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Patent
Signal Sciences | Date: 2015-08-28

A system for web application security includes an interface and a processor. The interface of a web server is to receive a pending request made to the web server using an in-line request process. The processor of the web server is to provide information regarding the pending request to an agent process; and in the event that an instruction to block the pending request is received from the agent process at the in-line request process within a time constraint, block the pending request using the in-line request process.


News Article | May 9, 2017
Site: www.prnewswire.com

The legacy WAF market is under delivering. DevOps, agile and cloud have created a huge innovation opportunity, contributing to the rapid growth experienced by Signal Sciences and its success with leading brands, including Under Armour, Etsy, Yelp, WeWork, Tenable, and Duo Security, among many others. In a key indicator of the solution's effectiveness, 95 percent of customers have Signal Sciences installed live in production with automated blocking enabled, a radical improvement over traditional legacy WAF installations averaging approximately 10–15 percent in any level of blocking. With its pioneering web protection platform, Signal Sciences is providing a menu of deployment options, breaking down silos between teams, and helping the entire enterprise operate more efficiently and at scale. "We couldn't afford to let security become a bottleneck for our digital business operations. With Signal Sciences WPP, we can empower our development and operations teams to protect our applications far more effectively, while maintaining the speed and agility demanded by today's customers," said JJ Agha, Director of Information Security, WeWork. "Applications are being created and modified faster than they can be protected. Signal Sciences has created the first, and most efficient, defensive approach to security that I've seen in the market," said Murat Bicer, General Partner at CRV. "In tripling both their revenue - and Fortune 500 customer count - over the last year, the company is becoming a clear leader in the web protection market. There is a growing enterprise community in Southern California, and Signal Sciences is one of the most promising companies to look out for." Signal Sciences WPP is the only solution in the application security market built by practitioners, for practitioners. The platform offers a menu of deployment options, including next-gen WAF and runtime application security protection (RASP) modules, and can also operate as a reverse proxy for legacy applications. "Security continues to slow down the adoption of DevOps and cloud as it grasps for solutions to these new business imperatives. We are changing that," said Andrew Peterson, CEO and Co-Founder of Signal Sciences. "Signal Sciences WPP allows appsec teams to collaborate with their development and operations teams to automate security and release secure software faster, thus enabling their business to run quicker." Signal Sciences Web Protection Platform is available immediately. Please visit here for more information. About Signal Sciences Signal Sciences built its industry-first web protection platform in response to frustrations of trying to use legacy technology while enabling business initiatives like DevOps and cloud adoption. Signal Sciences  works seamlessly across cloud, physical, and containerized infrastructure, providing actionable security prioritization based on where applications are targeted, and blocking attacks without breaking production traffic. The company's clients include Under Armour, Etsy, Yelp/Eat 24, Shutterstock, Prezi and more. The company is headquartered in Venice, CA. For more information, please visit www.signalsciences.com About CRV CRV has been a leading investor in early-stage technology companies for almost half a century. The firm has backed nearly 400 startups in its 47-year history, including foundational companies like Twitter, Zendesk, Amgen, Hubspot, Parametric Technologies, Yammer, EqualLogic and Sonus Networks. Half of the companies CRV has backed have gone public or been acquired. The firm focuses on enterprise, consumer and deep insight bioengineering. CRV has offices in Palo Alto, CA and Cambridge, MA. Visit us at CRV.com and follow us @CRV. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/signal-sciences-debuts-industry-first-web-protection-platform-300453947.html


