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An emerging field in the area of nutrition and cancer is the role of whole grains in cancer prevention. In a world where carbohydrates, particularly refined sources, are increasingly viewed as the culprit for obesity and associated chronic disease, are whole grains the safest carbohydrate to recommend for cancer prevention? Currently, consuming a plant-based diet containing whole grain foods is part of the American Cancer Society

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When immune cells infiltrate tumors in large numbers, patients do better. Now researchers aim to harness this immune response to predict outcomes. The Society for Immunotherapy of Cancer (SITC) in Milwaukee is coordinating an international effort to validate Immunoscore, an assay that quantifies this immune response.

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In 1998 the biotech company Genentech launched Herceptin for the treatment of certain types of breast cancer. Herceptin was an example of a ‘therapeutic antibody’ and was the first of its type for cancer treatment. Antibodies are proteins in our immune system that can target abnormal cells (or bacteria, toxins, viruses, etc.) in the body, and on arriving at the target can set in motion a whole set of biological events that in principle can remove or degrade to a non-dangerous state the abnormal cells.

Frequently, antibodies that we should produce as a natural response to cancer cells that may develop in an organ or tissue are somehow either inhibited from forming, or where they do form are poorly effective at destroying the cancer. To combat this ineffectiveness, specific antibodies against targets on the cancer cell can be made in the laboratory and then reintroduced into the human body, causing the cancer cell to ‘self-destruct’, or become sensitized to natural immune processes that aid the cancer cell killing.

In commenting on the efficacy of such antibodies in the treatment of cancer, delivered to an international antibody conference in San Diego in December 2012, Professor Dane Wittrup (MIT) reminded the audience how limited the response rate (~10%) of current antibody therapies has been. While there may be different views on the reasons for this, we can be reasonably certain that it is due, in part, to some or all of the following: the development of tumor resistance after repeated therapy, the presence of side effects serious enough to warrant interruption or even cessation of treatment, or limited antibody efficacy in the real tumor environment. Despite the investment of billions of dollars in antibody research it is clear that the human immune system still retains many secrets, the decoding of which has been, and continues to be, a long and complex process.

Current antibody therapies target specific ‘circuits’ in cancer cells that are important for the growth of the cancer, either shutting down or blocking key points in specific cellular circuitry, thereby reducing the cancer cell viability. Unfortunately, a cancer is a population of cells and as the inhibitory antibodies move into attack mode, biological changes within the cancer cells over time can activate alternative survival circuits that allow the cancer to evade the antibody effects, effectively becoming ‘resistant’. (For example, some breast cancers are known to become resistant over time to repeated treatment with Herceptin.) To counteract this effect, therapeutic modalities have been developed where two antibodies targeting different sites (circuits) within the cells, or an antibody coupled with a highly toxic drug or toxin molecule, are being adopted. While more effective than the single antibody approach, there is still a heavy hitting part of the immune system, the so-called Cytotoxic T-lymphocyte, or CTL (‘T’ for thymus-derived) mediated response, that often stands idle while the antibody arm of the immune system goes about its work. Why might that be?

In the late 1980s and early 1990s, research groups working at research laboratories in Marseille and a pharmaceutical company in Princeton described two new proteins associated with cells of the immune system that appeared to regulate their activity, allowing them to discriminate between normal tissues and abnormal tissues such as cancer cells. These new proteins were named ‘immune checkpoint receptors’ and are now known to be instrumental in deciding whether or not CTLs become active. When CTLs receive the correct activation signal, they are primed to engage an abnormal target with a view to destroying it in what is part of the ‘adaptive immune response’. Within the cells of the immune system, these checkpoint receptors are part of a complex activating and damping signaling system involving a receptor and a second molecule (or ‘ligand’) that interacts with the receptor in a sort of pas de deux. When the two find each other, as in normal tissues, a CTL attack is prevented (if this did not happen, an autoimmune response could be initiated). So, if the same ligand signal is somehow offered by a tumor cell masquerading as a normal cell, the ‘call to attack’ signals will be overridden and a CTL assault will not occur. In many tumors, just such biochemical changes are known to occur that fool the immune system into ‘thinking’ that the tumor consists of normal human cells thus avoiding attack by CTLs.

