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Oral microbiome and carcinogenesis
Šimáčková, Šárka ; Šmahelová, Jana (advisor) ; Horníková, Lenka (referee)
Microorganisms that colonize human body participate to well functioning of human organism and they are very important for human health. The composition of these communities (microbiomes) is specific for everyone and changes in the composition may participate to induce and progression of disease. These diseases also include carcinogenesis and tumors. Main goal of this work are specially tumors in head and neck area which risk factors are smoking, alcohol consumption and human papillomaviruses infection. Depending on these factors is influenced the composition of microbiome of oral cavity. Many studies show differences between oral microbiomes of patients with head and neck cancer and healthy people as controls. Keywords: microbiome, oral cavity, head and neck cancer, papillomavirus
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The detection of hypoxic markers in head and neck tumours
Šťovíčková, Eliška ; Šmahelová, Jana (advisor) ; Rösel, Daniel (referee)
Head and neck cancers (HNSCC) are heterogeneous group of tumours. Risk factors are mainly smoking and alcohol consumption. Some of these tumours are associated with human papillomavirus (HPV) infection, which is a significant positive prognostic factor. These tumours differ from HPV-negative tumours in clinicopathological characteristics, tumour microenvironment and response to treatment. Hypoxia is commonly found in tumors including HNSCC and is a significant prognostic and predictive factor. Elucidating the degree of hypoxia in relation to HPV infection could partly explain the differences in prognosis of these patients and allow more appropriate choice of therapy. Aspartate-β-hydroxylase is also a significant negative prognostic factor in a number of tumours, but its role in HNSCC has not yet been investigated. I focused on the detection of hypoxic markers and aspartate-β-hydroxylase expression in samples from HNSCC patients at the mRNA level by quantitative PCR and at the protein level by multispectral immunohistochemistry. The expression levels of these markers were compared in tumors stratified according to viral etiology and other characteristics such as smoking, localization or tumor stage. HPV infection had the highest impact on the expression of these markers, but the results cannot point to a...
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Detection and characterization of macrophages in the tumors of viral and non-viral etiology
Dalewská, Natálie ; Tachezy, Ruth (advisor) ; Krulová, Magdaléna (referee)
Head and neck cancers are etiologically associated with smoking and alcohol consumption. Part of these tumors is induced by HPV and their incidence is increasing in the last decade. Patients with virally induced tumors have better prognosis even though they are usually diagnosed with tumors in advanced stage. One of the possible explanations may be better stimulation of the immune system by viral antigens. Macrophages are cells of the innate immune system which belong to professional phagocytes. They are called TAM upon infiltration to the tumor where they represent heterogeneous group of cells. Two main phenotypes are antitumor M1 and protumor M2 macrophages. TAMs are a major component of tumor microenvironment of many types of tumors, one of them are also head and neck cancers. In my thesis I focused on the immunohistochemical detection of M1 and M2 macrophages in the head and neck tumors of viral and non-viral etiology and at the same time RT-qPCR analyses of gene expression of macrophage-associated and/or immunosuppressive genes IDO1, ARG1, CD163, NOS2 a PTGS2 was performed. My data showed that HPV- negative tumors had higher number of M2 macrophages with typical markers CD163, ARG1 and PTGS2. It is known that patients with these tumors have worse prognosis of the disease. Due to high...
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Analysis of miRNAs in HPV-associated carcinomas
Pagáčová, Lucie ; Tachezy, Ruth (advisor) ; Vopálenský, Václav (referee)
Papillomaviruses are small DNA viruses that are associated with the induction of epithelial tumors. HPV is an important infectious agent causing almost 100 % of cervical tumors but it can also cause tumors in other anogenital and head and neck locations in both men and women. Active HPV infection induces changes in miRNA expression that contribute to the tumor formation and progression. It is already known that papillomaviruses do not encode their own viral miRNAs but they affect the expression of cellular miRNAs. In my thesis I have in selected epithelial tumors (vulva, cervix, anus and tonsils) determined their etiology and analyzed the presence of miRNAs in tissues by next generation sequencing. From these data I determined the expression profiles of deregulated miRNAs in tumors relation to healthy tissues of corresponding location. Even though, sufficient number of samples was analyzed, it was not possible to detect HPV-core miRNA common to all analyzed HPV-induced tumors due to the absence of statistically relevant differentially expressed miRNAs in HPV positive vulvar tumors. Among the tumors of the other sites I found an overlap in three miRNAs. One of these miRNAs (miR-139-5p) and another one (miR-9-5p) which I have selected based on the study of other published data, were used for...
