Tumor molecular margins

Zmiany molekularne charakterystyczne dla guza nowotworowego, takie jak mutacje genetyczne czy zmieniony poziomswoistych transkryptów i białek, obserwowane są niekiedy w obrębie prawidłowych morfologicznie i histologicznietkanek otaczających nowotwór. Taki obszar tkanek otaczających nowotwór nazywany jest marginesem molekularnymguza. Zakłada się, że zmiany molekularne obserwowane w tym obszarze mogą być etapem poprzedzającymzmiany morfologiczne i histologiczne. Skuteczność operacyjnego leczenia nowotworów zależy od całkowitej resekcjiguza, a przyczyną niepowodzenia leczenia mogą być wznowy miejscowe, będące efektem pozostawienia pozapolem operacyjnym komórek nowotworowych. Nie można jednak wykluczyć, że wznowy miejscowe są efektemtransformacji nowotworowej sąsiadujących z guzem tkanek histologicznie prawidłowych, zainicjowanej występującymitu wcześniej zmianami molekularnymi. W takim ujęciu zdefiniowanie marginesów molekularnych guza i ichusunięcie razem z nowotworem może być kluczowe dla skuteczności leczenia operacyjnego. Istnieje szereg narzędzidiagnostycznych umożliwiających zdefiniowanie obszaru i określenie właściwości molekularnych marginesów guzanowotworowego. Do najczęściej stosowanych należą metody immunohistochemiczne i metody oparte na reakcjiPCR, umożliwiające analizę wybranych białek, transkryptów i genów. W ostatnim czasie podejmowane są równieżpróby wykorzystania do badania marginesów molekularnych guza nowotworowego zaawansowanych techniczniemetod genomiki i proteomiki. Do najbardziej obiecujących wśród nich należy metoda obrazowania molekularnegotkanek za pomocą spektrometrii mas (Imaging Mass Spectrometry).Molecular changes characteristic of malignant tumors such as genetic mutations or altered levels of specific transcriptsand proteins are sometimes observed within the morphologically and histologically normal tissue adjacent to thetumor. Such an area of morphologically normal yet molecularly changed tissue is called a molecular margin of tumor.It has been suggested that molecular changes observed in this area might be followed by a further transformationinto a malignant tumor. The efficacy of surgical treatment of the tumor depends on complete resection of cancercells, hence local recurrence and failure of the treatment might result from tumor cells residing outside the resectedarea. However, a local recurrence could also result from malignant transformation of cells in morphologically andhistologically normal tissue adjacent to the tumor where molecular cancer-initiating changes were pre-existing. Henceidentification and delineation of molecular margins of tumor (and removing them together with the cancer) mightbe crucial for the efficacy of the treatment. There are several diagnostic tools that can be used for identification andcharacterization of tumor molecular margins. The most commonly used include immunohistochemistry and PCR-basedmethods, which allows analysis of pre-selected proteins, transcripts and genes. Most recently, technically advancedmethods of genomics and proteomics have been also proposed in studies of molecular margins of cancer, includingmolecular imaging of tissue by mass spectrometry (so called Imaging Mass Spectrometry)

Heat shock response regulates stimulus-specificity and sensitivity of the pro-inflammatory NF-κB signalling

From Springer Nature via Jisc Publications RouterHistory: received 2020-01-24, accepted 2020-04-16, registration 2020-04-16, pub-electronic 2020-05-24, online 2020-05-24, collection 2020-12Publication status: PublishedFunder: Narodowe Centrum Nauki; doi: http://dx.doi.org/10.13039/501100004281; Grant(s): 2016/23/B/ST6/03455, 2015/19/B/ST7/02984, 2016/21/B/ST7/02241Funder: Politechnika Śląska; doi: http://dx.doi.org/10.13039/501100007835; Grant(s): 02/010/BK19/0143Funder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/K003097/1Funder: Politechnika Poznańska; doi: http://dx.doi.org/10.13039/501100004239; Grant(s): 825/RN2/RR4/2018Abstract: Background: Ability to adapt to temperature changes trough the Heat Shock Response (HSR) pathways is one of the most fundamental and clinically relevant cellular response systems. Heat Shock (HS) affects the signalling and gene expression responses of the Nuclear Factor κB (NF-κB) transcription factor, a critical regulator of proliferation and inflammation, however, our quantitative understanding of how cells sense and adapt to temperature changes is limited. Methods: We used live-cell time-lapse microscopy and mathematical modelling to understand the signalling of the NF-κB system in the human MCF7 breast adenocarcinoma cells in response to pro-inflammatory Interleukin 1β (IL1β) and Tumour Necrosis Factor α (TNFα) cytokines, following exposure to a 37–43 °C range of physiological and clinical temperatures. Results: We show that exposure to 43 °C 1 h HS inhibits the immediate NF-κB signalling response to TNFα and IL1β stimulation although uptake of cytokines is not impaired. Within 4 h after HS treatment IL1β-induced NF-κB responses return to normal levels, but the recovery of the TNFα-induced responses is still affected. Using siRNA knock-down of Heat Shock Factor 1 (HSF1) we show that this stimulus-specificity is conferred via the Inhibitory κB kinase (IKK) signalosome where HSF1-dependent feedback regulates TNFα, but not IL1β-mediated IKK recovery post HS. Furthermore, we demonstrate that through the temperature-dependent denaturation and recovery of IKK, TNFα and IL1β-mediated signalling exhibit different temperature sensitivity and adaptation to repeated HS when exposed to a 37–43 °C temperature range. Specifically, IL1β-mediated NF-κB responses are more robust to temperature changes in comparison to those induced by TNFα treatment. Conclusions: We demonstrate that the kinetics of the NF-κB system following temperature stress is cytokine specific and exhibit differential adaptation to temperature changes. We propose that this differential temperature sensitivity is mediated via the IKK signalosome, which acts as a bona fide temperature sensor trough the HSR cross-talk. This novel quantitative understanding of NF-κB and HSR interactions is fundamentally important for the potential optimization of therapeutic hyperthermia protocols. D-ESB-DSZSgbr1c4s2oumkVideo Abstrac

