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Role of Pregnancy-associated Proteins and other Biomarkers in Diagnostics and Pediction of Prognosis of Renal Cell Carcinoma
Čechová, Marcela ; Babjuk, Marek (advisor) ; Broďák, Miloš (referee) ; Hartmann, Igor (referee)
Role of Pregnancy-associated Proteins and other Biomarkers in Diagnostics and Prediction of Prognosis of Renal Cell Carcinoma Abstract The work describes the role of pregnancy-associated proteins, pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF), in relation to renal cell carcinoma (RCC) and their possible use as a biomarkers of this tumour. The theoretical part of the thesis summarizes the essential knowledge of RCC focused on prognostic factors of this malignancy and provides a comprehensive overview of potential biomarkers. In the experimental part serum concentrations of PAPP-A and PlGF in patients operated for clear cell RCC were evaluated and their potential value in diagnostics and prediction of prognosis of subjects with this most frequent histological subtype of RCC was assessed. Furthermore, the thesis evaluates the relation of selected single nucleotide polymorphisms of PAPP-A gene [C/G SNP (rs13290387) a Cys327Cys SNP (rs12375498)] to the most common histological subtypes of RCC (clear cell, papillary I and II type, chromophobe) and oncocytoma. Based on our results, PAPP-A does not seem to be a suitable marker for diagnosis or evaluation of prognosis in patients with ccRCC, however, PlGF appears to be a potential diagnostic and prognostic marker of this disease....
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Non-invasive diagnosis of urothelial carcinoma of the urinary bladder by evaluation of cell-free DNA and microRNA in urine
Brisuda, Antonín ; Babjuk, Marek (advisor) ; Hora, Milan (referee) ; Broďák, Miloš (referee)
Bladder cancer represents the most common malignancy of the uropoetic tract. Its incidence has been stable in the last couple of years in the Czech Republic, worldwide rises though. A ratio of incidence and mortality is considerable in bladder cancer since it is highest out of all genitourinary malignancies. An early diagnosis and adequate treatment is therefor determinig for its prognosis. There are several commercialy available urine tests, none of them is recommended as a standard diagnostic tool in any indication though. Urine cytology, as a complement of invasive cystoscopy, remains the only widely used method with all its limitations. Cell-free nucleic acids in urine (urine supernatant) belong amongs potential tumour biomarkers. Cell-free urinary DNA (ucfDNA) is excreted by cells undergoing necrosis or apoptosis although it can also originate from living cells. Their level in urine or serum can thus indicate a presence of malignancy. Micro RNA (miRNA) are short non-coding sequences of RNA produced outside of nucleus. They bind to complementary sequences of mRNA thus affecting its translation and protein formation. As such they play an important role in cell division and cancerogenesis. In our study, we correlated levels of ucfDNA in controls and patients with urothelial carcinoma of different...
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CA IX protein expression in urogenital tumors, mainly in renal clear cell carcinoma and urotelial carcinoma of lower urinary tract
Hyršl, Lubomír ; Babjuk, Marek (advisor) ; Pacík, Dalibor (referee) ; Hora, Milan (referee)
Except testicular tumors and prostate carcinoma, there is lack of tumor markers in urogenital tumors. Carbonic anhydrase IX protein (CA IX) is a cell membrane protein, which can be ectopically expressed in various human tumors. It is often expressed as a response of tumor cells to hypoxia, which escalates invasivity of the tumor. In consequence, CA IX was proposed as a marker of poor prognosis. Its presence was proved by immunohistochemistry in renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of urinary tract. We study CA IX as a possible tumor marker. Presence of CA IX protein in tumor tissue was examined by imunohistochemistry, in serum and urine CA IX concentrations by immunoprecipitation of CA IX followed by Western blotting in combination with enhanced chemiluminiscence or ELISA. From our results we proved positive concentrations of soluble CA IX (s-CA IX) in 74,3% serum and in 63,3% urine samples in RCC group. In TCC group s-CA IX was positive in 69,6 % urine samples. Serum concentrations were all negative in this group. There was rapid decrease of s-CA IX concentration in serum after surgical removal of tumor with half-time 1- 2 days. s-CA IX is not detectable in blood and urine in healthy volunteers. In these days s-CA IX is not suitable marker of RCC and TCC. Nevertheless,...
