Zuzana Horakova | Masaryk University (original) (raw)

Papers by Zuzana Horakova

Introduction: A spontaneous pseudomeningocele (PMC) (e.g.without previous surgery or injury) is a... more Introduction: A spontaneous pseudomeningocele (PMC) (e.g.without previous surgery or injury) is a rare pathology that may be mimicked as an unilateral polypoid mass in endoscopy or as a mucocele on CT /MRI, which only very exceptionaly doesn’t present with rhinoliquorhea. PMC develops when cerebrospinal fluid (CSF) becomes trapped behind the paranasal sinus mucosa or extracranial soft tissues, and may be associated with bony erosion. Case presentation: We present an exceptional case of a 47-year-old man with a rare spontaneus pseudomeningocele of the sphenoid sinus without any obvious clinical symptoms, which resembles a mucocele on CT and MRI scans and which was first correctly diagnosed after an exploratory sphenoidotomy. Due to postsurgical complications (a significant rhinoliquorhea), an endoscopic obliteration of the sphenoid cavity was necessary. Conclusion: In the report we intend to stress the pitfalls of an exceptional skull base pathology and its surgical complications in ...

Klinicka Onkologie, 2018

Background: Breast cancer (BC) is a frequent malignant dis ease which tends to develop distant me... more Background: Breast cancer (BC) is a frequent malignant dis ease which tends to develop distant metastases, but only very rarely in the head and neck region. Case report: We present two case reports of patients with metastases of invasive BC in this area. They are of different clinical ma nifestation with different time relation to the primary tumor and different symp tomatology. In the case of the first patient, a few years without evidence of malignant dis ease after treatment of primary tumor in complete remission. In the case of the second patient, as the first symp tom of undia gnosed dis ease. Metastases were clinically observed in the skull base and maxillary sinus, manifest ing neurologically with foramen jugulare syndrome and orbital symp toms, resp. In both cases, correlations between histological and clinical findings were essential for dia g nosis. Palliative multimodal treatment was then employed. Conclusion: Metastases of BC in the head and neck region occur only very rarely. The extremely variable symp tomatology de pends on the location of the metastasis and the affected structures. This might be a pitfall for dia gnostics, especially in cases of an unidentified primary breast tumor, which may result in a delay of correct dia gnosis. In addition, the correlation between histopathological and clinical findings might be of great relevance in these cases.

Cancer Genomics - Proteomics, 2019

Head & Neck, 2018

Background: Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) dese... more Background: Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment. Methods: p16/epidermal growth factor receptor (EGFR)/cluster of differentiation-44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients. Results: In the entire group and the p16 negative cohort, better 3-year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16−, EGFR+/p16−, and EGFR+/CD44+ groups and in the EGFR+/ CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup. Conclusion: Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.

Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, Jan 6, 2018

To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in o... more To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in oropharyngeal squamous cell carcinoma (OPSCC) and to correlate them with radiotherapy treatment outcomes and clinicopathological parameters. Prognostic impact of the American Joint Committee on Cancer (AJCC) 8th edition staging system in comparison with 7th edition was analyzed. The study included 77 OPSCC patients treated by definitive intensity-modulated radiotherapy (IMRT). Clinical staging was assessed according to the AJCC, both 7th and 8th edition. Immunohistochemical (IHC) analysis of CD44 and EGFR was performed on primary biopsy tumor tissues. To evaluate the HPV status, IHC detection of p16 was employed. The AJCC 8th edition staging system revealed correlations between overall survival (OS), progression-free survival (PFS), locoregional control (LRC), and clinical stage. EGFR and CD44 positivity (+) and p16 negativity (-) were associated with clinical stage IV of the disease. CD4...

Uvod: V poslednich letech se zaměřuje cela řada autorů na roli volných kyslikových radikalů (VR) ... more Uvod: V poslednich letech se zaměřuje cela řada autorů na roli volných kyslikových radikalů (VR) u onkologických pacientů. Vseobecný konsenzus předpoklada, že buňka dlouhodobě vystavena zvýsene oxidativni zatěži ma větsi tendenci k malignimu zvratu diky vycerpani kapacit reparovat řetězce DNA dlouhodobě poskozovane VR. Cilem je stanovit parametry oxidativniho stresu u skupiny onkologických pacientů ve srovnani se skupinou neonkologických pacientů. Metodika: Od cervence 2004 do cervence 2005 jsme stanovili parametry oxidativniho stresu u 67 pacientů se spinocelularnim karcinomem hlavy a krku, u kterých byla vytvořena tracheotomie během lecby. Do kontrolni skupiny jsme zařadili 7 neonkologických, u kterých byla provedena tracheotomie z jiných indikaci. Měřili jsme aktivitu glutation peroxidazy (GPx) a superoxid dismutazy (SOD) v alveolarnich makrofazich ziskaných bronchoalveolarni lavaži a jejich aktivitu v erytrocytech. Dale jsme zjistovali hladinu GPx, MDA, TNF Výsledky: Naměřili jsme vyssi průměrne množstvi TNF (2.50 vs. 2.29 ng/L) a MDA (2.27 vs. 2.20 nmol/g bilkovin) u onkologických pacientů. Průměr aktivit SOD v erytrocytech byl ve sledovanem souboru pacientů s nadory nižsi (19.70 vs. 21.28 U/mL, p=0,01). Průměrne množstvi GPx3 v plazmě (32.42 vs. 27.05 mg/mL) bylo vyssi v onkologicke skupině. Průměr aktivit GPx1 v erytrocytech (112.0 vs. 92.3 U/g Hb) a GPx1 v alveolarnich makrofazich (29.78 vs. 12.0 U/g bilkovin) byl vyssi u nadorových pacientů. Zavěr: Vyssi plazmaticke hladiny TNF a MDA bez adekvatniho kompenzatorniho zvýseni množstvi nebo aktivity AOE v plazmě u onkologických pacientů nas opravňuji předpokladat v souladu s pracemi Athara, Arikana, Drehera a jiných, že oxidativni stres hraje významnou roli i v karcinogenezi spinocelularniho karcinomu hlavy a krku. Pokles aktivity AOE 1. stupně (SOD) se soucasně zvýsenou aktivitou AOE 2. stupně (GPx) vede ke kumulaci superoxidových anionů. Nizký pocet pacientů v kontrolni skupině nas nuti přistupovat k výsledkům opatrně. Zkratky: VR-volne kyslikove radikaly, AOE-antioxidativni enzymy, GPx-glutation peroxidaza, SOD-zinecnato-měďnata superoxid dismutaza, MDA-malodialdehyd, TNF-tumor necrosis faktor

