Peptides offer fresh insights for cancer diagnosis and treatment

Genes and proteins play essential roles in the maintenance of health and the development of disease and are the focus of the fields of genomics and proteomics, respectively.

Genes, which are composed of 4 nucleic acids, provide the blueprint for constructing all living forms, while proteins, which are composed of some 20 amino acids, are the body’s tireless day laborers, building organs and tissues, forming a complex defense network of antibodies, transporting essential materials to far-flung destinations in the body and facilitating essential chemical reactions.BRCA1 is a human gene that produces tumor suppressor proteins, which repair damaged DNA and help maintain the stability of each cell’s genetic material. Mutations in this gene (and the related gene BRCA2), can disable this repair network, resulting in an increased risk of breast cancer. In the graphic, tumor-associated proteins resulting from mutations in BRCA1 are degraded into smaller fragments or peptides, which circulate in the bloodstream. These circulating peptides are then enriched using specialized nanoporous silica thin films or NanoTraps, then profiled using mass spectrometry to identify among four clinical groups. Such research may help clinicians determine which carriers of BRCA1 mutations are most likely to progress to breast cancer.Download Full Image

Less well known are the peptides, though they too are central players in life processes and can shed new light on a variety of diseases. Indeed, the rapidly expanding field of peptide research or peptidomics is poised to deliver fresh biological insights and new methods for the detection and treatment of a broad range of disorders, particularly cancer.

A new book, “The Enzymes: Peptidomics of Cancer-Derived Enzyme Products,” explores the peptidome in keen detail. The particular focus of the book is how peptides, small segments of linked amino acids, can provide researchers and clinicians with vital clues about cancer prognosis currently unavailable through conventional diagnostic methods.

Tony Hu, a researcher in Arizona State University’s Virginia G. Piper Biodesign Center for Personalized Diagnostics, co-edited the new book.

“Back in 2016, I was invited to UCLA to give a seminar. I talked with a professor there — Fuyuhiko Tamanoi — who served for many years as the editor for the book series ‘Enzyme,’” Hu said. “After he heard a bit about emerging peptide research, he decided it would make a fine topic for a new book, so we invited experts worldwide, from Europe, from China, Japan and the U.S. to explore different aspects of the peptidome.”

As Hu explained, the book is divided into three major areas. The first deals with the discovery of biomarkers — peptide signals present in blood or saliva that can be used for diagnostic purposes. The second part deals with peptide biofunction, which turns out to play a critical role in cancer. The third section is devoted to clinical application and regulation of peptide biomarkers. The book therefore spans research on the peptidome reaching from the laboratory bench to the patient bedside, making it the most comprehensive handbook of leading edge peptidomics to date.

Probing the peptidome

Peptides, like proteins, are composed of amino acids. They are generally far smaller molecules, typically composed of just 50 amino acids or less. They are often produced through the breakdown of larger, more complex proteins. This process of protein degradation is a common feature in cancer progression, invasion and metastasis. In the course of these processes, peptide byproducts of the tumor microenvironment circulate in the bloodstream, providing a potentially rich source of biomarkers for disease.

Although there are myriad cancer-specific proteins secreted by active tumors, which could potentially serve as biomarkers, the challenges of monitoring such proteins — particularly in a clinical environment — are often formidable due to fluctuations in their location and abundance. Hu believes that tumor-secreted peptides, which circulate in the blood, can provide an alternate window into underlying activity, providing more fine-grained diagnoses of a given cancer than can be gleaned from either the genes or proteins alone.

ASU researcher Tony Hu’s new book, “The Enzymes: Peptidomics of Cancer-Derived Enzyme Products,” focuses on the role of peptides in cancer detection and therapy. Photo by Deanna Dent/ASU Now

 A new field is born

“About 15 years ago, people started looking at peptides,” Hu said.

Peptides are a rich source of information about the proteins they are derived from and also can shed light on the body’s enzymatic network. As Hu explained, enzymatic activity is often a crucial component in cancer progression, but getting a precise handle on tumor-related enzyme activity has, until recently, proved challenging.

“We published a paper in Clinical Chemistry back in 2014,” Hu said. “There’s an enzyme that is pretty active at the local tumor site in breast cancer. When we profile this enzyme on the tumor tissue, it’s showing this dramatically increased expression compared to normal.”

The enzyme, however, dissolves in the blood and is undetectable. Testing such cancer patients shows blood enzyme levels close to normal.