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není uveden
Soukup, Viktor ; Babjuk, Marek (advisor) ; Mareš, Jaroslav (referee) ; Novák, Jaroslav (referee)
Immunohistochemical examination of microvascular density can be an additional prognostic factor in patients with superficial urinary bladder carcinoma, nevertheless, more extensive studies need to be carried out. Maximal microvascular density correlated with a recurrence free interval and in a case of bigger group of patients could be statistically significant. The statistical correlation between MVD and a nuclear p53 accumulation is that significant that we assume the p53 importance in the angiogenesis regulation of superficial urinary bladder carcinoma. The p53 positivity in non-tumor mucosa of urinary bladder in patients with superficial bladder cancer correlates with higher risk of tumor recurrence. According to our results the reason of urinary bladder carcinoma multifocality is genetic instability present in the whole urothelium at the time of tumor diagnosis. The PAX5 gene expression is a frequent finding in superficial transitional cell carcinoma of the bladder. From the prognostic point of view, high levels of PAX5 expression seem to be connected with higher recurrence and progression rates. The extent of lamina propria invasion seems to be a clinically relevant prognostic factor for progression of T1 bladder transitional cell carcinoma. Finding T1b tumor is connected with the risk of understaging....
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Non-invasive diagnosis of urothelial carcinoma of the urinary bladder by evaluation of cell-free DNA and microRNA in urine
Brisuda, Antonín ; Babjuk, Marek (advisor) ; Hora, Milan (referee) ; Broďák, Miloš (referee)
Bladder cancer represents the most common malignancy of the uropoetic tract. Its incidence has been stable in the last couple of years in the Czech Republic, worldwide rises though. A ratio of incidence and mortality is considerable in bladder cancer since it is highest out of all genitourinary malignancies. An early diagnosis and adequate treatment is therefor determinig for its prognosis. There are several commercialy available urine tests, none of them is recommended as a standard diagnostic tool in any indication though. Urine cytology, as a complement of invasive cystoscopy, remains the only widely used method with all its limitations. Cell-free nucleic acids in urine (urine supernatant) belong amongs potential tumour biomarkers. Cell-free urinary DNA (ucfDNA) is excreted by cells undergoing necrosis or apoptosis although it can also originate from living cells. Their level in urine or serum can thus indicate a presence of malignancy. Micro RNA (miRNA) are short non-coding sequences of RNA produced outside of nucleus. They bind to complementary sequences of mRNA thus affecting its translation and protein formation. As such they play an important role in cell division and cancerogenesis. In our study, we correlated levels of ucfDNA in controls and patients with urothelial carcinoma of different...
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Molecular mechanism of renal cell carcinogenesis
Chocholatý, Matúš ; Babjuk, Marek (advisor) ; Soukup, Viktor (referee) ; Eret, Viktor (referee)
The receptor for advanced glycation end products (RAGE), soluble RAGE (sRAGE) and its ligands are involved in the pathogenesis of cancer. Glyoxalase I (GLO1) is an enzyme which detoxifies advanced glycation end product (AGE) precursors. Four polymorphisms of RAGE (rs1800625 RAGE -429T/C, rs1800624 -374T/A, rs3134940 2184A/G, rs2070600 557G/A (G82S), and GLO1 rs4746 419A/C(E111A)) were determined by PCR-RFLP in 214 patients with ccRCC. A group of 154 healthy subjects was used as control. We found significant differences in the allelic and genotype frequencies of GLO1 E111A (419A/C) SNP between patients and controls-higher frequency of the C allele in ccRCC-58.6 vs. 44.5 % in controls, OR (95 % CI) 1.77 (1.32-2.38), p=0.0002 (corrected p=0.001); OR (95 % CI) CC vs. AA 2.76 (1.5-4.80), p=0.0004 (corrected p= 0.002); and AC+CC vs. AA 2.03 (1.23-3.30), p=0.0034 (corrected p=0.017). The values of sRAGE in a subgroup of 132 patients were evaluated before and three weeks, three and six months after surgery and in cancer relapse. According to relapse of the cancer, the patients were divided into two groups. The postoperative elevation of sRAGE was seen in group of ccRCC without relapse. Stable postoperative sRAGE were in group with relapse. We have not detected the difference between sRAGE in ccRCC group...
