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1.
Dalton Trans ; 53(13): 6031-6040, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38470348

ABSTRACT

BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [97/103Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (103Ru; ß-, γ) and ruthenium-97 (97Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [103Ru]BOLD-100 (3 and 30 mg kg-1) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, ex vivo autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg-1) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [103Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [97Ru]BOLD-100.


Subject(s)
Antineoplastic Agents , Neoplasms , Organometallic Compounds , Ruthenium Radioisotopes , Ruthenium , Animals , Mice , Humans , Tissue Distribution , Antineoplastic Agents/pharmacology
2.
Klin Onkol ; 34(4): 313-318, 2021.
Article in English | MEDLINE | ID: mdl-34649442

ABSTRACT

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with intermediate malignant potential. Although most often seen in the lungs, it can occur at multiple anatomical locations, including the gastrointestinal tract. An esophageal lesion is extremely rare, however. IMTs present most commonly in children and young adults. The main therapeutic approach is surgical resection. CASE REPORT: We report on the follow-up of a case in a 13-year-old boy with IMT in the esophagus. He underwent surgical resection in 2013 and is free of disease to date. CONCLUSION: Surgical resection is the most preferred therapy. If the resection is complete, the risk of recurrence is low. Nevertheless, every patient should be carefully followed up after the resection.


Subject(s)
Esophageal Neoplasms/surgery , Neoplasms, Muscle Tissue/surgery , Adolescent , Esophageal Neoplasms/etiology , Esophageal Neoplasms/pathology , Humans , Male , Neoplasms, Muscle Tissue/etiology , Neoplasms, Muscle Tissue/pathology
3.
Neoplasma ; 67(5): 1164-1169, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32657609

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (HSCT) has become a standard part of therapy for a variety of malignant and non-malignant disorders. With improved outcomes after HSCT, increasing attention has been drawn to late complications in long-term survivors. The development of secondary malignancies is recognized as one of the most serious complications. We have evaluated data from 426 patients (272 males, 154 females) who underwent allogeneic transplantation at a median age of 7.9 years from 1989 till 2017 and were alive more than one year after transplantation for the occurrence of secondary solid tumors. We have documented the occurrence of secondary solid tumors in 20 patients (4.7%). The median duration of the development of secondary solid cancer from HSCT was 11.7 (range, 5.4-21.5 years). 18 out of 20 patients (90%) had total body irradiation (TBI) 12-14.4 Gy as a part of a conditioning regimen. All but two had transplantation for malignant disease. All patients underwent surgery and/or chemo-radiotherapy. Eighteen are alive, and two died due to the progression of their secondary malignancy. The most frequent solid cancer was thyroid carcinoma (n=9). Cumulative incidence of secondary solid cancer in all groups was 15.2±3.9%, in a group using TBI based regimen 34.7±8.9%, in non-TBI (only chemo) group was 1.5±1.1%. Overall, the cumulative incidence is statistically significantly different between the TBI based and non-TBI (chemo only) group. The incidence and number of complications following allogeneic HSCT in childhood are increasing in time. The early diagnosis of secondary malignancies is one of the key tasks of long-life multidisciplinary post-transplant care.


Subject(s)
Hematopoietic Stem Cell Transplantation , Neoplasms, Radiation-Induced , Neoplasms, Second Primary/etiology , Transplantation Conditioning/adverse effects , Whole-Body Irradiation/adverse effects , Child , Female , Humans , Male , Risk Factors , Transplantation, Homologous
4.
Data Brief ; 28: 105029, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31909125

ABSTRACT

We report the proteomic datasets on the mouse macrophage cell line PMJ2R infected with tick-borne encephalitis virus (TBEV) for two and six days. Data were acquired using shotgun ultra-high resolution mass spectrometry. Peptide identifications were done using the Mascot version 2.4 (Matrix Science), and quantification was performed by a label-free approach. Protein profiles of early (two days) and late (six days) stages of infection were compared between each other and the respective control samples. Protein profiles of infected and control samples differed in the number of identified proteins and their relative abundances. Proteins detected in the TBEV-infected cells were involved in various processes related to the infection, including defense response against the virus, regulation of viral process, negative regulation of viral genome replication, RNA binding, or innate immune response. Also, proteins specific for the early and late stages of infection were identified.

