IDO, ITO, tryptophan, and Cancer Immunotherapy

One for the archives but this is interesting because it has long been known that tumours often express proteins that inhibit immune responses. http://medicalxpress.com/news/2012-01-cancer-therapy-preclinical.html ...

Scientists from the Ludwig Institute for Cancer Research (LICR) in Brussels identified a new target for cancer therapy, an enzyme which prevents the immune system from recognizing and destroying certain types of tumors. Called tryptophan 2,3-dioxygenase or TDO, the enzyme works by depriving immune cells of tryptophan, an amino acid essential to their activity. TDO is produced by a significant number of human tumors. Scientists also show that blocking TDO activity with a novel TDO inhibitor promotes tumor rejection in mice. The study findings were published online today in the January 30 issue of the Proceedings of the National Academy of Sciences (PNAS).

Do we control our Decisions?

Is there are real you?

The Geometry of Life

Long ago I heard about various bods trying to explore geometry as it relates to life. Now the research is getting interesting ... .

The basic idea of Dr. Andrulis' framework is that all physical reality can be modeled by a single geometric entity with life-like characteristics: the gyre. 

Cancer and Chromosomes - Again

Aneuploidy has been much neglected but is now gaining interest, possibly because after finding so many genetic alterations it has been realised that cancers are much more than about genes. There is one issue with this news release though. When they state:

"But in cancer, there are many cases of extra or missing chromosomes. Yet cancer cells thrive more effectively than other cells," Prof. Shamir says.


Yet in the paper I read the other day it was claimed that most cancer cells become senescent after 60-90 days(in their model at least). That makes sense because if a cell is being damaged or not working properly it will become senescent. Cancer cells don't thrive, the cancer stem cells may thrive, but even that is problematic. 

Cancer and Stem Cells

Ever wondered why a cancer treatment can so successfully reduce tumor size only to see it come back stronger than ever some months later? If you're prepared to investigate the mathematical model put forward in this paper then you'll have an interesting perspective on the challenge of cancer treatment and the realisation that modern cancer treatments are still missing a vital component in strategy.

Happy Dog.

Thorium and Climate Change

A friend of mine directed me to this TED talk. I have heard of the promise of thorium reactors and this talk by Kirk Sorensen is an excellent example of why we need to consider nuclear power for our future needs.




I do believe in AGW but I don't believe in props on sticks and shiny things facing the sky. These technologies have their place and will be important for our future energy needs but the current attempts to rely so much on these energy technologies is not only misguided it is a big mistake. We are planning to rely on environmentally contingent energy sources because we are convinced the environment is undergoing massive change. That does not make sense. We need energy sources that we have complete control over.

Because thorium is associated with nuclear people panic. It's that word thing again, too many people pay too much attention to words rather than meanings. Politicians use this to great effect the bastards. Thorium reactors, however, cannot melt down and the waste is very manageable. Recent designs in standard nuclear reactors has also led to the creation of meltdown proof reactors. The Chinese are the first nation to grid one of these new reactor designs.

Why thorium hasn't received more attention is beyond me. Except to say this: you cannot create fissile material with a thorium reactor. I don't think that is the major reason though, it is just typical of our species to fall into a mode of behavior and refuse to budge even when the evidence for change is overwhelming. Politicians use this to great effect the bastards.

We now cannot prevent climate change, it is already happening. We have to prepare for the future and if history is any guide the ability to harness and control energy is a key aspect of a civilisation's success. While I am an environmentalist I am also a realist. Human beings en masse will not change their behavior in time to prevent the ongoing environmental "degradation". ("Degradation" suggests some proper state for the earth. There isn't.) If we survive our civilisation will completely transform the ecology of this planet, and perhaps that last claim should be in the past tense. There is no balance, it is always changing, and as change agents we are Nature.

Listen to what Kirk Sorensen has to say. Because the whole climate change debate is largely driven by Green interests any type of nuclear power is off limits. Our future will demand nuclear power. If climate change is going to be as drastic as some of the alarmists claim then we're going to need huge amounts of manageable energy to address all the unexpected contingencies that will arise in the future. Controlled high energy sources, combined with automation, will enable us to transform the planet even further. We're going to do it because we've always done it and if you think you can stop it you are on the wrong planet.

House keeping and exercise

"House keeping" refers to an intra-cellular process that relates to the functions which involve removing excess and potentially dangerous molecules and detritus from the cell. It is crucial to cell function and survival. The main waste product that builds up is called lipofuscin, a set of lipids and proteins and lipoproteins that need regular removal before aggregation makes it too difficult to remove the same. Accumulation of lipofuscin can be taken as a marker of cell aging to developing strategies to maintain regular house keeping is very important because aggregates of molecules are extremely difficult to degrade.

For example, a key protein degradation pathway, the UPS pathway, has a severe limitation in that the organelle has a very narrow opening and hence will not allow aggregated proteins into the organelle to be digested. So it is essential we maintain UPS and the other key process mentioned in this article, autophagy, to maintain cellular health.

As this study highlights exercise is a good way to promote autophagy. So stop reading and go for a walk!

Chromosomes and Cancer

In my previous post, Cancer as a Metabolic Disease, I referenced an extensive review article that argues for a different etiology for cancer. Their argument is that it arises from mitochondrial dysfunction which in turn causes aneuploidy, the key focus of this recent research. As stated in the news release:

"The most common genetic change in cancer is the presence of an incorrect number of intact chromosomes within cancer cells -- a condition known as aneuploidy," 

 That remark is consistent with the claims of the earlier study. It is odd that only now is it beginning to receive more attention but that probably reflects the gene centric orientation of cancer research. It is tempting to think of these are competing paradigms but this is incorrect, the paradigms are complementary and together can provide a much better picture of what is happening in cancers. There is no single correct paradigm for understanding cancer. It can arise directly through specific mutations and through mitochondrial dysfunction. In the same way that cardiovsacular disease or neurodegeneration can arise through a number of risk factors, cancer can have multiple etiologies.

This suggests that those who propose magic bullets for cancer have completely misunderstood the nature of the pathology. Correct, they have. There are potentially many approaches to managing cancer, from increasing alkalinity to DCA, each cancer type may well respond to different strategies.

Cancer is NOT a single entity pathology!