Hello and welcome back to the Cancer Research Blog Carnival! There are a ridiculous number of posts for this edition. I’m diving in head first.

I have to get something out in the open right off the bat: I love the Guardian. Their science and health sections are fantastic as pop-sci news sources, and it is quickly supplanting the New York Times as my favorite softcore science journal.

Lucky for us, they write about cancer a lot, and they do it well. Science correspondent Ian Sample wrote recently about a study suggesting that breast self-exams aren’t all that useful in preventing deaths, and they may in fact be harmful to the population of women who perform them because of the greater number of breast biopsies this practice generates, some of which turn out to be unnecessary.¹ The article to which Ian is referring first came out quite a while ago, but in the context of the increasing cancer hyper-awareness mindset, it’s important to take this topic into serious consideration and re-examine its true benefits periodically. (The article has undergone updates recently, too, but the conclusion has not changed in the last five years. Food for thought.)

Sarah Boseley, the Guardian’s health editor, reported the following day on a study that found a disturbing trend among cancer patients in Britain: Compared to the rest of the developed world, they’re not doing so hot.² The article in question suggests that wide variations among cancer survival statistics from country to country may depend largely on wealth and health spending, but this doesn’t explain why Britain would perform so poorly. Take a look for yourself.

Ben Goldacre, blogger for the Guardian and proprietor of the Bad Science blog, has a few choice words for some journalists who increasingly—perhaps leading to the aforementioned cancer hyper-awareness—seem to making rather large leaps between basic scientific findings and reality on a larger scale. Ben, referring here to ongoing red wine hysteria:

The story follows a standard template which they clearly now teach as valid in all journalism schools: a food contains a chemical, the chemical does something in a dish on a lab bench, therefore the food kills cancer in people. Or rather, red wine contains resveratrol: this chemical has been found to increase the activity of an enzyme called quinone reductase, which converts a derivative of oestrogen back to oestrogen, and that derivative can damage DNA, and damaging DNA causes mutations, and mutations cause cancer, so therefore, in the world of journalists, red wine prevents breast cancer in people.

This is a phenomena we might call “data mist”: where someone gets one piece of research information lodged in their imagination and suddenly, for them, it explains the entirety of medicine.

Ouch.

This is definitely worth a read, although I must say that this Guardian link above is the censored version. You want the good stuff? Hit up this article on his own blog; same article, but with links, pictures, and a supplementary smackdown included.

Yun Xie of Ars Technica’s “science-centric journal” writes about an interesting new prospect of using magnetic nanobeads to target and remove residual cancer cells postoperatively.³ Cobalt spinel ferrite particles can be linked to polypeptides specific for certain types of cancer cells, injected, and later filtered out of the body, theoretically bringing the bound cancer cells along with them. Yun goes into a bit more deatil:

To test the efficacy of these modified nanoparticles, the researchers injected ovarian cancer cells into the abdominal cavities of mice. Then, they injected the mice with the magnetic nanoparticles and allowed the nanoparticles to bind to the cancer cells. By using an external magnet (2600 Gauss), the cancer cells could be moved to different locations in the abdominal cavity. Furthermore, when the researchers extracted and magnetically filtered fluids from the abdominal cavity, they found that the nanoparticles selectively targeted ovarian cancer cells.

She also goes on to suggest that this would be a fantastic supplement to techniques already in development that employ magnetic nanoparticles for efficient drug delivery.

My question, though, is this: Might this also be used following detection of early-stage tumors as a preventative measure against metastatic colonization of circulating or detached cells, especially in those tumors known to spread early? Presumably, this technology works even better on unanchored cells than on anchored ones, and this might also be a nice way to prevent tumors from forming at secondary sites in the first place.

