Some of America’s super-corps have remembered how the US became the dominant global technology force it is, and have vowed to use innovation over threats to counter Chinese dominance in 5G markets.…
Job Alert This week we've got job openings from all over the globe to tempt you, your friends or your past colleagues back into work, or indeed into new ventures.…
Technical folks looking to improve web privacy haven't been able to decide whether sound beyond the range of human hearing poses enough of a privacy risk to merit restriction.…
Annual Las Vegas hacker gathering DEF CON has officially called off its physical conference for this year due to the coronavirus pandemic.…
“The most difficult part was persuading our children that they had the freedom to make anything they wanted,” writes mom Anam Ahmed at Let Grow. (Click here!) …Like most kids, my children live prescheduled lives (at least they did in “the time before”). At school, someone tells them when to play outside and when to […]
Parents, kids: Fear not the silica gel pack. Sure it says DO NOT EAT and THROW AWAY. But you should only follow one of those rules. Instead, save the packs and use them a whole lot of ways: Place them on the car dashboard by the windshield to keep it from fogging up. […]
Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.
Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood. Neuropeptide Y (NPY) and NPY receptors represent a highly conserved, stress-activated system involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-β1 was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R activation and function in liver cancer. The TGF-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.
BACKGROUND The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONS Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).
The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant prostate cancer (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane protein that acts as a substrate for SRC family kinases (SFKs), is overexpressed in a subset of CRPC. Notably, CDCP1 cooperates with the loss of the tumor suppressor gene PTEN to promote the emergence of metastatic prostate cancer. Mechanistically, we find that androgens suppress CDCP1 expression and that androgen deprivation in combination with loss of PTEN promotes the upregulation of CDCP1 and the subsequent activation of the SRC/MAPK pathway. Moreover, we demonstrate that anti-CDCP1 immunoliposomes (anti–CDCP1 ILs) loaded with chemotherapy suppress prostate cancer growth when administered in combination with enzalutamide. Thus, our study identifies CDCP1 as a powerful driver of prostate cancer progression and uncovers different potential therapeutic strategies for the treatment of metastatic prostate tumors.
Linda McMahon is running for the US Senate in Connecticut. For twenty (20) years, she ran World Wrestling Entertainment (WWE) with her husband, Vince McMahon. A few years ago, a documentary film examined the WWE's celebration of violence against women. Her campaign doesn't want Connecticut voters to see that film. Watch these excerpts from the film to see why. Continue reading
After being elected in 2008 on "hope and change", "change you can believe in", and "change the way Washington works", President Obama now says that he cannot change Washington from the inside? Then why should we re-elect him in 2012? Continue reading
Democratic presidential candidate Sen. Bernie Sanders explains why he thinks he thinks his record of “strong and bold leadership” could help him best candidate Hillary Clinton in the Democratic primary. Continue reading
Senator Bernie Sanders does not think that Hillary Clinton can stand up and fight for the middle class. Continue reading
Even though Corporate America has anointed Hillary Clinton as its next President, Senator Bernie Sanders' populist message is already in a week's time raising individual contributions totaling millions of dollars from hundreds of thousands of people! Continue reading
“Thank you all very much for being here and for all the support that you have given me over the years: as the mayor of this great city, as Vermont’s only congressman and now as a U.S. senator. Thanks also … Continue reading
Chuck Todd tells Andrea Mitchell that Hillary Clinton will win the African-American and Hispanic vote in spite of the intellectual appeal of Bernie Sanders to liberal white voters Continue reading
An Offer in Compromise is an agreement between the taxpayer and the government that settles a tax liability for payment of less than the full amount owed. The Internal Revenue Service will generally accept an Offer in Compromise when it … Continue reading
Berlin needs an independent candidate on its Town Council to counter and prevent the dominance of a major political party from unilaterally imposing its agenda and will on the citizens of Berlin. Our Town Council has been voting along strict party lines on key issues even though members pledged to reach across the aisle. It has dismissed or circumvented the results of referendums, reducing them to mere dog-and-pony shows. Berlin has more unaffiliated voters than those of the two major parties. Let's petition, nominate, and place on the ballot an independent candidate to represent these citizens and prevent the control of our Town by the dominant party on the Town Council. If interested, please contact us: berlinctpropertyownersassn@gmail.com. Continue reading
