Those poor devils

Tasmanian devils are notoriously nasty, even to each other. They have teeth and aren’t afraid to use them. As a result, they tend to bite and nip at the faces of their brethren. And unfortunately, this has resulted in the spread of a contagious form of cancer that has wiped out 70% of the population.

But there is good news. Researchers have discovered that the reason the tumors are able to spread so efficiently (escaping immune system detection) is that its cells lack major histocompatibility complex molecules, or MHC molecules. The Tasmanian devil’s immune system can’t ‘see’ what’s coming. This, of course, isn’t unique amongst cancer cells, but what is a little different is that these MHC molecules aren’t simply broken via mutation. They are actually turned off due to regulation. This means they are intact and can be turned back on. (It also means that, in conjunction with the contagious factor, it wouldn’t be inappropriate to consider this cancer a separate organism, however parasitic.)

There is hope for the Tasmanian devil, albeit far down the road. Until then, quarantine and luck are the only viable solutions for saving this animal from extinction.


WHO issues warning about tanning beds

This is from 2009 (though it should be from 1995), but I just came across it:

In July, the International Agency for Research on Cancer (IARC), a working group of the World Health Organization, added ultraviolet (UV) radiation-emitting tanning devices – tanning beds and lamps – to the list of the most dangerous forms of cancer-causing radiation. It joins an assembly of hazardous substances including plutonium and certain types of radium, as well as radiation from the sun.

The IARC report cited research showing that tanning is especially hazardous to young people; those who use sunbeds before age 30 increase their lifetime risk of melanoma, the deadliest form of skin cancer, by 75 percent. The authors also pointed to studies showing a link between UV radiation from indoor tanning devices and melanomas of the skin and eyes. Melanoma will kill an estimated 8,650 people in the US this year alone. And melanoma isn’t the only problem: people who use tanning beds are 2.5 times more likely to develop squamous cell carcinoma and 1.5 times more likely to develop basal cell carcinoma. Squamous cell carcinoma kills an estimated 2,500 Americans a year.

I am absolutely convinced that people do not appreciate the tenacity and seriousness of cancer. There seems to be a it-won’t-happen-to-me attitude that pervades society. Or maybe quacks have lulled people into a false sense of security. Just take some garlic, laxatives, and a little black elderberry and you’ll be fine! For Christ’s sake. I recently developed a small splotch on my nose. It wasn’t a blackhead and it didn’t go away after a couple of weeks, so I made an appointment to get it checked out (alongside a physical). I figured it was nothing given its color and shape, but why take risks? It matters how quickly these things are identified. It turned out, as I figured, to be nothing more than a new freckle (probably a result of my time in Haiti or some of the nicer days we had not too long ago). I’m fine this time, but who knows about next time? I’m not somehow magically exempt from how biology works. Neither is anyone else. I am, however, exempt from a 75% increase in getting melanoma. Also, think about this:

Attack of the DNA robots

Whereas bombing raids in the early and mid part of the 20th century involved hardly any direction, any bombing that we do today is going to be highly precise. This so-called smart bombing has constituted one of the great military advances over the past several decades. It’s efficient, cost-effective, and saves civilian lives. Now keep that in mind as I move into the non-military world of fighting cancer.

In one form or another researchers have been working to create DNA carrying/laden devices for years now. The application potential is huge, but the area that has received some of the greatest focus has been cancer research. The drugs and treatments we have now are inexact and not always effective. Aside from often killing healthy cells, thus leading to weight and hair loss, general illness, and other negative side-effects, they don’t always kill every cancer cell. Even surgery can be a bad thing at times. Consider for a moment what tumors need. More than perhaps anything is a blood supply. (The same goes for your regular cells; your skin cells are too far from a blood source, hence why they are little more than dead keratin.) In order to get their supply of blood, tumors must induce angiogenesis, the growth of new blood vessels. They do this by releasing certain stimulators. They also release inhibitors, but not enough to overwhelm the stimulators. However, these inhibitors have no problem traveling through the blood stream. The result is often the suppression of secondary tumors, especially if they are nearby. So when a surgeon removes a primary tumor, those other, previously restricted secondary tumors will have a chance to grow. And that is no good, of course. In short, the more exact we can get in destroying cancerous cells, the better off we will be.