Fractions of heavy metals in the soil of the urban agglomeration with increased traffic

The paper presents the results of research on the content of selected heavy metals (Cu, Pb, Zn, Ni) depending on pH, organic carbon content and soil sorption in the direct location of busy streets around the campus of the Kielce University of Technology. Based on the conducted studies of the sequential fractionation of metals by the BCR method was found that the highest content of nickel fraction FI (exchangeable) was 142.75 mg/kg. However, the total nickel concentration in all research areas exceeded the value specified in the Journal of Laws approx. 2 times. The lowest content from the analyzed metals in the surface layer of soil was found for zinc, the content of which was 1.5% in relation to the standard. The average percentage share of the analyzed metals in the separated fractions, in relation to the total content, was in decreasing series for Ni: FIII > FI> FII> FIV; for Pb: FII > FI > FIV > FIII; for Cu: FII > FI > FIII > FIV and for Zn: FII > FIII > FI > FIV. The studied soils are characterized by a varied granulometric composition of sand fraction, from very thick (1000 μm–2000 μm) to very fine 2 μm–50 μm). Statistical calculations showed that the pH, Corg content and sorptivity of the studied soil correlate with each other

Sorption of Heavy Metals by Sewage Sludge and Its Mixtures with Soil from Wastewater Treatment Plants Operating in MBR and INR Technology

Sewage sludge is a very complex system, with solids and water. It is generated as waste from wastewater treatment. Sewage sludge is used to fertilize agricultural and forest areas and to rehabilitate devastated areas. It is a good organic fertilizer because it contains significant amounts of nutrients beneficial for plant development and humus-forming substances. The composition of sludge from municipal wastewater treatment plants is similar to soil organic matter, therefore it can be used to improve the physicochemical properties of soil, increasing its sorption capacity. Research material was collected in the Swietokrzyskie and Mazowieckie Voivodships. Sewage sludge was collected from the wastewater treatment plants in Sitkowka Nowiny (Sitkowka) and Kunow, as well as high-quality agricultural soil from Opatowiec and sandy-clay soil from Jastrzebie. Research was carried out on the sorption of heavy metals (Cd, Cr, Cu, Pb, Ni, Zn) by mixtures of sewage sludge with soil. The calculations were made for the concentrations of heavy metals in sewage sludge, soil, and sewage sludge–soil mixtures. The geoaccumulation index (Igeo) and the risk assessment code (RAC) were calculated. Increased sorption capacity was demonstrated in samples with a predominance of sewage sludge. It was shown that heavy metals from sewage sludge, after mixing with soil, changed their form from immobile to mobile

Zawartość wybranych metali ciężkich na terenie kampusu Politechniki Świętokrzyskiej

The content of heavy metals in soils is a serious problem, especially in the case of agricultural soils. Metals are entering human body not only with animal and plant products but also through the skin and by inhalation. They can cause poisoning or chronic disease of the body. The aim of the study was to assess the contamination of green areas of the Kielce University of Technology by following metals Cd, Cu, Pb, Ni, Zn and Al, due to the location of the university and its campus. The range of tests performed including pH, iodine value, organic carbon, granulometry and metal content indicate the varied and significant pollution and varying degree of soil degradation. The results of the study also show that the analysed soils are formations of equally and varigrained, sand fractions. The lead concentration has been exceeded, in relation to the standards, in the sampling areas impacted by high traffic (point No. 6 located in area of Kielce University of Technology at Millennium PP7 avenue and playgrounds for volleyball).Zawartość metali ciężkich w glebach jest poważnym problemem, szczególnie w przypadku gleb użytkowanych rolniczo. Metale, do organizmu człowieka przedostają się nie tylko z produktami roślinnymi i zwierzęcymi, ale również przez skórę i wdychanie. Mogą wywoływać zatrucia lub przewlekłe stany chorobowe organizmu. Celem pracy była ocena zanieczyszczenia terenów zielonych Politechniki Świętokrzyskiej metalami Cd, Cu, Pb, Ni, Zn i Al ze względu na lokalizację uczelni i jej kampusu. Wykonany zakres badań uwzględniający pH, liczbę jodową, węgiel organiczny, granulometrię i zawartość metali wskazuje na zróżnicowane i znaczące zanieczyszczenie oraz różny stopień degradacji gleby. Wyniki pokazują również, że analizowane gleby to utwory równo- i różnoziarniste, frakcje piaskowe. Stężenie ołowiu zostało przekroczone, w stosunku do standardów, w miejscach o dużym oddziaływaniu ruchu samochodowego (punkt nr 6 zlokalizowany na terenach Politechniki Świętokrzyskiej oraz boiska do piłki siatkowej)