This presents clinicians with two options: 1) Use a very invasive method to biopsy the tumor tissue in order to profile the enzyme directly, or 2) look at the peptide product produced by the enzyme, which can be profiled directly from the blood. When Hu and colleagues used this approach, they found a variation in peptide expression that precisely matched the enzyme activity at the tumor site. The results encouraged Hu that peptides indeed have much to tell us about underlying disease.

In other cases, the peptide itself is malfunctioning, which may be correlated with tumor progression. Further, peptides can provide vital clues concerning a tumor’s surrounding microenvironment, for example signaling a condition of low oxygen or hypoxia, an important precursor of cancer metastasis and an area of research Hu is currently involved in.

Another critical peptide under study is Hepcidin, a 25-amino acid peptide synthesized in the liver, which serves as the principle regulator of iron metabolism in vertebrates. It can also be used as a telltale indicator of elevated iron status, inflammation and infection associated with diseases including cancer and HIV.

In order to profile peptides from blood samples, mass spectroscopy is used, a technique allowing peptides to be accurately identified based on their molecular weights. Once an exotic technology confined to sophisticated laboratories, cutting-edge mass spec technology is now common in hospital settings around the world, further enabling peptide biomarker discovery to advance and enter routine clinical use.

Finding new avenues

As the authors note, specialized enzymes involved in protein degradation — known as proteases — are involved in all phases of cancer progression including early growth, angiogenesis, inflammation, survival and invasion. Their peptide byproducts offer insights into all of these processes. Evaluation of inflammation through peptide analysis could also be used as a rapid and direct indicator of drug toxicity in chemotherapy, a process that currently must rely on patient symptomatology.

Finally, advances in biotechnology have allowed a new class of safe and efficacious peptide drugs to be developed, furthering the aims of personalized medicine. Immunotherapy, in which the patients’ own immune system is used to attack cancer cells, is just one area where peptides are being applied therapeutically. The immune system responds to a cancer-linked peptide by mounting a robust defense — a technique currently being explored in the fight against prostate cancer.

“For these reasons, we believe peptides have been undervalued for a long time in cancer studies,” Hu said.

Accurate, early diagnostic and prognostic markers are still lacking for most cancers, posing the most significant challenge for successful diagnosis and treatment. Vital information, unavailable through proteomic study, is now becoming accessible through sensitive detection of circulating peptides. The new book throws light on an exciting and hopeful domain of research.

[“Source-asunow”]

Google Announces 4 New Indian Startups for Fresh ‘Launchpad Accelerator’ Batch

Google Announces 4 New Indian Startups for Fresh 'Launchpad Accelerator' Batch

Google on Friday announced the four shortlisted Indian startups for its hands-on mentorship programme ‘Launchpad Accelerator’. With this batch, a total of 30 Indian startups have so far joined the class.

The shortlisted startups – BabyChakra, m.Paani, NIRAMAI and SocialCops – will join a group of startups shortlisted from all over the world at the Google Developers’ Launchpad Space in San Francisco in the US.

Class 5 of the mentorship will kick off on January 29 and will include two weeks of all-expenses paid training, as part of the the full six-month programme.

“These startups have been shortlisted based on their unique value proposition and use of latest technologies like machine learning and artificial intelligence,” Roy Glasberg, Global Lead, Google Developers Launchpad, said in a statement.

BabyChakra is a trusted care companion to Indian parents, from pregnancy to parenting.

m.Paani powers real-time, direct to consumer engagement, marketing, loyalty and insights for mass market consumers and retailers.

NIRAMAI is a healthtech startup that has developed a novel breast cancer screening solution while SocialCops empowers organisations to make better decisions through data.

Launchpad Accelerator is Google’s six-month programme that includes an intensive two-week boot camp in San Francisco and mentoring from over 30 teams across Google and expert mentors from top technology companies in Silicon Valley and globally.

[“Source-gadgets.ndtv”]

Qualcomm Accused of Fresh Antitrust Violations by 4 Apple Contractors

Qualcomm Accused of Fresh Antitrust Violations by 4 Apple Contractors

HIGHLIGHTS

  • Contractors alleged that Qualcomm violated 2 sections of the Sherman Act
  • The allegations are part of broader dispute between Apple and Qualcomm
  • The lost licence revenue from Apple has been a hit to Qualcomm’s sales

iPhone chip supplier Qualcomm faces a fresh set of antitrust allegations from a group of four companies that assemble the iPhone and other products on behalf of Apple.

Foxconn parent Hon Hai Precision Industry Co, Wistron, Compal Electronics and Pegatron alleged that Qualcomm violated two sections of the Sherman Act, a US antitrust law.

The accusations, made in a filing late Tuesday in US District Court for the Southern District of California, are counterclaims to a Qualcomm lawsuit filed in May seeking to force the contractors to pay Qualcomm licence fees that Apple directed them to stop paying.

