Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived 72 correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8] 72 as the major isoform is likely due to increased plasma 77 -convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

No abstract

No abstract

Summary. Background: Elevated βIII-tubulin levels are associated with resistance to a broad spectrum of drugs in different carcinomas and with poor prognosis of various epithelial cancers. 5-Fluorouracil (5-FU) is a widely used standard drug in chemotherapeutic regimens for colorectal cancer treatment, although the resistance to 5-FU is a major obstacle to successful therapy. Aim: The aim of the study was to compare the invasive and adhesion properties and the expression levels of βIII-tubulin in a 5-fluorouracil (5-FU)-resistant colorectal cancer (CRC) cell line HCT116 and parental cells. Materials and Methods: The 5-FU-resistant cell line was established by continuous stepwise selection with increasing concentrations of 5-FU. Cell viability and properties were evaluated using MTT, adhesion and Transwell invasion assays, respectively. The expression of βIII-tubulin was revealed by immunoblot and immunofluorescence. Results: The derivative line is 25-fold more resistant to 5-FU and characterized by altered cell morphology. Twice as many cells of the 5-FU-resistant line fail to adhere as compared to the parental cell line. 5-FU-resistant cells are characterized by enhanced invasiveness, accompanied with the increased βIII-tubulin expression. In addition, we found that loss of βIII-tubulin expression was correlated with loss of 5-FU resistance. Conclusion: Our results indicate that even though 5-FU does not target microtubules, there appears to be a correlation between βIII-tubulin expression and resistance to 5-FU that is particularly important with regard to invasiveness. These findings indicate a possible contribution of βIII-tubulin to 5-FU resistance in vivo.