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Impact of pattern and functional properties of tumor-infiltrating immune cells for clinical outcome of head and neck cancer
Hladíková, Kamila ; Špíšek, Radek (advisor) ; Plzák, Jan (referee) ; Reiniš, Milan (referee)
Head and neck squamous cell carcinoma encompasses a complex and heterogeneous group of malignant diseases. Originally, this tumor type was associated with tobacco and alcohol consumption. However, a significantly expanding subset of tumors associated with oncogenic human papillomavirus infection arising in deep tonsillar crypts was identified within the last decades. Due to the essential role of the immune system in antiviral and anticancer immune response, the prognosis of patients is significantly influenced by the volume, composition and functional capacity of the immune infiltrate. The immunosuppressive landscape of head and neck cancer leads to unfavorable outcome of patients and decreased efficacy of immunotherapy. The response rate to standard treatment is high, however, standard therapy is accompanied by considerable toxicity influencing the quality of life. In 2016, the first immunotherapeutics for the treatment of patients with recurrent squamous cell carcinoma of the head and neck were approved - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab. This type of therapy, based on mitigation of immunosuppression, shows strong efficacy and less toxicity in combination with other therapies. Therefore, anti-PD-1 immunotherapy was recently approved in the first-line...
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Molecular analysis of head and neck carcinomas associated with HPV infection
Glendová, Kristýna ; Staněk, Libor (advisor) ; Tachezy, Ruth (referee)
Head and neck cancers (HNSCC) are highly heterogeneous disease, results from two major carcinogens - tobacco and/or alcohol, or HR HPV infection. This thesis was based on 60 biopsies of head and neck tumours embedded into paraffin after histological verification. HPV infection, including particular types was monitored in different HNSCC regions by multiplex qPCR. Subsequent IHC demonstrated expression of p16INK4A and p53 as a possible diagnostic biomarker. Based on the information, patients with HNSCC can benefit from antiEGFR therapy by Cetuximab, but so far without defined predictors, the analysis of point mutations of Ras gene family (Kras, Nras) and Braf gene was performed. These mutations were monitored as potential predictive biomarkers, in correlation with gender, age and other risk factors. For all statistical processing the Chi-x2 test was used. Key words: Head and neck cancers, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf
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Detection and characterization of macrophages in the tumors of viral and non-viral etiology
Dalewská, Natálie ; Tachezy, Ruth (advisor) ; Krulová, Magdaléna (referee)
Head and neck cancers are etiologically associated with smoking and alcohol consumption. Part of these tumors is induced by HPV and their incidence is increasing in the last decade. Patients with virally induced tumors have better prognosis even though they are usually diagnosed with tumors in advanced stage. One of the possible explanations may be better stimulation of the immune system by viral antigens. Macrophages are cells of the innate immune system which belong to professional phagocytes. They are called TAM upon infiltration to the tumor where they represent heterogeneous group of cells. Two main phenotypes are antitumor M1 and protumor M2 macrophages. TAMs are a major component of tumor microenvironment of many types of tumors, one of them are also head and neck cancers. In my thesis I focused on the immunohistochemical detection of M1 and M2 macrophages in the head and neck tumors of viral and non-viral etiology and at the same time RT-qPCR analyses of gene expression of macrophage-associated and/or immunosuppressive genes IDO1, ARG1, CD163, NOS2 a PTGS2 was performed. My data showed that HPV- negative tumors had higher number of M2 macrophages with typical markers CD163, ARG1 and PTGS2. It is known that patients with these tumors have worse prognosis of the disease. Due to high...
