Breast cancer belongs to the most commonly diagnosed malignancies worldwide, with its increasing incidence paralleled by advances in early diagnostics and effective treatments resulting in significantly improved survival rates. However, breast cancer survivors often experience significantly reduced quality of life linked to the long-term health burden as a consequence of aggressive oncological treatments applied. Their most frequently recorded complains include chronic fatigue, reduced physical activity, disordered sleep, chronification of pain, and severe mental health impairments-all per evidence are associated with compromised mitochondrial health and impaired homeostasis. Self-report of a breast cancer survivor is included in this article to illustrate currently uncovered patient needs. This article highlights mechanisms behind the suboptimal health of breast cancer survivors associated with mitochondrial damage, and introduces a novel, mitochondria-based holistic approach addressing rehabilitation concepts for breast cancer survivors following advanced principles of predictive, preventive and personalised medicine (3PM). By operating via mitochondrial function, the proposed holistic approach triggers systemic effects at molecular, sub/cellular and organismal levels positively affecting energy metabolism, repair mechanisms as well as physical and mental health creating, therefore, highly effective rehabilitation algorithms tailored to an individualised patient profile. The proposed methodology integrates mitochondrial health assessments utilising mitochondrial homeostasis biomarkers in tear fluid as a non-invasive diagnostic tool, tailored nutraceuticals and lifestyle adjustments. The introduced approach aligns with advanced principles of 3PM, offering a holistic and proactive framework for managing persistent post-treatment symptoms of suboptimal health in the cohort of cancer survivors. Furthermore, presented approach is also applicable to pre-habilitation programmes considering needs of other patient cohorts affected by chronic diseases such as CVD and orthopaedic disorders with planned major surgical incisions, who require individually adapted pre- and rehabilitation programmes. Implementing such innovative pre- and rehabilitation strategies may lead to a full recovery, sustainable health conditions and, therefore, facilitating patients' comeback to normal daily activities, family and professional life. Contextually, presented approach is considered a 'proof-of-principle' model for the 3PM-related paradigm shift from reactive medicine to a cost-effective holistic health management in both primary and secondary care benefiting a large spectrum of affected patient cohorts, individuals in suboptimal health conditions as well as society at large.
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: The management of patients with clear cell renal cell carcinoma (ccRCC) includes prognosis assessment based on TNM classification and biochemical markers. This approach stratifies patients with advanced ccRCC into groups of favorable, intermediate, and poor prognosis. The aim of the study was to improve prognosis estimation using microRNAs involved in the pathogenesis of ccRCC. PATIENTS AND METHODS: The study was based on a histologically-verified set of matched ccRCC FFPE tissue samples (normal renal tissue, primary tumor, metastasis, n=20+20+20). The expression of 2,549 microRNAs was analyzed using the SurePrint G3 Human miRNA microarray kit (Agilent Technologies). Prognostic value of significantly deregulated microRNAs was further evaluated on microRNA expression and clinical data of 475 patients obtained from TCGA Kidney Clear Cell Carcinoma (KIRC) database. RESULTS: There were 13 up-regulated and 6 down-regulated microRNAs in tumor tissues compared to control tissues. Among them, survival analysis revealed those with prognostic significance. Patients with high expression of miR-21, miR-27a, miR-34a, miR-106b, miR-210, and miR-342 showed significantly unfavorable outcome. The opposite was observed for miR-30e, patients with low expression had significantly shorter survival. CONCLUSION: The inclusion of these microRNAs in a prognostic panel holds the potential to enhance stratification scoring systems, on which the treatment of ccRCC patients is based.
- MeSH
- dospělí MeSH
- Kaplanův-Meierův odhad MeSH
- karcinom z renálních buněk * genetika patologie mortalita metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- nádorové biomarkery * genetika MeSH
- nádory ledvin * genetika patologie mortalita metabolismus MeSH
- prognóza MeSH
- regulace genové exprese u nádorů * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- stanovení celkové genové exprese * MeSH
- upregulace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.
- MeSH
- biologické markery * krev MeSH
- C-reaktivní protein * analýza metabolismus MeSH
- dospělí MeSH
- glykoproteiny krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- obezita * krev genetika MeSH
- obstrukční spánková apnoe * krev genetika MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sérový amyloidový protein metabolismus analýza genetika MeSH
- sexuální faktory MeSH
- troponin I krev MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy * genetika patologie MeSH
- mikro RNA * genetika MeSH
- mutace * MeSH
- nádorové biomarkery genetika MeSH
- nádory štítné žlázy * genetika patologie MeSH
- papilární karcinom štítné žlázy * genetika patologie MeSH
- protoonkogenní proteiny B-Raf * genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.
- Publikační typ
- časopisecké články MeSH
111 stran : ilustrace ; 21 cm
Příručka a učebnice obsahující testy z biologie vhodné k přípravě ke zkouškám na vysokou školu. Určeno studentům středních škol.
