| 231. |
- Wegiel, Barbara, et al.
(författare)
-
Cystatin C is downregulated in prostate cancer and modulates invasion of prostate cancer cells via MAPK/Erk and androgen receptor pathways
- 2009
-
Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 4:11
-
Tidskriftsartikel (refereegranskat)abstract
- Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2) and androgen receptor (AR) in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (p<0.001) and there was a statistically significant inverse correlation between expression of cystatin C and MMP2 (r(s) (2) = -0.056, p = 0.05). There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR) tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis.
|
|
| 232. |
- Wegiel, Barbara, et al.
(författare)
-
Interleukin-6 activates PI3K/Akt pathway and regulates cyclin A1 to promote prostate cancer cell survival
- 2008
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 122:7, s. 1521-1529
-
Tidskriftsartikel (refereegranskat)abstract
- Interleukin-6 (IL6) is a growth and survival factor in human prostate cancer (PCa) cells with aggressive phenotypes and has been implicated in the progression of hormone refractory PCas. In the present study, we characterized the IL6-triggered PI3K/Akt and MAPK/Erk signaling. We identified the A-type cyclin, cyclin A1 as an important downstream target of PI3K/Akt. Treatment of cells with PI3K inhibitor or cotransfection with a vector expressing wild-type PTEN decreased cyclin A1 promoter activity. Cyclin A1 promoter activity and its expression were upregulated by constitutively active myristoylated Akt and were downregulated by dominant negative Akt in response to IL6 stimulation. LNCaP cells overexpressing cyclin A1 are resistant to camptothecin-induced apoptosis. Conversely, targeted knockdown of cyclin A1 via shRNA in LNCaP IL6+ cells resulted in decreased survival after treatment with camptothecin. This suggests that cyclin A1 is an important downstream target of PI3K/Akt that transduces survival signals in response to IL6 stimulation. Xenograft tumors generated from LNCaP-IL6+ cells expressing IL6 had higher levels of cyclin A1 and had rapid tumor growth compared to LNCaP xenograft tumors. Taken together, IL6 might utilize PI3K/Akt and cyclin A1 to promote tumor cell survival in PCa. (c) 2007 Wiley-Liss, Inc.
|
|
| 233. |
|
|
| 234. |
- Wegiel, Barbara, et al.
(författare)
-
Multiple cellular mechanisms related to cyclin A1 in prostate cancer invasion and metastasis
- 2008
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:14, s. 1022-1036
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cyclin A1 is a cell cycle regulator that has been implicated in the progression of prostate cancer. Its role in invasion and metastasis of this disease has not been characterized.METHODS: Immunohistochemistry and cDNA microarray analyses were used to assess protein and mRNA expression of cyclin A1 and proteins with roles in metastasis, including vascular endothelial growth factor (VEGF), metalloproteinase 2 (MMP2), and MMP9, in human prostate cancer. Transient transfection and infection with viral vectors expressing cyclin A1 and short hairpin RNA (shRNA) targeting cyclin A1 were used to study the effects of altered cyclin A1 expression in PC3 prostate cancer cells. The BrdU assay, annexin V staining, and invasion chambers were used to examine cyclin A1 effects on proliferation, apoptosis, and invasion, respectively. The role of cyclin A1 and androgen receptor (AR) in transcription of VEGF and MMP2 was assessed by promoter mutation and chromatin immunoprecipitation. The effect of cyclin A1 expression on tumor growth and metastasis was analyzed in a mouse model of metastasis. All statistical tests were two-sided.RESULTS: Cyclin A1 protein and mRNA expression were statistically significantly higher in prostate cancers than in adjacent benign tissues. A statistically significant correlation between expression of cyclin A1 and of MMP2, MMP9, and VEGF was observed in prostate tumors from 482 patients (P values from Spearman rank correlation tests < .001). PC3 cells that overexpressed cyclin A1 showed increased invasiveness, and inhibition of cyclin A1 expression via shRNA expression reduced invasiveness of these cells. Eight of 10 mice (80%) bearing PC3 cells overexpressing cyclin A1 had infiltration of tumor cells in lymph node, liver, and lung, but all 10 mice bearing tumors expressing control vector were free of liver and lung metastases and only one mouse from this group had lymph node metastasis (P values from Fisher exact tests < .001). Cyclin A1, in concert with AR, bound to and increased expression from the VEGF and MMP2 promoters.CONCLUSIONS: Cyclin A1 contributes to prostate cancer invasion by modulating the expression of MMPs and VEGF and by interacting with AR.
|
|
| 235. |
|
|
| 236. |
- Welin, Stellan, 1947-, et al.