Fantastic news for me: There seems to be an inverse association between coffee drinking and the risk of liver cancer,⁴ says Walter of Highlight HEALTH. Researchers in Finland, where—unbeknownst to me until now—people apparently drink a lot of coffee, found that over two decades that those who drank the most coffee were least likely to develop liver cancer, and vice versa:

The researchers observed that the cumulative incidence curve of liver cancer decreased with increasing amounts of daily coffee consumption. When the analysis was restricted to surveys from participants that had clinical data available, a statistically positive association was found between serum gamma-glutamyltransferase (GGT) level and liver cancer risk. Joint association of coffee consumption and serum GGT level with liver cancer showed that participants who drank 0 — 1 cups of coffee and were in the top 25% of subjects sampled with respect to serum GGT had about 9.2 times increased risk for liver cancer compared to participants who drank at least 6 cups of coffee daily and were in the bottom 75% of subjects sampled with respect to serum GGT.

I’ve never been happier to be a coffee drinker, but this begs the question: Do sleep-deprived, caffeine-addicted medical professionals have a lower incidence of liver cancer than the general population? These are important questions, people.

Rane at InventorSpot writes about a very interesting story that’s been making big headlines in the cancer world recently. Researchers are turning the tables on tobacco and engineering it to grow an anticancer vaccine instead that would target cancer cells.⁵ This potentially has implications for virtually every cancer, but they’ve started with lymphoma for the time being.

The idea is to use the plants as a ‘factory’ in order to grow vaccines quickly and inexpensively. These vaccines would be tailored specifically to each person’s type of lymphoma.

Ronald Levy, who is the lead researcher of the study, said, ‘This is a vaccine which is custom made for each person, because each person’s tumor is different,’ [principal investigator Ronald] Levy told Bloomberg. ‘For something like this where we need a different product for every person and we needed it fast, this is a very nice technology. The irony is that this is a treatment for cancer we’re building out of tobacco.’

How interesting—and ironic, indeed. NPR’s Science Friday interviewed Dr. Levy on their show last week, and he discussed their research further on the air. Worth a listen.

Alexey at Hematopoiesis follows up with the second of a multipart series ( the first was included in CRBC #11) on stem cells, cancer progression, and metastasis, focusing this time on angiogenesis. Alexey debunks an oft-helf dogma of tumor biology that holds that in order for neoangiogenesis to occer, bone marrow-derived cells must escape the BM, home to the tumor, and set up shop to get the blood flowing. Not true, according to a recent paper in PNAS:⁶

Authors of the recent work, challenged modern concept of BM-derived endothelial progenitors contribution to tumor angiogenesis. The claim, pointed out in the title was that these cells do not contribute to vascular endothelium and are not needed for tumor growth. Researchers extensively studied all of the possibilities to induce angiogenesis with simultaneous mobilization of EPC from bone marrow, including tumor inoculation models. Also a few mouse models were used, including pairs of parabiotic mice, and wide range of methods were used in different time points in order to analyze the contribution of BM-derived cells to endothelium. Conclusion of all of these experiments was that ‘cancer growth does not required BM-derived endothelial progenitors’.

So, does this suggest, instead, that the vessels are formed by the tumors themselves? Perhaps, says Alexey, citing an earlier paper from a different group that seems to indicate such a role for tumor cells, at least in part:⁷

It seem like a tumor is able to build its own vasculature without angiogeneic precursors from BM. This conclusion is complemented by another work, published recently in PLoS ONE, which showed that precancerous stem cells in situ (within the tumor mass) can make vasculature for tumor itself. Very interesting findings!

Very interesting, indeed. Determining which of these two possibilities actually accounts for tumor neoangiogenesis could potentially have a profound impact on the strategies used to target tumor vasculature.

This is cool. Researchers in Italy have developed a way of measuring extracellular ATP within tumors…by having cells do it for them. By engineering a luciferase that is targeted to the cell membrane and excited by reacting with ATP, they can measure the amount of light given off, which is proportional to the concentration of extracellular ATP.⁸ Says Gianpaolo, behind the blog Reportergene,

The italian researcher Patrizia Pellegatti and colleagues from Ferrara University, have engineered a chimeric plasma membrane-targeted luciferase that allows in vivo real-time imaging of extracellular ATP. With this novel probe, they have measured the ATP concentration within the tumour niche of several experimentally-induced tumours.

