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Infectious agents causing-cancers
Olos, Tomáš ; Dáňová, Jana (advisor)
Cancer is one of the most serious problems of clinical medicine. At present, the cause of death of every fifth citizen of the CR and the incidence is rising. This civilization disease affects an extra lower age range. Compared to the past, this is mainly due to the fundamentally different composition of food that contains a preponderance of sugars and fats, but also stress and contamination of environmental substances with carcinogenic effect. Unsuitable diet and carcinogens present in the water, air and food cause the forming jednolivých higher number of tumor cells than the natural organism. The immune system may be weakened by stress and pollutants, it is not able to adequately respond to this situation. For the greatest amount of recovered material, I have most dealt with the issue of hepatocellular carcinoma and its relationship to hepatitis B an Powered by TCPDF (www.tcpdf.org)
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Immunotherapy of ovarian carcinoma with dendritic cells
Partlová, Simona ; Rožková, Daniela (advisor) ; Froňková, Eva (referee)
V ANGLICKÉM JAZYCE Immunotherapy of ovarian carcinoma with dendritic cells Anticancer immunotherapy is a therapeutical strategy aimed at elicitation and maintenance of immune responses against cancer cells. In this study we have focused on immunotherapy of ovarian cancer, because it is one of the most common gynaecological tumors with poor prognosis and high mortality. Our immunotherapy protocol involves preparing dendritic cells (DC) from monocytes isolated from patient's peripheral blood, which are subsequently pulsed with irradiated cells of established ovarian cancer cell line. These immature pulsed DC are maturated and subsequently co-cultivated with autologous T lymphocytes. The aim of this study was to demonstrate, that DC are able to elicit specific immune response after addition of suitable mature agens in combination with apoptotic ovarian tumor cells. Our observations indicate that 24 hours are sufficient for induction of tumor cells apoptosis. Additionally, we have shown that DC successfully ingested most of the apoptotic tumor cells after 4 hours of co-incubation. Furthermore, we have found out that ingestion of apoptotic cells by dendritic cells, which are stimulated with polyI:C, inhibits maturation of DC and consequently also production of cytokines IL-12p70, IL-6 and TNF-α. Whereas...
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název v anglickém jazyce není uveden
Krásná, Luboslava ; Veselý, Pavel (advisor) ; Křepela, Evžen (referee) ; Červinka, Miroslav (referee)
An in vitro cultivation technique has been developed that allows to reproducibly obtain and propagate a heterogenous population of epithelial cells from samples of normal mammary glands, breast tumours and subcutaneous metastases of breast cancer. The epithelial origin of cultured cells was proved by their cytokeratin profile, and EMA and ESA protein expression. The technique uses a feeder layer of irradiated NIH 3T3 cells to support clonal growth of even single isolated cells. Cultures were successfully established from 96% of surgical tumour biopsy specimens (69 out of 72, volume of sample about 1 cm3) and 67% of true-cut biopsy specimens (28 out of 42, volume 0.01 cm3). Two and more in vitro passages were obtained with 74% (53 out of 72) of surgical specimens and 31% (13 out of 42) of truecut biopsy specimens. This is the first report of successful in vitro propagation of cells obtained from breast cancer via true-cut biopsy. In cell populations analyzed for the growth properties, the culture lifetime, related to the number of colony-forming cells, varied for cells from benign tumours between 22 and 40 cell populations and for malignant tumours between 21 and 51. The population doubling time varied betwen 18 and 62 hours for benign cultures and 10 and 127 hours for malignant cultures, with average 32...
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Sojové isoflavonoidy, genistein a daidzein: Jejich biologické efekty na buněčné linie rakoviny prsu
Hůrková, Kristýna ; Šimůnek, Tomáš (advisor) ; Boušová, Iva (referee)
- 1 - ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kristýna Hůrková Supervisors: Profa . Dra . Natércia Teixeira, Profa . Dra . Georgina Correia da Silva, Doc.Pharm.Dr. Tomáš Šimůnek Ph.D. Title of diploma thesis: Soya isoflavones, genistein and daidzein: Their biological effects on breast cancer cell lines Cancer is one of the leading causes of death worldwide. Epidemiological studies suggested that there is a low incidence of breast cancer in countries with high soya intake. Soya contains the isoflavones daidzein (D) and genistein (G), which are responsible for the protective properties, although their exact effects have not yet been clarified. In this study we evaluated and compared the biochemical and biological effects of a soya extract biotransformed by Aspergillus Awamori (SBE) and of the pure major isoflavones, G and D in placental microsomes and in an estrogen-dependent breast cancer cell line stably transfected with the aromatase gene, the MCF-7aro cell line. The results showed that D did not induce marked alterations in any of the parameters studied. In placental microsomes G was not a potent aromatase inhibitor, inducing only a moderate reduction in the aromatase activity. In MCF-7aro cells it was observed a significant...