5.
Klin Onkol ; 32(6): 426-435, 2019.
Article in English | MEDLINE | ID: mdl-31842561

ABSTRACT

BACKGROUND: Our study aimed to evaluate incidence and mortality trends for childhood and adolescent cancers in the period 1994-2016 in the Czech Republic. MATERIAL AND METHODS: Data on childhood cancers, which are recorded in the Czech National Cancer Registry, were validated using a clinical database of childhood cancer patients and combined with data from the National Register of Hospitalised Patients and with data from death certificates. These validated data were used to establish cancer incidence. Data from death certificates were used to evaluate long-term trends in mortality. Incidence and mortality trends were assessed by the average annual percentage change. RESULTS: The age-standardised incidence trend for childhood cancers (i.e. those diagnosed in patients aged 0-19 years) showed a statistically significant slight long-term increase in the number of new cases, +0.5% annually on average (p < 0.01), more specifically an increase of +0.6% in girls and a statistically insignificant decrease of 0.1% in boys. In children aged 0-14 years, other malignant epithelial neoplasms and malignant melanomas showed the largest statistically significant average annual increase in incidence (+4.9%; p < 0.01), followed by central nervous system neoplasms (+1.3%; p < 0.05). Lymphomas, by contrast, showed a statistically significant average annual decrease in incidence in children aged 0-14 years (2.1%; p < 0.01). In adolescents aged 15-19 years, other malignant epithelial neoplasms and malignant melanomas also showed a statistically significant average annual increase in incidence (+5.2%; p < 0.01), followed by central nervous system neoplasms (+1.5%; p < 0.05). Mortality trends showed a statistically significant long-term decrease: on average, 5.1% annually in children aged 0-14 years (p < 0.01), and 3.7% annually in adolescents aged 15-19 years (p < 0.01). CONCLUSION: Available data make it possible to analyse long-term trends in childhood cancer incidence and mortality.


Subject(s)
Neoplasms/epidemiology , Adolescent , Adult , Child , Child, Preschool , Czech Republic/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Young Adult
6.
Klin Onkol ; 32(Supplementum1): 171-173, 2019.
Article in English | MEDLINE | ID: mdl-31064192

ABSTRACT

BACKGROUND: Medulloblastoma (MB) is the most common malignant tumour of the central nervous system in children. MB is considered to be high risk tumour propensity to metastasize. In the Czech Republic, approximately 10-12 children are affected annually by this tumour. Recent progress in molecular diagnostics helps to refine the diagnosis and estimate clinical prognosis of the disease. Currently, MBs are subclassified into WNT-activated, SHH-activated, group 3, and 4 based on molecular pathways that drive their tumorigenesis. Each subtype differs in its histopathology, clinical features, genomic changes and gene expressions. The aim of our study is to classify patients MBs into four basic molecular groups and compare our results with published data. MATERIAL AND METHODS: In our study we analysed expression profiles using Affymetrix GeneChip Human Gene 1.0. ST Array (Thermo Fisher Scientific, MA, USA). As input material RNA extracted from the fresh frozen tissue was used. Molecular classification based on the method established by P. Northcott in 2011 was performed. RESULTS: From April 2015 to February 2019, 21 patients with MBs were included in our study. Median age of the patients at the time of diagnosis was 6 years, 14 boys and 7 girls were enrolled. Gene expression profiling and molecular classification of MBs was performed. Based on this methodology, we found the most frequently represented subgroup of MB was group 4 (9 patients, 43%), followed by group 3 (5 patients, 24%), SHH-activated MB (4 patients, 19%) and the least represented subgroup was WNT-activated MB (3 patients, 14%). Results of molecular subgroup classification of MBs were successfully correlated with histopathological findings and other molecular-genetic examinations. CONCLUSION: Molecular classification of MBs has been established in our institution allowing better understanding of this heterogeneous disease and helping clinicians in therapeutic planning in affected patients. This work was supported by the Czech Ministry of Health grant No. 16-33209A. All rights reserved.  he authors declare they have no potential confl icts 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: 1. 3. 2019 Accepted: 4. 3. 2019.


