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Does the assesment of tumor markers in the context of the last negative conclusions still have any impact in ovarian cancer?
Svoboda, Tomáš ; Fínek, Jindřich (advisor) ; Skalický, Tomáš (referee) ; Hes, Ondřej (referee) ; Vyzula, Rostislav (referee)
Does the assessment of tumor markers in the context of the last negative conclusions still have any impact in ovarian cancer? Svoboda T.: Dept. Of Oncology and Radiotherapy, Univ.Hospital, Plzen, Czech Republic Summary: The incidence of ovarian cancer is very high in Europe and there is still a lot of encertainaity about the best screening method today. The regular use of ultrasound investigation and CA125 testing is not established as a screening, so the greatest number of patients diagnosed with this tumor has a locally advanced disease. Their prognosis is unfavourable even with the treatment by chemotherapy. We describe the role of main factors associated with the primary tumor (staging, grading, histological type) and it's treatment (surgery type and the influence of residual tumor, type and regimen of chemotherapy and inclusion of radiation therapy in the primary treatment) for disease-free and overall survival. We also confirmed that tumor markers (CA125 incl.) used in screening, during treatment measuring response to chemotherapy and for folow-up as an early predictor of disease recurrence have low specificity and sensitivity to be used today. They have role of a prognostic factor - at least some of them - unfortunately with no impact on survival even when palliative chemotherapy can start...
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Molecular biological detection of viral and bacterial pathogens and their relationship
Kašpírková, Jana ; Hes, Ondřej (advisor) ; Daum, Ondřej (referee) ; Boudová, Ludmila (referee) ; Putzová, Martina (referee)
1 We report a case of an eccrine syringofibroadenoma (ESFA) associated with well- differentiated squamous cell carcinoma. The patient was an 85-year-old man, who had a 2.5x2.5-cm, brown-colored ulcerated nodule, with a fragile, flesh-colored bleeding surface located beyond the metacarpophalangeal joint of the second finger of his left hand. Histopathologically, there were areas of a well-differentiated squamous cell carcinoma, alternating with the typical area of ESFA characterized by anastomosing cords, strands, and columns of epithelial cells extending from the crusted epidermis into a thickened, edematous, myxoid vascular-rich dermis. Immunohistochemically, the areas with dysplastic epithelium were positive for p16, whereas the benign ESFA parts tested negative. Human papillomavirus was detected in the lesional tissue by polymerase chain reaction, and the subsequent sequencing analysis demonstrated that the virus was close to human papillomavirus type 107. 2 The authors report a case of basaloid carcinoma involving the anus and rectum of a 57-year- old woman. Microscopically, the tumor showed unusual morphologic features strongly resembling a spiradenocylindroma because it consisted, in most parts, of basaloid cell nodules arranged in a jigsaw-puzzle fashion containing or surrounded by eosinophilic basal...
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Molecular genetic profiling of urogenital tumors
Martínek, Petr ; Hes, Ondřej (advisor) ; Šíma, Radek (referee) ; Daniš, Dušan (referee) ; Halbhuber, Zbyněk (referee)
The Ph.D. thesis is a collection of eleven commented articles on the topic of molecular-genetic profiling of urogenital tract tumors published in impact factor journals. In the introduction the origin and development of classification units is described including a brief overview of recent genetic profiles of selected types of renal carcinomas. Reviewed are major signaling pathways exploited in targeted therapy as well as the function of the corresponding drugs. Directions in which the research of new biomarkers is aimed are mentioned and the introduction ends with a short list of molecular genetic methods used in classification of renal carcinomas. In the results section are summarized the most important morphological, immunohistochemical, and molecular genetic findings of the studied sets of renal carcinomas. The data are compared with the present characteristics of known entities and hypotheses of possible new entities or relations between them are inferred. In the conclusions the suitability and limitations of the used molecular genetic methods are discussed in the context of the difficulties of the material analyzed and the designs of the studies.
