first_img Source:https://moffitt.org/newsroom/press-release-archive/2019/moffitt-cancer-center-researchers-identify-mechanism-of-resistance-to-braf-inhibitors-in-melanoma/ Reviewed by Kate Anderton, B.Sc. (Editor)Apr 15 2019Melanoma is one of the most aggressive types of skin cancer, but recent advances in targeted therapies have improved the prognosis for many patients. Unfortunately, for some patients these positive outcomes are not long lasting, due to the development of drug resistance and tumor recurrence. Moffitt Cancer Center researchers have discovered a mechanism by which melanoma cells become resistant to the commonly used drugs that target the BRAF protein and its signaling pathway. Their study was published online today by the journal Cancer Research.One of the most common genetic mutations found in melanoma is alteration of the BRAF gene. Mutations in BRAF are found in approximately 50 percent of all melanomas, leading to increased cell proliferation and survival. Several drugs are available that target BRAF and a downstream gene named MEK that cooperates with BRAF in cancer development. These drugs have resulted in significant improvements in patient outcomes; however, many patients eventually develop drug resistance.Related StoriesNuclear medicine imaging assesses melanoma patients’ response to immunotherapyNew liquid biopsy technique used to assess melanoma progressionGroundbreaking AI technology could predict melanoma metastasisMoffitt researchers conducted a series of laboratory experiments with cell lines and mouse models to determine how melanoma becomes resistant to these commonly used drugs. They discovered that melanoma cells that are resistant to BRAF inhibitors undergo a similar response mechanism as cells treated with stress-inducing factors, such as UV radiation and low oxygen. During each of these conditions, the cells increased expression of the protein histone deacetylase 8 (HDAC8).HDACs are proteins that regulate the expression level and activity of other proteins within the cell. HDACs are often deregulated in cancer and several drugs that target HDACs are approved for the treatment of different types of cancer. The researchers found that HDAC8 stimulated the activity of the AP-1 transcription factor that subsequently increased the expression of genes that are involved in cell motility and invasion.”Our work provides the first evidence that HDAC8 activity is increased in responses to multiple, diverse cellular stresses, and that this in turn initiates a transcriptional program that is associated with increased melanoma cell survival,” explained Keiran Smalley, Ph.D., director of the Donald A. Adams Melanoma and Skin Cancer Center of Excellence at Moffitt.This link between HDAC8 and drug resistance suggested to the researchers that drugs targeting HDACs may be able to overcome cellular resistance mechanisms to BRAF inhibitors. The researchers performed a series of mouse experiments and found that co-treatment with both HDAC and BRAF inhibitors inhibited melanoma tumor growth better than either agent alone.The researchers hope their work will lead to clinical studies that will examine the potential of HDAC inhibitors to prevent the development of drug resistance in melanoma. “These findings provide a strong rationale to pursue the development of more selective and potent HDAC8 inhibitors for future evaluation as drugs that can limit phenotype switching and therapeutic escape in melanoma,” said Smalley.last_img read more

first_img Source:BfR Federal Institute for Risk Assessment Reviewed by Kate Anderton, B.Sc. (Editor)Jul 16 2019Carbofuran is a plant protection product which can be used against certain insects, mites, ticks and nematodes. On the basis of the amount of the carbofuran residues and estimated dietary intake of red chilies, an exceedance of the acute reference dose (ARfD) is not to be expected for children or adults. The ARfD describes the quantity of a substance per kilogram of body weight that consumers can ingest with their food in one meal or in several meals spread over one day without any recognisable effect on health. The ARfD is therefore a limit value for risk assessment in relation to short-term intake.Other plant protection products were also detected in the 10 samples from the manufacturer (2308 grams in total), but their contribution is negligible in relation to carbofuran so that no health risk is to be expected from them either. As the number of samples is small, the results cannot be generalised for red chili.last_img read more

