6 research outputs found
Targeting the melanoma
Czerniak nale偶y do najbardziej z艂o艣liwych nowotwor贸w cz艂owieka, a liczba zachorowa艅 na ten typ nowotworu wzrasta na 艣wiecie w zastraszaj膮cym tempie. Kom贸rki czerniaka charakteryzuj膮 si臋 wyj膮tkow膮 oporno艣ci膮 na stosowane obecnie metody leczenia. Badania z ostatnich lat przyczyni艂y si臋 do lepszego poznania i zrozumienia biologii nowotworu i otwar艂y drog臋 nowym terapiom celowanym. Obecnie wiele czynnik贸w znajduje si臋 we wczesnych fazach bada艅 klinicznych, cz臋艣膰 z nich osi膮gn臋艂a ju偶 III faz臋, a w sierpniu 2011 rokuFDA zaaprobowa艂a nowy lek do walki z czerniakiem - Wemurafenib (PLX4032). Artyku艂 stanowi przegl膮d najwa偶niejszych bia艂ek, szlak贸w i sieci sygnalizacyjnych zaanga偶owanych w rozw贸j i progresj臋 czerniaka, ze szczeg贸lnym uwzgl臋dnieniem element贸w b臋d膮cych najbardziej obiecuj膮cymi celami dla terapii antynowotworowej.Melanoma is one of the most aggressive human cancers. Its cells are inevitably resistant to conventional therapies. In recent years, better understanding of melanoma biology, has led to the development of a number of new potential therapeutic agents. Many of these compounds are being tested in early phase of clinical trials, some have already reach phase III. In August 2011 the FDA approved a new drug - Wemurafenib (PLX4032) to treatment unresectable and/or metastatic melanoma. The current article is an overview of the major proteins, signaling pathways and networks involved in the development and progression of melanoma, with particular emphasis on elements that are the most promising targets for anticancer therapy
Long-term reduction of short-wavelength light affects sustained attention and visuospatial working memory with no evidence for a change in circadian rhythmicity
Effect of 伪3尾1 and 伪v尾3 integrin glycosylation on interaction of melanoma cells with vitronectin
The metastatic transformation of melanocytes is associated with altered expression of adhesion molecules, including 伪v尾3 and 伪3尾1 integrins. Integrin 伪v尾3 is a primary vitronectin (VN) receptor, while both integrin types take part in adhesion to VN when they are in complex with uPAR. Although their role in melanoma cell interaction with VN is of great interest, the influence of N-oligosaccharides attached to these glycoproteins is still unappreciated. The present study assesses the role of 伪v尾3 and 伪3尾1 integrins and the influence of their glycosylation status on WM9 and WM239 metastatic melanoma cell interactions with VN. Cell adhesion to and migration on VN were selected as the studied cell behaviour parameters. Functionblocking antibodies and swainsonine (SW) treatment were used in these tests. Both cell lines interacted with VN in an integrin-mediated but cell-line-specific manner. In WM9 cells, migration was not completely inhibited by antibodies against 伪3尾1 or 伪v尾3 integrins, suggesting the participation of other VN receptors. In both cell lines in coprecipitation test the formation of an integrins/uPAR complex was shown. In the presence of SW formation of the complex did not occur, suggesting the participation of glycosylation in this proccess. Additionally, the adhesion properties of WM9 cells were changed after SW treatment. Our results suggest that in these two metastatic cell lines integrin-linked N-oligosaccharides influence the VN adhesion receptor activity and function
Wp艂yw wczesnych zaka偶e艅 na ekspresj臋 moleku艂 CD11a, CD11b, CD11c, CD18, CD54 i CD62L na powierzchni neutrofili i monocyt贸w obwodowej krwi 偶ylnej u wcze艣niak贸w