Enter DNA nanobots.

I like to think of these as smart bombs of cancer cells. They are bits and pieces of DNA naturally self-assembled into a particular shape (the barrel in the background) that is prepared to deliver a payload. That payload (the purple/pink stuff) is attached to specific strands (the yellow/green stuff) inside the DNA barrel structure. This is all held together by strands of DNA which are programmed to recognize specific molecules on the target cells (in this case, cancer cells). When the DNA attaches to these molecules, it changes shape and opens up the barrel. The payload is then free to enter into the target cell, inducing apoptosis (cellular suicide). Experiments have shown that these DNA robots are able to avoid healthy cells during this process.

There are, of course, limitations to this technology. Take malaria, for instance. It would be difficult to target most strains (such as P. vivax and P. falciparum) because they get inside hemoglobin rather than attach to the outside of anything. That makes them effectively invisible to both our immune system and these nanobots. Strategies for fighting that disease will tend towards the sort of medications we’re using now combined with bed nets and efforts to destroy mosquito habitats.

Still, this is exciting. I say that about most cancer-related advances, but I don’t feel I’m ever overdoing it. Every little bit of progress is crucial, even the bits that don’t pan out. I have hopes for this one, though. Even if it doesn’t end up being pragmatic in application, it still has the potential to 1) increase our understanding of cancer and 2) be used in so many other ways. Three cheers for science.

Sources: Here and here.

How the future of cancer research is shaping up

There are two foundational concepts a person must understand before he can say he understands biology. First, all life has evolved from a common ancestor via natural selection. Miss this concept and one has no reference frame for anything within the entire field. It would be like trying to grasp physics without understanding gravity. Second, it’s all about shape. This can apply to many other fields, but it is an essential concept within biology. The molecules within living organisms are like pieces of a puzzle, or like keys and key holes. However one wishes to think about, biology really is about shape. Now with that in mind, I turn to some really awesome cancer research.

[Bruce] Levine and his colleagues designed a new gene that can be inserted into T cells to trick them into attacking cancerous B cells, the cause of chronic lymphocytic leukemia (CLL). The new gene encodes a receptor that, on one end, can bind to a molecule that’s unique to cancerous B cells. The other end of the receptor sets off a chain reaction when such a B cell is bound, eventually leading the T cell to destroy the cancerous cell. “Essentially, we’re converting T cells that would normally recognize other types of cells to be tumor specific,” Levine says.

In many ways, this is very much a basic immune response. The difference here is that gene transfer techniques have been used to modify the shape of the T cells to recognize particular cancerous cells, something which does not normally happen. As the article states, one patient went from having 170 out of 200 cells containing a cancer-causing mutation to having all signs of his leukemia vanish. The paper itself goes further and says tests showed 198 out of 200 cells to be negative for that mutation, which is within the normal range for such tests.

The insertion of these modified cells was not without complications. The cells themselves are without toxicity, but within two weeks the patient was experiencing a low-grade fever and chills, both of which intensified and required a short hospitalization. He also had tumor lysis syndrome, which could be expected – and is ultimately a good thing. It’s a common condition after certain types of cancer treatment (though it had not previously been reported in cellular immunotherapy). Basically, cell lysis is when a cell is destroyed and its contents spill out. Often, this constitutes a significant release of chemicals which cause a reaction. It can be quite dangerous, but then, so is cancer.

While this research is cause for a lot of excitement, I think, there also must be much reservation. The test subjects number a whopping three patients. Furthermore, they’ve only been tracked for approximately a year since treatment. It is fortunate that they still contain within them cells with the inserted gene – it’s self-propagating since it gets passed on with somatic division just like any other gene – but more time needs to pass before too much more can be said (not to mention the dramatic need for a much larger sample). There is also concern that there could be long-term deficiency of B cells in patients since the genetically modified cells do attack normal B cells as well as the cancerous ones. These are all things that can be clarified with continued research – and I’m confident “with continued research” is a phrase that is more than traditional lip service, in this case.

Why quacks should be more cautious

One of the hallmarks of quacks is that they’re willing to latch on to any bit of science that shows even the most remote, most distant promise. One familiar quack did this for a preliminary study not too long ago. And other quacks do it all the time. They hear about some result which indicates some positive benefit from something – usually a berry or herb – and they go nuts. Forget that they reject just about everything else science has to tell us. If it fits into their paradigm, it must be true.

