BACKGROUND AND OBJECTIVES: Oligodendrogliomas are primary brain tumors classified as isocitrate deshydrogenase-mutant and 1p19q codeleted in the 2021 World Health Organization Classification of central nervous system tumors. Surgical resection, radiotherapy, and chemotherapy are well-established management options for these tumors. Few studies have evaluated the efficacy of stereotactic radiosurgery (SRS) for oligodendroglioma. As these tumors are less infiltrative than astrocytomas and typically recur locally, focal therapy such as SRS is an appealing option. METHODS: This study was performed through the International Radiosurgery Research Foundation. The objective was to collect retrospective multicenter data on tumor control, clinical response, and morbidity after SRS for oligodendroglioma. Inclusion criteria were age of 18 years or more, single-fraction SRS, and histological confirmation of grade 2 or 3 oligodendroglioma. The primary end points were progression-free survival (PFS) and overall survival from SRS. Secondary end points included clinical evolution and occurrence of adverse radiation events or other complications. Descriptive statistics, Kaplan-Meier analyses, and univariate and multivariate analyses were performed. RESULTS: Eight institutions submitted data for a total of 55 patients. The median follow-up time was 24 months. The median age at SRS was 46 years, and the median Karnofsky Performance Status was 90%. The median marginal dose used was 15 Gy. The median PFS was 17 months, with actuarial rates of 60% at 1 year, 31% at 2 years, and 24% at 5 years after SRS. Factors significantly associated with worsened PFS were World Health Organization grade 3, previous radiotherapy and chemotherapy, and higher marginal dose. The median overall survival post-SRS was 58 months, with actuarial rates of 92% at 1 year, 83% at 2 years, and 49% at 5 years. Karnofsky Performance Status remained stable post-SRS in 51% and worsened in 47% of patients, most often because of tumor progression (73%). Radiation-induced changes occurred in 30% of patients, of which only 4 were symptomatic. CONCLUSION: SRS is a reasonable management option for patients with oligodendroglioma.
- MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Brain Neoplasms * surgery MeSH
- Oligodendroglioma * surgery pathology MeSH
- Radiosurgery * methods MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Neoplasm Grading MeSH
- World Health Organization * MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
INTRODUCTION: Pathogenesis of large B-cell lymphomas (LBCL) and follicular lymphomas (FL) is a multistep process associated with the development of diverse DNA alterations and consequent deregulation of critical cellular processes. Detection of tumor-associated mutations within non-tumor compartments (mainly plasma) is the basis of the 'liquid biopsy' concept. Apart from tumor mutational profiling, quantitative analysis of circulating tumor DNA (ctDNA) allows longitudinal assessment of tumor burden. ctDNA-based technologies provide a new tool for tumor diagnostics and treatment personalization. AREAS COVERED: Our review provides a comprehensive overview and summary of available ctDNA studies in LBCL and FL. The accuracy of ctDNA-based detection of lymphoma-associated DNA alterations is correlated to known LBCL and FL molecular landscape. Additionally, we summarized available evidence that supports and justifies the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy. Lastly, we discuss other clinically important ctDNA applications: monitoring of lymphoma clonal evolution within resistance and/or relapse development and utilization of ctDNA for diagnostics in non-blood fluids and compartments (e.g. cerebrospinal fluid in primary CNS lymphomas). EXPERT OPINION: Despite certain challenges, including methodological standardization, ctDNA holds promise to soon become an integral part of lymphoma diagnostics and treatment management.