As with many aspects of biological systems, the adaptive immune system is a balancing act between allowing effective immune responses to alien agents, such as bacteria, viruses, toxic molecules, and the like, and at the same time avoiding mounting similar responses to our own tissues, organs, and cells that could lead to ‘autoimmunity’. Immunologists use the term ‘tolerance’ to describe this protection that self-tissues and organs experience as the immune system goes about its work. Lupus erythematosus and multiple sclerosis are two examples of autoimmune responses where the normal regulatory controls have been interrupted and immune antibodies or cells have attacked normal, healthy tissues with often debilitating effects. It is currently thought that checkpoint receptors and their partner ligands play an important role in maintaining this tolerance state in normal healthy persons, preventing unwanted autoimmune responses.

But what if antibodies could be targeted to these checkpoint receptors, blocking the ability of the tumor cell to interact with the receptors on CTLs, and hijacking their deceptive “I am normal” signal? (see Figure 1). This would mean, of course, that in theory, any cell, normal or abnormal, could be a target for CTL killing since both types of cell would have their “I am normal” signal blocked. Dangerous? Possibly, if not controlled. Desirable? If a tumor is so aggressive (e.g. melanoma, pancreatic cancer, etc.) that some autoimmune side effects could be tolerated or clinically managed in order to rid the body of the cancer, perhaps the therapeutic modality would be justified.

Well, we can do better than ‘in theory’. In a recent study of patients with advanced melanoma, one of the most aggressive tumors known and refractory to most therapeutic regimes, two different antibodies against each of the two most characterized immune checkpoint receptors showed spectacular results. In summary, the Phase I/II clinical trial results showed that 40% of patients treated with the combined antibody therapy experienced tumor shrinkage, and 65% of patients experienced shrinkage or stable disease. While these results truly are impressive we cannot yet declare that the war against cancer is approaching resolution, despite the claims of some enthusiasts.

As I noted above, immune checkpoint receptors are important in avoiding immune responses to our own tissues and organs. If their regulatory role is undermined by antibody blockade then autoimmune effects could be anticipated. In fact, in all clinical trials so far conducted with antibodies against these targets, autoimmune responses have been seen, including colitis, dermatitis, hypophysitis, pneumonitis, and hepatitis. These are classes of side effects the clinical community is not accustomed to seeing during antibody therapy, and will require stringent observation during treatment while improved therapeutic regimes are developed that manage these autoimmune effects.

Despite the embryonic nature of this approach, we have truly entered a new age for antibody therapy. As with all checkpoints, two way traffic is ever present, and while in one direction there may be freedom, in the other may lie painful experiences that have to be managed. The key for the future success of this approach will be the development of immune strategies that allow the benefits of immune checkpoint inhibition in cancer treatment to be counterbalanced by clever therapy designs that avoid, or at least minimize, the associated disadvantages.

Header image: Breast cancer cell. Public domain via Wikimedia Commons.

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My career began in the 1970s in the field of cancer immunology, a subject, which nowadays is at the forefront of cancer research, holding the promise of delivering new therapies for treating patients suffering from a wide range of cancers. Many scientists working in the field are not readily aware that the very first research papers documenting immunity against cancer were published in 1955 in the British Journal of Cancer by Robert (Bob) Baldwin, working in Nottingham, England. Fifty years on from his pioneering work, we have a greater understanding of how the body’s immune system acts as a surveillance mechanism to constantly patrol the body and destroy newly formed tumor cells, and the conditions where tumors escape immune detection and their progress is unchecked. In the 1960s and 1970s there was an explosion in research aimed at stimulating host immunity, without the in-depth knowledge we now have on the genetic basis of cancer and malignant progression and spread of the cancer beyond the confines of the primary tumor.

