Martin Spacek

Charles University in Prague, Praha, Praha, Czech Republic

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Publications (11)18.59 Total impact

  • Folia Microbiologica 07/2012; 58(1). · 1.15 Impact Factor
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    ABSTRACT: The role of the TP53 gene's R72P polymorphism in non-Hodgkin lymphoma (NHL) has been analyzed in several studies but it has not been studied in Hodgkin lymphoma (HL). We have evaluated the role of R72P in 340 NHL and 298 HL patients. There was no difference in the R72P frequency between analyzed lymphoma cases and 749 controls. We found no association of R72P with the risk of NHL and HL development [OR(ArgPro/ProPro)=0.9 (95% CI 0.7-1.2) and 1.2 (95% CI 0.9-1.5), respectively] or with survival. Our results support the evidence that R72P is not a prognostic factor in Caucasian NHL patients, and they indicate its irrelevance for HL development or prognosis.
    Leukemia research 05/2011; 35(8):1117-9. · 2.36 Impact Factor
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    ABSTRACT: Heat-shock proteins (Hsps) are thought to play a role in the development of cancer and to modulate tumor response to cytotoxic therapy. In this study, Hsp27, Hsp60, Hsp90α, and HspBP1 gene expression was investigated in human leukemia cell lines as well as in leukemia cells derived from patients with the onset of the disease. Hsp70 membrane expression and expression of Hsp27, Hsp60, Hsp70, Hsp90α, and HspBP1 genes were also tested in samples from leukemia patients. Relative Hsps gene expression was examined in human leukemia cell lines and also in patients, using real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hsp70 cell surface expression was studied in patients with leukemia onset using flow cytometry. All tested cell lines showed significantly increased expression of Hsp60, Hsp90α, and HspBP1 genes compared with a cohort of healthy controls; additionally there was increased Hsp27 expression except for Jurkat and CCRF cells. Significantly higher gene expression of Hsp27, Hsp60, Hsp90α, and HspBP1 was observed in the peripheral blood of patients compared with bone marrow and healthy control samples, while Hsp70 expression was without any significant difference among cohorts. Hsp70 cell surface expression was found on defrosted and cultured leukemia cells but not on unprocessed biological samples from patients. Leukemia cells showed a heterogeneous pattern of Hsp gene expression among leukemia cell lines as well as in peripheral blood and bone marrow of patients.
    Tumor Biology 02/2011; 32(1):33-44. · 2.84 Impact Factor
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    ABSTRACT: Checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in Hodgkin lymphoma (HL) has not been studied so far. The most frequent CHEK2 alterations (including c.470T>C; p.I157T) cluster into the forkhead-associated (FHA) domain-coding region of the CHEK2 gene. We performed mutation analysis of the CHEK2 gene segment coding for FHA domain using denaturing high-performance liquid chromatography in 298 HL patients and analyzed the impact of characterized CHEK2 gene variants on the risk of HL development and progression-free survival (PFS). The overall frequency of CHEK2 alterations was significantly higher in HL patients (17/298; 5.7%) compared to the previously analyzed non-cancer controls (19/683; 2.8%; p= 0.04). Presence of any alteration within the analyzed region of the CHEK2 gene was associated with increased risk of HL development (OR = 2.11; 95% CI = 1.08 - 4.13; p= 0.04). The most frequent I157T mutation was found in 4.0% of HL patients and 2.5% of controls (p = 0.22), however, the frequency of 5 other alterations (excluding I157T) was significantly higher in HL cases and associated with increased risk of HL development (OR = 5.81; 95% CI = 1.12 - 30.12; p= 0.03). PFS in HL patients did not differ between CHEK2 mutation carriers and non-carriers. The predominant I157T mutation together with other alterations in its proximity represent moderate genetic predisposition factor increasing the risk of HL development.
    Neoplasma 01/2011; 58(5):392-5. · 1.64 Impact Factor