- MeSH
- Circulating Tumor DNA * blood genetics MeSH
- Lymphoma, Large B-Cell, Diffuse * diagnosis genetics therapy blood MeSH
- Lymphoma, Follicular * diagnosis genetics therapy blood MeSH
- Humans MeSH
- Mutation MeSH
- Biomarkers, Tumor * blood genetics MeSH
- Prognosis MeSH
- Liquid Biopsy methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Lower risk (LR) myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem and progenitor disorders caused by the accumulation of somatic mutations in various genes including epigenetic regulators that may produce convergent DNA methylation patterns driving specific gene expression profiles. The integration of genomic, epigenomic, and transcriptomic profiling has the potential to spotlight distinct LR-MDS categories on the basis of pathophysiological mechanisms. We performed a comprehensive study of somatic mutations and DNA methylation in a large and clinically well-annotated cohort of treatment-naive patients with LR-MDS at diagnosis from the EUMDS registry (ClinicalTrials.gov.NCT00600860). Unsupervised clustering analyses identified six clusters based on genetic profiling that concentrate into four clusters on the basis of genome-wide methylation profiling with significant overlap between the two clustering modes. The four methylation clusters showed distinct clinical and genetic features and distinct methylation landscape. All clusters shared hypermethylated enhancers enriched in binding motifs for ETS and bZIP (C/EBP) transcription factor families, involved in the regulation of myeloid cell differentiation. By contrast, one cluster gathering patients with early leukemic evolution exhibited a specific pattern of hypermethylated promoters and, distinctly from other clusters, the upregulation of AP-1 complex members FOS/FOSL2 together with the absence of hypermethylation of their binding motif at target gene enhancers, which is of relevance for leukemic initiation. Among MDS patients with lower-risk IPSS-M, this cluster displayed a significantly inferior overall survival (p < 0.0001). Our study showed that genetic and DNA methylation features of LR-MDS at early stages may refine risk stratification, therefore offering the frame for a precocious therapeutic intervention.
- Publication type
- Journal Article MeSH
Large-scale next-generation sequencing (NGS) studies revealed extensive genetic heterogeneity, driving a highly variable clinical course of chronic lymphocytic leukaemia (CLL). The evolution of subclonal populations contributes to diverse therapy responses and disease refractoriness. Besides, the dynamics and impact of subpopulations before therapy initiation are not well understood. We examined changes in genomic defects in serial samples of 100 untreated CLL patients, spanning from indolent to aggressive disease. A comprehensive NGS panel LYNX, which provides targeted mutational analysis and genome-wide chromosomal defect assessment, was employed. We observed dynamic changes in the composition and/or proportion of genomic aberrations in most patients (62%). Clonal evolution of gene variants prevailed over the chromosomal alterations. Unsupervised clustering based on aberration dynamics revealed four groups of patients with different clinical behaviour. An adverse cluster was associated with fast progression and early therapy need, characterized by the expansion of TP53 defects, ATM mutations, and 18p- alongside dynamic SF3B1 mutations. Our results show that clonal evolution is active even without therapy pressure and that repeated genetic testing can be clinically relevant during long-term patient monitoring. Moreover, integrative NGS testing contributes to the consolidated evaluation of results and accurate assessment of individual patient prognosis.
Multiple sex chromosomes usually arise from chromosomal rearrangements which involve ancestral sex chromosomes. There is a fundamental condition to be met for their long-term fixation: the meiosis must function, leading to the stability of the emerged system, mainly concerning the segregation of the sex multivalent. Here, we sought to analyze the degree of differentiation and meiotic pairing properties in the selected fish multiple sex chromosome system present in the wolf-fish Hoplias malabaricus (HMA). This species complex encompasses seven known karyotype forms (karyomorphs) where the karyomorph C (HMA-C) exhibits a nascent XY sex chromosomes from which the multiple X1X2Y system evolved in karyomorph HMA-D via a Y-autosome fusion. We combined genomic and cytogenetic approaches to analyze the satellite DNA (satDNA) content in the genome of HMA-D karyomorph and to investigate its potential contribution to X1X2Y sex chromosome differentiation. We revealed 56 satDNA monomers of which the majority was AT-rich and with repeat units longer than 100 bp. Seven out of 18 satDNA families chosen for chromosomal mapping by fluorescence in situ hybridization (FISH) formed detectable accumulation in at least one of the three sex chromosomes (X1, X2 and neo-Y). Nine satDNA monomers showed only two hybridization signals limited to HMA-D autosomes, and the two remaining ones provided no visible FISH signals. Out of seven satDNAs located on the HMA-D sex chromosomes, five mapped also to XY chromosomes of HMA-C. We showed that after the autosome-Y fusion event, the neo-Y chromosome has not substantially accumulated or eliminated satDNA sequences except for minor changes in the centromere-proximal region. Finally, based on the obtained FISHpatterns, we speculate on the possible contribution of satDNA to sex trivalent pairing and segregation.