The Application of Remote Sensing Techniques and Spectral Analyzes to Assess the Content of Heavy Metals in Soil – A Case Study of Barania Góra Reserve, Poland

The understanding of the spatial and temporal dynamics of farmland processes is essential to ensure the proper crop monitoring and early decision making needed to support efficient resource management in agriculture. By creating appropriate crop management strategies, one can increase harvest efficiency while reducing costs, waste, chemical spraying, and inhibiting the impact of biotic and abiotic factors on crop stress. Only reliable spatial information makes it possible to comprehend the influence of various factors on the environment. The main objective of the research presented in the paper was to assess the possibility of using maps of vegetation and soil indices, such as NDVI, SAVI, IRECI, CIred-edge, PSRI and HMSSI, calculated on the basis of images from the Sentinel-2 satellite, to qualitatively determine the increased amount of heavy metals in the soil in the areas of small agricultural plots around the Barania Góra nature reserve in Poland. The conducted pilot project shows that the spectral indices: NDVI, SAVI, IRECI, CIred-edge, PSRI, and HMSSI, calculated on the basis of images from Sentinel-2, have the potential to assess the content of nickel zinc, chromium and cobalt in the soil on agricultural plots. However, the confirmation of the obtained results requires continuation of the research

Properties of ashes formed after the combustion of sewage sludge

The objective of the research presented in the paper was to analyze the ash formed in the process of incineration in the thermal sewage sludge treatment facility being a part of Sitkówka-Nowiny wastewater treatment plant, located in the vicinity of Kielce. The research involved the investigation of heavy metal and total phosphorus content, leachability of certain ions and X-ray phase analysis. The comparison of the obtained results with those available in literature revealed similarities in the crystallographic structure of ashes from different treatment plants. Then, the differences observed in the content of heavy metals in particular ashes are related to the composition of sewage flowing into treatment plants. Attention was also paid to a significant sulphate content revealed in the leachability analysis, found both in the ash from Sitkówka-Nowiny treatment plant and in the ash analyses results available in the literature sources. High sulphate concentration can limit the use of ash for construction purposes

Properties of ashes formed after the combustion of sewage sludge

The objective of the research presented in the paper was to analyze the ash formed in the process of incineration in the thermal sewage sludge treatment facility being a part of Sitkówka-Nowiny wastewater treatment plant, located in the vicinity of Kielce. The research involved the investigation of heavy metal and total phosphorus content, leachability of certain ions and X-ray phase analysis. The comparison of the obtained results with those available in literature revealed similarities in the crystallographic structure of ashes from different treatment plants. Then, the differences observed in the content of heavy metals in particular ashes are related to the composition of sewage flowing into treatment plants. Attention was also paid to a significant sulphate content revealed in the leachability analysis, found both in the ash from Sitkówka-Nowiny treatment plant and in the ash analyses results available in the literature sources. High sulphate concentration can limit the use of ash for construction purposes

Late Effects of Ionizing Radiation on the Ultrastructure of Hepatocytes and Activity of Lysosomal Enzymes in Mouse Liver Irradiated In Vivo

The study aimed to investigate late radiation-induced changes in the histology, ultrastructure, and activity of lysosomal enzymes in mouse liver exposed to ionizing radiation. The experiment was conducted on C57BL/6J male mice whose distal part of the liver was exposed occasionally to single doses of radiation (6 MV photons) during targeted heart irradiation; estimated doses delivered to analyzed tissue were 0.025 Gy, 0.25 Gy, 1 Gy, and 2 Gy. Tissues were collected 40 weeks after irradiation. We have observed that late effects of radiation have an adaptive nature and their intensity was dose-dependent. Morphological changes in hepatocytes included an increased number of primary lysosomes and autophagic vacuoles, which were visible in tissues irradiated with 0.25 Gy and higher doses. On the other hand, a significant increase in the activity of lysosomal hydrolases was observed only in tissues exposed to 2 Gy. The etiology of these changes may be multifactorial and result, among others, from unintentional irradiation of the distal part of the liver and/or functional interaction of the liver with an irradiated heart. In conclusion, we confirmed the presence of late dose-dependent ultrastructural and biochemical changes in mouse hepatocytes after liver irradiation in vivo