Category Archives: Transhuman News

Published December 30, 2014

Scientists have begun clinical trials for the treatment of a gene mutation linked to multiple cancers, reveals a study published Tuesday in the journal Cancer Discovery.

In 1982, researchers discovered that the gene TRK caused a small percentage of colon cancers. In 2013 and 2014, studies linked the gene to at least 11 tumor types, including lung, breast and skin cancer. Modern technology has finally enabled researchers to test potential treatments for these gene abnormalities.

Now technology lets us find the gene in actual patient samples, and drugs are available to target these gene rearrangements making it possible to treat TRK cancers in clinical trials in ways we only dreamed of 32 years ago," Robert C. Doebele, investigator at the CU Cancer Center and associate professor of medical oncology at the CU School of Medicine, said in a news release.

In the womb, the TRK family of genes and the proteins they encode are crucial for the development and survival of neurons. After birth, they are programmed to go dormant, but when they improperly fuse with other nearby genes, the TRK genes can resume signaling cells to grow and become immortal. In adult tissue, this process can cause cancer.

"What we're finding is that while TRK fusions may not be the major cause in any single, major cancer, it's the cause of small percentages of many cancer types," Doebele said.

Doebeles study cites previous research that suggests TRK fusions are responsible for 3.3 percent of lung cancers, 1.5 percent of colorectal cancers, 12.3 percent of thyroid cancers, about 2 percent of glioblastomas, and 7.1 percent of pediatric gliomas (brain tumors). These numbers add up when they are considered together, Doebele said.

While treatments for TRK fusions were nonexistent a decade ago, today, a class of drugs has been developed to target this type of genetic abnormality. Tryrosine kinase inhibitors in particular can switch off these genes, and the Food and Drug Administration (FDA) has approved a drug that targets two different types of fusion genes in lung cancer.

"A lot of doctors in academia or community hospitals are ordering next-generation sequencing panels for their patients, Doebele said. If it turns out that patients' tumors have TRK alterations, I want their doctors to know that there are treatment options available via clinical trials.

View post:
Scientists begin testing drugs for gene mutation linked to multiple cancers

Contact Information

Available for logged-in reporters only

Newswise Case Western Reserve researchers have identified a two-pronged therapeutic approach that shows great potential for weakening and then defeating cancer cells. The teams complex mix of genetic and biochemical experiments unearthed a way to increase the presence of a tumor-suppressing protein which, in turn, gives it the strength to direct cancer cells toward a path that leads to their destruction.

If the laboratory findings are supported by tests in animal models, the breakthrough could hold the promise of increasing the effectiveness of radiation and chemotherapy in shrinking or even eliminating tumors. The key is to build up a good protein p53-binding protein 1 (53BP1) so that it weakens the cancer cells, leaving them more susceptible to existing cancer-fighting measures.

The breakthrough detailed appeared in the Nov. 24 online edition of the journal PNAS (Proceedings of the National Academy of Sciences).

Our discovery one day could lead to a gene therapy where extra amounts of 53BP1 will be generated to make cancer cells more vulnerable to cancer treatment, said senior author Youwei Zhang, PhD, assistant professor of pharmacology, Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center. Alternatively, we could design molecules to increase levels of 53BP1 in cancers with the same cancer-killing end result.

The cornerstone of the research involves DNA repair more specifically, double-stand DNA repair. DNA damage is the consequence of an irregular change in the chemical structure of DNA, which in turn damages and even kills cells. The most lethal irregularity to DNA is the DNA double-strand break in the chromosome. DNA double-strand breaks are caused by everything from reactive oxygen components occurring with everyday bodily metabolism to more damaging assaults such as radiation or chemical agents.

The body operates two repair shops, or pathways, to fix these double strand breaks. One provides rapid, but incomplete repair namely, gluing the DNA strand ends back together. The problem with the glue method is that it leaves the DNA strands unable to transmit enough information for the cell to function properly leading to a high cell fatality rate.

The second shop, or pathway, uses information from intact, undamaged DNA to instruct damaged cells on how to mend broken double strands. During his study, Zhang and fellow investigators discovered a previously unidentified function of a known gene, UbcH7, in regulating DNA double-strand break repair. Specifically, they found that depleting UbcH7 led to a dramatic increase in the level of the 53BP1 protein.

