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Cancer

Cancer, Immunology, Research, Stem Cells

How cancer stem cells dodge the immune system

How cancer stem cells dodge the immune system

Hidden cat

Cancer stem cells are tricky beasts. They are often resistant to common treatments and can hide out in the body long after the bulk of tumor cells have been eliminated. Over time, they’re thought to contribute to the recurrence of disease in seemingly successfully treated people.

Stanford head and neck surgeon John Sunwoo, MD, and graduate student Yunqin Lee have been investigating how stem cells in head and neck cancers manage to evade the body’s immune system. Although it’s been known that a type of head and neck cancer cells — CD44+ cells — are particularly resilient to treatment, it’s not been known exactly how they accomplish this feat.

Now, Sunwoo and Lee published today in Clinical Cancer Research a study that sheds some light on the issue. They found that a protein called PD-L1 is expressed at higher levels on the surface membrane of CD44+ cells than on other cancer cells. PD-L1  is believed to play a role in suppressing the immune system during pregnancy and in diseases like hepatitis. It does so by binding to a protein called PD-1 on a subset of immune cells (T cells) and dampening their response to signals calling for growth and activation.

As Sunwoo described to me in an email:

We believe that our work provides very important insight into how cancer stem cells, in general, contribute to tumor cell dormancy and minimally residual disease that may recur years later. Our findings also provide rationale for targeting the PD-1 pathway in the adjuvant therapy setting of head and neck cancer following surgical resection.

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Cancer, Mental Health, Pain, Patient Care, Public Health

Coping with depression: A free online resource for cancer patients and their families

Coping with depression: A free online resource for cancer patients and their families

4523771529_0431b725aa_z-2If you or someone you know has cancer you’ve probably discovered that the disease can affect more than your physical health: It can alter your mood, your relationships with others and your relationship with yourself.

Many patients and their loved ones also experience feelings of depression and helplessness when faced with a cancer diagnosis, and this common and complex issue is addressed in an excerpt from Everyone’s Guide to Cancer Supportive Care found in the resource section of the Ernest and Isadora Rosenbaum Library at Stanford’s Center for Integrative Medicine.

The “Coping With Depression” piece, written by clinical psychologist Andrew Kneier, PhD, walks the reader through various aspects of the topic, touching on ways cancer and depression are related, what you can do to protect yourself from negative feelings, and how to overcome such feelings. Perhaps one of the most interesting and helpful parts of the piece is its examination of how depression linked to cancer differs from other forms of depression:

Cancer patients often get depressed simply because having cancer can be a depressing experience. However, there is usually more to it than that. Most cancer patients are not clinically depressed. To varying degrees, they are frightened and upset, but this is not depression. When cancer causes depression, there are psychological or biological reasons for it. These causes are understandable, and they are treatable.

Whether you have cancer or not, the piece is worth a read.

Previously: Ernest and Isadora Rosenbaum Library: A free, comprehensive guide to living with cancerLooking at cancer as a chronic illnessEmotional, social support crucial for cancer patients and Stanford psychiatrist David Spiegel’s path west
Photo by Fiona Cullinan

Cancer, Global Health, Pediatrics, Stanford News

The “little angel” who helps young Latin American children with cancer

The “little angel” who helps young Latin American children with cancer

ZambranoEduardo Zambrano’s spare office in Stanford Hospital displays some of the essentials of his pathology practice: a large microscope which dominates his desktop and a cabinet overflowing with colorful, hand-painted wooden boxes, each one representing a Latin American child with cancer.

Over the last 12 years, Zambrano, MD, has received as many as 1,000 tumor samples from pediatric oncologists in Venezuela and other Latin American countries who treat desperately poor young patients with various forms of cancer. Each sample is carried on a glass slide or embedded in wax, then carefully wrapped in tissue paper and lovingly packaged in a wooden box painted by a patient’s mother or local artisan as a gesture of gratitude. The boxes are covered in suns, stars, flowers and other images of life and hope.

“To me, behind each one of these boxes is a child with cancer, and to know we’ve been able to help them is very special to me,” said Zambrano, chief of pathology at Lucile Packard Children’s Hospital Stanford. An expert in pediatric solid tumors, he volunteers his service on behalf of these youngsters.

A professor of pediatrics and of pathology who came to Stanford a year ago, he said he receives one or two of these boxes a week. He examines the samples under the microscope and then issues a diagnosis, some involving rare cancers. Clinicians ship the samples to him because in these low-resourced countries, they don’t have the means to accurately diagnose the problem.

“Very frequently the diagnosis (from the home country) is either incomplete because they don’t have the resources to perform confirmatory tests or it’s wrong because they don’t have expertise in pediatric tumors,” he said. “It’s frequent that I have to give them a significantly different diagnosis than what they sent.”

