Circulating tumor cells (CTCs) are released from primary tumors and transported through the body via blood or lymphatic vessels before settling to form micrometastases under suitable conditions. Accordingly, several studies have identified CTCs as a negative prognostic factor for survival in many types of cancer. CTCs also reflect the current heterogeneity and genetic and biological state of tumors; so, their study can provide valuable insights into tumor progression, cell senescence, and cancer dormancy. Diverse methods with differing specificity, utility, costs, and sensitivity have been developed for isolating and characterizing CTCs. Additionally, novel techniques with the potential to overcome the limitations of existing ones are being developed. This primary literature review describes the current and emerging methods for enriching, detecting, isolating, and characterizing CTCs.

• MeSH
• lidé MeSH
• nádorové cirkulující buňky * patologie   MeSH
• separace buněk metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The presence of circulating tumor cells (CTC) has been reported in patients with advanced colorectal cancer. Monitoring CTC (also known as a liquid-biopsy) has recently become the center of interest for low-invasive monitoring of cancer progression and predictive biomarkers testing. Along with high-cost technology and a complex methodology, a straightforward method based on magnetic beads enrichment followed by RT-PCR is set to allow for routine CTC analysis in colorectal cancer patients. OBJECTIVES: The main purpose of this study was to evaluate the possibility of CTC detection in routine monitoring of patients starting before and continuing after surgery. MATERIAL AND METHODS: The investigated group consisted of 30 patients mainly in advanced stages of colorectal cancer. In all patients, CTC detection was performed prior to surgery, in a subset of 14 patients additional sampling was done during and after surgery. In all cases, peripheral blood was processed using AdnaTest ColonCancer kit, which relies on enriching CTCs using EpCAM-functionalized magnetic beads and subsequently identifying tumorspecific CEA, EGFR and GA733-2 mRNA transcripts. RESULTS: Out of all the tested samples, CTC were found in one patient suffering from advanced disease with lung and liver metastases. There, however, the positive finding was confirmed in 3 consecutive samples acquired before, during and shortly after palliative R2 resection. CONCLUSIONS: The presence of CTC may be used to observe post-operative disease development. Due to the overall low CTC detection, further technology development may be necessary before its universal applicability to manage colorectal cancer patients.

• MeSH
• imunomagnetická separace metody   MeSH
• kolorektální chirurgie * MeSH
• kolorektální nádory patologie   chirurgie   MeSH
• lidé MeSH
• nádorové cirkulující buňky patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Hepatocellular carcinoma (HCC) is a severe neoplastic disease associated with high morbidity and mortality rates. HCC is often detected at advanced stages leading to ineffective curative treatments. Recently, liquid biopsy has emerged as a non-invasive method to identify highly specific HCC biomarkers in bodily fluids such as blood, serum, urine, and saliva. Circulating cell-free nucleic acids (cfNAs), particularly cell-free DNA (cfDNA) and cell-free RNA (cfRNA), have become promising candidates for biomarkers in liquid biopsy applications. While cfDNA presented significant challenges, researchers have turned their attention to cfRNA, which can be efficiently identified through various methods and is considered a potential biomarker for cancer diagnosis and prognosis. This review primarily focuses on studies related to detecting various cfRNA in body fluids as biomarkers. The aim is to provide a summary of available information to assist researchers in their investigations and the development of new diagnostic and prognostic tools.

• MeSH
• hepatocelulární karcinom * diagnóza   krev   genetika   MeSH
• lidé MeSH
• nádorové biomarkery * krev   genetika   analýza   MeSH
• nádory jater * diagnóza   genetika   krev   MeSH
• prognóza MeSH
• tekutá biopsie metody   MeSH
• volné cirkulující nukleové kyseliny * krev   analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Lung cancer (LC) and malignant mesothelioma (MM) are malignancies linked to environmental/occupational exposure, which are increasing in incidence. Despite advances in chemotherapy, radiation therapy and surgical management of LC and MM, the median survival remains less than 12 months. Early detection represents one of the most promising approaches to reducing the growing cancer burden by increasing chemotherapy treatment efficiency. At present, early diagnosis is rather difficult and depends on invasive sampling of pleural fluid or tissue. Currently the most widely used screening method for the surveillance of exposed subjects is computed tomography (CT), which is costly, exposes patients to repeated high doses of radiation, and typically detects the malignancy at its advanced stage. Recently, a virtually non-invasive 'liquid biopsy' has emerged as source to characterize tumour heterogeneity. The genetic/epigenetic changes during tumour evolution can be detected in fluids and used as cancer biomarkers. Therefore, increasingly interest has been paid to circulating (cell-free) nucleic acids (cfDNA/cfmiRNAs) epigenetically modulated during cell transformation. Hypermethylation of tumour suppressor genes is frequently observed in cancers, and such epigenetic changes are potential markers for detecting and monitoring tumours. The same predictive biomarkers can be used as therapy targets.

