129. Zaburzenia liczby kopii genów erbB-1 i erbB-2 i ich związek z danymi klinicznymi u leczonych operacyjnie chorych na niedrobnokomórkowego raka płuca

Szlak sygnałowy nabłonkowego czynnika wzrostu (ang. epidermal growth factor, EGF) i jego receptory (najważniejsze z nich to erbB-1 i erbB-2) odgrywają ważną rolę w patogenezie i progresji raka płuca. Kliniczne znaczenie nadekspresji tych receptorów pozostaje nadal przedmiotem kontrowersji a dotychczasowe badania przynosiły sprzeczne wyniki. Z uwagi na opracowane ostatnio leki o wybiórczym działaniu przeciwnowotworowym, działające poprzez powyższe receptory, poznanie rokowniczego znaczenia tych zaburzeń może odegrać ważną rolę w ustalaniu optymalnego sposobu leczenia. Celem pracy była ocena rokowniczego znaczenia anomalii średniej liczby kopii genów (ang. avarage gene copy numer, AGCN) u chorych na niedrobnokomórkowego raka płuca poddanych resekcji miąższu płucnego.Materiał i metodyDo badania włączono 112 chorych leczonych operacyjnie w latach 1996–1999. U 61 chorych (55%) rozpoznano postać raka płaskonabłonkowego, u 30 (27%) gruczolakoraka, u 10 (9%) raka wielokomórkowego i u 10 (9%) chorych postacie mieszane. Stopień zaawansowania nowotworu kształtował się następująco: I=54 (48%), II=11 (10%), III=40 (36%), IV=7 (6%). Materiał do analizy molekularnej stanowiło DNA izolowane ze świeżo mrożonych wycinków guza pobranych podczas zabiegu operacyjnego. AGCN określano za pomocą podwójnie różnicowej reakcji polimerazy i elektroforezy agarozowej.WynikiŚrednia wartość AGCN dla erbB-1 wynosiła 2,0 (zakres od 0,01 do 28,07), a dla erbB-2 1,34 (zakres od 0,11 do 9,9). Stwierdzono znamienną zależność pomiędzy AGCN dla obu genów. Nie stwierdzono znamiennego związku z jakimkolwiek głównym parametrem klinicznym. Do czasu przeprowadzenia analizy zmarło 73 chorych (65%). Po czasie obserwacji o medianie 5,1 roku nie stwierdzono wpływu AGCN na czas przeżycia (log-rank, P=0,9; 0,83; 0,8 odpowiednio dla erbB-1, erbB-2 i dla obu genów łącznie).WnioskiUzyskane wyniki wskazują na brak rokowniczego znaczenia AGCN erbB-1 i erbB-2 u chorych na raka płuca poddanych resekcji miąższu płucnego

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Hydrogeological settings and origin of groundwater composition in the southern part of the Gorce Mts, Kowaniec Mały catchment

The Gorce Mts of southern Poland occur in a natural upland area that is viewed as valuable and is protected. It has an inadequate and irregular network of long-term monitoring points at the national level with regard to groundwater quality and vulnerability to contamination. The paper discusses the results of an investigation of groundwater in the Kowaniec Mały drainage basin, in the southern part of the Gorce Massif. It provides new hydrogeochemical data that shed light on the origin and evolution of groundwater chemistry in this region. On the basis of a hydrogeological survey of 33 natural springs, trends in the spatial and temporal variation of the physicochemical properties of the groundwater are presented. Three hydrochemical types of water were distinguished, namely HCO3-Ca, HCO3-Ca-Mg and HCO3-SO4-Ca. The detailed analysis of ionic ratios shows that the dissolution of carbonates (mainly calcite) and aluminosilicates (mainly albite) played a fundamental role in the formation of the chemical composition of the groundwater in the study area. These processes are responsible for the presence of the dominant ions, such as HCO3- and Ca2+, as well as SiO2 and in part Na+ and K+. Chloride–sodium mineralization is connected first of all with recharge by rain water and the direct dissolution of halite, contained in the aquifer rocks or formed during the evaporation of the water. The most probable sources of dissolved SO42- are the atmospheric sulphates contained in recharge meteoric waters in the case of springs located at higher altitudes and the reduced inorganic sulphur compounds dispersed in fine-grained sedimentary rocks, mostly as pyrite, which undergoes oxidation during rock weathering. Ion exchange processes involving clay minerals also were present and affected mainly the concentrations of Na+ + K+ and Ca2+.</sup

Pigmented elastomeric composites with limited flammability

Otrzymano mieszanki kauczuków butadienowo-akrylonitrylowego (NBR) i butadienowo-styrenowego (SBR) z tritlenkiem antymonu (5—20 phr) i stabilnymi termicznie pigmentami — ftalocyjaniną cynkową oraz ftalocyjaniną chloroglinową, następnie je sieciowano za pomocą siarkowego układu sieciującego. Badano wpływ jednoczesnego zastosowania w mieszance kauczukowej Sb2O3 i pochodnych ftalocyjaniny na stabilność termiczną, palność, zagrożenie pożarowe i właściwości mechaniczne uzyskanych wulkanizatów. Stwierdzono, że wytworzone materiały elastomerowe wykazywały mniejszą palność, mniejsze zagrożenie pożarowe i większą odporność termiczną oraz charakteryzowały się lepszymi właściwościami mechanicznymi niż niezabarwione wulkanizaty niezawierające tritlenku amonu.The acrylonitrile-butadiene (NBR) and styrene-butadiene (SBR) rubber mixtures with antimony trioxide flame retardant (5—20 phr) and thermally stable pigments — zinc phthalocyanine and chloroaluminum phthalocyanine were prepared and crosslinked using sulfur-based curing system. The effects of the simultaneous use of Sb2O3 and phthalocyanine derivatives in the rubber mixture on the thermal stability, mechanical properties, flammability and fire hazard of the resulting vulcanizates were examined. It was found that the produced elastomeric materials showed a reduced flammability, lower fire hazard, better thermal stability and improved mechanical properties when compared to the colourless vulcanizates without antimony trioxide flame retardant

EGFR as a stable marker of prostate cancer dissemination to bones

Background Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination. Methods EGFR overexpression (EGFR(over)) was tracked in 1039 primary tumours, circulating tumour cells from 39 d'Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices. Results EGFR(over)was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFR(over)correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFR(over)was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness. Conclusions EGFR(over)is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones

Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression

Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients. In order to investigate the gene expression differences between tumors with low and high TSR, we applied multigene expression analysis (nCounter(R) PanCancer Progression Panel, NanoString) of 42 tissue samples. TSR scores were categorized into low (< 1 TSR) and high (& GE;1 TSR). In the pilot cohort, 31 patients (43.1%) were categorized as low and 41 (56.9%) as high TSR score, whereas 48 (23.0%) patients from the validation cohort were classified as low TSR and 161 (77.0%) as high. In both cohorts, high TSR appeared to indicate the shorter time to biochemical recurrence in PCa patients (Log-rank test, p = 0.04 and p = 0.01 for the pilot and validation cohort, respectively). Additionally, in the multivariate analysis of the validation cohort, TSR predicted BR independent of other factors, i.e., pT, pN, and age (p = 0.04, HR 2.75, 95%CI 1.07-7.03). Our data revealed that tumors categorized into low and high TSR score show differential expression of various genes; the genes upregulated in tumors with low TSR score were mostly associated with extracellular matrix and cell adhesion regulation. Taken together, this study shows that high stroma content can play a protective role in PCa. Automatic EpCAM-based quantification of TSR might improve prognostication in personalized medicine for PCa