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Logg inn Registrer ny bruker. All Rights Reserved is part of Write-On. Johaug og Bjørgen i bikini Close-up footage showing a half-naked Marit Bjørgen and other Norwegian cross-country skiers changing has provoked a string of complaints. Norske nyheter på engelsk fra Norge. The Foreigner er en engelskspråklig internett avis for de som bor eller som er interessert i Norge. Nevertheless, we are used to stripping off due to sports conditions, so we are not shy.

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Bruiser Jorge Luis Abreu Floor Manager Diana Donaldson Benedict's Secretary Shae Wilson Ticket Agent Rest of cast listed alphabetically: Don Abernathy Casino Gambler uncredited Karen-Marie Ali Hotel Patron uncredited Bonnie Joy Ashley High Roller uncredited Cathy Beasley Gambler uncredited Adam Best Conventioneer uncredited Yuki Bird Casino Gambler uncredited Palmer Bocim Cafe Patron uncredited Antonio D.

Casino Patron uncredited Felix J. Gambler uncredited Michael Bravo Mechanic uncredited Greg Brown Casino Patron uncredited Jeff Bullock Gambler uncredited Paul X. Reporter uncredited Nicole Chauvet Upscale Gambler uncredited Jaden Christopher High Roller uncredited David Cohen Gambler uncredited Natalie Cohen Received : 23 December Revised : 08 May Accepted : 01 June Published : 11 July Issue Date : 09 February Cells Journal of Cellular Physiology BMC Cancer Cancer Letters PLOS Genetics Advanced search.

Skip to main content. Register your interest. Subjects Cancer therapy. Access through your institution. Buy or subscribe. Change institution. Access options Subscribe to Journal Get full journal access for 1 year 1. Rent or Buy article Get time limited or full article access on ReadCube. Figure 1. Figure 2. Figure 3. The measurements of the cell growth rate were obtained using a CCK-8 kit.

The experiments were repeated three times. D Representative photographs of the tumour-bearing mice and the excised tumours at 30 days post-implantation. In OS, the up-regulation of miRa-5p could promote cell proliferation and tumour growth.

However, the regulatory mechanism for this is not clear yet. Therefore, we performed bioinformatics analyses to search for miRa-5p-targeted genes.

Through the combination of these bioinformatics prediction methods and a literature review, we found that PIAS3 a specific inhibitor of activated STAT3 and p27 a negative cell-cycle regulator are likely targets of miRa-5p. Accordingly, the over-expression of miRa-5p suppressed approximately Compared with the control, the over-expression of miRa-5p resulted in a significant decrease in the expression of PIAS3, while the knock-down of miRa-5p led to an increase in PIAS3 expression.

The above results demonstrated that miRa-5p regulated PIAS3 expression only via a translational inhibition mechanism, rather than by affecting its mRNA stability.

In addition, as shown in Fig. One representative image of three reproducible results is shown for the western blot assay. The over-expression of miRa-5p led to a 1. It was confirmed that PIAS3 could be targeted by miRa-5p, while it was not clear whether the predicted p27 could be another target of miRa-5p. Mutagenesis of the predicted miRa-5p binding sites restored the luciferase expression. Nevertheless, the results in Fig. Compared with the control, the over-expression of miRa-5p resulted in a significant decrease in the expression of p27, while the knock-down of miRa-5p led to an increase in p27 expression Fig.

The correlation between miRa-5p and p27 was further examined in OS tissues. The overall p27 protein level in OS samples was Accordingly, these results revealed that miRa-5p could regulate p27 expression only via a translational inhibition mechanism.

NS: no significant change. As a tumour suppressor, p27 influences cell cycle progression by negatively regulating the activity of cyclin-dependent kinases. In contrast, in anti-miRa-5p-transfected cells, an increase in the G1-phase cell population As shown in Figs 4G and S5 , an obvious decrease in the S-phase cell population S4 , suggesting that the ectopic over-expression of p27 was able to delay the G1-S phase transition of the cell cycle caused by miRa-5p over-expression.

Taken together, these data indicate that miRa-5p functions by targeting p27 in OS. S2 , we attempted to use miRa-5p as a therapeutic target in OS. We designed a miRa-5p AMO to inhibit miRa-5p expression in the nude mouse xenograft model of human osteosarcoma.