Among the most common tumors he sees are pediatric sarcomas, which can originate in various parts of the body; neuroblastomas; lymphomas; and brain tumors.

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Cancer, Patient Care, Stem Cells, Transplants

The inside scoop on bone marrow transplants

The inside scoop on bone marrow transplants

blood-156063_1280Your bones harbor blood manufacturing factories. Those factories, packed in the bone marrow, produce stem cells that develop into red blood cells, white blood cells and platelets. Cancers such as leukemia and a few genetic conditions can weaken the bone marrow, necessitating a bone marrow transplant.

Witold Rybka, MD, director of the Bone Marrow Transplantation Program at Penn State Hershey, fielded questions recently in this Q&A on the procedure. An excerpt:

What are the most common types of bone marrow transplants?

For an autologous transplant, the patient can bank his or her own stem cells before undergoing intensive treatment for certain diseases such as lymphoma, Hodgkin’s lymphoma or multiple myeloma. The patient’s body can then use its own banked stem cells to regenerate healthy marrow once treatment is complete. Other transplants are allogeneic, meaning that the patient must receive matching stem cells from a sibling, family member or unrelated donor.

What are the odds of finding a match within one’s own family?

The chance of finding a full match is one in four, so the larger your family, the better chance you have of finding a match among your relatives. Given the size of most American families, most donors must use an unrelated match from a registry of more than 17 million living donors worldwide.

Unfortunately, it’s possible that a patient who needs a bone marrow transfusion won’t get one. Most banked stem cells are from donors in North America and Europe, making it easier for white patients to find a match. For patients of other ethnicities, the chance of finding a donor is only 60 percent, Rybka said.

To learn more about bone marrow transplants, visit Be The Match.

Previously: Bone marrow transplantation: The ultimate exercise in matchmaking, Bone marrow transplantation field mourns passing of pioneer Karl Blume and One (blood stem) cell to rule them all? Perhaps not, say Stanford researchers
Image by OpenClipartVectors

Big data, Cancer, Genetics, Precision health, Research, Stanford News, Stem Cells

Stem-cell knowledge may help outcomes for colon-cancer patients, says Stanford study

Stem-cell knowledge may help outcomes for colon-cancer patients, says Stanford study

Pinpointing which colon cancer patients need chemotherapy in addition to surgery can be difficult. Studies have suggested that those with stage-2 disease aren’t likely to benefit from chemotherapy, so doctors may chose to bypass the treatment and its toxic side effects.

Now cancer biologist Michael Clarke, MD, working with former postdoctoral scholars Piero Dalerba, MD, and Debashis Sahoo, PhD, have found a way to identify a small but significant minority of stage-2 patients who differ from their peers: They have a poorer overall prognosis, but they are also more likely than other stage-2 patients to benefit from additional chemotherapy. The research was published today in the New England Journal of Medicine.

This research is one of the first examples of how we can use our growing knowledge of stem cell biology to improve patient outcomes

From our press release:

Clarke and his colleagues have been studying the connection between stem cells and cancer for several years. For this study, Dalerba and Sahoo sought to devise a way to identify colon cancers that were more stem-cell-like, and thus likely to be more aggressive. They looked for a gene that was expressed in more mature cells but not in stem or progenitor cells. They did this by using a novel bioinformatics approach that drew on their knowledge of stem cell biology to identify developmentally regulated genes important in colon tissue maturation.

Because they knew from previous research by Dalerba in the Clarke laboratory that stem and immature colon cells express a protein called ALCAM, Dalerba and Sahoo looked for genes whose protein product was negatively correlated with ALCAM expression. “We reasoned that those proteins would likely be involved in the maturation of colon tissue and might not be found in more aggressive, immature cancers,” Sahoo said.

Finally, to ensure their results would be useful to doctors, the researchers added another criterion: The gene had to make a protein that was easily detectable by an existing, clinical-grade test.

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Addiction, Cancer, Genetics, Public Health, Research, Stanford News

For some African Americans, light smokers may not have lower lung cancer risk than heavy ones

For some African Americans, light smokers may not have lower lung cancer risk than heavy ones

CigaretteAlthough the relationship between smoking and lung cancer has been established beyond any doubt, it’s still difficult to know how a patient’s ethnicity might play into risk assessment. But it’s clear that it has a role. Lung cancer is the leading cause of cancer death in this country, and it disproportionately affects African Americans. Doctors are struggling to understand the interactions between genes and environment that contribute to lung cancer risk in all populations.

Physician scientist Sean David, MD, DPhil, and a multidisciplinary team of colleagues recently published in EBioMedicine the results of a study suggesting that African Americans who carry a panel of risky genetic sequences may be at higher risk for the disease, even if they are light smokers.

