Pavel Fabian

Masaryk Memorial Cancer Institute, Brünn, South Moravian, Czech Republic

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Publications (52)62.19 Total impact

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    ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer next to hepatocellular carcinoma (HCC). Despite the significant difference of the therapeutic strategy for both diseases, their histological appearance may be very similar. Thus the correct diagnosis is crucial for treatment choice but is often difficult to achieve. The aim of our study was to evaluate anterior gradient 3 (AGR3) as a new diagnostic marker helping to distinguish between ICC and HCC. AGR3 is a putative transmembrane protein implicated in breast, prostate and ovary tumorigenesis and belongs to the family of protein disulphide isomerases. Since there is little information on how AGR3 is expressed in normal and diseased tissues and what its exact function is, we analyzed its expression pattern in normal liver and tumor tissue of ICC and HCC. The immunohistochemical analysis in normal tissue revealed specific AGR3 expression in intrahepatic bile duct cholangiocytes which was not present in liver hepatocytes. Consequently we analyzed AGR3 expression in 74 representative samples of puncture biopsies, tissue excisions and resection specimens from which 48 samples were diagnosed as HCC and 26 as ICC. Our results showed AGR3 expression negative and weakly positive respectively in hepatocellular carcinomas compared to stronger AGR3 positivity in cholangiocellular carcinomas. AGR3 expression statistically significantly correlated to acid mucopolysaccharide expression and negatively correlated to glypican-3 expression. We conclude that according to receiver operating characteristics (ROC) analysis AGR3 expression is relatively specific for ICC and is potentially linked to mucosecretion, which may indicate potential implication in treatment resistance.
    Experimental and Molecular Pathology 04/2014; · 2.13 Impact Factor
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    ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer next to hepatocellular carcinoma (HCC). Despite the significant difference of the therapeutic strategy for both diseases, their histological appearance may be very similar. Thus the correct diagnosis is crucial for treatment choice but is often difficult to achieve. The aim of our study was to evaluate anterior gradient 3 (AGR3) as a new diagnostic marker helping to distinguish between ICC and HCC. AGR3 is a putative transmembrane protein implicated in breast, prostate and ovary tumorigenesis and belongs to the family of protein disulphide isomerases. Since there is little information on how AGR3 is expressed in normal and diseased tissues and what its exact function is, we analyzed its expression pattern in normal liver and tumor tissue of ICC and HCC. The immunohistochemical analysis in normal tissue revealed specific AGR3 expression in intrahepatic bile duct cholangiocytes which was not present in liver hepatocytes. Consequently we analyzed AGR3 expression in 74 representative samples of puncture biopsies, tissue excisions and resection specimens from which 48 samples were diagnosed as HCC and 26 as ICC. Our results showed AGR3 expression negative and weakly positive respectively in hepatocellular carcinomas compared to stronger AGR3 positivity in cholangiocellular carcinomas. AGR3 expression statistically significantly correlated to acid mucopolysaccharide expression and negatively correlated to glypican-3 expression. We conclude that according to receiver operating characteristics (ROC) analysis AGR3 expression is relatively specific for ICC and is potentially linked to mucosecretion, which may indicate potential implication in treatment resistance.
    Experimental and Molecular Pathology 01/2014; · 2.13 Impact Factor
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    ABSTRACT: Inoperable c kit negative gastrointestinal stromal tumor (GIST) is commonly considered to be highly resistant to systemic therapy. We present a case of a woman with an abdominal sarcomalike tumor dia-gnosed at the age of 26. The patient underwent several surgical procedures and courses of cytostatic therapy without any substantial effect. Later, the tumor was reclassified as c kit negative GIST harbouring the mutation in exon 12 of PDGFRA gene. Hence, the therapy with imatinib mesylate was initiated, resulting in partial remission of metastatic lesions and further stabilization of the disease for five yeas to date. We therefore consider imatinib mesylate an appropriate therapy for c kit negative GIST bearing PDGFRA mutations. Key words: gastrointestinal stromal tumors - c kit receptor - PDGF alpha receptor - imatinib mesylate.
    Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2014; 27(1):52-55.
