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Pathology of adnex
BARANCOVÁ, Iveta
The term adnex comes from the latin word nexus or connection and i tis used in gynecology and dermatology. Gynecological adnexa involves the internal genitals of woman without uterus, so it involves the fallopian tubes and ovaries. In every woman´s life, there can be conditions when the woman feels abdominal pain. These abdominal pain can´t be serious, however if the pain persists, it needs to be examinated their origin. During diagnostics, it is also important to keep in mind that the woman is prone to various diseases associated with gynecological adnexa. This bachleor thesis deals with pathological conditions od gynecological adnexa, therefore inflammation of the fallopian tubes and ovaries, ovarian cysts, adnexal endometriosis and benign but also malignant neoplasms located in the fallopian tubes and ovaries. Because every woman is at risk of an ectopic pregnancy when she is of childbearin age, this type of pregnancy is considered as pathological, so it is included in this bachleor thesis as well. Forty samples of gynecological adnexa are processed for this thesis. A selected part of the adnex sample is documented in this thesis. Samples are processed in all sections of the histological laboratory. After that histological preparations are made and the diagnosis is made too. Histological preparations are stained with basic histological staining Hematoxylin-eosin, but also with special methods Hematoxylin-van Gieson and Goldner´s trichrome. The thesis also contains a statistical evaluation of the incidence of gynecological adnexa for the period from 2015-2019, which were diagnosed at the pathological department. Female sterilization is included in this evaluation too, because its number has increased over the period. The sterilization included in the evaluation was always performed with the patient´s consent and at her own reques, for example it is performed during the planned caesarean section.
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Derivation and characterization of tumor cell lines labeled with fluorescent proteins
Majerová, Miriam ; Šmahel, Michal (advisor) ; Drbal, Karel (referee)
The effective treatment of cancer is hindered by the mechanisms of tumor cells allowing them to escape from immunosurveillance. One such mechanism is the downregulation of MHC I expression by tumor cells. As a result, CD8+ T lymphocytes are not able to eliminate tumor cells. These cells are often characterized by different expression of MHC I, which leads to the heterogeneity of the tumor environment. This thesis describes a production of a model of MHC I heterogeneity in tumors. Expression plasmids carrying genes for FP were created. Tumor cell lines TC-1, TC-1/A9 and TC-1/dB2m with different expression of MHC I molecules were successfully labeled with these plasmids. When monitoring stability of FP expression by these cell lines, a decrease was observed both in vitro and in vivo. The assumption that the cytokine environment of the tumor induces FP expression could not be confirmed because of unstable FP expression. In a tumor from a mixture of TC-1+TC-1/dB2m cell lines, it was possible to distinguish between these two lines based on the expression of β2m. In a mixture of TC- 1/A9+TC-1/dB2m lines, that could not be done due to the heterogeneity of TC-1/A9 MHC I expression. The use of combined immunotherapy showed the greatest impact on immune cell infiltration in tumors from a mixture of TC-1+...