International Journal of Clinical Oncology, 2010

The aim of the study was to investigate the relationships among (a) glutathione peroxidase (GPx) ... more The aim of the study was to investigate the relationships among (a) glutathione peroxidase (GPx) and malondialdehyde (MDA); (b) oncological characteristics (i.e., TNM classification, tumor grade), and; (c) prognosis of head and neck squamous cell carcinoma. In a prospective cohort study, we followed 88 patients for 67.4 months (median 40.3) after surgery for head and neck squamous cell carcinoma. Activity of GPx was determined by ELISA and plasma MDA concentration by liquid chromatography. Lower GPx activity was observed in the T3/4 patients than in the T1/2 group. Tumor grade was significantly correlated with both GPx (P = 0.001) and MDA (P = 0.05, both Spearman). The perioperative level of MDA was higher in patients who later recurred during the follow-up period (n = 15) than in the complete remission group (P = 0.01, Mann-Whitney). Median disease-free interval and overall survival in the group with MDA > median were 29.5 and 32.0 months, respectively, and 38.4 and 40.3 months in the patient group with MDA ≤ median (P = 0.10 and P = 0.08, respectively; Kaplan-Meier). Patients with MDA levels higher than the median had a more than twofold greater risk of recurrence than patients with MDA levels smaller than the median (31.3 vs. 15.2%, P = 0.06, logrank). Our results suggest that an increased MDA level at the time of initial surgery is found in patients with a high risk of recurrence, which suggests that each patient can be categorized according to risk of recurrence based on their MDA level at the time of initial surgery.

Karcinomy hlavy a krku lze považovat za malignity s relativně vysokou incidenci typicke svým agre... more Karcinomy hlavy a krku lze považovat za malignity s relativně vysokou incidenci typicke svým agresivnim růstem. Vzhledem k anatomicke blizkosti životně důležitých struktur znamena jejich adekvatně radikalni chirurgicka lecba znacnou mutilaci pacienta. Naděje se proto upinaji ke stale preferovanějsi konzervativni nechirurgicke terapii (radio, chemoterapie nebo biologicka lecba). Tato lecebna strategie ovsem nese riziko, že pouze cca 50% nadorů lze hodnotit jako dostatecne sensitivni k těmto lecebným modalitam.

BOOK powered by: December 02 03 2015 hotel NH Collection Olomouc Congress Legionarska 21, 779 00 ... more BOOK powered by: December 02 03 2015 hotel NH Collection Olomouc Congress Legionarska 21, 779 00 Olomouc, Czech Republic ISBN 978-80-260-8368-9 ISSN 2336-8284 www.imtm.cz ADD PRECISION TO UNDERSTANDING CANCER GENETICS Resolving Tumor Heterogeneity by Digitally Sorting 100% Pure Cells DEPArray technology can sort and recover homogenous pools of phenotypically identical cells from heterogeneous cell suspensions obtained from disaggregated FFPE tissues, allowing precise characterization of quantitative genomic traits from your tissue sections. w w w. s i l i c o n b i o s y s t e m s . c o m Organizing Institutions Institute of Molecular and Translational Medicine

Talanta, 2019

Due to the close relationship between carcinogenesis and human papillomavirus (HPV), and since th... more Due to the close relationship between carcinogenesis and human papillomavirus (HPV), and since they are transmitted via huge number of asymptomatic carriers, the detection of HPV is really needed to reduce the risk of developing cancer. According to the best of our knowledge, our study provides the very first method for one-step detection of viral infection and if it has initiated the subsequent cancer proliferation. The proposed novel nanosystem consists of magnetic glass particles (MGPs), which were attached with DNA probe on their surface to hybridize with target DNAs. The MGP-probe-DNA hybrid was finally conjugated with CdTe/ZnSe core/shell quantum dots (QDs). The proposed detection system is based on a novel mechanism in which the MGPs separate out the target DNAs from different biological samples using external magnetic field for better and clear detection and the QDs give different fluorescent maxima for different target DNAs due to their ability to interact differently with different nucleotides. Firstly, the method was optimized using HPV genes cloned into synthetic plasmids. Then it was applied directly on the samples from normal and cancerous cells. After that, the real hospital samples of head and neck squamous cell carcinoma (HNSCC) with or without the infection of HPV were also analyzed. Our novel nano-system is proved successful in detecting and distinguishing between the patients suffering by HPV infection with or without subsequent cancer having detection limit estimated as 1.0 x 109 (GEq/mL). The proposed methodology is faster and cost-effective, which can be applied at the clinical level to help the doctors to decide the strategy of medication that may save the life of the patients with an early treatment.