  • P Fabian, R Nenutil
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    ABSTRACT: Biobanking is a well-organized, sophisticated system that consists in programmed storage of biological material and corresponding data that is accessible for scientific investigation. In this article, we briefly describe the principles of a tumour biobank; namely sample collection, storage and distribution. The key role of pathologists in the process of biobank sample selection is highlighted; it is an integral part of gross specimen handling as a diagnostic procedure. The harmonization of standard operating procedures is an important issue; the biological material stored in a biobank must be processed in a manner that allows compatibility with other biobanks. Material withdrawal must be accompanied by a Material Transfer Agreement to cover all technical and ethical/legal issues concerning the scientific utilization of the released material. Key words: biobanks - standards - translational research.
    Rozhledy v chirurgii: měsíčník Československé chirurgické společnosti 01/2014; 93(3):176-9.
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    ABSTRACT: Objectives. The aim of the study was to develop a clinical prediction model for assessing the probability of having invasive cancer in the definitive surgical resection specimen in patients with biopsy diagnosis of ductal carcinoma in situ (DCIS) of the breast, to facilitate decision making regarding axillary surgery. Methods. In 349 women with DCIS, predictors of invasion in the definitive resection specimen were identified. A model to predict the probability of invasion was developed and subsequently simplified to divide patients into two risk categories. The model's performance was validated on another patient population. Results. Multivariate logistic regression revealed four independent predictors of invasion: (i) suspicious (micro)invasion in the biopsy specimen; (ii) visibility of the lesion on ultrasonography; (iii) size of the lesion on mammography >30 mm; (iv) clinical palpability of the lesion. The actual frequency of invasion in the high-risk patient group in the test and validation population was 52.6% and 48.3%, respectively; in the low-risk group it was 16.8% and 7.1%, respectively. Conclusion. The model proved to have good performance. In patients with a low probability of invasion, an axillary procedure can be omitted without a substantial risk of additional surgery.
    BioMed Research International 01/2014; 2014:480840. · 2.71 Impact Factor
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    ABSTRACT: Background: The incidence of renal cell carcinoma in the Czech Republic is one of the highest in the world. Curative treatment is still possible only surgically, while in the palliative treatment, partial success was reached using targeted therapies. While prognostic factors and models are commonly used in clinical practice, unfortunately, predictive biomarkers have not been found. The aim of our study was to verify the validity of selected prognostic factors on a consecutive patient cohort from the Czech population. Patients and methods: The patient cohort consisted of 544 patients with RCC diagnosed and/or treated at our institute from 2003 to 2010. Individual clinical and histological prognostic factors and Heng prognostic model were validated. Results: Median time of follow-up for our cohort was 42 months (range 0.3-326 months), median age at diagnosis was 62 years, and almost 64% of patients were men. Distribution of clinical stages was as follows: 46.5% of I, II. 10.7%, III. 13.1%, IV. 20%. 26.4% of patients in stage I-III relapsed. We diagnosed mainly clear cell (84.6%) and papillary carcinoma (9.2%). Initially, 95.8% of patients underwent surgical treatment, systemic adjuvant and palliative treatment was applied in 3.7 and 37.7% of patients, respectively. Palliative targeted therapy was received by a total of 163 patients (30%). In first-line targeted therapy, the following median TTP was reached (in months): 10.8 for sunitinib, 6.3 for sorafenib and 5.2 months for immunotherapy. The most significant prognostic factors (p < 0.00001) were: stage of disease (HR = 9.61), size of the primary tumor (HR = 5.83), lymph nodes (HR = 8.26), presence of sarcomatoid tumor sections in the tumor (HR = 7.29), and tumor grade (HR = 4.0). Besides these, we also confirmed the prognostic importance of presence of eosinophilic granulations in the tumor (HR = 1.91, p = 0.02). When applying the Heng prognostic model, we achieved similar results for patients treated with targeted therapies. Conclusion: The obtained epidemiological and clinico-pathological data are consistent with previously published data. These prognostic factors can be used for a differentiated approach to patients with RCC, both for establishing follow-up plan for patients after surgery as well as indication for targeted therapies. Key words: renal carcinoma - immunotherapy - targeted therapy - sunitinib - sorafenib - prognosis.
    Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2013; 26(2):114-123.