INTRODUCTION: Cell adhesion molecules on neutrophils and monocytes play an important role in the immunity of newborns. MATERIAL AND METHODS: Eighty-two premature infants (47 with early-onset infection and 35 without infection, 37 male and 45 female, 40 delivered vaginally and 42 by Caesarean section) between the 3rd and 7th day of life were assessed for the expression rate of CD11a, CD11b, CD11c, CD18 CD54 and CD62L on granulocytes and monocytes using a Becton Dickinson FACS Canto II flow cytometer. Both groups were analysed for sex, body weight, gestational age, type of delivery and infection, and correlations between adhesion molecules were identified. RESULTS: Preterm infants with infection had a significantly higher mean CD62L level than preterm infants without infection. There was also a positive correlation between gestational age and CD11b and CD11c, as well as correlations between CD11b and CD11c, CD11b and CD54, and CD11c and CD54U. In preterm infants without infection, there was a significant correlation between body weight and CD11a level, and correlations between CD11a and CD18, as well as CD11a and CD54. The sex of the preterm infants and type of delivery in both groups had no significant effect on the mean levels of the analysed molecules. There was no significant relationship between the expression of the analysed molecules and the CRP concentration and platelet count in preterm infants with infection. CONCLUSIONS: 1. Early-onset infection in premature infants promotes increased expression of the CD62L molecule, which despite the lack of correlation with the CRP concentration and platelet count may prove useful in the diagnosis of infections. 2. CD11b expression in preterm infants with infections is affected by gestational age, while the expression of CD11a in preterm infants without infections is correlated with body weight. 3. Expression of the analysed molecules in premature neonates does not depend on sex or type of delivery.WST臉P: Moleku艂y adhezji kom贸rkowej na neutrofilach i monocytach odgrywaj膮 wa偶n膮 rol臋 w odporno艣ci noworodk贸w. MATERIA艁 I METODY: U 82 wcze艣niak贸w (47 z zaka偶eniem wczesnym i 35 bez zaka偶e艅; 37 p艂ci m臋skiej i 45 偶e艅skiej; 40 urodzonych si艂ami natury i 42 ci臋ciem cesarskim) mi臋dzy 3 a 7 dob膮 偶ycia dokonano oceny odsetka ekspresji CD11a, CD11b, CD11c, CD18, CD54 i CD62L na granulocytach i monocytach krwi cytometrem przep艂ywowym Becton Dickinson FACS Canto II, z uwzgl臋dnieniem p艂ci, masy cia艂a, wieku p艂odowego wcze艣niak贸w, typu porodu i zaka偶enia, oraz okre艣lono wzajemne korelacje mi臋dzy moleku艂ami. WYNIKI: U wcze艣niak贸w z zaka偶eniem stwierdzono istotne statystycznie zwi臋kszenie 艣redniego odsetka CD62L ni偶 u wcze艣niak贸w bez zaka偶e艅, dodatnie korelacje mi臋dzy wiekiem p艂odowym a CD11b i CD11c oraz wzajemne korelacje mi臋dzy CD11b i CD11c, CD11b i CD54 oraz CD11c i CD54. U wcze艣niak贸w bez zaka偶e艅 wykazano znamienn膮 zale偶no艣膰 mi臋dzy mas膮 cia艂a a CD11a oraz korelacje mi臋dzy CD11a i CD18 oraz CD11a i CD54. P艂e膰 wcze艣niak贸w i typ porodu w obu grupach nie mia艂y istotnego wp艂ywu na 艣rednie warto艣ci badanych moleku艂. Wykazano brak istotnych zale偶no艣ci mi臋dzy ekspresj膮 badanych moleku艂 a st臋偶eniem CRP i liczb膮 p艂ytek krwi u chorych wcze艣niak贸w. WNIOSKI: 1. Wczesne zaka偶enia u wcze艣niak贸w sprzyjaj膮 zwi臋kszeniu ekspresji moleku艂y CD62L, co mimo braku korelacji ze st臋偶eniem CRP i liczb膮 p艂ytek krwi mo偶e dowodzi膰 przydatno艣ci oznaczania tej moleku艂y w diagnostyce zaka偶e艅. 2. Na warto艣膰 ekspresji CD11b u wcze艣niak贸w z zaka偶eniem wp艂ywa wiek p艂odowy, a na CD11a masa cia艂a u wcze艣niak贸w bez zaka偶e艅. 3. Ekspresja badanych moleku艂 u wcze艣niak贸w nie zale偶y od ich p艂ci i typu porodu