Posts Tagged ‘Cancer’

Swedish study says antioxidants also protect cancer cells

October 13, 2015

A new paper from Sahlgrenska Academy in Gothenburg shows that

Antioxidants can increase melanoma metastasis in mice, K Le Gal et al, Science Translational Medicine, 07 Oct 2015:
Vol. 7, Issue 308, DOI: 10.1126/scitranslmed.aad3740

First antioxidants were good for you, then they were of doubtful benefit and now it seems they are positively bad. Many foods containing antioxidants have been touted for their health benefits and have included chocolate, fresh fruits and vegetables, nuts, whole grains, maize, legumes and eggs. Red wine was on the list but the benefits of Resveratrol have already come under a cloud for alleged data tampering.

Of course, perceived antioxidant benefits have not much influenced my own consumption of dark chocolate and red wine. But what the study finds is that  “the overall conclusion from the various studies is that antioxidants protect healthy cells from free radicals that can turn them into malignancies but may also protect a tumor once it has developed”.

So antioxidants can help prevent a cancer developing, but once the cancer is there antioxidants can speed up the progression of the cancer. Dark chocolate and red wine therefore remain on the  “good foods list” for those who do not have any cancerous cells.

Sahlgrenska Press Release:

Fresh research at Sahlgrenska Academy has found that antioxidants can double the rate of melanoma metastasis in mice. The results reinforce previous findings that antioxidants hasten the progression of lung cancer. According to Professor Martin Bergö, people with cancer or an elevated risk of developing the disease should avoid nutritional supplements that contain antioxidants.

Researchers at Sahlgrenska Academy, University of Gothenburg, demonstrated in January 2014 that antioxidants hastened and aggravated the progression of lung cancer. Mice that were given antioxidants developed additional and more aggressive tumors. Experiments on human lung cancer cells confirmed the results.
Given well-established evidence that free radicals can cause cancer, the research community had simply assumed that antioxidants, which destroy them, provide protection against the disease. Found in many nutritional supplements, antioxidants are widely marketed as a means of preventing cancer. Because the lung cancer studies called the collective wisdom into question, they attracted a great deal of attention.

The follow-up studies at Sahlgrenska Academy have now found that antioxidants double the rate of metastasis in malignant melanoma, the most perilous type of skin cancer. Science Translational Medicine published the findings on October 7.
“As opposed to the lung cancer studies, the primary melanoma tumor was not affected,” Professor Bergö says. “But the antioxidant boosted the ability of the tumor cells to metastasize, an even more serious problem because metastasis is the cause of death in the case of melanoma. The primary tumor is not dangerous per se and is usually removed.”

Experiments on cell cultures from patients with malignant melanoma confirmed the new results. “We have demonstrated that antioxidants promote the progression of cancer in at least two different ways,” Professor Bergö says.
The overall conclusion from the various studies is that antioxidants protect healthy cells from free radicals that can turn them into malignancies but may also protect a tumor once it has developed. 

Taking nutritional supplements containing antioxidants may unintentionally hasten the progression of a small tumor or premalignant lesion, neither of which is possible to detect.
“Previous research at Sahlgrenska Academy has indicated that cancer patients are particularly prone to take supplements containing antioxidants,” Dr. Bergö says. “Our current research combined with information from large clinical trials with antioxidants suggests that people who have been recently diagnosed with cancer should avoid such supplements.”

 

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A few extra copies of p53 and we could also suppress cancerous tumours

October 9, 2015

Elephants should get cancer 100 times more often than humans but instead they have a cancer mortality rate which is at 20-50% of the rate in humans. Cell for cell therefore, elephants are 200 to 500 times less likely to develop cancer than humans. Genetic studies may have revealed why that is so. They have 38 additional copies of a tumor suppressing gene (p53) while humans have only two.

Sounds fascinating. If we could only ingest some additional copies of a specific genes, of which humans have only two, we may be able to suppress cancerous tumours.

Wikipedia tells me that

Tumor protein p53, also known as p53, ……. is any isoform of a protein encoded by homologous genes in various organisms, such as TP53 (humans) and Trp53 (mice). …. p53 has been described as “the guardian of the genome” because of its role in conserving stability by preventing genome mutation. ….. The International Cancer Genome Consortium has established that the TP53 gene is the most frequently mutated gene (>50%) in human cancer, indicating that the TP53 gene plays a crucial role in preventing cancer formation. TP53 gene encodes proteins that bind to DNA and regulate gene expression to prevent mutations of the genome.

Now a new paper reports a study on why elephants rarely get cancers and finds that elephants have 38 copies of p53 whereas humans have only two.

Press Release Huntsman Cancer Institute:

Why Elephants rarely get cancer

…. elephants have 38 additional modified copies (alleles) of a gene that encodes p53, a well-defined tumor suppressor, as compared to humans, who have only two. Further, elephants may have a more robust mechanism for killing damaged cells that are at risk for becoming cancerous. In isolated elephant cells, this activity is doubled compared to healthy human cells, and five times that of cells from patients with Li-Fraumeni Syndrome, who have only one working copy of p53 and more than a 90 percent lifetime cancer risk in children and adults. The results suggest extra p53 could explain elephants’ enhanced resistance to cancer.