The anti-tumour activity of the miRa-5p AMO was then assessed in vivo. C The volumes of the xenograft tumours in nude mice determined at 9, 12, 15, 18, 21, 24, 27, 30, and 33 days tumours transplantation, followed by intratumoral treatment with miRa-5p AMO on day 9 after tumours transplantation.

D The weights of the xenograft tumours in nude mice measured at 33 days after tumours transplantation, followed by intratumoral treatment with miRa-5p AMO on day 9 after tumours transplantation. E A representative photograph of tumour-bearing mice 33 days after tumours transplantation and intratumoral injection with miRa-5p AMO. F A representative photograph of tumours excised from tumour-bearing mice, 33 days after tumours transplantation and intratumoral injection with miRa-5p AMO.

In the present study, we demonstrated that miRa-5p was up-regulated in OS patient tissues and cell lines and might promote OS cell proliferation.

This result was further supported by the findings showing that the over-expression of miRa-5p induced tumour growth and the knock-down of its expression had the opposite effect in a nude mouse xenograft model of OS. Previous studies have demonstrated that miRa-5p is involved in the progression of several cancers, including hepatocellular carcinoma HCC , small cell carcinoma of the cervix SCCC , gastric cancer, multiple myeloma and melanoma 21 , 22 , 23 , 24 , Interestingly, miRa-5p exerts diverse and conflicting biological effects in several cancers depending on the specific cell type and context.

Our results not only suggested an oncogenic role of miRa-5p in the development of OS but also provided a potential gene therapeutic target for OS. Based on three bioinformatics analyses, nineteen genes were predicted to be targets of miRa-5p, as shown in Supplementary Table 3. Kunita A, et al. Additionally, Klotho and ApoE have been reported as the targets of miRa-5p in gastric cancer and melanoma, respectively 23 , On the basis of the inverse correlation between the expression of miRa-5p and the protein levels of PIAS3 and p27 in OS patient tissues and other evidence, we considered that the pathway of miRa-5p targeting both PIAS3 and p27 is a possible mechanism that contributes to tumour growth in OS.

The over-expression of miRa has been reported in OS cell lines In this study, we found that the fold increases in the expression of miRa and miR were similar to that of miRa-5p in OS patient tissues data not shown , but the serum levels of miRa and miR in OS patients did not show significant differences Furthermore, we validated that miRa-5p could target p27 and affect cell cycle progression in OS.

Our findings elucidated that it is likely miRa-5p, acting as an oncogenic miRNA, that could lead to the loss of p27 and regulate the cell proliferation and cell cycle in OS. Cao et al. For newly diagnosed osteosarcoma patients, in order to clear the subclinical lesions more thoroughly and reduce the risk of recurrence, the current treatment usually consists of the combination of chemotherapy and radiation to inhibit growth before surgery, which inevitably results in severe side effects 2.

Since miRNAs can produce global effects on a series of genes, miRNAs might be ideal agents for a combined tumour therapy alternative to chemotherapy and radiation. Recent studies have shown that the delivery of miR by atelocollagen can significantly suppress the metastasis of osteosarcoma 7 , and various strategies for the delivery of miR mimics exhibit remarkable inhibition effects in mouse models of neuroblastoma, non-small-cell lung cancer NSCLC and colon cancer, among others.

In addition, phase I clinical trials of a liposome-based miR drug for hepatocellular carcinoma patients are currently under way 42 , Because cell proliferation is a prerequisite for metastasis, appearing as the most common cause of OS recurrence and death, we speculate that therapies targeting miRa-5p might be useful for OS treatment due to the dual targeting of miRa-5p to PIAS3 and p In this study, our results further revealed that reducing the miRa-5p level by biologically stable antisense oligonucleotides of miRa-5p significantly inhibited the growth of osteosarcoma tumours in nude mice, indicating that the administration of miRa-5p inhibitors could complement or improve current OS therapeutic strategies.

In conclusion, we identified that miRa-5p was significantly up-regulated in OS patient tissues and that its expression was inversely correlated with PIAS3 and p27 protein expression in OS. Additionally, a miRa-5p-targeted inhibitor could significantly enhance PIAS3 and p27 expression and ultimately suppress the tumour growth in a xenograft model of OS, which represents a potential therapeutic approach that may be valuable for OS therapy.