Provided by International Communication Association This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Jin Kang (Pennsylvania State University), and Lewen Wei (Pennsylvania State University) will present their findings at the 68th Annual Conference of the International Communication Association in Prague, Czech Republic. The researchers conducted an online survey with a total of 106 undergraduate students who had both fake Instagram (Finsta) and real Instagram (Rinsta) accounts. In the survey, the students were asked how Finsta was different from Rinsta in two different ways. One, was administered in an existing valid measure that taps onto four different user motivations, archiving, self-presentation, escapism and social interaction. In the Second, students elaborated their answers in an open-ended format.The data analyzed revealed Rinsta was rated higher for escapism and archiving. One might expect for the Finsta to be rated higher on these two motivations; higher on escapism as there are more pictures being updated from other users to distract their attention and higher on archiving as users can post pictures anytime. One potential explanation is that Finsta is just “too real.” As users post pictures that closely reflect the reality, Finsta may constantly remind users of their actual reality, rather than allowing them to immerse themselves in an illusion that “life is perfect,” as portrayed by other users.Research on self-presentation on social media is ever expanding. Finsta is another venue for individuals to express different aspects of the self to the public. This study shows that there are two things that make Finsta unique: 1. It is an agreed-upon place for everyone to be inappropriate and silly and 2. Most users are doing the opposite of the normally seen positive self-presentation on other platforms. If individuals display their best self (e.g., ideal-self) on places like Facebook, individuals are displaying their worse self on Finsta.”We showed exactly how Rinsta and Finsta are different in terms of user motivation. Contrary to popular belief, individuals used Rinsta to express one’s actual-self and used Rinsta to escape from reality. On Finsta, users posted inappropriate and silly pictures not just for self-expression, but also posted these pictures as a way to bond with their friends, that is, to make their friends laugh and to archive the crazy moments they shared together, said Kang. “Also, at least in our study, we found that creating Finsta mainly happened among female students which also raises an interesting future question of if female users have stronger need to express an inappropriate side of themselves than male users.””Let Me Be at My Ugliest: Instagram Users’ Motivations for Using Finsta (Fake Instagram),” by Jin Kang and Lewen Wei; to be presented at the 68th Annual International Communication Association Conference, Prague, Czech Republic, 24-28 May 2018. Explore further How teens use fake Instagram accounts to relieve the pressure of perfection Credit: CC0 Public Domain As Instagram is viewed as a place for building the ideal self, some users have created fake Instagram (Finsta) accounts to buck this trend. But are these “fake” accounts really there to express the real, sometimes ugly self, or is there a deeper motivation? A recent study by researchers at Pennsylvania State University, found that users align their real Instagram accounts (Rinsta) with their actual self and to escape from reality, whereas Finsta to foster social bonding. Citation: Motivation for using fake Instagram (Finsta) is not to reveal inappropriate self (2018, April 16) retrieved 18 July 2019 from https://phys.org/news/2018-04-fake-instagram-finsta-reveal-inappropriate.html read more

first_img Related News Tennis 10 Jul 2019 Factbox: Roger Federer versus Kei Nishikori Related News {{category}} {{time}} {{title}} LONDON (Reuters) – As Roger Federer prepares to take on Novak Djokovic in Sunday’s Wimbledon final, he knows there is little he can do now to improve his chances of winning a 21st Grand Slam title — all the work has been done.”This is like a school,” the Swiss 37-year-old said. “The day of the test, you’re not going to read… many books that day. You don’t have the time anyhow.”It’s quite clear the work was done way before. It’s been a rock solid year (for me)… the stars are aligned right now. From that standpoint I can go into the match very confident.”With eight Wimbledon titles in his locker, Federer has every right to be confident. But Djokovic is himself a four-times champion, and can equal the great Bjorn Borg with victory for a fifth crown.center_img Tennis 10 Jul 2019 Highlights: Wimbledon day nine Tennis 09 Jul 2019 Pella downs Raonic to reach first major quarter-final More importantly, the Serb beat Federer in the final here in 2014 and 2015.”We all know how good he is anywhere, but especially here,” Djokovic said of the Swiss.”This surface complements his game very much. He loves to play very fast. Takes away the time from his opponent. Just doesn’t give you any same looks.”He just rushes you to everything. So for players maybe like Nadal or myself that like to have a little more time, it’s a constant pressure that you have to deal with.”I’ve played with Roger in some epic finals here a couple years in a row, so I know what to expect. Of course, I’m going to be excited and nervous and everything that you can think of.”I’m going to do my best to control that in some way and be able to portray my best tennis in a balanced, hopefully, state throughout the match.”Federer was sublime in beating Rafa Nadal in Friday’s semi-final, whereas Djokovic was not tested nearly so much against Roberto Bautista Agut.The Swiss will need to match those heights again on Sunday to end a four-match losing streak against Sunday’s opponent.It would be unwise to bet against him managing that, but many commentators make top seed Djokovic the favourite.”For Sunday’s match, it’s hard to not see Novak as a pretty strong, clear favourite for the title because Federer’s weapon is probably his serve, and Novak finds a way to neutralise that,” said former world number one Mats Wilander.”Federer’s serve is not that hard, but well placed… so Novak will get a play on most serves and then he’s in the rally straight away.”If you look at everything, then you say that the weakest part of Djokovic’s game is as good as Federer’s, he’s stronger in a couple of places such as movement, the return of serve and the backhand. I think it’s going to be tough. I think Djokovic is going to feel pressure, that’s for sure, but then for Federer it might be his last chance.” (Editing by: Toby Davis)last_img read more