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    ABSTRACT: Endocrine resistance is a significant problem in breast cancer treatment. Thus identification and validation of novel resistance determinants is important to improve treatment efficacy and patient outcome. In our work, AGR2 expression was determined by qRT-PCR in Tru-Cut needle biopsies from tamoxifen-treated postmenopausal breast cancer patients. Our results showed inversed association of AGR2 mRNA levels with primary treatment response (P = 0.0011) and progression-free survival (P = 0.0366) in 61 ER-positive breast carcinomas. As shown by our experimental and clinical evaluations, elevated AGR2 expression predicts decreased efficacy of tamoxifen treatment. From this perspective, AGR2 is a potential predictive biomarker enabling selection of an optimal algorithm for adjuvant hormonal therapy in postmenopausal ER-positive breast cancer patients.
    Disease markers 01/2013; 35(4):207-12. · 2.14 Impact Factor
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    ABSTRACT: Background:Malignant melanoma is considered to be highly resistant to chemotherapy, radiotherapy, hormonotherapy and standard immunotherapy (interleukin 2, interferon alpha). Radical surgery in the early stages of the disease is still the most efficient method. Since the development of immunotherapy and targeted therapy, the role of palliative chemotherapy for advanced disease may be changing. Case: A case report regarding 44-year-old woman with extensive tumor of the pectoral wall with contralateral axillary lymphadenopathy is presented. On the basis of imaging methods, histology and immunohistochemistry, the tumor was defined as a sarcoma. Due to PAX7-FKHR fusion gene positivity, rhabdomyosarcoma was the most probable classification. The patient was treated with radical chemotherapy including iphosphamide, vincristine, actinomycin D and doxorubicin with the effect of partial regression of the tumor. This enabled radical surgery of the chest wall tumor. Pathology proved 70% necrosis of the tumor. A contralateral axillary dissection was performed with a finding of two lymph nodes infiltrated with melanoma. The immunohistochemistry markers S100, HMB-45 and Melan A were positive. This resulted in a reclassification of the chest wall tumor to malignant melanoma. The following PET/CT scan was negative. A massive progression of the disease occurred after 5 months. B-RAF mutation leads to a plan of targeted therapy with vemurafenib. Conclusion: The case demonstrates the limits of the sensiti-vity and specificity of immunohistochemical markers of melanoma and the ability of this tumor to imitate various tumors including soft tissue sarcomas. A rare -PAX7-FKHR fusion gene positivity considered specific for rhabdomyosarcoma was found. An extraordinary response to radical chemotherapy with surgical resection led to an improvement of the quality of life and to a prolonged survival comparable with the effect of new targeted treatment for malignant melanoma. Key words: malignant melanoma - rhabdomyosarcoma - immunohistochemistry - cytogenetics - PAX7-FKHR - chemotherapy.
    Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2013; 26(1):42-6.
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    ABSTRACT: Standardized gynecological oncological therapeutical guidelines are based on ordinary predictive factors, such as depth of stromal invasion, histopathological type of tumor, lymphovascular space invasion, lymph node metastases. Unfortunately, the power of these prognostic factors is not able to determine the safety of this procedure in the relation to disease recurrence in a group of patients who are indicated for conservative operations. This is the appropriate area for new, especially biomolecular prognostic factors (proteins: p63, TAp63, p16, p21, p27, COX-2, genes: hTERC, MYCC). Moreover, comprehensive evaluation of cervical cancer prognostic factors and assessment of new biomarkers of cancer can ease prediction of risk of spread outside primary localization and determine probability of disease recurrence. This information can help to individualize surgical, radiotherapeutic and chemotherapeutic treatment. Key words: carcinoma of the cervix - prognostic factors - lymphovascular space invasion - lymph node metastases - tumor size - protein - expression.
    Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2013; 26(2):83-90.
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    ABSTRACT: BACKGROUND: Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients. METHODS: We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling. RESULTS: Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified. CONCLUSIONS: Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established.
