Time for another round of the Cancer Research Blog Carnival. The fifth edition will be up on the Bayblab blog one week from today. Get your submissions in soon!

Wow. I’m kind of floored right now. Judah Folkman died last night. Orac has written up a nice piece about his death here and here, and while his praise for him is rather lofty, it is all absolutely, 100% deserved—perhaps even too muted. Alex Palazzo also linked to a great NOVA piece about him and his life’s work. The guy was without question a legend in cancer research and nothing short of a paradigm changer in areas not limited only to cancer research.

For instance, in the course of his life’s work, he invented a new technique for repairing patent ducti arteriosi and presented it to the American College of Surgeons while a freshman medical student; made significant contributions to the development of the implantable cardiac pacemaker; happened upon the concept of slow-release drugs; became the first-ever instructor of surgery to be promoted directly to professor of surgery and the youngest-ever professor of surgery in the history of Harvard, having been appointed surgeon-in-chief of Children’s Hospital in Boston at the age of 34; made one of the first huge public collaboratory agreements with a biotech company (forcing Harvard as an institution to reconsider the way it interacts with such an industry); and pioneered the successful culture of previously “impossible-to-culture” endothelial cells, which was seminal to any subsequent study of vascular biology; among many, many other landmarks. Absolutely incredible.

As it happens, you may have noticed that I’d been reading a book chronicling his life and research, Dr. Folkman’s War by Robert Cooke, which I actually just finished this afternoon. While it started off slowly, it turned out to be a very good book about a truly great physician and scientist. I am still amazed by all the things this guy did, the breadth of his work and vision, the work ethic by which he worked, and the sense that he had about research. A few choice quotes:

To reach his goal, Folkman had made a career of learning whatever he could about blood vessels. He liked to say that he hoped to someday put himself out of business. The only way to do that, he imagined, was to persist in his work, no matter the odds. It was a fine line, he knew, between being persistent and being stubborn. And the difference, in the end, was in results: ‘If your idea succeeds everybody says you’re persistent. If it doesn’t succeed, you’re stubborn.’ …he was ready to live up to this, his father’s private admonition: ‘Be a credit to your people.’”

One of the fundamental lessons Judah Folkman passed on to young people joining his laboratory was that success can often arrive dressed as failure. Success is great—satisfying, good for the ego, capable of bringing reward and prosperity—but doing experiments that invariably bring the expected results may mean the questions aren’t tough enough. To fail, then struggle to understand why, may offer more insight and greater learning. Asking ‘Why not?’ is often an important and productive stop on the way to learning ‘why.’”

One reason Folkman was able to persist so long, and remain on the staff at Children’s Hopsital and on the Harvard Medical School faculty, despite so much controversy and criticism, was his consummate skill as a physician, teacher, and pediatric surgeon. Critics had always sniped at his ideas and his style as a researcher, but there was never any question about Folkman’s skill as a physician and teacher. Year after year Folkman won medical students’ votes as one of the best teachers on the Harvard Medical School faculty. He was regularly tapped to lecture first-year medical students on what it means to be a doctor, occasions on which he emphasized over and over again the importance of being alert and alive to the patients’ feelings. He repeatedly argued that a physician’s bond with his or her patients should be so close that it transcends a strictly professional relationship. When you walk into the hospital room when your patient’s family is visiting, he lectured the medical students, the patient should immediately say to his relatives, ‘I want you to meet my doctor.’ If they don’t, something’s wrong.” ‘You are their doctor,’ Folkman tells he students. ‘There’s a certain point at which the begin to trust you, and you won’t abandon them. You won’t go on vacation and disappear. Or they can’t reach you. They’re scared to begin with, and if they get that sense, then they’re very scared. Folkman would never have his patients feel disconnected from their doctor. He always made sure they had his home telephone number…When young residents in training objected to that idea, groaning about never having any time of their own or about being awakened late at night, Folkman’s answer was blunt: ‘You chose medicine. It’s a service career. Long hours are part of the job. If you want a different kind of life, think about becoming a banker.’”

Snap.

Must be a good time to be at the University of Chicago. Another medical student/faculty combo has put out a fairly high profile paper, this one about religion and doctors and morality and conscience—above all, how clinicians disagree over precisely what conscience is from the context of religion versus secularism. It’s all very deep and—well, I’ll just repost the abstract for you to ponder. The whole thing is here (subscription required).