Robert Baldwin pioneered research into immune-stimulants, using for example bacteria, such as the attenuated BCG organism used to immunize against tuberculosis, and led the field in the production and clinical application of monoclonal antibodies; this has resulted in several antibody based therapies being introduced into the clinic. For example, Herceptin, an antibody that recognizes a protein known as Her2/neu, is used to treat a sub-group of breast cancer patients. Because other tumors express this protein, vaccine therapy against Her2/neu in prostate as well as breast cancer is undergoing trials at the present time. I was fortunate enough to work at the Nottingham Cancer Research Campaign Laboratories in the 1970s, where this experience acted as a springboard for my continuing interest and career in immunology, principally cancer immunology.

Having subsequently worked at Sheffield Medical School, and The National Cancer Institute in Bethesda and in Philadelphia, in 1996, I found myself back in Nottingham, heading my own team of scientists, now established as The John van Geest Cancer Research Centre, where our research interests are clearly focused on (1) identifying new cancer genes and antigens for developing personalized medical care through the use of cancer biomarkers, and (2) developing new forms of immunotherapy, where the combination of therapeutic vaccination and treatments designed to decrease the effectiveness of tumor escape from immune detection, are truly “center stage.” The work at our Institute and other institutes, will, I believe, make a real impact on patient survival and clinical management in the next decade. All of the major Pharmaceutical companies have entered the race to develop immunotherapy products and a variety of approaches are now undergoing clinical trials or are already approved for use by the FDA.

What makes us believe in the immune system as a means of treating cancer is the fact that in cases where the immunity is compromised, either through the use of immune-suppressive drugs or by infection with, for example, HIV, then cancers arise. We now have an in-depth understanding of how cancer occurs and progresses, the immune cells that mediate anti-cancer activity and the molecules that switch immunity off causing a “depression” in immune function. The controversial research into “cancer stem cells” now requires considerable resource and research input over the next decade or so. It will be important to define their role in tumor progression and determine their susceptibility to immunotherapy. Their mere existence in many cancers has been difficult to establish since they represent a minority population within tumors, although where they have been identified it is true to say that they appear to represent a highly aggressive, therapy resistant cell type with the ability to self-renew and give rise to differentiated cells within the tumor mass. This finding, together with our increasing understanding of “Tumor cell plasticity” will be important to consider as we aim to utilise the power of the immune system to successfully treat cancer.

Headline image: Cancer cells by Dr. Cecil Fox (Photographer) for the National Cancer Institute. Public domain via Wikimedia Commons.

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By Lauren Pecorino

There is a tendency to complain about policies when writing blogs, but I think it is time to commend the British campaigns and innovations in treatment. They have proven to be some of the best in the world and have had a major impact in the fight against cancer.

One of the best British campaigns is against cervical cancer. Getting personally posted invitations to attend your next PAP screening, supported by pamphlets of information, is something few women ignore. Those who try to ignore these invitations are rightly and relentlessly bombarded with regular reminders.

And, with the knowledge that a sexually transmitted virus, Human Papilloma Virus (HPV), is responsible for all cases of cervical cancer, the UK implemented a national school-based HPV vaccination programme that has proven to yield high uptake. By 2009, 70 percent of 12-13 year olds in the UK were fully vaccinated. These results are admirable compared to the results of alternative on-demand provisions offered by other countries including the USA. Note that the vaccine is recommended for early teens as it is a preventative vaccine and not a therapeutic vaccine, and must be administered before the initiation of sexual activity for it to be effective. The vaccine prevents about 70% of cervical cancers caused by two specific strains of HPV. PAP screening is still important to catch cases that are not prevented by the vaccine. An added bonus of this campaign is that the same vaccine also protects against some head, neck, and anal cancers caused by HPV infections.

Another great British effort is towards the prevention of lung cancer. The anti-smoking adverts have been haunting, especially the most recent one released by the UK Department of Health that shows a tumor growing on a cigarette. It is brilliant. I wish I had designed it. The advert strikingly conveys the message that if you saw the damage smoking causes, you would not smoke. The percentage of male cigarette smokers have fallen from 55% in 1970 to 21% in 2010 and a decreasing number of deaths due to lung cancer has followed this trend.

