236 research outputs found
Adsorption properties of Ni, Cu, and Zn in young alkaline lake sediments in South Hungary (Lake Fehér, Szeged)
Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin-GnRH-III conjugates developed for targeted drug delivery
Gonadotropin releasing hormone-III (GnRH-III), a native isoform of the human GnRH isolated from sea lamprey, specifically binds to GnRH receptors on cancer cells enabling its application as targeting moieties for anticancer drugs. Recently, we reported on the identification of a novel daunorubicin–GnRH-III conjugate (GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] with efficient in vitro and in vivo antitumor activity. To get a deeper insight into the mechanism of action of our lead compound, the cellular uptake was followed by confocal laser scanning microscopy. Hereby, the drug daunorubicin could be visualized in different subcellular compartments by following the localization of the drug in a time-dependent manner. Colocalization studies were carried out to prove the presence of the drug in lysosomes (early stage) and on its site of action (nuclei after 10 min). Additional flow cytometry studies demonstrated that the cellular uptake of the bioconjugate was inhibited in the presence of the competitive ligand triptorelin indicating a receptor-mediated pathway. For comparative purpose, six novel daunorubicin–GnRH-III bioconjugates have been synthesized and biochemically characterized in which 6Asp was replaced by D-Asp, D-Glu and D-Trp. In addition to the analysis of the in vitro cytostatic effect and cellular uptake, receptor binding studies with 125I-triptorelin as radiotracer and degradation of the GnRH-III conjugates in the presence of rat liver lysosomal homogenate have been performed. All derivatives showed high binding affinities to GnRH receptors and displayed in vitro cytostatic effects on HT-29 and MCF-7 cancer cells with IC50 values in a low micromolar range. Moreover, we found that the release of the active drug metabolite and the cellular uptake of the bioconjugates were strongly affected by the amino acid exchange which in turn had an impact on the antitumor activity of the bioconjugates
Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma
Uveal melanoma (UM) is the most common primary intraocular malignancy with a very poor prognosis. The most frequent chromosome aberration in UM is the monosomy of chromosome 3. Previously, we demonstrated that ~50% of UMs express type-I receptor for luteinizing hormone-releasing hormone (LH-RH-R). The gene encoding LH-RH-R is located in chromosome 4 (location: 4q21.2); however, the occurrence of numerical aberrations of chromosome 4 have never been studied in UM. In the present study, we investigated the abnormalities of chromosome 3 and 4, and the possible correlation between them, as well as with LH-RH-R expression. Forty-six specimens of UM were obtained after enucleation. Numerical aberrations of chromosome 3 and 4 were studied by fluorescence in situ hybridization (FISH). Chromosome 4 was detected in normal biparental disomy only in 14 (30%) samples; however, 32 cases (70%) showed more than 2 signals/nucleus. Monosomy of chromosome 3 could be found in 16 (35%) samples. In 6 specimens (13%), more than 2 copies of chromosome 3 were found, while normal biparental disomy was detected in 24 (52%) samples. Statistical analysis indicated a statistically significant (p<0.05) correlation between the copy number of chromosome 3 and 4. Moreover, moderate difference was revealed in the survival rate of the UM patients with various pathological profiles. No correlation was found between chromosome aberrations and LH-RH-R expression. Our results clearly demonstrate abnormalities in chromosome 3 and 4 and the incidence of the monosomy of chromosome 3 in human UM. In summary, our results provide new incite concerning the genetic background of this tumor. Our findings could contribute to a more precise determination of the prognosis of human UM and to the development of new therapeutic approaches to this malignancy
Characterization of Luteinizing hormone-releasing hormone (LH-RH-I) receptor type I as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines
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Effect of drought on yield components of maize hybrids : Zea mays L
When investigating drought tolerance, it must not be forgotten that drought stress is a complex phenomenon exhibiting quite different characters in different years and locations. For this reason, the plant response to drought is also a complex process. In our study, 83 maize hybrids originating from various countries were investigated over a period of two years, under irrigated and non-irrigated conditions. The drought tolerance of plants in the non-irrigated plots was analysed in terms of flowering synchrony and yield components. It could be concluded from the results that in response to long-term water deficit the period between tasselling and silking became longer, while the analysis of yield components revealed the greatest reductions in the number of kernels per ear and in the proportion of seed set. As the degree of proterandry increased, there was a decline in the grain yield, confirming that the analysis of this trait could be a way of predicting drought tolerance. Considerable differences in drought tolerance were observed between the genetic materials included in the analysis, suggesting the presence among these parental lines and hybrids of genotypes resistant to long-term water deficit, suitable for cultivation under dry conditions. An analysis of correlations between the traits revealed that proterandry should be treated as a priority trait when investigating drought stress tolerance, as better predictions can be made of both drought tolerance and potential yields, leading to more reliable selection for higher yields
A mikroRNS-ek jelenléte vesetumorokban és lehetséges diagnosztikai-prognosztikai szerepük = Expressions of microRNA and their possible role in diagnosis and prognosis of renal cell carcinoma
A vesedaganatos betegek száma világszerte emelkedik. Noha
a vesekarcinĂłma patolĂłgiája Ă©s biolĂłgiája egyre felderĂtettebbĂ©
válik, teljesen sikeres sebészeti, onkológiai, radiológiai megol-
dás vagy eredményesen alkalmazott célzott terápiás kezelés
továbbra is csak korlátozott lehetĹ‘sĂ©geket biztosĂt. Emiatt a
vesetumoros betegek prognózisa rossz. A késői felismerés, a
tumor-heterogenitás Ă©s legfĹ‘kĂ©ppen a korai diagnĂłzist segĂtĹ‘
molekuláris biomarkerek hiánya miatt a betegség diagnoszti-
kája Ă©s kezelĂ©se jelentĹ‘s hátránnyal bĂr.
Ăšj biomarkerek azonosĂtása a daganatkutatás egyik fontos
fela data, a diagnosztika hatĂ©konysága, a prognĂłzis megĂtĂ©lĂ©se
és az eredményesebb gyógykezelés érdekében. Ebben a tekin-
tetben ĂgĂ©retesnek mutatkozik olyan biomarkerek azonosĂtása,
amelyeknek mintázata tumoros szövetekben eltérő a normál-
szövethez képest. Genomiális és proteomika szinten is egyre
inkább bővül az adatbázisok száma a tumorspecifikus marke-
reket illetően. A szakirodalomban körülbelül egy évtizedre ve-
tĂthetĹ‘ vissza a mikroRNs-ek (miR) megjelenĂ©se, amelyek min-
tázatának leĂrásával ma már akár egy-egy daganattĂpus is jel-
lemezhető. Noha az utóbbi években a publikációk száma egyre
bővül, a miR-ekre vonatkozó ismeretek nem eléggé elterjedtek
az olvasók/szakemberek körében, magyar nyelvű összefoglaló
pedig igen korlátozottan található. Ebben a közleményben arra
törekszĂĽnk, hogy egy összesĂtĹ‘ kĂ©pet adjunk a miR-ek
vesetumorok kialakulásában betöltött funkcionális szerepéről,
és egyúttal hangsúlyozzuk a miR-ek lehetséges diagnosztikai
és prognosztikai szerepét is a vesedaganatos betegségek kap-
csán
The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma
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