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Content available remote DNAzyme as an efficient tool to modulate invasiveness of human carcinoma cells
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EN
In this study we evaluated efficiency of DNAzymes to modulate motility of cancer cells, an important factor in the progression and metastasis of cancers. For this purpose we targeted β1 integrins that are predominant adhesive receptors in various carcinoma cell lines (CX1.1, HT29, LOVO, LS180, PC-3). To evaluate invasiveness of cancer cells, we used a transwell migration assay that allowed analyzing chemotactic migration of colon carcinoma cell lines across an ECM-coated membrane. Their adhesive properties were also characterized by the analysis of adhesion to fibronectin, laminin and collagen. In addition, the expression of major integrin subunits, selected intact β1 integrins, and other adhesive receptors (ICAM, E-selectin, uPAR) was analyzed by flow cytometry. Inhibition of β1 integrin expression by DNAzyme to β1 mRNA almost abolished the invasiveness of the CX1.1, HT29, LS180, LOVO and PC-3 cells in vitro. These data show that DNAzymes to β1 integrin subunit can be used to inhibit invasiveness of carcinoma cells.
EN
Triterpene saponins (saponosides) are found in a variety of higher plants and display a wide range of pharmacological activities, including expectorant, anti-inflamatory, vasoprotective, gastroprotective and antimicrobial properties. Recently, a potential anticancer activity of saponins has been suggested by their cytotoxic, cytostatic, pro-apoptotic and anti-invasive effects. At high concentrations (more than 100 µM) saponins exert cytotoxic and haemolytic effects via permeabilization of the cell membranes. Noteworthy, the inhibition of cancer cell proliferation, the induction of apoptosis and attenuation of cell invasiveness is observed in the presence of low saponin concentrations. Saponins might affect the expression of genes associated with malignancy. These alterations are directly related to the invasive phenotype of cancer cells and depend on "cellular context". It illustrates the relationships between the action of saponins, and the momentary genomic/proteomic status of cancer cells. Here, we discuss the hallmarks of anti-cancer activity of saponins with the particular emphasis on anti-invasive effect of diverse groups of saponins that have been investigated in relation to tumor therapy.
EN
The article presents the results of research on the influence of the sinusoidal electromagnetic field with a frequency of 50 Hz on the metabolic activity of two cell lines normal BJ and cancer 143b, with different exposure times (0.5 h, 1 h, 2 h and 3 h). It is shown the difference in its effect on cancer and physiological line. In order to analyze the viability there was performed the MTT test.
PL
W artykule zostały zaprezentowane wyniki badań wpływu sinusoidalnego pola elektromagnetycznego o częstotliwości 50 Hz na aktywność metaboliczną dwóch linii komórkowych - normalnej BJ i nowotworowej 143b przy różnych czasach ekspozycji (0.5 h, 1 h, 2 h i 3 h). Wykazano różnice w oddziaływaniu na linię fizjologiczną oraz nowotworową. W celu dokonania analizy żywotności wykonano test MTT.
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tom T. 97, nr 10
1733--1736
PL
Polisacharydy zawarte w pyłku chryzantem ekstrahowano wodą i wytrącano przy użyciu alkoholu. Cukier o charakterze obojętnym i 2 cukry o charakterze kwasowym rozdzielono, stosując chromatografię jonowymienną. Skład monosacharydów oznaczono metodą wysokosprawnej chromatografii cieczowej. Działanie przeciwnowotworowe polisacharydów oceniano, badając ich wpływ na proliferację komórek nowotworowych. Hamowanie proliferacji HCT116 nie było znaczące, gdy stężenie wynosiło 5 mg/mL (p > 0,05), jednak działanie to w stosunku do komórek nowotworowych HCT116 i HT-29 było znaczące przy tym samym stężeniu (p < 0,05). Nieprzetworzone wyciągi polisacharydowe miały większy wpływ na proliferację komórek in vitro raka jelita grubego niż poszczególne polisacharydy.