The European Physical Journal D, 2017

Abstract In order to improve patients’ post-treatment quality of life, a shift from surgery to no... more Abstract In order to improve patients’ post-treatment quality of life, a shift from surgery to non-surgical (chemo)radio-treatment is recognized in head and neck oncology. However, about half of HNSCC tumors are resistant to irradiation and an efficient marker of individual tumor radiosensitivity is still missing. We analyzed whether various parameters of DNA double strand break (DSB) repair determined in vitro can predict, prior to clinical treatment initiation, the radiosensitivity of tumors. We compared formation and decrease of γH2AX/53BP1 foci in 48 h after irradiating tumor cell primocultures with 2 Gy of γ-rays. To better understand complex tumor behavior, three different cell type primocultures – CD90−, CD90+, and a mixed culture of these cells – were isolated from 1 clinically radioresistant, 2 radiosensitive, and 4 undetermined HPV–HNSCC tumors and followed separately. While DSB repair was delayed and the number of persisting DSBs increased in the radiosensitive tumors, the results for the radioresistant tumor were similar to cultured normal human skin fibroblasts. Hence, DSB repair kinetics/efficiency may correlate with clinical response to radiotherapy for a subset of HNSCC tumors but the size (and therefore practical relevance) of this subset remains to be determined. The same is true for contribution of different cell type primocultures to tumor radioresistance. Graphical abstract

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Jan 20, 2016

Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including t... more Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including the head and neck squamous cell carcinoma (HNSCC). Although there are many new and innovative approaches in the treatment of HNSCC, a clear marker of this disease is still missing. Three candidate miRNAs (miR-29c-3p, miR-200b-5p and miR-375-3p) were studied in connection with HNSCC using quantitative real-time PCR expression levels in 42 tissue samples of HNSCC patients and histologically normal tumour-adjacent tissue samples of these patients. Primary HNSCC carcinoma tissues can be distinguished from histologically normal-matched noncancerous tumour-adjacent tissues based on hsa-miR-375-3p expression (sensitivity 87.5 %, specificity 65 %). Additionally, a significant decrease of hsa-miR-200b-5p expression was revealed in tumour-adjacent tissue samples of patients with node positivity. Lower expression of hsa-miR-200b-5p and hsa-miR-29c-3p in HNSCC tumour tissue was associated with higher...

Oncology letters, 2016

Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival ... more Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival of patients with head and neck squamous cell carcinoma (HNSCC) is low (≤50%). A non-invasive marker of disease progression is sorely required. The present study focused on the plasmatic levels of epidermal growth factor receptor (EGFR) in HNSCC patients (N=92) compared with healthy (N=29) and diabetic [type 2 diabetes mellitus (T2DM); N=26] controls. Enzyme-linked immunosorbent assay using antibodies against the extracellular region of EGFR (L25-S645) was performed. No significant changes were observed between diabetic and healthy controls. However, there were significantly higher EGFR plasma levels in HNSCC patients compared with both control groups (P=0.001 and 0.005, respectively). Receiver operating characteristic curve analysis identified a sensitivity of 76.09%, a specificity of 67.27% and an area under curve of 0.727 for this comparison. No significant association was observed bet...

Uvod Platinove komplexy hraji důležitou roli v chemoterapii různých zhoubných nadorů [1,2]. Biolo... more Uvod Platinove komplexy hraji důležitou roli v chemoterapii různých zhoubných nadorů [1,2]. Biologicka aktivita prvniho cytostatika založeneho na platině cisplatiny (cis-diamminodichloroplatina(II)), ktere je stale jednim z nejvice použivaných cytotoxických agens, byla objevena již v roce 1965 Rosenborgem během studia vlivu elektrickeho proudu na růst bakterii [3]. Během nasledujicich 40 let byly syntetizovany a testovany stovky platnatých a platicitých komplexů jako možna protirakovinova leciva. Diky intenzivnimu vývoji v teto oblasti bylo vyvinuto v osmdesatých letech minuleho stoleti platinove lecivo druhe generace carboplatina [cis-diammino(1,1-cyklobutan-dikarboxylato)platina(II)] jako meně toxicka alternativa k cisplatině vykazujici take mensi pocet vedlejsich ucinků [4,5]. Dalsim zastupcem použivaných na platině založených cytostatik je oxaliplatina, ktera byla navržena v devadesatých letech minuleho stoleti jako třeti generace platinových leciv k překonani rezistence vůci cisplatině a carboplatině. I přesto, že jsou platinova cytostatika uspěsně použivana při lecbě nadorových onemocněni vice než 30 let, mechanismus jejich biochemickeho ucinku je stale nejasný. Vseobecně akceptovaný nazor popisujici jejich ucinek je, že platinove lecivo indukuje sve cytotoxicke vlastnosti prostřednictvim vazby do struktury jaderne DNA a nasledným narusenim transkripcnich anebo replikacnich mechanismů. Chaney et al. a dalsi objevili, že cisplatina, carboplatina a oxaliplatina tvoři stejne typu aduktů na stejných mistech ve struktuře DNA. Je tedy nezbytne nejen sledovat koncentraci platinoveho cytostatika v krvi pacienta, ale take studovat tvorbu Pt-DNA aduktů. Pro samotne stanoveni platinových cytostatik bylo navrženo mnoho technik jako HPLC spojena s různými typy detektorů anebo elektrochemicke metody. Na druhou stranu pro detekci Pt-DNA aduktů je využivano technik velmi malo a navic, biosensor pro detekci Pt-DNA aduktů jestě nebyl nikdy navržen. Na zakladě výse zminěných fakt jsme se v teto praci rozhodli navrhnout biosensor pro detekci Pt-DNA aduktů. Zavěr Vývoj jednoduchých a rychlých sensorů a biosensorů pro stanoveni různých latek je jednim z velmi důležitých ukolů bio-analyticke chemie. V teto praci se nam podařilo navrhnout biosensor pro stanoveni Pt-DNA aduktů. Navržený biosensor je schopen analyzovat 100 ng Pt-DNA aduktu v jednom mililitru.