What role should the physician’s conscience play in the practice of medicine? Much controversy has surrounded the question, yet little attention has been paid to the possibility that disputants are operating with contrasting definitions of the conscience. To illustrate this divergence, we contrast definitions stemming from Abrahamic religions and those stemming from secular moral tradition. Clear differences emerge regarding what the term conscience conveys, how the conscience should be informed, and what the consequences are for violating one’s conscience. Importantly, these basic disagreements underlie current controversies regarding the role of the clinician’s conscience in the practice of medicine. Consequently participants in ongoing debates would do well to specify their definitions of the conscience and the reasons for and implications of those definitions. This specification would allow participants to advance a more philosophically and theologically robust conversation about the means and ends of medicine.

This is yet another publication from Ryan Lawrence, a second-year student here, and Farr Curlin, an internist, ethicist, and (almost uncomfortably) outspokenly religious researcher of the role of religion in medicine (but overall a very thoughtful and very good guy). At this point, he’s perhaps the best known researcher on this topic in the country. Together, the two published five articles in 2007 alone, once in NEJM and thrice in AJOB, twice just with the two of them and thrice with other collaborators. Let’s just say it was a good year for them.

In addition, a great Cancer Research paper just came out of my lab on the role of paxillin in lung cancer, culminating several years’ worth of hard work and a hell of a lot of outside collaboration. You should check it out (subscription required, I believe).

The 5th edition of the Cancer Research Blog Carnival is up at the bayblab blog. Go forth and become knowledgeable.

Welcome once again to the Cancer Research Blog Carnival! I’m pleased to be hosting the fourth edition. There were a ton of great submissions, so without further ado, let’s get started.

Sure, smoking is bad for you, but could it also be bad for businesses? Devon Carlson at Ask The CareerCounselor thinks so, and she’s citing some data to back it up:

[A] study of more than 14,000 workers found that nonsmokers took an average of 25 sick leave days per year while their smoking colleagues who took 36 sick days annually. … “According to the Centers for Disease Control and Prevention, employee tobacco use costs companies an estimated $167 billion annually. In other words, for a company that employees 10,000 people, if just 20% of those workers smoke that company spends over $15 million per year on healthcare and other costs associated with the habit.”

Now, I’m no mathologist, but it seems to me that companies should have at least some interest in reducing smoking prevalence among their workers. It’ll not only save lives but also save them a nice chunk of change in the end. It’s a win-win.

Keith Robison over at Omics! Omics! offers a nice overview of the VEGF-targeted therapies that are currently in use and introduces us to a relatively new treatment known as VEGF Trap:

VEGF-Trap is a pastiche of carefully chosen protein parts: pieces of two different human VEGF receptors plus a bit from a human antibody (IgG1) constant region.”

When this protein construct latches onto free VEGF, its binding to its receptor is inhibited, which in theory reduces tumor-induced blood vessel formation. According to a recent study investigating the efficacy of this therapy, precise dosing via comparison of free vs. “trapped” VEGF in the bloodstream may be employed, in contrast with typical dosing schedules based on body weight, age, etc. that are often highly variable from individual to individual.

VEGF-Trap forms stable, inert, monomeric complexes with VEGF which remain in circulation. By measuring the amount of free and VEGF-complexed VEGF-Trap in circulation they can measure VEGF levels and identify a dose which ensures that maximal trapping occurs.”

Walter, the genius behind the fantastic Highlight Health, blogs about recent papers in Cancer Research that presented some alarming news about one common treatment for prostate cancer: We may be shooting ourselves in the foot. (Or the crotch?) It appears that androgen deprivation therapy, thought to slow growth of cancerous prostate cells and halt progression of prostate cancer, may also be upregulating Nestin, a protein that appears to play a role in metastasis:

[The reseachers] examined Nestin gene expression in prostate cancer samples from 254 patients that encompassed the entire clinical spectrum of the disease, from untreated localized tumors to lethal metastatic cases. Increased levels of Nestin gene expression were found exclusively in lethal cases following androgen deprivation therapy. … “…another study in a genetically engineered mouse model of human prostate cancer demonstrated that prolonged exposure of the mice to reduced levels of androgen accelerated prostate tumor development compared to mice exposed to physiologically normal levels of androgen.”

Doctor David tells us about an exciting new drug that is being used in treating a type of soft tissue sarcoma and offers up a few reasons that this is totally awesome.

In addition, he gives a really nice review of the different types of cancer vaccines out there:

A peptide vaccine is most like the flu shot—a patient is injected with a piece of a protein that comes from a cancer cell in the hopes that this will trigger the immune system to respond to the protein and kill whatever cells (cancer cells in this case) have the protein… A dendritic cell vaccine, in contrast, involves taking immune system cells from the patient, putting the piece of protein that is being targeted by the vaccine into these cells in the lab, and then injecting the manipulated cells into the patient.”

Good stuff to know. The research in this area is booming. Why not, after all, let your body attack cancer for you?