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High grade serous ovarian carcinoma: molecular background and platinum-based chemotherapy challenges
Ivančinová, Jana ; Heneberg, Petr (advisor) ; Brábek, Jan (referee)
Ovarian carcinoma (O.C.) represent a group of various disease entities derived from ovaries. The most common malignant gynaecological cancer is high-grade serous ovarian carcinoma (HGSOC). HGSOC is associated with a high mortality rate due to its aggressive behaviour and insufficient early-stage detection. The survival rate has not been significantly improved since 1970s. The most effective treatment of HGSOC patients is by cytoreductive surgery (for early stages I/II) and followed by platinum-based chemotherapy (HGSOC presented in advanced stage III/IV) combined with taxane or potentially with PARP inhibitors (for BRCA1/2 mutation carriers). Multiple factors affect the patient's outcome and prognosis. Chemoresistance, molecular mutational patterns, stage at presentation of HGSOC are one of the clinical challenges contributing to common relapses even though patients often initially respond well to the HGSOC chemotherapy. This thesis overviews the fundamental biology of HGSOC, the major obstacles in clinical management and its improvements by implementing of multitherapy approaches. Key words: CA-125; platinum−based chemotherapy treatment; homologous recombination deficiency; ovarian carcinoma; resistance; Tp53; mortality; survival rate
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Leukemic stem cells
Vobořil, Matouš ; Stöckbauer, Petr (advisor) ; Šídová, Monika (referee)
The biology of stem cells came to the foreground not only due to scientific but also due to clinical interest and it is one of the most developing fields of current biomedical research. The idea, that all tumor cells contain population of cells like stem cells, leads to the "cancer stem cells hypothesis". It says, that each tumor cell contains small population of cells capable to initiate and maintain the tumor growth. Tumors of the hematopoietic tissue were the first, where cancer or leukemic stem cells were isolated. Therefore, leukemic stem cells are so far the best understood cancer stem cells. However, despite the huge advances in the biology of leukemic stem cells, there are many properties still unknown. This thesis initially presents basic knowledges in the stem cell biology, including their origin and identification. Later it focuses on the stem cell hypothesis and describes of the main properties of stem cells in solid tumors. The main part of this thesis also shows in details the origin and properties of the leukemic stem cells and decribes some new directions in the targeted therapy of hematological malignancies.
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Case report of therapeutic care patient after brain tumor surgery in the temporal lobe
Soukup, Petr ; Křížková, Štěpánka (advisor) ; Kozáková, Alena (referee)
Title: Case report of therapeutic care patient after brain tumor surgery in the temporal lobe Object of paper: The primary aim of this work is to describe the subject of CNS - tumors lokalized in the brain, specifically in the temporal lobe and subsequently a case study of a patient with this diagnosis, which was established during a hospital university-internship. Abstract: The general part deals with the theoretical information about the nervous system and brain tumors. Where as the specific part shows a case report of pateint after a brain tumor surgery in the temporal lobe. The materialis and the fundation of this bachelor dissertation were gathered at the neurological in-patient ward in regional hospital Kladno. Key words: Tumor, physiotherapy (physical therapy), central nervous system, temopral lobe (lobus temporalis)
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The expression of miRNA in HPV-associated and HPV-independent head and neck tumors
Vojtěchová, Zuzana ; Tachezy, Ruth (advisor) ; Hejnar, Jiří (referee) ; Slabý, Ondřej (referee)
Head and neck cancers represent a group of tumors with two different etiologies. The first type is associated with the viral HPV infection, the second one is virus-independent and it is associated with smoking and alcohol consumption as two main risk factors. Numerous studies show that HPV-positive tumors are more frequent in younger patients, as well as that the prognosis and overall survival of these patients is remarkably better. Therefore, the modification of the treatment is considered. For this, however, specific, sensitive and clinically relevant biomarkers for accurate identification of tumor etiology is needed. Suitable candidates for such biomarkers are miRNAs, small non-coding regulatory molecules stable in archived samples, that have been shown as differentially expressed in human cancers and the expression pattern seems specific for tumors of different origin. The submitted thesis focuses on miRNA profiling in HPV-positive and HPV-negative tonsillar tumors and cervical carcinomas with the aim to find out the differences between regulation of important carcinogenetic pathways of tumors of viral and non-viral etiology. Our data have shown very large heterogeneity of the miRNA expression profiles of these tumors. Despite the well characterized and uniform samples collection, we have found...