• MeSH
• analýza přežití MeSH
• časná detekce nádoru metody   MeSH
• epigenomika * MeSH
• GPI-vázané proteiny krev   metabolismus   MeSH
• incidence MeSH
• lidé MeSH
• metylace DNA MeSH
• mezoteliom epidemiologie   genetika   mortalita   terapie   MeSH
• mikro RNA krev   genetika   MeSH
• nádorové biomarkery krev   genetika   metabolismus   MeSH
• nádory plic epidemiologie   genetika   mortalita   terapie   MeSH
• počítačová rentgenová tomografie metody   MeSH
• pracovní expozice MeSH
• prognóza MeSH
• supresorové geny MeSH
• tekutá biopsie metody   MeSH
• volné cirkulující nukleové kyseliny krev   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Head and neck cancer (HNC) remains one of the leading causes of mortality worldwide due to tumor diagnosis at a late stage, loco-regional aggression, and distant metastases. A standardized diagnostic procedure for HNC is a tissue biopsy that cannot faithfully portray the in-depth tumor dynamics. Therefore, there is an urgent need to develop simple, accurate, and non-invasive methods for cancer detection and follow-up. A saliva-based liquid biopsy allows convenient, non-invasive, and painless collection of high volumes of this biofluid, with the possibility of repetitive sampling, all enabling real-time monitoring of the disease. No approved clinical test for HNC has yet been established. However, epigenetic changes in saliva circulating cell-free DNA (cfDNA) have the potential for a wide range of clinical applications. Therefore, the aim of this review is to present an overview of cfDNA-based methylation patterns in saliva for early detection of HNC, with particular attention to circulating tumor DNA (ctDNA). Due to advancements in isolation and detection technologies, as well as next- and third-generation sequencing, recent data suggest that salivary biomarkers may be successfully applied for early detection of HNC in the future, but large prospective clinical trials are still warranted.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Volná cirkulující DNA (cf‑DNA) je charakterizována jako extracelulární DNA, která může být přítomna v nízkých koncentracích v krvi zdravých jedinců. Cf‑DNA je do krevního řečiště uvolňována apoptózou, ale i nekrózou. Zvýšené hladiny se vyskytují u patologických stavů, jako je zánět, stres či autoimunitní onemocnění. Výrazně zvýšené hodnoty cf‑DNA jsou patrné zejména u pacientů s malignitami, a to především v pokročilých stadiích nemoci. V takovémto případě je nádorově specifická cf‑DNA uvolňována nekrózou z buněk primárního nádoru a metastáz. V poslední době se hodně studií zabývá tzv. liquid biopsy (tekutou biopsií), která umožňuje poměrně snadnou detekci cirkulujících nádorových buněk i cirkulujících molekul nukleových kyselin z periferní krve k diagnostice nádorových onemocnění. Kvantitativní stanovení a detekce genetických a epigenetických změn v cf‑DNA u pacientů s různými malignitami má potenciální využití v molekulární diagnostice, prognóze, monitorování průběhu nemoci a odpovědi na léčbu. Tento článek je zaměřen na potenciální využití cf‑DNA jako krevního biomarkeru u vybraných solidních nádorů a hematologických malignit.

Circulating cell‑free DNA (cf‑DNA) is characterized as extracellular DNA that may be present in the blood of healthy individuals in low concentrations. Cf‑DNA is released by apoptosis or necrosis into the bloodstream. Increased levels are found in pathological conditions, such as inflammation, autoimmune diseases, or stress. Significant increase of cf‑DNA is particularly evident in patients with malignancies, especially in the advanced stages of the disease. In this case, the tumor specific cf‑DNA is released by necrosis from the cells of primary tumor and metastases. Recently, many studies concentrate on the so‑called ‘liquid biopsies’ that allow detection of circulating tumor cells and circulating nucleic acids from peripheral blood for tumor diagnostics. Quantitative methods and detection of genetic and epigenetic alternations of cf‑DNA in patients with different malignancies have potential applications in molecular diagnosis, prognosis, monitoring of disease progression and response to treatment. This review focuses on potential utility of cf‑DNA as a blood biomarker in selected solid tumors and hematologic malignancies. Key words: circulating cell‑free DNA – tumor marker – solid tumors – hematological malignancies This study was supported by grant of Internal Grant Agency of the Czech Ministry of Health NT14575. 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 “uniform requirements” for biomedical papers. Submitted: 13. 3. 2015 Accepted: 18. 5. 2015