Snap Inc.’s first earnings report since joining the New York Stock Exchange is expected to reveal an increase in users and ads on the Snapchat app. But whether the usage growth is sizable enough to satisfy investors is the biggest question looming over the young Los Angeles company ahead of its Wednesday announcement. Chatting with friends and watching mini TV-shows on Snapchat shouldn’t appeal to just the app’s core demographic of young users in developed countries — it should appeal to everyone, Snap Chief Executive Evan Spiegel has said. But his team cautions that Snapchat isn’t likely to pick up new users at the exceptional pace of the past. His team has suggested investors judge Snap based on average revenue per user, or its ad income divided by its number of users. With 158 million daily users at the end of 2016, or 48% more than the end of 2015, Snap generated about $1.05 in ad sales per individual. Revenue is expected to increase this year because Snap has a bigger ad sales team, new types of ads and more ways for people to buy ads. Brands as big as McDonald’s and as small as independent wedding planners can pitch to Snapchat users through videos, animations and graphics. Financial analysts at stock brokerages expect average revenue per user to double to $2.10 by the end of 2017 and reach five times as high during the following year. Though investors do desire sales growth, they’ve been conditioned by Snapchat predecessors such as LinkedIn, Facebook and Twitter to pay greater attention to usage data. Keep the users coming, and there will be boundless ways to make money off them, the thinking goes. To such investors, Snap may be worth only its current market capitalization of $27 billion if they’re sure the company will reach 500 million users in the 2020s and eventually, like Facebook, more than 1 billion. And they’re especially concerned about the growth in usage of Snapchat-inspired features on Facebook and its Instagram app. Skeptical investors view Snap as Facebook’s free research lab, from which the Menlo Park social media giant can pick successful ideas and expand at Snapchat’s expense. Snap has advised about “lumpy” user growth, or quarterly variances, depending on what new features are introduced in Snapchat, William Blair financial analyst Ralph Schackart wrote in a report last week. The company also has avoided actions that could boost usage in new countries or among older consumers, saying it would rather focus on improving the experience for its core users. “Despite this warning, we believe investors will still focus on quarterly [daily active users], especially with the rate at which Facebook continues to roll out features on its properties that are similar to features Snap offers,” Schackart said. He estimated Snap on Wednesday would announce 169 million users, up 39% from last year’s first quarter. Demand for Snap shares could be limited until more investors buy into the company’s message, especially if user growth is lackluster. Financial analysts say the anxiety is already reflected in Snap shares, which closed Monday at $22.46, below the company’s March 2 debut of $24. Investors who agree with Snap’s viewpoint say that Snapchat could surpass Facebook in average revenue per user and be profitable without ever having as many users. Only a consistent decline in users would force them to rethink their bet. “This is the microbrewery, not the giant AB InBev, and that’s a trend that is increasingly viable when thinking about younger consumers,” said Andrew Hall, vice president at Snap shareholder Narwhal Capital Management. Shifting focus away from usage growth from the beginning could benefit Snap. Online radio service Pandora Media spent many of its initial post-IPO earnings announcements heralding statistics such as active listeners and total listening hours. The data gave the company, which went public in 2011, a scare in 2014 when shares were clipped in half from an all-time high after user growth failed to meet expectations. After touting growth potential to investors, Twitter likewise tumbled in its first four earnings reports as shareholders zeroed in on disappointing usage data. Pushing other measurements has been difficult for Twitter co-founder Jack Dorsey, who returned to the chief executive role in 2015. Snap is concentrating on developing features and ads for the world’s top 10 advertising markets. Given Snapchat’s high saturation in those countries already, the company sees average revenue per user as a better signal of its performance. Still, financial analysts say scrutinizing the number of advertisers and their spending would be even more beneficial than average revenue per user. ARPU, as it’s referred to in shorthand, makes sense for subscription companies. But in the first years of this century, media technology companies including Yahoo started using the metric as much as telecommunications firms