Subject(s)
Biomarkers, Tumor/genetics , Cerebellar Neoplasms/classification , Cerebellar Neoplasms/pathology , Gene Expression Profiling , Genome, Human , Medulloblastoma/classification , Medulloblastoma/pathology , Cerebellar Neoplasms/genetics , Child , Computational Biology/methods , Czech Republic , Female , Humans , Medulloblastoma/genetics , Prognosis
7.
Klin Onkol ; 32(1): 70-74, 2019.
Article in English | MEDLINE | ID: mdl-30764633

ABSTRACT

BACKGROUND: Individuals with constitutional mismatch repair-deficiency syndrome (CMMR-D) are characterised by early occurrence of colon cancer, haematological malignancies, and brain tumors (malignant gliomas, high-grade gliomas) in childhood, adolescence, and early adulthood. High mutational tumor burden is typical of glioblastoma in CMMR-D patients and could be a reason why this type of glioblastoma responds well to immunotherapies, including those that employ checkpoint inhibitors. OBSERVATION: We describe a case of an adolescent with CMMR-D that had been genetically proven by whole exome sequencing (c.2T>A/p.M1K and c.2521delT/p.W841fs PMS2 gene mutation). The patient presented successively with colon cancer and glioblastoma with a high mutational burden. The individualized glioblastoma therapy was based on the biological tumor profile and included immunotherapy with a combination of vaccination with autologous dendritic cells producing IL-12 and nivolumab, in addition to radiotherapy with metronomic temozolomide. The patient is still alive 21 months after the initial glioblastoma diagnosis and shows a complete therapeutic response documented by repeated magnetic resonance examinations. CONCLUSION: Individuals with CMMR-D should be regularly examined using established algorithms. Whole body magnetic resonance imaging can play a key role, because it enables the early diagnosis of malignancy during the asymptomatic period. Malignancies in CMMR-D patients usually exhibit a hypermutated genotype and respond to immunotherapy. Conventional glioblastoma therapy is only palliative. Patients can benefit from an individualized therapeutic plan based on the tumor biological profile. Extensive molecular analysis of the tumor tissue is necessary. Key words hereditary cancer predisposition syndromes - glioblastoma - whole exome sequencing - immunotherapy - vaccines - checkpoint inhibitors This study was supported by the research project of the Czech Ministry of Health AZV 16-33209A (Next generation sequencing and express profiling as diagnostic tools for personalized therapeutic plans in children with solid tumors). 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: 26. 9. 2018 Accepted: 18. 11. 2018.


Subject(s)
Brain Neoplasms/therapy , Colorectal Neoplasms/therapy , Glioblastoma/therapy , Immunotherapy , Neoplastic Syndromes, Hereditary/therapy , Adolescent , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/genetics , Glioblastoma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Mismatch Repair Endonuclease PMS2/genetics , Mutation , Neoplastic Syndromes, Hereditary/diagnostic imaging , Neoplastic Syndromes, Hereditary/genetics , Treatment Outcome
8.
Neoplasma ; 65(4): 620-629, 2018.
Article in English | MEDLINE | ID: mdl-30064234