Joshua D. Schiffman, MD et al. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA, October 2015 DOI:10.1001/jama.2015.13134

According to Schiffman, elephants have long been considered a walking conundrum. Because they have 100 times as many cells as people, they should be 100 times more likely to have a cell slip into a cancerous state and trigger the disease over their long life span of 50 to 70 years. And yet it’s believed that elephants get cancer less often, a theory confirmed in this study. Analysis of a large database of elephant deaths estimates a cancer mortality rate of less than 5 percent compared to 11 to 25 percent in people.

In search of an explanation, the scientists combed through the African elephant genome and found at least 40 copies of genes that code for p53, a protein well known for its cancer-inhibiting properties. DNA analysis provides clues as to why elephants have so many copies, a substantial increase over the two found in humans. A substantial majority, 38 of them, are so-called retrogenes, modified duplicates that have been churned out over evolutionary time.  

Schiffman’s team collaborated with Utah’s Hogle Zoo and Ringling Bros. Center for Elephant Conservation to test whether the extra gene copies may protect elephants from cancer. They extracted white blood cells from blood drawn from the animals during routine wellness checks and subjected the cells to treatments that damage DNA, a cancer trigger. In response, the cells reacted to damage with a characteristic p53-mediated response: they committed suicide.

“It’s as if the elephants said, ‘It’s so important that we don’t get cancer, we’re going to kill this cell and start over fresh,’” says Schiffman. “If you kill the damaged cell, it’s gone, and it can’t turn into cancer.  This may be more effective of an approach to cancer prevention than trying to stop a mutated cell from dividing and not being able to completely repair itself.”

I don’t understand any of this but can imagine that in a 100 years or so, children will routinely be given “genetic p53 shots”  — as routinely as they get vaccinations today. It’s not as if we don’t already have the gene. So just arranging a few extra copies of a gene we already have, doesn’t sound Frankensteinian and should not lead to developing elephantine features.

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Get yourself a luck-bucket

January 2, 2015

The new paper in Science showing that two-thirds of all cancers are due to random cell mutations and not due to life-style, environmental conditions or inherited predispositions, is getting a lot of attention today.

Abstract: Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.

Nearly every newspaper headline describes these random cell mutations as being “bad luck”. And that got me to wondering about the nature of “luck” and our perceptions of “luck”.

To be “lucky” an event has to be improbable. The consequences of the lucky event may be good or bad. “Luck” or “fortune” if not qualified by the word “bad” are generally taken to be “good”. Any event which is expected is never classified as being “lucky”. That somebody will win the lottery is highly likely and is not a matter of luck. That one particular person shall win the lottery will always have a very low probability and therefore becomes a lucky happening. All those who didn’t win are not “unlucky” because their loss was expected. But to have the winning ticket which is then carried away in an improbable gust of wind could be considered “unlucky”.

I like to think of luck or fortune as a flowing river. But not everybody is near this river and not all the flow is advantageous. Some of the flow is downright poisonous. The person with “good luck” is then the person who is not only near the river but also has a bucket to capture some of the advantageous flow. The difference between the lucky person and the ordinary person is then access to the river and the existence and the suitability of the “bucket”. I think of a person with “bad luck” as one with an ineffective bucket who picks up some of the “poisoned” or disadvantageous flow. The bucket is both a container and a filter. The Romans praying to the Goddess Fortuna or Hindus praying to Lakshmi are effectively trying to buy their “luck catching buckets”. Sportsmen or gamblers going through superstitious rituals before a match or a play are trying to prepare their “luck buckets”. I used to have a “lucky tie” that I always wore to job interviews. I see athletes and footballers cross themselves before their race or their game but they are only praying for their buckets.

Statistically it may be inevitable that there will be some lottery winner. The intelligent designer of the lottery well knows that he will pay out. But he does not know to whom. And he cannot exercise the control to determine (except in a rigged lottery) the winner. There are – in a simple lottery – two random events to consider:

  1. the process by which the lottery tickets are distributed, and
  2. the process by which the number of the winning ticket is selected.

Suppose there are a million tickets numbered one to one million and that one of these numbers will be selected. There is a certainty that a winning ticket will be declared. The operator of the lottery has no need of and no recourse to luck. I have to first acquire a ticket and then my number has to be selected. The odds of my being in the game are somewhat less than one and only then would I have a one-in-a-million chance of winning. My luck-catching bucket does not have to control both these events but it does need to be able to ensure that I get a number and that the particular number allocated to me is also the particular number selected to win.

So the task is to get myself an effective luck-bucket which is not too unwieldy. An instruction manual on how to use it would be helpful But first I need a map showing me where the Luck River flows. But if I don’t have a lottery ticket my luck-bucket won’t help me. So perhaps the first thing to do is to get myself into the right game.

But my buying a lottery ticket is so improbable that this too is a matter of Luck.

There’s a hole in my bucket, dear Liza, dear Liza,
There’s a hole in my bucket, dear Liza, a hole.

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