such as Qwest. For a company such as Snap, ARPU is akin to valuing a newspaper based on how many words it prints in a given year, said Pivotal Research stock analyst Brian Wieser. “It might coincidentally turn out to be relevant,” he said. But a better indicator would be what percentage of their budget the biggest advertisers are committing to Snapchat. Questions about the latest deals with advertisers could come up when Spiegel and other executives address analysts Wednesday afternoon. How Snapchat views the competition from Facebook and whether it has rectified technical issues with its app for Android smartphones may come up too, said Christos Charalambous, senior strategist at Snap shareholder Edge Wealth Management. In the early stage of its growth cycle, Snap is not going to perfectly deliver on everything, Charalambous said. “But if the ARPU is growing, you give them the benefit of the doubt.” The brothers who turned the mixed-martial arts sports organization UFC into a global force are starting an investment fund based in West Hollywood. Lorenzo and Frank Fertitta sold UFC for $4 billion to talent agency WME | IMG last year. Frank Fertitta still runs casino operator Red Rock Resorts. But his brother will be running the new fund, which plans to invest a few million dollars to potentially $100 million in entertainment, technology and media companies. That includes sports, e-sports, hospitality and food and beverage. Sam Bakhshandehpour, former CEO of hotel and club company SBE Entertainment and a longtime investment banker at J.P. Morgan, is Fertitta Capital’s managing director. Bakhshandehpour, who left SBE two years ago, said he joined Fertitta to reunite with the firm’s CEO, Nakisa Bidarian. They’d grown close since working on a deal together a decade ago. Bakhshandehpour said the plan is to focus on consumer products and services developed in the U.S. The team would invest in recently launched start-ups seeking a few million dollars in cashas well as in more established companies looking for a much bigger check for international expansion. “We’re looking to be opportunistic,” Bakhshandehpour said. “You don’t want to box yourself in.” They can afford the flexibility because the Fertittas aren’t wedded to generating returns in a specific time frame. They plan to invest through ups-and-downs in the economic climate and select companies that can sustain themselves through declines in consumer spending. Bakhshandehpour said he and the Fertittas have made personal investments on the side prior to launching the fund, but he declined to disclose them. Azubu, a video-streaming service aimed at e-sports enthusiasts, laid off eight people last week as it winds down technology development at its Sherman Oaks headquarters, its CEO said. The company languished for several years under the strange financing scheme of its primary investor, who supplied cash in monthly installments that were regularly late and insufficient. Azubu acquired rival Hitbox at the end of last year with plans to focus on broadcasting European video game competitions and move past the money woes. Now combined, the companies expect to launch this week under the name Smashcast. The redesigned service will introduce commenting and broadcasting features that bring it more in line with leaders such as Facebook Live and Twitch. “As we solidified a new platform, it was time to determine how do we want to support that,” CEO Mike McGarvey said in explaining the layoffs. About 12 people remain in Sherman Oaks. McGarvey, based in San Francisco, plans to hire more staff there and in Vienna, where Hitbox was founded. “It’s refereshing that there’s passion and effectiveness out of Vienna that was missing” at Azubu, he said. Whether gaming companies and investors want to partner with Smashcast given its checkered history is to be seen. Signal Sciences, a Venice company developing tools to keep hackers from breaching online apps, received a $15-million investment led by Charles River Ventures. Since launching a year ago, Signal Sciences has signed up about 60 paying customers such as Yelp, Under Armour and WeWork, Chief Executive Andrew Peterson said. The start-up also opened an office in nearby Santa Monica. It’s now working to make its service compatible with a greater number of technologies, which should lead to a wave of new customers this year. Peterson said the biggest validation that Signal Sciences is headed in the right direction is that cybersecurity companies including Duo and Tenable, which offer different services, are among its users. Signal Sciences’ competition includes Imperva and Akamai. Cal Poly Pomona hosts a conference Saturday aimed at students interested in system administration, network administration and cybersecurity. AngelHack has its Los Angeles hackathon Saturday in downtown, where people can form teams and race to complete a software project over two days.