ABSTRACT

The purpose of this study is to summarize incidence and trends in the pediatric cancer burden in the Czech Republic over the period 1994-2014. The recently established Childhood Cancer Registry was combined with retrospective data from the Czech National Cancer Registry to analyze the annual patterns of incidence and long-term trends of pediatric cancer patients aged 0-14 years diagnosed between 1994 and 2014. Malignancies were classified according to the International Classification of Childhood Cancer. The distribution of incidence was stratified according to gender, age at diagnosis, type of cancer and geographic area. Annual age-standardized rates were adjusted using the world standard population. Changes over time were quantified as the average annual percentage change. This analysis comprised records of 5,605 children diagnosed with cancer within the period 1994-2014, annually 267 records on average; the overall age-standardized average annual incidence rate was 169 cases per million. Boys were affected more frequently than girls: the M/F crude incidence ratio was 1.2:1. The highest incidence rates were observed for ICCC groups I (27.8%), III (21.8%), II (12.4%) and IV (7.8%); other groups formed 30.2%. There are significant differences in the geographic distribution of incidence between regions. A borderline statistically significant increase (0.6%) in the overall average annual percentage change was detected between 1994 and 2014 (95% CI: 0.01 to 1.12; p = 0.05). This study provides reliable recent information on trends in the incidence of childhood cancers in the Czech Republic.


Subject(s)
Neoplasms/epidemiology , Adolescent , Child , Child, Preschool , Czech Republic/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Registries , Retrospective Studies
10.
Eur Radiol ; 28(12): 5182-5194, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29846804

ABSTRACT

PURPOSE: To compare the efficacy of use of digital breast tomosynthesis (DBT) with standard digital mammography (DM) workup views in the breast cancer assessment clinic. MATERIALS AND METHODS: The Tomosynthesis Assessment Clinic trial (TACT), conducted between 16 October 2014 and 19 April 2016, is an ethics-approved, monocenter, multireader, multicase split-plot reading study. After written informed consent was obtained, 144 females (age > 40 years) who were recalled to the assessment clinic were recruited into TACT. These cases (48 cancers) were randomly allocated for blinded review of (1) DM workup and (2) DBT, both in conjunction with previous DM from the screening examination. Fifteen radiologists of varying experience levels in the Australia BreastScreen Program were included in this study, wherein each radiologist read 48 cases (16 cancers) in 3 non-overlapping blocks. Diagnostic accuracy was measured by means of sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). The receiver-operating characteristic area under the curve (AUC) was calculated to determine radiologists' performances. RESULTS: Use of DBT (AUC = 0.927) led to improved performance of the radiologists (z = 2.62, p = 0.008) compared with mammography workup (AUC = 0.872). Similarly, the sensitivity, specificity, PPV, and NPV of DBT (0.93, 0.75, 0.64, 0.96) were higher than those of the workup (0.90, 0.56, 0.49, 0.92). Most radiologists (80%) performed better with DBT than standard workup. Cancerous lesions on DBT appeared more severe (U = 33,172, p = 0.02) and conspicuous (U = 24,207, p = 0.02). There was a significant reduction in the need for additional views (χ2 = 17.63, p < 0.001) and recommendations for ultrasound (χ2 = 8.56, p = 0.003) with DBT. CONCLUSIONS: DBT has the potential to increase diagnostic accuracy and simplify the assessment process in the breast cancer assessment clinic. KEY POINTS: • Use of DBT in the assessment clinic results in increased diagnostic accuracy. • Use of DBT in the assessment clinic improves performance of radiologists and also increases the confidence in their decisions. • DBT may reduce the need for additional views, ultrasound imaging, and biopsy.