But of course they’re jumping the gun. Again and again a study will come out which shows promise for some substance that will help in the fight against this or that disease, but once a few more groups start taking a look, things fizzle out. Often studies will even get to the clinical stage, only to turn out to be failures. (“Failures” in the sense of not working, not in terms of science.) Companies usually are decent at protecting themselves from getting that deep if there is no benefit to be had, but they aren’t perfect.

I go on about this because I am currently reading a review article about the protein p53. It is a protein which is involved in tumor suppression. When it mutates, usually by missense mutation, it becomes involved in tumor growth by virtue of loss of function, though evidence strongly suggests that it also confers a gain of function in terms of cancer growth. I’ve written about other tumor suppressing proteins here.

I had to stop when I got to a section about post-translational modifications of the protein:

Post-translational modifications of p53 such as phosphorylation, acetylation or sumoylation have been shown to be essential in determining and regulating p53 activity in vitro. However, their effects in vivo remain difficult to assess. Sabapathy (S1) generated a ‘knock-in’ mouse strain replacing the serine 312 residue, equivalent to the human serine 315, by alanine (S312A) to abolish phosphorylation. This residue has been proposed to have a role in the regulation of p53 protein stability. p53S312A/S312A knock-in mice are viable, fertile and not –pre-disposed to spontaneous tumor formation. In addition, the p53S312A protein was found to be activated as efficiently as wild-type p53 and its turnover rate was not affected, suggesting that despite in vitro evidence this phosphorylation event may not be critical for in vivo suppressive functions.

Let’s get some of the terms out of the way. “Phosphorylation”, “acetylation”, and “sumoylation” all refer to the addition of certain chemical groups (such as phosphates) to the protein – it’s basically attaching stuff to p53. “In vitro” pretty much refers to the testing of cells in a test tube (or Petri dish, or whathaveyou) whereas “in vivo” refers to testing done on whole organisms. “Sabapathy” is a person, not a biological term. “Knock-in” refers to a type of genetic engineering. “Wild type” means the default protein, or the protein as it “normally” would appear, unmutated. (I’ve always found the term counter-intuitive.)

Now, presuming anyone is still with me here, the important aspect of the above excerpt is where it says, “In addition, the p53S312A protein was found to be activated as efficiently as wild-type p53 and its turnover rate was not affected, suggesting that despite in vitro evidence this phosphorylation event may not be critical for in vivo suppressive functions.” In other words, the genetically altered ‘test tube’ results showed that the addition of a chemical group was important, but further evidence showed otherwise. One thing this means, as all scientists know, is that we ought not jump the gun.

Another way to think of these results is to compare red hots dogs and apples. Each one is known to contain nitrites, which is a chemical compound linked to cancer. However, whereas red hot dogs have a small connection to tumor development, apples have no connection. Why? There is a complex interaction between meat and nitrites which results in the production of the actual carcinogenic compound. Apples, on the other hand, even if they did interact with other chemicals (probably ones within the body), have components which would help the immune system and thus help prevent cancer, at least to some degree. Or to use another comparison, tobacco cigarettes and marijuana contain a ton of carcinogens, but only one (cigarettes) has a causative link to cancer. Presumably some other chemical(s) in marijuana counteracts the carcinogens. But however the cancer is prevented, it happens through a complex interaction that needs to be studied. Lab results are wonderful and they’re a major reason why we live so healthy and so long today, but they aren’t the final word. In fact, we ought not think of anything within biology as being the final word. We have large scale statistical results that will be true in virtually all cases, but there are no hard and fast rules for how organisms will interact with their environments. We need to test and test and test – and science will always do that – but the real solution here is that we need to be sure we aren’t jumping the gun. After all, no one wants to be a quack.

Cancer claims and reality

Yahoo! Health has a short article up that I just love. It helps to demonstrate some of the points I’ve recently been making about how science works, and it makes a good example of how easily misinformation can spread among the lay population when there isn’t proper follow-up into the reality of the evidence.