News Article | May 16, 2017
Site: www.prnewswire.com

"We are honored to be recognized by Gartner as a Cool Vendor in security. DevOps, agile and cloud have changed the way businesses operate. Application security now needs to be a real-time, everyday part of a modern development, operations, and security culture, not something that happens on its own timeline," said Andrew Peterson, CEO of Signal Sciences. "With the recent launch Signal Sciences Web Protection Platform, we're delivering a truly revolutionary solution that allows developers and operations teams to release secure software faster, helping enterprises operate more efficiently and at scale. We believe our inclusion in the Cool Vendor report by Gartner is a testament to the value our new platform is bringing to customers," added Peterson. Signal Sciences Web Protection Platform (WPP) provides comprehensive threat protection and security visibility for web applications, microservices, and APIs on any platform. Built by practitioners, for practitioners, it is the only solution in the application security market that works across any modern architecture and provides the broadest coverage against real threats and attack scenarios. The platform offers a menu of deployment options, including next-gen web application firewall (NGWAF) and runtime application security protection (RASP) modules, and can also operate as a reverse proxy for legacy applications. To access the "Cool Vendors in Security for Technology and Service Providers, 2017" report (Gartner subscription required), visit Gartner. Disclaimer: Gartner does not endorse any vendor, product or service depicted in our research publications, and does not advise technology users to select only those vendors with the highest ratings or other designation. Gartner research publications consist of the opinions of Gartner's research organization and should not be construed as statements of fact. Gartner disclaims all warranties, expressed or implied, with respect to this research, including any warranties of merchantability or fitness for a particular purpose. About Signal Sciences Signal Sciences' industry first web protection platform was built in response to frustrations of trying to use legacy technology while enabling business initiatives like DevOps and cloud adoption. Signal Sciences  works seamlessly across cloud, physical, and containerized infrastructure, providing actionable security prioritization based on where your applications are targeted, and blocking attacks without breaking production traffic. Signal Science's clients include Under Armour, Etsy, Yelp/Eat 24, Shutterstock, Prezi and more. The company is headquartered in Venice, CA. For more information, please visit www.signalsciences.com ___________________________ 1 Gartner "Cool Vendors in Security for Technology and Service Providers, 2017," by Ruggero Contu, Lawrence Pingree, Deborah Kish, Dale Gardner, May 4, 2017 To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/signal-sciences-named-a-gartner-cool-vendor-2017-300458000.html


News Article | February 23, 2017
Site: www.techrepublic.com

In 2017 DevOps will go mainstream," said Signal Sciences' co-founder & chief security officer Zane Lackey. Historically, in enterprise organizations software developers and IT engineers operate in discrete silos. DevOps, however, is changing the way legacy organizations manage technology. DevOps is the technology process that marries software development with IT operations. The trend emerged as an inevitable response to the rise of Agile and iterative software project management. The advantage, experts say, is that DevOps helps organizations scale, yet remain nimble. "While it's been steadily picking up speed, in 2017 DevOps will start being a symbol for teams with integrated skills to build, deploy, and maintain applications in a continuous way," Lackey said. DevOps is a particularly useful cybersecurity tool, Lackey said. The DevOps trend has emerged rapidly, "as [silos] realize the need to integrate with each other in order to survive," Lackey explained. "With IoT on the rise, security will continue to be the primary obstacle preventing consumers from fully welcoming connected devices into their homes and lifestyles. Consumers and businesses are getting smarter and security vendors will be held more accountable in keeping them safe ... DevOps requires a reinvention of security, including a cultural change. To meet this need, security as a whole will recognize the need to integrate into DevOps to survive." Many companies, however, remain wary of the potential security risks posed by DevOps. "Continuous delivery and continuous integration pipelines that are now widely adopted in Agile development and DevOps shops are just such a target," said Carson Sweet, CTO and co-founder of CloudPassage. "Consider the impact of advanced persistent threat (APT) malware, but applied at the application level instead of the system level. If a threat actor (one of the nasty people) is able to breach the software development pipeline, they can essentially control the company by subverting their software code and components." Healthcare and financial services, Sweet said, are high-stakes industries most at risk by APT threats. "These attacks are likely to be aggressive and very public, meaning that DevOps teams will need to live up to new standards of testing and prevention, preferably harmonizing these operations with existing devops tools and functions." What do you think: Is DevOps the next big thing, or is a trend that will soon fade? Take the TechRepublic poll and explain your thoughts in the comments below.