Subject(s)
Breast Neoplasms/diagnosis , Mammography/methods , Mass Screening/methods , Radiographic Image Enhancement/methods , Australia/epidemiology , Breast Neoplasms/epidemiology , Female , Humans , Incidence , ROC Curve
12.
Klin Onkol ; 29 Suppl 1: S83-8, 2016.
Article in Czech | MEDLINE | ID: mdl-26691947

ABSTRACT

BACKGROUND: Medulloblastoma, an embryonal neuroectodermal tumor of the cerebellum, is the most common malignant brain tumor in children. There are approximately 15 cases diagnosed in the Czech Republic each year. The recent World Health Organization classification recognizes several histopathological subtypes of medulloblastoma: classical, desmoplastic/ nodular with its extensive-nodularity variant, and anaplastic/ large-cell variant. Further molecular analysis identified four basic subgroups of medulloblastoma: WNT, SHH, Group 3, and Group 4. The subgroup of SHH meduloblastoma is associated with somatic mutations of SHH, PTCH1, SUFU, SMO and TP53, while the most common mutations found in infants up to three years of age were PTCH1 and SUFU. The majority of medulloblastomas are sporadic diseases, whereas only about 5- 10% of all cases occur in connection with hereditary genetic syndromes. CASE: We present a case of a 21-months old girl diagnosed with a localized posterior fossa tumor. The histopathological examination revealed a desmoplastic/ nodular medulloblastoma. The treatment comprised a radical exstirpation of the tumor followed by adjuvant chemotherapy. With the use of array-CGH, a partial biallelic deletion of the SUFU gene (locus 10q24.32) was detected in the tumor DNA, whereas a monoallelic deletion was found in the peripheral lymphocyte DNA of the patient. These findings were confirmed by an independent qPCR method. Monoallelic germline deletion of SUFU was also identified in the patients mother, who was a healthy carrier. Pedigree of the family suggested a transition of the germline deletion of SUFU, since another brain tumors (including one case diagnosed before the age of three years) were identified in previous generations. CONCLUSION: Germline mutations in SUFU gene are believed to predispose to infant desmoplastic/ nodular medulloblastomas, basal cell carcinomas and meningiomas. The susceptibility gene shows autosomal dominant inheritance with an incomplete penetrance. There is no evidence-based surveillance strategy suggested for the carriers of germline SUFU mutations/ deletions so far. Our recommendation is based both on a family history of our patient and similar cases described in the literature. Since the germinal mutations in SUFU are responsible for up to 50% of all desmoplastic medulloblastomas in children under three years of age, genetic testing of SUFU should be encouraged in this population of patients.


Subject(s)
Cerebellar Neoplasms/genetics , Germ-Line Mutation , Medulloblastoma/genetics , Repressor Proteins/genetics , Female , Humans , Infant
13.
Neoplasma ; 62(6): 958-65, 2015.
Article in English | MEDLINE | ID: mdl-26458311

ABSTRACT

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.

14.
Klin Onkol ; 28 Suppl 2: 2S47-51, 2015.
Article in Czech | MEDLINE | ID: mdl-26374158

ABSTRACT

BACKGROUND: Maffucci syndrome is a rare congenital nonhereditary disease characterized by multiple hemangiomas and enchondromas, which may progress into malignancy. The causal therapy does not exist, and therapy is aimed at complications. The determination of appropriate therapy is complicated, and a multidisciplinary approach is often essential. CASE: Authors are presenting the case of a 20-year -old patient with Maffucci syndrome. During her life, multiple enchondromas and progressing hemangiomas have been revealed and they have caused many complications, such as limited movement, growth failure, pain, fluidothorax and ascites. A profile of phosphorylation of selected tyrosine kinases and MAP kinases from progressing hemangioma was performed and with consideration of the result, it led to change of treatment strategy with encouraging clinical response lasting for six months.