Tumor Biology, 2015

Approximately 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and the overall... more Approximately 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and the overall 5-year survival rate is not higher than 50 %. There is much evidence that human papillomavirus (HPV) infection may influence the expression of commonly studied HNSCC markers. Our study was focused on the possible HPV-specificity of molecular markers that could be key players in important steps of cancerogenesis (MKI67, EGF, EGFR, BCL-2, BAX, FOS,

Tumor Biology, 2015

Your article is protected by copyright and all rights are held exclusively by International Socie... more Your article is protected by copyright and all rights are held exclusively by International Society of Oncology and BioMarkers (ISOBM). This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".

Pochopení molekulárních mechanismů karcinogeneze je nedílnou součástí pro pochopení chování nádor... more Pochopení molekulárních mechanismů karcinogeneze je nedílnou součástí pro pochopení chování nádorových buněk. V této studii byla vytvořena primokultura z histologicky definovaného spinocelulárního karcinomu hlavy a krku pomocí RT-PCR byla analyzována exprese genů Bax, Bcl-2 a p53. Oproti nenádorové tkáni byly identifikovány signifikantní rozdíly v expresi těchto genů. Výsledky byly korelovány s růstovou charakteristikou buněk. Výsledky spějí k lepšímu pochopení agresivního chování nádorů.

Karcinomy hlavy a krku jsou významným onkologickým problémem současnosti. Řada studií popisuje zm... more Karcinomy hlavy a krku jsou významným onkologickým problémem současnosti. Řada studií popisuje změny v hladinách metalotioneinu, protein, účastnících se antioxidačních pochodů a regulace apoptózy. Výsledky studií byly analyzovány meta-analýzou. U těchto nádorů byl identifikován signifikantní vzestup positivity imunohistochemického barvení oproti nenádorové tkáni. Takovýto postup může být benefitem pro rutinní diagnostiku.

Over 40,000 new cases of head and neck tumours are diagnosed in United States every year (1), thu... more Over 40,000 new cases of head and neck tumours are diagnosed in United States every year (1), thus, these tumours are an important issue, in male population, in particular. Histologically, tumours of head and neck comprise relatively uniform group of mostly spinocellular tumours with unique zinc and zinc-binding protein metallothionein (MT) metabolism (2). In these tumours, elevated levels of both zinc (II) and MT were observed by numerous studies. Therefore, a potential use of those substances as tumour markers was outlined. Thus, the aim of this pilot study was to analyse the level of MT in tissue first obtained samples of histologically verified spinocellular tumours using electrochemical detection. The MT levels were compared with levels in adjacent tissues and correlated with TNM staging. Total 30 tissue samples were collected and analysed due 2013 with following locations included: oral cavity and pharynx. Significantly higher (t-test, p < 0.05) MT content was determined in both locations compared to adjacent tissue. In contrast, no significant differences were determined between oral cavity and pharyngeal tumours. With regard to tumour staging, significant positive correlation was determined (r = 0.79, p < 0.05). These preliminary results indicate MT as an important molecule in the head and neck tumour development and a potential diagnostic biomarker for this tumor type, however further studies on increasing number of samples will provide more detailed conclusions. References: 1. Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. Ca-a Cancer Journal for Clinicians 63: 11-30, 2013. 2. Eckschlager T, Adam V, Hrabeta J, Figova K and Kizek R: Metallothioneins and Cancer. Curr Protein Pept Sci 10: 360-375, 2009.

International Journal of Molecular Medicine

Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of can... more Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males worldwide. Due to its high incidence and mortality, early diagnosis, identification of highly aggressive forms of clinically silent and understanding of disease pathogenesis with typical metabolic differences in order to develop specifically targeted therapy are needed [1]. As a results of numerous studies on cell as well as on prostate cancer patients, there have been found several compounds connected with tumourigenesis in prostate cells including Bcl-2. This intracellular protein belongs to a large group of proteins called “Bcl-2 family”. Bcl-2 acts as an inhibitor of apoptosis. It has been suggested that overexpression of the Bcl-2 oncoprotein in human cancer cells contributes to their resistance to chemotherapy- and radiotherapy-induced apoptosis and is connected with unfavourable prognosis. In the fact, the majority of human prostate tumours overexpress Bcl-2, wh...