• MeSH
• biopsie metody   MeSH
• DNA * diagnostické užití   genetika   krev   MeSH
• hematologické nádory genetika   krev   MeSH
• kolorektální nádory krev   MeSH
• lidé MeSH
• metylace DNA MeSH
• mutace MeSH
• nádorové biomarkery MeSH
• nádory plic genetika   krev   MeSH
• nádory prsu genetika   krev   MeSH
• nádory * genetika   krev   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Úvod: Nádorová kachexie představuje multifaktoriální syndrom charakterizovaný progresivní ztrátou tělesné hmotnosti, který postihuje velkou část pacientů s pokročilým nádorovým onemocněním. Kachexie bývá spojena se sníženou tolerancí léčby, sníženou odpovědí na terapii, poklesem kvality života i délky přežití, přičemž některé z mechanizmů kachexie jsou sdíleny napříč celým spektrem komplexních chorob, např. systémový zánět, zvýšená lipolýza, inzulinová rezistence. Do dnešní doby ovšem nedošlo k rozšíření účinného léčebného algoritmu, který by představoval efektivní terapeutickou modalitu pro kachexii. Faktor aktivující B buňky (BAFF) je novým členem rodiny TNF ligandů, je produkován zejména myeloidními buňkami a nedávno bylo prokázáno, že se účastní regulace přežití a maturace B buněk, ale i adipocytů. Představuje proto elegantního kandidáta spojujícího imunitní systém a metabolizmus tukové tkáně, tj. systémy z hlediska nádorové kachexie klíčové. Nedávno bylo navíc popsáno, že BAFF přímo ovlivňuje sekreci IL-6 a IL-10. Materiál a metody: V této studii byly měřeny cirkulující hladiny BAFF před zahájením léčby u skupiny 83 pediatrických onkologických pacientů (0–18 let) s nádorovou kachexií nebo bez ní. Výsledky: Kromě logických významných asociací cirkulujících hladin BAFF se závažností onemocnění u proliferací z B buněk jsme pozorovali významné zvýšení hladiny BAFF u pacientů s Ewingovým sarkomem a rhabdomyosarkomem ve srovnání s hladinami adekvátními pro daný věk dítěte. Závěr: Jedná se o první studii zkoumající hladinu BAFF před léčbou u širokého spektra pediatrických malignit s nádorovou kachexií či bez ní. Je nutný další výzkum k objasnění, zda BAFF může sloužit jako cirkulující biomarker pro detekci či monitorování nádorové kachexie.

Background: Cancer-related cachexia is a multifactorial syndrome characterised by progressive loss of body weight and it affects a large proportion of patients with advanced cancer. Cachexia is associated with reduced treatment tolerance, response to therapy, quality of life and duration of survival, whereas some of its mechanisms are shared across the whole continuum of diseases in the population, either cancer-related or non-cancer related e.g. systemic inflammation, increased lipolysis, insulin resistance and reduced physical performance. However, so far there has been only little effort to utilise the integrative physiology of adipose tissue to achieve therapeutic gain. B cell-activating factor (BAFF) is a novel member of the TNF ligand superfamily, is mainly produced by myeloid cells and has recently been shown to participate in B-cell survival and B- and T-cell maturation, but also in adipogenesis. Therefore, it represents an elegant candidate molecule linking the immune system and adipose tissue metabolism, both being involved deeply in the pathogenesis of cachexia. Moreover, it has been described very recently that BAFF directly influences secretion of IL-6 and IL-10. Material and Methods: In this study, ­pre-treatment circulating levels of BAFF were investigated in a cohort of 83 paediatric patients with malignancy (0–18 y) with or without cancer-related cachexia using ELISA-based methodology. Results: Apart from logical significant associations of BAFF circulating levels with disease severity in B-lineage malignancies (ALL or B-cell lymphomas), we observed significant elevation of BAFF in adolescent patients with Ewing sarcoma and rhabdomyosarcoma, compared to the circulating levels appropriate for given age. Conclusion: To the best of our know­ledge, this is so far the first study focusing on BAFF in paediatric malignancies with or without cancer-related cachexia. More research into whether BAFF can represent a useful circulating biomarker for detection and monitoring of the cancer-related cachexia is imperative.

• Klíčová slova
• faktor aktivující B buňky (BAFF), pediatrická onkologie, nádorové onemocnění,
• MeSH
• dítě MeSH
• faktor aktivující B-buňky * krev   MeSH
• index tělesné hmotnosti MeSH
• kachexie * komplikace   krev   MeSH
• kojenec MeSH
• lidé MeSH
• logistické modely MeSH
• mladiství MeSH
• nádory * epidemiologie   klasifikace   komplikace   metabolismus   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• průřezové studie statistika a číselné údaje   MeSH
• statistika jako téma MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• práce podpořená grantem MeSH

The concept of liquid biopsy as an analysis tool for non-solid tissue carried out for the purpose of providing information about solid tumors was introduced approximately 20 years ago. Additional to the detection of circulating tumor cells (CTCs), the liquid biopsy approach quickly included the analysis of circulating tumor DNA (ctDNA) and other tumor-derived markers such as circulating cell-free RNA or extracellular vesicles. Liquid biopsy is a non-invasive technique for detecting multiple cancer-associated biomarkers that is easy to obtain and can reflect the characteristics of the entire tumor mass. Currently, ctDNA is the key component of the liquid biopsy approach from the point of view of the prognosis assessment, prediction, and monitoring of the treatment of non-small-cell lung cancer (NSCLC) patients. ctDNA in NSCLC patients carries variants or rearrangements that drive carcinogenesis, such as those in EGFR, KRAS, ALK, or ROS1. Due to advances in pharmacology, these variants are the subject of targeted therapy. Therefore, the detection of these variants has gained attention in clinical medicine. Recently, methods based on qPCR (ddPCR, BEAMing) and next-generation sequencing (NGS) are the most effective approaches for ctDNA analysis. This review addresses various aspects of the use of liquid biopsy with an emphasis on ctDNA as a biomarker in NSCLC patients.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH