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EN
Multidrug resistance has for many years attracted attention of numerous investigators. Attempts have also been made to increase efficiency of anti-neoplastic therapy. For this reason, most of efforts have been devoted to analysing proteins engaged in the mechanism of multidrug resistance such as the N-glycosylated membrane protein glycoprotein P. Interestingly, glycosylation probably plays a significant role in the intracellular location and activity of modified proteins. Inhibitors of glycosylation have been demonstrated to alter the activity of glycoprotein P in various ways, depending on the cell line examined. These inhibitors markedly reduce multidrug resistance of cancer cells, thus promoting success of anti-neoplastic therapy. Here, we review the basic knowledge on N-glycosylation inhibitors, their effect on glycoprotein P and their therapeutic potential.
EN
PAX8 gene encodes one of the transcription factors engaged in the regulation of proper development of thyroid gland as well as Müllerian and renal/upper urinary tracts. So far, six alternatively spliced transcripts were reported, however, sequences of only four were deposited in the NCBI database. Here, we evaluate a fragment of a novel variant of PAX8 mRNA formed by an alternative 3' acceptor site located in the second exon. The molecular outcome encompasses extension of the 5' untranslated region of exon two by 97 nucleotides as is evident from mRNA. This new insert may impair binding of mRNA to the ribosome and in consequence significantly decrease expression of the PAX8 protein. Here, we show for the first time that the novel insert in exon two might be associated with congenital thyroid hemiagenesis and influence development of different types of cancer.
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