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EN
The aim of this study was to use a two-marker assay for the detection of breast cancer cells circulating in patients' blood. We have applied a PCR-based methodology to follow up the possibility of the development of metastatic disease in stage I and II patients who had undergone curative surgery. Since the number of circulating cancer cells in peripheral blood is very low, the technique for their detection needs to be not only highly sensitive, but also very specific. The reverse transcriptase-polymerase chain reaction (RT-PCR) technique may improve the sensitivity of breast cancer cell detection up to only a few cells per one million. The principle of the RT-PCR assay is to amplify a messenger RNA characteristic for breast epithelial cells in a blood sample. Since we do not expect such cells to be circulating in peripheral blood of healthy subjects, detection of the characteristic mRNA should indicate the presence of circulating breast cancer cells. We analyzed the usefulness of three mRNA markers: cytokeratin 19 (CK19), mammaglobin (hMAM) and β subunit of human chorionic gonadotropin (β-hCG) for this test. Blood samples (112) were obtained from 55 patients, in stages I and II, with or without metastasis to regional lymph nodes (N0 or N1). We found that a two-marker assay increases the sensitivity of detection of breast cancer cells in comparison with a single-marker one. Combination of two tumor-specific mRNA markers, hMAM/CK19 or β-hCG/CK19, allowed the detection of circulating breast cancer cells in 65% of N1 patients and 38% of N0 patients. By comparison, the combination hMAM/β-hCG allowed the detection of circulating breast cancer cells in the blood of 68% of N1 patients and 46% of N0 patients. Addition of the third marker did not significantly increase the detection sensitivity.
EN
Introduction. Over the last two decades, progress of science in the fields of immunology and molecular biology has brought understanding, at cellular level, of different pathophysiological processes involved in CRS. Nevertheless, the pathomechanisms of CRS remains unclear. SWI/SNF is a human ATP-dependent chromatin remodeling complex which plays an important role in several distinct cellular processes. SWI/SNF complex enables glucocorticoid receptor (GR) to function correctly and plays a role in regulation of inflammation. It has been hypothesized that SWI/SNF complex contributes to the pathogenesis of CRS. Aim. Assessment of the protein expression level of the SWI/ SNF complex subunits (BAF155, BRM and BRG1) in the group of patients with CRS. Materials. The study population consisted of 30 subjects, aged 19-81 (12 women and 18 men), including 10 patients with CRS without polyps, 10 patients with CRS and polyps, and 10 subjects without CRS constituting the control group. Results. Results of the observation revealed lower expression of the SWI\SNF complex in both CRS groups in comparison to the control group. Conclusions. SWI/SNF complex may play an important role in pathogenesis of CRS, probably through the influence on steroid hormone signaling and GR function. Further analysis of this issue is needed.
PL
Wprowadzenie. Rozwój nauki w zakresie immunologii i biologii molekularnej, zwłaszcza w ciągu ostatnich dwudziestu lat, pozwolił zrozumieć różne procesy patofizjologiczne zachodzące na poziomie komórkowym, zaangażowane w przewlekłe zapalenie zatok przynosowych (PZZP). Jednak niektóre patomechanizmy PZZP nadal pozostają nieznane. SWF/SNF jest kompleksem remodelującym chromatynę zależnym od ATP i odgrywa ważną rolę w różnych procesach komórkowych. SWI/SNF umożliwia prawidłowe funkcjonowanie receptora dla glikokortykosteroidów (GR) i reguluje stan zapalny. Przypuszczalnie ma on związek z procesem zapalnym w PZZP. Cel pracy. Ocena poziomu ekspresji białka podjednostek kompleksu SWI/SNF (BAF155, BRM i BRG1) u pacjentów z PZZP. Materiał. Badaniami objęto 30 osób w wieku od 19 do 81 lat (12 kobiet i 18 mężczyzn), w tym 10 pacjentów z PZZP bez polipów, 10 pacjentów z PZZP z polipami oraz 10 osób bez PZZP stanowiących grupę kontrolną. Wyniki. Wyniki obserwacji wykazały mniejszą ekspresję białek kompleksu SWI/SNF w obu grupach z PZZP w porównaniu do grupy kontrolnej. Wnioski. Kompleks SWI/SNF może odgrywać istotną rolę w patogenezie PZZP, prawdopodobnie poprzez wpływ na hormony steroidowe oraz funkcjonowanie receptora dla glikokortykosteroidów. Konieczna jest dalsza analiza tego zagadnienia.
EN
GIST is the most common mesenchymal tumour of gastrointestinal tract arising from mutation of KIT or PDGFRA gene. Surgery is the primary method of treatment, however a targeted therapy with imatinib is necessary due to recurrence. The aim of the study was to evaluate efficacy of the targeted chemotherapy in advanced gastrointestinal stromal tumours with non-exon 11 KIT mutations. Material and methods. Data from 279 patients with advanced GIST treated with imatinib between 2001 and 2011 were analysed in the study. Exon 11 KIT mutation was found in 192 patients (68.7%), non-exon 11 KIT mutation was found in 87 patients (31.3%): this group included lack of mutation - wild-type, exon 9 KIT mutations, exon 18 PDGFRA D842V mutations, non-D842V PDGFRA mutations as well as non-exon 9 and 11 KIT mutations. Analysis of progression-free survival and overall survival were done for the entire group of patients and for patients with particular mutations, and then effects on progression-free survival and overall survival of such factors as sex, age, imatinib dose were evaluated. Results. Occurrence of non-exon 11 KIT mutation increases the risk of disease progression by 20% in comparison to the presence of exon 11 KIT mutation, however it does not increase the risk of patient’s death. Percentage of 5-year progression-free survivals is the greatest in the case of PDGFRA mutation other than D842V mutation. Percentage of 5-year survivals in case of the presence of D842V PDGFRA mutation is more than twice worse than in the case of the other mutations. Lesion location in the gastrointestinal tract affected the risk of death, with the greatest percentage of 5-year survival for lesions located in the stomach. Such factors as sex, age at diagnosis (<50, ≥50 years) and imatinib dose did not affect the risk of disease progression and the risk of patient’s death. Conclusions. The ratio of overall survival of patients with advanced GIST with a mutation other than exon 11 KIT mutation treated with imatinib is similar to the ratio of overall survival of patients with GIST with exon 11 KIT mutation. An exception is the group of patients with GIST in whom the presence of D842V PDGFRA mutation was found. In general, longer survival has been found in patients with GIST located in the stomach in comparison to the small intestine or other less frequent locations. Percentage of 5-year progression-free survivals is the greatest in the case of PDGFRA mutation other than D842V mutation.
EN
The aim of this study was to evaluate the usefulness of quantitative real-time PCR (RQ-PCR) for the monitoring of molecular remission in follicular lymphoma (FL) patients during long-term follow-up. RQ-PCR by the use of TaqMan® detection system is a sensitive tool to monitor minimal residual disease (MRD) in FL through amplification of the t(14;18) fusion gene during and post-therapy. In most cases the breakpoint region occurs within the major breakpoint region (MBR). Among 75 patients diagnosed with FL, cells harboring the fusion gene BCL2/JH were found in peripheral blood of 31 patients (41%). We further monitored 30 of these patients in a period varying from 6 months to 5 years by RQ-PCR. In our study the level indicating the possibility of the presence of MRD was established at more than five t(14;18)-positive cells in the background of 83000 normal cells. The results of this work also confirmed that the presence of MRD detected by RQ-PCR is an indication for careful observation of patients because of a higher risk of disease recurrence.
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