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Activity of the cathepsin B in patient with the bladder cancer
Dušek, Pavel ; Babjuk, Marek (advisor) ; Soukup, Viktor (referee) ; Broďák, Miloš (referee)
Bladder cancer is the most common malignant neoplasm of the urogenital tract. Of non- invasive diagnostic methods in clinical practice normally only is used cytology to its limits. While there are several commercially available tests that have the character of a tumor marker. None of them, however, has not yet been recommended for the standard diagnosis or monitoring of patients with bladder cancer. Cathepsin B is a thiol - dependent protease found in normal circumstances in the lysosomes of mammalian cells. Cathepsin B are lysosomes involved in the degradation of proteins and has various functions in maintaining cell metabolism in normal conditions. The incidence of cathepsin B or its proteins and their high activity is described in a number of neoplastic diseases. About its importance for urological tumors has so far been only very few reports. Activity of the cathepsin B in patients with invasive bladder cancer were examined by determining its expression in tumor tissue and determining the concentrations of cathepsin B and pro-cathepsin B in their serum urine. Our results confirm that the diagnostic efficiency of the pro-cathepsin B urine urine is high. All so far published studies are focused on the investigation of biologically active proteins. Pro- cathepsin B is the biologically inactive...
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CA IX protein expression in urogenital tumors, mainly in renal clear cell carcinoma and urotelial carcinoma of lower urinary tract
Hyršl, Lubomír ; Babjuk, Marek (advisor) ; Pacík, Dalibor (referee) ; Hora, Milan (referee)
Except testicular tumors and prostate carcinoma, there is lack of tumor markers in urogenital tumors. Carbonic anhydrase IX protein (CA IX) is a cell membrane protein, which can be ectopically expressed in various human tumors. It is often expressed as a response of tumor cells to hypoxia, which escalates invasivity of the tumor. In consequence, CA IX was proposed as a marker of poor prognosis. Its presence was proved by immunohistochemistry in renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of urinary tract. We study CA IX as a possible tumor marker. Presence of CA IX protein in tumor tissue was examined by imunohistochemistry, in serum and urine CA IX concentrations by immunoprecipitation of CA IX followed by Western blotting in combination with enhanced chemiluminiscence or ELISA. From our results we proved positive concentrations of soluble CA IX (s-CA IX) in 74,3% serum and in 63,3% urine samples in RCC group. In TCC group s-CA IX was positive in 69,6 % urine samples. Serum concentrations were all negative in this group. There was rapid decrease of s-CA IX concentration in serum after surgical removal of tumor with half-time 1- 2 days. s-CA IX is not detectable in blood and urine in healthy volunteers. In these days s-CA IX is not suitable marker of RCC and TCC. Nevertheless,...
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není uveden
Soukup, Viktor ; Babjuk, Marek (advisor) ; Mareš, Jaroslav (referee) ; Novák, Jaroslav (referee)
Immunohistochemical examination of microvascular density can be an additional prognostic factor in patients with superficial urinary bladder carcinoma, nevertheless, more extensive studies need to be carried out. Maximal microvascular density correlated with a recurrence free interval and in a case of bigger group of patients could be statistically significant. The statistical correlation between MVD and a nuclear p53 accumulation is that significant that we assume the p53 importance in the angiogenesis regulation of superficial urinary bladder carcinoma. The p53 positivity in non-tumor mucosa of urinary bladder in patients with superficial bladder cancer correlates with higher risk of tumor recurrence. According to our results the reason of urinary bladder carcinoma multifocality is genetic instability present in the whole urothelium at the time of tumor diagnosis. The PAX5 gene expression is a frequent finding in superficial transitional cell carcinoma of the bladder. From the prognostic point of view, high levels of PAX5 expression seem to be connected with higher recurrence and progression rates. The extent of lamina propria invasion seems to be a clinically relevant prognostic factor for progression of T1 bladder transitional cell carcinoma. Finding T1b tumor is connected with the risk of understaging....
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