Èíâàçèâíûé ðîñò ÿâëÿåòñÿ ïåðâûì øàãîì ìåòàñòàòè÷åñêîãî êàñêàäà çëîêà÷åñòâåí-íûõ îïóõîëåé. Äâèãàòåëüíàÿ àêòèâíîñòü êëåòîê, íåîáõîäèìûé êîìïîíåíò èíâàçèè, òåñíî ñâÿçàíà ñ äèíàìèêîé ñòðóêòóð öèòîñêåëåòà. Âàaeíóþ ðîëü â îáåñïå÷åíèè êëåòî÷-íîé ïîäâèaeíîñòè èãðàþò ìèêðîòðóáî÷êè, êîòîðûå ñîñòîÿò èç òóáóëèíà -ãåòåðîäèìå-ðà, ñîäåðaeàùåãî a è b ñóáúåäèíèöû, ïðåäñòàâëåíûå ðàçëè÷íûìè èçîòèïàìè. Ïîÿâëå-íèå â îïóõîëè b III -òóáóëèíà èãðàåò âàaeíóþ ðîëü â ïðîãíîçå òå÷åíèÿ è õèìèîðåçèñòåíò-íîñòè ðÿäà îïóõîëåé ÷åëîâåêà. Äàííîå èññëåäîâàíèå ïîñâÿùåíî îïðåäåëåíèþ âîçìîae-íîñòè èñïîëüçîâàíèÿ b III -òóáóëèíà â êà÷åñòâå ìîëåêóëû-ìèøåíè äëÿ ïîäàâëåíèÿ èíâà-çèâíîãî ðîñòà. Óñòàíîâëåíî, ÷òî áëîêèðîâàíèå ýêñïðåññèè b III -òóáóëèíà â êëåòêàõ êîëîðåêòàëüíîãî ðàêà íå âëèÿåò íà èõ aeèçíåñïîñîáíîñòü, îäíàêî ñíèaeàåò àäãåçèþ ê âíåêëåòî÷íîìó ìàòðèêñó êëåòîê ëèíèè HT-29 íà 40 % (ð = 0,0044), HCT 116 -íà 15 % ( p = 0,0436) è èíâàçèâíóþ àêòèâíîñòü â 4 ðàçà ( p = 0,0000 è p = 0,0001 ñîîòâåòñòâåí-íî). Äàííûå ôàêòû ïîçâîëÿþò ðàññìàòðèâàòü b III -òóáóëèí â êà÷åñòâå ìîëåêóëû-ìèøå-íè ïðè ðàçðàáîòêå ïðîòèâîîïóõîëåâûõ ëåêàðñòâåííûõ ïðåïàðàòîâ.Êëþ÷åâûå ñëîâà: òóáóëèí; èíâàçèâíûé ðîñò; ìåòàñòàçèðîâàíèå; êîëîðåêòàëüíûé ðàê; êóëüòóðà êëåòîê. ÂÂÅÄÅÍÈÅÐàçðàáîòêà ñîâðåìåííûõ ëåêàðñòâåííûõ ïðåïàðàòîâ îñíîâûâàåòñÿ íà óñïåõàõ ìîëåêóëÿðíîé áèîëîãèè è òðàíñëÿöèîííûõ ìåäèöèíñêèõ èññëåäîâàíèé ïî âûÿâ-ëåíèþ êëþ÷åâûõ ìîëåêóë ïàòîãåíåòè÷åñêîãî êàñêàäà è èñïîëüçîâàíèþ èõ â êà÷åñòâå ìèøåíåé äëÿ ìåäèêà-ìåíòîçíîãî âîçäåéñòâèÿ. Íà äàííûé ìîìåíò â ôàðìà-öåâòè÷åñêîé ïðîìûøëåííîñòè íàøëè ïðèìåíåíèå 324 òàêèå ìîëåêóëû [8]. Áîëüøóþ ÷àñòü ìîëåêóë ìèøåíåé ñîñòàâëÿþò ðåöåïòîðû (45 %), ôåðìåíòû (28 %) è ãîð-ìîíû (11 %) [3]. Ðàñøèôðîâêà ãåíîìà ÷åëîâåêà â 2002 ã. ïîçâîëèëà âûÿâèòü îò 3000 äî 10000 ïîòåíöè-àëüíûõ ôàðìàêîëîãè÷åñêèõ ìèøåíåé [6]. Ñ ýòèõ ïîçè-öèé ïðåäñòàâëÿåòñÿ âàaeíûì óñòàíîâëåíèå íîâûõ çàêî-íîìåðíîñòåé èçìåíåíèé ìîëåêóëÿðíîãî ñîñòàâà êëå-òîê ïðè ðÿäå ïàòîëîãè÷åñêèõ ïðîöåññîâ ÷åëîâåêà, âêëþ÷àÿ îïóõîëåâûé ðîñò.Ìàëî èçó÷åííîé íà äàííûé ìîìåíò âðåìåíè îñòàåò-ñÿ îáëàñòü ïåðåñòðîéêè öèòîñêåëåòà ïðè ðàçëè÷íûõ ñîñòîÿíèÿõ êëåòêè. Îäíèì èç êîìïîíåíòîâ öèòîñêåëå-òà ÿâëÿþòñÿ ìèêðîòðóáî÷êè -äèíàìè÷åñêèå ñòðóêòó-ðû, îáåñïå÷èâàþùèå âíóòðèêëåòî÷íûé òðàíñïîðò â èíòåðôàçó, à òàêaeå îáðàçóþùèå âåðåòåíî äåëåíèÿ â ôàçó ìèòîçà. Ìèêðîòðóáî÷êè ñîñòîÿò èç òóáóëèíà -ãåòåðîäèìåðà, ñîäåðaeàùåãî a è b ñóáúåäèíèöû, êîòî-ðûå ìîãóò áûòü ïðåäñòàâëåíû ðàçëè÷íûìè èçîòèïàìè. Äëÿ a-ñóáúåäèíèöû èçâåñòíî 8 èçîòèïîâ, à äëÿ b--7 [7]. Òàêaeå èçâåñòíû ìíîãî÷èñëåííûå ïîñòòðàíñëÿöèîí-íûå ìîäèôèêàöèè êàê a-, òàê è b-òóáóëèíà, òàêèå êàê òè-ðîçèíèðîâàíèå, àöåòèëèðîâàíèå, ïîëèãëóòàìèíèðîâà-íèå, äåòèðîçèíèðîâàíèå, ôîñôîðèëèðîâàíèå è äð. [10].Äâèaeåíèå êëåòîê, ÷àñòíûì âàðèàíòîì êîòîðîãî ÿâ-ëÿåòñÿ èíâàçèâíûé ðîñò çëîêà÷åñòâåííûõ îïóõîëåé, òåñíî ñâÿçàíî ñ äèíàìèêîé ñòðóêòóð öèòîñêåëåòà. Óñ-òàíîâëåíî, ÷òî íàðÿäó ñ àêòèíîâûìè ìèêðîôèëàìåí-òàìè âàaeíóþ ðîëü â îáåñïå÷åíèè êëåòî÷íîé ïîäâèae-íîñòè èãðàþò ìèêðîòðóáî÷êè. Áîëåå òîãî, ôóíêöèîíè-ðîâàíèå àêòèíîâûõ ìèêðîôèëàìåíòîâ çàâèñèò îò ïî-ëèìåðèçàöèîííîé äèíàìèêè ìèêðîòðóáî÷åê [2].Ðà...