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Impact of pattern and functional properties of tumor-infiltrating immune cells for clinical outcome of head and neck cancer
Hladíková, Kamila ; Špíšek, Radek (advisor) ; Plzák, Jan (referee) ; Reiniš, Milan (referee)
Head and neck squamous cell carcinoma encompasses a complex and heterogeneous group of malignant diseases. Originally, this tumor type was associated with tobacco and alcohol consumption. However, a significantly expanding subset of tumors associated with oncogenic human papillomavirus infection arising in deep tonsillar crypts was identified within the last decades. Due to the essential role of the immune system in antiviral and anticancer immune response, the prognosis of patients is significantly influenced by the volume, composition and functional capacity of the immune infiltrate. The immunosuppressive landscape of head and neck cancer leads to unfavorable outcome of patients and decreased efficacy of immunotherapy. The response rate to standard treatment is high, however, standard therapy is accompanied by considerable toxicity influencing the quality of life. In 2016, the first immunotherapeutics for the treatment of patients with recurrent squamous cell carcinoma of the head and neck were approved - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab. This type of therapy, based on mitigation of immunosuppression, shows strong efficacy and less toxicity in combination with other therapies. Therefore, anti-PD-1 immunotherapy was recently approved in the first-line...
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Analysis of miRNAs in HPV-associated carcinomas
Pagáčová, Lucie ; Tachezy, Ruth (advisor) ; Vopálenský, Václav (referee)
Papillomaviruses are small DNA viruses that are associated with the induction of epithelial tumors. HPV is an important infectious agent causing almost 100 % of cervical tumors but it can also cause tumors in other anogenital and head and neck locations in both men and women. Active HPV infection induces changes in miRNA expression that contribute to the tumor formation and progression. It is already known that papillomaviruses do not encode their own viral miRNAs but they affect the expression of cellular miRNAs. In my thesis I have in selected epithelial tumors (vulva, cervix, anus and tonsils) determined their etiology and analyzed the presence of miRNAs in tissues by next generation sequencing. From these data I determined the expression profiles of deregulated miRNAs in tumors relation to healthy tissues of corresponding location. Even though, sufficient number of samples was analyzed, it was not possible to detect HPV-core miRNA common to all analyzed HPV-induced tumors due to the absence of statistically relevant differentially expressed miRNAs in HPV positive vulvar tumors. Among the tumors of the other sites I found an overlap in three miRNAs. One of these miRNAs (miR-139-5p) and another one (miR-9-5p) which I have selected based on the study of other published data, were used for...
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Head and neck carcinom irradiation off axis dose assessment
FIALOVÁ, Eliška
In the introduction of my bachelor thesis I am reviewing the problematics of head and neck tumors. This types of tumors belong under otorhinolaryngology - we are speaking about the tumors in the oral cavity, larynx, farynx, nasal cavity, paranasal sinuses and also salivary glands. Symptoms of tumors vary depending on their localization. Patients tend to consider early stage tumor to be something else and so the tumor has a chance to grow a long time unrecognized. Most prominent etiological risk include smoking and alcohol consumption. Other risk include low hygiene, social exclusion, weed smoking or ionizing radiation - in general, all of these can induce tumor growth. Tumor diagnosis often comes late. When choosing the appropriate treatment, all prognosis factors must be accounted for, in particular the stage of tumor (marked by TNM classification), its locality, histological type and patient's age and health condition and his wishes. Patients' wishes must be respected. The chapter "Methods of treatment" briefly summarizes characteristics of each method. As of next, I am looking at the modern radiation techniques. These techniques seem to have better results compared to their predecessors. The aim of conformal radiation technique (3DCRT) is to adjust the shape of the radiated volume to the irregular shape of the tumour. IMRT technique does this and also modifies the intensity (fluence) of the radiation beam. That enables the IMRT to affect more complex target shapes while sparing the surrounding tissue to a degree. IGRT method uses imaging of the targeted volume and its critical structures before the treatment itself. The field work was carried out at the oncological ward of the hospital in České Budějovice. Course of the treatment went standardly at the linear particle accelerator with patients being fixed with the radiation mask and equipped with personal electric dosimeter. I compared my measurements with those of Mgr. Renáta Chylíková who worked with the previous type of the accelarator machine. Patients undergoing oncological treatment receive higher doses than are the limits but since it is for the medical purposes, the doses are not subjected to limitation. Aim of the work was to test the manufacturer's claim that the mimoos dosage on the newest accelerator should be 60% lower compared to the older type. By comparing the results I found out the claim seems to be true.
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