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Expression of different forms of actine in some non-muscular and muscular tissues and tumors
Dundr, Pavel ; Povýšil, Ctibor (advisor) ; Marek, Josef (referee) ; Mačák, Jiří (referee)
Actins are ubiquitous eucaryotic proteins. Actin filaments are involved in diverse functions which include cell contraction, motility, adhesion, division, cell shape maintenance and muscle contraction. Four actin isoforms are tissue specific (α-smooth muscle actin, α-cardiac actin, α-skeletal actin and γ-smooth muscle actin). Two other actin isoforms (cytoplasmic β- and γ-actins) are ubiquitous. Alpha-smooth muscle actin (α-SMA) expression is typically found in vascular and enteric muscle tissue, in myoepithelial cells, myofibroblasts and pericytes. However, expression of this actin isoform could be detected in a variety of other cells and tumors with a preexisting different phenotype. Our study focused on the expression of actin isoforms in some muscular and non-muscular tissues and tumors. The goals of our study were: 1 Analysis of actin isoforms expression in normal, osteoarthrotic, posttraumatic and transplanted cartilage. 2 Analysis of actin isoform expression in some non-muscle tumors. 3 Analysis of actin isoform expression in uterine leiomyomas after therapy and in leiomyomas with inclusion bodies of the gastrointestinal tract and uterus and the detailed analysis of inclusion bodies. A total of 82 samples of cartilage, 591 samples of neuroectodermal tumors, 87 cases of breast carcinoma, and 29 cases...
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In situ analýzy zánětlivých kolitid Muc2-/- myší.
Drábková, Martina ; Vejsová, Marcela (advisor) ; Jílek, Petr (referee)
Author: Martina Drábková Title: In situ analyses of inflammatory colitis in Muc2-/- mice Diploma thesis Charles University in Prague, Faculty of pharmacy in Hradec Králové Pharmacy Background: Muc2 mucin is the main structural component of the intestinal mucus which forms important protective barrier avoiding the direct contact between the commensal bacteria and the epithelium. In order to understand the role of Muc2 mucin a Muc2 deficient mice strain has been developed. Initial observation showed that these mice already in few weeks after the birth develop spontaneous colitis and later on colon cancer. To better understanding what is going on in the colon and small intestine of Muc2-/- mice, in this thesis we focused on in situ analyses of distribution of different immune cells in these tissues. Methods: In our experiments three Muc2-/- , two Muc2+/- and three wild type mice on the C57BL/6 background were used. For the detection of distribution of different immune cells within lamina propria of small intestine and colon the immunohistochemistry analyses on sections from these tissues were performed. Results: In the lamina propria of distal colon of Muc2-/- mice we found an increase of neutrophils followed by increase of macrophages, CD4+ T cells and B cells/plasma cells compared to control and...
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IGFBP3 expressing rekombinant vaccinia virus used for tumor therapy
Musil, Jan ; Němečková, Šárka (advisor) ; Forstová, Jitka (referee)
IGFBP-3 expressing rekombinant vaccinia viruses used for tumor therapy Insulin-like growth factor-binding protein-3 (IGFBP-3) is a major regulator of endocrine effects of IGF and is capable to suppress the growth of variety of cancer. Several studies have shown that IGFBP-3 can induce the apoptosis of cancer cells via IGF-dependent and IGF-independent mechanisms. In our study, we have constructed recombinant vaccinia viruses (VACV) expressing IGFBP-3 under the control of the early H5 and synthetic early/late (E/L) promoter to investigate the potential effect on cancer growth in our cervical cancer model. We have shown that the expression of IGFBP-3 alone had no effect on tumor growth. On the other hand, the co-expression of IGFBP-3 enhanced the anti-cancer effect of immunization with the fusion protein SigE7LAMP, which gave rise to the anti-cancer immunity directed against HPV16 induced tumors. We have shown that the double-recombinant P13-SigE7LAMP-H5-IGFBP-3 can enhance the protective immune responses against MK16/ABC induced tumors. Furthermore, we have show that both double-recombinant viruses P13-SigE7LAMP-H5- IGFBP-3 and P13-SigE7LAMP-E/L-IGFBP-3 can increase the anti-cancer effect of SigE7LAMP expression in the therapy of TC-1 induced tumors. Key words: IGFBP-3, IGF, VACV, HPV16, E7 oncoprotein,...
