Band 9, Heft 6

Head and neck squamous cell carcinoma (HNSCC) is the fifth most prevalent cancer worldwide. Apart from various known clinicopathogical factors, it is still a major concern as many genetic and epigenetic alterations bring about the possibility of this deadly disease. The aim of this review is to explore the possible role of DNA repair pathways and the polymorphic status of DNA repair genes (XPA, XPC, XPD, XRCC1 and XRCC3) in the onset of HNSCC, along with sequence variations in genes such as Glutathione S-transferases (GSTT1, M1 and P1) that are significantly associated with HNSCC risk. We also focus on the p53 gene mutation induced by various etiological agents and threat factors with its implications towards HNSCC, and emphasise the current therapeutic interventions in treating HNSCC.

Porodaedalea pini has been found to be a pathogen of Pinus banksiana (1 specimen) and Pinus sylvestris (39 specimens) in north-western Poland. This fungus was initially identified by its host preferences and morphological characters of sporophores and basidiospores. The ITS 1/2 rDNA region was sequenced and analysed using the neighbor-joining, maximum likelihood and maximum parsimony methods. All P. pini from Poland, P. pini neotype and other P. pini isolates from Europe grouped together forming a moderately supported monophyletic clade. The clade included two groups which did not correlate with geographic ranges. Nucleotide polymorphism of the Polish isolates of P. pini was small. This study provides evidence for the taxonomy of some isolates of the Porodaedalea Holarctic Group in North America: grouping with P. laricis or with P. gilbertsonii suggests that the isolates belong to these species. The absence of P. pini (in a form recognized in Europe) in North America is suggested. Sequencing of the ITS 1/2 rDNA region with the basidiomycete-specific primers (ITS1-F and ITS4-B) proved to be a suitable and sufficient method for differentiation of species within the genus Porodaedalea.

Influenza is a contagious disease of humans and animals caused by viruses belonging to the Orthomyxoviridae family. The influenza A virus genome consists of negative sense, single-stranded, segmented RNA. Influenza viruses are classified into subtypes based on two surface antigens known as hemagglutinin (H) and neuraminidase (N). The main problem with influenza A viruses infecting humans is drug resistance, which is caused by antigenic changes. A few antiviral drugs are available, but the most popular is the neuraminidase inhibitor — oseltamivir. The resistance against this drug has probably developed through antigenic drift by a point mutation in one amino acid at position 275 (H275Y). In order to prevent a possible influenza pandemic it is necessary to develop fast diagnostic tests. The aim of this project was to develop a new test for detection of influenza A virus and determination of oseltamivir resistance/sensitivity in humans. Detection and differentiation of oseltamivir resistance/sensitivity of influenza A virus was based on real-time PCR. This test contains two TaqMan probes, which work at different wavelengths. Application of techniques like multiplex real-time PCR has greatly enhanced the capability for surveillance and characterization of influenza viruses. After its potential validation, this test can be used for diagnosis before treatment.

Hydroxyapatite is the main inorganic component of bones and teeth. In order to improve mechanical properties and surgical handiness of bioceramics, a plasticizing agent e.g. polysaccharide can be added. Chitosan is a polysaccharide with biological properties that make it an ideal component of bioceramics-based composites for medical application as bone substitute. In this study, biocompatibility of two types of novel krill chitosan-based composites was evaluated. In vitro experiments were carried out using human foetal osteoblast cell line. Cytotoxicity, cell adhesion, and bone ALP activity tests were performed to assess biocompatibility of the composites. Osteoblast growth on composites was observed using confocal microscope. Our results demonstrated that fabricated novel composites are non-toxic, are favorable to cell adhesion and growth, and provoke increase in b-ALP activity with time, thus inducing osteoblast differentiation. Based on this data composites have promising clinical potential as a bone defect filler in regenerative medicine. It is worth emphasizing that our work resulted in fabrication of flexible and surgical handy, bone substitutes that possess absolute biocompatibility with structural and mechanical properties similar to trabecular bone.

Combined approaches to the treatment of acute radiation disease are preferred to single-agent therapies due to proven or anticipated better outcomes comprising increased therapeutic efficacy and decreased incidence of undesirable side effects. Our studies on post-exposure treatment of mice irradiated by sublethal or lethal doses of ionizing radiation included testing the effectiveness of meloxicam, a cyclooxygenase-2 inhibitor, and IB-MECA, an adenosine A3 receptor agonist. The efficacy of meloxicam and IB-MECA to positively influence the progress of the acute radiation disease has been tested in situations of their combined administration with granulocyte colony-stimulating factor (G-CSF) or with each other. The results of our studies revealed a significantly improved regeneration of hematopoietic cell populations ranging from the bone marrow progenitor cells to mature blood cells following combined treatments. Also, survival of mice exposed to lethal radiation doses was highest in the animals treated with a combination of the two drugs. It can be inferred from the results that if the drug combinations employed were used in humans, e.g. in the treatment of victims of radiation accidents, a better therapeutic outcome could be expected. Therefore, further studies directed at clinical applications of meloxicam and IB-MECA in radiation victims is recommended.

This study examines some of the biological activities of an evening primrose flavanol preparation (EPFP) against non-invasive human breast cancer cells (MCF-7). The results are compared with those obtained for highly invasive human breast cancer cells (MDAMB-231). The results show, for the first time, that EPFP reduces MCF-7 cell number, IC50 = 75 µM gallic acid equivalents/GAE for 72 h incubation, and reduces migration to 52% of the control value at 100 µM L−1 GAE. EPFP caused favorable changes in Bcl-2/Bax mRNA ratio, which rendered MCF-7 cells more sensitive to apoptosis: the number of apoptotic cells increased 2.2-fold vs. control at 100 µM GAE. Furthermore, 100 µ M L−1 GAE EPFP caused a 1.8-fold reduction in the activity of metalloproteinase-9 (MMP-9) secreted to the culture medium by MCF-7 cells. Moreover, EPFP suppressed the expression of selected genes of matrix metalloproteinases (MMPs), a proliferation marker (Ki67), and vascular endothelial growth factor (VEGF). In conclusion, the results of this study suggest that EPFP may exhibit proapoptotic, antiproliferative, antimigratory, and antimetastatic potential towards both selected human breast cancer cell lines, which is more pronounced in the case of the highly invasive MDA-MB-231 cells.