Good thing we have these vaccines, too, because as Ian York writes on his blog Mystery Rays From Outer Space, it’s commonly thought that overt cancers have already escaped surveillance by the immune system:

The present model is that the immune system is just one checkpoint (though probably a fairly significant barrier) that the developing cancer cell must overcome. That means that by the time we can detect a cancer, it’s already been selected to be immune resistant. The cancers that were susceptible to the immune system were killed off when they were just a little cluster of cells, long before there was anything we could identify.”

Cancer vaccines, then, just give the immune system a little nudge.

As a follow-up, Ian also has a two-part series on cancer immunity in-depth: the three Es of cancer immunity (elimination, equilibrium, and escape), and another looking more specifically on the balance between tumor cells and the immune system. Together they’re a very nice explanation of a fascinating paper.

Abel Pharmboy over at Terra Sigillata highlights an unfortunate state of governmental and financial affairs for lymphoma patients that may prevent them from receiving a highly effective treatment, radioimmunotherapy. He quotes a recent Newsweek article that sheds light on the situation and also adds his own commentary:

‘What if they found a cure for a cancer that afflicts half a million people, but a combination of stupid bureaucrats and greedy doctors kept patients from getting it? ‘It’s the kind of scenario that seems like the province of conspiracy theorists or alternative-medicine wackos–but is actually happening right now with a proven treatment for certain common types of non-Hodgkins lymphoma, the sixth-most frequently occurring cancer in the United States.’ [The Newsweek author] does a fabulous job in describing the whole backstory on the potential loss of a truly disease-altering therapy that is among the most effective drugs in producing long-term cancer remissions.”

Deplorable.

Kamel of Bayblab fame (the godfathers of this prestigious and ubiquitous carnival) recently wrote about a novel drug currently in clinical trials that may abrogate the effects of commonly mutated players in cancer by encouraging cells to “ignore” nonsense mutations:

The p53 gene is mutated in over 50% of human tumours and of those mutants, almost 8% are nonsense mutations. Research has shown that reactivation of p53 has therapeutic potential in mouse models of cancer, leading to growth arrest and regression of tumours.”

(Incidentally, the Bayblab crew will be discussing these carnival inclusions in greater depth on the next episode of the wonderful Bayblab Podcast. Be sure to check it out.)

Finally, Matthew Zachary, the force behind I’m Too Young For This, tells us the emotional story of his battle with medulloblastoma and also tells us what he thinks of the word that gets thrown around all too often:

‘Cure’ has unfortunately become nothing more than a catchy, exploited, arbitrary and abstract health marketing term that has lost all sense of meaning and purpose — and I am not alone in this sentiment. Perhaps someday down the road a ‘cure’ may take the form of individualized genetic vaccines, which enable our bodies to manage cancer cells more effectively and prevent them from spreading. But we’re still going to get cancer. It just won’t be nearly as life threatening or life altering as it is today.”

Word to your mother. This is good reading.

That’s it! Hope you enjoyed the fourth edition. Look for #5 in early January.

Want to host a future edition? Get in touch with these folks.

Once again, the Cancer Research Blog Carnival is coming to you straight from this here weblog, and it will once again be all nosugrefnebified. (It’s a word. Look it up.) (Fine, it’s not a word, but it should be. Give it time.) (Okay, that was enough time. It’s now a word. Look it up.) Check back here on December 7 for all the hot cancer action.

This will be the fourth edition of the carnival. For previous editions, see #1, #2, and #3. If you would like to submit a piece on the topic of cancer resarch for the carnival, which will surely bring you grand acclaim and much notoriety, leave me a link to your post(s) on the carnival’s submission page, in a comment on this post, in an email to me, or anywhere else you think I might stumble upon it. As this will be going out to press on December 7, let’s shoot for a December 5-ish deadline.

If you would like to host any future editions, which will come out on the first Friday of every month, let The AC of the bayblab blog know.

At the risk of fully transforming this weblog into an unequivocal anti-smoking campaign, which, to be sure, I’m not consciously trying to do in the least, I found this story from NPR a few days ago interesting.

There were no cigarette executives on hand to deny that smoking is harmful, as in the famous Congressional tobacco hearings of the 1990s; the star of this Senate Commerce Committee hearing was  the Federal Trade Commission’s smoking robot…The machine has been used since the 1960s when tobacco companies started making ‘light’ and ‘mild’ brands in response to growing health concerns, but Federal Trade Commissioner William Kovacic testified that for some time, the agency has known the robot doesn’t accurately reflect what people inhale when they puff on a cigarette. … Cathy Backinger with the National Cancer Institute testified that tobacco company documents show cigarette makers have long known that smokers get just as much if not more tar and nicotine from ‘light’ brands, but still use the FTC ratings to market their products…’Smokers erroneously saw these products as viable alternatives to quitting, and as a result, many more smokers continue to smoke who might otherwise have quit.’ … Yesterday, [New Jersey Democrat Frank Lautenberg] said Congress has another urgent tobacco issue to tackle with the FTC smoking machine. ‘The FTC should not allow this rating system to continue if it cannot stand behind it, and big tobacco should not be able to hide behind the FTC method to justify the claim that ‘light’ and ‘low-tar’ cigarettes are healthier.” But cigarette makers say they don’t market ‘light’ brands as any safer than regular full-flavored cigarettes. Bill Phelps is a spokesman for Philip Morris USA: ‘Smokers should not assume that brand descriptors such as ‘light’ or ‘ultralight’ indicate the actual amount of tar and nicotine that’s inhaled from a particular cigarette.”