Introduction: A spontaneous pseudomeningocele (PMC) (e.g.without previous surgery or injury) is a... more Introduction: A spontaneous pseudomeningocele (PMC) (e.g.without previous surgery or injury) is a rare pathology that may be mimicked as an unilateral polypoid mass in endoscopy or as a mucocele on CT /MRI, which only very exceptionaly doesn’t present with rhinoliquorhea. PMC develops when cerebrospinal fluid (CSF) becomes trapped behind the paranasal sinus mucosa or extracranial soft tissues, and may be associated with bony erosion. Case presentation: We present an exceptional case of a 47-year-old man with a rare spontaneus pseudomeningocele of the sphenoid sinus without any obvious clinical symptoms, which resembles a mucocele on CT and MRI scans and which was first correctly diagnosed after an exploratory sphenoidotomy. Due to postsurgical complications (a significant rhinoliquorhea), an endoscopic obliteration of the sphenoid cavity was necessary. Conclusion: In the report we intend to stress the pitfalls of an exceptional skull base pathology and its surgical complications in ...

Klinicka Onkologie, 2018

Background: Breast cancer (BC) is a frequent malignant dis ease which tends to develop distant me... more Background: Breast cancer (BC) is a frequent malignant dis ease which tends to develop distant metastases, but only very rarely in the head and neck region. Case report: We present two case reports of patients with metastases of invasive BC in this area. They are of different clinical ma nifestation with different time relation to the primary tumor and different symp tomatology. In the case of the first patient, a few years without evidence of malignant dis ease after treatment of primary tumor in complete remission. In the case of the second patient, as the first symp tom of undia gnosed dis ease. Metastases were clinically observed in the skull base and maxillary sinus, manifest ing neurologically with foramen jugulare syndrome and orbital symp toms, resp. In both cases, correlations between histological and clinical findings were essential for dia g nosis. Palliative multimodal treatment was then employed. Conclusion: Metastases of BC in the head and neck region occur only very rarely. The extremely variable symp tomatology de pends on the location of the metastasis and the affected structures. This might be a pitfall for dia gnostics, especially in cases of an unidentified primary breast tumor, which may result in a delay of correct dia gnosis. In addition, the correlation between histopathological and clinical findings might be of great relevance in these cases.

Cancer Genomics - Proteomics, 2019

Head & Neck, 2018

Background: Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) dese... more Background: Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment. Methods: p16/epidermal growth factor receptor (EGFR)/cluster of differentiation-44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients. Results: In the entire group and the p16 negative cohort, better 3-year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16−, EGFR+/p16−, and EGFR+/CD44+ groups and in the EGFR+/ CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup. Conclusion: Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.

Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, Jan 6, 2018

To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in o... more To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in oropharyngeal squamous cell carcinoma (OPSCC) and to correlate them with radiotherapy treatment outcomes and clinicopathological parameters. Prognostic impact of the American Joint Committee on Cancer (AJCC) 8th edition staging system in comparison with 7th edition was analyzed. The study included 77 OPSCC patients treated by definitive intensity-modulated radiotherapy (IMRT). Clinical staging was assessed according to the AJCC, both 7th and 8th edition. Immunohistochemical (IHC) analysis of CD44 and EGFR was performed on primary biopsy tumor tissues. To evaluate the HPV status, IHC detection of p16 was employed. The AJCC 8th edition staging system revealed correlations between overall survival (OS), progression-free survival (PFS), locoregional control (LRC), and clinical stage. EGFR and CD44 positivity (+) and p16 negativity (-) were associated with clinical stage IV of the disease. CD4...

Uvod: V poslednich letech se zaměřuje cela řada autorů na roli volných kyslikových radikalů (VR) ... more Uvod: V poslednich letech se zaměřuje cela řada autorů na roli volných kyslikových radikalů (VR) u onkologických pacientů. Vseobecný konsenzus předpoklada, že buňka dlouhodobě vystavena zvýsene oxidativni zatěži ma větsi tendenci k malignimu zvratu diky vycerpani kapacit reparovat řetězce DNA dlouhodobě poskozovane VR. Cilem je stanovit parametry oxidativniho stresu u skupiny onkologických pacientů ve srovnani se skupinou neonkologických pacientů. Metodika: Od cervence 2004 do cervence 2005 jsme stanovili parametry oxidativniho stresu u 67 pacientů se spinocelularnim karcinomem hlavy a krku, u kterých byla vytvořena tracheotomie během lecby. Do kontrolni skupiny jsme zařadili 7 neonkologických, u kterých byla provedena tracheotomie z jiných indikaci. Měřili jsme aktivitu glutation peroxidazy (GPx) a superoxid dismutazy (SOD) v alveolarnich makrofazich ziskaných bronchoalveolarni lavaži a jejich aktivitu v erytrocytech. Dale jsme zjistovali hladinu GPx, MDA, TNF Výsledky: Naměřili jsme vyssi průměrne množstvi TNF (2.50 vs. 2.29 ng/L) a MDA (2.27 vs. 2.20 nmol/g bilkovin) u onkologických pacientů. Průměr aktivit SOD v erytrocytech byl ve sledovanem souboru pacientů s nadory nižsi (19.70 vs. 21.28 U/mL, p=0,01). Průměrne množstvi GPx3 v plazmě (32.42 vs. 27.05 mg/mL) bylo vyssi v onkologicke skupině. Průměr aktivit GPx1 v erytrocytech (112.0 vs. 92.3 U/g Hb) a GPx1 v alveolarnich makrofazich (29.78 vs. 12.0 U/g bilkovin) byl vyssi u nadorových pacientů. Zavěr: Vyssi plazmaticke hladiny TNF a MDA bez adekvatniho kompenzatorniho zvýseni množstvi nebo aktivity AOE v plazmě u onkologických pacientů nas opravňuji předpokladat v souladu s pracemi Athara, Arikana, Drehera a jiných, že oxidativni stres hraje významnou roli i v karcinogenezi spinocelularniho karcinomu hlavy a krku. Pokles aktivity AOE 1. stupně (SOD) se soucasně zvýsenou aktivitou AOE 2. stupně (GPx) vede ke kumulaci superoxidových anionů. Nizký pocet pacientů v kontrolni skupině nas nuti přistupovat k výsledkům opatrně. Zkratky: VR-volne kyslikove radikaly, AOE-antioxidativni enzymy, GPx-glutation peroxidaza, SOD-zinecnato-měďnata superoxid dismutaza, MDA-malodialdehyd, TNF-tumor necrosis faktor

