Researchers Are Using Viruses to Make Superbugs Commit Suicide

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The gene-editing technology called CRISPR has its origins as a bacterial immune system against viruses, a feature which could be turned against them in the future.

By arming bacteriophage viruses with the tools to force bacteria into falling on their own swords, scientists hope we will be able to develop powerful new ways to defeat antibiotic resistant pathogens and perhaps even shape our body’s microflora.

Research presented at the CRISPR 2017 conference in the US described the progress that has been made in modifying viruses that target specific bacteria with genes that make the host’s enzymes cut into its own DNA.

Clustered regularly interspaced short palindromic repeats – CRISPR for short – are sequences of DNA made of a repeating codes that form a long palindrome.

Bacteria produce them as a kind of immune system against viruses called bacteriophages, slipping bits of the virus’s genes scavenged out of the environment into the repeating codes.

With the viral DNA stored away in CRISPR sequences, any future infections can be detected quickly and a CRISPR-associated system (or cas) enzyme can then use the sequence as a beacon, latching onto the infecting virus genes and either snipping them selectively or tearing them to shreds.

About 25 years ago, researchers realised this cut-and-paste system of CRISPR sequences and cas enzymes could be used in the lab to edit sequences artificially, and a new engineering toolkit was born.

The technology has been in the news quite a bit in recent years as advances have been made in applying it to cancer treatments and even eliminating HIV infections.

While it might not be without certain risks, CRISPR gene editing has sparked a something of a minor revolution.

Bringing it back to its roots and turning it into a weapon against its creators has a sense of serendipity about it.

“I see some irony now in using phages to kill bacteria,” said the chief scientific officer of Locus Biosciences, Rodolphe Barrangou, at the CRISPR 2017 conference.

Using bacteriophages as a form of therapy to treat infection isn’t all that new, with trials dating as far back as the 1920s.

The use of phages is appealing because they are far more specific than antibiotics, targeting only specific types of bacteria and therefore posing no risk to our own health. The viruses can also penetrate the coatings of sticky film bacteria produce for protection and adherence.

Russia experienced a fair degree of success with phage therapy behind its Iron Curtain during the Cold War, but unable to patent the naturally occurring viruses and with the bacteria quickly adapting, red tape and limitations in technology have made it far easier to focus on antibiotics in the west.

With looming epidemics of superbugs on the horizon, attention is returning to bacteriophages as ways to kill bacteria, and CRISPR has put a new spin on the old idea.

A spin-off company from North Carolina State University, Locus Biosciences is testing the limits of CRISPR technology, including giving bacteriophages CRISPR sequences containing codes for antibiotic resistance genes.

Targeting bacteria with the genes, the CRISPR sequence would form a target for the bacteria’s own cas enzymes, effectively blocking resistance or even prompting the bacteria into chewing up its own DNA and self-destructing.

In recent years our eyes have been opened to how complex our relationship is with bacteria in our environment, and how dull our tools are for dealing with them.

Variations in our gut microflora has been linked with everything from Parkinson’s disease to autism to obesity, suggesting the species of bacteria we harbour could have major ramifications on many aspects of our health.

With its razor-honed surgical precision, it’s possible the technology could one day be used to select specific strains of bacteria in our gut, deleting them from the ecosystem and allowing us to edit our microbiomes.

Given we’re practically at the dawn of both CRISPR technology and our grasp on the complexity behind our body’s bacterial ecosystems, we can only speculate for the time being.

As antibiotics slowly lose their shine it’s probably worth paying close attention to radical new solutions such as these.

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Oncoceutics receives US patent for ONC201 in adenocarcinomas

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Oncoceutics, Inc. announced that the United States Patent and Trademark Office (USPTO) has issued patent #9,452,165 for the use of ONC201 to treat cancers that are categorized as adenocarcinomas. Adenocarcinomas are cancers that form from epithelial cells with glandular origins or characteristics. They represent approximately 50% of all cancers, and more than 80% of prostate, breast, endometrial, ovarian, pancreatic, and colorectal cancers are adenocarcinomas.

ONC201, a member of the imipridone family, has demonstrated excellent anti-cancer activity and safety in preclinical models and ongoing clinical trials, including in prostate and endometrial cancers.

This patent further expands the IP protection the company has generated around ONC201 and its use in cancer. Combined with the company’s four previously issued patents for ONC201, Oncoceutics now has patent protection for use in the vast majority of cancer types, in addition to protection around its proprietary di-salt formulation, and the use of ONC201 in combination with any other therapeutic agent.

