Tag Archives: DNA

A Weapon To Fight Lung Cancer

Researchers at the Children’s Medical Center Research Institute at UT Southwestern (CRI) have discovered a new metabolic vulnerability in small cell lung cancer (SCLC) that can be targeted by existing drug therapies.

SCLC is a deadly and aggressive form of lung cancer with few therapeutic options and an incredibly low five-year survival rate of 5 percent. Researchers at CRI believe the key to finding new therapies for this disease lies in better understanding the metabolism of SCLC.

Cancerous cells reprogram their metabolic pathways to grow and spread rapidly through the body. In some forms of cancer, cancer cells become highly dependent or “addicted” to specific metabolic pathways as a result of genetic mutations. Identifying these pathways can lead to new treatment options.

SCLC metabolism has not previously been studied in-depth,” said Dr. Ralph DeBerardinis, Professor at CRI and Director of CRI’s Genetic and Metabolic Disease Program.If we identify the metabolic pathways SCLC uses to grow and spread, then maybe we can find drugs to inhibit them. This could effectively cut off the fuel supply to these tumors.”

To discover new vulnerabilities in SCLC, researchers at CRI analyzed metabolism and gene expression in cells obtained from more than 25 human SCLC tumors. From the data, they identified two distinct categories of SCLC defined by the level of two oncogenes: MYC and ASCL1. Oncogenes are genes known to promote cancer formation and growth.

The study, published in Cell Metabolism, found that MYC stimulated synthesis of purine molecules. Purines are essential for cells to produce RNA and DNA, both of which are required for growth and division. MYC-expressing cells had a particular need for a specific type of purine called guanosine.

We were excited to discover that purine synthesis was so important for this subset of SCLC cells. There are already safe and effective inhibitors of guanosine synthesis used in patients for other diseases besides cancer. Our findings suggested that mice with MYC-expressing SCLC might benefit from treatment with drugs that inhibit purine synthesis,” said Dr. Fang Huang, a visiting scholar at CRI and first author on the paper.

To test the hypothesis, researchers treated mice from multiple different mouse models of SCLC with the drug mizoribine, a purine synthesis inhibitor. Treatment with this drug suppressed tumor growth and significantly extended the lifespan in mice with MYC-expressing SCLC.

Our findings suggest purine synthesis inhibitors could be effective in SCLC patients whose tumors have high levels of MYC. If we are right, this could quickly provide a new treatment for this disease, which has few options at present,” said Dr. DeBerardinis.

Source: https://www.utsouthwestern.edu/

Genetic Codes Mapping Of 3,000 Dangerous Bacteria

Scientists seeking new ways to fight drug-resistant superbugs have mapped the genomes of more than 3,000 bacteria, including samples of a bug taken from Alexander Fleming’s nose and a dysentery-causing strain from a World War One soldier. The DNA of deadly strains of plague, dysentery and cholera were also decoded in what the researchers said was an effort to better understand some of the world’s most dangerous diseases and develop new ways to fight them. The samples from Fleming – the British scientist credited with discovering the first antibiotic, penicillin, in 1928 – were among more than 5,500 bugs at Britain’s National Collection of Type Cultures (NCTC) one of the world’s largest collections of clinically relevant bacteria. The first bacteria to be deposited in the NCTC was a strain of dysentery-causing Shigella flexneri that was isolated in 1915 from a soldier in the trenches of World War One.

“Knowing very accurately what bacteria looked like before and during the introduction of antibiotics and vaccines, and comparing them to current strains, … shows us how they have responded to these treatments,” said Julian Parkhill of Britain’s Wellcome Sanger Institute who co-led the research. “This in turn helps us develop new antibiotics and vaccines.”

Specialists estimate that around 70 percent of bacteria are already resistant to at least one antibiotic that is commonly used to treat them. This has made the evolution of “superbugs” that can evade one or multiple drugs one of the biggest threats facing medicine today. Among the most serious risks are tuberculosis – which infects more than 10.4 million people a year and killed 1.7 million in 2016 alone – and gonorrhea, a sexually transmitted disease that infects 78 million people a year and which the World Health Organization says is becoming almost untreatable.

Source: https://www.reuters.com/

Nanoparticles Cross The Blood-Brain Barrier, Shrink Glioblastoma Tumors

Glioblastoma multiforme, a type of brain tumor, is one of the most difficult-to-treat cancers. Only a handful of drugs are approved to treat glioblastoma, and the median life expectancy for patients diagnosed with the disease is less than 15 months.

MIT researchers have now devised a new drug-delivering nanoparticle that could offer a better way to treat glioblastoma. The particles, which carry two different drugs, are designed so that they can easily cross the blood-brain barrier and bind directly to tumor cells. One drug damages tumor cells’ DNA, while the other interferes with the systems cells normally use to repair such damage.

In a study of mice, the researchers showed that the particles could shrink tumors and prevent them from growing back.

What is unique here is we are not only able to use this mechanism to get across the blood-brain barrier and target tumors very effectively, we are using it to deliver this unique drug combination,” says Paula Hammond, a David H. Koch Professor in Engineering, the head of MIT’s Department of Chemical Engineering, and a member of MIT’s Koch Institute for Integrative Cancer Research.

Source: http://news.mit.edu/

How To End Malaria

Gene-editing technologies that alter mosquitoesDNA could prove critical in the fight against malaria, Bill Gates said on Wednesday, and ethical concerns should not block progress in such gene-modifying research.

Speaking at the Malaria Forum conference in London, the billionaire Microsoft co-founder and philanthropist said that while gene editing raises “legitimate questions”, that should not jeopardize exploration of tools such as CRISPR gene editing and so-called “gene drive” technologies.

I’m very energized about the potential of gene drive. (It’s) the kind of breakthrough we need to support,” Gates said. “It may prove critical here.” 

Gene drive technologies alter DNA and drive self-sustaining genetic changes through multiple generations by overriding normal biological processes. CRISPR technology enables scientists to find and modify or replace virtually any gene. The techniques are being explored across science – from human medicine to livestock– and crop-breeding. In mosquitoes that transmit malaria, genetic alterations can be used to induce infertility to reduce populations, or alter the insects’ ability to carry and pass on the malaria parasite. 

The technologies can be extremely powerful, but they are also controversial, since such genetically engineered organisms released into the environment could have an unknown and irreversible impact on the ecosystem. Asked in a interview with Reuters about that controversy, Gates said there were understandable concerns about safety and efficacy that would need to be addressed in research and trials. But he countered: “Malaria itself is quite controversial – it kills about 400,000 kids a year. So we’re definitely not on the side of malaria.”

He also noted that at their summit in January, leaders of the African Union endorsed gene drive research as part of the fight against a disease that continues to kill their people.

Source: https://www.reuters.com/