Eyewitness News has learned that the Berlin High School football recruiting scandal may have cost Berlin taxpayers tens of thousands of dollars. Continue reading
Bernie Sanders and Jane Sanders are mere actors serving as pressure valves which release from time to time all excess heat emanating from failed policies, scandals, and the worsening economic conditions, so that a catastrophic systems’ collapse can be prevented. They are sheepdogs for Hillary Clinton, preventing progressives from supporting a third party progressive candidate and to herd them back into the corral of the Democratic Party. Continue reading
People from outside the major parties who are pursuing elected office are exercising their First Amendment rights, and calling them spoilers is an act of “political bigotry” that should never be tolerated by the American people, civil rights champion and four-time presidential candidate Ralph Nader told “Democracy Now!” Nader’s comments come one week before the 2016 nominees’ first presidential debates, which the Commission on Presidential Debates—a private corporation owned and controlled by the Republican and Democratic parties—announced Friday will exclude both Jill Stein of the Green Party and Gary Johnson of the Libertarian Party. Continue reading
This is the natural progression, this is the natural endgame of the Bill Clinton Democratic Party when he decided to change the Democratic Party from a party of workers and blue-collar people to a party of Silicon Valley and Wall Street. And Democrats have to acknowledge that. And if they don't, they ain't going nowhere. Continue reading
The sweetheart deal that Governor Malloy and his fellow Democrats in the General Assembly cut with state employee unions, the so-called SEBAC agreement, is protected by contract for a full decade —leaving meaningful reforms waaay down the road. The contract is the mother of all can-kicks. Continue reading
I remember reading somewhere that if the earth was shrunk to the size of a pool ball, or a pool ball expanded to the size of the earth, the earth would be the smoother of the two.
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4.10pm on 7/4/16 Fujifilm X-T1 XF 10-24mm f/4 R OIS 14.5mm f/5.6 1/125 aperture priority 0.7 average 200 no RAW Camera Raw Photoshop CC (2014) none 2x1 (& stretched a bit) |
A fundraising initiative spearheaded by Canadian comic retailers and creators aims to auction off items in order to support their struggling industry.
The post Zdarsky, Fabok, & more ask you to “Be Our Heroes” for Canadian retailers appeared first on The Beat.
As the 2015 Atlantic hurricane season gets underway, communities in severe weather-prone regions are anxiously tracking pending storms and working to create effective disaster response plans. IBM, through its strategic alliance with The Weather Company and its global B2B division WSI, today announced a new emergency management solution that features sophisticated analytics and the use of real-time weather data to help communities predict and plan for natural disasters far more accurately and deploy the right resources in advance.
If we want to answer any question like, how should we live, what should we do, what should we work on, what should we change, quit or start (not should really but could) it’s always best to do so from your values. If you aren’t sure about your personal values, now could be a great time to explore, clarify and prioritize your values so you can tap into your own source of wisdom and motivation, and answer all those ‘should’ questions for yourself.
DRESSING DOWN – Ex-AFL coach Dean Laidley’s arrest snaps are leaked to the press. Public interest or public shaming? Plus, Aussie journo Mark Di Stefano gets caught “hacking” the competition, a breakfast TV cooking segment gets too hot to handle, and West Virginia’s governor adds to the swear jar.
IBM MTN, a leading African telecommunications provider, Wageningen University (WU) in the Netherlands and Prodapt, today announced they are harnessing IBM Internet of Things (IoT) technology as part of the MTN Connected Wildlife Solution. The solution will help predict threats and combat the poaching of endangered rhinos at Welgevonden Game Reserve in South Africa, with the intent to expand the solution to other reserves in future.
The Weather Company, an IBM Business and Rogers Media announced today an agreement to provide weather information and content customized specifically for the Canadian market. With this agreement, The Weather Company will provide in-depth weather data and forecasts, as well as curated content, across Rogers Media properties. In turn, Rogers Media will provide locally relevant articles, photos and video content across the Canadian versions of The Weather Channel app and website (weather.com) to provide residents with the most pertinent information possible. The Weather Company and Rogers Media will also align to enhance advertising across both companies’ properties, with Rogers leveraging its ad sales capabilities to monetize The Weather Channel properties in Canada.