- Konspekt
- Biologické vědy
- Učební osnovy. Vyučovací předměty. Učebnice
- NLK Obory
- biologie
- NLK Publikační typ
- učebnice středních škol
- testy
AIMS: Endometrial cancer (EC) is the most common gynecological cancer worldwide and its incidence is rising. The cornerstone of its management is surgical treatment with nodal staging. A monocentric study investigating the potential of the molecular biology method of one-step nucleic acid amplification (OSNA) in sentinel lymph node (SLN) analysis was conducted at our institution between April 2016 and January 2018. Histopathological ultrastaging was used as the reference standard for SLN examination and OSNA as the index test. The aim of this study was to assess the long-term outcome of patients with discordant SLN and OSNA results. To our knowledge, this is the first study exploring this issue. METHODS AND RESULTS: Patients were followed in line with the current ESMO/ESGO/ESTRO recommendations. The institutional electronic database was retrospectively searched for patients' follow-up data from April 2016 till March 2023. Only patients who provided a written valid consent and had a positive OSNA and negative ultrastaging of their SLN analysis were included in the study. The primary endpoint was the retrospective analysis of their clinical outcome. Data from 58 patients enrolled into our previous study were reviewed and 12 discordant patients who met the inclusion criteria for this study were identified. The median follow-up was 83 months. Disease recurrence was detected in 3 (25%) patients, two of these were nodal and both patients died. One patient had a solitary lung metastasis which was surgically treated, and the patient was disease-free during the whole study period. CONCLUSION: The recurrence rate of patients included in the study was in the intermediate-high and high-risk group range, and hence, higher than expected based on ultrastaging results. Furthermore, benign epithelial inclusions do not seem to adversely affect OSNA SLN analysis in EC patients.
- MeSH
- biopsie sentinelové lymfatické uzliny * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru patologie genetika epidemiologie MeSH
- lymfatické metastázy patologie diagnóza MeSH
- nádory endometria * genetika patologie chirurgie MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sentinelová uzlina * patologie chirurgie MeSH
- staging nádorů * MeSH
- techniky amplifikace nukleových kyselin * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. METHODS: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. RESULTS: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). CONCLUSION: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. SIGNIFICANCE: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * genetika krev MeSH
- melanom * genetika krev patologie diagnóza chirurgie MeSH
- mutace * MeSH
- nádorové biomarkery * krev genetika MeSH
- nádory kůže * krev genetika patologie diagnóza chirurgie MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- protoonkogenní proteiny B-Raf * genetika krev MeSH
- S-100 kalcium vázající protein G, podjednotka beta * krev genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- tekutá biopsie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Targeted therapy has become increasingly important in treating lung adenocarcinoma, the most common subtype of lung cancer. Next-generation sequencing (NGS) enables precise identification of specific genetic alterations in individual tumor tissues, thereby guiding targeted therapy selection. This study aimed to analyze mutations present in adenocarcinoma tissues using NGS, assess the benefit of targeted therapy and evaluate the progress in availability of targeted therapies over last five years. PATIENTS AND METHODS: The study included 237 lung adenocarcinoma patients treated between 2018-2020. The Archer FusionPlex CTL panel was used for NGS analysis. RESULTS: Gene variants covered by the panel were detected in 57% patients and fusion genes in 5.9% patients. At the time of the study, 34 patients (14.3% of patients) were identified with a targetable variant. Twenty-five patients with EGFR variants, 8 patients with EML4-ALK fusion and one patient with CD74-ROS1 fusion received targeted therapy. Prognosis of patients at advanced stages with EGFR variants treated by tyrosine kinase inhibitors and patients with EML4-ALK fusion treated by alectinib was significantly favorable compared to patients without any targetable variant treated by chemotherapy (p=0.0172, p=0.0096, respectively). Based on treatment guidelines applicable in May 2023, the number of patients who could profit from targeted therapy would be 64 (27.0% of patients), this is an increase by 88% in comparison to recommendations valid in 2018-2020. CONCLUSION: As lung adenocarcinoma patients significantly benefit from targeted therapy, the assessment of mutational profiles using NGS could become a crucial approach in the routine management of oncological patients.
- MeSH
- adenokarcinom plic * farmakoterapie genetika MeSH
- erbB receptory genetika MeSH
- lidé MeSH
- mutace MeSH
- nádory plic * farmakoterapie genetika patologie MeSH
- protoonkogenní proteiny genetika MeSH
- tyrosinkinasové receptory genetika MeSH
- tyrosinkinasy genetika MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Non-invasive circulating tumor biomarkers in liquid biopsy, such as microRNAs (miRNA), provide for better personalization of treatment strategies. The aim of our study was to assess the prognosis of patients with melanoma undergoing tumor resection with curative intent based on analysis of selected circulating miRNAs. PATIENTS AND METHODS: A total of 22 patients with stage I to III melanoma were enrolled into this prospective study. Plasma samples were obtained pre-surgery and early post-surgery from peripheral blood draws. A panel of 23 candidate miRNAs was designed and expression of miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction with exogenous reference control cel-miR-39-3p. RESULTS: Higher preoperative expression levels of miR-99a (p=0.008), miR-320 (p=0.009), miR-1908 (p=0.001), miR-494 (p=0.018) and miR-4487 (p=0.048) were associated with a shorter disease-free interval. Similarly, higher preoperative plasma levels of miR-99a (p=0.017), miR-221 (p=0.026), miR-320 (p=0.016), miR-494 (p=0.009), miR-1260 (p=0.026) and miR-1908 (p=0.024) were associated with worse overall survival. No significant differences between pre- and postoperative plasma miRNA levels were observed. CONCLUSION: Liquid biopsy is a minimally-invasive approach which can lead to a better understanding of cancer behavior and offers the possibility of precise patient prognosis, allowing selection of the most appropriate treatment. Our study showed that preoperative plasma levels of miR-99a, miR-221, miR-320, miR-494, miR-1908 and miR-4487 were associated with disease-free interval and overall survival of patients with early-stage melanoma. This approach may help in decision-making about the appropriateness of modern adjuvant treatment administration in patients with resectable melanoma.