“This patent, which issued covering the use of ONC201 to treat adenocarcinomas, shows the wide utility of our lead clinical candidate to treat multiple forms of cancer,” said Martin Stogniew, PhD, chief development officer of Oncoceutics. “It, along with the company’s previously issued patents, gives Oncoceutics a large patent estate which we believe is extremely valuable.”

“Adenocarcinomas are among the deadliest forms of cancer for which we need new treatments to reduce morbidity and mortality,” said Wafik El-Deiry, MD, PhD, scientific founder of Oncoceutics and Deputy Cancer Center Director for Translational Research of the Fox Chase Cancer Center. “Progress in the laboratory research leading to this patent paves the way towards clinical translation of ONC201 in order to bring a new treatment option to patients with cancer.”

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Scientists have finally figured out how cancer spreads through the bloodstream

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In what could be a major step forward in our understanding of how cancer moves around the body, researchers have observed the spread of cancer cells from the initial tumour to the bloodstream.

The findings suggest that secondary growths called metastases ‘punch’ their way through the walls of small blood vessels by targeting a molecule known as Death Receptor 6 (no, really, that’s what it’s called). This then sets off a self-destruct process in the blood vessels, allowing the cancer to spread

According to the team from Goethe University Frankfurt and the Max Planck Institute in Germany, disabling Death Receptor 6 (DR6) may effectively block the spread of cancerous cells – so long as there aren’t alternative ways for the cancer to access the bloodstream.

“This mechanism could be a promising starting point for treatments to prevent the formation of metastases,” said lead researcher Stefan Offermanns.

Catching these secondary growths is incredibly important, because most cancer deaths are caused not by the original tumour, but by the cancer spreading.

To break through the walls of blood vessels, cancer cells target the body’s endothelial cells, which line the interior surface of blood and lymphatic vessels. They do this via a process known as necroptosis – or ‘programmed cell death’ – which is prompted by cellular damage.

According to the researchers, this programmed death is triggered by the DR6 receptor molecule. Once the molecule is targeted, cancer cells can either travel through the gap in the vascular wall, or take advantage of weakening cells in the surrounding area.

cancer-2MPI for Heart and Lung Research

The team observed the same behaviour in both lab-grown cells and mice. In genetically modified mice where DR6 was disabled, less necroptosis and less metastasis was recorded.

The scientists have reported their findings in Nature.

The next step is to look for potential side effects caused by the disabling of DR6, and to figure out if the same benefits can be seen in humans. If so – and there’s no guarantee of that – this has the potential to be a seriously effective way of slowing down the spread of cancer. 

There are other hypotheses on how some metastases get around the body to cause secondary growths, though. Scientists at the University of California, Los Angeles (UCLA) are currently investigating the idea that tumour cells could also spread through the body outside blood vessels and the bloodstream.

The researchers suggest that a mechanism known as angiotropism could be used by some melanoma cancers to cling to the outside of blood vessels, rather than penetrating them. If this is confirmed, they would escape the effects of disabled DR6 and chemotherapy alike.

“If tumour cells can spread by continuous migration along the surfaces of blood vessels and other anatomical structures such as nerves, they now have an escape route outside the bloodstream,” explained researcher Laurent Bentolila from UCLA. 

The findings from that research, also conducted on mice, have been published in Nature Scientific Reports.

As the two studies show, not all cancers behave in the same way, which makes figuring out how they operate doubly difficult. But the more we come to appreciate how complex and varied this disease can be, the better chance we have of fighting it.

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Microsoft says it will ‘solve’ cancer in the next 10 years

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Microsoft has announced an ambitious plan to use computer science to ‘solve’ cancer within the next decade.

While that plan involves many ambitious projects, one of the most interesting of proposals involves creating ultra-small DNA computers that can live inside a person’s body, monitoring for cancer cells and reprogramming them into healthy cells as soon as they pop up.

“I think it’s a very natural thing for Microsoft to be looking at because we have tremendous expertise in computer science and what is going on in cancer is a computational problem,” Chris Bishop from Microsoft Research told Sarah Knapton at The Telegraph.

“It’s not just an analogy, it’s a deep mathematical insight. Biology and computing are disciplines which seem like chalk and cheese but which have very deep connections on the most fundamental level.” 

To make their goal a reality, Microsoft, which isn’t known for stepping so far outside of the consumer electronics sphere, has gathered a team of biologists and computer scientists from around the world to work on various aspects of cancer research.

The details are still thin on the ground, but one team plans on using machine learning and computer vision – where computers glean information from images or videos – to give radiologists a better understanding of how a specific patient’s tumour is progressing.