This technique allowed them to test—real time and in vivo—their hypothesis that ATP is more concentrated in the interstitium of tumors than that of normal tissues. Quite elegant.

Imagine a world without chemotherapy. Imagine a world where cancer could be fought without side effects. Imagine a world where it didn’t matter how far along your cancer had progressed, treatment could still be rendered and completely effective.

Big words, eh? It may happen sooner than you think. A recent article in NEJM highlights a new experimental therapy that involves extraction of a melanoma patient’s T cells, ex vivo expansion of that population of T cells specific against his own tumor cells, and reimplantation of those pure melanoma-targeting cells.⁹ Sajid Surve has posted a nice discussion of the article at Brain Blogger:

The beauty and elegance of this new technique is that scientists are augmenting our body’s inherent ability to fight cancer. Because the patient was injected with his own T cells, there was no threat of rejection, and no side effects whatsoever. Additionally, by unleashing the patient’s immune system he was able to attack cancer cells wherever they were in his body, rather than just the primary site. It doesn’t matter if the cancer is multiplying in the lungs, in the brain, on skin, or in lymph nodes. As long as there is a blood supply, the body is able to fight back and win.

What would be amazing to me is if we eventually could do something similar but figure out a way to rapidly propagate specific populations of T cells inside the body without having to remove so many of them—perhaps virally or recombinantly. The cells would multiply inside the patient’s body and could theoretically be “turned off” when they’ve accomplished their goal.

…but maybe that’s just me.

Along the same lines, Ian at Mystery Rays from Outer Space shows us a nice paper demonstrating that T cells actually might have a non-negligible effect on established tumors, something that we’ve suspected for ages but that still doesn’t seem to be all that well-characterized. A group publishing in Clinical Cancer Research¹⁰ found that

there’s a strong link between good prognosis and phenotype. Tumors that seems to have good antigen presentation, have a better prognosis than those that have apparently blocked their antigen presentation pathways efficiently. (They were able to break it down further than that, to the specific types of molecules that may be important.) And these are not trivial differences; people with defective antigen presentation survived for 1 or 2 years, those with good antigen presentation averaged 4 or 5 years or longer.

The group also showed that the presence of T cell infiltrates in tumors is a very good thing, for those who had no T cells in their tumors were twice as likely to die.

Kamel at Bayblab discusses the recent warning given out by a higher-up at the University of Pittsburgh encouraging his colleagues to limit their cell phone use due to a possible brain cancer link. Despite there being very little evidence that this correlation exists, this is merely one of a string of such announcements, with neurosurgeon and CNN’s chief health correspondent Sanjay Gupta being perhaps the most well-known of them, preferring to instead use earpieces. But, regardless of what advice the general public should follow, there is potentially a larger societal question here: What gives them the right?

Kamel:

Given that the potential risks are small (but not negligible) and associated only with long term exposure, the question becomes what was the proper way to deal with the unpublished data from the University of Pittsburgh Cancer Institute? Again, it’s difficult to say without seeing the data in question, but given the information we have so far it’s hard to imagine a definitive, home-run conclusion (Herberman, who issued the warning, says as much in the news article). Should he have waited for peer review before sounding the alarm (would an extra few months before releasing it make a difference when talking about a 10 year latency)? Is it better to err on the side of caution? After all, he’s not calling for an end to cellphone use, but rather certain precautions, particularly with children.

Tough call, I say, in the face of such a dearth of data suggesting any correlation whatsoever. To be sure, this is defensive medicine on a gigantic scale—paralyzing medicine, even—and there’s a slippery slope that we’re rapidly approaching, in my opinion. What will they say next? Smoking causes cancer?!

UPDATE: Orac chimes in on this very topic, too.