- MeSH
- Characiformes * genetics MeSH
- Y Chromosome genetics MeSH
- In Situ Hybridization, Fluorescence * MeSH
- Karyotype MeSH
- Meiosis genetics MeSH
- Evolution, Molecular MeSH
- Sex Chromosomes * genetics MeSH
- DNA, Satellite * genetics MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: Dynamic systems theory and complexity theory (DST/CT) is a framework explaining how complex systems change and adapt over time. In psychotherapy, DST/CT can be used to understand how a person's mental and emotional state changes during therapy incorporating higher levels of complexity. This study aimed to systematically review the variability of DST/CT methods applied in psychotherapy research. METHODS: A primary studies search was conducted in the EBSCO and Web of Knowledge databases, extracting information about the analyzed DST/CT phenomena, employed mathematical methods to investigate these phenomena, descriptions of specified dynamic models, psychotherapy phenomena, and other information regarding studies with empirical data (e.g., measurement granularity). RESULTS: After screening 38,216 abstracts and 4,194 full texts, N = 41 studies published from 1990 to 2021 were identified. The employed methods typically included measures of dynamic complexity or chaoticity. Computational and simulation studies most often employed first-order ordinary differential equations and typically focused on describing the time evolution of client-therapist dyadic influences. Eligible studies with empirical data were usually based on case studies and focused on data with high time intensity of within-session dynamics. CONCLUSION: This review provides a descriptive synthesis of the current state of the proliferation of DST/CT methods in the psychotherapy research field.
- MeSH
- Humans MeSH
- Psychological Theory MeSH
- Psychotherapy * methods MeSH
- Systems Theory * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
Early identification of resistant cancer cells is currently a major challenge, as their expansion leads to refractoriness. To capture the dynamics of these cells, we made a comprehensive analysis of disease progression and treatment response in a chronic lymphocytic leukemia (CLL) patient using a combination of single-cell and bulk genomic methods. At diagnosis, the patient presented with unfavorable genetic markers, including notch receptor 1 (NOTCH1) mutation and loss(11q). The initial and subsequent treatment lines did not lead to a durable response and the patient developed refractory disease. Refractory CLL cells featured substantial dysregulation in B-cell phenotypic markers such as human leukocyte antigen (HLA) genes, immunoglobulin (IG) genes, CD19 molecule (CD19), membrane spanning 4-domains A1 (MS4A1; previously known as CD20), CD79a molecule (CD79A) and paired box 5 (PAX5), indicating B-cell de-differentiation and disease transformation. We described the clonal evolution and characterized in detail two cell populations that emerged during the refractory disease phase, differing in the presence of high genomic complexity. In addition, we successfully tracked the cells with high genomic complexity back to the time before treatment, where they formed a rare subpopulation. We have confirmed that single-cell RNA sequencing enables the characterization of refractory cells and the monitoring of their development over time.
... Definition and basic features of stem cells 176 -- 12.1.3 Proliferation capacity 176 -- 12.1.4 Differentiation ... ... ability 177 -- 12.1.5 Progenitors and precursors 178 -- 12.2 Occurrence of stem cells and their differentiation ... ... 215 -- 14.3 Charles Darwin - Darwinism 218 -- 14.4 Importance of fossils 220 -- 14.5 Mechanisms of evolution ... ... 220 -- 14.6 Molecular evolution 220 -- 14.7 Evolution of human 224 -- 14.8 Evolution of primates 224 ... ... -- 14.9 Evolution of Homo sapiens 225 ...