Right. Wait, what? What exactly does the “light” refer to then, Bill? Actual weight of the cigarette? More brilliant white paper?

Maybe I’m just going out on a limb here, but when I buy light mayonnaise, I usually expect there to be less fat in it. Same thing with dressings, peanut butter—pretty much everything. When I drink light beer, typically there are less calories. When I buy jambalaya that is advertised to have “lower sodium,” I expect—not always, but usually—there to be less sodium in it. Maybe your industry works differently or uses a different English dialect or something. Where I’m from though, which happens to be exactly where you’re from, “light” is used to assuage peoples’ health concerns and usually refers to a product that has “less bad shit.” You do know that tar and nicotine are bad for you, right?

I’m getting tired of this crap. It’s getting really old. On the bright side, as Leo reminds me, I won’t be out of a job anytime soon thanks to these people.

By the way, NPR‘s new media player is fantastic—probably the best web-based media player there is. Even if you don’t listen to this story, I still implore you to go to their site and check out whatever suits your fancy. You can aggregate any story you want into a fully customizable playlist, which totally rocks my socks off.

Whoa. Lots o’ good smoking-related news flying around in the past few days.

The World Lung Foundation announced recently that it expects the smoking-related death rate worldwide to double over the next two decades or so. As it stands now, of the 1.3 billion(!) smokers worldwide, about 5 million of them die every year with smoking as the culprit. Another interesting tidbit to tie into this: There are more smokers in China than there are people in the United States. (See 1.7: Cigarette consumption and Table B: The demographics of tobacco.) About 50% more. According to a rough calculation, almost 450 million of them. They smoke 1800 cigarettes per person every year. That’s almost 5 cigarettes smoked daily in China per person. Not per smoker; per person. One-third of the world’s annual cigarette consumption. These figures don’t even include kids who are exposed to their parent’s (or, if they’re really screwed, parents’) secondhand smoke, which in some countries is upwards of 80% of children.

This makes the WLF’s prediction entirely believable.

What is perhaps more alarming is the rate of smoking among health professionals in various countries. 42% in Turkey; 35% in Spain(!); 32% in Ecuador; 28% in France(!); well over 50% in Bulgaria and Armenia.

What is perhaps even more alarming is that in every single country above, which is not an exhaustive list, these rates are several percentage points, if not dozens, higher than in the general public. In some countries, health professionals are twice or even thrice more likely to smoke than the lay population.

Clearly, this is not helping things. This makes the WLF’s prediction entirely believable, if not utterly undershot.

Things are not much better at home. While “only” about 21% of Americans smoke every day or some days, and “only” around 3% of health professionals smoke regularly, the CDC reports that the progress we were once making now seems to have stagnated:

Most notably, funding for comprehensive state programs for tobacco control and prevention decreased by 20.3% from 2002 to 2006, and tobacco-industry marketing expenditures nearly doubled from 1998 ($6.7 billion) to 2005 ($13.1 billion).”

Pair this with the fact that, when this survey was conducted, 45% of smokers had tried, unsuccessfully of course, to quit smoking within the previous 12 months, and you’ve got yourself a nice little public health problem that’s not going away anytime soon. They are winning, and we are losing.

There is some respite in all of this, though. A new study out of UCSF showed that a nicotine reduction strategy could reduce smoking addiction pretty effectively, with a quarter of the subjects quitting entirely and a huge chunk smoking significantly less after the study. I like it.

Really fascinating story over the weekend in the NY Times, everyone’s favorite science journal, about a gentleman who presented to the ER with acute severe memory loss and insomnia. The physical exam and an LP were normal, and there was no evidence of epilepsy or autoimmune disease (lupus was on the differential—always is).

The very astute neurologist somehow recognized it as a cancer-related illness, and he turned out to have a mediastinal mass from Hodgkin’s lymphoma that had begun to cause inflammation in his brain. All I can say is: Wow.

I would not have put that on the differential in a million years, but then again, I’m not a neurologist, or a clinician of any sort, or a smart man.