What we propose is increasing the level of 53BP1 to force cancer cells into the error-prone pathway where they will die, Zhang said. The idea is to suppress deliberately the second accurate repair pathway where cancer cells would prefer to go. It is a strategy that would lead to enhanced effectiveness of cancer therapy drugs.

Read more from the original source:
Cancer Treatment Potential Discovered in Gene Repair Mechanism

Rhys Evans life could have been very different.

He could have been a bubble boy, forced to walk around in a protective see-through plastic canopy. You see, he was born with an immune system that barely worked. The slightest infection could have proved fatal. But Rhys is now 14years old and doing fine.

So how did Rhys avoid living in a bubble?

The simple answer is that Rhys got lucky his condition was diagnosed when he was a baby. Even more fortunately, doctors at Great Ormond Street Hospital were able to do something about it. They understood that Rhyss condition was caused by a genetic flaw and they thought that if they could correct this flaw then they could restore his immune system. That is exactly what happened, and why Rhys is now no different to any other young teenager.

Rhyss treatment is an example of gene therapy, which was the subject of a fascinating lecture that I attended last month. Leonard Seymour, professor of gene therapies in the Department of Oncology at Oxford University, gave four reasons why 2014 has been a breakthrough year for this revolutionary, but controversial, approach.

Let me begin by describing these successful trials.

Rhys Evans is not the only boy (it does not affect girls) to have received gene therapy for this syndrome 20 were given it at about the same time as Rhys. But he was lucky. In the trial, one in four ended up with leukaemia.

This year has seen the results of a new trial. In this, nine boys were treated and eight have been reported as still alive, 16 to 43 months after treatment. The ninth died from an infection already present when he began the gene therapy. Overall, the outcome is hugely promising and suggests that gene therapy could provide a permanent cure for patients who would otherwise receive a bone marrow transplant from a donor, with all the consequent risks of rejection.

HIV is a virus that weakens the immune system by destroying the white blood cells that fight disease and infection. In order to destroy the cells it has to enter them, and it does this via a protein called CCR5, found on the cell surface. Researchers have noticed that about 1% of patients contract HIV and yet come to no harm. The reason is that their cells have a rare genetic mutation which prevents them from displaying the CCR5 protein on their surface.

Now researchers have managed to engineer white blood cells so that they have this same rare mutation. They have injected billions of these genetically modified cells into 12 trial patients, and there is evidence that this procedure is safe and could suppress the virus.

See original here:
Why 2014 has been a breakthrough year for gene therapy

Published December 30, 2014

U.S. scientists have identified a molecular network of genes known to contribute to autism spectrum disorders, and they say their finding may help uncover new genes linked to these conditions.

"The study of autism disorders is extremely challenging due to the large number of clinical mutations that occur in hundreds of different human genes associated with autism," study author Michael Snyder, genetics and personalized medicine professor at Stanford University, said in a news release. "We therefore wanted to see to what extent shared molecular pathways are perturbed by the diverse set of mutations linked to autism in the hope of distilling tractable information that would benefit future studies."

According to the news release, researchers used gene expression data and genome sequencing to study the whole set of interactions within a cell, and they identified a module comprised of 119 proteins linked to autism genes.

The sequencing of the genomes was present in 25 study participants who had been diagnosed with autism, which confirmed the involvement of the module in autism. The autism candidate genes in the module were also present in more than 500 diagnosed patients who were analyzed by exome sequencing.

Researchers also found that the corpus callosum and oligodendrocyte cells in the brain can contribute to autism. Oligodendrocytes are myelin-forming cells of the central nervous system, and the corpus callosum is a huge band of myelinated fibers. Myelin, which is comprised of proteins and phospholipids, forms a sheath around nerve fibers and increases the speed at which impulses are conducted.

"In the future, we need to study how the interplay between different types of brain cells or different regions of the brain contribute to this disease, study author Jingjing Li, postdoctoral fellow at the Stanford Center for Genomics and Personalized Medicine, said in the news release.

Snyder said the module enriched in autism had two distinct components that exclusively interacted with each other: one that was expressed throughout different regions of the brain, and another that had enhanced molecular expression in the corpus callosum.

Based on their findings, the study authors hypothesized that disruptions in parts of the corpus callosum interfere with the circuitry that connects the two hemispheres of the brain, resulting in autism.

"Our study highlights the importance of building integrative models to study complex human diseases," Snyder said.

Go here to read the rest:
US researchers identify gene network linked to autism