First edition 227 stran : ilustrace ; 30 cm
- Conspectus
- Lékařské vědy. Lékařství
- Učební osnovy. Vyučovací předměty. Učebnice
- NML Fields
- biologie
- NML Publication type
- učebnice vysokých škol
Pathogen adaptations during host-pathogen co-evolution can cause the host balance between immunity and immunopathology to rapidly shift. However, little is known in natural disease systems about the immunological pathways optimised through the trade-off between immunity and self-damage. The evolutionary interaction between the conjunctival bacterial infection Mycoplasma gallisepticum (MG) and its avian host, the house finch (Haemorhous mexicanus), can provide insights into such adaptations in immune regulation. Here we use experimental infections to reveal immune variation in conjunctival tissue for house finches captured from four distinct populations differing in the length of their co-evolutionary histories with MG and their disease tolerance (defined as disease severity per pathogen load) in controlled infection studies. To differentiate contributions of host versus pathogen evolution, we compared house finch responses to one of two MG isolates: the original VA1994 isolate and a more evolutionarily derived one, VA2013. To identify differential gene expression involved in initiation of the immune response to MG, we performed 3'-end transcriptomic sequencing (QuantSeq) of samples from the infection site, conjunctiva, collected 3-days post-infection. In response to MG, we observed an increase in general pro-inflammatory signalling, as well as T-cell activation and IL17 pathway differentiation, associated with a decrease in the IL12/IL23 pathway signalling. The immune response was stronger in response to the evolutionarily derived MG isolate compared to the original one, consistent with known increases in MG virulence over time. The host populations differed namely in pre-activation immune gene expression, suggesting population-specific adaptations. Compared to other populations, finches from Virginia, which have the longest co-evolutionary history with MG, showed significantly higher expression of anti-inflammatory genes and Th1 mediators. This may explain the evolution of disease tolerance to MG infection in VA birds. We also show a potential modulating role of BCL10, a positive B- and T-cell regulator activating the NFKB signalling. Our results illuminate potential mechanisms of house finch adaptation to MG-induced immunopathology, contributing to understanding of the host evolutionary responses to pathogen-driven shifts in immunity-immunopathology trade-offs.
BACKGROUND: Only little is known about trends in temperature-mortality associations among the most vulnerable subgroups, especially in the areas of central and eastern Europe, which are considered major climatic hotspots in terms of heatwave exposure. Thus, we aimed to assess trends in temperature-related mortality in the Czech Republic by sex, age and cause of death, and to quantify the temporal evolution of possible inequalities. METHODS: We collected daily time series of all-cause (1987-2019) and cause-specific (1994-2019) mortality by sex and age category, and population-weighted daily mean 2-metre temperatures for each region of the Czech Republic. We applied a quasi-Poisson regression model to estimate the trends in region-specific temperature-mortality associations, with distributed lag non-linear models and multivariate random-effects meta-analysis to derive average associations across the country. We then calculated mortality attributable to non-optimal temperatures and implemented the indicator of sex- and age-dependent inequalities. RESULTS: We observed a similar risk of mortality due to cold temperatures for men and women. Conversely, for warm temperatures, a higher risk was observed for women. Results by age showed a clear pattern of increasing risk due to non-optimum temperatures with increasing age category. The relative risk (RR) related to cold was considerably attenuated in most of the studied subgroups during the study period, whereas an increase in the RR associated with heat was seen in the overall population, in women, in the age category 90+ years and with respect to respiratory causes. Moreover, underlying sex- and age-dependent inequalities experienced substantial growth. CONCLUSIONS: Our findings suggest ongoing adaptation to cold temperatures. Mal/adaptation to hot temperatures occurred unequally among population subgroups and resulted in growing inequalities between the sexes and among age categories.
- MeSH
- Humans MeSH
- Mortality MeSH
- Cold Temperature * MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Temperature MeSH
- Hot Temperature * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Geographicals
- Czech Republic MeSH
