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Clinical use of neopterin, a laboratory biomarker of immune activation, in the assessment of prognosis, monitoring response to therapy and complications in cancer patients
Trivedi, Sachin Vipinchandra ; Melichar, Bohuslav (advisor) ; Dvořák, Josef (referee) ; Kocáková, Ilona (referee)
Clinical use of neopterin, a laboratory biomarker of immune activation, in prognosis, monitoring response to therapy and complications in cancer patients Introduction Neopterin is a biomarker of immune activation and is synthesized from GTP in a reaction catalyzed by enzyme GCH-1. Neopterin levels reflect the body's response to inflammatory conditions such as infections, injuries, chronic diseases, and cancer. Its levels also fluctuate with anticancer therapies that demonstrate immune activity. Remarkably neopterin has also been found to be a marker of poor prognosis in cancer. Aim To investigate clinical use of neopterin, a biomarker of immune response, in the assessment of prognosis, monitoring response to therapy, and complications in cancer patients. Methodology In a two-part study, serial urinary neopterin were measured in two different cohorts of patients who underwent anticancer therapy. In part one, samples from 45 patients with diagnosis of metastatic colorectal cancer who were being treated with chemotherapy + cetuximab were analyzed. In part two, samples from 10 patients with diagnosis of gynecological malignancy, mostly cervical cancer undergoing chemoradiotherapy were analyzed. Results In patients with metastatic colorectal carcinoma, higher neopterin levels were associated with poor prognosis....
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Quantification of procalcitonin in human serum by affinity surfaces and mass spectrometry
Dvořák, Josef ; Pompach, Petr (advisor) ; Kozlík, Petr (referee)
Sepsis is a worldwide health condition. It is caused by disproportionatly large immunity system response for patogene presence. Fast and accurate diagnosis of sepsis can make difference between life and death. For clinical diagnosis of sepsis is used serum protein procalcitonin (PCT) as biomarker. Procalcitonin concentration level in patient bloodstream increases up to thousand times in short time period. Severity of sepsis can be determined by correlation with its concentration in bloodstream. To determine PCT level in patient bloodstream a broad variety of specialized instrument is used. All methods have same principle of measurement - PCT-antibody interaction. Procalcitonin level is then quantified by calibration curve method. During these measurements non-specific protein-antibody interactions can occur and distort the quantification of PCT level. Mass spectrometry due to its properties comes into consideration as an alternative method, that can be used for PCT determination. Aim of this diploma thesis was in situ enrichment of PCT on surface modified affinity carriers with immobilized antibody against PCT. These carriers are compatible with matrix assisted laser desorption/ionization time of flight mass spectrometry. Mass spectrometry provides mass spectrum, where PCT and other signals...
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Quantification of procalcitonin in human serum by affinity surfaces and mass spectrometry
Dvořák, Josef ; Pompach, Petr (advisor) ; Kozlík, Petr (referee)
Sepsis is a worldwide health condition. It is caused by disproportionatly large immunity system response for patogene presence. Fast and accurate diagnosis of sepsis can make difference between life and death. For clinical diagnosis of sepsis is used serum protein procalcitonin (PCT) as biomarker. Procalcitonin concentration level in patient bloodstream increases up to thousand times in short time period. Severity of sepsis can be determined by correlation with its concentration in bloodstream. To determine PCT level in patient bloodstream a broad variety of specialized instrument is used. All methods have same principle of measurement - PCT-antibody interaction. Procalcitonin level is then quantified by calibration curve method. During these measurements non-specific protein-antibody interactions can occur and distort the quantification of PCT level. Mass spectrometry due to its properties comes into consideration as an alternative method, that can be used for PCT determination. Aim of this diploma thesis was in situ enrichment of PCT on surface modified affinity carriers with immobilized antibody against PCT. These carriers are compatible with matrix assisted laser desorption/ionization time of flight mass spectrometry. Mass spectrometry provides mass spectrum, where PCT and other signals...
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The inhibitors of tyrosine kinases and their effect on the expression of biotransformation enzymes
Dvořák, Josef ; Dračínská, Helena (advisor) ; Moserová, Michaela (referee)
Tumor diseases are one of the most common causes of death in the human population. One of the many possible causes of tumor growth is abnormal function of tyrosine kinases, which are involved in signal transfer and regulation of the most important cell processes. These processes include the control of cell growth, division and cell differentiation and apoptosis. For the therapy of tumor diseases caused by the abnormal function of tyrosine kinases, their specific inhibitors are developed. For the targeted treatment of thyroid tumors, the tyrosine kinases vandetanib and lenvatinib are newly used. In this bachelor thesis, the effect of vandetanib and lenvatinib on the gene expression of the cytochrome P450 family of 2 (CYP2A2, CYP2B1, CYP2C11, CYP2D1, CYP2E1) biotransformation enzymes has been investigated as they are involved in the biotransformation reactions of a large portion of the available drugs on the market. To examine the relative gene expression of CYP2, quantitative PCR of samples of cDNA, synthesized from isolated RNA from rat liver and kidney exposed to the above-mentioned tyrosine kinase inhibitors, was used. The results suggest, that vandetanib and lenvatinib do not have a significant effect on the gene expression of cytochrome P450 family 2 in rat liver and kidney tissue. KEY WORDS:...