    Radiation Oncology 11/2012; 7(1):195. · 2.11 Impact Factor
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    ABSTRACT: Trastuzumab is effective in about half of HER2-positive breast cancer patients. The PI3K/Akt signalling pathway plays an important role in the process of primary and secondary resistance to anti-HER2 targeted therapy. We evaluated the relationship between expression, activation and subcellular localization of selected Akt isoforms and response to trastuzumab-based anti-HER2 targeted therapy in patients with HER2-positive metastatic breast cancer. Seventy-four women with verified HER2-positive breast cancer were treated with trastuzumab for metastatic disease. Immunohistochemistry was used to evaluate Akt1, Akt2, pAkt Thr308 and pAkt Ser473 expression. For pAkt, cytoplasmic and nuclear fractions were assessed separately. Even though Akt isoforms were expressed in the majority of tumours, activated Akt (pAkt) was present in the cytoplasm only and not in the nucleus in >20% of tumours, and there was no pAkt at all in another 7-13% of tumours. Patients whose tumours showed strong Akt2 expression and had pAkt (pAkt-Thr308 and/or pAkt-Ser473) detectable in the cytoplasm as well as nucleus (n+c), exhibited improved time to progression (TTP) and overall survival from the initiation of trastuzumab therapy (OSt). Patients with tumours with strong Akt2 and pAkt Thr308 (n+c) had superior TTP (17.0 vs. 7.6 months, P=0.024; HR 0.52) and OSt (51.8 vs. 16.8 months, P=0.0009; HR 0.34) compared to other tumours. Similar results were found for strong Akt2 and pAkt Ser473 (n+c): TTP 13.1 vs. 7.2 months (P=0.085, HR 0.62) and OSt 50.8 vs. 17.0 months (P=0.009; HR 0.45). This study is the first to prove the significance of Akt kinase isoform, activity and compartmentalization for the prediction of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer.
    International Journal of Oncology 07/2012; · 2.66 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC) is characterized by its resistance to radiotherapy and/or chemotherapy. On the other hand, it is an immunogenic tumor - it is able to stimulate antitumor responses. A prognostic significance of HLA-G expression by neoplastic cells in RCC is not well characterized; significance HLA-E expression in RCC is not characterized at all. In our study, we evaluated the expression of HLA-G and HLA-E specific mRNA transcripts produced by neoplastic cells in 38 cases of RCC and in 10 samples of normal kidney parenchyma. The results were statistically correlated with various clinico-pathological parameters. We confirmed that HLA-G is downregulated in normal kidney tissue; if it is up-regulated in RCC, then it is connected to worse prognosis. On the other hand, HLA-E mRNA transcripts were present in both normal kidney tissue and RCC and their increasing concentrations counterintuitively carried better prognosis, more favorable pT stage and lower nuclear Fuhrmann's grade. Considering the fact that there is known aberrant activation of HLA-G and HLA-E expression by interferons, identification of HLA-G and HLA-E status could contribute to better selection of RCC patients who could possibly benefit from more tailored neoadjuvant biological/immunological therapy. Thus, these molecules could represent useful prognostic biomarkers in RCC, and the expression of both these molecules in RCC deserves further study. THE VIRTUAL: Slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7383071387016614.
    Diagnostic Pathology 05/2012; 7:58. · 2.41 Impact Factor
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    ABSTRACT: BACKGROUND: MicroRNAs (miRNAs) constitute a robust regulatory network with post-transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumor suppressors. DESIGN: We determined the expression profile of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoral tissues and identified 42 differentially expressed miRNAs. We chose miR-215, miR-375, miR-378, miR-422a and miR-135b for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro analyses. RESULTS: MiR-215, miR-375, miR-378 and miR-422a were significantly decreased, whereas miR-135b was increased in CRC tumor tissues. Levels of miR-215 and miR-422a correlated with clinical stage. MiR-135b was associated with higher preoperative serum levels of CEA and CA19-9. In vitro analyses showed that ectopic expression of miR-215 decreases viability and migration, increases apoptosis and promotes cell cycle arrest in DLD-1 and HCT-116 colon cancer cell lines. Similarly, over-expression of miR-375 and inhibition of miR-135b led to decreased viability. Finally, restoration of miR-378, miR-422a and miR-375 inhibited G1/S transition. CONCLUSIONS: These findings indicate that miR-378, miR-375, miR-422a and miR-215 play an important role in CRC as tumor suppressors, whereas miR-135b functions as an oncogene; both groups of miRNA contribute to CRC pathogenesis. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
    Journal of Cellular and Molecular Medicine 03/2012; · 4.75 Impact Factor
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    ABSTRACT: Breast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC) represents the major phenotype of basal-like molecular subtype of breast cancer, characterized by higher incidence in young women and a very poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs playing significant role in the pathogenesis of many cancers including breast cancer. Therefore, miRNAs are also potential prognostic and/or predictive biomarkers in triple-negative breast cancer patients. Thirty-nine TNBC patients with available formalin-fixed paraffin-embedded (FFPE) tissues were enrolled in the study. MiR-34a, miR-34b, and miR-34c were analyzed using qRT-PCR and correlated to clinico-pathological features of TNBC patients. Expression levels of miR-34b significantly correlate with disease free survival (DFS) (p = 0.0020, log-rank test) and overall survival (OS) (p = 0.0008, log-rank test) of TNBC patients. No other significant associations between miR-34a, miR-34b, and miR-34c with available clinical pathological data were observed. MiR-34b expression negatively correlates with disease free survival and overall survival in TNBC patients. Thus, miR-34b may present a new promising prognostic biomarker in TNBC patients, but independent validations are necessary.