Antiperspirant and Deodorant

The link: A decade ago, an E-mail warning women that using antiperspirant could cause breast cancer went viral. Since then, some research has suggested that aluminum in antiperspirants and preservatives called parabens in both antiperspirants and deodorants mimic the hormone estrogen, which in high amounts can increase a woman’s breast cancer risk.

The reality: There is no evidence that antiperspirants or deodorants cause cancer. Although a 2004 study heightened concern when researchers found parabens in breast cancer tissue samples, suggesting the chemicals may have caused the tumors, the investigators did not check for the presence of parabens in healthy tissue. Evidence suggests that 99 percent of us are exposed to parabens from numerous sources, including various cosmetics and foods, according to the American Cancer Society. Little evidence indicates they may be harmful. The organization says more study is needed to be certain that there is no risk. A 2002 study of hundreds of women with and without breast cancer, found no sign the antiperspirants or deodorants upped cancer risk.

The rising cost of cancer

Cancer costs more and more every year for a couple of key reasons. First, people are always getting tested and diagnosed at higher rates. This is a big reason why cancer rates were seemingly so low just 100 years ago. Second, cancer is most prevalent as we age. As the baby boomers grow older, we are going to find more and more incidences of cancer. (There are, of course, more reasons, including inflation and other economic factors.)

Government researchers have recently figured several estimates for the cost of cancer care in 2020. They include:

* Using data from a 2005 national database, the team estimated medical costs associated with cancer were $127.6 billion in 2010.

* Assuming stable costs and survival rates, cancer costs will reach $158 billion in 2020.

* If the costs of cancer diagnostic tests and treatments rise 2 percent per year, the cost of treating cancer could rise to $173 billion by 2020.

* If treatment costs rise 5 percent per year, treating cancer in the United States could jump to $207 billion a year.

* In 2010, breast cancer was the most costly to treat at an estimated $16.5 billion, followed by colorectal cancer at $14 billion, lymphoma at $12 billion, lung cancer at $12 billion and prostate cancer at $12 billion.

* If cancer incidence and survival rates remain stable, the number of cancer survivors in 2020 will increase by 31 percent to about 18.1 million.

* Because of the aging of the U.S. population, the largest increase in cancer survivors over the next 10 years will be among Americans age 65 and older.

Short of a cure, the best way we can reduce these numbers will be to do all we can to avoid known carcinogens. That means doing everything we can to limit smoking. (I favor an outright ban.) It means discouraging tanning booths. (I favor an outright ban.) It means encouraging people to use sunscreen. (A requirement would be far from anything practical, thus I do not favor it.) It means getting kids to eat healthier. It means getting adults to eat healthier. It means doing a whole lot of things we all know we ought to be doing.

I expect a continued rise in costs.

Sunny cream

As my guide in Africa frequently said, bring much sunny cream. It’s going to protect against both sunburns and cancer. (Get the stuff with UVB and UVA protection.)

If anyone is wondering, yes, I’ve been trawling a few random naturopath sites. I find it extremely disheartening that these evil little quacks are so eager to increase the rate of cancer by discouraging the use of sun lotion. I’m sure a few wouldn’t mind having more ‘patients’ to abuse financially, but I think the majority of them just hate science so much that they’re willing to do anything so long as it builds up their anti-science street cred among fellow quacks.

Photolyase and cancer

Upon arriving at the beach yesterday, I lathered on the sun screen. Being relatively fair-skinned, I’ve learned my lesson in forgetting or not using enough of the stuff, and I wasn’t about to get all burned up. I don’t like eating lobster; I certainly don’t want to look like one.

But that isn’t the only reason I throw the stuff on so heavily. I’m also well aware of the tenacity and, if such a word is appropriate, vulgarity of cancer. Tanning is just a bad idea unless someone really wants to be diseased. It may look good (and not always), but I doubt that has ever brought solace to any cancer patients. Laying out in the sun without protection (as I saw a few people doing all day – it was at least 85 F, not a cloud in the sky) or jumping in one of those tanning cancer tubes is a sure-fire way to cause potentially deadly somatic cell mutations.

The way this works is that UV light slaps into the double helix structure of DNA causing an incorrect fusion in base pairs on the same side of the helix. Imagine – and apologies for the violence of it all – getting punched in the mouth. Instead of your teeth vertically matching as they do now (at least relatively), a couple teeth on the bottom row are now horizontal and facing each other. This calls for a dentist.