EN
Polysaccharides were extd. from Dendranthema indicum var. Asteraceae bee pollens with H2O (yield 7.9%), pptd. with EtOH and sepd. by ion-exchange chromatog. into a neutral sugar and 2 acidic ones. The monosaccharide compn. was detd. by high performance liq. chromatog. They contained rhamnose, galacturonic acid, glucose, galactose and arabinose. The anticancer activity of the polysaccharides was evaluated by studying their effect on proliferation of HCT116 and HT-29 cancer cells. The inhibitory effect of individual sugars on the proliferation of HCT116 was not significant when their concns. were 5 mg/mL, but the total polysaccharides showed a significant effect on proliferation of HCT116 and HT-29 tumor cells at the same concn
PL
Choroby nowotworowe przyjmują na świecie postać epidemii. W 2012 roku chorobą nowotworową było dotkniętych 14, 1 milionów osób, z czego 7, 4 miliona to mężczyźni, a 6, 7 miliona to kobiety. Szacuje się, że liczba nowych przypadków wzrośnie do 22 milionów w ciągu najbliższych dwóch dekad. W związku z tak liczną zachorowalnością na nowotwory stale poszukuje się nowych terapii mających na celu zahamowanie ich rozwoju. Udowodniono, że ekspozycja komórek nowotworowych na działanie pola elektromagnetycznego o niskich częstotliwościach indukuje w nich programowaną śmierć komórkową, hamuje proces angiogenezy a nawet blokuje proces metastazy wzmacniając odpowiedź układu immunologicznego na komórki nowotworowe. W ostatnich latach przeprowadzono wiele badań in vitro i in vivo, w których udokumentowano przeciwnowotworowy wpływ pola elektromagnetycznego o różnej częstotliwości i natężeniu na komórki nowotworowe, co może stanowić nowe podejście w kontrolowaniu ich wzrostu.
EN
Cancer is a leading cause of death worldwide. In 2012, there were 14.1 million new cancer cases diagnosed; more than 7 million among men and 6,7 million among women. The World Health Organization expects that number of new cases of cancer will rise to 22 milions over the next two decades. Due to high incidence, the scientists are still searching for new therapies aimed at the inhibition of the diseases development. It has been shown that exposure of cancer cells to low frequency electromagnetic field affects biology of cancer cells, e.g., induces programmed cell death, inhibits angiogenesis and metastasis and enhances the immune system activation. In recent years, numerous in vitro and in vivo studies revealed anticancer properties of the electromagnetic field of various frequency and intensity. It may provide a novel approach to control growth of cancer and could be used for medical treatments.
EN
Natural polyphenolic compounds produced by plant exhibit many pharmacological effects including antioxidant, chemopreventive as well as anticancer properties. This study was conducted to investigate the effect of cynarin ( from Artichoke, Cynara scolymus) and isoliquiritin (from Licorice, Glycyrrhiza uralensis) on doxorubicin (positive control) cytotoxicity in different cell lines including normal (Fibroblasts MCR-5 and Myoblasts H9c2) and cancer (colorectal HCT-116 and hepatocellular HEP-G2) cell lines. The cytotoxic effect of doxorubicin, isoliquiritin and cynarin alone or in different combination was studied on cancer cell lines as well as normal cell lines. The results obtained indicated that both cynarin and isoliquiritin enhance the cytotoxicity of doxorubicin. Both cynarin and isoliquiritin also reduce the cardiotoxicity of doxorubicin on normal cardiac cell lines. The combination of the three compounds (cynarin, isoliquiritin and doxorubicin) result in decrease the cytotoxicity of doxorubicin, which may indicate the presence of interaction and/or antagonism effect between cynarin and isoliquiritin. Cynarin was found to enhance the growth of (HCT-116 and HEP-G2) this might suggest avoiding use of Artichoke in subjects’ susceptibility for these cancers. All results were evaluated using statistical path and showed significant findings. The mechanism of enhanced doxorubicin’s cytotoxicity by cynarin or isoliquiritin also require further investigation to explain the increasing and/or the decreasing effect of these polyphenolic compounds on cytotoxicity of doxorubicin. The current finding can help to start with safe minimum dose of two or three combination of compounds in the context of clinical trials and practice.