Subject(s)
Enchondromatosis/therapy , Mitogen-Activated Protein Kinases/metabolism , Protein-Tyrosine Kinases/metabolism , Adult , Enzyme Activation , Female , Humans , Phosphorylation
15.
Klin Onkol ; 28(3): 163-70, 2015.
Article in Czech | MEDLINE | ID: mdl-26062617

ABSTRACT

Methotrexate is an anti-cancer drug used to treat several malignancies including pediatric acute lymphoblastic leukemia and choriocarcinoma. Despite recent advances in cancer chemotherapy, it remains a mainstay of therapy since its discovery in the early second half of the previous century. Moreover, low-dose methotrexate is a gold standard antirheumatic drug in the treatment of rheumatoid arthritis, psoriasis, systemic scleroderma and other autoimmune disorders. Side effects of methotrexate treatment are well known and described; however, their occurrence may often be unpredictable due to lack of specific biomarkers of toxicity. Methotrexate plasma levels are routinely monitored by therapeutic drug monitoring, nevertheless, occurrence and concentrations of its metabolites are not measured. During methotrexate treatment 7- hydroxymethotrexate and 2,4- diamino- N10- mehylpteroic acid appear in plasma. The latter can further be hydroxylated and glucuronidated resulting in five possible extracellular methotrexate metabolites. In addition, methotrexate is intracellularly converted to its active polyglutamylated forms. Therapeutic efficacy is dependent on formation of methotrexate polyglutamates as it keeps intracellular pool of the drug and enhances its affinity towards various target enzymes. In this study, we describe pharmacokinetic and pharmacodynamic characteristics of methotrexate metabolites. We also review methotrexate blood brain barrier transport to cerebrospinal fluid regarding its use in the prevention of leukemic central nervous system involvement and management of methotrexate toxicity with the use of carboxypeptidase- G2. Finally, we discuss laboratory methods for monitoring methotrexate metabolites and benefits of simultaneous determination of methotrexate and metabolites as possible biomarkers of therapeutic efficacy and clinical toxicity.


Subject(s)
Antimetabolites, Antineoplastic/pharmacokinetics , Methotrexate/analogs & derivatives , Methotrexate/pharmacokinetics , Antimetabolites, Antineoplastic/therapeutic use , Biomarkers, Tumor/analysis , Drug Resistance, Neoplasm , Humans , Methotrexate/metabolism , Methotrexate/therapeutic use , Tetrahydrofolate Dehydrogenase/metabolism
16.
Ticks Tick Borne Dis ; 6(5): 559-67, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25976235

ABSTRACT

Spatial distribution of Ixodes ricinus tick host-seeking activity, as well as prevalence of Borrelia burgdorferi sensu lato and tick-borne encephalitis virus (TBEV) were studied in the TBE endemic area of South Bohemia (Czech Republic). High variability in tick abundance detected in a network of 30 study sites was most closely associated with characteristics of vegetation cover. Of 11,182 tested tick samples, 12% carried DNA of spirochete from B. burgdorferi s.l. complex. B. afzelii and B. garinii prevailed among spirochete species. The presence of B. spielmanii in the region was confirmed. The median number of borrelial genome copies in positive samples reached 6.6 × 10(3) by real-time PCR. The total prevalence of TBEV in pooled samples reached 0.32% (20,057 samples tested), at least one TBEV positive tick was present in 21 out of 30 sampling sites.


Subject(s)
Borrelia burgdorferi/isolation & purification , Encephalitis Viruses, Tick-Borne/isolation & purification , Ixodes/physiology , Animals , Czech Republic/epidemiology , Encephalitis, Tick-Borne/epidemiology , Encephalitis, Tick-Borne/virology , Female , Lyme Disease/epidemiology , Lyme Disease/microbiology , Male
17.
Phys Rev Lett ; 114(4): 041101, 2015 Jan 30.
Article in English | MEDLINE | ID: mdl-25679883

ABSTRACT

In order to resolve a recent discrepancy in the half-life of 60Fe, we performed an independent measurement with a new method that determines the 60Fe content of a material relative to 55Fe (t1/2=2.744 yr) with accelerator mass spectrometry. Our result of (2.50±0.12)×10(6) yr clearly favors the recently reported value (2.62±0.04)×10(6) yr, and rules out the older result of (1.49±0.27)×10(6) yr. The present weighted mean half-life value of (2.60±0.05)×10(6) yr substantially improves the reliability as an important chronometer for astrophysical applications in the million-year time range. This includes its use as a sensitive probe for studying recent chemical evolution of our Galaxy, the formation of the early Solar System, nucleosynthesis processes in massive stars, and as an indicator of a recent nearby supernova.