    Diagnostic Pathology 03/2012; 7:31. · 2.41 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC) represents a heterogeneous group of breast cancers that do not express ER-α, PgR and Her-2 receptors. Generally, these tumors are aggressive and more common in younger women, in which an association of TNBC with mutations in the BRCA1 gene was documented. The aim of our study was to create a representative group of patients with TNBC, which could be analyzed and the data gathered to build basic epidemiological, molecular and clinical characteristics of Czech patients with TNBC. We performed basic clinical-pathologic correlations in a group of 335 patients diagnosed and/or treated for TNBC at the Masaryk Memorial Cancer Institute between 2004 and 2009. We also performed immunohistochemical examination of expression of cytokeratin 5/6, cytokeratin 14 and EGFR to identify the basal-like subset of TNBC. The median age of patients with TNBC was 56 years, range 25-88 years. A total of 9.25% of TNBC cases were diagnosed in patients under the age of 34, and another 15.22% of cases were in the age group of 35 to 44 years. 'Basal-like' carcinomas accounted for 75% of TNBC. We confirmed the aggressive nature of this disease: in the follow-up period we observed a relapse in 25% of patients: 55% of deaths due to disease progression occured within 2 years after diagnosis of the disease. Treatment strategies include chemotherapy, in most cases (88.4%). Chemotherapy was mostly based on regimens with anthracyclines or in combination with taxanes. The most important negative prognostic factors in relation to OS (disease specific OS) were: higher clinical stage (p < 0.0001), pN - positive status (p < 0.0001), high proliferative activity (as measured by Ki-67, cut-off 50%, HR = 0.4740, p = 0.0411) and positive expression of CK5/6 (HR = 0.4274, p = 0.0338). In relation to DFS, the negative prognostic significance was found for these factors: higher clinical stage (p < 0.0001), pN positive status (p < 0.0001), high proliferative activity (Ki-67, cut-off 50%, HR = 0.04993, p = 0.0240). DFS was longer in patients with a higher number of applied cycles of anthracycline-based chemotherapy (> 4 cycles, HR = 1.7273, p = 0.0467). TNBC is an aggressive form of breast cancer, which may occur in patients of all ages, but more frequently in younger patients. Only early detection of disease and intensive treatment gives a high chance of cure. Unfortunately, no reliable predictive factors have been identified so far. Better therapeutic results can be expected from targeted therapy.
    Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2012; 25(3):188-98.
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    ABSTRACT: Although the role of the non-classical human leukocyte antigen E (HLA-E) was originally thought to be limited to the development of a maternal tolerance to a semiallogeneic fetal graft, it is now known that HLA-E exerts multiple immunoregulatory functions. The significance of the presence of HLA-E in neoplastic cells and/or background microenvironment cells in classical Hodgkin lymphoma (cHL) is not well characterized. In our study, we evaluated the presence of HLA-E in both neoplastic and background cells in 40 cases of cHL. We found HLA-E in both neoplastic and background cells. There was a positive statistical correlation between the expression of HLA-E in neoplastic cells and the clinical stage of the disease, which indicates an immune-tolerogenic property of this multiple-purpose molecule. The presence of HLA-E in background cells seems to be prognostically neutral but its significance still needs to be determined. The mechanisms regulating the immunopathology of cHL neoplastic cells with respect to the presence of these molecule deserve further studies.