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Role of STAT3 signalling in oncogenesis and cancer therapy
Machalová, Veronika ; Hodný, Zdeněk (advisor) ; Brábek, Jan (referee)
STAT3 (Signal Transducer and Activator of Transcription 3) is considered to be one of the possible targets of cancer treatment. The ability of STAT3 constitutive activation to form tumors is a foundation of such theories. Additionally, constitutively activated STAT3 is present in many types of cancer with high occurrence, such as breast and prostate carcinoma. This protein is required in normal body cells as well. STAT3 is a transcription factor targeting many genes that are essential for the cell. STAT3 is activated by phosphorylation of its tyrosine residue and homodimerization. Proteins transcribed with help of STAT3 function in cell cycle progression, cell growth, replication, negative regulation of apoptosis, and other roles, typical for cancer. Moreover, STAT3 is modulating mitochondrial function and maintaining ROS production in mitochondria, but in form of transcriptionally inactive monomers. The purpose of this Thesis is to review known data about STAT3 in oncogenesis and by that, to show STAT3 has great potential to become the target of cancer treatment. This Thesis contains a short overview of known STAT3 inhibitors as well. Key words: Signal Transducer and Activator of Transcription 3 (STAT3), JAK/STAT3 pathway, constitutive activation, cancer, tumor, inhibitor, mitochondria, apoptosis
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Methylation of the regulatory sequences of integrated and extrachromosomal form of HPV 16 in tonsillar tumors
Pokrývková, Barbora ; Tachezy, Ruth (advisor) ; Hubáček, Petr (referee)
Human papillomavirus is connected with induction of cervical carcinoma as well as for some other anogenital carcinomas and subset of carcinomas of head and neck. Presence of viral E6 and E7 oncoproteins may induce cell transformation, higher load of oncoproteins is caused by the regulatory E2 protein inactivation. Aims of recent study are mechanisms of E2 protein inactivation. One option is integration of viral DNA into the host genome, which is located into the E2 gene region. Some carcinomas, where virus with extrachromosomal form was presented, were found. It appears that epigenetic changes can play the role in the development of this type of tumors, especially DNA methylation or mutation in the regulatory region of the virus. The methylation degree analysis on samples of tonsillar carcinomas with extrachromosomal and integrated form of the virus was conduced, as well as viral load of both groups was compared and the expression of E6 and E7 gene was confirmed. The results of methylation analysis showed increased methylation of the virus with integrated DNA. Mutations in the E2 protein binding sites are not revealed. The expression of the viral oncogenes were confirmed in all tumors regardless of the form of the viral genome. The mechanism of tumors induction, especially for virus with...
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Extracellular microRNAs in hematological malignancies and their use for diagnosis and treatment monitoring
Šulcová, Dominika ; Pospíšil, Vít (advisor) ; Čermák, Vladimír (referee)
MicroRNAs are short non-coding RNAs that negatively regulate gene expression at post-transcriptional level by interfering with mRNA translation and stability. Recently, microRNAs were surprisingly found to be present in various body fluids including blood plasma and serum, cerebrospinal fluid, saliva, milk or urine. These extracellular microRNAs are resistant to RNases and stable in high temperature or pH. Extreme stability of extracellular microRNAs is caused by their association with protective protein complexes (mostly with Argonaute proteins). MicroRNAs are frequently deregulated in cancer and specific tumor- related microRNAs can be also detected in body fluids, indicating that extracellular microRNAs can be used as tumor specific markers. This Bachelor thesis reviews basic principles of microRNA function and biogenesis with focus on extracellular microRNAs and their role in intercellular communication, and it highlights the role of extracellular microRNAs in hematological malignancies and their possible use in diagnosis and treatment.
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Anti-tumor activity of mesenchymal stem cells
Džuganová, Barbora ; Krulová, Magdaléna (advisor) ; Indrová, Marie (referee)
Mesenchymal stem cells (MSCs) are multipotent cells with the ability to migrate to inflammation sites and to tumor sites. They are able to regenerate the damaged tissues and also easy to isolate and cultivate. Furthermore, they can inhibit tumor cells and modulate the immune response. They are non-toxic in the organism and genetic modification of them can enhance their antitumor effect. MSCs can also serve as a vehicle for delivery of the therapeutic agent to the tumor. These properties make them special for anti-tumor therapy. Under some conditions, MSCs can also stimulate the tumor growth. This work discusses conditions in which MSCs inhibit the growth of cancer cells, as it is not yet clear on which precise mechanisms this inhibition is based.
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