18.
Curr Oncol ; 21(6): e790-3, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25489269

ABSTRACT

BACKGROUND: Children with high-grade glioma still have a poor prognosis despite the use of multimodal therapy including surgery, radiotherapy, and chemotherapy. New therapeutic strategies and methods evaluating such therapies are needed. OBSERVATION: Here we describe a child with anaplastic oligodendroglioma of the spinal cord who was unable to tolerate standard chemoradiotherapy and who had still-vital residual tumour during therapy. A good response was obtained with low-dose metronomic treatment containing vinblastine. The treatment was guided according to gradual response assessed using various positron-emission tomography tracers. CONCLUSIONS: Metronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours.

19.
Klin Onkol ; 27(5): 331-9, 2014.
Article in Czech | MEDLINE | ID: mdl-25312710

ABSTRACT

Neuroblastoma (NBL) is a typical childhood tumor developing from the precursor cells of the sympathetic nervous tissue and accounting for approximately 7% of total malignancies in pediatrics and 15% of deaths associated with this malignancy. MicroRNAs (miRNAs) are small single-stranded RNA molecules that are involved in posttranscriptional regulation of gene expression, whereas the pathophysiology of neuroblastoma tumor growth involves both upregulation of the protooncogenic miRNAs as well as downregulation of the tumor-suppresor ones. Comparison of the expression profiles of miRNAs in specific subtypes of neuroblastoma seems to be a useful tool adding to the classification of the diseases, and the assessment of the levels of specific miRNAs may be useful for estimation of the individual treatment response as well as prognosis of the patient. This paper provides the basic review of the studies focused on the role of miRNAs in pathogenesis of neuroblastoma and provides a survey of current/ possible use of these miRNAs in diagnostics, therapy or prognosis estimation in the neuroblastoma patients.


Subject(s)
MicroRNAs/physiology , Neuroblastoma/physiopathology , Child , Humans , Neuroblastoma/diagnosis , Neuroblastoma/genetics , Neuroblastoma/therapy , Prognosis
20.
Epidemiol Infect ; 142(4): 882-5, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23842543

ABSTRACT

Non-tuberculous mycobacteria are increasingly described as infectious agents in immunocompromised patients. A 17-year-old male patient suffering from secondary non-Hodgkin's lymphoma and treated with chemotherapeutic agents was admitted to hospital due to pleuropneumonia. Mycobacterium neoaurum was cultured repeatedly from his sputum and, Mycobacterium avium subsp. avium (M. a. avium) was detected by IS901 qPCR from detached fragments of his intestinal mucosa. We attempted to determine the possible sources of infection by analysing environmental samples from the closed oncology unit and conventional unit in the hospital, and from the patient's home residence and places which he frequented. The environment of the patient harboured mycobacteria (41 isolates in total); however, M. neoaurum was not recovered. M. a. avium was detected by qPCR in the environmental samples from a small flock of hens kept by his neighbour. Although it was not confirmed by DNA fingerprinting methods, the M. a. avium infection could have been acquired through the eating of incompletely cooked eggs.


Subject(s)
Immunocompromised Host , Mycobacterium Infections, Nontuberculous , Mycobacterium avium/isolation & purification , Nontuberculous Mycobacteria/isolation & purification , Tuberculosis , Adolescent , Antineoplastic Agents/therapeutic use , Antitubercular Agents/therapeutic use , Ciprofloxacin/therapeutic use , Environmental Microbiology , Humans , Intestinal Mucosa/microbiology , Lymphoma, Non-Hodgkin/drug therapy , Male , Sputum/microbiology
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