    Pathology - Research and Practice 12/2011; 208(1):45-9. · 1.21 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma in adults. There are specific alterations that appear repeatedly in DLBCL cases and play a role in lymphomagenesis or progression of the disease. Some aberrations were used as prognostic markers in the pre-rituximab era. Addition of rituximab to the classical anthracycline-based chemotherapy significantly increased the survival rate in DLBCL. Only few prognostic factors have been re-evaluated for patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). We performed complex analysis of the p53 tumor suppressor in collection of 75 DLBCL cases. Fifty-four patients were de novo cases, twenty-one cases developed into DLBCL by transformation from less aggressive disease. We determined functional status by analysis of separated alleles in yeast (FASAY) and analyzed the p53 mutations by cDNA sequencing. We assessed the level of the p53 protein by immunoblot analysis. We used FISH to analyze loss of the p53 and ATM (ataxia telangiectasia mutated) gene deletions. We detected 16 p53 mutations (21.3%) including the mutation activating non-sense-mediated RNA decay pathway. Deletion of the p53 allele was more common in cases with p53 mutation. Mutations and/or deletions of p53 had statistically significant negative impact on progression-free survival and tended to decrease also overall survival in 46 de novo DLBCL patients treated with R-CHOP. p53 aberrations are negative predictors for survival of DLBCL patients treated with R-CHOP.
    International Journal of Oncology 08/2011; 39(6):1413-20. · 2.66 Impact Factor
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    ABSTRACT: VOD Zhoubné onemocnění tlustého střeva (dg. C18), rektosig-moideálního spojení (C19) a konečníku (C20) je jednou z nej-častějších malignit v České republice. Nejčastější léčebnou modalitou u kolorektálního karcinomu je kurativní resekce ná-doru. Pacientům s karcinomem tlustého střeva klinického sta- Karlova v Praze, Lékafiská fakulta Hradec Králové, Ústav klinické biochemie a diagnostiky FN 3 P & R LAB a.s., Nov˘ Jiãín 4 CGB laboratofi a.s., Ostrava 5 Univerzila Palackého v Olomouci, Ústav molekulární a translaãní medicíny LF 6 Fakultní Thomayerova nemocnice s poliklinikou v Praze, Oddûlení patologie a molekulární medicíny 7 Bioptická laboratofi s.r.o., PlzeÀ 8 Univerzita Karlova v Praze, 1. lékafiská fakulta, Ústav patologie VFN 9 Univerzita Karlova v Praze, Lékafiská fakulta Hradec Králové, FingerlandÛv ústav patologie FN SOUHRN
    01/2011;
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    ABSTRACT: Targeted therapy has become an integral part of treatment procedures of malignant tumors. Colorectal carcinomas are frequently targeted with monoclonal anti-EGFR antibodies (cetuximab and panitumumab). Activating somatic mutations in codons 12 and 13 of the exon 2 of KRAS gene are considered negative predictive factors of response to anti-EGFR therapy in patients with metastatic colorectal cancer. In the Czech Republic, evaluation of mutational status of KRAS gene is performed in several referral laboratories. In 2009, these laboratories performed 2580 tests of the KRAS mutational status--out of these, 60.2% cases reported non-mutated, wild-type KRAS. In one of the referral laboratories, we demonstrate the logistics of KRAS testing procedure. Stratification of patients with metastatic colorectal tumors based on their KRAS mutational status has evolved to a standard procedure. Laboratories performing these methods shall therefore adhere to the recommendations of the professional and accredited societies.
    Casopís lékar̆ů c̆eských 01/2011; 150(6):321-6.
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    ABSTRACT: ABSTRACT: Correction: After the publication of this research article, Journal of Experimental & Clinical Cancer Research 2010, 29:90, the authors noticed an error with Figure one. Graph D which should have indicated miR-106b expression levels in renal parenchyma (RP) and renal cell carcinomas (RCC), was mistakenly displayed as a duplicate of Graph C. The corrected Figure one is provided here.
    Journal of Experimental & Clinical Cancer Research 08/2010; 29(1):105. · 3.07 Impact Factor

Publication Stats

510 Citations
62.19 Total Impact Points

Institutions

  • 2006–2014
    • Masaryk Memorial Cancer Institute
      Brünn, South Moravian, Czech Republic
  • 2007–2012
    • Masaryk University
      • Fakulta Lékařská
      Brno, South Moravian Region, Czech Republic
  • 2004
    • University Hospital Brno
      Brünn, South Moravian, Czech Republic
  • 2000
    • Palacký University of Olomouc
      Olmütz, Olomoucký, Czech Republic