Starving Cancers

This news item is interesting because it represents a novel strategy to delay tumour progression but that strategy is also unlikely to eradicate the tumour.

Short fasting cycles work as well as chemotherapy in mice
Even fasting on its own effectively treated a majority of cancers tested in animals, including cancers from human cells.

It touches on the Warburg Effect. You can read the Wiki entry on this but it has some errors. Notably:

• Glycolysis is not just anaerobic, it can also be aerobic. Hence the claims by some that oxygen therapy should kill cancers is just plain wrong. As I said to a friend recently, if oxygen is the enemy of cancer then explain lung and brain cancer. Can't be done. 
• The collapse of mitochondrial function still remains a mystery. Any cell may contain hundreds of mitochondria so we can rule our mtDNA changes, the causal agents here must be humoral. One possible candidate is UCP proteins, these proteins uncouple mitochondrial respiration from producing ATP. Brown adipose tissue uses this property to generate heat in our bodies. So we have a situation where this is a specific class of normal cells with UCP being ubiquitous but not driving cancer. That may be irrelevant because to my knowledge in adulthood we do not produce new fat cells, only make existing fat cells fatter. So fat cells may be oncologically disabled. 

Why Does Fasting Have This Effect?

The Warburg Effect, which is surprisingly common if not pervasive in cancer cells, makes the cell entirely dependent on sugar. Caloric Restriction does very much lower the incidence of cancer but comes at a big cost. That being:

• Compromised fertility
• Potentially reduce immunological status. 
• Hypoglycemia
• In humans I suspect over the long term it damages cognition(Neurons are entirely dependent on sugar, astrocytes absorb sugar from the bloodstream, convert it to pyruvate, which is then excreted to the extra cellular space, where it is then picked up by neurons. 

Caloric Restriction is impractical and unnecessary. Short intermittent fasting can do provide many of the same benefits. It is my view that if you are concerned about cancer prevention then learning to fast is a good idea. Stop the cancer before it stops you because nearly all of us have nascent tumours. It is a probability game and intermittent fasting helps stack the odds in your favour by promoting cell death in pre-cancerous and cancerous cells.

Fasting can induce sugar loss but keep in mind that despite all the hype about the dangers of sugar we'd be dead without it. Our brains our critically dependent on sugar, whether it be from glucose, fructose, or carbs(reduced to sugar via our bodies), we need that sugar in our bodies, hence the large reserves stored in our liver and muscles as glycogen. It therefore becomes problematic that collapsing sugar levels is a key component in the anti-cancer effects of CR and fasting. In fact, without experiencing hypoglycemia, which knocks you to the floor and carries its own risks, including brain damage, I'm not sure how collapsing sugar intake can be beneficial in treating cancers. So .... .

A very notable effect found in Caloric Restriction studies is that very substantial decline in Insulin Growth Factor prodn. We are talking about multiple declines in concentration here, not just a dip but a big decline. Sugar levels play an important role in regulating insulin growth factor levels. Insulin growth factor, stimulated for release and production from the liver by Human Growth Hormone, is the key growth factor. This addresses the above quandary because reducing sugar levels will have an immediate impact on growth factor production. As there is an increasing view that cancers are being driven by cancer stem cells, and these cells are signalled by growth factors, and the recent trend towards identifying inhibitors of growth factor receptors in cancerous cells, this suggests that real benefit of fasting is not sugar restriction per se but rather its impact on growth factor production.

This study highlights an ongoing and mysterious problem with cancers treatments:

As with any potential cancer treatment, fasting has its limits. The growth of large tumor masses was reduced by multiple fasting and chemotherapy cycles, but cancer-free survival could not be achieved. Longo speculated that cells inside a large tumor may be protected in some way or that the variety of mutations in a large mass may make it more adaptable.

Clonal selection, somatic evolution, what a damned nuisance! It large tumours it may even be the case that the surviving cells are feeding off the debri from all those dead cells! Don't know. Alternatively, even in apoptosis, there is some degree of inflammation present and this may drive increased blood supply when large numbers of apoptotic cells are present as inflammation generally increases blood and nutrient flow to a given region. That is the primary purpose of inflammation, it "opens up" the blood vessels to allow in various immune cells, growth factors, and nutrients to enter into the damaged tissue. Don't friggin know!

New Approach to Cancer Stem Cells

This will be the most important focus of future cancers research.

Collaborative Research Sheds Light On New Cancer Stem Cell Therapies

...

A collaborative anti-cancer research jointly conducted by The Hong Kong Polytechnic University (PolyU), Peking University Shenzhen Graduate School and Nevada Cancer Institute has led to the development of a novel class of chemical inhibitors that specifically target cancer cells with pluripotency.

1. Felix Cheung. Cancer biology: Ridding the seeds of evil. Nature China, 2012; DOI: 10.1038/nchina.2012.1
2. J. Wang, F. Lu, Q. Ren, H. Sun, Z. Xu, R. Lan, Y. Liu, D. Ward, J. Quan, T. Ye, H. Zhang. Novel Histone Demethylase LSD1 Inhibitors Selectively Target Cancer Cells with Pluripotent Stem Cell Properties.Cancer Research, 2011; 71 (23): 7238 DOI: 10.1158/0008-5472.CAN-11-0896

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.