Friday, March 24, 2017

Molecular Oncology: Accept No Substitutes

Telegraph |  Two thirds of cancers are unavoidable even if you live a healthy life, a study has shown.
Scientists in the US found cancers are caused by random mistakes in the genetic code that occur when cells divide.

The findings challenge the widespread view that cancer mutations are generally inherited or triggered by environmental factors.  Instead, the vast majority of cancers are probably down to unlucky defects in replicating DNA that occur out of the blue, they suggest.

Lead scientist Dr Cristian Tomasetti, from Johns Hopkins Kimmel Cancer Center in the US, said: "It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer.

"But it is not as well-known that each time a normal cell divides and copies its DNA to produce two new cells, it makes multiple mistakes.

"These copying mistakes are a potent source of cancer mutations that historically have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes."

The research, published in the journal Science, indicates that almost two-thirds of cancer-causing mutations are due to DNA copying errors.

Tuesday, March 21, 2017

Obesity, Toxic Fat. Diabetes - What If Our Current Understanding Is All Wrong?

theatlantic |  Scott was not named for the Scott Summers of Marvel fame (more commonly known as Cyclops), but this was the analogous origin story of a scientist. His father’s diagnosis was Scott’s transformative moment—his spider bite, radiation blast, or, in the case of Cyclops, attack of his family’s spacecraft by the interstellar Shi’ar Empire. And unlike some children who promise to cure their parents but then go into finance or real estate, Summers actually went to graduate school and got a Ph.D. in physiology.

When Scott left the Midwest to work in a lab at the University of Pennsylvania, he got his first insight toward a hypothesis that he believes could revolutionize our understanding of human metabolism and disease—and could help explain why skinny people aren’t necessarily metabolically healthy, or vice versa.

“We now know that both lean and obese individuals are susceptible to diabetes,” Summers, now the chair of nutrition and integrative physiology at the University of Utah, explained to me. “We think it’s basically because of their lipid compositions, and the accumulation of one type in particular—called ceramides—that might be increasing susceptibility of people to diabetes.”

At the heart of this idea is the model that says obesity is associated with diabetes and heart disease because all three are due to an error in the way the body stores energy. We carry most fat as triglycerides in adipose (“fat”) cells, which contain tremendous amounts of energy.

“That’s a pretty safe way to store it,” Summers explains. At least, it’s not necessarily unhealthy to have this type of fat. “But some of that stored fat can actually spill out into another pathway and give rise to ceramides. We think those tend to be pretty toxic.”

Ceramides are a family of waxy lipids that have even been called “toxic fat,” as they were in the press release for Summers’s latest study in the journal Cell Metabolism. The researcher Bhagirath Chaurasia, who works with Summers, clarified that “toxic fat” is an accurate, non-sensational term, in that ceramides are involved in the process of lipotoxicity. That is, they cause dysfunction in other lipids. Because in addition to storing triglycerides, adipose cells also help the body sense its nutritional status by secreting compounds that communicate with other cells. Among those signals are ceramides, and alterations in this process seem to be at the root of much metabolic disease.