International Journal of Clinical Oncology, 2010

The aim of the study was to investigate the relationships among (a) glutathione peroxidase (GPx) ... more The aim of the study was to investigate the relationships among (a) glutathione peroxidase (GPx) and malondialdehyde (MDA); (b) oncological characteristics (i.e., TNM classification, tumor grade), and; (c) prognosis of head and neck squamous cell carcinoma. In a prospective cohort study, we followed 88 patients for 67.4 months (median 40.3) after surgery for head and neck squamous cell carcinoma. Activity of GPx was determined by ELISA and plasma MDA concentration by liquid chromatography. Lower GPx activity was observed in the T3/4 patients than in the T1/2 group. Tumor grade was significantly correlated with both GPx (P = 0.001) and MDA (P = 0.05, both Spearman). The perioperative level of MDA was higher in patients who later recurred during the follow-up period (n = 15) than in the complete remission group (P = 0.01, Mann-Whitney). Median disease-free interval and overall survival in the group with MDA &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; median were 29.5 and 32.0 months, respectively, and 38.4 and 40.3 months in the patient group with MDA ≤ median (P = 0.10 and P = 0.08, respectively; Kaplan-Meier). Patients with MDA levels higher than the median had a more than twofold greater risk of recurrence than patients with MDA levels smaller than the median (31.3 vs. 15.2%, P = 0.06, logrank). Our results suggest that an increased MDA level at the time of initial surgery is found in patients with a high risk of recurrence, which suggests that each patient can be categorized according to risk of recurrence based on their MDA level at the time of initial surgery.

Karcinomy hlavy a krku lze považovat za malignity s relativně vysokou incidenci typicke svým agre... more Karcinomy hlavy a krku lze považovat za malignity s relativně vysokou incidenci typicke svým agresivnim růstem. Vzhledem k anatomicke blizkosti životně důležitých struktur znamena jejich adekvatně radikalni chirurgicka lecba znacnou mutilaci pacienta. Naděje se proto upinaji ke stale preferovanějsi konzervativni nechirurgicke terapii (radio, chemoterapie nebo biologicka lecba). Tato lecebna strategie ovsem nese riziko, že pouze cca 50% nadorů lze hodnotit jako dostatecne sensitivni k těmto lecebným modalitam.

BOOK powered by: December 02 03 2015 hotel NH Collection Olomouc Congress Legionarska 21, 779 00 ... more BOOK powered by: December 02 03 2015 hotel NH Collection Olomouc Congress Legionarska 21, 779 00 Olomouc, Czech Republic ISBN 978-80-260-8368-9 ISSN 2336-8284 www.imtm.cz ADD PRECISION TO UNDERSTANDING CANCER GENETICS Resolving Tumor Heterogeneity by Digitally Sorting 100% Pure Cells DEPArray technology can sort and recover homogenous pools of phenotypically identical cells from heterogeneous cell suspensions obtained from disaggregated FFPE tissues, allowing precise characterization of quantitative genomic traits from your tissue sections. w w w. s i l i c o n b i o s y s t e m s . c o m Organizing Institutions Institute of Molecular and Translational Medicine

Talanta, 2019

Due to the close relationship between carcinogenesis and human papillomavirus (HPV), and since th... more Due to the close relationship between carcinogenesis and human papillomavirus (HPV), and since they are transmitted via huge number of asymptomatic carriers, the detection of HPV is really needed to reduce the risk of developing cancer. According to the best of our knowledge, our study provides the very first method for one-step detection of viral infection and if it has initiated the subsequent cancer proliferation. The proposed novel nanosystem consists of magnetic glass particles (MGPs), which were attached with DNA probe on their surface to hybridize with target DNAs. The MGP-probe-DNA hybrid was finally conjugated with CdTe/ZnSe core/shell quantum dots (QDs). The proposed detection system is based on a novel mechanism in which the MGPs separate out the target DNAs from different biological samples using external magnetic field for better and clear detection and the QDs give different fluorescent maxima for different target DNAs due to their ability to interact differently with different nucleotides. Firstly, the method was optimized using HPV genes cloned into synthetic plasmids. Then it was applied directly on the samples from normal and cancerous cells. After that, the real hospital samples of head and neck squamous cell carcinoma (HNSCC) with or without the infection of HPV were also analyzed. Our novel nano-system is proved successful in detecting and distinguishing between the patients suffering by HPV infection with or without subsequent cancer having detection limit estimated as 1.0 x 109 (GEq/mL). The proposed methodology is faster and cost-effective, which can be applied at the clinical level to help the doctors to decide the strategy of medication that may save the life of the patients with an early treatment.