Click here to view the embedded video.

The UK is also a model of good practice in that it is the only country in the world which has a network of free ‘stop-smoking’ services, recently supported by specialized training for National Health Service Stop Smoking practitioners.

We can help the national campaign at a personal level by being more opinionated and outspoken when it comes to letting those around us know that smoking is harmful and “uncool”- especially among the young. We must ensure the message is passed down to new generations.

Finally, the UK is at the leading edge in using stem cells to help replace organs damaged by cancer. Tracheal transplants using tracheal scaffolds from cadavers seeded with the patient’s own stem cells have been used to replace damaged tissue for patients with tracheal cancer. Currently scientists at University College London are developing very similar procedures to grow a new nose for a patient who had lost their nose to cancer. These innovative approaches are the result of a continuously open, well-supported but regulated stem cell research policy, not yet seen in the USA.

Well done Great Britain!

Lauren Pecorino received her PhD from the State University of New York at Stony Brook in Cell and Developmental Biology. She crossed the Atlantic to carry out a postdoctoral tenure at the Ludwig Institute for Cancer Research, London. She is a Principal Lecturer at the University of Greenwich where teaches Cancer Biology and Therapeutics. The teaching of this course motivated her to write The Molecular Biology of Cancer: Mechanisms, Targets, and Therapeutics, now in its second edition. Feedback on the textbook posted on Amazon from a cancer patient drove her to write a book on cancer for a wider audience: Why Millions Survive Cancer: the Successes of Science.

Read a World Cancer Day Q&A with Lauren Pecorino.
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The post World Cancer Day 2013: The Best of British appeared first on OUPblog.

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On World Cancer Day 2012, we speak with Dr Lauren Pecorino, author of Why Millions Survive Cancer: the Successes of Science, to learn the latest in the field of cancer research. – Nicola

There are so many myths about cancer that it is sometimes difficult to understand exactly what it is. Can you briefly explain how cancer develops?

Cancer is a disease of the human genome. Many agents that cause cancer cause permanent changes to your genes. These permanent changes are called mutations. Cancer is usually caused by the accumulation of mutations over time. This is why cancer risk increases with age. The altered genes may produce faulty proteins that lead to abnormal cell growth and this appears as a tumour. Cancer is characterized by abnormal cell growth and the ability of tumour cells to spread throughout the body. It is this second characteristic, called metastasis that is the most difficult aspect to treat.

It is said that cancer now affects one in three people over a lifetime. What’s the latest progress in the field of cancer research?

There has been tremendous progress in the field of cancer management. The good news is that trends in death rates are decreasing for many cancers though that is not to say for all cancers. There are millions of cancer survivors who have had their diagnosis ten or more years ago. Many people are now living with cancer. Conventional treatments such as surgical procedures have been refined and new drugs that target tumour-specific molecules have proved efficient and promises less side effects.

In addition, we are learning to make lifestyle choices that science has shown reduces cancer risk — the most obvious being not smoking. We also have cancer screening programmes that can catch cancer early and even prevent cancer by treating pre-cancerous growths. The latest means for preventing a specific type of cancer is a cancer vaccine. Interestingly the vaccine designed to prevent cervical cancer vaccine also prevents several other cancers caused by the human papilloma virus such as some head and neck cancers.

What do you see as the priorities for future cancer research? Where will the next great advances be?

I see four main priorites for future cancer research.

1 –  To develop better and less invasive diagnostics so that we can detect cancer earlier. It is well-known that catching cancer earlier gives a better outcome or prognosis.

2 –  To expand our understanding of the individual molecular differences between tumors and to be able to fully practice personalized medicine which allows a better match between a patient and a drug. This understanding will need to be supported by technology that allows a patient’s tumour DNA to be sequenced (similar to the methods used for the Human Genome Project).

3 –  To understand if we can turn a cancer cell back into a normal cell. This may sound strange but lessons from stem cells and cloning tell us that changing one cell type into another is possible.

