[Ascites May Provide Useful Information for Diagnosis of Ovarian Cancer]. / Ascitická tekutina u nádoru vajecníku muze poskytnout informace vhodné pro diagnostiku.

BACKGROUND: Ovarian cancer is the most lethal gynecological cancer, almost 80% of all patients succumb the disease within 5 years of diagnosis. High mortality is caused especially by nonspecific symptoms, diagnosis in late stages and the absence of a specific biomarker. Currently, the most common diagnostic biomarkers are the membrane glycoprotein Cancer Antigen 125 (CA 125), the Human Epididymal Protein 4 (HE4) and the Carcinoembryonic Antigen (CAE). None of these biomarkers is specific only for ovarian cancer and increased levels may be caused by other diseases. Therefore, current research is focused on finding new biomarkers for diagnosis and prognosis of ovarian cancer. Interesting clinical material is ascites, the fluid accumulated in abdominal cavity, which is typical for ovarian cancer and it is present in almost 90% of all cases of stage III and IV. MATERIAL AND METHODS: For this study, samples of ascites from patients with benign and malignant ovarian tumors were used. For full glycomic and proteomic analysis, only 5 µL of ascites were used. Glycans were released from proteins by the enzyme PNGase F and proteins were digested to peptides by trypsin. Samples were purified and measured using a mass spectrometer. RESULTS: Glycan and protein profiles of patients with benign and malignant ovarian cancer were compared. In patient with a benign tumor, more simple glycans with lowm/z were increased while in the patient with a malignant tumor, higher, more complex glycans were increased. In the malignat tumor in comparison to benign tumor, 127 unique proteins were identified, especially proteins of the annexin, mucin and peroxiredoxin families. CONCLUSION: This investigation is a pilot study focused on comparison of protein and glycan composition of ascites in patients with benign and malignant ovarian cancer. Significant differences were found on both glycan and protein levels. Results will be verified on a larger set of patients and compared with a set of control samples.Key words: glycomics - proteomics - ascitic fluid - ovarian cancer This study was supported by projects of the Ministry of Education Youth and Sports - National Sustainability Program I - LO1413; Ministry of Health, Czech Republic - conceptual development of research organization (MMCI, 00209805); Czech Science Foundation 16-04496S. 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.

Genotyping of EGFR Mutations from Bronchial Cytological Specimens in Slovakian Lung Cancer Patients.

Non-small cell lung cancer (NSCLC) is a histologically and molecularly heterogeneous disease predominating in Slovakia among newly diagnosed oncological disorders and leading in the number of associated deaths. NSCLC diagnostics has advanced especially in molecular typing of epidermal growth factor receptor (EGFR) and subsequent targeted molecular therapy using tyrosine-kinase inhibitor(s) (TKI). The selection of patients for targeted therapy, we describe in this study, is mostly guided through bronchial smears rather than more invasive biopsies. We identified 32 adenocarcinomas, 40 squamous-cell carcinomas, 12 large-cell carcinomas, along with two unspecified carcinomas, in the NSCLC group who had bronchial smears taken. The assessment of tumor cell number, and genomic DNA allowed for screening of clinically relevant somatic EGFR mutations in 86 patients. Using quantitative PCR, 12 patients (14 %) were recommended for EGFR-TKI therapy. The most prevalent EGFR HIT-a in the somatosome, terms introduced and defined in this study, were exon 19 deletions, which were found in combination with the TKI-resistant p.T790M mutation in exon 20 in one patient. The study describes a method that is minimally invasive, reliable, and meets all criteria of routine molecular diagnostics. A multidisciplinary approach of EGFR genotyping from bronchial smears implemented in the study allows expanding targeted molecular therapy in NSCLC patients.

[Sugars Interfere or Glycomics in the Field of Cancer Biomarkers]. / "Cukry zasahují" aneb glykomika na poli nádorových biomarkeru.

Glycomics is concerned with detection and characterization of glycans present in biological samples. It is well-known that glycan structures impart high degree of structural diversity to biomolecules and thus add wide -ranging biological functions, such as cellular recognition, adhesion or involvement in cellular signaling pathways. They substantially participate in oncogenesis, e. g. in phases of invasion, metastasis and angiogenesis. Therefore, analysis of glycan structures in tumor tissues or body liquids is a promising tool for searching for potential tumor biomarkers essential for an early diagnosis of the neoplastic disease. The presented review describes the process of glycosylation and the origination of N  and O  glycans, presenting examples of glycan profiling in pancreatic, prostate and ovarian cancer.

[New trends in the study of protein glycosylation in oncological diseases]. / Nové trendy ve studiu glykosylace proteinu u onkologických onemocnení

Glycomics and glycoproteomics represent relatively new directions in detail analyses of complex bio-logical media. These areas of increasing importance to cancer research complement the more established genomic profiling and proteomics. Glycoproteins are being increasingly recognized as important in cellular interactions and adhesion. Structural alterations of their glycan moieties seem to occur in different cancer conditions. We review current directions in glycomic profiling and glycoproteomic investigations of bio-logical fluids and tissues pertaining to cancer. The used methods rely on capillary separation techniques, mass spectrometry, and the glycan and lectin arrays. They all show considerable promise for new diagnostic and prognostic measurements.

[Normal course of autoimmune thyroid disease in diabetic children]. / Prirozený prubeh autoimunitního onemocnení stítné zlázy u diabetických detí.

