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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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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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Systemic inflammatory and immune response in the treatment of tumor diseases
Holečková, Petra ; Melichar, Bohuslav (advisor) ; Macháček, Jindřich (referee) ; Plzák, Jan (referee)
Systémová a zánětlivá imunitní odpověď při léčbě nádorových onemocnění Imunitní a zánětlivá odpověď je organizmem rozvíjena při každém vnitřním či vnějším inzultu, proto hraje významnou úlohu také při vzniku, růstu a terapii karcinomů. Neméně důležitým mechanismem je oxidační stres. Snížená hladina vitamínu E a A koreluje se zvýšenou hladinou markerů systémového zánětu u pokročilých karcinomů a je špatným prognostickým faktorem. Neopterin je produkován z guanosin - trifosfátu aktivovanými makrofágy v reakci katalyzované GTP - cyklohydrolázou I a je jedním z biomarkerů imunitní odpovědi a reprezentuje molekulu asociovanou s antioxidační rovnováhou. Jeho vysoká koncentrace je asociována se špatnou prognózou maligního onemocnění Karcinomy ORL oblasti jsou relativně časté nádory s vysokou mortalitou. V jejich léčbě jsou uplatňovány multimodální přístupy. Tato intenzivní léčba indukuje řadu specifických akutních i pozdních nežádoucích účinků, které zhoršují kvalitu života nejen v průběhu léčby, ale i po ní. Poznatky o neopterinu, retinolu a - tokoferolu u pacientů s karcinomem ORL oblasti jsou velmi omezené. U nemocných s karcinomy ORL oblasti byl měřen neopterin v moči, retinol a - tokoferol v séru pomocí HPLC. Vysoká hladina neopterinu v moči a nízká hladina retinolu v séru predikovala špatnou...
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Laboratory parameters in the detection of the effect of anticancer therapy on immune system
Králíčková, Pavlína ; Melichar, Bohuslav (advisor) ; Tesařová, Petra (referee) ; Litzman, Jiří (referee)
Laboratory parameters in the detection of the effect of anticancer therapy on immune system Summary We can consider the immune response to cancer cells as the last barrier in carcinogenesis. Chemotherapeutics interfere directly or indirectly with tumour microenvironment. Our work was divided into two parts. The aim of our study was to describe the distribution of lymphocyte subsets in peripheral blood and urinary neopterin in breast cancer patients in relatation to the treatment in the part one, and elucidate the correlation between CD14+CD16+ monocytes, urinary neopterin and risk factors of atherosclerosis in the part two. We show that the changes of lymphocyte subpopulations are present even at the time of cancer diagnosis. The treatment could positively affect the anticancer response. The changes of these lymphocytes subsets during therapy in patients with metastatic stage of disease are less expressed. The restoration of the immune system is a long-term process. The systemic inflammatory response connected with tumour presence could contribute to the accented atherosclerosis, possible long-term complication in cancer patients.
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Risk factors for atherosclerosis in patients with Breast cancer
Kalábová, Hana ; Melichar, Bohuslav (advisor) ; Kubecová, Martina (referee) ; Tesařová, Petra (referee)
2. Summary Atherosclerosis and cancer are two of the most frequent causes of death in the developed world (Ng et al. 2006). There are a lot of similar risk factors both for atherosclerosis and for cancer (for example age, smoking, high intake of lipids, minimal physical activity leading to obesity and others). Atherosclerosis and cancer activate the immune system (Wachter et al. 1989) and the investigation of ischemic syndrome (often caused by atherosclerosis) contributed to finding some common molecular trails in the development of both of these diseases in last years (Pehrsson et al. 2005). Thanks to the progress in oncology treatment, patients with cancer survive longer, however, it is also very probable that a complex cancer therapy can lead to complications of atherosclerosis. The goal of this study was to clarify the influence of breast cancer itself and oncology treatment on atherosclerosis and its complications.
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Detection of minimal residual disease in patients with early breast cancer
Janků, Filip ; Matouš, Bohuslav (advisor) ; Brdička, Radim (referee) ; Melichar, Bohuslav (referee)
Breast cancer is one of the most serious health problems in our society. In the Czech Republic there are nearly 6000 women newly diagnosed annually. Despite the increasing incidence the mortality is leveling off or even decreasing in many countries (152,153). It is probably attributed to earlier diagnosis and the introduction of screening mammograms in many developed countries (154), and new findings in molecular biology of tumors. Several molecular factors are already routinely used in routine clinical practice as prognostic (estrogen and progesterone receptors, HER-2/neu, p53, Ki-67, vascular endothelial growth factor-VEGF), and predictive factors (estrogen and progesterone receptors, HER-2/neu) or therapeutic targets of anticancer treatment (estrogen and progesterone receptors, EGFR, HER- 2/neu, HER3, HER4, VEGF, mTOR) (7,45,155-157). The detection of minimal residual disease in early breast cancer is another attempt to implement modern diagnostic technologies in order to improve treatment outcomes. The aim of the study was to investigate diagnosis and prognostic implications of minimal residual disease in axillary lymph nodes, and bone marrow of patients with early breast cancer. The most promising material was bone marrow. From the clinical point of view it is necessary to validate both...
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