Darvesh A.S.,Northeast Ohio Medical University | Bishayee A.,Signal Sciences
Nutrition and Cancer | Year: 2013

The prophylactic and therapeutic properties of tea have been attributed to green tea catechins and black tea theaflavins besides several other polyphenolic compounds. Tea polyphenols possess potent antioxidant and antiinflammatory properties and modulate several signaling pathways. These biochemical facets of tea polyphenols are responsible for its anticancer properties. Several lethal cancers, such as liver cancer, develop within a background of oxidative stress and inflammation. Liver cancer, also known as hepatocellular carcinoma (HCC), has been shown to occur throughout the world including Asia, Africa, Western Europe, and the United States. Phytochemicals, such as tea polyphenols, provide an effective and promising alternative for the chemoprevention and treatment of HCC. In this article, we systematically review, for the first time, the effects of tea polyphenols in the preclinical in vitro and in vivo HCC models. The review also examines, in critical detail, the biochemical mechanisms involved in the chemopreventive and antineoplastic effects of tea polyphenols in hepatic cancer. Finally, we highlight the role of synergy, bioavailability and pharmacokinetics of tea polyphenols, current status of clinical trials, discuss future directions, and comment on the future challenges involved in the effective use of tea polyphenols for the prevention and management of liver cancer. © 2013 Copyright Taylor and Francis Group, LLC.