Keith at Omics! Omics! presents a recent paper that presents findings of a new proteasome inhibitor, Argyrin A.¹¹ While it has many similarities to Velcade, the only currently available proteasome inhibitor, there are a lot of key differences that are not fully addressed by the paper’s authors and that, well, boggle the mind, not the least of which is that Argyrin A doesn’t really seem to act like a prototypical proteasome inhibitor.

…when I browse through their lists of genes for Argyrin A in the supplementary data, I don’t see a bunch of genes which are a distinct part of the proteasome inhibition signature.
…
One other curiosity. They do report looking for the Unfolded Protein Response (UPR) and report seeing it in the Velcade treated cells but not Argyrin A treated ones. The UPR is the cell’s response to misfolded proteins — and since disposal of misfolded proteins is a role of the proteasome, it has never surprised anyone that the UPR is induced by proteasome inhibitors. Can you really have a proteasome inhibitor that doesn’t induce the UPR? If this is truly the case, it is very striking and deserves its own study.

Keith nails it. Artifactual or not, there are many unanswered questions here. It’s definitely a story worth following.

Just in case you were wondering: The Were You Wondering… blog writes about 24 potentially harmful food additives that—of course—could, and probably do, cause cancer in some minute amount of cases, but in reality aren’t all that worrisome on an individual, tiny-quantities level. But, you know, just in case…put the red dye #3 syringe down. You have a problem.

Also from the same blog comes something quite a bit more worrisome: Northwestern University researchers have found that major medical centers tend to be a bit more thorough when searching for nodal metastases than smaller hospitals. This is bad:

It is vitally important to carefully check for remaining malignant cells after treatment for pancreatic cancer because the 5 year survival rate is less than 5% and most people die within the first 3 to 6 months of diagnosis!

Word to your mother.

Doctor David, a pediatric oncologist, writes a bittersweet post about something that’s often overlooked when thinking about cancer: appearances. The appearance of many cancer patients changes radically, not only from the cancer itself but from the disfiguring, destructive treatments required to even have a chance at life. Doctor David appreciates how his patients can make the best of it, and one stands out above the rest:

Warren was 9 when he was diagnosed with retinoblastoma, cancer arising in the back of the eye. Most retinoblastoma patients are infants, and Warren is the oldest retinoblastoma patient I have ever cared for. When he was diagnosed, his tumor was so advanced that there was no hope of saving the vision in his right eye, so it was removed, a procedure known as “enucleation.” After healing from the surgery, Warren received a prosthetic eye. The prosthesis was so real looking, that one of my colleagues had to ask Warren which eye he had lost!

It gets better from there… trust me.

Berci at ScienceRoll tells us about a trailblazing patient who’s chosen to share his battle with cancer with the world through what essentially amounts to lifecasting.

• his X-rays are online
• he blogs about his ‘journey’
• he twitters about his experiences inside and outside the hospital
• he makes pictures with his cellphone and puts these online through mobypicture
• he creates movies inside the hospital and he is interviewed by visitors
• you can make an appointment using a google online agenda

Berci calls him an e-patient, and I’d say that’s pretty accurate.

Finally, Thomas at Hope for Pandora, inspired by a tree, has a riddle that will make you feel like a complete idiot when you see the answer:

A surgeon, a pathologist and an oncologist are hiking through forest when they encounter a burly tree (shown at left). Curious by nature, they sit down to ponder their discovery. Of course, the surgeon proposes to cut open one burl. The pathologist thinks that’s a good idea; she whips out her pocket microscope to examine it. The oncologist goes on about a two-hit hypothesis and proposes dumping toxic chemicals onto the tree’s base. What do you call this conclave of MDs which also happens to be a name for the piece of wood being examined by the pathologist?

Answer here.

Whew! Thanks to Bayblab for guiding the Cancer Research Blog Carnival to its twelfth edition! It just keeps getting bigger and better, and I’m excited to see what the next month holds for cancer research. If you’d like to host the next edition, get in touch with the Bayblab folks.

References

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