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Expression of CD44 molecules in urothelial bladder cancer
Kuncová, Jitka ; Mandys, Václav (advisor) ; Smetana, Karel (referee) ; Hes, Ondřej (referee) ; Záťura, František (referee)
The main aim of presented work was to contribute to clarify the significance of changes in expression of adhesion molecules and CD44 in the malignant behavior of urothelial carcinomas of the urinary bladder. The individual stages to meet this goal were: 2.1 Detailed determination of expression of CD44s and CD44v6 protein in urothelial carcinomas of the urinary bladder in relation to the degree of tumor differentiation. 2.2 Determine the relationship of CD44 protein expression changes depending on the characteristics histomorphologic urothelial carcinoma of the urinary bladder, and other indicators of biological behavior of tumor (proliferative activity, p53 expression). 2.3 Evaluation of expression of CD44s and CD44v6 protein in two phenotypically distinct cell lines, urothelial carcinomas (HT1197 and 5637) and determine relationships CD44 expression on morphological and growth characteristics of tumor cells of these lines.
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Receptors involved in regulations of inflammatory reactions in renal diseases
Eis, Václav ; Mandys, Václav (advisor) ; Hes, Ondřej (referee) ; Zemanová, Zdeňka (referee)
Eis, V., Luckow, B., Vielhauer, V., Sireke, J., Linde, Y., Segerer, S., Perez de Lema, G., Cohen, C. D., Kretzler, M., Mack, M., Horuk, R., Murphy, P. M., Gao, J.-L., Hudkins, K. L., Alpers, C. E., Gröne, H.-J., Schlöndorff, D., Anders, H.-J.: Chemokine receptor CCR1 but not CCR5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction. J Am Soc Nephrol, 15, 2004; 2: 337-347. We examined the role of chemokine receptor CCR1 and CCR5 in renal inflammatory infiltrate and subsequent interstitial fibrosis. Unilateral ureteral obstruction model in mice deficient for CCR1 or CCR5 was used for experiments. Analysis of UUO kidneys from CCR1-deficient mice or BX471 treated mice revealed a reduction of interstitial macrophages and lymphocytes compared with wild type controls. In contrast, renal leukocytes and fibrosis were unaffected in CCR5-deficient mice with UUO. Interstitial fibroblasts, renal TGF-β1 mRNA expression, interstitial volume and collagen I depositions were significantly reduced in CCR1-deficient mice. Lack of CCR5 does not affect renal fibrosis after UUO. Thus, CCR1 but not CCR5 is required for leukocyte recruitment and fibrosis after UUO in mice. Anders, H.-J., Belemezova, E., Eis, V., Segerer, S., Vielhauer, V., Perez de Lema, G., Kretzler, M., Cohen, C. D.,...
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Uncommon tumors of urogenital tract, their biological behaviour, morphology and cytogenetics
Michalová, Květoslava ; Hes, Ondřej (advisor) ; Dundr, Pavel (referee) ; Křen, Leoš (referee)
Current doctoral thesis is dealing with biological behavior, morphology and cytogenetical features of rare urogenital tumors with a particular emphasis on renal tumors. Dr. Kvetoslava Michalova (birth name Peckova) was focused on this topic during her postgradual study at Charles University in Prague, Medical Faculty in Pilsen, in years 2014-2017. In her publication activity, the author focused on rare tumors of urogenital tract. The 20 publications published over a span of three years are presented in a form of a commentary. Seven of them are first-author papers and these are briefly introduced below. The first paper entitled "Renal cell carcinoma with leiomyomatous stroma- further immunohistochemical and molecular genetic characteristics of unusual entity" dealt with the relationship between renal cell carcinoma (RCC) with leiomyomatous stroma (LS) and clear cell RCC with reactive LS. It led to the conclusion, that only genetic analysis of VHL gene mutation, VHL hypermatylation and chromosome 3p loss of heterozygosity can be used as a distinguishing tool. The "real" RCC with LS lack the above described genetic abnormalities which is in contrary to the clear cell RCC, which is characterized by them. The distinction between these two entities is of clinical importance, as the "real" RCC with LS...