News Article | December 13, 2016
Site: www.techrepublic.com

If 2016 was the year hacking went mainstream, 2017 will be the year hackers innovate, said Adam Meyer, chief security strategist at SurfWatch Labs. Meyer analyzes large and diverse piles of data to help companies identify emerging cyber-threat trends. "2017 will be the year of increasingly creative [hacks]," he said. In the past, cybersecurity was considered the realm of IT departments, Meyer explained, but no longer. As smart companies systematically integrate security into their systems, the culture hackers too will evolve. "Cybercriminals follow the money trail," Meyer said, and smart companies should adopt proactive policies. Ransomware attacks grew quickly, he said, because the attacks are "cheap to operate, and many organizations are not yet applying the proper analysis and decision-making to appropriately defend against this threat." SEE: How risk analytics can help your organization plug security holes (Tech Pro Research) It's equally cheap to identify internal vulnerability to hacks and to apply preventative best practices, Meyer said. But for many companies it's not as easy to understand the cybersecurity threats most likely to impact business. To help, TechRepublic spoke with a number of prominent security experts about their predictions for near-future cybersecurity trends likely to impact enterprise and small business in 2017. Cyber-offense and cyber-defense capacities will increase - Mark Testoni, CEO at SAP's national security arm, NS2 We will see an increased rate of sharing of cyber capabilities between the commercial and government spaces. Commercial threat intelligence capabilities will be adopted more broadly by organizations and corporations... High performance computing (HPC), in conjunction with adaptive machine learning (ML) capabilities, will be an essential part of network flow processing because forensic analysis can't stop an impending attack. HPC + adaptive ML capabilities will be required to implement real-time network event forecasting based on prior network behavior and current network operations... [Companies will] use HPC and adaptive ML to implement real-time behavior and pattern analysis to evaluate all network activity based on individual user roles and responsibilities to identify potential individuals within an organization that exhibit "out of the ordinary" tendencies with respect to their use of corporate data and application access. Ransomware and extortion will increase - Stephen Gates, chief research intelligence analyst at NSFOCUS The days of single-target ransomware will soon be a thing of the past. Next-generation ransomware paints a pretty dark picture as the self-propagating worms of the past, such as Conficker, Nimda, and Code Red, will return to prominence—but this time they will carry ransomware payloads capable of infecting hundreds of machines in an incredibly short timespan. We have already seen this start to come to fruition with the recent attack on the San Francisco Municipal Transport Agency, where over 2,000 systems were completely locked with ransomware and likely spread on its own as a self-propagating worm. As cybercriminals become more adept at carrying out these tactics, there is a good chance that these attacks will become more common. As more devices become internet-enabled and accessible and the security measures in place continue to lag behind, the associated risks are on the rise. Aside from the obvious risks for attacks on consumer IoT devices, there is a growing threat against industrial and municipal IoT as well. As leading manufacturers and grid power producers transition to Industry 4.0, sufficient safeguards are lacking. Not only do these IoT devices run the risk of being used to attack others, but their vulnerabilities leave them open to being used against the industrial organizations operating critical infrastructure themselves. This can lead to theft of intellectual property, collecting competitive intelligence, and even the disruption or destruction of critical infrastructure. Not only is the potential scale of these attacks larger, most of these industrial firms do not have the skills in place to deal with web attacks in real-time, which can cause long-lasting, damaging results. This alone will become one of the greatest threats that countries and corporations need to brace themselves for in 2017 and beyond. IoT security threats have been talked about, but not really worried about by most because a serious incident had yet to occur. With the 2016 DDoS attack on Dyn, and the ripple effect it created, we will see more scrutiny on security within the IoT marketplace. Vendors will work in new security precautions, but at the same time, criminals will also increase their attention on new ways to leverage IoT devices for their own malicious purposes. There are plenty of "As-A- Service" attack capabilities on the Dark Web for hire now and we should expect creative new IoT hack services to pop up in the near future. As organizations adopt more effective strategies to defeat malware, attackers will shift their approach and start to use legitimate credentials and software - think physical insiders, credential theft, man-in-the-app. The increased targeting of social media and personal email bypasses many network defenses, like email scans and URL filters. The most dangerous aspect is how attackers manipulate victims with offers or threats that they would not want to present to an employer, like employment offers or illicit content. Defenders will begin to appreciate that inconsistent user behaviors are the most effective way to differentiate malware and insider threats from safe and acceptable content. A big part of the challenge with cyberattacks is how businesses think threats can be filtered at the perimeter. Be warned that this is not the case. Attackers are aware of how to directly target users and endpoints using social engineering. The industry needs to be more proactive in thinking about how to reduce the attack surface, as opposed to chasing known threats and detecting millions of unknown threats. With an increasingly mobile workforce and threats coming through both personal and business devices and services, the impact of perimeter defenses has decreased. Security needs to be built from the endpoint outwards. Business security spending will increase - Ed Solis, Director of Strategy & Business Development at CommScope Security is part of every business and IT discussion these days and it will only become more intense in 2017. We see an increase in the demand for video for surveillance, both for government and private businesses. This issue includes physical security—securing the building, people, and assets—as well as network and data security... In 2017, security conversations will continue to intensify around not only securing data and networks but physical security as well-think buildings, people, and assets. We also expect to see an increased demand for video surveillance across the public sector and private business. Security will no longer be an afterthought - Signal Sciences' Co-Founder & Chief Security Officer, Zane Lackey 2017 will be a critical year for security, starting with how it's built into technology. DevOps and security will change the way they work together as they realize the need to integrate with each other in order to survive. With IoT on the rise, security will continue to be the primary obstacle preventing consumers from fully welcoming connected devices into their homes and lifestyles. Consumers and businesses are getting smarter and security vendors will be held more accountable in keeping them safe.