This could open up a more nuanced type of personalised medicine.

Another team is working on algorithms to predict the best plan of attack for each specific tumour type.

Then there’s the group working on that ‘moonshot‘ idea to make computers out of DNA that will monitor and reprogram cancer cells inside the body.

The thinking is that, every time cancerous cells arise in the body, the computer would know, and “reboot the system and clear out the diseased cells”, explains Knapton.

Despite these varied approaches, Microsoft says that all of the projects – no matter how different – follow two similar computer science approaches: information processing and machine learning.

“One approach is rooted in the idea that cancer and other biological processes are information processing systems,” the company said.

“Using that approach the tools that are used to model and reason about computational processes – such as programming languages, compilers and model checkers – are used to model and reason about biological processes.”

The team says that machine learning will allow researchers to better analyse millions and millions of files of biological data in search of new treatment approaches, a process that – until recently – has been done by hand.

Machine learning could have the power to finally speed this up faster than ever thought possible.

“We’re in a revolution with respect to cancer treatment. Even 10 years ago people thought that you treat the tissue: you have brain cancer, you get brain cancer treatment. You have lung cancer, you get lung cancer treatment,” said David Heckerman, director of Microsoft’s genomics team, in a press statement.

“Now, we know it’s just as, if not more, important to treat the genomics of the cancer, e.g. which genes have gone bad in the genome.”

As for their ambitious timeline, saying that they will have cancer ‘solved’ in less than a decade, many of the researchers working on the project are confident that this can be achieved.

“If we are able to control and regulate cancer then it becomes like any chronic disease and then the problem is solved,” senior researcher Jasmin Fisher told The Telegraph.

“I think for some of the cancers five years, but definitely within a decade. Then we will probably have a century free of cancer.”

Only time will tell if they are right or not, but we have our fingers crossed that something good will come of their new mission.

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ICMR issues consensus document for management of non-Hodgkin’s lymphoma

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The Indian Council of Medical Research (ICMR) has issued the consensus document for management of non-Hodgkin’s lymphoma (high grade) which will provide guidance to practicing doctors and researchers for the management of patients suffering from non- Hodgkin’s lymphoma – high grade and also focusing their research efforts in Indian context.

Lymphoma is a type of cancer that develops in the lymphatic system, the body’s disease fighting network. It is estimated that around 1,000 people worldwide are diagnosed with lymphoma every day. Globally the incidence of disease is 385741 cases with mortality of 199650 cases. India accounts for 23801 cases with a mortality of 16597 cases.

This document will help practicing doctors, clinicians, researchers and patients in complex decision making process in management of the disease. It represents the current thinking of national experts on subject based on available evidence.

The ICMR had earlier constituted sub-committees to prepare consensus document for management of various cancer sites. This document is the result of the hard work of various experts across the country working in the area of oncology. This consensus document on management of non- Hodgkin’s lymphoma – high grade summarizes the modalities of treatment including the site-specific anti-cancer therapies, supportive and palliative care and molecular markers and research questions. It also interweaves clinical, biochemical and epidemiological studies.

The purpose of this document is to revamp recommendations for evaluation, staging and response assessment of patients with non-Hodgkin’s lymphoma. The availability of more effective therapies for lymphoma and the increasingly sensitive and specific technologies has made this consensus the need of hour. However, good clinical judgement, a careful history and physical examination are the cornerstones of patient follow up. The objective of this guideline is to provide healthcare professionals with clear guidance on the management of patients with Non Hodgkin Lymphoma – High Grade. The guidance may not be appropriate for all patients with NHL but this compilation of Indian Data gives us an insight to best practice. This disease strata is currently undergoing extensive investigations and it is likely that paradigms will shift over the next several years.

Lymphomas are a very complex group of diseases with differing behaviours and treatment options. It is typically classified into two groups, Hodgkins lymphoma (HL) and non-Hodgkins lymphoma (NHL). NHL’S are subclassfied as low grade (indolent) and high grade. The high grade NHL is generally curable with cytotoxic therapy while the low grade lymphomas are controllable for long periods.

While lymphoma is potentially fatal, some forms are curable and a patient’s survival may be greatly enhanced by early diagnosis. Almost all lymphoma types can be cured or managed as a chronic disease, but its complexity and variation do not allow for a one-size-fits-all treatment approach. Instead, it necessitates highly specialized and individualized approaches. The cause of the majority of lymphoma cases is unknown, however, there could be several factors that may influence one’s risk of developing lymphoma. The relative effects of these factors in any given case of cancer vary and are very difficult to determine with accuracy at present.

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