Different organisms have different mechanisms (dentists) for correcting damaged DNA. Naked mole rats, for example, have two genes for contact inhibition instead of the single gene virtually all other mammals have. This has resulted in no one ever recording an instance of cancer in the ugly little critters. If humans had this mechanism, cancer probably wouldn’t be nearly the problem it is.

Instead we get a number of repair mechanisms, chief among them base excision, nucleotide excision, and mismatch repair. (The mechanism in naked mole rats doesn’t repair mutated cells; it merely stops them from proliferating.) Unfortunately, the repair fidelity, just like the copying fidelity, of DNA is not perfect. Mistakes are made, mistakes are missed. We get cancer.

Part of our plight arises from something we’ve lost over evolutionary time. Most plants and other animals have a protein called photolyase which specifically seeks out UV damaged DNA.

Researchers at Ohio State University were recently able to observe exactly how photolyases perform their protective duty. The photolyase protein captures energy from visible light and uses it to project a single proton and a single electron towards a dimer in DNA. The two tiny particles then initiate a series of reactions that knock the contorted nucleotides back into place across the ladder, without needing to remove them like normal human proteins do. A proton and electron finally return to the photolyase protein, presumably so it can dash off to fix the next dimer it finds.

In other words, this dentist isn’t very gentle. He just punches your contorted teeth back into position. (Okay, it’s more elegant than that, but I had to finish the analogy.)

The article goes on to speculate as to the potential utilization of this protein in humans.

Given that photolyases were lost in evolution, it was possible that other proteins in the cell that allowed photolyases to do their job were also lost. But mice that were given the gene for the photolyase protein showed remarkable protection from UV damage. This means that in mice, the rest of the cellular infrastructure that photolyases need is still there. Chances are good that it’s there for humans as well.

There are other instances of mice being able to utilize genes not otherwise found in them, almost as if they’ve had them all along. For example, when injected with snippets of DNA for making red photo-pigment, normally dichromatic mice suddenly had trichromatic vision. This indicates an earlier evolved ability to see colors in the mammalian line that was later lost. In all likelihood, the appropriate gene(s) was probably just turned off out of a lack of need, leaving in place much of the cellular machinery needed to utilize red photo-pigment. I suspect the same is true with photolyase. If this can be extended to humans, a significant leap in the fight against many skin cancers may be on the horizon.

Promising skin cancer news

One of the oldest treatments for cancer in the modern era is to stimulate the immune system. William Coley was one of the pioneers in this technique, coming up with Coley’s Toxin in the late 19th century. This was a mixture that basically involved infecting patients with the bacteria Streptococcus pyogenes. Coley claimed fantastic results, but he kept his records poorly. I don’t know if he ever lied – there is no direct evidence which says he did – but his results were almost always questionable. Besides that, he tended to lose patients to bacterial infections from time to time.

Cancer research lost some of its focus on the immune system in the early part of the 20th century, Coley’s toxin was reclassified into oblivion by the FDA, and governments really didn’t supply the funds for research they should have. Research, however, has long come back around to looking at the immune system and how it can help fight cancerous cells. One of the most recent results has to do with a new drug, Ipilimumab, which is for patients with melanoma

The results, reported Saturday at a cancer conference, left doctors elated.

“We have not had any therapy that has prolonged survival” until now, said Dr. Lynn Schuchter of the Abramson Cancer Center at the University of Pennsylvania, a skin cancer specialist with no role in the study or ties to the drug’s maker.

The drug, ipilimumab, (ip-ee-LIM-uh-mab), works by helping the immune system fight tumors. The federal Food and Drug Administration has pledged a quick review, and doctors think the drug could be available by the end of this year.

Ipilimumab is a T-cell potentiator. T-cells basically have antigens which help to regulate immune responses. These antigens inhibit ‘overreactions’ within the immune system. What ipilimumab does is block this inhibition. It says to the immune system, ‘Run wild, you’re free!’

The increased survival rate is great when measured by percentage – 67% – but the practical numbers only mean a few more months of life. That’s how a lot of cancer research goes, unfortunately, and it makes it all so much less of an elation. But this is still hopeful. It’s good progress on the cancer front. (But do keep in mind, this is just one study for one type of cancer, interesting and promising as it may be.)