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Warsaw, Poland

Krawczyk P.,Medical University of Lublin | Nicos M.,Medical University of Lublin | Powrozek T.,Medical University of Lublin | Mlak R.,Medical University of Lublin | And 9 more authors.
Oncology Letters | Year: 2013

The HER2 (ErbB2/neu) protein is a member of the HER (ErbB) receptor family (EGFR, HER2, HER3 and HER4) that expresses tyrosine kinase activity in the intracellular domain. EGFR and HER2 overexpression is observed in numerous types of cancer, nevertheless, the susceptibility of patients with non-small cell lung cancer (NSCLC) to therapy with EGFR and HER2 tyrosine kinase inhibitors (TKIs) depends on mutations present in the respective coding genes (driver mutations). In the present study, PCR and amplified DNA fragment length analysis (FLA) were used along with the multi-temperature single-strand conformation polymorphism (MSSCP) technique in order to identify the 12 base pair insertion in exon 20 of the HER2 gene in 143 patients with NSCLC metastasis to the central nervous system. The prevalence of the HER2 gene mutation was correlated with mutations in the EGFR and BRAF genes. The insertion in exon 20 of the HER2 gene was observed in a single 77-year-old, non-smoking male, with poorly-differentiated adenocarcinoma of the lung (1.5% of adenocarcinoma patients). No other genetic abnormalities were identified in this patient. In the therapy of NSCLC patients with HER2 gene mutations, drugs that inhibit the EGFR and HER2 receptors, for example afatinib, may be effective. The identification of other driving mutations in NSCLC cells appears to be key to the appropriate qualification of molecular targeted therapies. Source

Nicos M.,Medical University of Lublin | Nicos M.,Medical University of Warsaw | Powrozek T.,Medical University of Lublin | Krawczyk P.,Medical University of Lublin | And 8 more authors.
Medical Oncology | Year: 2014

Discoidin death receptor 2 (DDR2) receptor belongs to a DDR family that shows a tyrosine kinase activity. The somatic mutations in DDR2 gene, reported in non-small cell lung cancer (NSCLC), are involved in up-regulation of cells' migration, proliferation and survival. A S768R substitution in DDR2 gene was commonly reported in squamous cell lung carcinoma. Clinical data of patients carrying the DDR2 gene mutation suggest that its presence can be independent of gender and age. The effectiveness of an oral dual-specific (Src and Abl) multikinase inhibitors-dasatinib-was observed in different cell lines and in some NSCLC patients with identified DDR2 mutation. In the present study, we have used three molecular methods (ASP-real-time PCR, ASP-DNA-FLA PCR and direct sequencing) to detect the DDR2 gene mutation in 143 patients with NSCLC metastases to the central nervous system (CNS). The prevalence of the DDR2 gene mutation was correlated with the occurrence of mutations in the EGFR, KRAS, HER2 and BRAF genes. We identified three patients (2.1 % of studied group) with DDR2 mutation. The mutation was observed in two patients with low differentiated squamous cell lung cancer and in one patient with adeno-squamous cell carcinoma (ADSCC). In ADSCC patients, DDR2 mutation coexisted with G12C substitution in KRAS gene. According to the current knowledge, examination of the presence of the DDR2 gene mutation in metastatic lesion is the first such report worldwide. The information, that these driver mutations are present in CNS metastases of NSCLC, could broaden therapeutic choices in such group of patients. © 2014 The Author(s). Source

Elpek K.,Medical University of Gdansk | Pajak B.,BioVectis Ltd. | Pajak B.,Mossakowski Medical Research Center | Siedlecki P.,Polish Academy of Sciences | And 6 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

Pandemic influenza A(H1N1)pdm09 virus is a global health threat and between 2009-2011 it became the predominant influenza virus subtype circulating in the world. The research describes the MSSCP (Multitemperature Single Strand Conformation Polymorphism) analysis of the hemagglutinin (HA) region encompassing major neutralizing epitope in pandemic influenza isolates from Taiwan. Several genetically distinct changes appeared in isolates obtained in 2010 and 2011. The majority of changes in HA protein did not result in significant modifications, however three modifications were localized in epitope E of H1 and one was part of the interface binding antibodies BH151 and HC45 possibly making the current vaccine less effective.-Taking into account the possibility of the emergence of influenza A with antibody evading potential, the MSSCP method provides an alternative approach for detection of minor variants which escape detection by conventional Sanger sequencing. © 2014 Landes Bioscience. Source

Lepek K.,Medical University of Gdansk | Pajak B.,BioVectis Ltd. | Pajak B.,Mossakowski Medical Research Center | Pajak B.,Warsaw University of Life Sciences | And 5 more authors.
BioMed Research International | Year: 2015

Monitoring and control of infections are key parts of surveillance systems and epidemiological risk prevention. In the case of influenza A viruses (IAVs), which show high variability, a wide range of hosts, and a potential of reassortment between different strains, it is essential to study not only people, but also animals living in the immediate surroundings. If understated, the animals might become a source of newly formed infectious strains with a pandemic potential. Special attention should be focused on pigs, because of the receptors specific for virus strains originating from different species, localized in their respiratory tract. Pigs are prone to mixed infections and may constitute a reservoir of potentially dangerous IAV strains resulting from genetic reassortment. It has been reported that a quadruple reassortant, A(H1N1)pdm09, can be easily transmitted from humans to pigs and serve as a donor of genetic segments for new strains capable of infecting humans. Therefore, it is highly desirable to develop a simple, cost-effective, and rapid method for evaluation of IAV genetic variability. We describe a method based on multitemperature single-strand conformational polymorphism (MSSCP), using a fragment of the hemagglutinin (HA) gene, for detection of coinfections and differentiation of genetic variants of the virus, difficult to identify by conventional diagnostic. © 2015 Krzysztof Lepek et al. Source

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