“Qualcomm has confirmed publicly that this lawsuit against our clients is intended to make a point about Apple and punish our clients for working with Apple,” Theodore J. Boutrous, a lawyer for the four companies, said in a statement. “The companies are bringing their own claims and defenses against Qualcomm.”

ALSO SEEQualcomm CEO Says Settlement Likely in Apple Dispute

The allegations are part of broader dispute between Apple and Qualcomm, which supplies so-called modem chip technology that lets iPhones connect to cellular data networks, over the nature of Qualcomm’s business model of linking the sale of chips and patent licences, which has come under scrutiny by regulators in South Korea, the United States and several other countries.

In January, Apple sued Qualcomm alleging that the company had withheld nearly $1 billion of patent licence rebates it owed Apple in retaliation for Apple’s cooperation with South Korean regulators. Apple told its contract manufacturers to withhold licence payments from Qualcomm while the dispute played out, which prompted Qualcomm to sue them in May.

“Despite Apple’s claims against Qualcomm, Apple suppliers remain contractually obligated to pay royalties to Qualcomm under their licence agreements with us, including for sales of iPhones to Apple,” Qualcomm President Derek Aberle said of the dispute on the company’s conference call in April.

Much of the language in the contractors’ allegations mirror Apple’s objections to Qualcomm’s business model. A senior Apple official confirmed that the company is helping to fund the contractors’ legal defense as part of an indemnification agreement among the firms. Apple has also formally joined the contractor case as a defendant.

The lost licence revenue from Apple has been a hit to Qualcomm’s sales. Analysts expect $5.2 billion (roughly Rs. 33,453 crores) in revenue for the June quarter, down from $6 billion a year earlier.

[“Source-gadgets.ndtv”]

Indiamart raises fresh funds from Amadeus Capital, Westbridge and Intel

The company offers a platform and tools to over 1.4 crore buyers to search from over 2.57 crore products and get connected with over 18 lakh suppliers.

The company offers a platform and tools to over 1.4 crore buyers to search from over 2.57 crore products and get connected with over 18 lakh suppliers.

New Delhi: Indiamart.com, one of the largest online listing platforms for small and medium businesses has raised an undisclosed amount in Series C funding led by Amadeus Capital, a top company executive said Wednesday.

Westbridge, UK based Quona Capital and existing investor Intel Capital too participated in the round, said Dinesh Agarwal, founder and chief executive at IndiaMart.

Indiamart, which has raised close to Rs.65 crore since inception in 1996, will use the funds largely for Tolexo, its new online marketplace for businesses.

The current round is expected to have raised Rs.130-140 crore, said two people familiar with the discussion, who did not want to be identified.

The company will also use the funds towards financing small and medium enterprises and payments space, said Agarwal. “This will largely be done through third party tie-ups to start with; we could lend smaller amounts on our own too by creating escrow accounts,” said Agarwal.

The company, which has been largely focusing around small and medium businesses, is now expanding its reach to large businesses as well. “We have started to think that at this scale, we are useful for large companies and suppliers. It is prudent for the business to focus on both small and large businesses and some part of the funds will go towards this segment as well.” The company has already started working with large suppliers such as Godrej Interio, consumer electronics firm BenQ and other large component makers.

Indiamart started out as an online directory for businesses in India. It is currently backed by Intel Capital with Bennett, Coleman & Co. Ltd as one of its investors. It launched Tolexo, an online retail marketplace for consumers and businesses to shop on the web, in June 2014.

Tolexo currently lists a million products and has about 7,000-plus sellers on its platform. The company in 13 months of operations had more than 200,000 customers, who transacted on its website. It claims to be registering a double digit growth.

Indiamart is expecting this to be its last round before an initial public offering. “I hope this is our last round before going public. We have got systems and processes in place…,” said Agarwal.

Getting Westbridge on board is part of Agarwal’s strategy to prepare the company for a public listing. Westbridge backs publicly traded firms Infoedge and Justdial. Agarwal had announced his IPO plans in 2014, saying the company was preparing for an overseas IPO in 2015. However, a weak market has pushed the company’s plans to list.

Indiamart, which had revenues of Rs.215 crore for the year ending March 2015, is likely to close this year with sales hitting north of Rs.300 crore. The company claims to be cash-positive for over two years now.

The company offers a platform and tools to over 1.4 crore buyers to search from over 2.57 crore products and get connected with over 18 lakh suppliers. It currently has over 3000 employees located across 55 plus offices in the country.

[“source-Livemint”]