease outcomes. The primary disease stage or time to metastatic stage did not influence the predictive power of blood 25-OHD levels, implying that the time-course pattern of 25-OHD but not the first single measurement may be an independent prognostic factor.

[Vitamin D as an important steroid hormone in breast cancer]. / Vitamin D jako významný steroidní hormon u karcinomu prsu.

Vitamin D is the third steroid hormone playing important bio-logical roles in the development of breast cancer. Decreased plasma levels of its 25- hydroxyderivative, 25OHD, display robust associations with higher incidence of breast cancer and shorter overall survival. Although no consensus exists, most authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas levels higher than 375 nmol/ l can be potentially toxic with higher risk of hypercalcemia. To date, no data are available on the optimal levels of vitamin D related to the risk of breast cancer development, its phenotype features and the course of the disease. Published studies mostly describe associations among higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be associated with higher disease incidence and also be of negative prognostic significance in breast cancer. This review presents an overall summary of the current knowledge and publications on vitamin D and breast cancer.

The biobanking research infrastructure BBMRI_CZ: a critical tool to enhance translational cancer research.

We introduce the national research biobanking infrastructure, BBMRI_CZ. The infrastructure has been founded by the Ministry of Education and became a partner of the European biobanking infrastructure BBMRI.eu. It is designed as a network of individual biobanks where each biobank stores samples obtained from associated healthcare providers. The biobanks comprise long term storage (various types of tissues classified by diagnosis, serum at surgery, genomic DNA and RNA) and short term storage (longitudinally sampled patient sera). We discuss the operation workflow of the infrastructure that needs to be the distributed system: transfer of the samples to the biobank needs to be accompanied by extraction of data from the hospital information systems and this data must be stored in a central index serving mainly for sample lookup. Since BBMRI_CZ is designed solely for research purposes, the data is anonymised prior to their integration into the central BBMRI_CZ index. The index is then available for registered researchers to seek for samples of interest and to request the samples from biobank managers. The paper provides an overview of the structure of data stored in the index. We also discuss monitoring system for the biobanks, incorporated to ensure quality of the stored samples.

[Profiles of low-molecular proteome spectrum obtained through SELDI-TOF mass spectrometry in the sera of patients with metastatic malignant melanoma: pilot study]. / Profily nízkomolekulárniho proteomového spektra získané pomocí hmotnostní spektrometrie SELDI-TOF v sérech pacientus diseminovaným maligním melanomem: pilotní studie.

BACKGROUNDS: Recently, research at genetic and molecular levels has extensively accelerated due to advances in new technologies. Since the mid-90s, a relatively new discipline--clinical proteomics, has evolved, which focuses on studying gene products--proteins. The evaluation of protein profiles may contribute to the more accurate stratification of patients in the future, in terms of both prediction of treatment results and prognosis. In pursuing this objective, proteomic approaches are currently used for the identification of new biomarkers. This is also the case with malignant melanoma, a disease without typical serum marker possessing high sensitivity and high specificity. METHODS: We analyzed human blood serum samples from 25 patients with metastatic malignant melanoma treated with palliative chemotherapy at the Masaryk Memorial Cancer Institute, Brno, in 2004-2006. The analysis was performed by Surface Enhanced Laser Desorption/lonisation Time of Flight Mass Spectrometry (SELDI-TOF-MS). Our patients were divided into two subgroups: a group relatively resistant to chemotherapy--14 patients--and a group with certain clinical benefit from the treatment (complete and partial remission, stabilized disease)--11 patients. We were searching for a new biomarker or typical protein profile in the selected two subgroups. Then, we recategorized our patients into three groups according to the similarity of their protein profiles regardless of sensitivity to chemotherapy. Finally, we evaluated differences in laboratory and clinical parameters, between both the groups of chemo-resistant and chemo-sensitive patients, and newly defined subgroups with similar protein profiles. CONCLUSION: We did not identify any significant differences in protein profiles or laboratory parameters in the predefined chemo-sensitive or chemo-resistant groups of patients. However, with regard to the new groups with similar protein profiles, we identified a subgroup of patients with different laboratory and clinical parameters. The results are very interesting and merit further research.