4 –  To better understand metastasis and how we can better treat it. The spreading of cancer cells throughout the body is the most difficult aspect of treating

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By Gayle Sulik Some people don't even know that disease-specific ribbons besides pink exist. Nan Hart wrote on the discussion board of the Ovarian Cancer National Alliance (Sept. 19th) that after her daughter got a teal ribbon tattoo on her wrist, one of her daughter's coworkers asked why her breast cancer ribbon wasn't pink? Umm...Because it's not a breast cancer ribbon? The assumption that one ribbon

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On medical progress and stage 4 breast cancer

By Gayle A. Sulik

Elizabeth Edwards died from stage 4 breast cancer (also known as metastatic breast cancer) on December 7th, 2010 at the age of 61. Ms. Edwards was a well-known public figure, notably the wife of former Senator John Edwards, and an accomplished lawyer, author, and health advocate. Her death inspired new discussions of Stage 4 breast cancer, finally shining a light on what has been a relatively invisible segment of the breast cancer community: the diagnosed who live from scan to scan, treatment to treatment, with the knowledge that neither medical progress nor positive attitude will likely keep them from dying from breast cancer.

Following Ms. Edwards’ breast cancer diagnosis in 2004, she quickly became a celebrity survivor. She expressed optimism about cure and continued to pursue an active personal and professional life. After learning in 2007 that she had a recurrence which had already spread to her bones, Ms. Edwards still looked for a “silver lining” despite the fact that her breast cancer was no longer considered to be curable. At that point, doctors called her breast cancer “treatable” – meaning that she would be in some kind of therapy for the rest of her life.

Ms. Edwards knew that she might not live to see her children grow up. Yet  public discussions were hesitant to acknowledge this reality. I remember the PBS news report that featured clips from a press conference in which Edwards’ medical doctor, Lisa Carey of the University of North Carolina Breast Center, stated that many women with stage 4 breast cancer “do very well for a number of years.”

In the interview that followed with Dr. Julie Gralow of Fred Hutchinson Cancer Research Center, the discussion of prognosis was similarly vague. Dr. Gralow rightly revealed that doctors have “no crystal ball” to see the future and that average survival rates cannot be used to predict an individual’s life span. However, she also circumvented the prognosis issue by using phrases such as “years of survival” and living out “long lives.” We heard about “terrific new therapies,” “great treatments…that don’t cause a lot of symptoms,” and and a new “era of personalized cancer therapy.” Dr. Gralow stressed that Ms. Edwards gives hope to those who are fighting metastatic breast cancer and that “her biggest issue is that she has a couple of young kids to raise.”

Immediately following Ms. Edwards’ death, Dr. Barron Lerner wrote a warm, thoughtful, and informative essay in The New York Times about the lessons society can learn from Ms. Edwards, including the limits of current treatments and the dubiousness of the term “survivor” that, while empowering in some ways can be misleading in others. For the 49,000 new people each year who develop what amounts to be a

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This weekend, I felt like I was in a beehive. All around me were swarms of black and yellow Tshirts, posters, and baseball caps. People buzzed about everywhere filling out registration forms or pinning on numbers. We were three thousand strong, and we were united.
“Livestrong” was created to raise money for cancer research, but a few days ago, it raised more than that. In all of the participants of the “Livestrong” Run, I saw hopes being raised. I saw awareness raised, and not just cancer awareness. I saw the idea that people can unite for the good of all come to life.
I had never before witnessed something like that. It was truly a sight.
When people join together, it makes them strong individually. Many think that the world can’t unite, but after seeing such a wonderful congregation at the Run, I disagree with the skeptics. Surely not one of us is perfect, but we all have the ability to put aside our differences to fight for what we believe in.
Does that still sound like a load of preschool garbage?
Let me explain.
Being a part of the fight against cancer was a liberating experience. I watched as people who had battled the disease crossed the finish line, and were handed a yellow rose for their achievement. That is something everyone needs to see in their lifetime.
This not-so-small-scale example of human unity and courage is enough to convince even the most skeptical person that we are all capable of joining hands across the nation and across the globe. And, in reaching out to others, we ourselves become better, more admirable, more confident people.
Do something, big or small, right now. Plan to join in the next charity run. Plant a tree. Donate some old clothes to a shelter. Anything that you do in your lifetime to help others enriches you tenfold.
Need some persuasion?
Try it out.