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The role of dendritic cells in various pathological states
Sochorová, Klára ; Bartůňková, Jiřina (advisor) ; Tučková, Ludmila (referee) ; Stříž, Ilja (referee)
Dendritic cells (DCs) represent one of the most important components of the immune system. DCs are the most effective antigen presenting cells with a unique ability to stimulate naive T cells. They ensure the crosstalk between innate and adaptive immunity. They participate in anti-infectious and anti-tumor immune reaction as well as in the induction of tolerance. It is clear, that the defect in DC can be fatal for the organism. In our work we studied the biology of DCs and the disturbances of DCs function in pathological states. We analyzed DCs in patients with Bruton's tyrosin kinase deficiency, we compared the effect of vitamin D analogs, calcitriol and paricalcitol, on DCs and we set up the protocol of DC generation for the immunotherapy of ovarian cancer. In the study concerning btk deficiency and dendritic cell function we found profound impairment of IL-6 and TNF production in response to the stimulation by Toll-like receptor ligand 8. In the second part of our work we compared the effect of calcitriol and paricalcitol on DCs. Both drugs inhibited DCs maturation and decreased their ability to induce proliferation of antigen specific T cells. In the third part of our work we set up the protocol for the DCs, which are able to induce tumor specific immune responses. We optimized the form of tumor antigen...
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Immuno-biological Aspects of Head and Neck Squamous Cell Carcinoma
Bouček, Jan ; Říhová, Blanka (advisor) ; Fučíková, Terezie (referee) ; Šlapák, Ivo (referee)
The process of tumorigenesis is conditioned by change or the series of changes at a gene level. The development of cancer is largely pre-ordained by this change, but very important role is played by other factors. In case of solid tumors it is mainly a tumor microenvironment, where the tumor cells are in contact with stromal cells, especially fibroblasts, and immune cells. Tumor microenvironment can also critically modify the nature and intensity of anti- tumor immune response. Squamous cell carcinomas of the head and neck are the sixth most common cancer, which affect each year more than half a million patients worldwide. Despite advances and improvements in all treatment modalities, achieved therapeutic results even in Western countries are not satisfactory and remain at approximately the same values for several decades. At prezent, the 5 years survival rate, regardless of the location and stage of disease, is approximately only 40%. In the prezented work the immunological and biological aspects of squamous cell carcinoma of the head and neck are discussed. It summarizes the recent findings on the molecular basis of the behavior of tumor cells and the influence and significance of regulation of the immune system for the clinical course of disease and the modern therapeutic approaches.
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Evaluation of REE at patients with advanced bronchogenic carcinoma.
Kurucová, Kristina ; Hronek, Miloslav (advisor) ; Hrnčiarik, Michal (referee)
10 Abstract For patients with lung cancer are characterized phenomena such as cancer cachexia and increased resting energy expenditure. This increased resting energy expenditure leads to weight loss. This study was focused on patients with advanced non-small cell lung cancer (stage III and IV) undergoing chemotherapy. Resting energy expenditure was measured at three intervals by using indirect calorimetry in 10 patients (7 men, 3 women) with NSCLC undergoing chemotherapy (mean age 64,3 years ± 7,79 years) at a Department of Centre for Research and Development. Resting energy expenditure was measured before chemotherapy, during and after chemotherapy. We observed increased resting energy expenditure in these patients both before chemotherapy alone, as well as throughout chemotherapy. During chemotherapy there was decrease in REE. The average value of REE in the first test (% of predicted of HB) was 116,6 % ± 15,95 %, in the second measurement was mean value 113,9 % ± 14,73 % and for the third examination we noticed that the average value 106,5 % ± 12,66 %. We can confirm that resting energy expenditure in patients with NSCLC is increased during chemotherapy slowly decreased. Keywords: non-small cell lung cancer, resting energy expenditure, indirect calorimetry, Harris-Benedict equation
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