Wu Y.J.,Signal Sciences | Abhayapala T.D.,Signal Sciences
IEEE Transactions on Audio, Speech and Language Processing | Year: 2011

Spatial multizone soundfield reproduction overan extended region of open space is a complex and challenging problem in acoustic signal processing. In this paper, we provide a framework to recreate 2-D spatial multizone soundfields using a single array of loudspeakers which encompasses all spatial regions of interest. The reproduction is based on the derivation of an equivalent global soundfield consisting of a number of individual multizone soundfields. This is achieved by using spatial harmonic coefficients translation between coordinate systems. Amultizone soundfield reproduction problem is then reduced to the reproduction over the entire region. An important advantage of this approach is the full use of the available dimensionality of the soundfield. This paper provides quantitative performances of a 2-D multizone system and reveals some fundamental limits on 2-D multizone soundfield reproduction. The extensions of the multizone soundfield reproduction design in reverberant rooms are also included. © 2010 IEEE.


Bishayee A.,Signal Sciences
Advances in Experimental Medicine and Biology | Year: 2014

Persistent inflammation is known to promote and exacerbate malignancy. Primary liver cancer, mostly hepatocellular carcinoma (HCC), is a clear example of inflammation-related cancer as more than 90% of HCCs arise in the context of hepatic injury and inflammation. HCC represents the fifth most common malignancy and the third leading cause of cancer-related death worldwide with about one million new cases diagnosed every year with almost an equal number of deaths. Chronic unresolved inflammation is associated with persistent hepatic injury and concurrent regeneration, leading to sequential development of fibrosis, cirrhosis, and eventually HCC. Irrespective of the intrinsic differences among various etiological factors, a common denominator at the origin of HCC is the perpetuation of a wound-healing response activated by parenchymal cell death and the resulting inflammatory cascade. Hence, the identification of fundamental inflammatory signaling pathways causing transition from chronic liver injury to dysplasia and HCC could depict new predictive biomarkers and targets to identify and treat patients with chronic liver inflammation. This chapter critically discusses the roles of several major cytokines, chemokines, growth factors, transcription factors, and enzymes as well as a distinct network of inflammatory signaling pathways in the development and progression of HCC. It also highlights and analyzes preclinical animal studies showing innovative approaches of targeting inflammatory mediators and signaling by a variety of natural compounds and synthetic agents to achieve effective therapy as well as prevention of hepatic malignancy. Additionally, current limitations and potential challenges associated with the inhibition of inflammatory signaling as well as future directions of research to accelerate clinical development of anti-inflammatory agents to prevent and treat liver cancer are presented. © Springer Basel 2014.


Bishayee A.,Signal Sciences
Advances in Experimental Medicine and Biology | Year: 2014

Persistent inflammation is known to promote and exacerbate malignancy. Primary liver cancer, mostly hepatocellular carcinoma (HCC), is a clear example of inflammation-related cancer as more than 90 % of HCCs arise in the context of hepatic injury and inflammation. HCC represents the fifth most common malignancy and the third leading cause of cancer-related death worldwide with about one million new cases diagnosed every year with almost an equal number of deaths. Chronic unresolved inflammation is associated with persistent hepatic injury and concurrent regeneration, leading to sequential development of fibrosis, cirrhosis, and eventually HCC. Irrespective of the intrinsic differences among various etiological factors, a common denominator at the origin of HCC is the perpetuation of a wound-healing response activated by parenchymal cell death and the resulting inflammatory cascade. Hence, the identification of fundamental inflammatory signaling pathways causing transition from chronic liver injury to dysplasia and HCC could depict new predictive biomarkers and targets to identify and treat patients with chronic liver inflammation. This chapter critically discusses the roles of several major cytokines, chemokines, growth factors, transcription factors, and enzymes as well as a distinct network of inflammatory signaling pathways in the development and progression of HCC. It also highlights and analyzes preclinical animal studies showing innovative approaches of targeting inflammatory mediators and signaling by a variety of natural compounds and synthetic agents to achieve effective therapy as well as prevention of hepatic malignancy. Additionally, current limitations and potential challenges associated with the inhibition of inflammatory signaling as well as future directions of research to accelerate clinical development of anti-inflammatory agents to prevent and treat liver cancer are presented. © 2014 Springer Basel.

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