The European Physical Journal D, 2017

Abstract In order to improve patients’ post-treatment quality of life, a shift from surgery to no... more Abstract In order to improve patients’ post-treatment quality of life, a shift from surgery to non-surgical (chemo)radio-treatment is recognized in head and neck oncology. However, about half of HNSCC tumors are resistant to irradiation and an efficient marker of individual tumor radiosensitivity is still missing. We analyzed whether various parameters of DNA double strand break (DSB) repair determined in vitro can predict, prior to clinical treatment initiation, the radiosensitivity of tumors. We compared formation and decrease of γH2AX/53BP1 foci in 48 h after irradiating tumor cell primocultures with 2 Gy of γ-rays. To better understand complex tumor behavior, three different cell type primocultures – CD90−, CD90+, and a mixed culture of these cells – were isolated from 1 clinically radioresistant, 2 radiosensitive, and 4 undetermined HPV–HNSCC tumors and followed separately. While DSB repair was delayed and the number of persisting DSBs increased in the radiosensitive tumors, the results for the radioresistant tumor were similar to cultured normal human skin fibroblasts. Hence, DSB repair kinetics/efficiency may correlate with clinical response to radiotherapy for a subset of HNSCC tumors but the size (and therefore practical relevance) of this subset remains to be determined. The same is true for contribution of different cell type primocultures to tumor radioresistance. Graphical abstract

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, Jan 20, 2016

Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including t... more Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including the head and neck squamous cell carcinoma (HNSCC). Although there are many new and innovative approaches in the treatment of HNSCC, a clear marker of this disease is still missing. Three candidate miRNAs (miR-29c-3p, miR-200b-5p and miR-375-3p) were studied in connection with HNSCC using quantitative real-time PCR expression levels in 42 tissue samples of HNSCC patients and histologically normal tumour-adjacent tissue samples of these patients. Primary HNSCC carcinoma tissues can be distinguished from histologically normal-matched noncancerous tumour-adjacent tissues based on hsa-miR-375-3p expression (sensitivity 87.5 %, specificity 65 %). Additionally, a significant decrease of hsa-miR-200b-5p expression was revealed in tumour-adjacent tissue samples of patients with node positivity. Lower expression of hsa-miR-200b-5p and hsa-miR-29c-3p in HNSCC tumour tissue was associated with higher...

Oncology letters, 2016

Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival ... more Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival of patients with head and neck squamous cell carcinoma (HNSCC) is low (≤50%). A non-invasive marker of disease progression is sorely required. The present study focused on the plasmatic levels of epidermal growth factor receptor (EGFR) in HNSCC patients (N=92) compared with healthy (N=29) and diabetic [type 2 diabetes mellitus (T2DM); N=26] controls. Enzyme-linked immunosorbent assay using antibodies against the extracellular region of EGFR (L25-S645) was performed. No significant changes were observed between diabetic and healthy controls. However, there were significantly higher EGFR plasma levels in HNSCC patients compared with both control groups (P=0.001 and 0.005, respectively). Receiver operating characteristic curve analysis identified a sensitivity of 76.09%, a specificity of 67.27% and an area under curve of 0.727 for this comparison. No significant association was observed bet...

Uvod Platinove komplexy hraji důležitou roli v chemoterapii různých zhoubných nadorů [1,2]. Biolo... more Uvod Platinove komplexy hraji důležitou roli v chemoterapii různých zhoubných nadorů [1,2]. Biologicka aktivita prvniho cytostatika založeneho na platině cisplatiny (cis-diamminodichloroplatina(II)), ktere je stale jednim z nejvice použivaných cytotoxických agens, byla objevena již v roce 1965 Rosenborgem během studia vlivu elektrickeho proudu na růst bakterii [3]. Během nasledujicich 40 let byly syntetizovany a testovany stovky platnatých a platicitých komplexů jako možna protirakovinova leciva. Diky intenzivnimu vývoji v teto oblasti bylo vyvinuto v osmdesatých letech minuleho stoleti platinove lecivo druhe generace carboplatina [cis-diammino(1,1-cyklobutan-dikarboxylato)platina(II)] jako meně toxicka alternativa k cisplatině vykazujici take mensi pocet vedlejsich ucinků [4,5]. Dalsim zastupcem použivaných na platině založených cytostatik je oxaliplatina, ktera byla navržena v devadesatých letech minuleho stoleti jako třeti generace platinových leciv k překonani rezistence vůci cisplatině a carboplatině. I přesto, že jsou platinova cytostatika uspěsně použivana při lecbě nadorových onemocněni vice než 30 let, mechanismus jejich biochemickeho ucinku je stale nejasný. Vseobecně akceptovaný nazor popisujici jejich ucinek je, že platinove lecivo indukuje sve cytotoxicke vlastnosti prostřednictvim vazby do struktury jaderne DNA a nasledným narusenim transkripcnich anebo replikacnich mechanismů. Chaney et al. a dalsi objevili, že cisplatina, carboplatina a oxaliplatina tvoři stejne typu aduktů na stejných mistech ve struktuře DNA. Je tedy nezbytne nejen sledovat koncentraci platinoveho cytostatika v krvi pacienta, ale take studovat tvorbu Pt-DNA aduktů. Pro samotne stanoveni platinových cytostatik bylo navrženo mnoho technik jako HPLC spojena s různými typy detektorů anebo elektrochemicke metody. Na druhou stranu pro detekci Pt-DNA aduktů je využivano technik velmi malo a navic, biosensor pro detekci Pt-DNA aduktů jestě nebyl nikdy navržen. Na zakladě výse zminěných fakt jsme se v teto praci rozhodli navrhnout biosensor pro detekci Pt-DNA aduktů. Zavěr Vývoj jednoduchých a rychlých sensorů a biosensorů pro stanoveni různých latek je jednim z velmi důležitých ukolů bio-analyticke chemie. V teto praci se nam podařilo navrhnout biosensor pro stanoveni Pt-DNA aduktů. Navržený biosensor je schopen analyzovat 100 ng Pt-DNA aduktu v jednom mililitru.