EN
In this paper we investigate a mathematical model of cancer invasion of tissue, which incorporates haptotaxis, chemotaxis, proliferation and degradation rates for cancer cells and the extracellular matrix, kinetics of urokinase receptor, and urokinase plasminogen activator cycle. We solve the model using spectrally accurate approximations and compare its numerical solutions with laboratory data. The spectral accuracy allows to use low-dimensional matrices and vectors, which speeds up the computations of the numerical solutions and thus to estimate the parameter values for the model equations. Our numerical results demonstrate correlations between numerical data computed from the mathematical model and in vivo tumour growth rates from prostate cell lines.
EN
Over the past decade, a handful of evidence has been provided that nonsteroidal anti-inflammatory drugs (NSAIDs) display effects on the homeostasis of the endoplasmic reticulum (ER). Their uptake into cells will eventually lead to activation or inhibition of key molecules that mediate ER stress responses, raising not only a growing interest for a pharmacological target in ER stress responses but also important questions how the ER-stress mediated effects induced by NSAIDs could be therapeutically advantageous or not. We review here the toxicity effects and therapeutic applications of NSAIDs involving the three majors ER stress arms namely PERK, IRE1, and ATF6. First, we provide brief introduction on the well-established and characterized downstream events mediated by these ER stress players, followed by presentation of the NSAIDs compounds and mode of action, and finally their effects on ER stress response. NSAIDs present promising drug agents targeting the components of ER stress in different aspects of cancer and other diseases, but a better comprehension of the mechanisms underlying their benefits and harms will certainly pave the road for several diseases’ therapy.
PL
Zaburzona równowaga pomiędzy proliferacją a dojrzewaniem i różnicowaniem komórek nowotworowych powoduje szybki wzrost guza, prowadząc do zwiększenia zapotrzebowania na składniki odżywcze, m.in. glukozę i tlen. Pierwszą odpowiedzią komórek nowotworowych na niewystarczającą ilość składników odżywczych jest zmiana metabolizmu na beztlenowy (efekt Warburga). Glukoza niezbędna do przeprowadzenia tego procesu dostarczana jest za pomocą transporterów – najczęściej białek GLUT1 i SGLT1. Zmiana poziomu i wzoru ekspresji transporterów glukozy w komórkach nowotworowych w porównaniu z komórkami odpowiednich tkanek prawidłowych świadczy o adaptacji, do której doszło w obrębie guza. Dotychczasowe badania pozwoliły ustalić, w których rodzajach nowotworów dochodzi do zmian w ekspresji białek GLUT1 i SGLT1 oraz pokazały, że zmiany te mogą mieć bezpośredni związek z zaawansowaniem choroby i rokowaniem dla pacjentów. Niniejsza praca ma charakter przeglądowy i stanowi zestawienie zmian w poziomie ekspresji transporterów glukozy w niektórych typach nowotworów. Określenie poziomu ekspresji tych białek w komórkach nowotworowych może mieć kluczowe znaczenie dla spersonalizowanej terapii przeciwnowotworowej.
EN
Due to imbalance between proliferation, differentiation and maturation, cancer cells grow rapidly and require elevated levels of oxygen and glucose. The main strategy of cancer cells is to prevent starvation is the anaerobic adaptation of cellular metabolism known as the Warburg’s effect. Increased glucose uptake is maintained by alterating the level and the pattern of glucose transporters expression, mainly GLUT1 and SGLT1. In many cancer types, these proteins are present despite their absence in healthy tissue. Previous researches revealed cancer types in which GLUT1 and SGLT1 expression are altered. There is a strong direct correlation between their expression pattern, cancer stage and prognosis for the patient. This review provides an overview of changes in the level of glucose transporters expression in some cancer types. Determination of glucose transporters expression levels in cancer cells could be crucial for personalized cancer treatment.
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