The study involved analyses of more than 7,000 Women’s Health Initiative participants and nearly 2,000 participants in a lung cancer case-control study with collaborators from multiple institutions in the United States.

As David explained to me in an email:

All smokers are at heightened risk for lung cancer, particularly those possessing high-risk genotypes. Our study suggests that African American light smokers are not at lower risk than heavy smokers if they possess certain genotypes, but that smoking more cigarettes does markedly increase lung cancer risk in individuals without these high-risk genotypes. These conclusions reinforce the message that light or heavy smoking is a risky proposition for African Americans, who can benefit from smoking cessation and evidence-based lung cancer screening services.

The researchers identified six nucleotide changes that appeared to affect the relationship between cigarettes smoked per day and lung cancer risk in African American smokers – all on chromosome 15. Although the nucleotide changes, called single nucleotide polymorphisms, or SNPs, had been associated with lung cancer risk in previous studies, this is the first time the risk has been tied to daily cigarette exposure in African Americans.

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Cancer, Events, Stanford News, Women's Health

There’s something about Harry: Harry Connick Jr. sings in support of women’s cancer research

Harry Connick Jr2 - 560

The heavy rain started just as the salad plates were taken away (“How appropriate,” I thought – given the name of the event I was attending), but few people inside the Sharon Heights Golf and Country Club in Palo Alto were paying attention to what was happening outside. Most eyes, including those of Stanford President John Hennessy, PhD, and Lloyd Minor, MD, dean of the medical school, were instead directed to a small stage at the front of the room holding a sleek black piano, several brass-holding men clad in suits, and Harry Connick Jr.

The acclaimed vocalist/pianist was in Palo Alto for Under One Umbrella, an annual event benefiting the Stanford Women’s Cancer Center, and he wowed the crowd with his commanding voice, big smile, and charming personality.

“I wrote this song for my wife, but there are so many attractive people here that you should consider it yours,” he told the largely female audience with a grin before launching into his 2013 song “One Fine Thing.” And later, he jokingly scolded the appreciative crowd when they gave him an enthusiastic standing ovation: “You’re not supposed to act like that at a damn luncheon.”

Moments earlier, Connick had been introduced with great fanfare by Jonathan Berek, MD, director of the center, who called the crooner not only an “internationally celebrated” entertainer but an “active philanthropist” and a “special guy.” (“I’ve never received so many compliments in my life,” Connick later laughed. “I’m going to make him my ringtone.”) And Connick also has a personal connection to what brought the roughly 300 people together on that rainy afternoon: As he shared during a serious moment between songs, his mother died of ovarian cancer when he was 13.

“Man, do we get it,” he said of those who have been affected by cancer. “It’s so nice to be among people who know what it’s all about.”

Connick took a few moments on the stage to call out Berek on his accomplishments – “It’s not often that you’re humbled sitting next to someone,” he said of the pre-performance time they spent together – and the work of others here, which was nicely highlighted in a 8-minute, Berek-produced film shown at the event.

During the piece, Beverly Mitchell, MD, director of the Stanford Cancer Institute, called the women’s cancer center “one of the jewels in our crown.” And Berek, before introducing Connick, noted the “tremendous expansion” of the “innovative and extensive” research programs that has occurred since the first Under One Umbrella event in 2008. (Much of this is, of course, thanks to Under One Umbrella, which has raised more than $26 million over seven years for the center.)

Berek also reminded attendees of the importance of patients – “They are both our benefactors and our inspiration” – but it was evident that most in the room also took inspiration from our researchers and clinicians. “I’m glad I can be a small part of this, but know how honored I am to be among the people who will eradicate” these diseases, Connick told the crowd.

Previously: Country music stars thank Under One Umbrella for supporting Stanford Women’s Cancer Center, Stanford Women’s Cancer Center: Peace of mind and advanced care under one umbrella and Garth Brooks and Trisha Yearwood help fundraising effort for Women’s Cancer Center at Stanford
Photo by Drew Altizer

Cancer, Imaging, In the News, Medicine and Society, Women's Health

This breast cancer is mine: When doctors get sick

This breast cancer is mine: When doctors get sick

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As the death last year of neurosurgeon Paul Kalanithi, MD, reminded us all, successful physicians aren’t protected from the onslaught of medical maladies that can strike anyone at any time.

Take Kimberly Allison, MD, a breast cancer researcher whose personal experience with the disease is featured in a recent Newsweek article and whose own breast cancer cells are shown above.

In 2008, Allison found a “shelf-like formation” under her arm. Only 33, she calls the experience “completely disorienting.” One minute she’s a doctor. The next, a patient.