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Porovnání ukazatelů jatečné hodnoty dvou hybridních kombinací jatečných prasat
DVOŘÁK, Josef
There were gaged indexes of 32 fattening cycles of hybrid Topigs and 31 fattening cycles of hybrid Danbred. Starting live weight of hybrid Topigs was 30.1 kg and hybrid Danbred 28.1 kg (P < 0.05). Final live weight of hybrid Topigs was 112.5 kg and hybrid Danbred 114 kg. Average daily gain of hybrid Topigs was 0.81 kg/pcs and hybrid Topigs was 0.9 kg/pcs (P < 0.05). Consumption of complete feed mixture per kilogram of gain of hybrid Topigs was 2.82 kg and hybrid Danbred 2.76 kg. The loss caused by death of pigs in the fattening period was 1.39% f hybrid Topigs was 3.87 % and hybrid Danbred (P < 0.05). There were looked carcass value of 2 374 pcs of hybrid Topigs and 2 468 pcs of hybrid Danbred. Average weight of carcass of hybrid Topigs was 88.1 kg with average part of muscles 57.5%. Average weight of carcass of hybrid Topigs was 91.4 kg (P < 0.05) with average part of muscles 59.1% (P < 0.05). As regards hybrid Topigs, there were classified 12,2% of carcasses in the quality class "S", 72% in the quality class "E" and 15,8% in the quality class "U". And of hybrid Danbred, there were classified 32.9 % of carcasses in the quality class "S", 61,9% in the quality class "E" and 5.2 % in the quality class "U". There were classified 78.5% of hybrid Topigs and 69.7% of hybrid Danbred in weight range 8099.9 kg.
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Clinical use of neopterin, a laboratory biomarker of immune activation, in the assessment of prognosis, monitoring response to therapy and complications in cancer patients
Trivedi, Sachin Vipinchandra ; Melichar, Bohuslav (advisor) ; Dvořák, Josef (referee) ; Kocáková, Ilona (referee)
Clinical use of neopterin, a laboratory biomarker of immune activation, in prognosis, monitoring response to therapy and complications in cancer patients Introduction Neopterin is a biomarker of immune activation and is synthesized from GTP in a reaction catalyzed by enzyme GCH-1. Neopterin levels reflect the body's response to inflammatory conditions such as infections, injuries, chronic diseases, and cancer. Its levels also fluctuate with anticancer therapies that demonstrate immune activity. Remarkably neopterin has also been found to be a marker of poor prognosis in cancer. Aim To investigate clinical use of neopterin, a biomarker of immune response, in the assessment of prognosis, monitoring response to therapy, and complications in cancer patients. Methodology In a two-part study, serial urinary neopterin were measured in two different cohorts of patients who underwent anticancer therapy. In part one, samples from 45 patients with diagnosis of metastatic colorectal cancer who were being treated with chemotherapy + cetuximab were analyzed. In part two, samples from 10 patients with diagnosis of gynecological malignancy, mostly cervical cancer undergoing chemoradiotherapy were analyzed. Results In patients with metastatic colorectal carcinoma, higher neopterin levels were associated with poor prognosis....
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The prognostic significance of change of the epidermal growth factor receptor expression in patients with rectal adenocarcinoma treated with neoadjuvant radiochemotherapy
Richter, Igor ; Dvořák, Josef (advisor) ; Kubecová, Martina (referee) ; Matula, Pavol (referee)
Aim of the study: The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Material and methods:50 patients with with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m2 in two daily oral administrations. Surgery was indicated 4-8 weeks from the chemoradiotherapy completion. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. Results:All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. 4 patients have had complete pathologic remission. 26 patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26,1 %). A statistically significantly shorter overall survival (p < 0.0001) and...
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Structure of self-small groups and modules
Dvořák, Josef ; Žemlička, Jan (advisor) ; Šaroch, Jan (referee)
Title: Structure of self-small groups and modules Author: Josef Dvořák Department: Department of Algebra Supervisor: Mgr. Žemlička Jan, Ph.D. Supervisor's e-mail address: zemlicka@karlin.mff.cuni.cz Abstract: The thesis sums up the basic properties of self-small groups. Furthermore it thoroughly builds the theory od quotient categories by Serre classes, with focus on quotient category modulo the class B of boun- ded groups, which, as demonstrated, is equivalent to the quasicategory, i.e. category of abelian groups with Hom-sets being Q⊗Z HomA (A, B). This approach is developed into the theory of generalized quasi-categories. The dualities between quasi-caterogories od torsion-free and quotient-divisible categories of finite rank, resp. between categories of finite-rank self-small groups are studied and they are emloyed to the partial solution of Fuchs' problem no. 34. Keywords: self-small group, quotient divisible group, quasicategory, quo- tient category 1
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