(författare)
-
Lönsamt utbyte? Embryonala stamceller i gränslandet mellan klinik, universitet och marknad
- 2007
-
Ingår i: Att forma vår framtid. Bioteknikens möjligheter och problem. - Lund : Nordic Academic Press. - 9789189116900 ; , s. 220-234
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Människans livsvillkor har förändrats dramatiskt genom historien i takt med att tekniken utvecklats. Ny kunskap ger nya möjligheter. Föräsndringen kommer med all säkerhet att fortsätta. Men hur?År 2003 förklarade The International Human Gemone Organisation att arbetet med att kartlägga människans arvsmassa hade förverkligats snabbare än förväntat. Därmed öppnades möjligheter att än en gång förändra människans livsvillkor, och på ett mera grundläggande sätt än tidigare. Nu kan vi inte bara förändra vår omgivning utan dessutom med genteknik och nanoteknik påverka vad en människa är. Den möjligheten är en etisk utmaning.Vad betyder riskbedömningar, etik, livsåskådningar och kulturella föreställningar när vi väljer hur den nya tekniken ska användas? Att forma vår framtid belyser dagens arbete med stamcellsforskning och nanoteknik. Texterna diskuterar frågor som hantering av genetisk information, kommersialisering och postgenom forskning i ett globalt perspektiv.
|
|
| 237. |
- Wilhelmsson, Dan, 1969-
(författare)
-
Aspects of offshore renewable energy and the alterations of marine habitats
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several Western European countries are planning for a massive offshore renewable energy (i.e. wind and wave energy) development (ORED) along the European Atlantic coast and in the Baltic Sea. Acknowledging the scale of ORED, there is an increasing interest in the opportunities offered by the fishery closures and the addition of artificial hard substrata. This is in tandem with uncertainties on positive and negative effects on benthic assemblages and specific species of this large-scale deployment of artificial reefs. This thesis focuses on the artificial reef effects of ORED, dealing with benthic assemblages on and in the vicinity of wind- and wave power foundations. Field surveys within offshore wind- and wave farms as well as targeted field experiments were conducted. Results suggest that wind- and wave power foundations can positively affect local abundances and diversity of several species of fish and decapods. Reef profile up to 1 m above the seabed may enhance benthic fish numbers. Structural complexity in the form of single-entrance holes positively affected numbers of edible crab (Cancer pagurus), but no effect on fish was shown. Enhanced structural complexity may, moreover, adversely affect abundances of some species through an induced predation pressure. Micro-habitat use by fish and lobsters (Homarus gammarus) encountered was described, and preferences of the edible crab were shown. Filtrating organisms (i.e. blue mussels Mytilus spp. and barnacles Balanus spp.) seem to be particularly favoured by the conditions on offshore energy installations. The material and orientation of the substrate influenced colonisation patterns of epibiota. Moreover, wind turbines may alter the habitat composition on adjacent seabeds. ORED could induce local ecological changes and put areas and species of conservation interest at risk. If well planned and co-ordinated, on the other hand, ORED could even be beneficial to the subsurface marine environment in several aspects.
|
|
| 238. |
- Wojda, F., et al.
(författare)
-
Laser-driven plasma waves in capillary tubes
- 2009
-
Ingår i: Physical Review E (Statistical, Nonlinear, and Soft Matter Physics). - 1539-3755. ; 80:6
-
Tidskriftsartikel (refereegranskat)abstract
- The excitation of plasma waves over a length of up to 8 cm is demonstrated using laser guiding of intense laser pulses through hydrogen-filled glass capillary tubes. The plasma waves are diagnosed by spectral analysis of the transmitted laser radiation. The dependence of the spectral redshift-measured as a function of filling pressure, capillary tube length, and incident laser energy-is in excellent agreement with simulation results. The longitudinal accelerating field inferred from the simulations is in the range of 1-10 GV/m.
|
|
| 239. |
|
|
| 240. |
|
|