As a pathologist, she was equipped to examine her own cells, as described in the article:

Slow-growing cancers appear almost like normal cells under a microscope’s lens. But then, Allison says, there are “big, bad and ugly” aggressive cancers. Instead of being neatly arranged into structures, these cancer cells swell and lose their tidy alignment. That’s what Allison saw when she peered through the microscope at her own cells.

This story has a happy ending. Allison penned a book on her experience, and she is now advancing the science on the particular type of breast cancer that struck her.

For more on Allison’s experience, check out this 1:2:1 podcast with Allison and Paul Costello, chief communications officer at the School of Medicine.

Previously: “You have cancer”: On being a doctor and receiving the news, Stanford neurosurgeon/cancer patient Paul Kalanithi: “I can’t go on. I will go.” and Stanford neurosurgeon Paul Kalanithi, who touched countless lives with his writing, dies at 37
Image courtesy of Kimberly Allison

Cancer, In the News, Palliative Care, Stanford News

Paul Kalanithi’s book will probably make you cry

Paul Kalanithi's book will probably make you cry

Just over a year ago, I received a first draft of an article for Stanford Medicine magazine that electrified me. It was gorgeous. It was heartbreaking. Its last words delivered a jolt of joy and made me cry. And this was just a first draft.

Now that essay, published in our spring 2015 issue as “Before I go,” is part of “When Breath Becomes Air,” the book Stanford neurosurgery resident Paul Kalanithi, MD, wrote in his last months of life about confronting an early death. The book is as compelling and beautiful as the essay. And just as likely to make you cry. Our next issue of Stanford Medicine will include an excerpt.

That I received the essay at all seemed at the time a small miracle. In September 2014, Kalanithi had agreed to write for the magazine, and two months later I had more than a magazine editor’s usual trepidation about whether the writer would meet the deadline.

I knew the cancer was wriggling through all medical defenses and that he was still fighting it with chemotherapy. I suspected the chemotherapy side effects were brutal. (I now know he wore silver-lined gloves to protect his fingertips, cracked from chemotherapy, while using his computer’s trackpad.) I hoped he was spending his last days doing what was most important to him, so I was loath to pressure him to finish his draft. Yet I selfishly hoped he had enough time to get the story done.

My deadline worries evaporated on Nov. 6 when, right on time, Kalanithi sent a first draft. It was magnificent. A month later the polished version came in, we published it and it proceeded to blow the minds of readers around the world.

Janet Maslin speaks for me in her New York Times review of the book:

Part of this book’s tremendous impact comes from the obvious fact that its author was such a brilliant polymath. And part comes from the way he conveys what happened to him — passionately working and striving, deferring gratification, waiting to live, learning to die — so well. None of it is maudlin. Nothing is exaggerated. As he wrote to a friend: “It’s just tragic enough and just imaginable enough.” And just important enough to be unmissable.

Kalanithi’s wife, Lucy Kalanithi, MD, a physician at Stanford, wrote the book’s epilogue and has penned an essay in the New York Times on their marriage before and after his death. It’s also unmissable.

Previously: Stanford neurosurgeon Paul Kalanithi, who touched countless lives with his writing, dies at 37 and For this doctor couple, the Super Bowl was about way more than football  and Stanford neurosurgeon/cancer patient Paul Kalanithi: “I can’t go on. I will go on.”
Photo courtesy of Lucy Kalanithi

Cancer, Imaging, Women's Health

Education reduces anxiety about mammography

Education reduces anxiety about mammography

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My close childhood friend Kelly died from breast cancer when she was only 32 years old. This inspired me to choose a research position at Berkeley Lab to help develop new breast-imaging scanners to improve early detection. Given my expertise in this field, my friends come to me with their confusion and ask, “At what age and how frequently should I get a mammogram?”

There has been a lot of debate surrounding mammography screening since 2009 when the United States Preventive Services Task Force revised the guidelines for average-risked women, limiting routine screening to biennial mammography for women 50 to 74 years of age.

The researchers recommended increasing the screening age in part because of the harmful anxiety caused by false-positive results, which are more common in younger women. The American Cancer Society recently released a new set of guidelines that recommends yearly mammograms starting at age 45, but they also considered the pain, anxiety and other potential side effects of mammography.

A recent article published in the Journal of the American College of Radiology describes a successful intervention to reduce this anxiety. The authors organized interactive one-hour educational sessions on mammography, which were led by a trained breast radiologist.

Before the lecture, a questionnaire was administered to the participants to identify their anxiety and previous mammography experience — 117 responded. Those respondents who reported having anxiety about mammography screening indicated “unknown results” and “anticipation of pain” as the primary sources of their anxiety.

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