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Clinicaly-pathological and moleculary-genetical characteristics of tumors of urogenital tract
Branžovský, Jindřich ; Hes, Ondřej (advisor) ; Daniš, Dušan (referee) ; Mandys, Václav (referee)
Tumors of urogenital tract are a highly heterogenous group of lesions. In last 30 years, there were several classifications, which couldn't fully describe all neoplasias, especially those arising in kidneys, because many newly discovered tumorous entities still emerge. The most active institution concentrating on tumors of urogenital tract is International Society of Urological Pathology (ISUP). As well as is diagnostics complicated, therapy of these tumors is also complicated in the same way. In some exchanging patterns main terapeutical procedures consist of surgical intervention, chemotherapy and radiotherapy. Biological targeted therapy is a treatment, that is very popular in these days. There has been discovered only slice from the whole problematics of tumoral genetics, so that meens lots of work to be done. This kind of resaech, as well as precise categorisation, is possible only at those places, that are capable of collecting realy large sum of tumors and pseudotumors, including leasions rare or new and yet not fully described. Powered by TCPDF (www.tcpdf.org)
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Hypertensive organ injury on the basic of 5/6 nephrectomy in REN2 transgenic rats
Kujal, Petr ; Vernerová, Zdeňka (advisor) ; Hes, Ondřej (referee) ; Ryšavá, Romana (referee)
Hypertension is a major determinant of rate of progression of CKD. Treatment of systemic hypertension is now generally accepted as the most important clinical strategy to slow the progression of CKD to ESRD. Renin-angiotensin (RAS) and endothelin (ET) systems are important contributors to the pathogenesis of hypertension. The interaction between the RAS and ET systems also plays a crucial role in the development of hypertension- associated end-organ damage. Antihypertensive drugs that block the renin-angiotensin system (RAS) are now believed to provide class- specific renoprotective actions beyond their blood pressure lowering effects. Our first study was performed to compare the organ-protective effects of a RAS-dependent and a RAS-independent antihypertensive therapy in heterozygous (mRen-2)27 transgenic rats (TGR) after 5/6 renal ablation (5/6 NX). Normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats after 5/6 NX served as controls. RAS-dependent and -independent antihypertensive therapies induced equal reductions of BP and almost identical cardio- and renoprotective effects on the progression of CKD after 5/6 NX, in both HanSD and TGR. These findings suggest that the cardio- and reno-protection, at least in rats after 5/6 NX, is mainly mediated through BP- dependent mechanisms....
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Implementation of Immunohistochemical and Molecular-Genetic Methods in Differential Diagnosis of Urogenital and Gynecologic Tract Lesions
Ondič, Ondrej ; Hes, Ondřej (advisor) ; Mandys, Václav (referee) ; Vernerová, Zdeňka (referee)
This thesis focuses on gynecopathology. It consists of a collection of seven papers published in pathology journals with impact factor. Introduction section contains selection of examples showing scientific application of molecular genetic methods. Further on the aims of individual research projects are described. The first project comprises histomophologic study of skin endometriosis addressing "mullerian" differentiation. A case report of a rare tumor namely borderline papillary serous tumor of the fimbriated end of the fallopian tube follows with molecular genetic analysis of KRAS, BRAF and p53 gene mutation status. Prospective longitudinal study on high grade squamous dysplasia (HSIL) of the cervix in HPV vaccinated women, so called DAV (dysplasia after vaccination), aims to elucidate pathogenesis of this phenomenon. Two other studies focus on incidence of fumarate hydratase deficient leiomyomas of the uterus and hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC). The aim of those studies is to improve our diagnostic capability and increase detection rate of the patients with HLRCC syndrome. Finally a new subtype of HSIL namely bizarre cell dysplasia is described in two separate studies. Conclusion remarks contemplate the role of molecular genetics in surgical pathology.
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Tumors of Urogenital Tract, Molecular Genetic Characteristics and Impact on Biological Behavior
Pivovarčíková, Kristýna ; Hes, Ondřej (advisor) ; Mandys, Václav (referee) ; Vernerová, Zdeňka (referee)
The Ph.D. thesis is a collection of seven commented articles on the topic of molecular-genetic of urogenital tumors. The spectrum of urogenital lesions is very wide, there is lots of new insights in field of urogenital pathology. Therefore, presented Ph.D. thesis is focused only on small part of urogenital neoplasms - renal cell carcinomas characterized by papillary growing pattern. The introduction presents different entities with papillary morphology, there are specified basic morphological, immunohistochemical and molecular-genetic characteristic of these lesions, their differential diagnosis is commented. In the results, there are presented recently published studies dealing with newly described entities of renal neoplasias, heterogenity of molecular genetic studies in individual tumorous groups is established, prognostic significance is commented, typical pitfalls are introduced. In the conclusions, the limitations of the use molecular-genetic methods are discussed and clinical outcome and significance is evaluated.
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