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    ABSTRACT: Epstein-Barr virus (EBV) is associated with approximately one-third of Hodgkin lymphoma (HL) cases. EBV-DNA is often present in the plasma and whole blood of EBV-associated HL patients. However, the significance of EBV-DNA monitoring is debated. In a cohort of 165 adult HL patients, EBV-DNA viral load was prospectively monitored both in the plasma and whole blood. Diagnostic tissue samples of all patients were histologically reviewed; in 72% nodular sclerosis was detected, 24% presented with mixed cellularity (MC), and 5% had other type of HL. Tissues from 150 patients were also analyzed for the presence of latent EBV infection using in situ hybridization for EBV-encoded RNA (EBER) and immunohistochemistry for latent membrane protein (LMP1). Using these methods, 29 (19%) patients were classified as EBV positive. Using real-time quantitative PCR, 22 (76%) of EBV-positive HL patients had detectable EBV-DNA in the plasma and 19 (66%) patients in whole blood prior to therapy. In the group of EBV-negative HL cases, three (2%) patients had detectable plasma EBV-DNA and 30 (25%) patients whole blood EBV-DNA before treatment. EBV-positive HL was significantly associated with EBV-DNA positivity both in the plasma and whole blood in pretreatment samples, increasing age and MC subtype. Serial analysis of plasma EBV-DNA showed that response to therapy was associated with decline in viral load. Moreover, significantly increased plasma EBV-DNA level recurred before disease relapse in one patient. Our results further suggest that the assessment of plasma EBV-DNA viral load might be of value for estimation of prognosis and follow-up of patients with EBV-positive HL.
    Apmis 01/2011; 119(1):10-6. · 1.92 Impact Factor
  • Lydie Fialová, Martin Spacek, Pavel Vychytil
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    ABSTRACT: This article presents a translation of the World Medical Association Statement on Conflict of Interest (2009) and Statement concerning the Relationship between Physicians and Commercial Enterprises (2009). The introduction illuminates the objectives of this recommendation in the context of healthcare in the Czech Republic.
    Casopís lékar̆ů c̆eských 01/2011; 150(10):554-7.
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    ABSTRACT: Membrane-bound heat shock protein 70 (HSP70) was found to be tumor-specific and was proposed as a target for immunotherapy. In the present study, we analyzed cell surface and relative gene expression of HSP70 in cell lines established from patients with different acute myeloid leukemia (AML) subtypes, together with the expression of natural killer (NK) cell activation/inhibitory ligands. Six AML cell lines were included in this study. The relative gene expression of HSP70 was analyzed using the real-time reverse-transcriptase polymerase chain reaction. Surface expression of HSP70 and NK cell ligands was analyzed using flow cytometry. All cell lines overexpressed HSP70; however, its mRNA levels were not elevated. The expression of NKG2D activation ligands was heterogeneous. Our study is the first to describe long-term stationary cell surface expression of HSP70 in different subtypes of AML. Combined with the results of the gene expression experiments these data provide more evidence to the idea of a self-limiting mechanism for HSP70 expression.
    Journal of Receptor and Signal Transduction Research 06/2010; 30(3):161-9. · 1.63 Impact Factor
  • Acta Haematologica 01/2010; 124(1):23-6. · 0.89 Impact Factor
  • Journal of Clinical Virology 09/2009; 46. · 3.47 Impact Factor
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    ABSTRACT: p53 is implemented in many processes controlling cell fate. Recently it has been reported that besides post-translational modifications and regulation of protein-protein interactions, the activity of p53 is also substantially controlled at transcriptional level. In 109 out of 127 (86%) patients with chronic lymphocytic leukemia (CLL) we have identified a novel p53 splicing variant, lacking the whole coding sequence of exon 6. This splicing p53 isoform ("delta ex6") is devoid of transactivational activity and is differentially expressed in CLL patients as compared to healthy controls. The overexpression of "delta ex6" p53 variant in CLL patients supports the recent evidence on dysregulation of p53 splicing pattern in malignancies.
    Leukemia Research 04/2008; 32(3):395-400. · 2.69 Impact Factor
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    ABSTRACT: B-cell chronic lymphocytic leukemia (B-CLL) represents a heterogeneous disease with highly variable prognosis. Clinical staging systems (Rai, Binet) fail to accurately predict the prognosis of individual patients, especially in early stages. Modern prognostic markers, mainly the mutational status of the variable regions of immunoglobulin heavy chains (IgVH) and genetic aberrations, allow more accurate risk stratification. Assessment of the expression of intracellular protein tyrosine kinase ZAP-70 represents not only a potential surrogate marker for the technically difficult and routinely unavailable assessment of the IgVH mutational status, but might also be an independent prognostic factor. Study of ZAP-70 function in B-cells has broadened our knowledge on the pathogenesis of B-CLL. Routine ZAP-70 assessment has been hindered so far mainly by the lack of harmonization and standardization of the available methods of detection.
    Vnitr̆ní lékar̆ství 01/2007; 52(12):1194-9.