Tumor Biology, 2015

Approximately 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and the overall... more Approximately 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and the overall 5-year survival rate is not higher than 50 %. There is much evidence that human papillomavirus (HPV) infection may influence the expression of commonly studied HNSCC markers. Our study was focused on the possible HPV-specificity of molecular markers that could be key players in important steps of cancerogenesis (MKI67, EGF, EGFR, BCL-2, BAX, FOS,

Tumor Biology, 2015

Your article is protected by copyright and all rights are held exclusively by International Socie... more Your article is protected by copyright and all rights are held exclusively by International Society of Oncology and BioMarkers (ISOBM). This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".

Pochopení molekulárních mechanismů karcinogeneze je nedílnou součástí pro pochopení chování nádor... more Pochopení molekulárních mechanismů karcinogeneze je nedílnou součástí pro pochopení chování nádorových buněk. V této studii byla vytvořena primokultura z histologicky definovaného spinocelulárního karcinomu hlavy a krku pomocí RT-PCR byla analyzována exprese genů Bax, Bcl-2 a p53. Oproti nenádorové tkáni byly identifikovány signifikantní rozdíly v expresi těchto genů. Výsledky byly korelovány s růstovou charakteristikou buněk. Výsledky spějí k lepšímu pochopení agresivního chování nádorů.

Karcinomy hlavy a krku jsou významným onkologickým problémem současnosti. Řada studií popisuje zm... more Karcinomy hlavy a krku jsou významným onkologickým problémem současnosti. Řada studií popisuje změny v hladinách metalotioneinu, protein, účastnících se antioxidačních pochodů a regulace apoptózy. Výsledky studií byly analyzovány meta-analýzou. U těchto nádorů byl identifikován signifikantní vzestup positivity imunohistochemického barvení oproti nenádorové tkáni. Takovýto postup může být benefitem pro rutinní diagnostiku.

Over 40,000 new cases of head and neck tumours are diagnosed in United States every year (1), thu... more Over 40,000 new cases of head and neck tumours are diagnosed in United States every year (1), thus, these tumours are an important issue, in male population, in particular. Histologically, tumours of head and neck comprise relatively uniform group of mostly spinocellular tumours with unique zinc and zinc-binding protein metallothionein (MT) metabolism (2). In these tumours, elevated levels of both zinc (II) and MT were observed by numerous studies. Therefore, a potential use of those substances as tumour markers was outlined. Thus, the aim of this pilot study was to analyse the level of MT in tissue first obtained samples of histologically verified spinocellular tumours using electrochemical detection. The MT levels were compared with levels in adjacent tissues and correlated with TNM staging. Total 30 tissue samples were collected and analysed due 2013 with following locations included: oral cavity and pharynx. Significantly higher (t-test, p < 0.05) MT content was determined in both locations compared to adjacent tissue. In contrast, no significant differences were determined between oral cavity and pharyngeal tumours. With regard to tumour staging, significant positive correlation was determined (r = 0.79, p < 0.05). These preliminary results indicate MT as an important molecule in the head and neck tumour development and a potential diagnostic biomarker for this tumor type, however further studies on increasing number of samples will provide more detailed conclusions. References: 1. Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. Ca-a Cancer Journal for Clinicians 63: 11-30, 2013. 2. Eckschlager T, Adam V, Hrabeta J, Figova K and Kizek R: Metallothioneins and Cancer. Curr Protein Pept Sci 10: 360-375, 2009.

International Journal of Molecular Medicine

Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of can... more Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males worldwide. Due to its high incidence and mortality, early diagnosis, identification of highly aggressive forms of clinically silent and understanding of disease pathogenesis with typical metabolic differences in order to develop specifically targeted therapy are needed [1]. As a results of numerous studies on cell as well as on prostate cancer patients, there have been found several compounds connected with tumourigenesis in prostate cells including Bcl-2. This intracellular protein belongs to a large group of proteins called “Bcl-2 family”. Bcl-2 acts as an inhibitor of apoptosis. It has been suggested that overexpression of the Bcl-2 oncoprotein in human cancer cells contributes to their resistance to chemotherapy- and radiotherapy-induced apoptosis and is connected with unfavourable prognosis. In the fact, the majority of human prostate tumours overexpress Bcl-2, wh...