China from to The surgically removed tissues were quickly frozen in liquid nitrogen until analysis. A signed informed consent was obtained from each patient. And the clinical information of these patients is listed in Supplementary Table 1. The investigations were conducted according to the Declaration of Helsinki principles. Ville Miettunen of Finland crashes out in the men's moguls. Russia's Sergey Volkov tumbles during the men's moguls. Australia's David Morris falls February 10 during a training session for the men's aerials competition.

Dale Begg-Smith of Australia crashes in men's moguls. Jussi Penttala of Finland crashes in men's moguls. Chilean skier Noelle Barahona lies on the snow after she fell during the downhill portion of the super-combined event on February Great Britain's Jack Whelbourne, right, falls as he competes in the 1,meter short track final on February Snowboarder Otso Raisanen of Finland crashes during slopestyle training on February Short track speedskater Jessica Smith of the United States falls as Valeriya Reznik of Russia skates past her during the meter preliminaries on February South Korea's Sin Da-Woon, left, falls as he competes in the 1,meter short track semifinals on February South Korea's Lee Han-Bin falls during the 1,meter semifinals.

The Netherlands' Sanne van Kerkhof, right, falls next to Italy's Lucia Peretti as they compete in the 3,meter short track relay February Canada's Charles Hamelin celebrates after winning the 1,meter final on February Severin Freund of Germany crashes upon landing during the first round of the men's normal hill ski jumping event on Sunday, February 9. Freund's crash continues. Jason Brown of the United States falls February 9 while competing in the men's free skate portion of the team figure skating event.

Canada's Kaetlyn Osmond falls as she performs in the women's free skate portion of the team figure skating event. Canada's Megan Heinicke, left, and Poland's Monika Hojnisz collapse in the snow after competing in the 7. Biathlete Ekaterina Shumilova of Russia collapses on the snow February 9 after crossing the finish line in the women's 7.

Biathlete Tora Berger of Norway collapses at the end of the women's 7. Simon Ammann of Switzerland reacts after landing his final jump in the men's normal hill ski jumping event February 9.

Italian skier Christof Innerhofer reacts after winning the silver medal in the men's downhill February 9. Dario Cologna of Switzerland won the men's skiathlon February 9.

Yekaterina Smolina of Russia slides on the ice after being checked by Anja Weisser of Germany during their ice hockey game February 9. Swiss skier Dario Cologna, foreground, lies on the snow alongside other competitors in the men's skiathlon. Callum Smith of Great Britain rests at the finish line of the men's skiathlon. Slovenia's Robert Kranjec lies in the snow after falling in the men's normal hill ski jumping event Saturday, February 8.

Japan's Mao Asada falls as she performs in the team figure skating event on February 8. Slovenia's Robert Kranjec falls while competing in the men's normal hill ski jumping event.

Dmitry Malyshko of Russia collapses in the snow after competing in the kilometer biathlon sprint. Switzerland's Nadja Jnglin-Kamer crashes near the finish line February 8 during a training run for the women's downhill. Jnglin-Kamer is seen near the finish line after her crash. Jeremy Abbott of the United States falls as he performs in the team figure skating event.

Tarjei Boe, a biathlete from Norway, falls to the ground after competing in the kilometer sprint. Norway's Hedvig Wessel takes a tumble during qualifying for the women's moguls event on February 8. Dutch speedskater Jorrit Bergsma is seen after the men's 5,meter race on February 8. Hedvig Wessel of Norway crashes out in the women's moguls on February 8. Snowboarder Lucien Koch of Switzerland falls during the men's slopestyle semifinals on February 9.

Germany's Nathalie Weinzierl takes a fall during the team figure skating event. South Korean ski jumper Choi Heung-Chul falls while competing in the men's normal hill event February 8. Falling down in Sochi. Photos: Falling down in Sochi. Aiming for Gold. Sochi The verdict. Sochi's top sporting moments. The athletes on show in Sochi provided moments of drama and destiny that captured the imagination and settled in the collective memory.

Here's Sochi's real winner. Russia may have topped the medals table at the first Winter Olympics it staged, but which country was most successful per capita? Sochi: The coolest gear on show. From eye-popping helmet designs to F1-influenced bobsleigh, the Sochi offered a bewildering array of technological innovation. Sochi's artistic ending.

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