BACKGROUND: Autoimmune thyroid disease (AITD) represents the most frequent associated manifestation of the autoimmune disease in children with Type 1 diabetes mellitus (T1DM). The aim of the study was to evaluate the prevalence and natural course of AITD in unselected cohort of diabetic children. METHODS AND RESULTS: TSH, free thyroxin, thyreoglobulin autoantibodies (Ab-hTG), peroxidase autoantibodies (Ab-TPO) and thyroid sonography were prospectively evaluated (1 to 6 years; 323 patient-years) in 110 patients with T1DM (age 2.1-20.8 years; 60 boys). Mild elevation of Ab-hTG and/or Ab-TPO levels (> 100, < 1000 mIU/l) was found in 19 patients (17%; boys:girls 1:2.2). Out of these, only 2 had increased thyroid volume and/or abnormal echotexture. In 9 of these patients, levels of autoantibodies subsequently declined below 100 mIU/l, remained unchanged in 9 patients and only in one case increased over 1000 mIU/l ("benign form" of AITD). All patients remained euthyroid. Severe elevation of Ab-hTG and/or Ab-TPO (> 1000 mIU/l) was found in 12 patients (11%; boys:girls 1:1). Out of these, eight had increased thyroid volume and ten had abnormal echotexture. Subclinical hypothyroidism developed within the observation period in nine of them (boys:girls 2:1). CONCLUSIONS: AITD was found in 31 (28%) children and adolescents with T1DM. Whereas mild elevation of Ab-hTG and/or Ab-TPO levels was not accompanied with morphological changes of the thyroid and did not predict functional disorder, severely elevated levels were associated with the early risk of subclinical hypothyroidism.

Insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in cystic fibrosis: a positive effect of antibiotic therapy and hyperalimentation.

UNLABELLED: Patients with cystic fibrosis (CF) are underweight and growth retarded. This study tested the link between serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels and body height, nutritional status, pulmonary function tests and activity of inflammation in 92 subjects with CF (age 2.1-18.8 y). It also analysed the effect of short-term antibiotic treatment and hyperalimentation on IGF-I and IGFBP-3 levels in 33 subjects (age 3.6-33.7y) on 41 occasions. Both IGF-I (-1.19 +/- 0.17 SD) and IGFBP-3 levels (-0.66 +/- 0.12 SD; both p < 0.0001 vs 0) were decreased in cross-sectional measurements. Their standardized values were inversely proportional to age (IGF-I: r = -0.23, p = 0.03; IGFBP-3: r = -0.29, p = 0.005) and positively correlated with SDS of height (IGF-I: r = 0.40, p < 0.0001; IGFBP-3: r = 0.36, p = 0.0005) and of mid-arm circumference (IGF-I: r = 0.39, p = 0.0001; IGFBP-3: r = 0.38, p = 0.0002), and with pulmonary function tests. After a short-term course of intensive antibiotic therapy and hyperalimentation, IGF-I normalized (from -0.66 +/- 0.20 to 0.00 +/- 0.25 SD; p < 0.0001) and IGFBP-3 increased (from -0.78 +/- 0.15 to -0.53 +/- 0.16 SD; p = 0.002). IGFBP-3 correlated inversely with erythrocyte sedimentation rate (r = -0.40, p = 0.01). CONCLUSION: The levels of IGF-I and IGFBP-3 are markedly decreased in patients with CF and tend to normalise after a short course of antibiotic treatment and hyperalimentation.

Discordant growth pattern and ovarian function in monozygotic twins with 45,X/46,XX mosaicism.

BACKGROUND: We report on phenotypically discordant female monozygotic twins with 45X/46,XX mosaicism in both lymphocytes and fibroblasts. RESULTS: At 11.5 years, twin A was prepubertal, her height was 126.8 cm (-3.15 SD), bone age (BA) 9.7 years (TW2), FSH 47 IU/l and IGF-I 280 ng/ml (-0.89 SD), but twin B was pubertal (P2, B3), her height was 143.4 cm (-0.92 SD), BA 13.6 years (TW2), FSH 3.4 IU/l and IGF-I 380 ng/ml (-0.21 SD). One year later, twin A had grown 11.1 cm due to growth hormone therapy and had IGF-I 1,400 ng/ml (+5.91 SD), whereas the growth velocity of twin B (no therapy) was 5.9 cm, IGF-I 540 ng/ml (+0.57 SD) and she started regular menstruation at 12.1 years. CONCLUSION: To our knowledge, this is the first report on monozygotic twins with Turner mosaicism in both lymphocytes and fibroblasts who developed a discordant phenotype probably due to an unequal distribution of the two cell lines in distinct tissues.

[Effect of tylosin in pigs]. / Ucinek tylosinu u prasat

The effect of tylosine and sulphadimidine, chlortetracycline, and bacitracin in feed was studied in 1275 piglets from 120 litters; the values obtained were compared with the control group given no antibiotics. Three Tylan injections were applied to a half of the animals on the 2nd, 5th, and 28th day after birth. The Tylan program did not lead to any significant reduction of piglet mortality before the 50th day of life. In neither of the groups did Tylan injections reduce mortality at the level of statistical significance. From the age of 56 days, the Tylan-application program provides statistically significant weight gains, as compared with other groups. The group with Czechoslovak antibiotics had the same weight as the group fed without antibiotics. The occurrence of pathological and anatomic findings on lungs showed no statistically significant differences in the two groups. The presence of tylosine in blood could not be ascertained after the oral application of even much higher doses than those used in the Tylan-application program. Small incidence of rhinitis does not allow for drawing any conclusions concerning the effects of Tylan.