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Peering out their early morning window the children smile, quietly enjoying the moment of realization of the snow day before them. Looking through our Internet widows today we see another snow day is upon us, with many more to follow in the coming weeks, as bloggers from all walks of children's literature begin featuring Snowflakes for Robert's Snow: for Cancer's Cure. From now through early

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 We writers all dream our characters will turn into literary super heroes and earn us a lottery full of money. But do we ever dream they can fight disease and help for a brighter future? Hardly ever.

I have to admit I never even imagined that was possible. How on earth could little Shante' do something like that? I got the surprise of a lifetime last week when I found out that she will contribute in the fight against cancer.

The illustrator of my picture book, Marion Eldridge, used Shante' in her snowflake design this year for Robert's Snow. (http://www.jimmyfund.org/eve/event/roberts-snow/default.html) If you've never heard of Robert's Snow, it's an auction of snowflakes designed by children's illustrators to benefit the Dana-Farber Cancer Institute. It was started by illustrator Grace Lin as her husband Robert fought cancer, a battle he lost last month. I actually got teary eyed when I saw Shante' in that snowflake. I hope some wealthy person (are you reading this Oprah?) will fall in love with her, as Marion and I have, and bring in tons of money for cancer research.

You can see the snowflake on Marion's new blog:

http://marion-eldridgenews.blogspot.com/

 

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by Barbara Lehman
Houghton Mifflin 2007

What a disappointment.

A bored, lonely boy attempts to amuse himself one rainy day when he discovers a key under the furniture. Trying all the locked places he can think of he eventually finds its mate is a trunk that contains a ladder that leads underground. Following the underground tunnel he emerges on an island containing a lighthouse and a group of children and sunshine. They play together, eat together, and let the boy take a turn lighting the beacon. At the end of the day he takes his leave and returns to his dull home life.

At night he can't shake the image of the day's events and the next morning he ventures back into the tunnel only to be met by the children from the island who dared to venture to visit him. They return to his home and in the end happily play in his room.

There is a very weird class thing going on here that makes me uncomfortable. The boy is shown eating alone at one point in front of a formally set table, servants at the ready, dressed in a tie and a little boy suit. He may be the classic boy trapped in the tower of luxury but in the end he doesn't escape, he merely invites he new (and always shoeless) playmates into his home. That the boy is white and the playmates are represented by minorities doesn't help.

The question is, if the tunnel has always been there, if these children have always had a way to escape the island, why didn't they find the boy first? Could these be the children of the servants? When you get a wordless picture book you get to make the story up yourself, but you must use the clues available to you. So what is it Lehman wants us to read into all this?

Where Lehman previously gave us the parallel universe of The Red Book it all it's wordless glory, and the Museum Trip gave is a magical daydream, Rainstorm gives us a rather dull tale of privileged boredom and no mystery or fantasy whatsoever.

I'm not just hard on the book in comparison to Lehman's other books; it's difficult to not set this up alongside recent wordless picture books that are more clever (Adventures of Polo) or more detailed in their fantasy (most David Weisner books, especially Flotsom). Fantasy and escape don't need concrete explanations, but the questions they raise should invite equally fanciful interpretation. There isn't a lot to hang onto here, much less interpret, beyond the little dot of a moon in the night sky that actually belongs to the beacon and is as easily missed as it can be ignored.

It also isn't a question of the fantasy, the pacing of the book feels labored and pointless. Easily a third of the pictures could be removed and the story would retain its integrity. But a book with one third fewer illustrations would be very thin, and the story's shortcomings would be readily apparent.

The exercise feels as distant, closed off and cold, sheltered and empty

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